CZ20021974A3 - Substituted phthalocyanines, process of their preparation and pharmaceutical preparation in which these compounds are comprised - Google Patents

Abstract

This invention relates to a process for the preparation of phthalonitrile sulfonate esters, a process for the preparation of substituted phthalonitriles using said phthalonitrile sulfonate esters, a process for the preparation of substituted phthalocyanines using said substituted phthalonitriles, a process for the preparation of phthalonitrile halides, a process for the preparation of substituted phthalocyanines using said phthalonitrile halides, novel phthalonitrile sulfonate esters, novel substituted phthalonitriles, novel substituted phthalocyanines and certain uses of said novel substituted phthalocyanines.

Description

Technical field

The present invention relates to a process for the production of esters of phthalonitrile sulfonates, a process for the preparation of substituted phthalonitriles using said phthalonitrile sulfonates esters, a process for the production of substituted phthalocyanines using said substituted phthalonitriles, a process for the production of phthalonitrile halides, new substituted phthalocyanines and some uses of these new substituted phthalocyanines.

BACKGROUND OF THE INVENTION

In recent years, intensive research has been conducted on the synthesis of substituted phthalocyanines. This research is partly due to the fact that substituted phthalocyanines have several desirable properties and can therefore be used in a wide variety of applications. These desirable properties of substituted phthalocyanines can often be influenced by the substituents of this ring system. Generally, these substituents can be divided into two categories, referred to as peripheral (i.e., 2, 3,

9, 10, 16, 17, 23, 24) and non-peripheral substituents (i.e., substituents at the 1, 4, 8, 11, 15, 18, 22, 25 position), the numbering of said ring system being shown in Scheme 1.

• • • v • v • v · v · v · v · v · v · v · v · v · v · v · v

Scheme 1

GB 2,229,190 discloses non-peripherally substituted phthalocyanines wherein at least some of these phthalocyanines are in the form of thin films, such as Langmuir-Blodgett films, in a liquid crystalline state, or, after dissolution or dispersion in a carrier material, transparent in visible areas of light and strongly absorb ultraviolet (UV) or infrared (IR) radiation. As a result, these phthalocyanines are capable of absorbing the energy emitted by lasers, so that the compounds can be used in products intended for use with the laser, such as laser optical memories and laser projection displays. The substitution of the substituents and the central ion M is then a means for tuning the wavelength absorbed by said substituted phthalocyanines which is carried out to capture the wavelengths of said lasers.

GB 2,295,547 discloses the use of a similar family of non-peripherally substituted phthalocyanines as photosensitizers in photodynamic therapy. European Patent Application Publication No. EP 0 906 758 discloses various zinc-containing phthalocyanines which are substituted with hydrophilic substituents which are linked to a phthalocyanine ring via an oxygen atom, which serves as a phototherapeutic or photodiagnostic agent. In cancer photodynamic therapy, the coloring compounds are administered to a subject afflicted with cancer. These coloring compounds can be absorbed by the tumor at least to some extent. Upon selective irradiation with a suitable radiation source, tumor tissue is destroyed by photogeneration of cytotoxic agents, such as singlet oxygen or a free radical, such as a hydroxyl or peroxide radical, said photogeneration of cytotoxic agents being mediated by the aforementioned staining compounds.

Until now, substituents have often been introduced into the phthalocyanine structure by cyclization of appropriately substituted precursors, which are usually phthalonitrile derivatives.

Alkoxylated phthalonitriles are synthesized from hydroxylated phthalonitriles (see Scheme 2) or by nucleophilic aromatic substitution of nitrated or chlorinated phthalonitriles (see Scheme 3). As described in British Patent No. GB 2,229,190 and European Patent Application No. EP 0 906 578 and as shown in Scheme 2, hydroxylated phthalonitriles can be reacted with a suitable base and a halogenated alkane to form alkoxylated phthalonitriles. Alternatively, the process described in European Patent Application No. EP 0 906 578, shown in Scheme 3, wherein nitrated or chlorinated phthalonitrile may be used may be used. 4 4

4,444,444

4444 44 44 44 44 4444

react with appropriate phthalonitriles. bases and alcohol to form alkoxylated Scheme 2 - OH AND STEED AND 1 Λ .CN and rY ^CN 1 'CN OH STEED

i) a base, a halogenated alkane of the formula RX

Scheme 3 γ RO

where Y = Cl or NO ₂

i) a base, an alcohol of formula ROH

The preparation of alkylated phthalonitriles is more complex. To date, two synthesis procedures have been developed

3,6-dialkylphthalonitriles, both of which are a key step in the formation of the aromatic ring by the Diels-Alder reaction, either by reaction of furan (see Scheme 4) or by reaction of thiophene-1,1-dioxide (see Scheme 5) with fumaronitrile . As described in British Patent No. 2,229,190 and shown in Scheme 4, furan can be 2,5-alkylated using a suitable base and a halogenated alkane. The resulting 2,5-dialkylfuran can be reacted with fumaronitrile by reacting the resulting product with a suitable product.

• 9 • 9 9 9 9 • 9 9 9 9

9 9 9 9 · · 99999 99

9

9999 99 99 99 base forms 3,6-dialkylphthalonitrile. Alternatively, as described in British Patent No. 2,229,190 and shown in Scheme 5, thiophene can be alkylated with a suitable base and a halogenated alkane. The resulting 2,5-dialkylthiophene can be oxidized to give the corresponding

1,1-dioxide. This dioxide can be further reacted with fumaronitrile to form 3,6-dialkylphthalonitrile.

Scheme 4

i) a base, a halogenated alkane of the formula RX;

ii) fumaronitrile NCCH = CHCN; iii) a base

Scheme 5

R

R

i) a base, a halogenated alkane of the formula RX; ii) an oxidizing agent; iii) fumaronitrile NCCH = CHCN

Substituted phthalocyanines are prepared by cyclization of suitably substituted phthalonitriles. As described in British Patent No. GB 2,229,190 and European Patent Application EP 0 906 578 and as shown in Scheme 6, substituted phthalonitrile can be reductively cyclized by treatment with

9 ··· 9 · * 9 9999

999 9900 9 9 9

99999 99,999 9 9

9,999,999

9999 99 99 99 99 9999 of a suitable base to form a substituted phthalocyanine. This substituted phthalocyanine can be metallized by reaction with a suitable metal compound. Alternatively, by reaction with a suitable metal compound, in the presence of a suitable base, the substituted phthalonitrile can be reductively cyclized directly to the metallized substituted phthalocyanine.

Scheme 6

R

i) bases; ii) a metal compound;

iii) a metal compound, a base

The main disadvantage of the substituted phthalocyanine synthesis processes used hitherto is that it is not possible to introduce a large number of potentially useful substituents into the phthalocyanine structure, since the functionality of these substituents is incompatible with the reaction conditions used in these processes. Therefore, the present invention describes a new 9 9 9 9 9 9 9 9 9 99 9 9 9 9 99999 99 999 9 9

9 9 9999 999

9999 99 99 99 999999 synthetic route to substituted phthalocyanines by cyclization of substituted phthalonitriles, which are prepared by substitution reactions of phthalonitrile sulfonate esters. Although aryl iodides, aryl bromides, aryl triflates and arylnonaphlates are used as substitution partners (see M.

Rottlander, P. Knochel, J. Org. Chem., 1998, 63, 4523; Lipshutz BH, Buzard DJ, Yun CS, Tetrahedron Lett., 1999,

40, 201), their use in the substitution reaction for the preparation of phthalonitriles has never been suggested. To date, substitution reactions of phthalonitrilsulfonate esters have never been used to prepare substituted phthalocyanines.

SUMMARY OF THE INVENTION

A first aspect of the present invention is a process for the preparation of a substituted phthalocyanine of formula (I)

wherein m independently of each other are 0, 1, 2, 3 or 4, with all four m not being 0 at the same time;

· A · a · a · a · a · i · a «a ···

R ¹ are independently selected from the group consisting of optionally substituted alkyl having from 1 to 20 carbon atoms; an optionally substituted -alkenyl group containing from 2 to 20 carbon atoms; an optionally substituted alkynyl group containing from 2 to 20 carbon atoms; -R ⁴ -OR ⁵ ; -R ⁴ -SR ⁵ ; -R ⁴ -SO 3 H; -R ⁴ -SO ² R ⁵ ; -R ⁴ -SO ² N (R ⁵ ) 2; -R ⁴ -N- (R ⁵ ) 2; -R ⁴ -P- (R ⁵ ) 2; group

-R ⁴ -P (O) (OR ⁵ ) ₂ ; an optionally substituted -R ⁴ -aryl group; an optionally substituted -R ⁴ -heteroaryl group; group

-R ⁴ -COR ⁵ ; -R ⁴ -COOR ⁵ and -R ⁴ -CON (R ⁵ ) ₂ ; wherein R ⁴ are independently selected from. a group comprising a chemical bond, a - (CH ₂ ) _q - group wherein q is an integer from 1 to 20, and a - (CH ₂ ) group _and CH = CH (CH ₂ ) b "z wherein a and b are integers from 0 to 20, wherein the sum of a and b is from 0 to 20; and

R ⁵ are independently selected from the group consisting of alkyl of 1 to 20 carbon atoms, alkenyl of 2 to 20 carbon atoms, optionally substituted aryl, optionally substituted heteroaryl, hydrogen, or two R ⁵ groups may together to form a saturated or unsaturated ring;

·················································· Are independently selected from the group consisting of

are independently 0,

1, 2 or 3;

are independently selected from fluoro, chloro, bromo and iodo; and

M is a metal atom, in the oxidation state of M ²⁺ , chloride, metal, metal bromide, metal oxide, silicon with two axial substituents n or two hydrogen atoms, each of which is bound by one of these hydrogen atoms;

which includes the following stages:

(a) converting a phthalonitrile alcohol of formula II

(II) to the sulfonate ester of formula III

(III)

CN

F · * 0 * »« E 00 «0

- _Λ 0 00 0 0 00 0 0 0 0 0 _L (J * ·· ♦ ·· * 0 0 * • 000 0 0 0 0 0 · 0 0 · • 0 0000 0 0 0 0000 00 00 00 00 000000 where

R ⁶ is either an alkyl group containing from 1 to 12 carbon atoms which may be optionally substituted by one or more fluorine and / or chlorine atoms, or an aryl group which may be optionally substituted by one or more substituents selected from the group consisting of methyl, nitro , methoxy, fluoro, chloro and / or bromo; wherein when m is 2, 3 or 4, the R ⁶ groups may be the same or different from each other;

(b) converting the sulfonate ester of formula III to a substituted phthalonitrile of formula IV

and (c) cyclizing the substituted phthalonitrile of formula I-V, either alone or together with any other phthalonitrile of formula IV.

For the purposes of this invention, "alkyl or alkyl group" means a hydrocarbon containing α-carbon atom in sp ³ hybridization, which may be linear or branched and which may be optionally substituted, which hydrocarbon may contain at least one double bond and / or at least one triple binding. The term "aryl or aryl group" as used herein refers to an aromatic hydrocarbon containing an aromatic α-carbon atom in the sp ² hybridization, which may optionally be substituted. An example of an aryl group is

. The term "-heteroaryl or heteroaryl" as used herein refers to an aromatic hydrocarbon containing an aromatic α-carbon atom in sp ² hybridization containing as part of the aromatic ring system at least one heteroatom selected from the group consisting of nitrogen, oxygen and sulfur and which may be optionally substituted. An example of a heteroaryl group is

wherein X = NH, O or S. "Alkenyl or alkenyl" as used herein means a hydrocarbon containing the α-carbon atom in sp ² hybridization, which may be branched or unbranched and which may be optionally substituted. Examples of alkenyl are -CH = CH ₂ , -CH = CH-CH ₃ , -CH = CH-C ₆ H ₅ , -CH = CH-CH = CH _2, and -CH = CH-CH ₂ -CH = CH ₂ . "Alkynyl or alkynyl" as used herein means a hydrocarbon containing the α-carbon atom in sp hybridization, which may be branched or unbranched and which may be optionally substituted. Examples of an alkynyl group is a group -C? CH, _-C-C-CH3, -C = CC ₆ H _5, and -C? C-C? CH. The terms "terminal alkenyl group" and "terminal alkynyl group" mean a terminal "alkenyl group" and a terminal "alkynyl group", respectively.

• 9

According to the invention, the alkyl group may be optionally substituted by one or more substituents selected from the group consisting of fluorine atom, chlorine atom, bromine atom, iodine atom, hydroxy group, -R ⁴ -OR ⁵ group, -R ⁴ -SR ⁵ group, amino group, -NHR ⁵ , -N (R ⁵ ) 2, N (R ⁵ ) ^3+, and / or -R ⁴ -N- (R ⁵ ) ₂ . The alkenyl group may be optionally substituted with one or more substituents selected from the group consisting of fluorine, chlorine, bromine, iodine, hydroxy, -R ⁴ -OR ⁵ , -R ⁴ -SR ⁵ , amino, -NHR ⁵ , -N (R ⁵ ) 2, N (R ⁵ ) ^3+, and / or -R ⁴ -N- (R ⁵ ) ₂ · The alkynyl group may be optionally substituted with a substituent selected from the group consisting of a fluorine atom, an chlorine, bromine, iodine, hydroxy, -R ⁴ -OR ⁵ , -R ⁴ -SR ⁵ , amino, -NHR ⁵ , -N (R ⁵ ) 2, N (R ⁵ ) ^{3+, -R4} N- ^(R5) 2, -Si ^(R5) 3, -C5H4N, -C4H3S and / or group -CgHs · the aryl group may be optionally substituted by one or more substituents selected C 1 -C 10 alkyl, C 2 -C 10 alkenyl, nitro, methoxy, s -CH ₂ OH, fluorine, chlorine, bromine, hydroxy, amino, -NHR ⁵ , -N (R ⁵ ) 2, N (R ⁵ ) ³⁺ , -NHCOR ⁵ , -COR ⁵ , COOR ⁵ and / or -CON (R ⁵ ) ₂ . The heteroaryl group may be optionally substituted with one or more substituents selected from the group consisting of alkyl of 1 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, nitro, methoxy, fluoro, chloro, bromo, hydroxy, amino , group

9 · 0 · 0 · 0 · · · · · · · · · · · · · · · · · · · · · ·

0 9 0 0 0

Λ Λ Λ · ····

-NHR ⁵ , -N (R ⁵ ) 2, N (R ⁵ ) ³⁺ , -NHCOR ⁵ , -COR ⁵ , COOR ⁵ and / or -CON (R ⁵ ) ₂ .

For the purposes of the present invention, "non-peripheral substituent" means a substituent in a compound of formula I or V that is attached at the position and relative to the point at which the pyrrole ring is attached to the aromatic ring containing the R ² group, or any of the two cyano groups in the compounds of formulas IV, VI or VII. A substituent that cannot be described as non-peripheral as defined above is referred to herein as "peripheral." For example, in Scheme 1, the non-peripheral substituents are in positions 1, 4, 8, 11, 15, 18, 22 and 25 and the peripheral substituents are in positions 2, 3, 9, 10, 16, 17, 23 and 24.

When the group R ² group, then the compounds of formulas II, III and IV according to the present invention are substituted benzenes. When the group R ² group, then the compounds of formulas II, III and IV of the present invention substituted naphthalenes. When the group R ² group, then the compounds of formulas II, III and IV according to the present invention are substituted anthracenes. When the group R ² group, then the compounds of formulas II, III and IV according to the present invention are substituted phenanthrene.

• ·

The substituted phthalocyanine consists of a basic structure and four substitution units X. The four substitution units X are indicated by a circle in formulas I and V below. As can be seen, depending on the nature of the groups R ¹ , R ³ , R ⁸ and R ⁹ be substituted or unmixed phthalocyanines. Non-mixed phthalocyanine is a phthalocyanine formed from four identical substitution units X. In contrast, mixed phthalocyanine is a phthalocyanine containing at least two different substitution units. In a preferred embodiment, the mixed phthalocyanine comprises two different substitution units X ¹ and X ² , wherein the ratio Χ ³ : Χ ² may be 1: 3, 2: 2 or 3: 1. If the ratio X ¹ : X ² is 2: 2, then two identical substitution units X ¹ or X ² may be adjacent or opposite to each other.

By the process of the first aspect of the present invention, it is possible to prepare non-mixed or mixed phthalocyanines.

· * * * * * * * * © © © © © © © © © © © © © © © © © © © © © © ··· ···· ·· ·· ·· ·· ····

The group M is preferably an isotope of copper, nickel, lead, vanadium, palladium, platinum, cobalt, niobium, aluminum, tin, zinc, magnesium, calcium, indium, gallium, iron, germanium, lanthanide, silicon with two axial substituents or two hydrogen atoms . More preferably, the group is a diamagnetic metal, silicon having two axial substituents or two hydrogen atoms. Even more preferably, the M group is an isotope of zinc, aluminum, magnesium, palladium, platinum, silicon with two axial substituents or two hydrogen atoms.

If the phthalocyanine of the formula I is a non-mixed phthalocyanine or, if the phthalocyanine of the formula I is substituted with the group -SR ⁵ , it is preferably not the sum of maps 4 or 8. The compound of the formulas I and / or and / or V.

Optionally, a multimer comprising two or more compounds of formula (I) and / or (V), which are bound together by covalent bonds, may be prepared according to the invention. In a preferred embodiment, said covalently bonded compounds of formula I and / or V are covalently bonded together via the substituents R ¹ , R ⁸ and / or R ⁹ .

• · · method of production

IV

Another aspect of the present invention is a substituted phthalonitrile of formula

(IV) where

R ¹ , R ² , R ³ and p have the same meaning as in the first aspect of the invention; and m is the number 1, 2, 3 or 4, which comprises the following steps:

(a) converting a phthalonitrile alcohol of formula II

(ID on sulfonate ester of formula III wherein (R ^ SO) *

(III) · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · ·

R ⁶ has the same meaning as in the first aspect of the invention; and (b) converting the sulfonate ester of formula III to a substituted phthalonitrile of formula IV *.

Preferably, the conversion of a sulfonate ester of formula III to a substituted phthalonitrile of formula IV involves the cross-addition of said sulfonate ester of formula III with an organozinc reagent of formula R ^x ZnX or an organo-copper reagent of formula R ¹ CuX catalyzed by palladium or nickel. wherein in the above formulas R ^{1 has the} same meaning as in the first aspect of the invention and X represents a halogen atom. A preferred halogen atom is a chlorine, bromine or iodine atom.

Alternatively, the conversion of a sulfonate ester of formula III to a substituted phthalonitrile of formula IV involves the cross-addition of a sulfonate ester of formula III with a trialkylborane of formula B (R ^X ) ₃ under palladium catalysis,

R ¹ are independently selected from the group consisting of optionally substituted alkyl having from 1 to 20 carbon atoms; a -FC-OR ^{5 group} ; -R ⁴ -SR ⁵ ; -R ⁴ -N (R ⁵ ) 2; -R ⁴ -P- (R ⁵ ) 2; an optionally substituted -R ⁴ -aryl group; an optionally substituted -R ⁴ -heteroaryl group; -R ⁴ -COR ⁵ ; -R ⁴ -COOR ⁵ and -R ⁴ -CON (R ⁵ ) ₂ ; wherein R ⁴ are independently selected from the group consisting of - (CH ₂ ) _q -, wherein c {is an integer from 1 to 20, and - (CH ₂ ) _and CH = CH (CH ₂ ) _b -, wherein a and b »44

4 4

4 4 4 4 4 4 are integers from 0 to 20, where the sum of a and b is from 0 to 20; and

R ⁵ are independently selected from the group consisting of alkyl of 1 to 20 carbon atoms, alkenyl of 2 to 20 carbon atoms, aryl, heteroaryl, hydrogen, or two R ⁵ groups may be taken together to form a saturated or unsaturated ring.

In a preferred embodiment, the compound of formula B (R ¹ ) 3 is 9-borabicyclo [3.3.1] nonane (or 9-BBN), i. a compound of formula R ¹ B (C ₈ H ₁₄ ).

Alternatively, the conversion of the sulfonate ester of formula III to the substituted phthalonitrile of formula IV, a cross-coupling of the sulfonate ester of formula III with a boronic acid R ¹ B (OH) 2 or a boronic ester of formula R ¹ -B (OR ⁷⁾ 2 in catalysis by palladium or nickel, wherein:

R ¹ is selected from the group consisting of alkenyl of 2 to 20 carbon atoms; optionally substituted aryl and optionally substituted heteroaryl; and

R ⁷ independently represent an alkyl group containing from 1 to 10 carbon atoms and both R ⁷ together with the -OBO- group form a ring.

In a preferred embodiment, the boronic acid R ¹ B (OR ⁷⁾ 2 is selected from the group consisting of Fe · ···· compound of the formula RN (-OCH2CH2CH2O-), compounds of the formula RN (-OCH2CH2O-) and compound of formula R ¹ B (OC (CH _{3) 2} C (CH _{3) 2} O-).

Alternatively, converting a sulfonate ester of formula III to a substituted phthalonitrile of formula IV with _N Ar comprises reacting a sulfonate ester of formula III with a nucleophile of formula HO-R ⁵ , HS-R ⁵ or HN (R ⁵ ) 2, HP (R ^5). Or with an iodide anion, wherein

R ⁵ are independently selected from the group consisting of alkyl of 1 to 20 carbon atoms, alkenyl of 2 to 20 carbon atoms, aryl, heteroaryl, hydrogen, or two R ⁵ groups may be taken together to form a saturated or unsaturated ring.

Alternatively, the conversion of a sulfonate ester of formula III to a substituted phthalonitrile of formula IV comprises palladium catalyzed addition of a sulfonate ester of formula III with an R ¹ H addition partner, wherein R ¹ represents an optionally substituted terminal alkenyl group containing from 2 to 20 atoms or an optionally substituted terminal alkynyl group containing from 2 to 20 carbon atoms.

In a preferred embodiment, the R ¹ groups are independently selected from the group consisting of an alkyl group containing from 1 to 20 carbon atoms optionally substituted by one or more substituents selected from the group consisting of fluorine atom, chlorine atom, bromine atom, iodine atom, hydroxy group, • 0 • 0 • 000 · 000

-R ⁴ -OR ⁵ , -R ⁴ -SR ⁵ , amino, -NHR ⁵ , -N (R ⁵ ) ₂ , -N (R ⁵ ) 3 ⁺ and / or -R ⁴ -N- (R ⁵ ) 2; an alkenyl group having from 2 to 20 carbon atoms optionally substituted by one or more substituents selected from the group consisting of fluorine, chlorine, bromine, iodine, hydroxy, -R ⁴ -OR ⁵ , -R ⁴ -S -R ^5, amino, -NHR ^5, -N (R ⁵⁾ _2, -N ^{(R5) 3+} and / or ^-R4 N- ^(R5) 2; an alkynyl group containing from 2 to 20 carbon atoms optionally substituted by one or more substituents selected from the group consisting of fluorine, chlorine, bromine, iodine, hydroxy, -R ⁴ -OR ⁵ , -R ⁴ -SR ⁵ , amino, -NHR ⁵ , -N (R ⁵ ) 2, -N (R ⁵ ) ³⁺ , -R ⁴ -N- (R ⁵ ) 2, -Si (R ⁵ ) 3, - C ₅ H ₄ N, -C ₄ H ₃ S, and / or -C ₆ H ₅ ; -R ⁴ -OR ⁵ ; -R ⁴ -SR ⁵ ; -R ⁴ -SO 3 H; -R ⁴ -SO ² R ⁵ ; -R ⁴ -SO ² N (R ⁵ ) 2; -R ⁴ -N- (R ⁵ ) 2; -R ⁴ -P- (R ⁵ ) 2; -R ⁴ -P (O) (OR ⁵ ) 2; -R ⁴ -aryl, which is optionally substituted with one or more substituents selected from the group consisting of alkyl of from 1 to 10 carbon atoms, alkenyl of from 2 to 10 carbon atoms, nitro, methoxy, -CH 2 OH, fluoro, chlorine, bromine, hydroxy, amino, -NHR ⁵ , -N (R ⁵ ) 2, -N (R ⁵ ) ³⁺ , -NHCOR ⁵ , -COR ⁵ , -COOR ^5, and / or or -CON (R ⁵ ) ₂ ; -R ⁴ -heteroaryl optionally substituted with one or more substituents selected from the group consisting of alkyl of 1 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, nitro, methoxy, fluoro, chloro, atom bromine, hydroxy, amino, -NHR ⁵ , 9 9 9 9

9 99

9

9999 99

99

9 9 9

9 99

9 9 9

99

99 · 9 9

9 · ·

9 9

9 9

9999

-N (R ⁵ ) 2, -N (R ⁵ ) ³⁺ , -NHCOR ⁵ , -COR ⁵ , -COOR ⁵ and / or -CON (R ⁵ ) 2; -R ⁴ -COR ⁵ ; -R ⁴ -COOR ⁵ and -R ⁴ -CON (R ⁵ ) 2; wherein R ⁴ and R ⁵ have the same meaning as in the first aspect of the invention.

In an even more preferred embodiment, the R ¹ groups are independently selected from the group consisting of an alkyl group containing from 1 to 20 carbon atoms optionally substituted by one or more substituents selected from the group consisting of fluorine atom, chlorine atom, bromine atom, iodine atom, hydroxy group , amino, -NHR ⁵ , -N (R ⁵ ) 2 and / or -N (R ⁵ ) 3 ⁺ ; aC 1 -kenyl group containing from 2 to 20 carbon atoms; an alkynyl group containing from 2 to 20 carbon atoms; -SR ⁵ ; a group -N (R ⁵⁾ _2; -R ⁴ -aryl which is optionally substituted with one or more substituents selected from the group consisting of alkyl of 1 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, nitro, methoxy, fluoro, chloro, atom bromo, hydroxy, amino, -NHR ⁵ , -N (R ⁵ ) 2, -N (R ⁵ ) ³⁺ , -NHCOR ⁵ , -COR ⁵ , -COOR ^5, and / or -CON ^(R5) _2; wherein R ⁴ and R ⁵ have the same meaning as in the first aspect of the invention.

In a preferred embodiment, at least one R ¹ group is not an unsubstituted alkyl group containing from 1 to 20 carbon atoms.

The group R ¹ may be a peripheral or a non-peripheral substituent. In a preferred embodiment of the invention at least one R ¹ group is a non-peripheral substituent.

»« * * 9 9 99 99 99 99 99 99 99 99 99 99 99 99 999 99 99 999 9 9 9 9 9 9 9 9 9

The compound of formula I and / or IV may be substituted or linked to an amino acid, fatty acid, nucleic acid, di-, tri- or up to decapeptide, polypeptide, protein, carbohydrate, polysaccharide or polymer. Preferably, the compound of formula (I) and / or (IV) is substituted or linked to an amino acid, fatty acid, nucleic acid, di-, tri- or up to decapeptide, polypeptide, protein, carbohydrate, polysaccharide or polymer via R ¹ .

Another aspect of the present invention is a process for the preparation of a phthalonitrilsulfonate ester of formula III

(III) where

R @ ² , R @ ³ , R @ ⁶ and R @ ^{3 are} as defined in the first aspect of the invention; and m is the number 1, 2, 3 or 4, which comprises the following steps

99 99 «99 99 99

9 * 9 · 9999 9999 * 99 99 99 99 ·

999 99 99 999 9 9

9,999,999

(A) the conversion of a phthalonitrile alcohol of formula II

(II) to the sulfonate ester of formula III.

In a preferred embodiment, R ² is

In a preferred embodiment R ⁶ are independently selected from the group consisting of methyl, -C ₂ H ₅ group, -C3H7, -CH (CH3) _2, -C4H9 group -CsHi7 group -CHC1 ₂ radical, _-CF3, -C4F9 group, a group -CgH _5, or - (C6H4) _-4-CH3, - (C ₆ H ₄₎ 2-NO ₂ radical,

- (C ₆ H ₄₎ 3-NO ₂ - (C ₆ H ₄₎ 4-NO ₂ radical, a - (CGH ₄₎ -2-Br, - (C ₆ H ₄₎ -4-Br , - (C ₆ H ₄₎ -4-C1, - (C ₆ H ₄₎ -4-F, - (C ₆ H _{3) 2} -2,5-Cl, - (C ₆ H ₃ ) -3,4-Cl ₂ group

- (C ₆ H ₃ ) -3,4- (OCH ₃ ) 2 and - (C ₆ H ₃ ) -2,4- (NO ₂ ) ₂ . In an even more preferred embodiment, R ^{6 are} independently selected from the group consisting of methyl, trifluoromethyl and -C ₄ F ₉ .

In a preferred embodiment, p = 0.

99 9 9 9 99 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 · 99 99 99 9999

Another aspect of the present invention is a process for making a substituted phthalocyanine of formula V

wherein m is independently 0, 1, 2, 3 or 4;

R ¹ are independently selected from the group consisting of optionally substituted alkyl having from 1 to 20 carbon atoms; an optionally substituted alkenyl group containing from 2 to 20 carbon atoms; an optionally substituted alkynyl group containing from 2 to 20 carbon atoms; -R ⁴ -OR ⁵ ; -R ⁴ -SR ⁵ ; -R ⁴ -SO 3 H; -R ⁴ -SO ₂ R ⁵ ; -R ⁴ -SO ² N (R ⁵ ) 2; -R ⁴ -N- (R ⁵ ) 2; -R ⁴ -P- (R ⁵ ) 2; group

-R ⁴ -P (O) (OR ⁵ ) 2; an optionally substituted -R ⁴ -aryl group; an optionally substituted -R ⁴ -heteroaryl group; -R ⁴ -COR ⁵ ; -R ⁴ -COOR ⁵ and -R ⁴ -CON (R ⁵ ) 2; where

R ⁴ are independently selected from the group consisting of a chemical bond, - (CH ₂ ) _q -, wherein q

W4 * 99 is an integer from 1 to 20, and the group - (CH ₂ ) _and CH = CH (CH ₂ ) b ~ f wherein a and b are integers from 0 to 20, wherein the sum of a and b is from 0 to 20; and

R ⁵ are independently selected from the group consisting of alkyl of 1 to 20 carbon atoms, alkenyl of 2 to 20 carbon atoms, optionally substituted aryl, optionally substituted heteroaryl, hydrogen, or two R ⁵ groups may together to form a saturated or unsaturated ring;

R ² is independently selected from the group consisting of

are independently 0,

R ³ are independently selected from fluoro, chloro, bromo and iodo; and

R ⁸ are independently selected from the group consisting of optionally substituted alkyl groups containing from 1 to 20 carbon atoms;

q is 1 or 2;

P «* · * · t« · t 4 ·· «

0 0 0 0 0 0 0 0

0 4 β 0 · ··

* 0 • 0 • 0 0

R ⁹ are independently selected from chloro, bromo, iodo, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, and optionally substituted heteroaryl; and

M is a metal atom in the oxidation state of M ²⁺ , metal chloride, metal bromide, metal oxide, silicon with two axial substituents or two hydrogen atoms, each of which is bound by one of these hydrogen atoms;

which summarizes the following stages:

(a) converting a phthalonitrile halide of formula VI

where

R ¹⁰ are independently selected from the group consisting of chlorine, bromine and iodine; 9 9 9 9 9999

999 9999 99 ·

99999 99,999 9 9

9,999,999

9999 99 99 99 99 9999 to the substituted phthalonitrile of formula VII

where

R ⁿ are independently selected from the group consisting of optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl and optionally substituted heteroaryl; and (b) cyclizing the substituted phthalonitrile of formula VII, either alone or together with any other phthalonitrile of formula IV

to form a phthalocyanine of formula V;

or which alternatively comprises the following steps:

(a) cyclization of a substituted phthalonitrile halide of formula VI, either alone or together with any of the compounds of formula (VI); Another phthalonitrile of formula IV to form a substituted phthalocyanine of formula V; and (b) optionally converting a group R ⁹ which represents a chlorine atom, a bromine atom or an iodine atom into an optionally substituted alkyl group, an optionally substituted alkenyl group, an optionally substituted alkynyl group, an optionally substituted aryl group, an optionally substituted heteroaryl group.

In the preparation of a substituted phthalocyanine of formula V according to this aspect of the present invention, it is possible to obtain a non-mixed or mixed phthalocyanine.

The group M is preferably an isotope of copper, nickel, lead, vanadium, palladium, platinum, cobalt, niobium, aluminum, tin, zinc, magnesium, calcium, indium, gallium, iron, germanium, lanthanide, silicon with two axial substituents or two hydrogen atoms . More preferably, the group is an isotope of a diamagnetic metal, silicon having two axial substituents or two hydrogen atoms. Even more preferably, the M group is an isotope of zinc, aluminum, magnesium, palladium, platinum, silicon with two axial substituents or two hydrogen atoms.

In a preferred embodiment, the R ¹ groups are independently selected from the group consisting of an alkyl group containing from 1 to 20 carbon atoms optionally substituted by one or more substituents selected from the group consisting of fluorine atom, chlorine atom, bromine atom, iodine atom, hydroxy group, -R ⁴ -O-R ⁵ , -R ⁴ -SR ⁵ , amino, -NHR ⁵ , -N (R ⁵ ) ₂ , -N (R ⁵ ) ^3+, and / or -R ⁴ -N- (R ⁵ ) 2;

·

0 · · · · ·

0 0 0 0 0 0 0 0 0 0 0 0

An alkenyl group containing from 2 to 20 carbon atoms optionally substituted by one or more substituents selected from the group consisting of fluorine atom, chlorine atom, bromine atom, iodine atom, hydroxy group, -R ⁴ -OR ⁵ ; -R ⁴ -SR ⁵ , amino, -NHR ⁵ , -N (R ⁵ ) ₂ , -N (R ⁵ ) ^3+, and / or -R ⁴ -N- (R ⁵ ) 2; an alkynyl group containing from 2 to 20 carbon atoms optionally substituted by one or more substituents selected from the group consisting of fluorine, chlorine, bromine, iodine, hydroxy, -R ⁴ -OR ⁵ , -R ⁴ -SR ⁵ , amino, -NHR ⁵ , -N (R ⁵ ) 2, -N (R ⁵ ) ³⁺ , -R ⁴ -N- (R ⁵ ) 2, -Si (R ⁵ ) ₃ group, -C5H4N, -C ₄ H ₃ S, and / or -C ₆ H 5; -R ⁴ -OR ⁵ ; -R ⁴ -SR ⁵ ; -R ⁴ -SO 3 H; -R ⁴ -SO ² R ⁵ ; -R ⁴ -SO ² N (R ⁵ ) 2; -R ⁴ -N- (R ⁵ ) 2; -R ⁴ -P- (R ⁵ ) 2; -R ⁴ -P (O) (OR ⁵ ) ₂ ; -R ⁴ -aryl which is optionally substituted with one or more substituents selected from the group consisting of alkyl of 1 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, nitro, methoxy, fluoro, chloro, atom bromo, hydroxy, amino, -NHR ⁵ , -N (R ⁵ ) 2, -N (R ⁵ ) ³⁺ , -NHCOR ⁵ , -COR ⁵ , -COOR ^5, and / or -CON ^(R5) _2; -R ⁴ -heteroaryl optionally substituted with one or more substituents selected from the group consisting of alkyl of 1 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, nitro, methoxy, fluoro, chloro, atom bromo, hydroxy, amino, -NHR ⁵ , -N (R ⁵ ) 2, -N (R ⁵ ) ³⁺ , -NHCOR ⁵ , -COR ⁵ , -COOR ^5, and / or -CON ^(R5) _2; -R ⁴ -COR ⁵ ; -R ⁴ -COOR ⁵ ;

4 4 4

4444 44 44 44 4 · 4444

-R ⁴ -CON (R ⁵ ) ₂ ; wherein R ⁴ and R ⁵ have the same meaning as in the first aspect of the invention.

In an even more preferred embodiment, the R ¹ groups are independently selected from the group consisting of an alkyl group containing from 1 to 20 carbon atoms optionally substituted by one or more substituents selected from the group consisting of fluorine atom, chlorine atom, bromine atom, iodine atom, hydroxy, amino, -NHR ⁵ , -N (R ⁵ ) 2 and / or -N (R ⁵ ) 3 ⁺ ; an alkenyl group containing from 2 to 20 carbon atoms; an alkynyl group containing from 2 to 20 carbon atoms; -SR ⁵ ; a group -N (R ⁵⁾ 2 ;. -R ⁴ -aryl, which is optionally substituted with one or more substituents selected from the group consisting of -alkyl of 1 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, nitro, methoxy, fluoro, chloro, bromine, hydroxy, amino, -NHR ⁵ , -N (R ⁵ ) 2, -N (R ⁵ ) ³⁺ , -NHCOR ⁵ , -COR ⁵ , -COOR ⁵ and / or - CON (R ⁵ ) ₂ ; wherein R ⁴ and R ⁵ have the same meaning as in the first aspect of the invention.

In a preferred embodiment, at least one R ¹ group is not an unsubstituted alkyl group containing from 1 to 20 carbon atoms.

The group R ¹ may be a peripheral or a non-peripheral substituent. In a preferred embodiment of the invention at least one R ¹ group is a non-peripheral substituent.

• '___

The compound of formula (V) may be substituted or linked to an amino acid, a fatty acid, a nucleic acid, a di-, tri- or even decapeptide, polypeptide, protein, carbohydrate, polysaccharide, or polymer. Preferably, the compound of formula V is substituted or linked to an amino acid, a fatty acid, a nucleic acid, a di-, tri- or even decapeptide, polypeptides, protein, carbohydrate, polysaccharide or polymer via the R ¹ group.

In a preferred embodiment of the present invention, the phthalocyanine of formula V is not a mixed phthalocyanine, or when said phthalocyanine of formula V is substituted with -SR ⁵ , the sum of maps 4 or 8 is not.

The group R ² is preferably a group

In a preferred embodiment, p = 0.

According to a preferred embodiment of the present invention, the R ⁸ groups are independently selected from the group consisting of alkyl groups containing from 1 to 20 carbon atoms optionally substituted by hydroxy. Even more preferably, the R ⁸ groups are independently selected from the group consisting of alkyl groups containing from 1 to 20 carbon atoms. Even more preferably, the R ⁸ groups are independently selected from the group consisting of alkyl groups containing from 1 to 10 carbon atoms.

The R ⁹ groups are preferably independently selected from the group consisting of bromine, iodine, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, and optionally substituted heteroaryl. Preferably, R ^{9 is} selected from the group consisting of bromine, iodine, -CH = CH 2, -C ^CH, -C (C-Si (R ⁵ ) 3, -C ^C ₅ H ₄ N, - CC ^ C ₄ H ₃ S, -C? CC ₆ H ₅ group, -C5H5N, -C ₄ H ₃ S and optionally substituted -CgHs. More preferably, R ^{9 is} selected from bromine, iodine, -CH = CH 2, -C CH2CH, -C -CC-SiMe 3, -C =C-SiPr 3, -CrC-C 5 H 4 N, -C = C ^_ C 4 H ₃ S, -C = C-C 6 H _5, -C ₅ H ₅ N, -C ₄ H ₃ S, -C5H5, -C 6 H chink _{4 -CH2} OH and cutaway ₄ -OCH ₃ .

The compound of formula I and / or V may optionally form a sandwich complex containing two or more compounds of formula I and / or V.

Optionally, it is possible to prepare a multimer comprising two or more compounds of formula I and / or V, which are linked to each other by covalent bonds. In a preferred embodiment, said covalently bonded compounds of formula I and / or V are covalently bonded together via the substituents R ¹ , R ⁸ and / or R ⁹ .

Another aspect of the present invention is a process for preparing a phthalonitrile halide of formula VI

· <<<<<<· · · · ·· e · ·· ·· ····

R ⁸ are independently selected from the group consisting of alkyl groups having from 1 to 20 carbon atoms which are optionally substituted;

q is 1 or 2; and

R ¹⁰ are independently selected from the group consisting of chloro, bromo and iodo;

which includes the following stages:

(a) halogenating 2,3-dicyanohydroquinone to form a dihalogenated product, (b) alkylating said dihalogenated product to form an alkylated mono- or dihalogenated product.

According to a preferred embodiment of the present invention, the R ⁸ groups are independently selected from the group consisting of alkyl groups containing from 1 to 20 carbon atoms optionally substituted by hydroxy. Even more preferably, the R ⁸ groups are independently selected from the group consisting of alkyl groups containing from 1 to 20 carbon atoms. Even more preferably, the R ⁸ groups are independently selected from the group consisting of alkyl groups containing from 1 to 10 carbon atoms.

φ · · φ φ φ φ φ · · · · · · · · φ φ φ φ φ φ φ · · · · φ φ φ φ φ φ φ φ φ φ φ

Another aspect of the phthalonitrilsulfonate of the present invention is a substituted ester III wherein

R ² are independently

(III) self-selected from the group consisting of

m is 1, 2, 3 or 4;

R ⁶ is either an alkyl group containing from 1 to 12 carbon atoms which may be optionally substituted by one or more fluorine and / or chlorine atoms, or an aryl group which may be optionally substituted by one or more substituents selected from the group consisting of methyl, nitro , methoxy, fluoro, chloro and / or bromo; wherein when m is 2, 3 or 4, the R ⁶ groups may be the same or different from each other;

p is 0, 1, 2 or 3; and

R ³ is selected from the group consisting of a fluorine atom, a chlorine atom, a bromine atom and an iodine atom, wherein when p is 2 or 3, the R ³ groups may be the same or different from each other.

· · 1 1 · 1 1 1 «1 1 1 1 1 1 1 1

111 11 11 111 1 ·

1111 111 1111 99 11 11 1 · 1111 vy

In a preferred embodiment, R ² is

In a preferred embodiment, the R ⁶ groups are independently selected from the group consisting of methyl, -C ₂ H ₅ , -C ₃ H ₇ , -CH (CH ₃ ) 2, -C ₄ H ₉ , -C ₈ H ₁₇ , - CHCl 2, -CF ₃ , -C ₄ F ₉ , -C ₆ H ₅ , - (C ₆ H ₄ ) -4-CH ₃ , - (C ₆ H ₄ ) -2-NO ₂ ,

- (C ₅ H ₄ ) -3-NO 2, - (C ₅ H ₄ ) -4-NO ₂ , - (C ₆ H ₄ ) -2-Br, - (C ₆ H ₄ ) -4- br, - (C ₆ H ₄₎ -4-C1, - (C ₆ H ₄₎ -4-F, - (C ₆ H _{3) 2} -2,5-Cl, - (C ₆ H ₃ ) -3,4-Cl ₂ group

- (C ₅ H ₃ ) -3,4- (OCH ₃ ) 2 and - (C ₆ H ₃ ) -2, 4- (NO ₂ ) ₂ . In an even more preferred embodiment, R ^{6 are} independently selected from the group consisting of methyl, trifluoromethyl and -C ₄ F ₉ .

Preferably p = 0.

Another aspect of the present invention is a substituted phthalonitrile of Formula IV

wherein m is 1, 2, 3 or 4;

R ¹ are independently selected from the group consisting of C 1 -C 20 alkyl, 0 0 00 0 0, 0 9 0 4, 0 0 0 0 000 0000 00 0, 00 00 0000 which is optionally substituted by one or more substituents selected from the group consisting of fluorine, chlorine, bromine, iodine, hydroxy, -R ⁴ -OR ⁵ , -R ⁴ -SR ⁵ , amino, -NHR ⁵ , -N (R ⁵ ) ₂ , -N (R ⁵ ) ^3+, and / or -R ⁴ -N- (R ⁵ ) 2, an alkenyl group containing from 2 to 20 carbon atoms optionally substituted by one or more substituents selected from the group consisting of fluorine, chlorine, bromine, iodine, hydroxy, -R ⁴ -OR ⁵ , -R ⁴ -SR ⁵ , amino, -NHR ⁵ , -N (R ⁵ ) ₂ , -N (R ⁵ ) ³⁺ and / or -R ⁴ -N- (R ⁵ ) 2; an alkynyl group containing from 2 to 20 carbon atoms optionally substituted by one; m or more substituents selected from the group consisting of fluorine, chlorine, bromine, iodine, hydroxy, -R ⁴ -OR ⁵ , -R ⁴ -SR ⁵ , amino, -NHR ⁵ , -N (R) ⁵ ) 2, -N (R ⁵ ) 3 ⁺ , -R ⁴ -N- (R ⁵ ) 2, -Si (R ⁵ ) 3, -C ₅ H ₄ N, -C ₄ H ₃ S, and / or or -C ₆ H ₅ ; -R ⁴ -OR ⁵ ; -R ⁴ -SR ⁵ ; -R ⁴ -SO 3 H; -R ⁴ -SO ² R ⁵ ; -R ⁴ -SO ² N (R ⁵ ) 2; -R ⁴ -N- (R ⁵ ) 2; -R ⁴ -P- (R ⁵ ) 2; -R ⁴ -P (O) (OR ⁵ ) ₂ ; -R ⁴ -aryl which is optionally substituted with one or more substituents selected from the group consisting of alkyl of 1 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, nitro, methoxy, fluoro, chloro, atom bromo, hydroxy, amino, -NHR ⁵ , -N (R ⁵ ) 2, -N (R ⁵ ) ³⁺ , -NHCOR ⁵ , -COR ⁵ , -COOR ^5, and / or -CON ^(R5) _2; -R ⁴ -heteroaryl group, which is optionally • 9 ·· ·· 9 *

99 φ 9 99 ·

9 9 9 9 9

99,999 9 9

9 9 9 9 9

99 99 9999

R is selected from the group substituted by one or more substituents selected from the group consisting of alkyl of 1 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, nitro, methoxy, fluoro, chloro, bromo, hydroxy, amino , -NHR ⁵ , -N (R ⁵ ) 2, -N (R ⁵ ) ³⁺ , -NHCOR ⁵ , -COR ⁵ , -COOR ^5, and / or -CON (R ⁵ ) 2 ; -R ⁴ -COR ⁵ ; -R ⁴ -COOR ⁵ and -R ⁴ -CON (R ⁵ ) 2; where

R ⁴ are independently selected from the group consisting of chemical bond, - (CH ₂ ) _q -, wherein q is an integer from 1 to 20, and

- (CH _{2) a} CH = CH (CH ₂₎ b R ^_ where a and b are integers from 0 to 20 and the sum of a and b is from. 0 to 20; and

R ⁵ are independently selected from the group consisting of alkyl of 1 to 20 carbon atoms, alkenyl of 2 to 20 carbon atoms, aryl, heteroaryl, hydrogen, or two R ⁵ groups may be taken together to form a saturated or unsaturated ring;

including

it is 0, 1, 2 or 3;

• · »44

4 4 · 4 · 4 · 4 · 4 · 4 · 4 · 9 · 4 · 4 · 44

4494 ·· 44 44 ·· 4494

R ³ are independently selected from fluoro, chloro, bromo and iodo;

with the proviso that when R ¹ represents an unsubstituted C 1 -C 20 alkyl, trifluoromethyl, -OR ⁵ , -CH ₂ OR ⁵ or -S-aryl group, m is 3 or 4 or p is equal to 1, 2 or 3.

In a preferred embodiment, at least one R ¹ group is not an unsubstituted alkyl group containing from 1 to 20 carbon atoms.

The R ¹ groups are preferably independently selected from the group consisting of an alkyl group containing from 1 to 20 carbon atoms optionally substituted by one or more substituents selected from the group consisting of fluorine atom, chlorine atom, bromine atom, iodine atom, hydroxy group, - oR ^5, SR ^5, amino, -NHR ^5, -N (R ⁵⁾ 2 and / or -N (R ⁵⁾ 3 ^+; an alkenyl group having from 2 to 20 carbon atoms optionally substituted by one or more substituents selected from the group consisting of fluorine atom, chlorine atom, bromine atom, iodine atom, hydroxy group, a c-C group

-OR, -SR, amino, -NHR,

-N (R ⁵ ) 2, and / or -N (R ⁵ ) 3 ⁺ ; an alkynyl group containing from 2 to 20 carbon atoms optionally substituted by one or more substituents selected from the group consisting of fluorine, chlorine, bromine, iodine, hydroxy, -OR ⁵ , -SR ⁵ , amino, -NHR ⁵ , -N (R ⁵ ) 2, -N (R ⁵ ) ³⁺ , -Si (R ⁵ ) ₃ , -C ₅ H ₄ N, -C ₄ H ₃ S, and / or a -C8H5 group; group φφ φφ • φ φ φφφ φ

φ φ φ φ λ λ • • • • φ φ φ φ φ φ φ φ φ φ

-OR ⁵ ; -SR ⁵ ; -SO ² R ⁵ ; a group -N (R ⁵⁾ 2; -P- (R ⁵ ) 2; -P (O) (OR ⁵ ) 2; -aryl which is optionally substituted with one or more substituents selected from the group consisting of alkyl having from 1 to 10 carbon atoms, alkenyl having from 2 to 10 carbon atoms, nitro, methoxy, fluoro, chloro, bromo, hydroxy, -OR ⁵ , -SO ₃ H, amino, -NHR ⁵ , -N (R ⁵ ) 2, -N (R ⁵ ) ³⁺ , -NHCOR ⁵ , -COR ⁵ , -COOR ⁵ and / or -CON (R ⁵ ) ₂ ; -heteroaryl, optionally substituted with one or more substituents selected from the group consisting of alkyl of from 1 to 4 carbon atoms, alkenyl of from 2 to 10 carbon atoms, nitro, methoxy, fluoro, chloro, bromo, hydroxy, amino, -NHR ⁵ , -N (R ⁵ ) 2, -N (R ⁵ ) ³⁺ , -NHCOR ⁵ , -COR ⁵ , -COOR ^5, and / or -CON (R 5) ⁵ ) 2; -COR ⁵ ; -COOR ⁵ and -CON (R ⁵ ) 2; wherein the R ⁵ groups are independently selected from the group consisting of an alkyl group having from 1 to 20 carbon atoms, an alkenyl group having from 2 to 20 carbon atoms, an aryl group, a heteroaryl group, a hydrogen atom, or two R ⁵ groups may be taken together or an unsaturated ring.

More preferably, the R ¹ groups are independently selected from the group consisting of C 1 -C 20 alkyl optionally substituted by one or more substituents selected from the group consisting of fluorine, chlorine, bromine, iodine, hydroxy, -OR ⁵ , -SR ⁵ , amino and / or -NHR ⁵ ; an alkenyl group containing from 2 to 20 carbon atoms which is aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa Aaa a and aaa aaaa optionally substituted with one or more substituents selected from the group consisting of fluorine, chlorine, bromine, iodine, hydroxy, -OR ⁵ , -SR ⁵ , amino, and / or - NHR ⁵ ; (C 2 -C 20) alkynyl optionally substituted by one or more substituents selected from the group consisting of fluorine, chlorine, bromine, iodine, hydroxy, -OR ⁵ , -SR ⁵ , amino, and / or -NHR ⁵ ; -OR ⁵ ; -SR ⁵ ; -SO ² R ⁵ ; a group -N (R ⁵⁾ 2; -P- (R ⁵ ) 2; an aryl group optionally substituted by one or more substituents selected from the group consisting of alkyl of 1 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, nitro, methoxy, fluoro, chloro, bromo, hydroxy , -OR ⁵ , -SO 3 H, amino, and / or -NHR ⁵ ; -heteroaryl optionally substituted by one or more substituents selected from the group consisting of alkyl of 1 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, nitro, methoxy, fluoro, chloro, bromo, hydroxy , amino and / or -NHR ^5; -COR ⁵ ; -COOR ⁵ and -CON (R ⁵ ) 2; wherein the R ⁵ groups are independently selected from the group consisting of an alkyl group having from 1 to 20 carbon atoms, an alkenyl group having from 2 to 20 carbon atoms, an aryl group, a heteroaryl group, a hydrogen atom, or two R ⁵ groups may be taken together or an unsaturated ring.

More preferably, R ¹ is independently selected from the group consisting of an alkyl group containing from 1 to 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9

99999 99 999 9 9 fe ·········· fefe ·· fefe fefe fe ··· carbon atoms which is substituted by one or more substituents selected from the group consisting of fluorine atom, chlorine atom, bromine atom, iodine, hydroxy, amino, -NHR ⁵ , -N (R ⁵ ) 2 and / or -N (R ⁵ ) 3 ⁺ ; an alkenyl group containing from 2 to 20 carbon atoms; an alkynyl group containing from 2 to 20 carbon atoms; -SR ⁵ ; a group -N (R ⁵⁾ _2; an aryl group optionally substituted by one or more substituents selected from the group consisting of alkyl of 1 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, nitro, methoxy, fluoro, chloro, bromo, hydroxy , amino, -NHR ⁵ , -N (R ⁵ ) 2, -N (R ⁵ ) ³⁺ , -NHCOR ⁵ , -COR ⁵ , -COOR ^5, and / or -CON (R ⁵⁾ ) ₂ ; wherein the R ⁵ groups are independently selected from the group consisting of an alkyl group having from 1 to 20 carbon atoms, an alkenyl group having from 2 to 20 carbon atoms, an aryl group, a heteroaryl group, a hydrogen atom, or two R ⁵ groups may be taken together or an unsaturated ring.

More preferably, the R ¹ groups are independently selected from the group consisting of an alkyl group containing from 1 to 20 carbon atoms which is fully substituted with substituents selected from the group consisting of a fluorine atom, a chlorine atom and / or a bromine atom; an alkenyl group containing from 2 to 20 carbon atoms; an alkynyl group containing from 2 to 20 carbon atoms; -SR ⁵ ; an aryl group optionally substituted by one or more substituents selected from the group consisting of methyl, nitro, methoxy, fluoro, chloro, bromo, 99 and / or hydroxy and / or amino; wherein the R ⁵ groups are independently selected from the group consisting of an alkyl group having from 1 to 20 carbon atoms, an alkenyl group having from 2 to 20 carbon atoms, an aryl group, a heteroaryl group, a hydrogen atom, or two R ⁵ groups may be taken together or an unsaturated ring.

The group R ¹ may be a peripheral or a non-peripheral substituent. In a preferred embodiment of the invention at least one R ¹ group is a non-peripheral substituent.

The compound of formula (IV) may be substituted or linked to an amino acid, a fatty acid, a nucleic acid, a di-, tri- or even decapeptide, polypeptide, protein, carbohydrate, polysaccharide, or polymer. Preferably, the compound of formula (IV) is substituted or linked to an amino acid, a fatty acid, a nucleic acid, a di-, tri- or even decapeptide, polypeptide, protein, carbohydrate, polysaccharide or polymer via a group R ¹ .

The group R ² is preferably a group

In a preferred embodiment, δ = 0.

* 9 99 9 * IV 99 * 9

9999 9 9 9 9 999 9

999 99 99 9

999 99 99 999 9 9

9,999,999

9999 »9» ^Λ 9 »99 494 ·

Another aspect of the invention is a substituted phthalocyanine of formula I

wherein m are independently 0, 1, 2, 3 or 4;

R ¹ are independently selected from the group consisting of C 1 -C 20 alkyl optionally substituted by one or more substituents selected from F, Cl, B, I, OH, -R ⁴ -OR ⁵ , -R ⁴ -SR ⁵ , amino, -NHR ⁵ , -N (R ⁵ ) ₂ , -N (R ⁵ ) ^3+, and / or -R ⁴ -N- (R ⁵⁾ ) 2; an alkenyl group containing from 2 to 20 carbon atoms optionally substituted by one or more substituents selected from the group consisting of fluorine atom, chlorine atom, bromine atom, iodine atom, hydroxy group, -R ⁴ -OR ⁵ , -R ⁴ -SR ⁵ , amino, -NHR ⁵ , -N (R ⁵ ) ₂ , -N (R ⁵ ) ^3+, and / or -R ⁴ -N- (R ⁵ ) 2; an alkynyl group > 4 &gt;

«9

9 «9»

9 99

Containing from 2 to 20 carbon atoms optionally substituted by one or more substituents selected from the group consisting of fluorine, chlorine, bromine, iodine, hydroxy, -R ⁴ -OR ⁵ , -R ⁴ -S; —R ⁵ , amino, -NHR ⁵ , -N (R ⁵ ) 2, -N (R ⁵ ) ³⁺ , -R ⁴ -N- (R ⁵ ) 2, -Si (R ⁵ ) 3, -C5H4N group, -C4H3S and / or a group -C 6 H _5; -R ⁴ -OR ⁵ ; -R ⁴ -SR ⁵ ; -R ⁴ -SO 3 H; -R ⁴ -SO ² R ⁵ ; -R ⁴ -SO ² N (R ⁵ ) 2; group

-R ⁴ -N- (R ⁵ ) 2; -R ⁴ -P- (R ⁵ ) 2; -R ⁴ -P (O) (OR ⁵ ) ₂ ; -R ⁴ -aryl which is optionally substituted with one or more substituents selected from the group consisting of alkyl of 1 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, nitro, methoxy, fluoro, chloro, atom bromo, hydroxy, -OR ⁵ , -SO 3 H, amino, -NHR ⁵ , -N (R ⁵ ) 2, -N (R ⁵ ) ³⁺ , -NHCOR ⁵ , -COR ⁵ , -COOR ⁵ and / or -CON (R ⁵ ) ₂ ; -R ⁴ -heteroaryl optionally substituted with one or more substituents selected from the group consisting of alkyl of 1 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, nitro, methoxy, fluoro, chloro, atom bromo, hydroxy, amino, -NHR ⁵ , -N (R ⁵ ) 2 - -N (R ⁵ ) ³⁺ , -NHCOR ⁵ , -COR ⁵ , -COOR ^5, and / or -CON ( R ⁵ ) 2; -R ⁴ -COR ⁵ ; -R ⁴ -COOR ⁵ and -R ⁴ -CON (R ⁵ ) 2; where

R ⁴ are independently selected from the group consisting of a chemical bond, - (CH ₂ ) _q -, wherein 3 is an integer from 1 to 20, and the group "4" is an integer from 1 to 20;

· * * * * * * * * · · · ·

- (CH ₂ ) _and CH = CH (CH ₂ ) b -, wherein a and b are integers from 0 to 20, wherein the sum of a and b is from 0 to 20; and

R ⁵ are independently selected from the group consisting of alkyl of 1 to 20 carbon atoms, alkenyl of 2 to 20 carbon atoms, optionally substituted aryl, optionally substituted heteroaryl, hydrogen, or two R ⁵ groups may together to form a saturated or unsaturated ring;

R ² is selected from the group consisting of

p is 0, 1, 2 or 3, with the proviso that all indexes m and all indexes p simultaneously have a value of 0;

R ³ are independently selected from fluoro, chloro, bromo and iodo;

M is a metal atom in the oxidation state of M ²⁺ , metal chloride, metal bromide, metal oxide, silicon with two axial substituents or two hydrogen atoms, each of which is bound by one of these hydrogen atoms;

With the proviso that when all R ¹ groups are the same and represent unsubstituted alkyl groups containing from 1 to 20 carbon atoms, trifluoromethyl groups, -OR ⁵ groups, -CH ₂ OR ⁵ groups, or -S-aryl groups, m is 3 or 4, or p is 1, 2, or 3.

The substituted phthalocyanine of formula I according to this aspect of the present invention may be a non-mixed or mixed phthalocyanine.

In a preferred embodiment, at least one R ¹ group is not an unsubstituted alkyl group containing from 1 to 20 carbon atoms.

The R ¹ groups are preferably independently selected from the group consisting of an alkyl group containing from 1 to 20 carbon atoms optionally substituted by one or more substituents selected from the group consisting of fluorine atom, chlorine atom, bromine atom, iodine atom, hydroxy group, - oR ^5, SR ^5, amino, -NHR ^5, -N (R ⁵⁾ 2 and / or -N (R ⁵⁾ 3 ^+; an alkenyl group having from 2 to 20 carbon atoms optionally substituted by one or more substituents selected from the group consisting of fluorine, chlorine, bromine, iodine, hydroxy, -OR ⁵ , -SR ⁵ , amino, - -NHR ^5, -N (R ⁵⁾ 2 and / or -N (R ⁵⁾ 3 ^+; an alkynyl group containing from 2 to 20 carbon atoms optionally substituted by one or more substituents selected from the group consisting of fluorine, chlorine, bromine, iodine, hydroxy, -OR ⁵ , -SR ⁵ , amino, - NHR ⁵ , -N (R ⁵ ) 2, -N (R ⁵ ) ³⁺ , -Si (R ⁵ ) 3, -C5H 4 N,

9 a -C ₄ H ₃ S group and / or a -C ₅ H _{5 group} ; -OR ⁵ ; -SR ⁵ ; -SO ² R ⁵ ; a group -N (R ⁵⁾ 2; -P- (R ⁵ ) 2; -P (O) (OR ⁵ ) 2; an aryl group optionally substituted by one or more substituents selected from the group consisting of alkyl of 1 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, nitro, methoxy, fluoro, chloro, bromo, hydroxy , -OR ⁵ , -SO 3 H, amino, -NHR ⁵ , -N (R ⁵ ) 2, -N (R ⁵ ) ³⁺ , -NHCOR ⁵ , -COR ⁵ , -COOR ⁵ and / or -CON (R ⁵ ) ₂ ; -heteroaryl optionally substituted by one or more substituents selected from the group consisting of alkyl of 1 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, nitro, methoxy, fluoro, chloro, bromo, hydroxy , amino, -NHR ⁵ , -N (R ⁵ ) 2, -N (R ⁵ ) ³⁺ , -NHCOR ⁵ , -COR ⁵ , -COOR ^5, and / or -CON (R ⁵⁾ ) 2; -COR ⁵ ; -COOR ⁵ and -CON (R ⁵ ) 2; wherein the R ⁵ groups are independently selected from the group consisting of an alkyl group having from 1 to 20 carbon atoms, an alkenyl group having from 2 to 20 carbon atoms, an aryl group, a heteroaryl group, a hydrogen atom, or two R ⁵ groups may be taken together or an unsaturated ring.

More preferably, the R ¹ groups are independently selected from the group consisting of C 1 -C 20 alkyl optionally substituted by one or more substituents selected from the group consisting of fluorine, chlorine, bromine, iodine, hydroxy, -OR ⁵ , -SR ⁵ , amino and / or -NHR ⁵ ;

An alkenyl group containing from 2 to 20 carbon atoms optionally substituted by one or more substituents selected from the group consisting of fluorine, chlorine, bromine, iodine, hydroxy, -OR ⁵ , -SR ⁵ , amino, and / or -NHR ^5; (C 2 -C 20) alkynyl optionally substituted by one or more substituents selected from the group consisting of fluorine, chlorine, bromine, iodine, hydroxy, -OR ⁵ , -SR ⁵ , amino, and / or -NHR ⁵ ; -OR ⁵ ; -SR ⁵ ; -SO ² R ⁵ ; a group -N ^(R5) .2; -P- (R ⁵ ) 2; an aryl group optionally substituted by one or more substituents selected from the group consisting of alkyl of 1 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, nitro, methoxy, fluoro, chloro, bromo, hydroxy , -OR ⁵ , -SO 3 H, amino, and / or -NHR ⁵ ; -heteroaryl optionally substituted by one or more substituents selected from the group consisting of alkyl of 1 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, nitro, methoxy, fluoro, chloro, bromo, hydroxy , amino and / or -NHR ^5; -COR ⁵ ; -COOR ⁵ and -CON (R ⁵ ) ₂ ; wherein the R ⁵ groups are independently selected from the group consisting of an alkyl group having from 1 to 20 carbon atoms, an alkenyl group having from 2 to 20 carbon atoms, an aryl group, a heteroaryl group, a hydrogen atom, or two R ⁵ groups may be taken together or an unsaturated ring.

• »’

98 9 9 9

9999

More preferably, R ¹ is independently selected from the group consisting of C 1 -C 20 alkyl substituted with one or more substituents selected from fluorine, chlorine, bromine, iodine, hydroxy, amino , -NHR ⁵ , -N (R ⁵ ) 2 and / or -N (R ⁵ ) 3 ⁺ ; an alkenyl group containing from 2 to 20 carbon atoms; an alkynyl group containing from 2 to 20 carbon atoms; -SR ⁵ ; a group -N (R ⁵⁾ _2; an aryl group optionally substituted by one or more substituents selected from the group consisting of alkyl of 1 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, nitro, methoxy, fluoro, chloro, bromo, hydroxy , amino and / or -NHR ⁵ , -N (R ⁵ ) 2, -N (R ⁵ ) ³⁺ , -NHCOR ⁵ , -COR ⁵ , -COOR ^5, and / or -CON ( R ⁵ ) ₂ ; wherein the R ⁵ groups are independently selected from the group consisting of alkyl of 1 to 20 carbon atoms, alkenyl of 2 to 20 carbon atoms, aryl, heteroaryl, hydrogen, or two R ⁵ groups may be taken together to form a saturated group or an unsaturated ring.

More preferably, the R ¹ groups are independently selected from the group consisting of an alkyl group containing from 1 to 20 carbon atoms which is fully substituted with substituents selected from the group consisting of a fluorine atom, a chlorine atom and / or a bromine atom; an alkenyl group containing from 2 to 20 carbon atoms; an alkynyl group containing from 2 to 20 carbon atoms; -SR ⁵ ; an aryl group optionally substituted with one or more substituents selected from the group consisting of:

From the group consisting of methyl, nitro, methoxy, fluoro, chloro, bromo, hydroxy and / or amino; wherein the R ⁵ groups are independently selected from the group consisting of an alkyl group having from 1 to 20 carbon atoms, an alkenyl group having from 2 to 20 carbon atoms, an aryl group, a heteroaryl group, a hydrogen atom, or two R ⁵ groups may be taken together or an unsaturated ring.

The group R ¹ may be a peripheral or a non-peripheral substituent. In a preferred embodiment of the invention at least one R ¹ group is a non-peripheral substituent.

The compound of formula (I) may be substituted or linked to an amino acid, a fatty acid, a nucleic acid, a di-, tri- or even decapeptide, polypeptide, protein, carbohydrate, polysaccharide, or polymer. Preferably, the compound of formula (I) is substituted or linked to an amino acid, a fatty acid, a nucleic acid, a di-, tri- or even decapeptide, polypeptide, protein, carbohydrate, polysaccharide or polymer through the group R ¹ .

In a preferred embodiment of the invention, the phthalocyanine of formula I is a non-mixed phthalocyanine, or when said phthalocyanine of formula I is substituted with -SR ⁵ , the sum of maps 4 or 8 is not.

Preferably, R ² is fc fc fc fcfc fcfc fcfc fcfc fcfc fcfc fcfc fcfc fcfc fcfc fcfc fcfc fcfc · • fc

In a preferred embodiment, p = 0.

The group M is preferably an isotope of copper, nickel, lead, vanadium, palladium, platinum, cobalt, niobium, aluminum, tin, zinc, magnesium, calcium, indium, gallium, iron, germanium, lanthanide, silicon with two axial substituents or two atoms hydrogen. More preferably, the group is an isotope of a diamagnetic metal, silicon having two axial substituents or two hydrogen atoms. Even more preferably, the M group is an isotope of zinc, aluminum, magnesium, palladium, platinum, silicon with two axial substituents or two hydrogen atoms.

More preferably p = 0;

R ¹ are independently selected from the group consisting of C 2 to C 20 alkyl which is fully substituted with substituents selected from fluoro, chloro and / or bromo; an alkenyl group containing from 2 to 20 carbon atoms; an alkynyl group containing from 2 to 20 carbon atoms; -SR ⁵ ; an aryl group optionally substituted by one or more substituents selected from the group consisting of methyl, nitro, methoxy, fluoro, chloro, bromo, hydroxy and / or amino; wherein the R ⁵ groups are independently selected from the group consisting of an alkyl group having from 1 to 20 carbon atoms, an alkenyl group having from 2 to 20 carbon atoms, an aryl group, a heteroaryl group, a hydrogen atom, or two R ⁵ groups may be taken together or an unsaturated ring;

* 9

9

9 9 9 99 •

· 9 · 9

group is a group R ^2;

the group M is an isotope of zinc, aluminum, magnesium, palladium, platinum, silicon with two axial substituents or two hydrogen atoms.

The compound of formula I and / or V may optionally form a sandwich complex containing two or more compounds of formula I and / or V.

Optionally, a multimer comprising two or more compounds of formula (I) and / or (V), which are bound together by covalent bonds, may be prepared according to the invention. In a preferred embodiment, said covalently bonded compounds of formula I and / or V are covalently bonded together via the substituents R ¹ , R ⁸ and / or R ⁹ .

The substituted phthalocyanine of the invention is optionally bound to a carrier or trapped or incorporated into a macromolecular carrier. In a preferred embodiment said carrier is an amino acid, a fatty acid, a nucleic acid, a di-, tri- or up to decapeptide, polypeptide, carbohydrate, polysaccharide or polymer. When said substituted phthalocyanine is bound to a carrier, it is preferably bound via R ¹ , R ⁸ or R ⁹ .

If the macromolecular carrier is a polypeptide, the polypeptide is preferably an antibody.

When said macromolecular carrier is a polymer, the substituted phthalocyanine of the invention is preferably trapped or incorporated into a solid polymer or bound to a soluble polymer. In a more preferred embodiment, said solid polymer is selected from the group consisting of polyesters, polyorthoesters, polyanhydrides, tyrosine-derived pseudopolyamino acids and polyphosphazenes, or said soluble polymer is selected from the group consisting of N- (2-hydroxypropyl) methacrilamide (HMPA) copolymers, polyvinylpyrrolidone (PVP) , polyethylene glycol (PEG) polymers, copolymers or block copolymers, amino acid polymers and polyesters. In a preferred embodiment of the present invention, the solid or soluble polymer is a biodegradable polymer.

In a preferred embodiment, the substituted phthalycyanine of the invention is for use as a medicament. The medicament is preferably intended for use in the photodynamic therapy of a human or animal disease.

Thus, a further aspect of the present invention is a pharmaceutical composition comprising the substituted phthalocyanine of the invention or a pharmaceutically acceptable salt thereof in admixture or in association with a pharmaceutically acceptable carrier, diluent or excipient.

Preferably, said pharmaceutical composition is in a form suitable for topical, subcutaneous, mucosal, parenteral, systemic, intraarticular, intravenous, intramuscular, intracranial, rectal or oral administration.

The pharmaceutical composition of the present invention is preferably intended for use in the photodynamic therapy of human 9 99 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9

99 or animal diseases. The human or animal disease is preferably characterized by benign or malignant cell proliferation or neovascularization regions. Preferably, said human or animal disease is a viral, fungal or bacterial or prion-induced disease.

Preferably, said human or animal disease is a tumor, rheumatoid arthritis, inflammatory arthritis, haemophilia, osteoarthritis, vascular stenosis, vascular restinosis, atheromas, hyperplasia, vascular internal wall hyperplasia, benign prostatic hyperplasia, psoriasis, mycosis or liqueus fungoides, eczema, eczema, eczema .

The radiation source is preferably a laser or an incoherent radiation source emitting light of optimal wavelength.

Another aspect of the invention is the use of the substituted phthalocyanines of the present invention for the manufacture of a phototherapeutic agent for use in photodynamic therapy. In a preferred embodiment, said phototherapeutic agent is used to treat a disease characterized by benign or malignant cell proliferation. Preferably, said phototherapeutic agent is used to treat a viral, fungal, bacterial or prion-induced disease. Preferably, said phototherapeutic agent is used for the treatment of a disease such as tumor, rheumatoid arthritis, inflammatory arthritis, hemophilia, osteoarthritis, vascular stenosis, vascular restinosis, atheromas, hyperplasia, vascular internal wall hyperplasia, benign prostatic hyperplasia, psoriasis, mycosis fungoes , keratosis from radiation or lichen.

• 4

4

444 4 ·

4

4 ··· • 43 4

4 4 4

4 4 ·

44

Another aspect of the present invention is the use of the substituted phthalocyanine of the invention for the production of a photodiagnostic agent for identifying regions that are pathologically infected by cell proliferation.

Another aspect of the present invention is a material comprising the substituted phthalocyanine of the present invention, wherein the optical or physical properties of the material may vary due to incident radiation. In a preferred embodiment, the incident radiation is electromagnetic radiation. More preferably, the incident radiation is electromagnetic radiation having a wavelength in the range of 200 nanometers to

1000 nanometers.

As shown in Scheme 7, a substituted phthalocyanine of formula I may be prepared by cyclizing the substituted phthalonitrile of formula IV, either alone or in admixture with another phthalonitrile of formula IV. For the phthalonitriles of formula IV, this may be prepared from a phthalonitrile sulfonate ester of formula III, which may be prepared from a suitable phthalonitrile alcohol of formula II.

Scheme 7

The phthalonitrile sulfonate ester of formula III can be prepared from the phthalonitrile alcohol of formula II under suitable conditions. As an illustration of the preparation of esters of phthalonitrilsulfonates of formula III, the preparation of 3,6- (trifluoromethanesulfonyloxy) phthalonitrile (triflate), 2,3-dicyano-1,4- (trifluoromethanesulfonyloxy) naphthalene (triflate) and 3,6- ( nonafluorobutanesulfonyloxy) phthalonitrile (nonaflate).

Aryltriflates (i.e., trifluoromethanesulfonyl) are usually prepared in excellent yields by reacting phenols with trifluoromethanesulfonic anhydride in the presence of a base such as triethylamine or pyridine at low temperature.

ΦΦ φ φ · * · · φ φ φ φ · · · · · · · · · φ φ φ φ φ φ φ φ φ φ φ · φ φ φ φ φ φ

Itterφφ · φφφ φφφφφφ (see Ritter, Synthesis, 1993, 735; J. Stang, M. Hanack, L. R. Subramanian, Synthesis, 1982, 82). However, said reaction of 2,3-dihydroquinone with triethylamine or pyridine and trifluoromethanesulfonic anhydride at -20 ° C was not effective because said starting compound is poorly soluble in both solvents. The addition of a co-solvent such as dichloromethane also failed to increase the yield of the reaction. However, hydroquinone could be converted to the corresponding triflate in high yield (91 percent) using 2,6-lutidine or 2,4, β-collodine as a base in the presence of dichloromethane.

Trifluoromethanesulfonic anhydride was then added dropwise at -20 ° C to a solution of dihydroquinone in dichloromethane / lutidine (3: 1). After stirring the mixture for one day at room temperature, simple aqueous work-up of the reaction mixture, followed by recrystallization from dichloromethane / petroleum ether or ethyl acetate / cyclohexane, gave 3,6- (trifluoromethanesulfonyloxy) phthalonitrile in good yield, hitherto not described. in the form of yellow crystals. It was prepared in a similar manner

2,3-Dicyano-1,4- (trifluoromethanesulfonyloxy) naphthalene.

Arylnonaphlates (nonafluorobutanesulfonyl) are usually prepared by reacting phenols with nonafluorobutanesulfonyl fluoride. However, all attempts to prepare 2,3-dicyanohydroquinone nonaflate under the conditions described above failed, probably due to the lesser ability of the fluoride anion to behave as a leaving group compared to the triflate anion.

However, the use of sodium hydride as the base in tetrahydrofuran has resulted in a distinct reaction in high yield, with a simple aqueous solution of sodium hydride. work up of the reaction mixture was isolated, previously not described, 3,6- (nonafluorobutanesulfonyloxy) phthalonitrile.

Accordingly, the present invention provides a phthalonitrile sulfonate ester of formula III and a process for its preparation.

The substituted phthalonitrile of formula IV can be prepared from a sulfonate ester of formula III under various conditions, such as, for example, palladium-catalyzed cross-coupling with an organo-zinc reagent or a copper-copper reagent (method A), palladium-catalyzed cross-linking with a trialkylborane ( method C), palladium catalyzed cross-linking with boronic ester (method D), _{N N} Ar reaction with nucleophiles (method E), or palladium catalyzed addition with a suitable addition partner (method F). The methods are described below.

Methods A and B - Cross-addition between palladium or nickel catalyzed palladium or nickel catalyzed phthalonitrile sulfonate ester of formula III and organo-zinc reagent or organo-copper reagent to form alkylated phthalonitrile of formula IV:

A palladium-catalyzed cross-coupling reaction between aryl iodide and an organozinc reagent (the so-called Negishi reaction) was first described in 1977 in publication E.

Negishi, A. O. King, N. Okukado, J. Org. Chem., 1977, 42, 1821. The reaction was somewhat overlooked until the late 1980s, when interest in this reaction was renewed (see P Knochel, JJ Perea, P.Jones, Tetrahedron, 1998, 54,

8275). Unlike organolithium compounds or

Grignard reagents that are also subject to cross-linking reactions are organo-zinc reagents unreactive to a wide variety of functional groups (see P. Knochel, R. D. Singer, Chem. Rev., 19-93, 93, 2117). This is important because it allows the compounds involved in the reaction, whether the organo-zinc reagent itself or the addition partner, to contain a wide range of functional groups. Tolerated functional groups include ketones, esters, amides, nitriles, acetals, alkenes and alkynes. In addition to aryl and alkenyl halides, aryl and alkenyl triphlates can also be used as addition partners in this reaction (K. Ritter, Synthesis, 1993, 735; P. Knochel, J. Perea, P. Jones, Tetrahedron, 1998, 54, 8275; E. Erdik (Tetrahedron, 1992, 48, 95.77).

Polyfunctional organo-zinc halides can be readily prepared by direct insertion of zinc into alkyl iodides. Thus, decylzinc iodide was prepared by adding a concentrated solution (approximately 3 molar) of 1-iododecane in tetrahydrofuran (THF) to a suspension of zinc dust (3 equivalents) in tetrahydrofuran (THF) at 40 ° G. The zinc dust was activated with a small amount of dibromoethane and trimethylsilyl chloride (TMSCl) prior to the addition of said halide. After heating the mixture at 40 ° C for 12 hours, the preparation of decylzinc iodide was complete.

There are also several variants to this procedure. Organo-zinc compounds can also be prepared by metathesis of Grignard or organolithium reagent with anhydrous zinc bromide or zinc chloride in tetrahydrofuran (THF). This method was also used in the preparation of decylzinc chloride.

9 · · · · · · · · ·

··

However, there are many problems associated with the use of this synthesis approach, including the fact that the magnesium chloride formed in the reaction as a by-product tends to clog the stirrer and makes it difficult to transfer the product through the capillary. Another problem in using this synthesis approach is the fact that zinc chloride is very hygroscopic and therefore very difficult to dry. However, 1-octinylzinc chloride was successfully prepared by metathesis of 1-octinyllithium zinc chloride at -78 ° C.

A third method that can be mentioned in this context is to insert more activated zinc (Rieke zinc), which is prepared by reducing zinc halides, to less active alkyl bromides or even aryl bromides. Thus, the reaction of zinc chloride with finely chopped lithium in the presence of naphthalene produces a very reactive zinc, which reacts with, for example, methyl 3-bromobutyrate in boiling tetrahydrofuran (THF) to form a secondary zinc reagent (see L. Zhu, RM Wehmeyer). , RD Rieke, J. Org. Chem., 1991, 56, 1445; V. V. Hanson, RD Rieke, J. Am. Chem. Soc., 1995, 117, 10775; V. V. Hanson, RD Rieke,

Tetrahedron, 1997, 53, 1925).

Many aryl and heteroaryl zinc halides can be prepared by one of the three methods described above (P. Knochel,

J. J. A. Perea, P. Jones, Tetrahedron, 1998, 54, 8275).

A preferred procedure for preparing such a simple alkyl zinc reagent, such as decylzinc iodide, is by direct insertion of zinc into iododecane. 1-Octinylzinc iodide was best prepared by metathesis of 1-octinyllithium and zinc chloride at -78 ° C. A somewhat exotic zinc reagent, which was 6-chlorhexyl zinc bromide [Cl (CH ₂ ) ₂ ZnBr], was obtained from Aldrich Chemical Company using Rieke zinc to prepare this compound. Rieke zinc solution in tetrahydrofuran (THF) is also commercially available from Aldrich Chemical Company.

Initially, the cross-reactions were carried out under more conventional palladium catalysis conditions (i.e., method A). Various palladium catalysts have been used for this reaction, including Pd (PPh ₃ ) ₄ (E. Erdik, Tetrahedron, 1992, 48,

9577), bis (tri-o-tolylphosphine) palladium dichloride (E. Nakamura, I. Kuwajima, Tetrahedron Lett., 1986,

27, 83), PdCl ₂ (dppf) (see T. Hayashi, Konishi M., Kobori Y, Kumada M., Higuchi T., Hirotsu K., J. Am. Chem. Soc., 1984, 106 158) and bis (tri-o-furylphosphine) palladium dichloride (V. Farin, B. Krishnan, J. Am. Chem. Soc.

1991, 113, 9585). The last three catalysts, which carry loosely bonded sterically bulky phosphine ligands, prevent the formation of biaryls by transferring a phenyl group from the triphenylphosphine ligand, and using them results in excellent results.

As a representative example of a cross-coupling reaction according to Method A, Pd (PPh ₃ ) ₄ -catalyzed cross-addition of 3,6- (trifluoromethanesulfonyloxy) phthalonitrile with decylzinc iodide is described below. In this reaction, lithium chloride was added to the reaction mixture as a cocatalyst. Although its role is not well known, lithium chloride helps prevent biaryl formation and stabilizes the catalyst (see M. Fujita, H. Oka, K. Ogura, Tetrahedron Lett., 1995, 36, 5247;

K. Ritter, Synthesis, 1993, 735).

·· · * ·

9 9 9 · 9 9 9

9 9 9 9

999 99 99 99

To a solution of 3,6- (trifluoromethanesulfonyloxy) phthalonitriles, molar percent Pd (PPh ₃ ) ₄ and 3 equivalents of lithium chloride in tetrahydrofuran (THF) was added 2.5 equivalents of decylzinc iodide and the resulting reaction mixture was heated to reflux for 12 hours under argon. . After cooling and filtering to remove precipitated palladium, TLC analysis showed the mixture to contain 3,6-didecylphthalonitrile (by comparison with a known sample) and a slower product believed to be 3-decyl-6- (trifluoromethanesulfonyloxy) phthalonitrile. Thus, it has been found that palladium is a functional cross-addition catalyst according to Method A.

Nickel catalysis (method B) is an attractive alternative to palladium catalysis, both because of the cost of the metal and because of the increased reactivity of the nickel during the oxidation insertion into the carbon halide or carbon triflate bond. Snieckus and coworkers investigated the cross-coupling reaction of organotriflates with aryl zinc reagents under various conditions (CA Quesnell, A. B. Familoni, V. Snieckus, Synlett, 1994, 349). They included many nickel catalysts in their experiments, including Ni (acac) ₂ , Ni (acac) ₂ / PPh ₃ and NiCl ₂ (PPh ₃ ) _2. All catalysts were active to some extent, but PPh ₃ stabilized nickel catalysts were among the most active. Quite recently, Lipshutz and coworkers have described a nickel catalyzed cross-addition of aryl chlorides and one aryltriflate with an alkyl zinc reaction. with NiCl ₂ (PPh ₃ ) ₂ / 2PPh ₃ as the catalyst (see BH Lipshutz, PA Blomgren, SK. Kim, Tetrahedron Lett., 1999, 40, 197).

• 99

V »*»

9 9

9 9 9

99

99

9 9 ·

9 9

9 9

9 9

9999

Exemplary cross-additions of Method B disclose cross-additions of 3,6- (trifluoromethanesulfonyloxy) phthalonitriles with decylzinc iodide, 6-chlorhexylzinc bromide and 1-octinylzinc chloride catalyzed by NiCl 2 (PPh ₃ ) _{2 /} 2PPh ₃ .

The nickel catalyst was formed in situ by reacting 10 mole percent NiCl ₂ (PPh ₃ ) ₂ and 20 mole percent PPh ₃ in tetrahydrofuran (THF) at room temperature with 20 mole percent n-butyllithium to form a blood-colored nickel catalyst which was Ni (PPh ₃ ) ₄ . DIBAL or MeMgBr may be used instead of n-butyllithium to form the catalyst (CA Quesnell, OB Familoni, V. Snieckus, Synlett, 1994, 349). To this catalyst was added solid 3,6- (trifluoromethanesulfonyloxy) phthalonitrile in an argon stream at room temperature. The resulting solution was cooled to -78 ° C, treated with a tetrahydrofuran (THF) solution containing 2.5 equivalents of decylzinc iodide and

2.5 equivalents of lithium chloride. The reaction mixture was allowed to warm to room temperature and stirred at this temperature for 16 hours. The mixture was then quenched with 5% hydrochloric acid and extracted with ethyl acetate. The organics were washed with acid and base, dried and concentrated until precipitation of a solid began. The resulting solution was allowed to crystallize, yielding 3, β-didecylphthalonitrile contaminated with PPh ₃ . Triphenylphosphine can be removed by stirring the solid in acetonitrile in which 3,6-didecylphthalonitrile is not soluble. Subsequent filtration of the resulting suspension gave the product as white crystals with a yield of 60 to 70 percent.

0 «· ·

0 • 00 »

0 «·

0 · ·· · 0 · · 0 00

0 0

0 0 0 0 0 0 0

0 0 0

0 ·· 0

Using 6-chlorhexyl zinc bromide as the zinc reagent under the above described reaction conditions, 3,6-bis (6'-chlorhexyl) phthalonitrile was readily prepared in a yield of 61 percent. The introduction of a halogenated alkyl chain using the previously described, known thiophene and furan synthesis approach is not readily accomplished. It was prepared in a similar manner

3,6-bis (4'-chlorobutyl) phthalonitrile, 3,6-bis (4-pivaloyloxybutyl) phthalonitrile, 3,6-bis (4-tert-butyldimethylsilyloxybutyl) phthalonitrile and 3,6-bis (1,1H-2) (2-H-perfluorodecyl) phthalonitrile. Of course, one skilled in the art of organic chemistry will recognize that functionality in the substituent chain can be altered by standard procedures involving functional group interconversions. For example, 3,6-bis (6'-chlorhexyl) phthalonitrile was reacted with imidazole to give 3,6-bis (6'imidazol-1-ylhexyl) phthalonitrile. Some of the functional groups described herein can be readily converted to terminal hydroxy groups that are attached at the substituent ends. Conversion of appropriately substituted phthalonitriles can be used to form dimeric or oligomeric structures by standard reactions such as the reaction of terminal alcohol groups with diesters or dicarboxylic acid dichlorides.

The use of an alkynyl zinc chloride reagent, which is prepared by reacting an alkynyl lithium reagent with zinc chloride, has produced alkynylated phthalonitriles. Thus, 3,6-bis (1'-octinyl) phthalonitrile was prepared by cross-coupling from 1-octinylzinc chloride.

This type of chemical reaction is generally readily feasible, although care must be taken to avoid the presence of water in the reaction mixture. Lipshutz states that in · *

ΦΦ • φ

in the case of less reactive aryl chlorides, the addition of the organo-zinc reagent is best carried out at -78 ° C. An attempt to make the same addition using decylmagnesium chloride instead of decylzinc iodide was unsuccessful and only polymeric products were obtained in this reaction. This result is probably due to the much more reactive Grignard reagent likely attacking the nitrile functionality.

Method C - Cross-addition between palladium-catalyzed phthalonitrile sulfonate ester of formula III and trialkylborane to form alkylated phthalonitrile of formula IV:

The reaction of aryl halides and aryl triflates with boron reagents has been extensively investigated by Suzuki et al. (N. Miyaura, A. Suzuki, Chem. Rev., 1995, 95, 2547). Cross-addition of aryl compounds with an alkyl boronic reagent (the Suzuki-Miyaur reaction) is an effective tool for forming aryl-alkyl bonds between carbon atoms and has been studied for both aryl halides (N. Miyaura, T. Ishiyama, H. Sasaki, M. Ishikawa, M. Sato, A. Suzuki, J. Am. Chem. Soc., 1989, 111, 314), as well as for aryltriflates (see T. Oh-e, N. Miyaura, A. Suzuki, J. (Org. Chem., 1993, 53, 2201).

Alkyl boron reagents are readily available by hydroboration of alkenes, so that at least theoretically it is possible to introduce a wide range of alkyl groups in this way. The most commonly used reagent for transferring an alkyl group is

9-alkyl-9-borabicyclo [3.3.1] nonane (or 9-alkyl-9-BBN), ♦ · · · ·

The primary alkyl groups are preferably transferred via this derivative. This derivative is prepared from alkene and 9-borabicyclo [3.3.1] nonane (9-BBN). However, the use of simple trialkylbores, which are prepared by reaction of alkenes with BH ₃ , is cheaper because 9-borabicyclo [3.3.1] nonane (9-BBN) is relatively expensive.

The above-described cross-linking involves the reaction of the aryl triflate with a palladium catalyst, a boron reagent and a base at an elevated temperature (i.e., at a temperature ranging from 50 ° C to 90 ° C), usually in a solvent such as tetrahydrofuran (THF) or 1,4 -dioxane. The use of the base is necessary for the reaction to proceed at all, since this base greatly increases the nucleophilicity of the organoboron compound, thereby accelerating the subsequent transmetallation reaction with the organopalladium complex (K. Matos, JA Soderquist, J. Org. Chem., 1998, 63, 461). Many different bases have been used in this reaction, although some of the best bases such as sodium methoxide (NaOMe) (A. Furstner, G. Seidel, J. Org. Chem., 1997, 62, 2332) and sodium hydroxide are used. (NaOH) (T. Ohe, Miyaura N., Suzuki A., J. Org. Chem., 1993, 53, 2201) are clearly incompatible with the nitrile functionality.

For this reason, the use of weaker bases such as potassium carbonate (K ₂ CO ₃ ) and potassium phosphate (K ₃ PO ₄ ) has been investigated (K. Matos, JA Soderquist, J. Org. Chem., 1998, 63, 461). In addition, several different palladium catalysts have been investigated, with the best results being achieved with PdCl ₂ (dppf).

The results obtained under the different reaction conditions, but always using tridecylborane, are summarized in Table 1. For all 4

4 444 4 β • 4

·· · 4 · 4 · · ·

4 4 4

4 4

In 4449 reactions, lithium chloride (3 equivalents) was added to the reaction mixture as a cocatalyst. The best results were obtained when tridecylborane was prepared in situ, ie. such that a solution of borane (0.33 equivalents) in tetrahydrofuran (THF) was added to 1-decene at 0 ° C. After stirring for 4 hours, the reaction to form tridecylborane was complete and the base was added to the reaction mixture. The mixture was stirred for 1 hour to form a borate complex, palladium catalyst and 3,6- (trifluoromethanesulfonyloxy) phthalonitrile were added thereto, and the resulting mixture was heated to boiling for 10 hours. The solvents were removed under reduced pressure and the residue was purified by column chromatography to give 3,6-didecylphthalonitrile in a lower yield. The low yields were probably due to the effect of the base on phthalonitrile, since the reaction also produced a large amount of black tar-like product.

Table 1

Catalyst Base Solvent Temperature Yield Pd (PPh _{3) 4} K ₂ CO ₃ THF Reflux (55) None product Pd (PPh _{3) 4} K ₃ PO ₄ THF Reflux (55) None product Pd (PPh _{3) 4} NaOH (aq) THF Reflux (55) None product Pd (PPh _{3) 4} K ₃ PO ₄ Dioxane Reflux (85) None product* PdCl ₂ (dppf) K ₃ PO ₄ THF Reflux (55) 38% * PdCl ₂ (dppf) K3CO3 THF Reflux (55) 29% * * tridecyl .boran was created in situ

• · ··· * ·

Method D - Cross-addition between palladium or nickel-catalyzed phthalonitrile sulfonate ester of formula III and boronic acid or ester thereof to give substituted phthalonitriles of formula IV:

Cross-addition of an aryl compound and a boronic acid or ester thereof (the Suzuki reaction) is a general method of adding an aromatic ring to an unsaturated addition partner. The reaction comprises palladium or nickel catalyzed addition of a boronic acid or ester thereof with an aryl halide or triflate under mildly basic conditions. Said mildly basic conditions allow * any of the addition partners to contain a wide range of functional groups.

As specific examples of cross-coupling reactions according to Method D, cross-additions of 3,6-bis (trifluoromethanesulfonyloxy) phthalonitriles to phenylboronic acid are described herein.

Pd (PPh ₃ ) ₄ catalysed 3-methoxyphenylboronic acid and 4-methoxyphenylboronic acid. To a solution of 3,6-trifluoromethanesulfonyloxy) phthalonitrile in toluene was added 2.5 equivalents of lithium chloride and 6 molar percent Pd (PPh ₃ ) under argon. · Phenylboronic acid and sodium carbonate as a base were added sequentially to the reaction mixture, and the resulting mixture was refluxed for 14 hours. Simple aqueous work-up of the reaction mixture followed by recrystallization from toluene yielded 3, β-diphenylphthalonitrile in 79% yield. Similarly, 3,6-bis (4-methoxyphenyl) phthalonitrile and 3,6-bis (3-methoxyphenyl) phthalonitrile were prepared by cross-linking 3,6- (trifluoromethanesulfonyloxy) phthalonitriles with 4-methoxyphenylboronic acid and 3-methoxyphenylboronic acid, respectively. .

9 «99»

9

Method E - S _N Ar reacting a phthalonitrile sulfonate ester of formula III with a nucleophile to form a substituted phthalonitrile of formula IV:

Nucleophilic aromatic substitution (S _N Ar) reactions are in progress; very difficult for electron and steric reasons. However, in the case of S _N Ar reactions, which still take place, it is assumed that these reactions take place via the Meisenheimer complex or the benzyne intermediate. Arenas containing strongly electron-acceptor groups at the ortho and / or para position to the site of substitution may be subject to S _N Ar reactions that take place through an addition / elimination mechanism (ie, through the Meisenheimer complex). The reaction of arenes with a strong base may elicit an S _N Ar reaction through an elimination / addition mechanism (i.e. via a benzyne intermediate).

As an exemplary embodiment of Method E, the S _N Ar reaction of 3,6-bis (trifluoromethanesulfonyloxy) phthalonitrile with alkylthiols starting from hexylthiol to dodecylthiol is further described. Typically, the reaction of 3,6-bis (trifluoromethanesulfonyloxy) phthalonitrile dissolved in N, N-dimethylformamide (DMF) with dodecylthiol and potassium carbonate resulted in S _N Ar substitution of the triflate after stirring the reaction mixture at room temperature for 72 hours. Reaction of 3,6-bis (trifluoromethanesulfonyloxy) phthalonitrile with other alkylthiols under similar conditions also resulted in S _N Ar substitution of the triflate. These reactions thus represent an easy synthesis route to previously unknown 3,6-bis (alkylsulfanyl) phthalonitriles.

It is also possible to prepare amino-substituted phthalonitriles by Method E, in which case the reaction is carried out

444 4444 use amines, such as piperidine, morpholine, as nucleophiles, pyrrolidine or piperazine, and an example of the feasibility of this reaction is the reaction of said triflate with piperidine. S _N Ar reactions can be promoted by using cesium carbonate as the base and nonaflate instead of the triflate (see, e.g., L. Neuville, A. Bigot, M.

E. T. H. Dau, J. Zhu, J. Org. Chem., 1999, 64, 7638). Alternatively, palladium catalyzed amination may be used to prepare these derivatives (A.J. Belfield, Tetrahedron, 1999, 55, 11399).

Method F - Addition between palladium-catalyzed palladium-catalyzed phthalonitrilsulfonate ester of formula III and an unsaturated addition partner to form alkylated phthalonitriles of formula IV:

The addition of an alkene and an aryl halide or triflate is known as the Heck reaction. The reaction is again catalyzed by palladium and usually proceeds at high temperature and in the presence of an amine base.

As an example of the addition reaction of Method F, palladium catalyzed addition of 3,6-bis (trifluoromethanesulfonyloxy) phthalonitriles with 1-decene is described herein. The reaction was carried out using 3,6-bis (trifluoromethanesulfonyloxy) phthalonitriles and 1-decene under conventional conditions. Thus, a mixture of 3,6-bis (trifluoromethanesulfonyloxy) phthalonitriles, 1-decene, mole percent Pd (PPh ₃ ) ₄ , lithium chloride and triethylamine was heated at 100 ° C in N, N-dimethylformamide (DMF) for 24 hours. This reaction resulted in the formation of a material from which none of the expected products could be isolated. Mon · · «· · · * * * * * * * * · · · · · · · <<<<<<< Unsuccessful testing of various solvents (DMF, CH ₃ CN) and catalysts (Pd (PPh ₃ ) ₄ , PdCl ₂ (dppf), Pd (OAc) ₂ / PPh ₃ ) concluded that the organic base (i.e., triethylamine) adversely affects the progress of the reaction, probably by attacking said triflate. Repetition of the reaction using a spherically hindered base, namely 2,6-lutidine, resulted in the isolation of the expected dialkenylphthalonitrile. Reaction yields could probably be increased by using other bases, both organic (e.g. DBU) and inorganic (e.g. Cs ₂ CO ₃ ), and novel catalysts (such as palladacyclics, Ni (PPh ₃ ) ₄ , etc.) .

The present invention thus provides a substituted phthalonitrile of formula IV and a process for its preparation.

The unmetallised or metallized substituted phthalocyanine of formula I may be prepared under suitable conditions from the substituted phthalonitrile of formula IV. 3,6bis (dodecylsulfanyl) phthalonitrile has been successfully cyclized to both metal-free phthalocyanine and zinc-containing phthalocyanine using ammonia gas in DMAE. The cyclization of the present invention to form metallated derivatives can also be carried out using DBU as the base. In this way, zinc-containing phthalocyanines were prepared using a homologous series of 3,6-bis (alkylsulfanyl) phthalonitriles in which the alkyl group was a hexyl to undecyl group, and magnesium-containing phthalocyanines bearing eight hexylsulfanyl to undecylsulfanyl groups. DBU catalyzed reaction of 3,6-bis (hexylsulfanyl) phthalonitrile with lead acetate and indium chloride resulted in the formation of the corresponding octakis (hexylsulfanyl).

«

4 phthalocyanines containing lead and chloroindium. Analogs of these metal-free compounds are also available by acid-catalyzed hydrolysis of the magnesium-containing derivatives, for example the demetalate of octakis (nonylsulfanyl) phthalocyaninomagnesium derivative. The Q-band of these phthalocyanines is significantly shifted towards the red region and is in the wavelength range from 780 nanometers to 830 nanometers. To date, octa-S-aryl phthalocyanines, which likewise contain eight groups on the phthalocyanine core, have been prepared by replacing the eight chlorine atoms in the octachlorophthalocyanine. These compounds have been found to be dyes that absorb near-infrared radiation, and are therefore suitable for use in protective printing (see European Patent Application No. EP 85301291.2).

Other 3,6-bis (substituted) phthalonitrile precursors can be cyclotetramerized in a similar manner to give the corresponding metallized or unmetallic phthalocyanines.

3,6-Bis (6'-imidazol-1-yl-hexyl) phthalonitrile provides access to the corresponding zinc-containing octakis (6'-imidazol-1-yl-hexyl) phthalocyanine, a derivative that is soluble in an aqueous acid solution . Similarly, 3,6-bis (1,1-H-2,2-Hperfluordecyl) phthalonitrile can be converted to the corresponding octakis (1,1-H-2,2-H-perfluordecyl) phthalocyanine, which is soluble in fluorinated solvents.

Of course, 1: 3 and 2: 2 mixed substituted phthalocyanines can also be prepared by methods A to F described above by cyclizing a substituted phthalonitrile of formula IV together with another substituted phthalonitrile of formula IV instead of being the first of said phthalonitriles • fe · ·

9 · fefe · fefe · fefe. Fefefefe ffefefefe of formula IV cyclized alone. For example, 1,4-diphenyl-8,11,15,18,22,25-hexakis (decyl) phthalocyaninosin (II) complex was prepared by cross-cyclotetration of 3,6-diphenylphthalonitrile and 3,4-bis-dececylphthalonitrile and 1,4-bis (4-methoxyphenyl) -8,11,15,18,22,25-hexakis (decyl) phthalocyaninosin (II) complex was prepared by cross-tetramerization of 3,6-bis (4-methoxyphenyl) phthalonitrile and 3,5-didecylphthalonitrile.

Similarly, 1,4-bis (3-methoxyphenyl) phthalonitrile and 3,6-didecylphthalonitrile are used to prepare 1,4-bis (3-methoxyphenyl) 8.11.15.18.22.25-hexakis (decyl) phthalocyaninosin zinc complex. In the above reactions, 3, 6-didecylphthalonitrile can be used in excess. The group of byproducts of these reactions comprises symmetrically substituted

1.4.8.11.15.18.22.25-octakis (decyl) phthalocyaninatosin (II) complex and 2: 2 mixed substituted phthalocyanines in which pairs of identically substituted isoindole units are opposite or adjacent to each other. this mixture of isomers was characterized in the case of mixed cyclization of 3,6-diphenylphthalonitrile and 3,6-didecylphthalonitrile.

1: 3 and 2: 2 mixed phthalocyanines containing functional groups on the outer aromatic rings can provide access to other derivatives using standard chemical procedures. Thus, for example, demethylation of methoxy groups with suitable reagents such as boron tribromide in the cases cited leads to the formation of the corresponding phenol derivatives. These derivatives can be used to link two or more phthalocyanine molecules via diester bridges to form dimeric or oligomeric derivatives.

···

444 • 4 ♦

4 4

4 4

4 4444

Reaction of 3, β-bis (6'-imidazol-1-yl-hexyl) phthalonitriles with

3,6-didecylphthalonitrile, using an excess of the latter, resulted in a mixture of the cyclized product resulting from the cyclization of 3,6-didecylphthalonitrile and a 1: 3 mixture of the product substituted by two 6'-imidazol-1-yl-hexyl groups and six decyl groups. The reaction was carried out using DBU and zinc acetate to form the corresponding zinc phthalocyanine complexes.

Furthermore, it is also possible to synthesize, for example, mixed phthalocyanines which contain, for example, hydroxyalkyl or hydroxyalkoxy side chains on one phthalonitrile and hydrophobic substituents on the other phthalonitriles, wherein the hydroxyalkyl or hydroxyalkoxy side chains are in excess.

Accordingly, the present invention provides a metallized or unmetallised substituted phthalocyanine of formula I and a process for its preparation.

As shown in Scheme 8, a metallized or unmetallised substituted phthalocyanine of formula V can be prepared by cyclizing a substituted phthalonitrile of formula VI or formula VII, either by cyclizing the phthalonitrile itself or together with another phthalonitrile of formula IV.

• 99 • 9 9 • 9 9 • 9

• 9 · ·

9 9 · 9 9

9 9 * ·

Scheme 8

The substituted phthalonitrile (VI) itself can be prepared from 2,3-dicyanohydroquinone as shown in Scheme 9.

• · ·

The phthalonitrile-3-halide of formula (VI) may be prepared by halogenating 2,3-dicyanohydroquinone and subsequent alkylation under appropriate conditions.

Thus, for example, bromination of 2,3-dicyanohydroquinone is formed

4,5-dibromo-3,6-dihydroxyphthalonitrile. The use of the so-called Gunther method (T. Gunther, Justus Liebigs Ann. Chem., 1906, 349, 56), which involves the use of bromine in acetic acid, results in a product in which a small amount of bromine is found by analysis. However, by bromination of 2,3-dicyanohydroquinone with N-bromosuccinimide (NBS) (see French Patent No. FR 1313082; Chem. Abs., 1962, 57, 11283h) followed by reduction of the 2,3-dibromo-4,5-dicyanobenzoquinone thus formed. sodium bisulfite produced 4,5-dibromo-3,6-dihydroxyphthalonitrile in 66% yield.

Unexpectedly, the alkylation of 4,5-dibromo-3,6-dihydroxyphthalonitrile provides access to both 4,5-dibromo-3,6-dibutoxyphthalonitrile and 4-bromo-3,6-dibutoxyphthalonitrile. Reaction of iodobutane in the presence of potassium carbonate in

• · · · · · · · ·

methyl ethyl ketone (MEK) then forms a mixture of 4,5-dibromo-3,6dibutoxyphthalonitrile (6 percent) and 4-bromo-3,6-dibutoxyphthalonitrile (39 percent). The latter is produced exclusively in a 42 percent yield in the case of a later addition of iodobutane to said basic solution. Thus, it follows that the role of the base is to eliminate hydrogen bromide from

4,5-dibromo-3, β-dihydroxyphthalonitrile, which elimination is likely to occur via the corresponding tautomer. The resulting monobromobenzoquinone can then be reduced back to monobromohydroquinone, which subsequently participates in conventional Williamson ether synthesis. In this type of alkylation reaction it was not possible to find such conditions under which it would arise

4,5-dibromo-3, β-dibutoxyphthalonitrile preferably over 4-bromo-3,6-dibutoxyphthalonitrile. Instead, 4,5-dibromo-3,6-dibutoxyphthalonitrile can be obtained in a simple manner and in a satisfactory yield (84 percent) from 4,5-dibromo-3,6-dihydroxyphthalonitrile under Mitsunobu reaction conditions.

Accordingly, the present invention provides a phthalonitrile halide of formula VI and a process for its preparation.

Unmetallized or metallized substituted phthalocyanines of formula V can be prepared from a phthalonitrile halide of formula VI in two different ways. In the first synthesis process (referred to as process A), a phthalonitrile halide of formula VI can be converted to a substituted phthalonitrile of formula VII which is cyclized, either alone or together with another phthalonitrile of formula IV, to give a substituted phthalocyanine of formula V (in which R ⁹ = R ^u). In an alternative case (i.e., method B), the phthalonitrile halide of formula VI is cyclized, e.g.

9 • 9 • 99

9 · 9 · 9 • 9 9

9

9

9999 again, either alone or together with another phthalonitrile of formula IV, to form a substituted phthalocyanine halide of formula V (wherein R ⁹ = R ¹⁰ ). This substituted phthalocyanine halide of formula V (wherein R ⁹ = R ¹⁰ ) can optionally be converted to a substituted phthalocyanine of formula V (wherein R ⁹ = R ¹¹ ).

For example, 4,5-dibromo-3,6-dibutoxyphthalonitrile and 4-bromo-3, β-dibutoxyphthalonitrile were independently tetramerized, with octabromoctabutoxyphthalocyaninatonicin complex prepared from the first phthalonitrile and tetrabromo-octabutoxyphthalocyaninizone form from the second phthalonitrile. ).

Substituted phthalocyanines containing one phthalonitrile monomer that differs from the other three (i.e. 1: 3 mixed substituted phthalocyanines) can be synthesized using, for example, solid phase synthesis (Tetrahedron Lett., 1982, 23, 3023; J. Org Chem., 1991, 56, 82). The use of polystyrene-based resins as a solid phase has been discussed in European Patent Application Publication No. EP 0 906 758. Of course, also phthalocyanines containing four identical phthalonitrile monomers can be synthesized by solid phase synthesis. 1: 3 and 2: 2 mixed substituted phthalocyanines can in principle be prepared by various methods, such as cyclotetramerization (G. de la Torre, P. Vazquez, F. Agullo-Lopez, Z. Torres, J. Chem. Mat., 1998, 8, 1671, J. Bakboord, MJ Cook, E. Hamuryudan, J. Porphyrins Phthalocyanines, 2000, 4,510). In order to demonstrate the applicability of methods A and B described above, method B was carried out in which crosses were performed.

9 «

9 9 · · 9 · ·

Cyclotetramerization to give 1: 3 mixed substituted phthalocyanines. In this reaction, two suitably substituted phthalonitriles of formulas VI and IV reacted and the desired product was separated from the resulting mixture by chromatography. For example, the 1: 9 mixed cyclotetramerization of 4,5-dibromo-3,6-dibutoxyphthalonitrile and 3,6-didecylphthalonitrile was carried out with lithium butoxide in butanol and in the presence of nickel acetate. Chromatographic separation of the 3,6-didecylphthalonitrile autocondensation product, i.e. 1,4,8,11,15,18,22,25-octadecylphthalocyaninatonicelium complex, was easily separated in the first fraction. The second fraction contained two components which were separated on another column, one of which was the desired 1,4-dibutoxy-2,3-dibromo-1,11,15,18,22,25-hexakis (decyl) phthalocyaninatonicel complex , which was identified as a 1714 D cluster in the low resolution FAB mass spectrum, with elemental analysis and ¹ H NMR spectrum of this product consistent with the expected structure. 1,4-Dibutoxy-2-bromo-8,11,15,18,22,25-hexakis (decyl) phthalocyaninatonicellate complex was similarly synthesized by mixed cyclotetramerization of 4-bromo-3,6-dibutoxyphthalonitrile and

3,6-didecylphthalonitrile.

The latter cyclization was also investigated in the absence of a nickel salt to prepare a metal free 1,4-dibutoxy-2-bromo-8,11,15,18,22,25-hexakis (decyl) phthalocyanine. In this synthesis, lithium butoxide in butanol is used as the base at different temperatures and during different reaction times, in the presence or absence of Pd (PPh ₃ ) ₄ as cocatalyst. Cases where mixtures of these were used were investigated

»Ft ft ft ft ft ft ft ft ft ft ft ft ft ft ft ft ft ft ft ft ft ft ft (((((((((((((((((((((((() excess 3, β-didecylphthalonitrile) and in a 1: 1 ratio.

When the ratio of precursors was 1: 1, the reaction carried out in a mixture of dry butanol and lithium butoxide at boiling point for 20 hours produced a mixture of octakis (decyl) phthalocyanines and a 1: 3 mixed product of 1,4-dibutoxy-2. - bromo 8,11,15,18,22,25-hexakis (decyl) phthalocyanine (in the form of lithiated derivatives). Mass spectrometry revealed that the reaction mixture also contained 2: 2 mixed products and compounds in which the butoxy groups replaced the bromine substituents. Quite unexpectedly, the addition of Pd (PPh ₃ ) ₄ as a catalyst has resulted in an increase in the yield of both octakis (decyl) phthalocyanines and the 1: 3 mixture product of 1,4-dibutoxy-2-bromo-8,11-, 15- 18,22,25hexakis (decyl) phthalocyanine. In addition, the mixed product was a major product. However, this product is contaminated with up to about 15 percent of the palladium metallated derivative, i.e. 1,4-dibutoxy-2-bromo-8,11,15,18,22,25hexakis (decyl) phthalocyaninatopalladium, wherein the pure metal-free compound, can be isolated by column chromatography. The metal-free compound can be readily converted by reaction with zinc acetate to 1,4-dibutoxy-2-bromo-8,11,15,18,22,25-hexakis (decyl) phthalocyaninosin zinc complex. This compound can also be obtained by reaction

Of 3,6-didecylphthalonitrile with 3,6-dibutoxy-4-bromophthalonitrile in DBU in the presence of zinc acetate.

For the conversion of ϊ, 4-dibutoxy-2,3-dibromo-8,11,15,18,22,25hexakis (decyl) phthalocyaninatonicelic complex and 1,4-dibutoxy-2-bromo-8,11,15,18,22,25 -hexakis (decyl) phthalocyaninatonicellate complex to the corresponding ethinylated derivatives • φ φφ · · φ 9 • • 9 9 »» »* * * *

9 9

ΦΦ ΦΦ

ΦΦ 99 «

9

999 9 has been tested as Sonogashira addition (K. Sonogashira, Y. Tohda, N. Hagihara, Tetrahedron Lett., 1975, 16, 4467; S. Thorand, N. Krause, J. Org. Chem., 1999, 63, 8551), which led to the formation of ethynylated phthalocyanines in which the ethinyl groups were protected with trimethylsilyl (TMS) groups and Stille addition (DE Rudisill, JK Stille, J. Org. Chem., 1989, 54, 5856) , which led to the formation of unprotected ethynylated phthalocyanines.

The conditions of Sonogashira addition were first applied to

1,4-dibutoxy-2-bromo-8,11,15,18,22,25-hexakis (decyl) phthalocyaninatonicelic complex using triethylamine as solvent. Reaction of this compound with 6 equivalents of trimethylsilylethine at 80 ° C for 36 hours and in the presence of 20 mole percent Pd (PPh ₃ ) ₂ Cl ₂ and 30 mole percent copper (I) iodide was not observed to cross-link, although after 24 hours, additional catalyst was added to the reaction mixture. However, after changing the solvent to a tetrahydrofuran / triethylamine (5: 1) mixture, increasing the amount of cuprous iodide to 39 mole percent and adding triphenylphosphine to the reaction mixture, the 1,4-dibutoxy-2-bromo-8,11,15,18,22 was converted, 25-hexakis (decyl) phthalocyaninatonicellate complex to the corresponding ethynylated phthalocyanine, whose ethynyl groups are protected with trimethylsilyl (TMS) groups, in a satisfactory yield of 62 percent after chromatographic purification. When analyzing the product, a 1653 D cluster was identified in the low resolution FAB mass spectrum and a 0.49 ppm chemical shift signal corresponding to nine protons of trimethylsilyl groups was measured in the ³ Η NMR spectrum.

4 4

4

4

4444

Stille addition of 1,4-dibutoxy-2-bromo-8,11,15,18,22,25hexakis (decyl) phthalocyaninatonicelium complex using tributyl (ethinyl) tin and Pd (PPh ₃ ) ₄ as a catalyst stabilized by the addition of triphenylphosphine (PPh ₃ ) and lithium chloride, afforded unprotected ethynylated phthalocyanine in 48 percent yield. The obtained product was identified by elemental analysis and ¹ H NMR spectroscopy.

The Sonogashira addition conditions described above were applied to 1,4-dibutoxy-2,3-dibromo-8,11,15,18,22,25-hexakis (decyl) phthalocyaninatonicellate complex to give an ethynylated phthalocyanine in 35% yield. ethynyl groups were protected with trimethylsilyl (TMS) groups. This product was identified by a 1747 D cluster in the MALDI-tof mass spectrum and a characteristic singlet in the ¹ H NMR spectrum which corresponded to eighteen protons of trimethylsilyl groups. Further confirmation of the structure was obtained by measuring the ¹³ C NMR spectrum. In the spectrum obtained, all 16 expected aromatic ¹³ C signals could be well distinguished, and the two carbon atoms of the ethynyl group had a chemical shift of 104.74 ppm and 100.97 ppm. Removal of trimethylsilyl (TMS) protecting groups by treatment with aqueous potassium hydroxide in a mixture of tetrahydrofuran (THF) and methanol afforded the corresponding unprotected ethynylated phthalocyanine in 79% yield.

This compound is characterized by a 1606D FAB mass spectrum cluster with ¹ H NMR and ¹³ C NMR spectra containing signals that were fully consistent with the product structure.

• · ··· · fc · · · · ···

Application of the Stille addition conditions described above resulted in a satisfactory conversion of 1,4-dibutoxy-2,3-dibromo-8,11,15,18,22,25hexakis (decyl) phthalocyaninatonicellate complex directly to the corresponding unprotected ethynylated phthalocyanine in yield. 54 percent. The Stille addition thus offers a significant improvement over the Sonogashira method in terms of overall reaction yield. Furthermore, the separation of fully and partially admixed products in this case is less difficult and does not require as careful chromatography as in the Sonogashira procedure.

Sonogashira addition using Pd (PPh. ₃ ) ₂ Cl ₂ / CuI as the catalyst, or addition using another catalyst such as Pd ₂ (dba) ₃ . AsPh ₃ , can be used to convert 1,4-dibutoxy-2-bromo-8,11,15,18,22,25-hexakis (decyl) phthalocyaninatosine to the corresponding substituted ethynylated derivatives. Reaction with 2-methyl-3-butin-2-ol gave the corresponding substituted ethinylphthalocyanine, by reaction with other functionalized ethines such as ethyl propiolate, N-methylpropargylamine and 1C-ethinyl-2,3,4,6-tetraacetylglucopyranose, it is possible to prepare other new phthalocyanines.

As for method A, it was also practically tested.

4-Bromo-3,6-dibutoxyphthalonitrile and 4,5-dibromo-3,6-dibutoxyphthalonitrile were cross-coupled with boronic acid in the presence of a palladium catalyst (ie under Suzuki reaction conditions). For example, 4-bromo-3,6-dibutoxyphthalonitrile and 10 mole percent Pd (PPh ₃ ) ₄ were stirred in dimethyl ether (DME) under nitrogen for 10 minutes. 2-Thiopheneboronic acid and a 2 molar aqueous sodium carbonate solution were added sequentially. The resulting mixture was * 9 • 9 9 9

9 · 9 • 999 ·

9 99

• 9 • 9 • 9

9 9 · 9 99

9 * 99

9 9 • 9 • 99

The mixture was heated at reflux for 9 hours. After cooling, simple aqueous work-up followed by recrystallization, 4- (2-thienyl) -3,6-dibutoxyphthalonitrile was obtained in 62% yield. The following compounds were prepared in a similar manner:

4-pyridyl-3,6-dibutoxyphthalonitrile, 4-phenyl-3,6-dibutoxyphthalonitrile, 4,5-diphenyl-3,6-dibutoxyphthalonitrile,

4- (p-hydroxymethylphenyl) -3,6-dibutoxyphthalonitrile a

4- (p-N, N-dimethylaminophenyl) -3,6-dibutoxyphthalonitrile,

4- (p-aminophenyl) -3,6-dibutoxyphthalonitrile, 4- (p-methoxyphenyl) -3,6-dibutoxyphthalonitrile and 4- (p-carboxyphenyl) -3,6-dibutoxyphthalonitrile. Functionalized phenyl rings in these 4-aryl-3,6-dibutoxyphthalonitriles provide access to other derivatives through functional group interconversions. Thus, by the mesylation of 4- (p-hydroxymethylphenyl -) - 3,6-dibutoxyphthalonitrile and subsequent reaction with tyrosine methyl ester in the presence of a base, the corresponding 4-p-benzyloxy-O-tyrosine-methyl-ester-phthalonitrile can be prepared.

The versatility of using the Suzuki reaction to 4-bromo and 4,5-dibromo-3,6-dibutoxyphthalonitriles provides in principle access to other amino acid derivatives, such as phthalonitriles, in which phenylalanine groups are directly added to the phthalonitrile nucleus and are preferably used for their preparation phenylalanine boronic acid derivatives and its esters with protected NH ₂ and CO ₂ H groups (see F. Firooznia, C. Gude, K. Chan and Y. Satoh,

Tetrahedron Letters, 1998, 39, 3985).

Application of Heck reaction conditions (addition of alkenes to aromatic rings) and Negishi reaction conditions to 4-bromo a

4,5-dibromo-3,6-dibutoxyphthalonitrile, which are used as: 99 9 99 • 4 »4

9 94

9 4 9

4 9 9

94

44

4 4 4

9 4

9 9 4

4 4

4444 precursors, provides another means for introducing functional groups at positions 4 and 4.5, respectively

3,6-dibutoxyphthalonitrile. Thus, the reaction of 4-bromo-3,6-dibutoxyphthalonitrile with 4-chlorobutylzinc bromide and 4-ethoxy-4-oxobutylzinc bromide leads to the formation of the corresponding functionalized phthalonitriles, which in principle are precursors of other functionalized alkyl substituents or can be linked together to form dimeric phthalonitrile . Reactions

3,6-dibutoxy-4- (4'-ethoxy-4'-oxobutyl) phthalonitrile with 3,6didecylphthalonitrile and zinc acetate in butanol and in the presence of a DBU catalyst, 1,4-dibutoxy-2- (4'-oxobutyl) - 8,11,15,18,22,25-hexaki-s (decyl) phthalocyanine zinc complex. In this reaction, it has been demonstrated that under the reaction conditions described above, transesterification occurs in which a butoxy group derived from the solvent used is introduced into the ester group so that different alkoxy groups can be introduced into the ester function by suitable solvent selection.

The 1: 3 mixed substituted phthalocyanines are obtained by cross-cyclotetramerization of the 4-substituted and 4,5-disubstituted-3,6-dibutoxyphthalonitriles described above as Method B. In this way various metallized and unmetallized 1,4-dibutoxy-2- substituted 8,11,15,18,22,25-hexakis (decyl) phthalocyanines and 1,4-dibutoxy-2,3-disubstituted-8,11,15,18,22,25-hexakis (decyl) phthalocyanines.

Of course, it is possible to cyclize the phthalonitriles of formula VII themselves to form additional phthalocyanines. Thus, 3,6-dibutoxy-4,5- (tris (isopropyl) silylethinyl) phthalo is possible.

9 9 99 99 99 99 99

Convert the nitrile to the corresponding octabutoxyocta (tris (isopropyl) silylethinyl) phthalocyaninatonicellate complex.

Reaction of the latter compound with tetrabutylammonium fluoride removes triisopropylsilyl (TIPS) groups to form octabutoxyoctaethinylphthalocyaninatonicellate complex.

Accordingly, the present invention also provides an unmetallised or metallized substituted phthalocyanine of formula V and a process for its preparation.

Some phthalcyanines have been investigated for their liquid-crystalline properties. To date, columnar mesophase behavior of non-peripherally substituted phthalocyanines has been described, both phthalocyanines homogeneously substituted by eight alkyl groups (A. A. Cherodian, A.

N. Davies, R.M. Richardson, M.J. Cook, Ν. McKeown B., Thomson A.J., Feijoo J., Ungar G., Harrison K. J., Mol. Cryst. Liq. Cryst., 1991, 196, 103; Cook, M. J., Cracknell, S. J., Harrison, K. J., J. Mater. Chem., 1991, 1, 703; A.V. Belushkin, M.

Cook J., Frezzato D., Haslam S., Ferrarini A., Martin Martin,

J. McMurdo, P. L. Nordio, R. M. Richardson, A. Stafford, Mol. Physics, 1998, 93, 593) and phthalocyanines substituted with eight alkyloxymethyl groups (A. N. Cammidge,

Cook, M. J., Harrison, K. J., Thomson, A. J., Chem. Soc.

Perkin Trans. 1, 1991, 3053) and 1: 3 inhomogeneously substituted derivatives containing at least six alkyl chains (see I. Chambrier, M.J. Cook, S.J. Cracknell, J.

McMurdo, J. Mater. Chem., 1993, 3,841; M.J. Cook, J.

McMurdo, D. A. Miles, R. H. Poynter, J. M. Simmons, S. D. Haslam, R. M. Richardson, K. Welfordt, J. Mater. Chem., 1994,. · 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 <

·· ····

4, 1205). Non-peripherally substituted octaalkoxy derivatives do not exhibit mesophase properties (see M. J.

Cook,

Dunn A.J. Howe S.D. Thomson A.J. Chem. Soc. Perkin Trans. 1, 1988, 2453).

The liquid-crystalline behavior of the prepared 1: 3 mixed phthalocyanines was investigated by optical polarization microscopy and the results are summarized in Table 2. In this table, K indicates crystalline state, D indicates mesophase (disco) and I indicates isotropic liquid. Except for 1,4-dibutoxy-2,3- (2'-trimethylsilylethynyl) 8,11,15,18,22,25-hexakis (decyl) phthalocyaninatonicellate complex, all these phthalocyanines showed mesophase behavior, indicating that the introduction of two alkoxy groups do not inhibit liquid crystallinity to non-peripheral positions.

In accordance with the above examples, in the first mesophase after cooling, a "fan-shaped birefringent texture characteristic of the discrete, hexagonally disordered phase (D _h d) · 1,4-Dibutoxy-2-bromo-8,11,15,18," The 22,25-hexakis (decyl) phthalocyaninatonicelium complex exhibited a second mesophase, which was formed only during cooling. This phase was mobile and deformed when subjected to external pressure. This mesophase then gave an indeterminate texture that could not be identified and is designated as D _x .

• ·

Table 2 - Phase transition temperatures measured for different 1,4-dibutoxy-2,3-substituted-8,11,15,18,22,25hexakis (decyl) phthalocyaninatonicellic complexes

2,3-substitution Transition temperature <° C) K-> D _hd Dhd ^- K-> I I-> K ^I— > ^D hd Dhd ^- ^ D _x D _X -> K D _hd- > K 2,3-CCSiMe ₃ 69 <RT 2,3-CCH 83 91 88 76 2-CCSiMe ₃ 46 113 112 <RT 2-CCH 36 131 130 <RT 2,3-Br 72 67.5 57 2-Br .30 106 104 35 <RT

RT = room temperature

The indicated phase transition temperatures were measured by polarized light microscopy during the first heating and cooling cycle. Higher mesophase temperature is denoted as D _hd . The lower temperature of mesophase D _x is unknown.

Symmetry of the molecule has a considerable influence on mesophase behavior. Thus, nonasubstituted phthalocyanines have a symmetry of C _s , whereas decasubstituted phthalocyanines have a symmetry of C _2v . Phthalocyanines symmetry C ₃ have lower transition temperatures K »D _HD than the analogous phthalocyanines C _2v symmetry. This phenomenon can be attributed to the fact that phthalocyanines with higher symmetry form better composite crystals. Furthermore, it has been found that phthalocyanines with a symmetry of C ₃ exhibit a higher clarification temperature (K? 1 or Dhd-1) as well as their counterparts with symmetry of C _2v . Mesophase D _{hd of} phthalocyanines with C ₃ symmetry is much more mobile and less viscous than in the case of C _2v phthalocyanines.

Phthalocyanines with a symmetry of C _s also tend to supercool, i.e. crystallize, by standing overnight at room temperature. In contrast, the phthalocyanines with the symmetry of _C2v crystallize immediately after cooling. The transition to the crystalline form is characterized by a change in color, but not by a change in texture, in particular when the transition to the crystalline phase is a pale green color of the "fans". Replacement of bromine atoms with unprotected ethinyl groups led to an increase in the clarification temperature.

Substituted phthalocyanines exhibit many desirable properties and are useful for a wide variety of different applications.

Some of the substituted phthalocyanines of the present invention exhibit markedly photodynamic properties and significant absorption of radiation in the red region of visible light. Thus, the compounds are useful both alone and in the form of conjugates with macromolecular carriers (such as polymers or antibodies) in the treatment of viral, fungal or bacterial diseases and diseases characterized by areas of neovascularization or benign or malignant cell proliferation, particularly in the treatment of diseases such as tumors, rheumatoid arthritis, inflammatory arthritis, hemophilia, osteoarthritis, vascular stenosis, vascular restinosis, atheromas, hyperplasia, vascular internal wall hyperplasia, benign prostatic hyperplasia, psoriasis, mycosis fungoides, eczema, keratosis from radiation or keratosis. In addition, since these compounds are fluorophores, they can be used as diagnostic agents to identify pathologically affected areas.

4444 44

3 «» 3 4 «

4 44

44 ► 4 · ► 4 ·

Once the organic compounds containing the chromofluorophore phthalocyanine macrocycle are photoactivated by radiation, these compounds are capable of generating hyperactive oxygen derivatives, especially singlet oxygen or oxygen radicals, which are characterized by a high degree of cytotoxicity, thus potentially interesting for various therapeutic applications such as photodynamic therapy, and / or for diagnostic applications (see E. Ben-Hur and I. Rosenthal, Int. J. Radiat. Biol., 1985, 47, 145).

Photosensitization is a process in which a photochemical reaction is induced by the presence of a substance (the so-called photosensitizer) that absorbs radiation, but remains substantially unchanged at the end of the reaction, the absorbed light energy being transmitted to the main reagents. For example, when exposed to hydrogen at a wavelength of 253.6 nanometers, there is no absorption of radiation at all and hydrogen remains completely intact. However, when mercury vapors are added to hydrogen, mercury atoms are excited under the same conditions. When such an excited mercury atom collides with a hydrogen molecule, it can transmit some of its hydrogen energy and cause dissociation of said hydrogen energy. This makes hydrogen seemingly sensitive to radiation it does not absorb. In some cases, the photosensitizer disintegrates to produce a product that may also have suitable photodynamic properties. Similarly, oxygen can be made susceptible to electromagnetic radiation that it does not normally absorb through the presence of phthalocyanines or other substances.

0 ·

0 0 0 0

0 »000 ··

Complex organic compounds, some of which may contain metals or metal salts.

In the photodynamic therapy of tumors, the substituted phthalocyanines of the present invention are administered to an individual afflicted with the tumor and are at least to some extent absorbed by the tumor. After administration of the compounds to a patient, photodynamic therapy using radiation sources and drug delivery systems known to those skilled in the art may be practiced in a conventional manner (Phys. Med. Biol., 1986, 31, 327). . Upon selective irradiation from an appropriate radiation source, tumor tissue is destroyed by photogeneration of compounds such as singlet oxygen or other cytotoxic compounds such as free radicals, such as the hydroxyl or peroxide radical, the photogeneration being mediated just mentioned dye.

Biological studies on the use of substituted phthalocyanines in photodynamic therapy have been performed with water-soluble sulfonated metallophthalocyanines (see I. Rosenthal, Photochem. Photobiol., 1991, 53, 859). The use of phthalocyanines containing hydroxyl substituents, amino substituents or quaternary ammonium substituents for the photosensitization of cancer cells has also been described (CC Leznoff et al., Photochemistry and Photobiology, 1989, 49, 279; D. Wohrle et al., Photochemistry and Photobiology, 1990, 51, 351, D. Wohrle et al., Dyes and Pigmente, 1992, 18, 91-102;

H. Dummin, J. Photochem. Photobiol., 1997, 37,219). Also • ·, ”, ♦ ........

.. · · · · • .. :: .. .. :: :::::::::::

phthalocyanine cancer phototherapy tests performed in laboratory animals have been described (H. Barr et al., Br. J. Surg., 1990, 77, 93;

K. Schieweck et al., Proc. SPIE, 1994, -2078,107;

C. Ometto and Associates, Br. J. Cancer, 74, 1891 (1996);

J. Rousseau et al., J. Photochem. Photobiol., B: Biol., 1990, 6, 121). Minnoch and coworkers (<J. Photochem. And Photobiol., 1996, 32, 159) and Brown and coworkers (Photochem. And Photobiol., 1967, 65 (3)) described in vitro activity of four phthalocyanine derivatives, both against microorganisms and against cell lines.

For a compound to be successfully used as a photosensitizer for use in photodynamic therapy, it must, at least in part, meet various criteria, the group of which includes:

(a) high quantum yield of reactive substances such as singlet oxygen or free radicals;

(b) relatively low toxicity to the subject being treated;

c) the ability to be activated by high wavelength radiation (preferably in the red or near infrared region of the spectrum), which is capable of penetrating deeper into tissues compared to shorter wavelength radiation;

d) selectively accumulating said compound with cells responsible for said pathological condition and rapidly eliminating said compound from tissues not affected by said pathological condition;

e) the ability of the compound to be bound to macromolecules! carriers while maintaining photo-sensitizing efficacy.

Some substituted phthalocyanines are adapted for use as photosensitizers in the wavelength of electromagnetic radiation. The radiation may then be electromagnetic radiation from the entire spectrum of a suitable wavelength. Preferably, said electromagnetic radiation is a radiation whose wavelength is in the range from the ultraviolet to the infrared region of the spectrum, more preferably said wavelength is in the range of the visible red to the infrared region of the spectrum. Red light shows deeper tissue penetration than shorter wavelength light. In a preferred embodiment, the photosensitizer absorbs laser light of a suitable wavelength, but it is also possible to use other radiation sources, such as a tungsten halogen lamp.

It has been found that if the metal is diamagnetic, metallized phthalocyanines have a better photosensitizer activity than unmetallized phthalocyanines. Especially phthalocyaninozinc complexes have been found to be suitable for use in photodynamic therapy. On the contrary, the presence of a paramagnetic metal inactivates phthalocyanine (see I. Rosenthal, E. Ben-Hur, "Phtalocyanines in Photobiology in Phtalocyanines, Properties and Applications, editors CC Leznoff and A. Β P. Lever, VCH Publishers, 1989 ).

The presence of hydrophilic substituents or binding of phthalocyanine to hydrophilic carriers can accelerate the metabolism of phthalocyanines, allowing rapid in vivo elimination of the chromophore, thus preventing the phototoxic effect of the compound used in the skin.

• ·

Some substituted phthalocyanines exhibit photodynamic activity even at low oxygen concentrations, so they can also be used for the specific treatment of anaerobic microorganisms or for the treatment of cancer characterized by a low oxygen environment.

Substituted phthalocyanines may also be coupled to various carriers to improve their pharmacological properties. Normally, such carriers are selected from the group consisting of amino acids, fatty acids, nucleic acids, di-, tri-, or even decapeptides, polypeptides, proteins, carbohydrates, polysaccharides, polymers, and antibodies that can be engineered to bind them at the tumor site. Said antibodies may be prepared from cultured tumor samples, and examples of such antibodies include PLAP (placental alkaline phosphatase), human milk fat globulin (HMFG), carcino embryonic antibody (CEA), and human chorionic gonadotrophin (HCG).

The linkage between the phthalocyanine and the carrier may occur between the carboxyl group and the amino group or may be formed using other known functional and reactive groups.

Pharmaceutical compositions comprising the substituted phthalocyanine of the present invention, as such or in the form of a conjugate with a carrier, or a pharmaceutically acceptable salt thereof, in admixture with a pharmaceutically acceptable carrier, diluent or excipient may be formulated according to well known principles and such compositions may take the form of dosage units, as appropriate, determined in accordance with conventional pharmacological methods. Listed

The dosage forms may provide a daily dose of the active compound in a single dose or in several smaller sub-doses. The dosage can be determined by conventional pharmacological methods and is usually in the range of 1 milligram / kg body weight to 60 milligrams / kg body weight. Other active compounds may be included in the pharmaceutical composition of the present invention, or the compounds may be administered separately, or the treatment of a patient with the pharmaceutical composition of the invention may be accompanied by additional therapy. If desired, the pharmaceutical compositions of this invention may be in a form suitable for topical, subcutaneous, mucosal, parenteral, systemic, intrarticular, intravenous, intramuscular, intracranial, rectal or oral administration. Suitable carriers and diluents for use in the present invention are well known in the art of pharmacology, and the pharmaceutical compositions of the present invention may also contain excipients and other ingredients to provide for easier and more effective administration.

Thus, the present invention provides a substituted phthalocyanine of formula I or V, which is optionally bound to a suitable carrier, for use as a medicament, particularly for use in photodynamic therapy. The present invention further provides a pharmaceutical composition comprising a phthalocyanine of formula I or V, or a pharmaceutically acceptable salt thereof, which is particularly suitable for use in photodynamic therapy. The present invention further provides the use of a substituted phthalocyanine of formula I or V for the preparation of a phototherapeutic or photodiagnostic agent.

It to this it to it it to it it to it it to it

Some of the substituted phthalocyanines of the present invention are in the form of thin films, such as Langmuir-Blodgett films and rotary coatings, in a liquid-crystalline state, or when dissolved or dispersed in a carrier material in the visible light region, mostly transparent but absorb strongly ultraviolet or infrared radiation, preferably infrared radiation in the wavelength range from 750 nanometers to 870 nanometers, and preferably exhibit absorption maxima in this wavelength range. Such substituted phthalocyanines can be used in conjunction with a laser, wherein laser rays are used to irradiate the surface of a material to produce an inscribed pattern on that surface. The technique is based on the local absorption of the energy of the laser beam, which results in local heating and thus changes in the optical properties of the otherwise transparent material that is contacted with the laser beam. As the beam travels over the surface of the material, its trajectory remains behind the beam. Important applications based on this principle are laser optical data storage devices and laser projection displays in which the beam is directed through the cell containing the material described above and subsequently projected onto the screen. Such devices have been described in F. J. Khan, Appl. Phys. Lett., 1973, 22, 111 and Harold and Steel in Proceeding of Euro Display, September 1984, volume 84, pp. 29-31, Paris, France), said material being a smectic, liquid-crystalline material. An important group of devices described above are devices in which liquid-crystalline material is used as an optical data storage medium.

• ·

In the above applications, the use of semiconductor lasers, especially Ga _x Al 1 - _x As lasers (where x is a number from 0 to 1, preferably 1), is very popular, as these lasers can provide laser energy at near-infrared wavelengths, which is invisible (and therefore cannot interfere with the visible display) and because this type of laser can provide a useful source of well-defined, intense thermal energy. Galliumarsenide lasers provide laser light with a wavelength of approximately 850 nanometers and are most suitable for use in the above applications. With increasing aluminum content (x < 1), the wavelength of the laser radiation can be reduced to approximately 750 nanometers.

The high stability of the phthalocyanine ring system is a prerequisite for further use of the substituted phthalocyanines of the present invention, especially when the phthalocyanines are complexed with a central metal ion M whose different oxidation states may cause the material to have semiconductor, photoconductor or electrochromic properties. Such features can be utilized in various sensors, catalysts and displays.

Another possible use of the substituted phthalocyanines of the present invention results from their stereochemistry and spatial orientation capability, so that some of these phthalocyanines may have liquid crystalline properties while others may produce them. Langmuir-Blodgett films or spin films. Other phthalocyanines according to the invention can absorb electromagnetic radiation and can be used in various solutions designed for this purpose.

4

4

4 4 4

4 4 · 4

4 · 4

4

For example, in liquid crystals. Another possibility, when M is a large metal, such as palladium or platinum, is to use the substituted phthalocyanines of the present invention as one-dimensional conductors, such as potential or molecular wires.

Further, the substituted phthalocyanines of the present invention can be polymerized. The polymerization may occur through double bonds contained in unsaturated side chains or by the formation of ester or amide groups, or by any other suitable polymerization method known to those skilled in the art. Any polymerization can be performed with little or no effect on the phthalocyanine ring itself, since this ring is highly stable.

Accordingly, the present invention provides a material comprising a substituted phthalocyanine of formula I or V whose optical or physical properties can be altered by incident electromagnetic radiation.

Description of the drawings

Figure 1 shows the typical shape of the 1,4- (bis (3-methoxyphenyl) -8,11,15,18,22,25-hexakis (decyl) phthalocyaninatosinium complex (sample AA35) measured in toluene / pyridine with wavelength excitation

355 nanometers. The residual signal (magnified ten times) is shown with a 20 mV offset. The fluctuating signals observed during the first 2 to 3 microseconds are due to the fluorescence of said sensitizer.

• 4

4

444 • 4 • 444 44 • 4 J

Figure 2 is a graph showing the linear relationship between singlet oxygen emission intensity and laser energy for perinaftenone samples and 1,4- (bis (3-methoxyphenyl) - *

8,11,15,18,22,25-hexakis (decyl) phthalocyanine-zinc complex (sample AA35). The slope values of 0.38 and 0.25 for these and other solutions of different absorbances were used to determine hodnoty _Δ .

Figure 3 is a graph showing the relationship between the intensity of singlet oxygen emission (which is normalized for incident laser energy) and the fraction of radiation absorbed by 1,4- (bis (3-methoxyphenyl) -8,11,15,18,22,25-hexakis (decyl) phthalocyaninosin zinc complex (sample AA35) (1-10 ^A ).

DETAILED DESCRIPTION OF THE INVENTION

The following examples serve to better illustrate the above description of the invention without limiting its scope in any way.

Example 1

Preparation of 3, β-bis (trifluoromethanesulfonyloxy) phthalonitrile A two-necked flask equipped with a thermometer and a pressure equalizing dropping funnel was dried over the flame while flushing with argon. In this flask 5.2 g (0.0325 mol) of 2,3-dicyanohydroquinone were dissolved in 30 ml of dichloromethane and 16 ml of dry lutidine and the resulting yellow solution was cooled to -20 ° C. A solution of 22.1 g (0.078 mol) was added dropwise over 30 minutes.

4

4 4

4 ··

100 ·

4

4444 trifluoromethanesulfonic anhydride in 10 ml dry dichloromethane. The reaction mixture was allowed to warm to room temperature and stirred for an additional 14 hours. Dichloromethane was removed from the reaction mixture under reduced pressure, and the remaining solution was washed with 2 x 20 mL of 5% hydrochloric acid, 2 x 20 mL of 5% sodium hydroxide (to remove starting materials and monotriflate product) and 20 mL of brine. The mixture was then dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was recrystallized from ethyl acetate / cyclohexane to give 12.71 g (92 percent) of 3, β-bis (trifluoromethanesulfonyloxy) phthalonitriles as pale yellow crystals.

M.p. 109-111 ° C.

For C ₁₀ H2N ₂ O ₆ S2F ₆

Found: C 28.46%; H, 0.29%; N, 6.50%.

Calculated: C 28.31%; H 0.48%; N, 6.60%.

⁴ H NMR (270 MHz, CDC1 ₃₎ δ 7.87 (s, 2H) ppm.

¹³ C NMR (270 MHz, CDCl 3) δ 148.89 (ArC-O), 128.66 (ArC-H), 118.55 (q, J = 321 Hz, -CF ₃ ), 112.88, 109, 32 ppm. ν _max (KBr) 3116 (m), 2254 (m, CN), 1473 (s), 1440 (s), 1231 (s), 1132 (s) cm ^-1 .

MS (70 eV, EI) 423.9 (5.81%, M) ⁺ .

Example 2

Preparation of 2,3-dicyano-1,4-bis (trifluoromethanesulfonyloxy) naphthalene

As in the previous example, 1.99 grams (9.47 millimoles) of 2,3-dicyano-1,4-dihydroxynaphthalene was dissolved in 25 milliliters of dry dichloromethane and 10 milliliters.

Dry lutidine and the resulting brown solution was cooled to -20 ° C. 3.5 ml of a solution of 5.89 g (2.2 equivalents) of trifluoromethanesulfonic anhydride in 5 ml of dichloromethane were added dropwise over 30 minutes, the resulting solution was allowed to warm to room temperature and stirred at this temperature for 18 hours. The mixture was worked up as above to give the crude product, which was recrystallized from methanol to give 2.65 g (59 percent) of 2,3-dicyano-1,4-bis (trifluoromethanesulfonate).

sulfonyloxy) naphthalene in the form light yellow of crystals. Melting point 114 to 115 ° C. For C ₁₄ H ₄ N ₂ O ₆ S ₂ F ₆ Found: C 35.58%; H 0.74%; N 5.82%. Calculated: C 35.45%; H 0.85%; N 5.90%. ¹ H NMR (270 MHz, CDCl ₃ ) δ 8.38 (2H, dd) 8.12 (2H, dd) ppm

¹³ C NMR (270 MHz, CDCl 3) δ 147.22 (ArC-O), 133.62 (ArC-H), 129.54, 123.85 (ArC-H), 118.46 (CF ₃ , q, J = 321 Hz), 110.39, 106.04 ppm.

Example 3

Preparation of 3,6-bis (nonafluorobutanesulfonyloxy) phthalonitrile 2.53 grams (0.0158 millimoles) of 2,3-dicyanohydroquinone and one crystal of 18-crown-6-ether were dissolved in 60 ml of dry tetrahydrofuran (THF) and the resulting solution was cooled to 0 ° C. 1.45 grams (0.0363 millimoles) of sodium hydride (60% dispersion in mineral oil) was added portionwise to the solution, and 10.85 grams (0.036 millimoles) of nonafluorobutanesulfonyl fluoride was added dropwise at 0 ° C. The reaction mixture was allowed to warm to room temperature and stirred for 24 hours

999

102 ··

This results in a pale green solution. The mixture was diluted with 50 mL of diethyl ether and washed with 30 mL of 5% sodium hydroxide, 30 mL of 5% hydrochloric acid and 30 mL of brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The crude product was recrystallized from dichloromethane / methanol (99: 1) to give 3,6-bis (nonafluorobutanesulfonyloxy) phthalonitrile as white crystals.

¹ H NMR (300 MHz, acetone-d 6 δ 7.85 (s, 2H) ppm).

Example 4

Preparation of zinc dust (see D. D. Perrin, W. L. F. Armarego, "Purification of Laboratory Chemicals, 3rd edition)

120 grams of zinc dust was stirred in 300 ml of 2% hydrochloric acid for 2 minutes, and then the acid was removed by decantation. The remaining dust was successively mixed with 300 ml of 2 percent hydrochloric acid, 3 x 300 ml water and 2 x 200 ml 95 percent ethanol, allowing the dust to settle before decanting the solvent. Finally, the zinc dust was washed with 200 ml diethyl ether, filtered off and dried under vacuum for 24 hours. The dust obtained was stored over phosphorus pentoxide.

103

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Example 5

Preparation of n-decylzinc iodide (see Β H. Lipshutz in "Organometellics in Synthesis. A Manual, edited by M. Schlosser, John Wiley and Sons, 1994, Chichester)

In a two-necked, fire-dried, flask equipped with a reflux condenser and a rubber whisper, 10 grams (approximately 3 equivalents) of acid zinc dust and 3 milliliters of dry tetrahydrofuran (THF) were added under an argon atmosphere. A solution of 1.14 g (6.07 mmol) of dibromoethane in 2 ml of tetrahydrofuran (THF) was added via syringe and the reaction mixture was heated to boiling with a hot air gun. The mixture was then allowed to cool back to room temperature. This procedure was repeated once more and then 0.66 g (6.07 mmol) of trimethylsilyl chloride was added to the reaction mixture.

The mixture was again heated with a hot air gun and allowed to cool. The rubber septum was replaced by a pressure equalizing dropping funnel filled with a solution of 13.68 g (51 millimoles) of 1-iododecane in 25 ml of dry tetrahydrofuran (THF) and the reaction mixture was heated to 45-45 ° C. At this temperature, iododecane was added dropwise over 30 minutes and the resulting mixture was stirred at 40 ° C for an additional 12 hours. The reaction mixture was then allowed to cool and excess zinc allowed to settle (which took 4 hours). The resulting gray zinc reagent was transferred by capillary to a dry storage vessel and the remaining zinc was washed with milliliters of tetrahydrofuran (THF), allowed to settle, and the solution over zinc was transferred to a storage vessel to give 37 mL of a 1.24 molar solution of n-decylzinc iodide in tetrahydrofuran ( THF) (90% yield)

104

»» ÍW · 9 »

9 9 9

9 · 9

9 ···

IR »99 99 9999

NB. The complete iododecane reaction can be tested by hydrolyzing said zinc reagent and performing gas chromatography (GC).

Example 6

Preparation of 3,6-didecylphthalonitrile (Method A)

To a two-necked, flame-dried flask was added, under argon, 1 gram (2.36 mmol) of 3,6-bis (trifluoromethanesulfonyloxy) phthalonitrile, 0.30 g (7.0 mmol) of lithium chloride, 136 mg (5 mole percent) tetrakis (triphenylphosphine) palladium and 10 ml dry tetrahydrofuran (THF). After stirring at room temperature for 10 minutes, 20 ml of a 0.35 molar solution of decylzinc iodide in tetrahydrofuran (THF) (7.0 mmol) was added via syringe, the resulting solution was stirred at room temperature for 30 minutes and then heated to boiling for 12 hours. The solution was allowed to cool, filtered and the solvents were removed under reduced pressure. Thin layer chromatography (TLC) (eluting with petroleum ether / dichloromethane (1: 1)) revealed that the reaction mixture contained a mixture of 3,6-didecylphthalonitrile and a slower product, which was probably 3-decyl-6 (trifluoromethanesulfonyloxy). phthalonitrile.

Example 7

Preparation of 3,6-didecylphthalonitrile (Method B)

To a two-necked, flame-dried flask was added 0.154 (10 mole percent) bis (triphenylphosphine) nickel dichloride and 0.124 grams at room temperature and under an argon atmosphere.

105 ··· · · · · · · · · · · · · · · · · · · ·

1 * 9 9 9 9 9 9 9 9 9 (20 mole percent) triphenylphosphine. Next, 5 mL of dry tetrahydrofuran (THF) and 0.2 mL of a 2.5 molar solution of n-butyllithium in hexanes (20 mol%) were added to the flask to form a blood red suspension.

To this suspension was added 1 g (2.36 mmol) of solid 3,6-bis (trifluoromethanesulfonyloxy) phthalonitrile under a rapid stream of argon, and the resulting light brown solution was cooled to -78 ° C. 5.6 ml of a 1.24 molar solution of decylzinc iodide in tetrahydrofuran (THF) (7.0 mmol) were added via syringe to the reaction mixture containing 0.30 g (7.0 mmol) of lithium chloride.

The resulting solution was warmed to room temperature over approximately 1 hour and stirred at this temperature for an additional 16 hours. Then 10 ml of 5% hydrochloric acid and 20 ml of ethyl acetate were added carefully to the reaction mixture. The organic layer was separated, washed with 10 mL of 5 percent hydrochloric acid and 10 mL of brine. The aqueous residue was back extracted with 10 mL of ethyl acetate and the combined organic layers were dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The crude product was stirred in 10 mL of acetonitrile for 30 minutes and filtered to give 0.67 g (70 percent) of pure.

3,6-didecylphthalonitrile, which conformed to a known standard.

Example 8

Preparation of 3,6-bis (4'-chlorobutyl) phthalonitrile (Method B)

A mixture of 625 milligrams (2.4 millimoles) of triphenylphosphine,

1.5 grams (35 millimoles) of lithium chloride and 780 milligrams (1.2 millimoles) of bis (triphenylphosphine) nickel dichloride were 10 minutes

106 were stirred in 25 ml of tetrahydrofuran (THF). To the resulting blue solution was added at room temperature 1 ml of a 2.5 molar solution of n-butyllithium in hexanes. The solution turned dark red, 5 grams (12 millimoles) of solid 3,6-bis (trifluoromethanesulfonyloxy) phthalonitrile was added in a rapid stream of nitrogen, and the resulting light brown solution was cooled to -78 ° C. 50 ml of a 0.5 molar solution of chlorobutylzinc bromide in tetrahydrofuran (THF) (25 mmol, obtained from Aldrich) was added via syringe, the solution was allowed to warm to room temperature and stirred at this temperature for an additional 12 hours under nitrogen. The mixture was quenched with 50 mL of 5 percent hydrochloric acid and extracted with 3 x 20 mL of ethyl acetate. The combined organic layers were washed with 10 ml of 5% hydrochloric acid, 10 ml of 5% sodium hydroxide, 10 ml of brine and dried over anhydrous magnesium sulfate. The desiccant was removed by filtration and the solvents were removed under reduced pressure. The residue was purified by silica gel column chromatography (eluting with petroleum ether (40-60 ° C) / dichloromethane (1: 1)) to remove triphenylphosphine. The eluent was then changed to dichloromethane to give 1.92 g (6.2 millimoles, 52 percent) of 3,6-bis (4'-chlorobutyl) phthalonitrile as a pale yellow oil which solidified on standing.

Mp 61 ° C ^X H NMR (270 MHz, CDC1 ₃₎ δ 7.6 (s, 2H), 3.6 (t, 4H), 2.9 (t,

4H), 1.77 (m, 8H). ppm.

m / z 308 (M, 21.47%), 310 (M + 2, 15.42%).

107 · «· • • • • • • •

Example 9

Preparation of 3,6-bis (6'-chlorhexyl) phthalonitriles (Method B) As in the previous example, 0.5 grams (1.18 millimoles) of 3,6-bis (trifluoromethanesulfonyloxy) phthalonitriles was added to the nickel catalyst prepared of 78 milligrams of NiCl ₂ (PPh ₃ ) ₂ and 62.5 milligrams of PPh ₃ . The reaction mixture was cooled to -78 ° C and 5.5 mL of a 0.5 molar solution of 6-chlorohexylzinc bromide in tetrahydrofuran (THF) (2.75 mmol, obtained from Aldrich) was added via syringe. The solution was allowed to warm to room temperature and stirred at this temperature for an additional 16 hours. The mixture was quenched with 5% hydrochloric acid and treated as described above. The crude product obtained was purified by silica gel column chromatography (eluting with petroleum ether / dichloromethane (1: 1)), whereby triphenylphosphine was first isolated, followed by 3,6-bis (6'-chlorhexyl) -

phthalonitrile, the amount was 0.26 gram (60.5 percent Melting point 44.5 to 45.5 ° C. For C ₂ oH ₂ 6N2Cl 2 Found: C 66.07%; H 7.17 at " o, N 7.67%. Calculated: C 65.75%; H 7.17 O 0 z N 7.67%.

¹ H NMR (300 MHz, CDCl ₃ ) δ 7.48 (s, 2H), 3.54 (t, 4H, -OCH ₂ ),

2.87 (t, 4H, CH ₂ C1), 1.83 - 1.63 (m, 8H), 1.53 to 1.26 (m,

8H) ppm.

Example 10

Preparation of 3,6-bis [6 '- (imidazol-1-yl) hexyl] phthalonitriles A mixture of 720 milligrams (1.97 millimoles) of 3,6-bis (6'-chlorohexyl) phthalonitrile, the preparation of which is described in Example 9, • 0 »0

108

0 ♦

0 0 0 ·

0 0 0 ·

00 0 · 0 · ·

0 0 0 0 0 0 · 0 0 · 0 · 00

270 mg (4 millimoles) of imidazole, 10 equivalents of potassium carbonate, and a catalytic amount of tetra-butylammonium iodide in 10 ml of N, N-dimethylformamide (DMF) were heated at 60 ° C under nitrogen for 72 hours. After cooling, 100 ml of water was added to the reaction mixture. A light brown oil formed at the bottom of the flask and was separated. To this oil was added dichloromethane and the organic layer was washed with 2 x 20 mL water, 20 mL brine and dried over anhydrous magnesium sulfate. The desiccant was removed by filtration and the filtrate was concentrated in vacuo.

The crude product was separated by silica gel chromatography (eluting with dichloromethane followed by elution with methanol). Evaporation of the methanol fraction yielded 550 mg (1.3 mmol, 66 percent) of 3,6-bis [6 '- (imidazol-1-yl) hexyl] phthalonitrile as a thick light yellow oil.

¹ H NMR (270 MHz, CDCl ₃ ) δ 7.62 (s, 2H), 7.59 (br s, 2H), 7.2 (br s, 4H), 4.2 (t, 4H), 2 91 (t, 4H), 1.86 (m, 4H), 1.75 (m, 4H), 1.4 (m, 8H) ppm.

m / z 446 (M + H ₂ O).

Example 11

Preparation of 3,6-bis (4'-ethoxy-4'-oxobutyl) phthalonitriles (Method B)

A mixture of 375 milligrams (1.4 millimoles) of triphenylphosphine,

0.9 grams (21 millimoles) of lithium chloride and 470 milligrams (0.72 millimoles) of bis (triphenylphosphine) nickel dichloride were stirred under nitrogen in 15 milliliters of tetrahydrofuran (THF) for 10 minutes. To the resulting blue solution was added 0.6 mL of a 2.5 molar solution of n-butyllithium in hexanes at room temperature. The solution turned dark red,

109 · * ·· ·· ·· φ φ φ φ ♦ · Φ

Φ Φ · · φ · · Φ · · · · · · · · · · · · · ·

<ΦΦ • ♦ · <

Φ Φ ♦

3 grams (7.1 millimoles) of solid 3,6-bis (trifluoromethanesulfonyloxy) phthalonitrile were added in one portion to a rapid stream of nitrogen, and the resulting light brown solution was cooled to -78 ° C. 30 ml of a 0.5 molar solution of 4-ethoxy-4-oxobutylzinc bromide in tetrahydrofuran (THF) (15 mmoles, obtained from Aldrich) was added via syringe, the solution was allowed to warm to room temperature and stirred at this temperature for an additional 12 hours under nitrogen. atmosphere. The mixture was quenched with 50 mL of 5 percent hydrochloric acid and extracted with 3 x 20 mL of ethyl acetate. The combined organic layers were washed with 10 ml of 5% hydrochloric acid, 10 ml of 5% sodium hydroxide, 10 ml of brine and dried over anhydrous magnesium sulfate. The desiccant was removed by filtration and the solvents were removed under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluting with dichloromethane) to remove triphenylphosphine. The eluent was then changed to ethyl acetate to give 1.6 g (4.5 millimoles, percent) of 3,6-bis (4'-ethoxy-4'-oxobutyl) phthalonitrile as a pale yellow oil which solidified on standing.

Melting point 51 ° C ⁴ H NMR (270 MHz, CDCl ₃ ) δ 7.6 (s, 2H), 4.15 (q, 4H), 2.95 (t, 4H), 2.4 (t, 4H) ), 2.04 (m, 4H), 1.25 (t, 6H) ppm. m / z 311 (M-OEt, 5.59%).

110 · 1 1 1 1 1 1 1 1 1 1 1 1

Example 12

Preparation of 3,6-bis (4'-pivaloylbutyl) phthalonitriles (Method B)

a) 4-iodo-1- (pivaloyl) butane

To a stirred solution of 23.3 g (0.32 mmol) of dry tetrahydrofuran (THF) and 12.06 g (0.1 mmol) of pivaloyl chloride in 200 ml of dry acetonitrile was added 30 g (0.2 mmol) of sodium iodide. The flask was sealed with a drying tube and the mixture was stirred at room temperature for 12 hours. The resulting orange solution was quenched with 200 mL of saturated sodium bisulfite solution and extracted with 3 x 80 mL of diethyl ether. The combined organic layers were washed with 80 mL of 5% sodium hydroxide, 80 mL of saturated sodium bisulfite solution, 80 mL of brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The crude oil obtained was filtered through silica gel (eluting with diethyl ether / petroleum ether (1: 2)). Evaporation of the first fraction yielded 22.81 g (80.3 percent) of 4-iodo-1- (pivaloyl) butane.

¹ H NMR (300 MHz, CDCl ₃ ) δ 4.09 (t, 2H, J = 6.3 Hz), 3.22 (t,

2H, J = 6.8 Hz), 1.96-1.86 (m, 2H), 1.80-1.71 (m, 2H),

1.21 (s, 9H) ppm.

IR (neat) 1729 (s, CO).

b) Addition reactions

To a three-necked, flame-dried flask was added 0.63 g (10 mole percent) of bis (triphenylphosphine) nickel dichloride and 0.50 g (20 mole percent) of triphenylphosphine under an argon atmosphere. 20 ml of dry N, N-dimethylformamide (DMF) a were successively added

111 fc »

0.8 ml of a 2.5 molar solution of n-butyllithium in hexanes (20 mol%) to form a blood red suspension. To this suspension was added suddenly 4 grams (9.43 millimoles) of solid 3,6 (trifluoromethanesulfonyloxy) phthalonitrile and about 1.2 grams of solid lithium chloride in a rapid stream of argon. The resulting light brown solution was cooled to -78 ° C and 20 mL of a 1.2 molar solution of 4-pivaloylzinc iodide in tetrahydrofuran (THF) (0.024 mol) was added via syringe. The solution was allowed to warm to room temperature over 1 hour and stirred at this temperature for an additional 12 hours. 100 mL of ethyl acetate was added to the reaction mixture, and the mixture was washed twice with 40 mL of 5% hydrochloric acid, 40 mL of brine, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The obtained residue was further purified by silica gel column chromatography (eluting with dichloromethane). Triphenylphosphine was first isolated. Other fractions then contained the desired product, which was contaminated with triphenylphosphine and starting materials. The second silica gel column chromatography (eluting with petroleum ether / ethyl acetate 85:15 to 100: 30) gave 2.57 g (62 percent) after evaporation of the second fraction.

3,6-bis (4'-pivaloylbutyl) phthalonitrile as a colorless oil.

For C 26 H 36 N 2 O 4

Found: C 70.87 g. · o f H 8.21 O,. O z N 6.28 O, Ό · Calculated: C 70.88 g,. 0 f H 8.24 g. Ό z N 6, 36 G. 0 · ¹ H NMR (300 MHz, CDCl 3) δ 43, 43 (s) 2H), 4.10 (t, 4H, J = 7.7

Hz), 2.91 (t, 4H, J = 7.2 Hz), 1.78-1.61 (m, 8H), 1.20 (s, 18H) ppm.

112 fefefefe fefe fefe ¹³ C NMR (300 MHz, CDCl ₃ ) δ 178.63, 145.71, 133 48, 115, 89, 114.86, 63.43, 38.58, 38.03, 33.80, 26.07, 27.00 ppm.

MS (70eV, EI) 440.1 (2.7%, M ⁺ ).

Example 13

Preparation of -3-, 6-bis (4'-tert-butyldimethylsiloxybutyl) phthalonitrile (Method B)

4-Iodo-1- (tert-butyldimethylsilyloxy) butane (as described in Synthesis, 1999, 1231 and Synthesis, 1998, 56) was converted to the corresponding zinc derivative and used in the procedure described in the previous example. to give 3,6-bis (4'-tert-butyldimethylsilyloxybutyl) phthalonitrile as a colorless oil in a yield of 27.6 percent.

IR (neat) 2229 (CN).

¹³ C NMR (300 MHz, CDCl ₃ ) δ 146, 13, 133.351, 115.83, 115.13, 62.49, 33.99, 32.01, 26.86, 25.84, 18.20, - 5.48 ppm.

1 H NMR (300 MHz, CDCl ₃ ) δ 7.45 (s, 2H), 3.61 (t, 4H), 2.86 (t, 4H), 1.78-1.67 - (m, 4H) 1.60-1.52 (m, 4H), 0.86 (s, 9H), 0.02 (s, 6H) ppm.

Example 14

Preparation of 3,6-bis (1,1-H-2,2-H-perfluordecyl) phthalonitrile (Method B)

This compound was prepared from 1,1H-2,2-H-perfluordecylzinc iodide according to the procedure described in Example 13. After stirring the reaction mixture at room temperature for 16 hours, the residue was dissolved in 250 ml of ether / tetrahydrofuran (THF: 4: 1). ) and the resulting solution was washed

113

1111 111

112 11 · 1 1 1 9 11 i lili

112 · 1 »*

111 «» 9111 milliliters of 5% hydrochloric acid. The resulting precipitate was filtered off and the organic layer was washed with 40 ml of brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was stirred in 20 ml of acetonitrile and filtered. The two solids were combined and recrystallized from α, α, α-trifluorotoulene to give 1.56 g (58 percent) of 3,6-bis (1,1-H-2,2-H-perfluordecyl) phthalonitrile. For C28H10N2F34

Found: C 33.01%; H 0, 82%; N 2.93%. Calculated: C 32.96%; H 1, 06%; N 2.75%. IR (film) 2229 (CN). ^{Χ Η} NMR (300 MHz, CsF ₆ comprising 10% C ₆ D ₆ ) δ 7.36 ' (s, 2H) 3.16

(t, 7.9 Hz), 2.57-2.41 (m, 4H) ppm.

Example 15

Preparation of 3,6-bis (1'-octinyl) phthalonitrile (Method B)

To a two-necked flask was added under argon

2.20 g (0.02 mol) of 1-octine and 10 ml of dry tetrahydrofuran (THF). The mixture was cooled to -78 ° C and 8 mL of a 2.5 molar n-butyllithium solution (0.02 mol) was added dropwise. The reaction mixture was stirred at -78 ° C for 30 minutes, and 20 mL of a 1 molar zinc chloride solution in diethyl ether (obtained from Aldrich) was added over 10 minutes to the resulting yellow solution. The resulting white suspension was stirred at -78 ° C for 1 hour and in the meantime a nickel catalyst was prepared in another two-necked flask so that 0.53 g (0.0008 mol) of bis (triphenylphosphine) nickel dichloride and 0.42 g (0.0016 g) were prepared. mol) of triphenylphosphine was dissolved in 20 ml of dry 44

114 • 44

4 4 4

4 4 4

4 4 4

4 4 4 «· ♦ · * 4 4 t« 4 4

4 4

4 4 • 4 4 4 4 4 tetrahydrofuran (THF). To this solution was added dropwise 0.65 mL of a 2.5 molar solution of n-butyllithium in hexane (0.0016 mol) to give an active red colored catalyst. To this catalyst was added 3.40 g (0.008 mol) of 3,6- (trifluoromethanesulfonyloxy) phthalonitrile in solid form under a rapid stream of argon, cooled to -78 ° C and the prepared 1-octinylzinc chloride solution was added via capillary. The reaction mixture was allowed to warm to room temperature over approximately 1 hour and stirred at this temperature for an additional 24 hours. The reaction mixture was then concentrated under reduced pressure and the residue was dissolved in 100 mL of ethyl acetate. The solution was washed with 2 x 20 ml of 5 percent hydrochloric acid, 2 x 20 ml of 5 percent sodium hydroxide and 20 ml of brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The obtained residue was further purified by silica gel column chromatography (eluting with dichloromethane / petroleum ether (1: 2 to 1:10)). The first fraction contained triphenylphosphine, while evaporation of the second fraction gave 1.31 g (48 percent) of 3,6-bis (1'-octinyl) phthalonitrile as a pale yellow oil which solidified on standing.

NMR (60 MHz, CDCl ₃ ) δ 7.60 (s, 2H), 2.3 (t, 4H), 1.7-1.2 (m, 16H), 0.9 (t, 6H) ppm.

Example 16

Preparation of 3,6-didecylphthalonitrile (Method C)

To a two-necked, flame-dried flask was added 0.51 grams (3.64 millimoles) of 1-decene and 5 milliliters dry tetrahydrofuran under an argon atmosphere. The solution was cooled to 0 [deg.] C. and 1.2 ml of 1 molar was added dropwise.

115

4 solution of borane (BH ₃ ) (1.2 millimoles) in tetrahydrofuran (THF).

The reaction mixture was stirred at 0 ° C for 4 hours, treated with 4 mL of dry tetrahydrofuran (THF) and

0.85 g (4 millimoles) of anhydrous potassium phosphate and the resulting mixture was stirred at room temperature for 1 hour.

Then, 0.08 g (1.9 mmol) of anhydrous lithium chloride, 0.25 g (0.59 mmol) was added to the reaction mixture.

Of 3,6-bis (trifluoromethanesulfonyloxy) phthalonitrile, and at a 10 minute interval, 21 mg (5 mole percent) of Pd (dppf) Cl ₂ (i.e.

(1,1'-bis (diphenylphosphino) ferrocene) dichloropalladium). The mixture was heated at reflux for 10 hours, cooled and the palladium salts removed by filtration. The filtrate was concentrated under reduced pressure and the crude black product was purified by silica gel column chromatography (eluting with toluene) to give 0.09 g (38 percent) of 3,6-didecylphthalonitrile.

Example 17

Preparation of 3,6-diphenylphthalonitrile (Method D)

0.5 g (1.18 mmoles) of 3,6-bis (trifluoromethanesulfonyloxy) phthalonitrile and 0.13 g (3 mmoles) of anhydrous lithium chloride were stirred under argon in 15 ml of dry toluene for 30 minutes. 84.0 mg of tetrakis (triphenylphosphine) palladium were added to the mixture, and the reaction mixture was stirred for an additional 10 minutes. Then, 0.43 g of phenylboronic acid and 2 ml of a 2 molar aqueous sodium carbonate solution were added sequentially. The resulting mixture was heated to reflux for 14 hours, cooled and diluted with 15 mL of ethyl acetate. The mixture was washed with 2 x 10 ml 10% potassium hydroxide, 10 ml 5% acid

116 • 9 9 9 · * ·· • 99 9 9 99 9

9

9999 99 9

9 9 9 ·· ···· · · · ♦ ·

9 9

9 ·

9

Hydrochloric acid and 10 milliliters of brine, dried, filtered and concentrated under reduced pressure. The crude product was recrystallized from toluene to give 0.26 g (79 percent) of 3,6-diphenylphthalonitrile. Mp 221-223.5 ° C.

NMR (270 MHz, CDCl ₃ ) δ 7.80 (s, 2H), 7.63-7.51 (m, 10H).

Example 18

Preparation of 3,6-bis (4-methoxyphenyl) phthalonitrile (Method D) 0.5 grams (1.18 millimoles) of 3,6-bis (trifluoromethanesulfonyloxy) phthalonitriles and 0.13 grams (3 millimoles) of anhydrous lithium chloride was 30 minutes stirred under argon in 15 mL dry toluene. 84.0 mg (10 mol%) of tetrakis (triphenylphosphine) palladium was added to the mixture, and the reaction mixture was stirred for an additional 10 minutes. Then, 0.45 g (3.5 mmol, 2.5 equivalents) of 4-methoxyphenylboronic acid and 2 ml of a 2 molar aqueous solution of cesium carbonate were added sequentially. The resulting mixture was heated to reflux for 14 hours, cooled and diluted with 15 mL of ethyl acetate. The organics were washed with 2 x 10 ml 10% potassium hydroxide, 10 ml 5% hydrochloric acid and 10 ml brine and dried over anhydrous magnesium sulfate. The desiccant was removed by filtration and the filtrate was concentrated under reduced pressure. The crude product was recrystallized from toluene to give 0.29 g (0.86 mmol, 73 percent) of 3,6-bis (3-methoxydiphenyl) phthalonitrile as white crystals.

Mp 213-215 ° C.

⁴ Η NMR (300 MHz, CDC1 ₃₎ δ 7.74 (s, 2H), 7.55 (d, 4H, J = 8.5

Hz), 7.06 (d, 4H, J = 8.6 Hz), 3.89 (s, 6H) ppm.

♦ ♦ • *

117 • 9 9 9 4 4 • 44 4 · 4

44 9494

¹³ C NMR (300 MHz, CDCl ₃ ) δ 161.07, 145.29, 134.0, 130,32, 128.91 116 22, 115.49, 114.77, 55.56 (CH ₃₎ ppm. For C 22 H 16 N 2 O 2 Found: C 77.38%; H 4.68%; N 8.21%. Calculated: C 77.63%; H 4.74%; N 8.23%. m / z (EI) 340 (21 %), 262 (100%) • Vmax (nujol) 2224 (CN) cm ^-1 .

Example 19

Preparation of 3,6-bis (3-methoxyphenyl) phthalonitrile (Method D) 0.5 grams (1.18 millimoles) of 3,6-bis (trifluoromethanesulfonyloxy) phthalonitrile and 0.13 grams (3 millimoles) of anhydrous lithium chloride was 30 minutes stirred under argon in 15 mL dry toluene. 84.0 mg (10 mol%) of tetrakis (triphenylphosphine) palladium was added to the mixture, and the reaction mixture was stirred for an additional 10 minutes. Then, 0.45 g (3.5 millimoles, 2.5 equivalents) was gradually added to the mixture.

3-methoxyphenylboronic acid and 2 ml of a 2 molar aqueous solution of cesium carbonate. The resulting mixture was heated to reflux for 14 hours, cooled and diluted with 15 mL of ethyl acetate. The organics were washed with 2 x 10 ml 10% potassium hydroxide, 10 ml 5% hydrochloric acid and 10 ml brine and dried over anhydrous magnesium sulfate. The desiccant was removed by filtration and the filtrate was concentrated under reduced pressure. The crude product was recrystallized from toluene to give 0.28 g (0.82 mmol, 70 percent) of 3,6-bis (3-methoxydiphenyl) phthalonitrile as white crystals.

Mp 236-239 ° C.

, - 4

4 4

444 • 4 • 4

118

44

4 4 4

4 4

4 4

4 <4 4 4444 ¹³ C NMR (300 MHz, CDCl ₃ ) δ 160.22, 145.97, 137.84, 134.12,

130.45, 121.26, 115.96, 115.78, 115.55, 114, 57, 55.59 ppm. For C 22 H 16 N 2 O 2 Found: C 77.54%; H, 4.64 O,. S r N 8.24 O About · Calculated: C 77.63%; H, 4.74 Q,. 0 y N 8.23 0. About · ¹ H NMR (300 MHz, CDCl 3) δ 7.79 (s, 2H), 7.45 (t, 2H, J = 8 Hz) 7.16 (ddd, 2H, V = 1, 0.8, 4.9 and 1 Hz), 7.11 (t, 2H, J = 2.5 and 1.6 Hz), 7.06 (ddd, 2H, J = 1, 0.8, 4.9) and 1 Hz), 3.89 (with,

6H) ppm.

m / z (EI) 340 (100%). in _max (nujol) 2224 (CN) cm-1

Example 20

Preparation of 3,6-bis (dodecylsulfanyl) phthalonitrile (Method E) 2.00 grams (4.71 millimoles) of 3,6-bis (trifluoromethanesulfonyloxy) phthalonitrile and 4.51 grams (22.4 millimoles) of dodecanethiol were stirred under a nitrogen atmosphere. in 20 ml of dry N, N-dimethylformamide (DMF). To the solution was gradually added 5 grams (excess) of anhydrous potassium carbonate over 4 hours, and the reaction mixture was stirred at room temperature for another 72 hours. The mixture was then poured into 100 ml of cold water and filtered. The filtrate was washed with 50 ml of water and 50 ml of methanol. The mother liquor and the extracts were combined and extracted with 2 x 100 mL ethyl acetate. The combined organics were washed with 50 mL of 5 percent sodium hydroxide and 50 mL of brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The resulting yellow solid was mixed with the solid from the above filtration and recrystallized from dichloromethane / ethyl acetate. The resulting yellow needles were

4 • 4

119

44 was filtered and washed with petroleum ether (to remove traces of dodecanethiol) to give 1.74 g (70 percent) of 3,6-bis (dodecylsulfanyl) phthalonitrile.

Melting point 97.8-101.2 ° C.

⁴ Η NMR (270 MHz, CDC1 ₃₎ δ 7.49 (s, 2H), 3.01 (t, 4H), 1.70 1.20 (m, 40H), 0.88 (t, 6H) ppm .

Example 21

Preparation of 3,6-bis (decylsulfanyl) phthalonitriles (Method E)

In a conventional procedure, 2.3 grams (excess) of finely ground potassium carbonate and 3.30 grams (19.0 millimoles) of decanethiol were stirred under nitrogen in 10 milliliters of dry N, N-dimethylformamide (DMF). 2.00 grams (4.7 mmol) of 3,6-bis (trifluoromethanesulfonyloxy) phthalonitrile was gradually added over 2 hours and the reaction mixture was stirred at room temperature for 72 hours. The mixture was poured into 150 ml of cold 5% sodium hydroxide and filtered. The mother liquor was extracted with 3 x 50 mL ethyl acetate. The combined organics were washed with 50 mL of 5% sodium hydroxide, 50 mL of 5% hydrogen chloride and 50 mL of brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting yellow solid was mixed with the solid from the above filtration and recrystallized from dichloromethane / ethyl acetate. The resulting yellow needles were filtered and washed with petroleum ether and dried to give 3,6-bis (decylsulfanyl) phthalonitrile in 68% yield.

For C28H44N2S2

Found: C 71.31%; H, 9.38%; N, 5.85%.

Calculated: C 71.14 ^{Χ Η} NMR (300 MHz, CDC1 ₃₎ δ Hz), 1.68 (quint, 4H, 7.4, 6H, J = 6.7 Hz) ppm.

120

9 »9 9 999 9 999 999

9 9 99 9 9 9

9 9 9 · 9 ♦ 9 99

9 9 ·

9 9

9 9

9 9

9 «9999%; H, 9.39%; N, 5.93%.

7.50 (s, 2H), 3.02 (t, 4H, J = 7.5 Hz), 1.47-1.25 (m, 28H), 0.88 (t,

Examples 22 to 27

The following compounds were prepared in an analogous manner:

3,6-bis (dodecylsulfanyl) phthalonitrile Yield: 70 percent.

For C ₃ 2H ₅₂ N ₂ S ₂

found: C 71, 94 O,. 0 f H 9.74 O,, o z N 5.03%. calculated: C 72, 67 O,. Ό Z H 9.91 O.. 0 Z N 5.30%. ¹ H NMR (270 MHz, CDC1 ₃ ) δ 7.49 (s , 2H), 3, 01 (t, 4H, J = 7.4 Hz), 1,72- 1, 64 (m, 4H) 1.50 - 1.24 (m, 36H), 0.88 (t, 6H,

= 6.4 Hz) ppm.

3,6-bis (undecylsulfanyl) phthalonitrile Yield: 63%, mp 92-93 ° C. For C ₃ H ₄₈ N ₂ S ₂

found: C 71.53 %; H 9.62 %; N 5.40%. calculated: C 71.94 %; H 9.66 %; N 5.59%. ¹ H NMR (300 MHz, CDC1 ₃ ) δ 7.50 ( : s, 2H) 3.02 (t, 4 H, J = 7.2 Hz), 1,72- 1, 64 (m, 4H) 1.50 - 1.25 (m, 32H), 0.88 (t, 6H,

= 6.7 Hz) ppm.

3,6-bis (nonylsulfanyl) phthalonitrile Yield: 65 percent, mp 86-88 ° C. For C ₂₆ H ₄₀ N ₂ S ₂

121 · 4 · 4 · t

·

found: C 70, 11 %; H 8.91 0,. 0 y N 6.10%. calculated: C 70.22 %; H 9.07 g,. 0 y N 6.30 O 0 · @ ¹ H NMR (300 MHz, CDC1 ₃ ) δ 7.51 ( : s, 2H) 3, 02 (t, 4H, J = 7.4 Hz), 1.73- 1, 63 (m, 4H) 1.52 - 1.25 ( m, 24H) ·, 0r89 ( t, 6H,

= 6.0 Hz) ppm.

¹³ C NMR (75 MHz, CDCl ₃ ) δ 141, 60, 132.30, 117.37, 33.91, 31.88, 29.44, 29.25, 29.20, 28.74, 22.70 ,

114.06, 14.12 ppm.

3,6-bis (octylsulfanyl) phthalonitrile Yield: 27 percent, mp 91-92 ° C. For C ₂ 4H ₃ 6N ₂ S ₂

found: C 69.20%; H 8.74%; N 6.56%. calculated: C 69.19%; H 8.72%; N 6.73%. ⁴ Η NMR, (300 MHz, CDCl ₃ ) δ 7.50 (s, 2H), 3.03 (t, 4H, J = 7.4 Hz), 1.69 (quint, 4H, 7.4 Hz), 1.45 (quint, 4H), 1.28 (m, 16H), 0.89 (t, 6H, J = 6.7 Hz) ppm.

3,6-bis (heptylsulfanyl) phthalonitrile Yield: 46 percent.

For C ₂₂ H ₃₂ N ₂ S ₂

found: C 67.50 %; H 8.21%; N, 7.07 O. 0 · calculated: C 68.01 %; H 8.31%; N, 7.21 O About · ⁴ H NMR (300 MHz, CDCl 3)? MHz, CDCI3) δ 7.51 (s, 2H), 3.03 (t, 4H, J) = 7.5 Hz), 1.70 ( quint , 4H, 7.4 Hz), 1.46 (m, 4H). 1.31 (m, 12H),

0.91 (t, 6H, J = 6.7Hz) ppm.

3,6-bis (hexylsulfanyl) phthalonitrile Yield: 53 percent, mp 82-83.5 ° C.

For C 20 H 28 N 2 S 2 found: C 66.60%; H 7.81%; N 7.72%.

calculated: C 66.62%; H 7.83%; N, 7.77%.

• 4 ♦ · · »

9 9

899 ·

9

122

• 9

9 89

8

9

8 8 9

8 8

8 8

8 9

8909 ^{Χ Η} NMR (300 MHz, CDC1 ₃₎ δ 7.51 (s, 2H), 3.03 (t, 4H, J = 7.4 Hz), 1.73 - 1.63 (m, 4H), 1.50-1.24 (m, 12H), 0.90 (t, 6H, J = 6.9 Hz) ppm.

Example 28

Preparation of 1,4-bis (decylsulfanyl) -2,3-naphthalonitrile (Method E)

0.5 grams (1.05 millimoles) of 1,4-bis (trifluoromethanesulfonyloxy) -2,3-naphthalonitrile and 0.56 grams (3.15 millimoles, equivalents) of decanethiol were stirred under a nitrogen atmosphere in 5 milliliters of dry N, N -dimethylformamide (DMF). 1.14 g (excess) of anhydrous cesium carbonate was gradually added over 4 hours and the reaction mixture was stirred at room temperature for 72 hours. The mixture was then poured into 25 ml of cold water and filtered. The solid was washed with 25 mL of water. The mother liquor and aqueous extracts were combined and extracted with 2 x 25 mL ethyl acetate. The combined organic extracts were washed with 25 ml of 5% sodium hydroxide, 25 ml of brine, dried over anhydrous sodium sulfate and evaporated to dryness. The resulting yellow solid was combined with the previously isolated solid product and recrystallized from acetone to give 0.30 g (46 percent) of 1,4-bis (decylsulfanyl) 2,3-naphthalonitrile.

Mp 76 ° C

For C ₃₂ H ₄₆ N ₂ S ₂ found: C 73.35%; H 8.83%; N, 5.24%.

calculated: C 73.51%; H 8.86%; N, 5.35%.

123 ♦ · · · · · · · · ·

·

9 • 9

99

9 9 9

9 9

9 9

9 9

9999 ^Χ NMR (270 MHz, CDCl ₃ ) δ 8.81 4H, J = 7.3 Hz), 1.6-1.2 (m, (m, 2H), 7.87

32H), 0.87 (t, (m, 2H)), 3.07 (t, 6H, J = 6.85) ppm.

Example 29

Preparation of 3,6-bispiperidinylphthalonitrile (Method E) Milliliters of dry piperidine (distilled over CaH ₂ ) were stirred under argon. To the piperidine was added 0.5 g (1.18 mmol) of 3,6-bis (trifluoromethanesulfonyloxy) phthalonitrile, and the reaction mixture was stirred for 72 hours. The flask was placed in the refrigerator and 3,6-bispiperidinylphthalonitrile precipitated as yellow crystals which were filtered off and washed with acetonitrile. 160 mg (0.54 mmol, 46 percent) of the product was obtained.

^{Χ Η} NMR (270 MHz, DMSO-CZ _s) δ 6.77 (s, 2H), 2.8 (br s, 8H), 1.5 (br s, 12H) ppm.

Preparation 30

Preparation of 3,6-bis (1'-decenyl) phthalonitrile (Method F)

0.5 grams (1.18 millimoles) of 3,6-bis (trifluoromethanesulfonyloxy) phthalonitrile and 0.13 grams (3 millimoles) of lithium chloride were dissolved in 3 milliliters of dry N, N-dimethylformamide (DMF) under nitrogen. 0.50 grams (3.6 millimoles) of 1-decene, 72 milligrams (about 5 mole percent) of tetrakistriphenylphosphine) palladium and 0.5 milliliters of 2,6-glutidine were added to the solution at 10 minute intervals, and the resulting mixture was heated at 100 DEG C. for 16 hours. Noc: 2 ° C. The reaction mixture was cooled, poured into excess water (40 mL) and extracted with 3 x 20 mL.

124 ···· ««

999 •

99 ♦ · * «<<9 9 9 9 9

9 98 9 9 9

9 9 9 9 9 9

9 9 9 9 9

99 99 9999 ethyl acetate. The combined organics were washed with 20 mL of 5% sodium hydroxide, 20 mL of 5% hydrochloric acid and brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude black tar was purified by silica gel column chromatography (eluting with petroleum ether / dichloromethane (1: 1 to 0: 1)). Triphenylphosphine was contained in the first fraction and 0.04 g (8.4 percent) of 3,6-bis (1'-decenyl) phthalonitrile was isolated in the second fraction.

Preparation of phthalocyanine derivatives from the compounds described above containing the same substituents on each ring

Example 31

Preparation of 1,4,8,11,15,18,22,25-octakis (1,1-H-2,2-Hperfluordecyl) phthalocyanine

0.5 grams (0.5 millimoles) of 3,6-bis (1,1-H-2,2-Perfluordecyl) phthalonitriles was heated to boiling in 10 milliliters of DMAE under a constant stream of ammonia for 1 hour. At the end of this time, 36 mg (0.33 equivalents) of zinc acetate dihydrate (99.999 percent pure) was added and the mixture was boiled for a further 24 hours. After cooling, the solvent was removed under reduced pressure, the solid residue was washed with methanol and chromatographed on silica gel (eluting with trifluorotoluene). The green fraction was isolated and recrystallization of 1,4, 8,11, 15, 18,22 ', 25-octakis (1,1H-2,2-H-perfluordecyl) phthalocyanine from trifluorotoluene yielded 130 mg (25 percent) of product. .

· »··

125 • ·· ··· · ·

⁴ H NMR (270 MHz, C ₆ F ₆ + 2% C ₆ D ₆ , 50 ° C) δ 8.04 (s, 8H), 5.15 (t, 16H), 3.21 (m, 16) ppm.

Example 32. . . .

Preparation of 1,4,8,11,15,18,22,25-octakis [6- (imidazol-1-yl) hexyl] phthalocyaninosin (II) complex

950 milligrams (2.2 millimoles) of 3,6-bis [6 '- (imidazol-1yl) hexyl] phthalonitrile was heated to boiling in 15 milliliters of butan-1-ol in the presence of 150 milligrams (0.7 millimoles) of zinc acetate dihydrate (purity 99.999 percent).

A large excess of DBU was added to the reaction mixture and boiling was continued for a further 12 hours. The solvent was removed from the reaction mixture under reduced pressure, 40 ml of water was added to the residue, and the solid green product was filtered off and washed with water. The solid obtained was dissolved in 10 ml of hot methanol and 40 ml of water was added. The precipitated 1,4,8,11,15,18,22,25-octacis [6 (imidazol-1-yl) hexyl] phthalocyanine zinc complex was filtered off and dried overnight at 40 ° C.

_Max (abs.) 705 nm (THF).

Example 33

Preparation of 1,4,8,11,15,18,22,25-octakis (dodecylsulfanyl) phthalocyanine-zinc complex

1.03 g (1.95 mmol) of 3,6- (dodecylsulfanyl) phthalonitrile was heated to boiling in 20 ml of DMAE under a constant stream of ammonia. After 1 hour of boiling, 0.13 g (0.3 equivalents) of zinc acetate dihydrate was added to the mixture. Heating the mixture to boil under a stream of ammonia • «

126 ···················· · ·· ·· ·· ···· continued for another 18 hours. After cooling, the solvent was removed under reduced pressure and the solid residue was chromatographed on silica gel (eluting with dichloromethane / triethylamine (100: 1)). The first reddish-brown fraction was combined and concentrated under reduced pressure. The obtained purple solid was recrystallized twice from tetrahydrofuran (THF) / acetone / methanol to give 130 mg

1,4,8,11,15,18,22,25-octakis (dodecylsulfanyl) phthalocyanine-zinc complex.

For C28H208N8SgZn

found: C 70.20%; H, 9.57%; N 4.89%. calculated: C 70.49%; H, 9.61%; N 5.14%. @ ¹ H NMR (270 MHz, C ₆ D _6/1 drop pyr-d _5/50 ° C) δ 7.85 (s, 8H) , 3.37 (t, 16H) 2 04 (quint, 16H), 1.66 (br quint, .16H) , 1,45 - - 1,25

(m, 128H), 0.96 (t, 24H) ppm.

_{Λ max} (THF) 780 nm;

_Max (toluene / 1% pyridine) 777 nm.

The NB reaction had to be allowed to proceed for more than 16 hours at the boiling point, otherwise the starting material was isolated from the mixture.

Example 34

Preparation of 1,4,8,11,15,18,22,25-octakis (decylsulfanyl) phthalocyanine-zinc complex

A solution of 1.01 g (2.14 mmol) of 3,6-bis (decylsulfanyl) phthalonitrile in 9 ml of dry pentanol was heated to boiling under nitrogen. To the mixture was added 0.23 g (1.50 mmol) of DBU and the mixture was heated for an additional 1 hour. Then, 0.14 g (0.64 millimoles) of zinc acetate dihydrate (99.999 percent pure) was added to the reaction mixture, and

The mixture was heated for an additional 20 hours. The mixture was cooled and the solvents were removed under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluting with dichloromethane / triethylamine (100: 1)). The first reddish-brown fraction was combined and concentrated under reduced pressure. The crude product was first triturated with 3 x 20 mL hot acetone to remove yellow colored impurities and then recrystallized from tetrahydrofuran (THF) / methanol to yield 0.68 g (65.0 percent).

1,4,8,11,15,18,22,25-octakis (decylsulfanyl) phthalocyaninosin zinc complex.

For CnsHnsNsSgZn

found: C 69.01%; H 9.05%; N 5.71%. calculated: C 68.76%; H 9.07%; N 5.73%. MS (MALDI) isotopic cluster 1956 (M ⁺ ); unit 3910. ¹ H NMR (270 MHz, C ₆ D ₆ containing 1 % pyr-d ₅ ) δ 7 87 (s, 8H)

3.38 (t, 16H, J = 7.25 Hz), 2.11 - 2.01 (m, 16H), 1.68 - 1.58 (m, 16H), 1.52 - 1.18 ( m, 96H), 0.90 (t, 24H, J = 6.6 Hz) ppm. _Max (abs.) 781 nm (THF);

_Max (em.) 804 nm (THF).

Examples 35 to 39

In a manner analogous to that of Example 34, the following compounds were prepared:

1,4,8,11,15,18,22,25-octakis (undecylsulfanyl) phthalocyanine-zinc complex Yield: 32.8 percent.

For C20H192N8SgZn: C, 69.64; H, 9.33%; N, 5.39.

128

4 · 4 · 4 · 4

4 4 4 4

4444 · 44

4 4 4 4 • 444 44 «44 44 calculated: C 69.97%; H, 9.35%; N 5.42%.

¹ H NMR (270 MHz, C ₆ D ₆ containing 1% pyr-d ₅ , 50 ° C) δ 7.86 (s, 8H), 3.37 (t, 16H, J = 7.4 Hz), 2 10-2.01 (m, 16H), 1.68 1.60 (m, 16H), 1.52-1.20 (m, 112H), 0.91 (t, 24H, J)

6.8 Hz) ppm.

_Max (abs.) 781 nm (THF); _Max (em.) 8 04 nm (THF).

1,4,8,11,15,18,22,25-octakis (nonylsulfanyl) phthalocyanine-zinc complex Yield: 14.8 percent.

Found: C 67.69% for C 14 H 16 N 8 S 9 Zn; H, 8.71%; N, 5.91%.

calculated: C 67.73%; H, 8.74%; N, 6.08%.

NMR (270 MHz, C ₆ D ₆ containing 1% pyr-d ₅ , 50 ° C) δ 7.87 (s, 8H), 3.40 (t, 16H, J = 7.4 Hz), 2.08 2.02 (m, 16), 1.67 160 (m, 16H), 1.55-1.19 (m, 80H), 0.89 (t, 24H, J =

6.6 Hz) ppm.

Λ _max (abs.) 782 nm (THF);

Mmax (em.) 802 nm ’(THF).

1,4,8,11,15,18,22,25-octakis (octylsulfanyl) phthalocyanine-zinc complex Yield: 12.0 percent.

For C9 ₆ Hi44N ₈ S ₈ Zn

found: C 66.74%; H 8.51 9- * 0 y N 6.48%. calculated: C 66.63%; H 8.39 o. · o r N 6.48%. ^{@ 4} H NMR (270 MHz, G ₆ D ₆ , 50 ° C) δ 7, 84 (s, 8H) , 3.34 (t, 16H, J 7.4 Hz), 2, 01 (m (16H), 1.62 (m, 16H), 1.3 (br m, 64H), 0 90

(t, 24H, J = 6.8Hz) ppm. Λ _max 783 nm (THF).

129 · ef fe f f f ef f ef ef ef f f ef ef ef ef ef ef «« «« «« «« «« «« · «« «« «·« · «« fefe fefe fefe ····

1,4,8,11,15,18,22,25-octakis (heptylsulfanyl) phthalocyanine-zinc complex

Yield: 10.6 percent. .

For CggHi28NgSgZn

found: C 65.25 O. o z H 8.03 O. o Z N 6, 78 0, o · calculated: C 65.32 o. o z H 7.98 O,. 0 z N 6, 93 O, 0. ¹ H NMR (270 MHz, C ₆ D ₆ , 50 ° C) δ 7, 82 (s, 8H) , 3.32 (t, 16H, J 7.4 Hz), 1, 99 (m, (16H), 1 , 60 (m, 16H), 1.3 (br m, 48H) , o, 89

(t, 24H, J = 6.8 Hz) ppm.

Λ _max 782 nm (THF).

1,4,8,11,15,18,22,25-octakis (hexylsulfanyl) phthalocyanine-zinc complex

Yield: 32.8 percent. For CgoHnsNgSgZn found: C 63.84%; H, 7.43%; N 7.37%. calculated: C 63.73%; H, 7.49%; N 7.43%. 1 H NMR (270 MHz, C ₆ D ₆ containing 1% pyr-d ₅ , 50 ° C) δ 7.81

8H), 3.30 (t, 16H, J = 7.4 Hz), 1.97 (m, 16H), 1.58 (m, 16H), 1.33 (m, 32H), 0.89 ( t, 24H, J = 6.8 Hz) ppm.

Λ _max (abs.) 782 nm;

Λ _max (em.) 801 nm (THF).

Example 40

Preparation of 1,4,8,11,15,18,22,25-octakis (decylsulfanyl) phthalocyanine-magnesium complex

A solution of 0.3 g (0.64 mmol) of 3,6-bis (decylsulfanyl) phthalonitrile in 3 mL of dry pentanol was heated to boiling under nitrogen. 0.07 grams was added to the mixture.

130

f) · · · · · · · · · · · · · · · · · ·

DBU (0.46 mmol) was added and the mixture was heated for an additional 1 hour. Then, 18.2 mg (0.19 mmol) of anhydrous magnesium chloride was added to the reaction mixture and the mixture was heated for an additional 20 hours. The mixture was cooled and the solvents were removed under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluting with dichloromethane / triethylamine (100: 1)). The first reddish-brown fraction was combined and concentrated under reduced pressure. The crude product was first triturated with 3 x 10 mL hot methanol to remove yellow colored impurities and then recrystallized from tetrahydrofuran (THF) / methanol to give 0.21 g (69.0 percent).

1,4,8,11,15,18,22,25-octakis (decylsulfanyl) phthalocyanine-magnesium complex.

Pro CnzHnsNgSgMg found: C 70.36%; H, 9.38%; N 5.77%. calculated: C 70.23%; H, 9.26%; N 5.85%. ¹ H NMR (270 MHz, C ₆ D ₆ containing 1% pyrr- ₅ , 50 ° C) δ 7.86 (s,

8H), 3.38 (t, 16H, J = 7.4 Hz) 2.05 (quint, 16H, J = 7.4 Hz), 1.68-1.58 (m, 16H), 1.52 1.26 (m, 96H), 0.90 (t, 24H, J = 6.6 Hz) ppm.

Λ _max (abs.) 77 6 nm (THF);

_Max (em.) 793 nm (THF).

Examples 41 to 44

In a manner analogous to that of Example 34, the following compounds were prepared:

1,4,8,11,15,18,22,25-octakis (nonylsulfanyl) phthalocyaninemagnesium complex

131 • • • • · · * • · · · · »· · · · · • · · · · · « ♦ · ·· · · · · · · For C10H16NgSgMg found: C 69.44%; H 8.76%; N 5.99%. calculated: C 69.27%; H 8.94%; N 6.21%. ¹ H NMR (270 MHz, CgD ₆ containing 1 % pyr-d ₅ 50 ⁰ C). δ. 7.86 (s,

8H), 3.38 (t, 16Η, J = 7.25 Hz), 2.04 (quint, 16H, J = 7.4 Hz), 1.67-1.59 (m, 16H), 1, 52-1.18 (m, 80H), 0.90 (t, 24H, J = 6.9 Hz) ppm.

_Max (abs.) 772 nm (THF);

_Max (em.) 796, 8 nm (THF).

1,4,8,11,15,18,22,25-octakis (octylsulfanyl) phthalocyanine-magnesium complex For C 8 H 11 N 8 S 5 Mg found: C 68.29%; H 8.69%; N, 6.50%.

calculated: C 68.18%; H, 8.58%; N, 6.63%.

¹ H NMR (270 MHz, C ₆ D ₆ containing 1% pyr-d ₅ , 50 ° C) δ 7.86 (s, 8H), 3.37 (t, 16H, J = 7.4 Hz), 2 .03 (quint, 16H, J = 7.4Hz), 1.68-1.57 (m, 16H), 1.52-1.25 (m, 64H), 0.91 (t, 24H, J = 6.8 Hz) ppm.

_Max (abs.) 774 nm (THF);

Λ max (em) 794 nm (THF).

1,4,8,11,15,18,22,25-octakis (heptylsulfanyl) phthalocyaninemagnesium complex

For C8H12N3SgMg found: C 68.29%;

calculated: C 66.97%;

¹ H NMR (270 MHz, C ₆ D ₆ , 50 ° C) 7.4 Hz), 2.02 (quint, 16H, J

H 8.69%; N, 6.50%. H 8.18%; N, 7.10%. δ 7.84 (s, 8H); 3.35 (t, 16H, J) = 7.4 Hz), 1.6 (m, 16H), 1.315

(m, 48H), 0.89 (t, 24H, J = 6.6 Hz) ppm.

132 ··· 0 · * ··· · 0 · 0 · 0 · 0 · 0 · 0 · ·

0 0 0 · 00 «0

1,4,8,11,15,18,22,25-octakis (hexylsulfanyl) phthalocyaninemagnesium complex

Found: C, 65.51; H, calculated: C 65.52%; H ^{Χ Η} NMR (270 MHz, C ₆ D _S containing 8H), 3.34 (t, 16H, J = 7.25 Hz) Hz), 1,65- 1.57 (m, 16H), 1.45

7.60%; N

7.70%; N% pyr-d ₅ , 50 2.00 (quint,

7.64%.

7.64%.

° C) δ 7.83 (s,

16H, J = 7.5-1.25 (m, 32H), 0.89 (t, 24H,

J = 6.9 Hz) ppm.

Λ _max (abs.) 77 3 nm;

Λ _max (em.) 792 nm (THF).

Example 45

Preparation of 1,4,8,11,15,18,22,25-octakis (nonylsulfanyl) phthalocyanine milligrams 1,4,8,11,15,18,22,25-octakis (nonylsulfanyl) phthalocyaninomagnesium complex was dissolved in 4 milliliters trifluoroacetic acid and the resulting solution was stirred at room temperature under argon for 2 hours. The reaction mixture was poured into 80 mL of water / ice and extracted with 2 x 50 mL of dichloromethane. The resulting dichloromethane extract was washed with 40 mL of 5% sodium hydroxide, 40 mL of brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was further purified by silica gel column chromatography (eluting with dichloromethane / triethylamine (99: 1)). The first fraction was collected, evaporated and the solid residue was recrystallized from tetrahydrofuran (THF) / acetone to give 1,4,8,11,15,18,22,25-octakis (nonylsulfanyl) phthalocyanine.

133 • fc fc fcfcfcfc • · · · · · fc ····· Fcfcfc fcfc fcfc fcfc fcfc fcfcfcfc For C104H162N8S8 found: C 70.06%; H, 9.20; N 6.12%. calculated: C 70.14%; H, 9.17%; N 6.29%. NMR (270 MHz, C ₆ D ₆ containing 1% pyr-d ₅ , 50 ° C). δ 7.70 (s,

2H), 3.21 (t, 16Η, J = 7.25 Hz), 1.92 (quint, 16H, J = 7.4 Hz), 1.66-1.55 (m, 16H, 1.50) - 1.24 (m, 80H), 0.91 (t, 24H,

J = 6.9 Hz), 0.07 (s, 2H) ppm.

Example 46

Preparation of 1,4,8,11,15,18,22,25-octakis (hexylsulfanyl) phthalocyaninato-lead complex

0.5 g (1.39 mmol) of 3,6-bis (hexylsulfanyl) phthalonitrile was dissolved in 7 ml of dry pentane-1-ol and the resulting solution was heated to boiling under nitrogen. DBU (0.14 mL, 0.97 mmol) was added and the mixture was heated to boiling for an additional 1 hour. Then, 0.15 g (0.42 mmol) of lead acetate was added to the reaction mixture, and the mixture was heated to reflux for an additional 18 hours. The mixture was cooled and the solvents were removed under reduced pressure. The residue obtained was filtered through silica gel (which had previously been equilibrated with dichloromethane / triethylamine (99: 1)), eluting with dichloromethane. The solid residue obtained after evaporation of the solvents was recrystallized from tetrahydrofuran / acetone to give 87 mg (15 percent) of 1,4,8,11,15,18,22,25 octocis (hexylsulfanyl) phthalocyaninato-lead complex as a dark red to brown crystals.

Melting point 145-148 ° C.

For C ₈₀ Hii2NgSsPb Found: C, 58.29%; 5 6.65%; N, 6.65%.

134

9 9 9 ♦ · * · 9 9 9 9 »» W · 00 0 9 9 9 0 000 0 0 0 0 00 0 * 0000 99 999 0 0 · 0000 0 0 00 0000 00 00 0 0 00 0000 calculated: C 58.25%; H 6.84%; N, 6.79%.

¹ H NMR (270 MHz, C ₆ D ₆ 1 drop pyridine-d ₅ , 50 ° C) δ 7.76 (8H, s, Ar-H), 3.27 (16H, t, J = 7.42, -S-CH ₂ -), 2.02 - 1.91 (16H, m, -S-CH2-CH2-), 1.64 - 1.53 (16H, m, -S-CH ₂ -CH ₂ - CH ₂ -), - 1.32 (32H, m, -S-CH ₂ -CH ₂ -CH ₂ -CH ₂ -CH ₂ -), 0.85 (24H, t, J = 0.7, R- _CH3) ppm. m / z (MALDI) 1650 (M + 1, 100%).

Λ _max 827 nm (toluene).

Example 47

Preparation of 1,4,8,11,15,18,22,25-octakis (hexylsulfanyl) phthalocyaninatochlorine dithium complex

0.5 g (1.39 mmol) of 3,6-bis (hexylsulfanyl) phthalonitrile was dissolved in 7 ml of dry pentane-1-ol and the resulting solution was heated to boiling under nitrogen.

DBU (0.14 mL, 0.97 mmol) was added and the mixture was heated to boiling for an additional 1 hour. Then, 93 mg (0.42 mmol) of indium chloride was added to the reaction mixture and the mixture was heated to reflux for an additional 18 hours. The mixture was cooled and the solvents were removed under reduced pressure. The residue was filtered through silica gel (previously equilibrated with dichloromethane / triethylamine (99: 1)), eluting initially with dichloromethane to remove the yellow colored impurities, then tetrahydrofuran (THF) to elute the dark colored fraction. This second fraction was re-chromatographed on silica gel (previously equilibrated with dichloromethane / triethylamine (99: 1)), eluting with dichloromethane first and then with dichloromethane / tetrahydrofuran (THF) (95: 5). The first dark blue colored fraction was recovered from which solvents and this were removed

135 «« · to to to t t t t t t t t t to t to to to to to to 135 to to to to The solid residue obtained was recrystallized from tetrahydrofuran (THF) / acetone to give 17 milligrams (3 percent) of 1,4,8,11,15,18,22,25-octakis (hexylsulfanyl) phthalocyaninatochloroindite. complex in the form of a dark blue to black solid.

Melting point 202 to 204 ° C. For C80H112N8S ₈ InCl found: C 60.66%; H, 7.11%; N 6.84% calculated: C 60.33%; H, 7.09%; N 7.04% ¹ H NMR (270 MHz, C ₆ C > 6 1 drop pyridine-c (5.50 ° C) δ 7.79 (8H, Ar-H), 3.23 (16H, t , j = 7, -S-CH ₂ -), 1.96 - 1.87 (16H, m, - CH ₂ -CH ₂ -), 1, 65 - 1, 55 (16H, m, -S-CH ₂ -CH ₂ -CH ₂ -), 1.45 - 1.32

(32H, m, -S-CH 2 -CH 2 -CH 2 -CH 2 -CH 2 -), 0.92-0.90 (24H, m,

R-CH ₃₎ in ppm.

Λ _max 827 nm (THF).

Example 48

Preparation of 1,4,8,11,15,18,22,25-octakis (dodecylsulfanyl) phthalocyanine

0.21 g (0.40 mmoles) of 3,6- (dodecylsulfanyl) phthalonitrile was heated to boiling in 10 ml of DMAE under a constant stream of ammonia. After heating for 2 hours, 19.8 mg (0.48 equivalents) of lithium chloride was added to the mixture, and the mixture was heated under reflux with ammonia for a further 20 hours. After cooling, the solvent was removed under reduced pressure. The solid residue was stirred for 30 minutes in 10 ml of glacial acetic acid to give a pale red reaction mixture. The acetic acid was removed under reduced pressure, the residue was dissolved in dichloromethane and the resulting solution washed with saturated sodium carbonate solution, saturated

136 • 4 4 4 44 4 4 4 4 4 44

444 · 4 4 4 44 4 · 4 4 »· 44 444 4

4,444 4 4 «

4 44 4444 with ammonium chloride solution, brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure.

The crude product was further purified by silica gel column chromatography (eluting with dichloromethane / triethylamine (100: 1)). The first reddish brown fraction was combined, concentrated under reduced pressure, and the purple solid obtained was recrystallized from tetrahydrofuran (THF) / acetone to give 44.1 mg of 1,4,8,11,15,18,22,25 -octakis (dodecylsulfanyl) phthalocyanine.

Mp 88-88.5 ° C.

For C128H210N8S8 found: C 72.53%; H, 9.97%; N, 5.29.

calculated: C 72.60%; H 10.00%; N, 5.29.

Λ _max (toluene) δ 97 nm.

Study of synthesis procedures using methods A and B

Example 49

Preparation of 4,5-dibromo-3,6-dihydroxyphthalonitriles To a stirred solution of 3 grams (18.7 millimoles) of 2,3-dicyanohydroquinone in 12 milliliters of tert. of n-butyl alcohol at 45 ° C was added portionwise over 15 minutes 7 grams (38.8 millimoles) of NBS. The mixture was stirred for an additional 2 hours and an additional 7 grams (38.8 millimoles) of NBS was added over 15 minutes. After an additional two hours, the reaction mixture was allowed to cool to room temperature and poured with vigorous stirring into an aqueous solution of sodium bisulfite (6 grams in 60 mL, excess), which was cooled to 0 ° C. The mixture was stirred for 10 minutes, the resulting precipitate was filtered off and filtered

137 • 0 ·· • 0 · 0

0 0

Wash with 30 milliliters of cold water. The product was dried under vacuum at 60 ° C for 24 hours to give 3.94 g (66.1 percent) of 4,5-dibromo-3,6-dihydroxyphthalonitrile as a cream colored powder which was used in the next step without further purification. degree. However, for analysis, a sample of the product was recrystallized from acetone / water.

248 DEG C. (decomposition).

Found: C 30.47%; H 0.42%; N 8.70%

Br, 50.22%.

calculated: C 30.22%; H 0.63%; N 8.81%

Br, 50.27%.

¹³ C NMR (270 MHz, acetone-d ₆ ) δ 151.74 (CO), 123.08 (C-Br),

113.07 (CN), 102.46 (C-CN) ppm.

ν _max (nujol) 3250 (br), 2232 (m) cm ^-1 .

Example 50

Preparation of 4,5-dibromo-3,6-dibutoxyphthalonitrile

A mixture of 2.50 g (7.86 mmol) of 4,5-dibromo-3,6-dihydroxyphthalonitrile, 4.95 g (18.9 mmol) of triphenylphosphine and 1.5 g (20.2 mmol) of 1-butanol was dissolved. in 80 mL of dry tetrahydrofuran (THF) and the resulting solution was cooled to 0 ° C. A solution of 4.35 g (21.5 mmol) of diisopropyl azadicarboxylate in 30 ml of tetrahydrofuran (THF) was added dropwise over 30 minutes. The resulting solution was allowed to warm to room temperature and stirred at this temperature for an additional 10 hours. Evaporation of tetrahydrofuran (THF) under reduced pressure gave a dark red oil, which was dissolved in 20 mL of diethyl ether. The solution was filtered to remove it.

138 • ·· »· <

♦ • ♦ ♦ •

Undissolved triphenylphosphine oxide, concentrated and separated by column chromatography (eluting with dichloromethane / petroleum ether (1: 2)). The product was recrystallized from cyclohexane to give 2.75 g (83.6 percent).

4,5-dibromo-3,6-dibutoxyphthalonitrile as white crystals. Mp 72-73 ° C.

For C ₆ H ₁₈ N ₂ O ₂ Br 2 (430.14)

found: C 44.51%; H 4.28%; N 6, 47% Br, 37.33. calculated: C 44.68%; H 4.22%; N 6, 51% Br, 37.15. ¹ H NMR (270 MHz, GDC1 ₃ ) δ 4.24 (t, J = 6.4Hz, 4H-), 1.92 (quint, J = 7.0 Hz, 4H), 1.67 -1.53 (m, 4H); 1.04 (t, J = 7.3 Hz, 6 H -1 ppm ¹³ C NMR (270 MHz, CDCl 3) δ 156 , 37 (ArC-0) 61 (A) rC-Br) r 112.33 (CN) , 109 22 (ArC-CN) 76.43, 31.95, 18 , 92, 13.73 ppm. Vmax (nujol) 2230 (m) cm ¹ . MS (70eV, EI): m / z (%): 432 (3.1), 430 (5.2), 428 (3.5) [M ^& lt ^{; +} & gt ^; ].

Example 51

Preparation of 4-bromo-3,6-dibutoxyphthalonitrile

A mixture of 3 grams (9.4 millimoles) of 4,5-dibromo-3,6-dihydroxyphthalonitrile, 3 grams (excess) of finely divided potassium carbonate and 0.26 grams (0.7 millimoles) ΤΒΆΒ was heated at 80 ° C for 12 hours. milliliters of methyl ethyl ketone (MEK). The reaction mixture was cooled, and 3.70 g (20 millimoles) of 1-iodobutane was added. The mixture was heated to boiling for a further 72 hours. After cooling, the reaction mixture was filtered and washed with ethyl acetate. The organics were removed under reduced pressure and the residue dissolved in

139

4 · 4 4 »· 4 ·« 4 4 «64 4» 64 4 • 4 · • 4 · 4 • 4 9 4 4 «9 9 • 9449 444 ·· · · · · 9 4 · ·

100 ml ethyl acetate. The solution was washed with 25 mL of 5% hydrochloric acid, 25 mL of saturated potassium carbonate solution, 25 mL of water, milliliters of brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (eluting with petroleum ether / dichloromethane (2: 1)) and recrystallized

from cyclohexane, to obtain 1 , 43 grams (43 percent) 4-bromo-3,6-dibutoxyphthalonitrile. 102.5-104 ° C. For C ₆ H ₁₉ N ₂ O ₂ Br (351,24) found: C - 54.71%; H 5.43%; N • 7,89% Br, 22.67. calculated: C 54.85%; H 5.47%; N 8,00% Br, 22.54. ¹ H NMR (270 MHz acetone-dg) δ 7.88 (s, 1 H), 4.30 (t, 2H, J = 6.4 (Hz), 4.18 (t, 2H, J = 6.4Hz) 1.86 (m, 4H), 1.56 (m, 4H); 1.00 (t, 3H, J) = 7.3 Hz), 0.99 (t, 3H, J = 7.3 H [z] ppm.

¹³ C NMR (300 MHz, acetone-dg) δ 157.68 (ArC-O), 152.80 (ArC-O), 124.94, 123.33 (ArC-H), 112.81 (CN) , 112.69 (CN), 111.39 (ArC-CN), 103.83 (ArC-CN), 75.75, 70.40, 31.81, 30.57, 18.70, 18.66, 13.07, 12.98 ppm.

in _max (nujol) 2230 (m) cm ^-1 .

MS (70eV, EI): m / z (%): 350.1 (4.8), 352.1 (4.5) [M ⁺ ].

Example 52

Preparation of 1,4-dibutoxy-2,3-dibromo-8,11,15,18,22,25hexakis (decyl) phthalocyaninatonicelic complex

To a mixture of 2.56 grams (6.27 millimoles) of 3,6-didecylphthalonitrile (prepared as described in ···)

9

140 ♦ · 9 99 99

99 «99 99 99 • 99 99 99 99 ·

999 · 9 99 999 9 · • 9 · 9 9 9 999 ♦ ··· ·· 99 * 9 Μ 9999

McKeown, N. B., Chambrier, I., Cook, J., J. Chem. Soc. Perkin Trans. 1, 1990, 1169) and 0.30 grams (0.70 millimoles) of 4,5-dibromo-3, β-dibutoxyphthalonitrile in 20 milliliters of boiling butanol were added approximately 50 milligrams (7.5 millimoles) of freshly purified lithium in an argon atmosphere. The reaction mixture was heated to boiling in the dark for 16 hours, cooled and added

0.53 grams (2.1 millimoles) of nickel acetate acetate hydrate and the resulting mixture was heated to reflux for a further 2 hours. After cooling, the solvents were removed under reduced pressure and the residue was triturated with methanol to give a green solid. Purification by column chromatography (eluting with petroleum ether) yielded 0.71 g (24 percent) of 1,4,8,11,15,18,22,25-octakis (decyl) phthalocyaninatonicellic complex in the first fraction. After switching the eluent to petroether / dichloromethane (1: 1), a second fraction was isolated and further purified by silica gel column chromatography (eluting with petroleum ether / dichloromethane (19: 1)) to recrystallize from tetrahydrofuran ( THF) / methanol obtained 45.7 milligrams (3.8 percent)

1,4-dibutoxy-2,3-dibromo-8,11,15,18,22,25-hexakis (decyl) phthalocyaninatonicellic complex.

Melting point 72 ° C (K-1), 67 ° c (I-D) 57 ° C (D -K). For C ₁₀ H ₁₅ N ₈ O ₂ Br ₂ Ni (1716, 84) found: C 70.40 O., o Z H 8.90 %; N 6.30%. calculated: C 70.04 0,. Ό Z H 8.82 %; N 6.53%. ¹ H NMR (300 MHz, C ₅ D ₆ ) δ 7 , 82 (with, 4H), 7 , 81 (s, 2H), 4.75 (t, 4H, J = 7.5Hz) 4.66 - 4 , 57 (3 overlap seeding t, 12H), 2.34 - 2.17 (m, 16H), 1.92 - 1 , 11 (m, 88H), 0.95 (t, 6H, J = 7.4

Hz), 0.87-0.80 (m, 18H) ppm.

UV / Vis (3.68 x ΙΟ ⁶ M in toluene, log ε) λ 716 (5.10), 698 (5.03), 636 (4.39) nm.

141 ♦ · 9 9 9 9 9 9

MS (FAB): m / z: isotopic cluster at 1716 [M ⁺ + H].

Example 53

Preparation of 1,4-dibutoxy-2,3- (2'-trimethylsilylethinyl) 8,11,15,18,22,25-hexakis (decyl) phthalocyaninatonicellate complex

To a stirred solution of 40 milligrams (23.3 micromoles)

1,4-dibutoxy-2,3-dibromo-8,11,15,18,22,25-hexakis (decyl) phthalocyaninatonicelium complex in 3.5 ml dry degassed triethylamine, which was placed in a pressure tube with a screw cap filled with argon 7 milligrams (10 micromoles) of bis (triphenylphosphine) palladium chloride, 2.2 milligrams (11.6 micromoles) of cuprous iodide and 25 milligrams (255 micromoles) of TMSA were added sequentially at 10 minute intervals. The rubber septum which had so far sealed the pressure tube was replaced with a screw cap under a rapid stream of argon, and the reaction mixture was stirred and heated to 100 ° C for 16 hours. The mixture was cooled and an additional 4.1 milligrams of bis (triphenylphosphine) palladium chloride added under argon,

1.7 milligrams of cuprous iodide and 25 milligrams of TMSA. The mixture was heated at 100 ° C for an additional 12 hours, cooled, filtered, and concentrated under reduced pressure. The resulting residue was dried at 0.5 mm of mercury for 12 hours to remove excess TMSA and triethylamine traces and then purified by silica gel column chromatography (eluting with petroleum ether / dichloromethane (97: 3)). The first fraction contained 3.4 mg of unreacted starting material. The second fraction contained the mixture and the following green colored fractions, which contained only a small amount of the substance, were discarded.

142 ·· · 9 · 9 · · · · · · · ·

The second fraction was further purified by silica gel column chromatography (eluting with petroleum ether / dichloromethane (first 98.5: 1.5 then 97: 3)) to isolate 1,4-dibutoxy-2 in the second fraction, 3- (2'-trimethylsilylethynyl) -8,11,15,18,22,25-hexakis (decyl) phthalocyaninatonicelic complex, after recrystallization from -tetrahydrofuran (THF) / methanol, 13.2 mg (35 percent)

Mp 69 ° C.

¹ H NMR (270 MHz, CDCl ₃ ) δ 7.78 (br s, 4H), 7.75 (s, 2H), 4.60 (t, 4H, J = 7.2 Hz), 4.47 ( t, 4H, J = 6.9 Hz), 4.35 - 4.26 (m, 8H), 2.10 - 1.90 (m, 16H), 1.60 - 1.08 (m, 88H) 0.95 (t, 6H, = 7.4 Hz), 0.80 '(t, 12H, J = 6.6 Hz), 0.79 (t, 6H, J = 6.6 Hz), 0.43 (s, 18H) ppm.

¹³ C NMR (67.5 MHz, CDCl ₃ ) δ 154.18 (ArCO), 147.99, 139, 19, 138.13, 137.77, 134.75, 134.66, 134.43, 130, 83, 130.47,

130.29, 130.19, 129.16, 128.17, 127.81, 127.47, 104.74 (C = Csi), 100, 97 (ChCl 3), 75.43 (OCH ₂ ), 32, 66, 32.56, 32.18, 31.88, 31.50, 30.53, 29.90, 29, 85, 29, 72, 29, 67, 29, 61, 29, 45, 29.31, 22.64, 22, -55, 19, 37, 14.20, 14.07, 0.20 ppm. ν _max (KBr) 2929 (s), 2861 (m), 2155 (w), 1598 (w), 1457 (w), 1200 (w), 1092 (m) cm ^-1 .

UV / Vis (2.80 x 10 ^-6 M in toluene, log ε) λ 732 (4.99), 702 (4.95) nm.

MS (FAB) m / z: isotopic cluster in 1747 [M ⁺ + H].

143 »· ♦ ·

Example 54

Preparation of 1,4-dibutoxy-2,3-di (ethynyl) -8,11,15,18,22,25hexakis (decyl) phthalocyaninatonicelic complex

To a solution of 48.6 milligrams (28.3 micromoles) of 1,4-dibutoxy-2,3-dibromo-8,11,15,18,22,25-hexakis (decyl) phthalocyaninatonicelic complex, 10 milligrams (233 micromoles) of anhydrous lithium chloride and 9.5 milligrams (36 micromoles) of triphenylphosphine in 6 milliliters of dry degassed toluene was added under argon atmosphere 10.5 milligrams (9.0 micromoles) of tetrakis (triphenylphosphine) palladium. The mixture was stirred for 10 minutes, 60 mg (190 micromoles) of tributyl (ethynyl) tin was added, and the resulting reaction mixture was heated to 100 ° C for 16 hours, cooled, and degassed under reduced pressure. The residue was triturated with acetone to remove excess tributyl (ethinyl) tin and the residue was washed with tetrahydrofuran (THF) from the filter paper. Tetrahydrofuran (THF) was evaporated under reduced pressure and the obtained residue was purified by column chromatography (eluting with petroleum ether / dichloromethane (19: 1)). The product was recrystallized from tetrahydrofuran (THF) / methanol to give 27.2 mg (60 percent) of 1,4-dibutoxy-2,3-di (ethynyl) 8,11,15,18,22,25 -hexakis (decyl) phthalocyaninatonic acid complex.

Melting point 83 ° C (K-D), 91 ° C (D-I).

For C104H152N8O2N.CH3OH (1637.14) found: C, 76.99%; H, 9.56%; N, 6.98%.

calculated: C. 77.03%; H, 9.60%; N 6.84%.

^{Χ Η} NMR (270 MHz, C ₆ D ₆₎ δ 7.81 to 7.78 (m, 6H), 4.83 to 4.76 (m, 8H), 4.61 to 4.56 (m, 8H 3.53 (s, 2H), 2.33-2.21 (m, 16H),

144 · * ♦ «# # # # # # # # # # # # # # # # # # # #

4,444,444

4944 44 44 44 »4,444«

1.93 - 1.11 (m, 88H), 0.96 (t, 6H, J = 7.4 Hz), 0.92 - 0.81 (m, 18) ppm.

¹³ C NMR (67.5 MHz, C ₅ D ₆ ) δ 154.86, 148.47, 148.40, 142.86,

139.57, 138.37, 138.01, 135.40, 135.31, 131.45, 130.93,

130.89, 130.00, 121.68, 87.63, 80.13, 75.87, 33.23, 32.93,

32.20, 31.16, 31.09, 30.57 - 29.6, 23.04, 23.01, 19.70, 14.33,

14.26 ppm.

UV / Vis (2.51 x 10 ^-6 M in toluene, log ε) λ 729 (4.99), 698 (4.88), 666 (4.44), 628 (4.23) nm.

MS (FAB): m / z isotopic cluster at 1606 [M ⁺ + H].

Example 55

Preparation of 1,4-dibutoxy-2,3-di (ethynyl) -8,11,15,18,22,25hexakis (decyl) phthalocyaninatonicelic complex

To a solution of 9.2 milligrams (5.3 micromoles) of 1,4-dibutoxy-2,3 (2'-trimethylsilylethynyl) -8,11,15,18,22,25-hexakis (decyl) phthalocyaninatonicellate complex in 5 ml of tetrahydrofuran (THF) and 1 ml of methanol were added potassium hydroxide solution (0.1 ml of a solution containing one flake of hydroxide in 0.5 ml of water) and the reaction mixture was stirred in the dark under argon for 12 hours. One drop of 5% hydrochloric acid was added to the mixture and the solvents were removed under reduced pressure. The residue was triturated with methanol and further purified by silica gel column chromatography (eluting with petroleum ether / dichloromethane (10: 1)) to give 1,4-dibutoxy-2 (6.7 mg, 79%) after evaporation of the appropriate fraction, 3-di (ethynyl) 8,11,15,18,22,25-hexakis (decyl) phthalocyaninatonicelic complex, which coincided with the sample prepared in Example 54.

·· ** I ·

145 • 4 · 4 · 4 · 4 · 4 · 44 · 44 · 44 · «« · »4 44 4444

Example 56

Preparation of 1,4-dibutoxy-2-bromo-8,11,15,18,22,25 --- hexakis (decyl) phthalocyaninatonicelic complex

1,4-Dibutoxy-2-bromo-8,11,15,18,22,2 5-hexakis (decyl) phthalocyaninatonicelic complex was prepared by mixed cyclotetramerization of 4-bromo-3,6-dibutoxyphthalonitrile and

3,6-didecylphthalonitrile using the procedure of formation

1,4-dibutoxy-2,3-dibromo-8,11,15,18,22,25-hexakis (decyl) phthalo-

cyaninatonicellate complex ve 4pr ocentním yield and who was described above in Example adu 52. Mp 30 ° C (K-D) 106 Noc: 2 ° C (D-I). For C ₁₀ H 15 N ₂ O ₂ BrNi 1 (1635,95) found: C 74.08%; H 9.52%; N 6.19%. calculated: C 73.42%; H 9.30%; N 6.85%. ¹ H NMR (300 MHz, C ₆ D ₆ ) δ 7.82 (br s, 4H), 7 , 77 (with, 2H), 7.68 (s, 1H), 4.83-4.7 8 (br. T, 4. Η), 4.66 (t, 2H, J = 7.0 Hz), 4.63 - 4.57 (2 x t, 8H), 4.22 (t, 2H, J = 6, 8 Hz) , 2.34-2.22

(m, 14H), 2.13 (quint, 2H, J = 7.2 Hz), 1.93-1.10 (m, 88H), 0.99 (t, 3H, J = 7.4 Hz) 0.91-0.76 (m, 21H) ppm.

¹³ C NMR (67.5 MHz, CDCl ₃ ) δ 151.54, 147.74, 147.67, 147.46, 147.13, 146.70, 146.52, 143.68, 142.61, 139 , 03, 138.94

137.93, 137.70, 137.66, 134.84, 134.77, 134.70, 134.65,

134.47, 134.38, 130.87, 130.28, 130.17, 130.10, 125.19,

119.52, 116, 37, 75.10 (OCH ₂ ), 69.76 (OCH ₂ ), 32.74, 32.62,

32.31, 32.15, 31.86, 31.81, 31.65, 31.48, 31.16, 30.46, 30.26, 29, 90, 29.80, 29, '71, 29 , 65, 29.62, 29.45, 29.36, 29.29, 29.24, 22.63, 22.57, 19.45, 19.36, 14.05 ppm.

UV / Vis (3.37 x ΙΟ ⁶ M in toluene, log ε) λ 714 (5.10), 700 (sh),

635 (4.47) nm.

146 * 9 · 9 9 9 9 9 9 9 9 9 99 9

999 99 99 99

999 99 99 99 «8 ·

9,999,999

9900 99 99 99 9 «·· * ·

Example 57

Preparation of 1,4-dibutoxy-2- (2'-trimethylsilylethynyl) 8,11,15,18,22,25-hexakis (decyl) phthalocyaninatonicellate complex

1,4-Dibutoxy-2- (2'-trimethylsilylethynyl) 8,11,15,18,22,25-hexakis (decyl) phthalocyaninatonicellate complex was prepared in 62% yield according to the procedure of Example 53, which described Preparation 1,4 -dibutoxy-2,3- (2'-trimethylsilylethynyl) -8,11,15,18,22,25-hexakis (decyl) phthalocyaninatonicellate complex, provided as solvent

tetrahydrofur mixture was used anu (THF) / tr methylamine (5: 1). Melting point 46 ° C (KD), 113 Pro C ₁₀₅ Hi ₅ oN ₈ 0 ₂ SiNi (1653,25) C (D-1). Found: C 76, 95%; H 9.67%; N 6.84%. calculated: C 76.28%; H 9.75%; N 6.78%. ⁴ Η NMR (270 MHz, toluene-dg) δ 7, 81 (s. 6H), 7, 65 (s, 1H), 4.86 4.78 (br t, 6H), 4.68-4.58 (2xT, 8H), 4.26 (brt, 2H) 2.38-2.20 (m, 16H), 1.90-1, 24H), 0.49 (s, 9H) ppm. 10 (m, 88 H), 0.99 - 0.76 (m, UV / Vis (3.44 x 10 ^-6 M in toluene, (5.02), 640 (4.43), 346 (4.59) log ε) λ 722 (5) nm. 09), 700

MS (FAB): m / z: isotopic cluster at 1653 [M ⁺ + H].

Example 58

Preparation of 1,4'-dibutoxy-2- (ethynyl) - 8,11,15,18,22,25hexakis (decyl) -phthalocyaninatonicelic complex

1,4-Dibutoxy-2- (ethynyl) -8,11,15,18,22,25-hexakis (decyl) phthalocyaninatonicellate complex was prepared in 48 percent

147 »»

«··· ··

443 4 4 ·· 9 «· * 4 ·

43 ·· 4 4 4 4

4 4 4 4 4

44,444 · ·

4 4 4 4 β-4

4,444,444,444 as described in Example 54, which described the preparation of 1,4-dibutoxy-2,3-di (ethynyl) -8,11,15,18,22,25hexakis (decyl) phthalocyaninatonicellate complex.

Melting point 36 ° C (K-D), 131 ° C (D-I).

For C 10 H 15 _{S 2} N ₈ 0 ₂ Ni (1518.07) found: C 77.80%; H, 9.68%; N, 7.09%.

calculated: C 77.49%; H, 9.69%; N, 7.09%.

NMR (270 MHz, C ₅ D ₆ ) δ 7.81 - 7.78 (m, 6H), 7.75 (s, 1H). 4.87 - 4.82 (m, 6H), 4.66 - 4.55 (m 8H) 4.27 (t, 2H, J = 7.0) Hz), 3.28 (s, 1H), 2.31-2.23 (m, 16H) 1.98-1.06 (m, 88H), 0.99 (2 x t, 6H), 0.94-0.77 (m, 18H) ppm. ν _max (KBr) 3304 (m), 2965 (sh), 2927 (with) 2853 (s), 1467 (m), 1318 (m), 1187 (mf, 1102 (m) cm -1 ⁾ . UV / Vis (5.20 x 10 ^-5 M in toluene, log ε) λ 721 (5.07), 701 (5.01), 641 (4.39), 347 (4.54) nm. Example 59

Preparation of 1,4-dibutoxy-2,3-di (4'-ethynylpyridine) 8,11,15,18,22,25-hexakis (decyl) phthalocyaninatonicelic complex

To a solution of 40 milligrams (25.0 micromoles) of 1,4-dibutoxy-2,3di (ethinyl) -8,11,15,18,22,25-hexakis (decyl) phthalocyaninatonicellate complex and 31 milligrams (150 micromoles) of 4- of iodopyridine in 6 ml of dry and degassed toluene / triethylamine (5: 1) mixture was added 2.3 milligrams (10 mole percent) of tris (dibenzylideneacetone) palladium [Pd ₂ (dba) ₃ ] and 3.0 milligrams (40 moles) in an argon atmosphere. mole percent) triphenylarsin. The reaction mixture was heated at 80 ° C for 24 h, cooled and the solvents were removed under reduced pressure. The residue was triturated with acetone and

148 e 9 9 t · t · t · 0 ♦ ♦ 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 · · · · · · · ·

9499 49 purified by column chromatography (eluting with petroleum ether / dichloromethane (DCM) / triethylamine (25: 2: 0.25)) to remove unreacted starting materials. After the eluent was changed to tetrahydrofuran (THF) / petroleum ether (1: 1), the fraction was isolated after evaporation and recrystallized. from tetrahydrofuran (THF) / methanol, 31.2 mg (71 percent) of 1,4-dibutoxy-2,3-di (4'-ethynylpyridine) 8,11,15,18,22,25-hexakis (decyl) was obtained ) phthalocyaninatonicellate complex.

For C114H158N10O2N1O: C, 77.80%; H 8.90%; N 7.83%.

calculated: C ~ 77.83%; H, 9.05%; N. 7.96%.

¹ H NMR (270 MHz, C ₆ D ₆ , 50 ° C) δ 8.57 (dd, 4H, J = 4.5 & 1.5 Hz),

7.87-7.81 (m, 6H), 7.42 (dd, 4H, J = 4.3 &lt; 5 &gt; Hz), 4.89 (t,

4H, J = 6.9Hz), 4.81 (t, 4H, J = 7.4Hz), 4.64-4.57 (m,

8H), 2.33-2.22 (m, 16H), 1.95-1.09 (m, 88H), 0.94 (t, 6H,

J = 7.4 Hz), 0.87-0.76 (m, 18H) ppm.

Example 60

Preparation of 1,4-dibutoxy-2-bromo-8,11,15,18,22,25-hexakis (decyl) phthalocyanines

To 10 ml of dry n-butanol was added 60 milligrams (8.5 millimoles) of lithium metal and the mixture was heated until the lithium had reacted. The resulting solution was cooled to room temperature and 350 mg (0.85 mmol) of 3,6-didecylphthalonitrile, 300 mg (0.85 mmol) of 4-bromo-3,6-dibutoxyphthalonitrile and 49 mg (0.85 mmol) were added under nitrogen. 0.0425 millimoles, 5 mole percent) tetrakis (triphenylphosphine) palladium and the resulting mixture was 12 hours fc ·

149 • fc ··· · fc ··························· Heat in the dark to 60 ° C. After cooling to room temperature, 2 ml of glacial acetic acid was added to the mixture and stirring was continued for another 30 minutes. The solvent was removed under reduced pressure and the residue was washed with 3 x 50 mL of methanol. The crude phthalocyanine mixture was separated by column chromatography on silica gel (eluting with petroleum ether). In the first fraction, 50 milligrams of 1,4,8,11,15,18,22,25-octakis (decyl) phthalocyanine was isolated, which complied with the corresponding standard. After the eluent was changed to petroleum ether / dichloromethane (10: 1), a second fraction was isolated. This second fraction was further purified by preparative thin layer chromatography (eluting with 3: 1 petroleum ether / dichloromethane). After evaporation of the solvents and recrystallization from tetrahydrofuran (THF) / methanol, 150 mg of 1,4-dibutoxy-2-bromo-8,11,15,18,22,25-hexakis (decyl) phthalocyanine was obtained as a dark green solid. .

⁴ H NMR (300 MHz, C ₆ D ₆ ) δ 7.93 (s, 1H), 7.91 (br s, 3H), 7.81 (s, 2H), 7.75 (s, 1H), 4.95 - 4.88 (m, 8H), 4.26 (t, 2H), 2.40 - 2.22 (m, 14H), 2.15 (quint, 2H), 1.96 (br quint 2H, 1.78 1.08 (m, 86H), 1.01 (t, 3H), 1.00 (t, 3H), 0.91-0.75 (m,

18), -0.35 (s, 2H).

MALDI-MS: Center cluster 1579.

λ _max (abs.) 720.648 nm (THF).

Example 61

Preparation of 1,4-dibutoxy-2-bromo-8,11,15,18,22,25hexakis (decyl) phthalocyaninosin zinc complex (Method 1)

1.00 g (2.54 millimoles) of 3,6-didecylphthalonitrile,

0.30 g (0.82 millimoles) of 4-bromo-3,6-dibutoxyphthalonitrile, 1.18 g (8.2 milliliters) of 1,8-diazabicyclo [5.4.0] undec-7-ene

150 «· 0 ···· 0 0 * · • 00 0000 0 · ·

00000 00 000 0 ·

0 000 000 000

0000 00 4 · 90 * · 00 · 0 (DBU) and 0.27 grams (1.23 millimoles) of zinc acetate dihydrate (99.999 percent pure) were heated to boiling in 20 milliliters of dry butanol for 3 days under nitrogen. heating was in the dark. After cooling to room temperature, the solvents were removed from the mixture under reduced pressure and the residue was washed with 3 x 50 ml of methanol. The crude material was separated by silica gel column chromatography (eluting with petroleum ether (40-60 ° C) / dichloromethane (4: 1)). The first fraction contained 240 milligrams (5.8 percent) of 1,4,8,11,15,18,22,25-octakis (decyl) phthalocyaninosin zinc complex. After the eluent was changed to petroleum ether (40-60 ° C) / dichloromethane (1: -1), a second fraction was isolated. This second fraction was further purified by preparative thin layer chromatography (TLC) of silica gel (eluting with petroleum ether (40-60 ° C) / dichloromethane (3: 2)). After evaporation of the solvents and recrystallization! from tetrahydrofuran (THF) / methanol, 50 mg (0.03 mmol, 3.7 percent) of the desired product was obtained as a dark green solid.

¹ H NMR (300 MHz, C ₆ D ₆ ) δ 7.85 - 8.0 (m, 7H), 5.08 (t, 2H), 4.96 (t, 4H), 4.79 (m, 8H), 4.35 (t, 2H), 1.1-2.5 (m, 104H), 0.84 (m, 24H) ppm.

Λmax (abs) 716.5 nm (THF).

Example 62

Preparation of 1,4-dibutoxy-2-bromo-8,11,15,18,22,25hexakis (decyl) phthalocyaninosin zinc complex (Method 2)

To 20 mL of dry n-butanol was added 0.2 grams (30 millimoles) of lithium metal and the mixture was heated under nitrogen until lithium had reacted. The resulting solution was left

151 0 0 · 000 · 000 · 000 · 0 00 · 00 0000 Cool to room temperature and add 3.49 grams (8, 4-bromo-3,6-dibutoxyphthalonitrile and 0.9 g (4.25 ml) of zinc acetate dihydrate (99.999 percent pure). The mixture was heated to reflux for 20 hours in the dark. After cooling to room temperature, the solvents were removed under reduced pressure and the residue was washed with 3 x 50 mL of methanol. The crude material was separated by column chromatography on silica gel (eluting with petroleum ether (40-60 ° C) / dichloromethane (4: 1)). The first fraction contained 300 milligrams of symmetrical 1,4,8,11,15,18,22,25-octakis (decyl) phthalocyanine zinc complex. After the eluent was changed to petroleum ether (40-60 ° C) / dichloromethane - (1: 1) a second fraction was isolated. This second fraction was further purified by preparative thin layer silica gel chromatography (eluting with petroleum ether (40-60 ° C) / dichloromethane (3: 2)).

Evaporation of the solvents and recrystallization from tetrahydrofuran (THF) / methanol yielded 126 mg (2.7 percent) of 1,4-dibutoxy-2-bromo-8,11,15,18,22,25-hexakis (decyl) phthalocyaninosin (II). of the complex as a dark green solid, which was identical to the compound prepared in Example 61.

Example 63

Preparation of 1,4-dibutoxy-2-bromo-8,11,15,18,22,25hexakis (decyl) phthalocyaninosin zinc complex (Method 3) milligrams (0.025 millimoles) of 1,4-dibutoxy-2-bromo 8,11,15, The 18,22,25-hexakis (decyl) phthalonitrile was dissolved in 10 ml of dry n-butanol at boiling point. To solution • · <000

0

0 0 0 0

152 mg (0.076 mmol) of anhydrous zinc bromide was added and the mixture was heated at reflux for an additional 45 minutes. The solvents were removed under reduced pressure and the residue was purified on thin layer chromatography plates (eluting with petroleum ether (40-60 ° C) / dichloromethane (3: 1)). The product obtained was recrystallized from tetrahydrofuran (THF) / methanol after evaporation of the solvents. 20 mg (49 percent) of the product were obtained in the form of a dark green powder having the same characteristics as the corresponding standard.

Example 64

Preparation of 1,4-dibutoxy-2- [1- (3-hydroxy-3-methyl) butinyl] 8,11,15,18,22,25-hexakis (decyl) phthalocyaninosin (II) complex

To a solution of 30 milligrams (0.018 millimoles) of 1,4-dibutoxy-2-bromo-8,11,15,18,22,25-hexakis (decyl) phthalocyaninosin (II) complex in 5 milliliters of dry triethylamine in a screw cap screw tube was in argon atmosphere in 3.84 milligrams (30 mole percent) of bis (triphenylphosphine) palladium dichloride, 1.56 milligrams (45 mole percent) of copper (I) iodide, and 15 milligrams (10 equivalents) of 2-methyl-3-butin-1-ol were added sequentially over 10 minutes. The resulting solution was degassed three times with argon, followed by stirring in the dark in an oil bath at 80 ° C for 24 hours. The reaction mixture was cooled and again under argon was added 3.84 mg of bis (triphenylphosphine) palladium dichloride,

1.56 mg of cuprous iodide and 15 mg (10 equivalents) of 2-methyl-3-butin-1-ol. The tube was resealed and the reaction mixture was heated at 80 ° C for an additional 24 hours. Progress

153 a a a a a a a a a a a a a a a a a · · Β · 9 9 9

The reaction was monitored by thin layer chromatography (TLC). After all the starting material was consumed, the reaction mixture was cooled, filtered and the filter cake was washed with diethyl ether until the effluents were colorless. The organics were combined and concentrated under reduced pressure. The crude product was further purified by preparative thin layer chromatography (TLC) (eluting with dichloromethane) and recrystallized from tetrahydrofuran (THF) / methanol to give 20 mg (0.012 mmol, 67.5 percent) of 1,4-dibutoxy-2- [ 1- (3-hydroxy-3-methyl) butynyl] -8,11,15,18,22,25hexakis (decyl) phthalocyaninosin zinc complex.

¹ H NMR (300 MHz, C ₆ D ₆ ) δ 7, 94-8.02 (m, 6H), 7.82 (s, 1H),

5.09 (br t, 6H), 4.85 (m, 8H), 4.46 (t, 2H), 2.42 (m, 12H),

1.0-2.0 (m, 104H), 0.88 (m, 18H) ppm.

_Max (abs.) 721, 702 nm (THF).

MALDI-MS: cluster 1645.

Example 65

Preparation of 2- (4-pyridyl) -4,4,5,5-tetramethyl-1,3-dioxaborolane

To a suspension of 5 grams (24 millimoles) of 4-iodopyridine in 250 milliliters of dry diethyl ether cooled to -78 ° C was slowly added 12 milliliters of a 2.5 molar solution of n-butyllithium in hexanes (30.1 millimoles). After 20 minutes, 6.9 g (30.1 mmol) of tributoxybore was added to the mixture and allowed to warm to room temperature over 2 hours.

3.8 grams of pinacol was added to the reaction mixture and 10 minutes later 1.47 grams (24.6 millimoles) of glacial acetic acid.

The mixture was filtered through a pad of celite, the filter cake was washed with 100 mL diethyl ether and the combined organic

154 fe · fe · fe · fe · fe · fe · fe · fe · fe · fe · fe · fe · fe · fe · fe · fe · fe · fe · fe · fe · fe · fe · fe · fe · fefe fefe fefe fefe ··· ···· The proportions were concentrated under reduced pressure. The crude product was recrystallized from cyclohexane to give 3.14 g (15.4 mmol, 64 percent) of the desired product.

Melting point 150-152 ° C (literature (C. Coudreb, - Synthetic Commun., 1996, 26, 3543) 151 ° C).

¹ H NMR (300 MHz, CDCl ₃ ) δ 8.65 (d, 2H, J = 6Hz), 7.65 (d, 2H, J = 6Hz), 1.38 (s, 12H) ppm.

Example 66

Preparation of 4-pyridyl-3, β-dibutoxyphthalonitrile

0.66 g (4.4 millimoles) of cesium fluoride. 0.25 grams (10 mole percent) of tetrakis (triphenylphosphine) palladium and 0.45 grams (2.2 millimoles) of 2- (4-pyridyl) -4,4,5-, 5-tetramethyl-1,3-dioxoborolan were at 10 minutes in a nitrogen atmosphere. To this mixture was added a solution of 0.38 g (1.1 mmol) of 4-bromo-3,6-dibutoxyphthalonitrile in 20 mL of 1,2-dimethoxyethane (DME), and the resulting mixture was heated to boiling for 48 hours, every 24 hours. 0.25 g (10 mole percent) of fresh tetrakis (triphenylphosphine) palladium was added to the reaction mixture. After cooling, 50 ml of water was added to the mixture, and the organics were extracted with 100 ml of diethyl ether, washed with brine and dried over anhydrous magnesium sulfate. The drying agent was filtered off and the solvents were evaporated under reduced pressure to give a solid which was recrystallized from cyclohexane to give 0.2 g (0.6 millimoles, percent) of the desired product as white needles. M.p. 150-151 ° C.

155 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 ¹ Η NMR (300 MHz, CDCl ₃ ) δ 8.76 (d, 2H), 7.46 (d, 2H) ), 7.13 (s, 1H), 4.12 (t, 2H), 3.71 (t, 2H), 1.85 (qn, 2H), 1.48-1.6 (m,

4H), 1.39 (m, 2H), 1.02 (t, 3H), 0.83 (t, 3H) ppm.

¹³ C NMR (300 MHz, CDCl ₃ ) δ 157.79 (ar. CO), 153.4 - (ar. CO), 150.58 (2 x pyr. C), 143.49 (ar. C-pyr) ), 139, 63 (2 x pyr. C),

123.55 (2 x CN), 118.88 (ar. CH), 113.23 (ar. C-CN), 112.76 (ar. C-CN), 112.23 (pyr-C-ar) , 76.28, 70.30, 31.86, 30.9, 19.08, 18.81, 13.73, 13.58 ppm.

Example 67

Preparation of 4- (2-thienyl) -3,6-dibutoxyphthalonitrile 0.5 grams (1.42 millimoles) of 4-bromo-3,6-butoxyphthalonitrile and 0.16 grams (10 mole percent) of tetrakis (triphenylphosphine) palladium was 10 g. The reaction mixture was stirred under nitrogen for 20 minutes in 20 ml of dimethoxyethane (DME). 0.27 g (2.1 mmol) of 2-thiopheneboronic acid and 2 ml of a 2 molar aqueous sodium carbonate solution were added sequentially.

The mixture was heated to reflux for 12 hours. After cooling, 100 ml of saturated potassium carbonate solution was added to the reaction mixture, and the organics were extracted with 2 x 100 ml of diethyl ether, washed with 100 ml of 5% hydrochloric acid, 100 ml of water, brine and dried over anhydrous magnesium sulfate. The drying agent was filtered off and the solvents were evaporated under reduced pressure to give an orange solid, which was recrystallized from cyclohexane to give 0.31 g (0.88 mmol, 62 percent) of the desired product as pale yellow crystals.

¹ H NMR (300 MHz, CDCl ₃ ) δ 7.59 (d, 1H), 7.45 (d, 1H), 7.34 (s,

1H), 7.16 (qn, 1H), 4.13 (t, 2H), 3.96 (t, 2H), 1.77 *

156 • · t 156 • t t t t t t t t t t t t a a a t a a a t a a a t t a

1.9 (m, 4H), 1.43-1.61 (m, 4H), 1.0 (t, 3H), 0.94 (t, 3H) ppm.

Example 68 - Preparation of 4-phenyl-3,6-dibutoxyphthalonitrile

0.6 grams (1.7 millimoles) of 4-bromo-3,6-butoxyphthalonitrile and 0.19 grams (10 mole percent) of tetrakis (triphenylphosphine) palladium were stirred for 10 minutes under nitrogen in 50 milliliters of dimethoxyethane (DME). To the solution was added 0.23 g (1.87 mmol) of phenylboronic acid and 2 ml of a 2 molar aqueous sodium carbonate solution successively.

The mixture was heated to reflux for 12 hours. After cooling, 100 ml of saturated potassium carbonate solution was added to the reaction mixture, and the organics were extracted with 2 x 100 ml of diethyl ether, washed with 100 ml of 5% hydrochloric acid, 100 ml of water, brine and dried over anhydrous magnesium sulfate. The drying agent was filtered off and the solvents were evaporated under reduced pressure to give an orange solid, which was recrystallized from cyclohexane to give 0.38 g (1.09 mmol, 64 percent) of the desired product as orange crystals.

^{Χ Η} NMR (300 MHz, CDC1 ₃₎ δ 7.45 to 7.54 (m, 6H), 7.13 (s, 1H)

4.11 (t, 2H), 1.84 (qn, 4H), 1.49-1.6 (m, 4H), 1.29 (m, 2H), 1.01 (t, 3H), 0 .78 (t, 3H) ppm.

157 • · 4 4 · 4 4 «4« • 444 * 4 ·· 444 4 4

4 * 444,444

4444 44 44 44 4

Example 69

Preparation of 4,5-diphenyl-3,6-dibutoxyphthalonitrile 0.5 grams (0.16 millimoles) of 4,5-dibromo-3,6-butoxyphthalonitrile and 0.13 grams (10 mole percent) of tetrakis (triphenylphosphine) palladium was stirred for 10 minutes under nitrogen in 20 mL of dimethoxyethane (DME). 0.31 g (2.55 mmol) of phenylboronic acid and 2 ml of a 2 molar aqueous sodium carbonate solution were added sequentially. The mixture was heated to boiling and reaction progress was monitored by thin layer chromatography (TLC) (eluting with ethyl acetate / hexane (1: 3)). After 24 hours, an additional 0.13 g (10 mole percent) of tetrakis (triphenylphosphine) palladium was added to the reaction mixture and refluxing was continued for a further 12 hours. After cooling, 100 ml of water was added to the reaction mixture, and the product was extracted with 3 x 100 ml of diethyl ether. The organic phase was washed with brine and dried over anhydrous magnesium sulfate. The drying agent was filtered off and the solvents were evaporated under reduced pressure to give a solid which was recrystallized from cyclohexane to give 130 mg (0.4 mmol, 34 percent) of the desired product as yellow crystals.

¹ H NMR (300 MHz, CDCl ₃ ) δ 7.17-7.23 (m, 6H), 6.97-7.03 (m,

4H), 3.56 (t, 4H), 1.44 (qn, 4H), 1.14 (m, 4H), 0.72 (t, 6H) ppm.

158 * · to to to to to to to to to to to to to to to to to to to to to to to · ·· ·· ·· this ··

Example 70

Preparation of 4- (pN, N-dimethylaminophenyl) -3,6-dibutoxyphthalonitrile -0.5 grams (1.42 millimoles) of 4-bromo-3,6-butoxyphthalonitrile and 0.2 grams (10 mole percent) of tetrakis (triphenylphosphine) The palladium was dissolved in 20 ml of dimethoxyethane (DME) and allowed to stir for 30 minutes under a nitrogen atmosphere.

To the solution was gradually added 0.4 grams (2.84 millimoles)

4- (N, N-dimethylaminophenyl) boronic acid and 2 mL of 2 molar sodium carbonate solution. The mixture was heated at reflux for 16 hours and then allowed to cool to room temperature. The reaction mixture was then partitioned between 100 mL of water and 100 mL of ether. The ether layer was washed with 2 x 100 mL brine and dried over anhydrous magnesium sulfate, filtered, and evaporated under reduced pressure. The yellow solid obtained was purified by column chromatography (eluting with ethyl acetate / hexane (3: 1)). The isolated product was recrystallized from cyclohexane to give 0.3 g (0.76 mmol, 53.9 percent) of 4- (p-N, N-dimethylaminophenyl) -3, β-dibutoxyphthalenitrile as yellow fluffy crystals.

¹ H NMR (300 MHz, CDCl ₃ ) δ 7.85 (d, 2H), 7.09 (s, 1H), 6.78 (d, 2H), 4.09 (t, 2H), 3.65 (t, 2H), 3.04 (s, 6H), 1.83 (quint, 2H), 1.15 (quint, 4H), 1.34 (sex, 2H), 0.98 (t, 3H) 0.84 (t, 3H) ppm.

159 ·

4 9 9 9

4 · 9 · 4

494 · 4 49 · · 4 · 9 94 44

Example 71

Preparation of 3,6-dibutoxy-4-p-methoxyphenylphthalonitrile

0.5 g (1.42 millimoles) of 4-bromo-3,6-butoxyphthalonitrile a

0.2 grams (10 mole percent) of tetrakis (triphenylphosphine) palladium was dissolved in 20 ml of dimethoxyethane (DME) and allowed to stir under nitrogen for 30 minutes.

0.43 g (2.84 millimoles) was added gradually to the solution.

4-p-methoxyphenylboronic acid and 2 ml of a 2 molar sodium carbonate solution. The mixture was heated at reflux for 16 hours and then allowed to cool to room temperature. The reaction mixture was then partitioned between 100 mL of water and 100 mL of ether. The ether layer was washed with 2 x 100 mL brine and dried over anhydrous magnesium sulfate, filtered, and evaporated under reduced pressure. The brown solid, 0.31 g, was purified by column chromatography (eluting with ethyl acetate). The isolated product was recrystallized from cyclohexane to give the desired 3,6-dibutoxy-4-pmethoxyphenylphthalenitrile.

¹ H NMR (300 MHz, CDCl ₃ ) δ 7.67 (d, 2H), 7.17 (s, 1H), 7.04 (d, 2H), 4.11 (t, 2H), 3.63 (t, 2H), 3.03 (s, 6H), 1.81 (p, 2H), 1.13 (p, 4H), 1.31 (sex, 2H), 0.96 (t, 3H) 0.83 (t, 3H) ppm.

Example 72

Preparation of 3,6-dibutoxy-4-carboxyphenylphthalonitrile

0.25 g (0.7 mmol) of 4-bromo-3,6-butoxyphthalonitrile a

0.1 grams (10 mole percent) of tetrakis (triphenylphosphine) palladium, 0.92 grams (5.69 millimoles) of cesium carbonate and 0.23 grams (1.42 millimoles) of p-carboxyphenylboronic acid

• · 4

4

160 • 4 • 444 44

4 · 44 ··

6 ·· 4 45 4

4 43 4 4 ·

44,449 · ·

9 4 4 9

44 94 44 ·· was placed under nitrogen for 1 hour. To this mixture was added 21 mL of toluene / ethanol / water (3: 3: 1) and the reaction mixture was heated to reflux for 12 hours. After cooling, the reaction mixture was acidified with 20 mL of concentrated hydrochloric acid and extracted with 2 x 100 mL of dichloromethane (DCM). The combined organic layers were dried over anhydrous magnesium sulfate, filtered and evaporated to give a yellow solid which was recrystallized from ethanol to give 0.06 g (0.168 millimoles, percent) of 3,6-dibutoxy-4-carboxyphenylphthalonitrile.

^{ς Η} NMR (300 MHz, CDC1 ₃₎ δ 8.23 (d, 2H), 7.67 (d, 2H), 7.16 (s, 1H), 4.08 (t, 2H), 3.64 (t, 2H), 3.05 (s, 6H), 1.84 (p, 2H), 1.15 (p, 4H), 1.33 (sex, 2H), 0.94 (t, 3H) 0.85 (t, 3H) ppm.

Example 73

Preparation of 4-p-aminophenyl-3,6-dibutoxyphthalonitrile

0.05 grams (0.142 millimoles) of 4-bromo-3, β-butoxyphthalonitrile and 0.02 grams (10 mole percent) of tetrakis (triphenylphosphine) palladium, 0.09 grams (0.569 millimoles) of cesium carbonate and 0.06 grams (0.284 grams) millimoles of p-aminophenylboronic acid was placed under nitrogen for 1 hour. To this mixture was added 10 mL of dry dimethoxyethane (DME) and the reaction mixture was heated to reflux for 12 hours. After cooling, the reaction mixture was partitioned between 20 mL of ether and 20 mL of water. The organic layer was dried over anhydrous magnesium sulfate, filtered and evaporated to give a yellow solid residue 0.021 g which was recrystallized from ethanol to give 4-p-aminophenyl-3,6-dibutoxyphthalonitrile.

161

Φ · · · φ • • • • * * * • • • φ φ φ φ φ φ φ φ φ φ φ φ φ · · · · · φ φ

NMR (300 MHz, CDCl ₃ ) δ 7.38 (d, 2Η), 7.17 (s, 1Η), 6.75 (d, 2Η), 4.07 (t, 2Η), 3.62 (t , 2Η), 3.07 (s, 6Η), 1.85 (ρ, 2Η), 1.16 (ρ, 4Η), 1.32 (sex, 2Η), 0.93 (t, 3Η), 0 .84 (t, 3Η) ppm.

Example 74

Preparation of 4- (p-hydroxymethylphenyl) -3,6-dibutoxyphthalonitrile A mixture of 500 mg (3.311 mmol) of 4- (hydroxymethyl) benzeneboronic acid, 764 mg (2.17 mmol) of 4-bromo-3,6-dibutoxyphthalonitrile, 85.7 mg ( 0.327 millimoles of triphenylphosphine, 42.8 milligrams (0.241 millimoles) of palladium chloride and 50 milligrams of sodium carbonate were placed under nitrogen for 30 minutes. After this time, 35 mL of solvent was added to the mixture. toluene / ethanol / water (3: 3: 1). The reaction mixture was heated under reflux for 24 hours under nitrogen and then freed of solvents under reduced pressure. The residue was dissolved in 50 mL of dichloromethane and the solution was filtered through celite to remove palladium residues. The filtrate was evaporated under reduced pressure and the residue was purified by silica gel column chromatography (eluting with dichloromethane / ethyl acetate (9: 1)) to give 700 mg (1.85 mmol, 85 percent) of 4- (p-hydroxymethylphenyl) - 3,6-dibutoxyphthalonitrile.

^{Χ Η} NMR (300 MHz, CDC1 ₃₎ δ 7.54 (d, 2H, J = 8.4 Hz), 7.48 (d,

2H, J = 8.4 Hz), 7.12 (s, 1H), 4.80 (s, 2H), 4.11 (t, 2H, J = 6.5 Hz), 3.64 (t, 2H, J = 6.4 Hz), 1.84 (qn, 2H, J = 6.6 Hz), 1.47-1.58 (m, 4H), 1.26 (qn, 2H, J = 7) 3 Hz) 0.98 (t, 3H,

J = 7.4 Hz), 0.80 (t, 3H, J = 7.4 Hz) ppm.

For C ₂₃ H ₂₆ N ₂ O ₃

Found: C 72.82%; H 6.93%; N, 7.22%.

162 «« • 8 9

9 9 9 99 99 «1 2 3 4 5 6 7 8 9 9 9 9 9

999 99 99 999 9 9 • 9 9 9 9 9 9 9 • 999 99 99 99

Calculated:

C 73.01%; H 6.88%; N

7.41%.

Example 75

Preparation of 4- (p-methanesulfonyloxymethylphenyl) -3,6-dibutoxyphthalonitrile

100 mg (0.26 mmol) of 4- (p-hydroxymethylphenyl) 3,6-dibutoxyphthalonitrile was dissolved in 30 ml of dichloromethane (DCM) containing 30 mg (0.29 mmol) of triethylamine. The reaction mixture was stirred, cooled to 0 ° C, and 33 mg (0.29 mmol) of methanesulfonyl chloride was added dropwise. The resulting mixture was allowed to warm to room temperature, stirred for an additional 2 hours, and then washed with 2 x 25 ml of 10% hydrochloric acid and 25 ml of brine and dried over anhydrous magnesium sulfate. The mixture was filtered and the filtrate was evaporated under reduced pressure. The resulting yellow oil was purified by silica gel chromatography (eluting with dichloromethane (DCM)) to give 85 mg (70 percent) of 4- (p-methanesulfonyloxymethylphenyl) -3,6-dibutoxyphthalonitrile.

For C 24 H 28 N 2 O 5 S

Found: Calculated:

62.97%; 63.15%;

6.13%;

6.14%;

6.10%. 6, 14%.

6.6 Hz), 1.4

δ 7,59 (2H, d, J = 8 2 Hz), 7.54 (2H, d, J = (1H, s) , 5, 30 (2H, s) , 4.12 (2H, t, J = 6.3 Hz J = 6.4 Hz), 3.04 (3H, s), 1.85 (: 2H, quint J - 1,60 (4H, m), 1.27 (2H, quint, J = 7.2 Hz), J = 7.3 Hz), 0.79 (3H, t, J = 7.4 Hz).

163 • 9 * 9 • 9 9 9 • 9 • 99 · 99 * ♦ 99 · 9 9

9 99

9 9 9

9 · 9 ·

9 * »8 9

9 9

9 9

9 9

9999

Example 76

Preparation of 4-p - [(O-tyrosinylmethyl) oxymethylphenyl] -3,6-dibutoxyphthalonitrile -Mixture of 500 milligrams (1.08 millimoles) of 4- (p-methanesulfonyloxymethylphenyl) -3,6-dibutoxyphthalonitrile, 318 milligrams (1.63 millimoles) DL -p-tyrosine, 600 milligrams (excess) of potassium carbonate and 50 milligrams (0.154 millimoles) of tris (3,6-dioxaheptyl) amine (TDA-1, purchased from Aldrich) in 30 milliliters of methyl ethyl ketone (MEK) were heated under argon atmosphere. 48 hours at boiling point. After cooling, the resulting solid was filtered off and washed with dichloromethane (DCM). The residual solution was evaporated under reduced pressure to give a yellow oil, which was chromatographed on silica gel (eluting with dichloromethane (DCM) / ethyl acetate (2: 3)) to give 210 mg (34 percent) of 4-p - [(0-) Oxymethylphenyl] -3,6-dibutoxyphthalonitrile tyrosinylmethyl ester.

¹ H NMR (CDCl ₃ ) δ 7.55 (4H, s), 7.11 - 7.14 (3H, m), 6. 93 (2H, d, J = 8.7 Hz) r 5.12 (2H, s), 4.11 (2H, t, J = 6.4 Hz), 3, 65 (2H, t, J = 6) 3 Hz), 3.68 - 3,75 (4 H, m), 3.06 (1 H, dd, J = 4.1 and 13.5 Hz) F 2.84 (1H, dd, J = 7 , 7 and 13 , 5 Hz), 1.21 - - 1,86 (10H, bm) 0.9 8 (3H, t, J = 7.4 Hz) , 0.79 (3 H, t, J = 7, 4 Hz) Preparation 77

Preparation of 3,6-di (butyloxy) -4- (4'-ethoxy-4'-oxobutyl) phthalonitrile

A mixture of 250 mg (0.95 mmol) of triphenylphosphine,

0.6 grams (14 millimoles) of lithium chloride and 313 milligrams (0.5 millimoles) of bis (triphenylphosphine) nickel dichloride in

164

0 • 4 ·· 44

0 0 0 0 0 0 0 0 0 0 0 0 0

00 milliliters of dry tetrahydrofuran (THF) was stirred for 10 minutes under a nitrogen atmosphere. To the resulting blue solution was added 0.4 ml of a 2.5 molar solution of n-butyllithium in hexanes at room temperature. The color of the solution turned dark red. To this solution was added 3.5 grams (10 millimoles) of solid at once under a rapid stream of nitrogen

Of 3,6-bis (butyloxy) -4-bromophthalonitrile and the resulting light brown solution was cooled to -78 ° C. At this temperature, 20 ml of a 0.5 molar solution of 4-ethoxy-4-oxobutylzinc bromide in tetrahydrofuran (THF) (10 mmol) (obtained from Aldrich) was added via syringe to the reaction mixture. The solution was allowed to warm to room temperature and stirred at this temperature under nitrogen for an additional 12 hours. The reaction mixture was quenched with 50 mL of 5 percent hydrochloric acid and the resulting mixture was extracted with 3 x 20 mL of ethyl acetate. The combined organic layers were washed with 10 ml of 5% hydrochloric acid, 10 ml of 5% sodium hydroxide solution, 10 ml of brine and dried over anhydrous magnesium sulfate. The desiccant was removed by filtration and the filtrate was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluting with petroleum ether (40-60 ° C) / dichloromethane (1: 1)) to remove triphenylphosphine. The eluent was exchanged for dichloromethane and the fluorescent fraction was collected. ¹ H NMR spectroscopy confirmed that this fraction contained 3,6-dibutyloxyphthalonitrile, which, after evaporation, gave 570 mg as a white powder. Further, a fluorescent fraction that could not be identified was eluted from the column and the fraction was recovered last, yielding 1.9 g (4.9 millimoles, 49 percent) of 3, β-di (butyloxy) 165 • 4> 4 ·· ·· ♦ 4 <· · f f · 4 4 f f f 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4

4- (4'-ethoxy-4'-oxobutyl) phthalonitrile as a pale yellow oil which solidified on standing.

Mp 43-48 ° C.

¹ H NMR (270 MHz, CDCl ₃ ) δ 7.0 (s, 1H), 4.1 (q, 2H), 4.04 (m, 4H), 2.69 (t, 2H), 2.31 (t, 2H), 1.9 (m, 2H), 1.78 (m, 4H),

1.5 (m, 4H), 1.24 (t, 3H), 0.95 (m, 6H) ppm.

m / z 386 (M, 14/9%).

Example 78

Preparation of 3, β-bis (butyloxy) -4- (4'-chlorobutyl) phthalonitrile A mixture of 125 milligrams (0.5 millimoles) of triphenylphosphine,

0.3 grams (7 millimoles) of lithium chloride and 156 milligrams (0.24 millimoles) of bis (triphenylphosphine) nickel dichloride in 5 milliliters of dry tetrahydrofuran (THF) were stirred for 10 minutes under a nitrogen atmosphere. To the resulting blue solution was added 0.2 mL of a 2.5 molar solution of n-butyllithium in hexanes at room temperature. The solution turned dark red. To this solution was added 1.4 grams (4 millimoles) of solid at once under a rapid stream of nitrogen

Of 3,6-bis (butyloxy) -4-bromophthalonitrile and the resulting light brown solution was cooled to -78 ° C. At this temperature, 10 ml of a 0.5 molar solution of 4-chlorobutylzinc bromide in tetrahydrofuran (THF) (5 mmol) (obtained from Aldrich) was added via syringe. The solution was allowed to warm to room temperature and stirred at this temperature under nitrogen for an additional 12 hours. The reaction mixture was quenched with 20 mL of 5 percent hydrochloric acid and the resulting mixture was extracted with 3 x 10 mL of ethyl acetate. The combined organic layers were washed with 10 mL of 5 percent hydrochloric acid,

166 fefe fefe ·· · fe · fefefe · 8 · fefefe fefe · fefe · fefe · fefe fefe · fefe · fefe · · fefe fefe fefe · ml · fefe fefe fefe · ml · fefe fefe fefe · fefe fefe fefe · milliliters of brine and dried over anhydrous magnesium sulfate. The desiccant was removed by filtration and the filtrate was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluting with petroleum ether (40 to 60 ° C) / dichloromethane (1: 1)) to remove triphenylphosphine. A second fraction containing 0.9 grams of unreacted starting material was collected.

The eluent was exchanged for dichloromethane to give 200 mg (0.55 mmol, 39% or 39 percent based on the amount of starting material isolated) of 3,6-bis (butyloxy) -4- (4'-chlorobutyl) after evaporation of the appropriate fraction. phthalonitrile in the form of a pale yellow oil which solidified on standing.

¹ H NMR (270 MHz, CDCl ₃ ) δ 7.19 (s, 1H), 4.8 (t, 2H), 4.6 (t,

2H), 3.59 (t, 2H), 2.7 (t, 2H), 1.82 (m, 8H), 1.45-1.6 (m,

4H), 0.95 - 1.03 (m, 6H) ppm.

m / z 362 (M, 1.6%), 364 (M + 2, 0.53%).

Example 79

Preparation of 3,6-dibutoxy-4,5- (tris (isopropyl) silylethinyl) phthalonitrile

A solution of 1.00 g (2.33 mmol) of 4,5-dibromo-3,6-dibutoxyphthalonitrile was dissolved in 6 ml of freshly distilled triethylamine. The resulting solution was degassed by brief heating under argon. Then, 0.164 g (10 mole percent) of PdCl ₂ (PPh ₃ ) ₂ , 1.06 g (5.82 mmol) of TIPS-acetylene and 0.06 g (13 mole percent) of copper (I) iodide were added sequentially to the solution. The reaction mixture was heated to boiling for 16 hours, cooled and the palladium salts removed by filtration.

167 • 0 · ♦ · * ·· • * 0 0 0 0 0 0 00 00 · 00 ® ® 0 0 0 0 0 0 0 0

0 000 000 000 00 00 00 09

0 0 0 0 0 • 0 ♦

0 0 «

The obtained filtrate was washed with ethyl acetate and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (eluting with petroleum ether / dichloromethane (DCM) (1: 2)) to give a fraction, after evaporation and recrystallization of the residue, 0.82 g (56 percent) 3.6. -dibutoxy-4,5- (tris (isopropyl) silylethynyl) phthalonitrile.

For C 38 H 60 O 2 N 2 S 12

Found: C 72, 11 %; H 9.37%; N 4, 28%. Calculated: C 72, 10 %; H 9.55%; N 4, 42%. ^{Χ Η} NMR (300 MHz, CDCI3) δ 4.26 ( t: 4H, J = 6.8 Hz), 1.83 (quint, 4H, J = 7.2 Hz) r 1,56 - 1.45 (m, 4H). 1,2 - 1.08 (br

s, 42H), 0.97 (t, 6H, J = 7.4 Hz) ppm.

¹³ C NMR (300 MHz, CDCl ₃ ) δ 160.03, 127.13, 112.94, 109.05, 108.60, 98.43, 75.98, 31.94, 18.80, 15.58 , 13.73, 11.28 ppm.

Example 80

Preparation of 1,4-dibutoxy-2-pyridyl-8,11,15,18,22,25hexakis (decyl) phthalocyanine

2.2 g (7.65 mmol) of 3,6-didecylphthalonitrile and 0.3 g (0.85 mmol) of 4-pyridyl-3,6-dibutoxyphthalonitrile were heated to boiling in 10 ml of butanol.

To the solution was slowly added portionwise 0.12 grams (17 millimoles) of lithium metal, and the mixture was heated to reflux for 12 hours in the dark. After cooling, 10 ml of glacial acetic acid was added to the mixture, and the mixture was stirred for 30 minutes. The solvents were removed under reduced pressure and methanol was added to the green suspension obtained. The resulting solid was filtered and washed with ethanol. The product was separated by column chromatography

168 fcfc silica gel (eluting with petroleum ether 40-60 ° C) to remove 1.4 g of fcfc fc fcfc fcfc fcfc fcfc fcfc fcfc fcfcfcfc , 8,11,15,18,22,25-octakis (decyl) phthalocyanine. The eluent was then changed to petroleum ether (40-60 ° C) / dichloromethane (9: 1) and the second green fraction was collected. This fraction was purified by further silica gel chromatography (eluting first with petroleum ether (40-60 ° C) followed by petroleum ether (40-60 ° C) / dichloromethane (19: 1)). Recrystallization of the obtained product from tetrahydrofuran (THF) / methanol afforded 43 mg (0.03 mmol, 3.2 percent) of the product as a green powder.

¹ H NMR (300 MHz, benzene-d 6) δ 8.99 (d, 2H), 7.89-7.96 (m,

8H), 7.79 (s, 1H), 4.99 (t, 2H), 4.92 (t, 2H), 4.97 (qn, 8H),

4.49 (qn, 2H), 2.24-2.42 (m, 14H), 2.05 (qn, 2H), 0.99 1.89 (m, 93H), 0.65 - 0.86 (m, 21H), -0.48 (s, 2H) ppm.

For C105H157N9O2

Found: C 79.74%; H

Calculated: C 79.95%; H

Λ _max (THF): 723 (ε = 1.4 x 10 ⁴ ) nm. MALDI-MS:

9.88%; 10.03%;

7.73%. 7.99%.

isotopic cluster 1577 [M].

Example 81

Preparation of 1,4-dibutoxy-2-thienyl-8,11,15,18,22,25-hexakis (decyl) phthalocyanine

0.37 g (1.06 mmol) of 4-thienyl-3,6-dibutoxyphthalonitrile and 3.9 g (9.55 mmol) of 3,6-didecylphthalonitrile were dissolved in 15 ml of butanol and heated to boiling. To the solution was slowly added portionwise 0.4 grams (57 millimoles) of lithium metal and the mixture was heated at reflux for a further 12 hours. After cooling it was

169 «« * »» 169 «« · »169» »169» »169» » 10 ml of glacial acetic acid was added to the mixture, and the mixture was stirred for 30 minutes. Solvents were removed from the reaction mixture under reduced pressure and the residue was washed with methanol (3 x 100 mL). The product was separated by column chromatography on silica gel (eluting with petroleum ether 40-60 ° C) to remove 1,4,8,11,15,18,22,25-octakis (decyl) phthalocyanine. The eluent was then changed to petroleum ether (40-60 ° C) / dichloromethane, in which the proportion of dichloromethane was gradually increased from 5 percent to 25 percent. The second fraction thus obtained was purified by further silica gel column chromatography (eluting with the same solvent mixture). It was also necessary to carry out a third purification by column chromatography on silica gel (eluting with 25% dichloromethane in petroleum ether (40-60 ° C)) to give a fraction containing pure product, which was evaporated and recrystallized from tetrahydrofuran (THF) / methanol to give the title compound. 32 mg (20 micromoles, 1.9 percent) of the desired product was obtained as a green powder.

³ H NMR (300 MHz, C ₅ D ₆ ) δ 8.29 (dd, 1H), 7.91 (q, 1H), 7.88 (s, 1H), 7.82 (s, 4H) ', 7.69 (s, 2H), 7.27 (dd, 1H), 4.98 (t, 2H), 4.85 (t, 2H), 4.78 (t, 2H), 4.46- 4.65 (m, 10H), 2.07-2.4 (m, 16H), 1.6-1.83 (m, 12H), 0.97-1.58 (m, 79H), 68 0.96 (m, 21H), -0.35 (s, 2H) ppm.

For C104H156N8O2S

Found: Calculated:

79.18%; 78.94%;

9.87%; 9.94%;

6.86%. 7.08%.

MALDI-MS: isotopic cluster 1582 [M ⁺ ].

Amax (THF): Abs. 727 (ε = 1.85 x 10 ⁴ ) nm.

170

4 9 • 9 44 ·· 44 • 4 • 4 • • 4 4 4 · • w • • 4 4 • • 4 • · 4 • 444 4 • 4 4 . 4 9 4 9 4 4 • • 4 4 • 44 4 444 · • 4 Í34 44 4444

Example 82

Preparation of 1,4-dibutoxy-2-phenyl-8,11,15,18,22,25-hexakis (decyl) phthalocyanine. .

0.37 g (1.06 mmol) of 4-phenyl-3,6-dibutoxyphthalonitrile and 3.9 g (9.55 mmol) of 3,6-didecylphthalonitrile were dissolved in 15 ml of butanol and heated to boiling. To the solution was slowly added 0.4 grams (57 millimoles) of lithium metal, and the mixture was heated at reflux for a further 12 hours. After cooling, 10 ml of glacial acetic acid was added to the mixture, and the mixture was stirred for 30 minutes. Solvents were removed from the reaction mixture under reduced pressure and the residue was washed with methanol (3 x 100 mL). The product was separated by column chromatography on silica gel (eluting with petroleum ether 40-60 ° C) to remove 1,4,8,11,15,18,22,25-octakis (decyl) phthalocyanine. The eluent was then changed to petroleum ether (40-60 ° C) / dichloromethane, in which the proportion of dichloromethane was gradually increased from 5 percent to 25 percent. The second fraction thus obtained was purified by further silica gel column chromatography (eluting with the same solvent mixture). It was also necessary to perform a third purification by column chromatography on silica gel (eluting with 25% dichloromethane in petroleum ether (40-60 ° C)) to give a fraction containing pure product, evaporating and recrystallizing the residue from tetrahydrofuran (THF) / methanol. 22 mg (14 micromoles, 1.3 percent) of the desired product is obtained as a green powder.

⁴ H NMR (300 MHz, C ₆ D ₆ ) δ 8.18 (d, 2H), 7.89-8.0 (m, 3H), 7.83 (m, 3H), 7.83 (s, 2H), 7.62 (s, 1H), 7.55 (t, 2H), 7.3-7.41 (m, 2H), 4.92-5.09 (m, 4H), 4.63 4.81 (m, 8H), 4.48 (t,

171

4H), 1.95-2.48 (m, 18H), 1.55-1.94 (m, 16H), 0.15-1.54 (m, 94H), -0.27 (s, 2H ) ppm.

Example 83

Preparation of 1,4-dibutoxy-2,3-diphenyl-8,11,15,18,22,25hexakis (decyl) phthalocyanine

A mixture of 0.2 grams (0.47 millimoles) of 4,5-diphenyl-3,6-dibutoxyphthalonitrile and 0.7 grams (1.88 millimoles) of 3,6-didecylphthalonitrile in 10 milliliters of butanol was brought to reflux.

To the solution was slowly added portionwise 0.12 grams (17 millimoles) of lithium metal, and the mixture was heated to reflux for 12 hours in the dark. After cooling, 10 ml of glacial acetic acid was added to the mixture, and the mixture was stirred for 30 minutes. Solvents were removed from the reaction mixture under reduced pressure and the residue was purified by silica gel column chromatography (eluting with petroleum ether 40 to 60 ° C) to remove 1,4,8,11,15,18,22,25-octakis (decyl). ) phthalocyanine. The eluent was then changed to dichloromethane / petroether (40-60 ° C) (1:19). The product contained in this fraction was recrystallized from tetrahydrofuran (THF) / methanol to give 50 mg (0.03 mmol, 6.5 percent) of the product as a green powder.

^Δ NMR (300 MHz, C ₆ D ₆ ) δ 7.96 (s, 4H), 7.88 (s, 2H), 7.72 (d, 4H), 7.3 (t, 4H), 4 96 (t, 4H), 4.76 (t, 8H), 4.48 (t, 4H),

2.4 (m, 10H), 2.09 (qn, 4H), 1.69-1.87 (m, 12H), 1.57-1.67 (m, 4H), 1.4-1, 57 (m, 12H), 0.89-1.39 (m, 74H), 0.74 0.87 (m, 14H), -0.17 (s, 2H) ppm.

For C112H162N8O2

Found: C 81.58%; H, 9.94%; N, 6.34%.

172 <· 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 4 9 9 ·

Calculated: C 81.4%; H, 9.88%; N, 6.78%.

_Max (THF): Abs. 725 (ε = 9.19 x 10 ⁴ ) 711 (ε = 9.12 x 10 ⁴ ) nm. MALDI-MS: isotopic cluster 1652 [M ⁺ ].

Example 84

Preparation of 1,4-dibutoxy-2- (p-hydroxymethylphenyl) 8,11,15,18,22,25-hexakis (decyl) phthalocyanines

To a vigorously stirred solution of 1.01 grams (2.4 millimoles)

3,6-didecylphthalonitrile and 0.233 grams (0.6 millimoles)

4- (p-hydroxymethylphenyl) -3,6-dibutoxyphthalonitrile in 25 mL of butanol was added 0.1 grams (14 millimoles) of lithium metal and the mixture was stirred and heated for 12 hours. After cooling to room temperature, 30 ml of glacial acetic acid was added to the mixture and stirred for 20 minutes. The reaction mixture was then poured into 100 ml of methanol and stirred for an additional 5 minutes. The resulting precipitate was collected by filtration and air dried for 10 minutes. The green product was separated by column chromatography on silica gel (eluting with toluene). The first isolated fraction contained symmetrical

1,4, 8, 11,15,18,22,25-octakis (decyl) phthalocyanine. Methanol was added to the second fraction containing the desired product dissolved in toluene to precipitate 1,4-dibutoxy-2- (p-hydroxymethylphenyl) -8,11,15,18,22,25hexakis (decyl) phthalocyanines, which, after drying, was in the form of a green powder of 100 milligrams (0.062 millimoles, 10 percent).

⁴ H NMR (300 MHz, CDCl ₃ ) δ 8.01 (d, 2H, J = 8.1 Hz), 7.94 (d,

4H, J = 8.7 Hz), 7.80 (s, 2H), 7.63 (d, 2H, J = 8.3 Hz), 7.59 (s, 1H), 4.9 (d (2H, J = 5.6 Hz), 4.61-4.72 (m, 6H), 4.40 173 [deg.]

9 9 9 9 • 9 99 9999

4.47 (m, 8H), 4.25 (t, 2H, J = 7.1 Hz), 2.31 (qn, 2H, J = 6.6 Hz), 0.71-2.17 (m (126H), 0.61 (t, 3H, J = 7.4Hz) ppm.

Example 85

Preparation of 1,4-dibutoxy-2-pyridyl-8,11,15,18,22,25hexakis (decyl) phthalocyaninosin zinc complex

0.4 grams (0.25 millimoles) of 1,4-dibutoxy-2-pyridyl8,11,15,18,22,25-hexakis (decyl) phthalocyanines and 0.2 grams (1.09 millimoles) of zinc acetate dihydrate ( about purity

99.999 percent) was added to 10 mL of butanol. The mixture was boiled at reflux for 4 hours and the solvents were removed under reduced pressure. The obtained green residue was recrystallized from tetrahydrofuran (THF) / methanol to give 0.2 g (0.12 millimoles, percent) of the product as a green powder.

¹ H NMR (300 MHz, benzene-dg containing 1 drop of pyridine-d 5) δ 8.96 (s, 2H), 8.5 (s, 2H), 7.92-7.99 (m, 8H), 7 55 (s, 1H), 5.19 (t, 2H), 5.07 (t, 2H), 4.88 (m, 8H), 4.57-4.62 (t, 2H), 2, 47-2.52 (m, 14H), 2.07 (qn, 2H), 1.81 (m, 12H), 0.99 1.79 (m, 100H) ppm.

Axmax (THF): Abs. 718 (ε = 1.44 χ 10 ⁵ ) Em. 725 nm.

Example 86

Preparation of 1,4-dibutoxy-2-thienyl-8,11,15,18,22,25hexakis (decyl) phthalocyaninosin zinc complex milligrams. (0.03 millimoles) 1,4-dibutoxy-2-thienyl8,11,15,18,22,25-hexakis (decyl) phthalocyanines and 200 milligrams (1 millimoles) of zinc acetate dihydrate (of purity)

99.999 percent) was added to 12 mL of butanol. Mixture

174 ....., .., .. ..

,,,, »« · ♦ ··. ·, ··. ··· ·. .

• ····· ·· · «·. The mixture was heated to boiling for 4 hours and, after cooling, the solvents were removed under reduced pressure. The green residue obtained was recrystallized from tetrahydrofuran (THF) / methanol to give 20 mg (12.1 micromol, 41 percent) of the product as a green powder.

¹ H NMR (300 MHz> benzene-dg) δ 8.09 (dd, 1H), 8.0 (q, 1H), 7.99 (s, 1H), 7.91 (s, 4H), 7, 87 (s, 2H), 7.29 (dd, 1H), 5.13 (t, 2H), 5.03 (t, 2H), 4.91 (t, 2H), 4.81 (m, 8H) 4.64 (t, 2H);

2.5 (m, 12H), 2.19-2.37 (m, 8H), 1.85 (m, 8H), 1.72 (m, 4H), 0.72-1.6 (m, 96H) ppm.

Example 87

Preparation of 1,4-dibutoxy-2,3-diphenyl-8,11,15,18,22,25hexakis (decyl) phthalocyaninosin zinc complex

0.04 g (0.0242 millimoles) of 1,4-dibutoxy-2,3-diphenyl8,11,15, 18,22,25-hexakis (decyl) phthalocyanines and 0.02 g (excess) of zinc acetate dihydrate (o purity

99.999%) was dissolved in 10 ml of dry butanol and heated at reflux for 4 hours. After removal of the solvent, the product was purified by column chromatography (eluting with petroleum ether / tetrahydrofuran (THF) 15: 1) and recrystallized from tetrahydrofuran (THF) / methanol to give 0.01 g (0.0058 millimol, 24 percent). 1,4-Dibutoxy-2,3-diphenyl-8,11,15,18,22,25-hexakis (decyl) phthalocyanine-zinc complex of the product as a waxy green solid.

¹ H NMR (300 MHz, C ₆ D ₆ ) δ 8.00 (q, 4H), 7.81 (s, 4H), 7.78 (s,

2H), 7.32 (t, 4H), 5.11 (t, 4H), 4.83-4.77 (m, 8H), 4.66 (t,

175

4 4 4 9 4 9 44 44 9 9 4 9

9 9 9 94 · 9 8 9 9 9 4 9 99 9949

4H), 2.56-2.46 (m, 14Η), 2.43-2.21 (m, 6Η), 1.85 (m, 10Η), 1.50 - 1.19 (m, 68H) , 0.91 to 0.72 (m, 16H) and _max (abs.) 712 nm (THF); _Max (em.) 720 nm (THF).

- 1.81 ppm.

Example 88

Preparation of 1,4-dibutoxy-2-p-N, N-dimethylaminophenyl) 8,11,15,18,22,25-hexakis (decyl) phthalocyaninatosin (II) complex

0,61 g (1,5 millimoles) of 3,6-didecylphthalonitrile,

0.196 g (0.5 millimoles) of 4- (p-N, N-dimethylaminophenyl) -3,6-dibutoxyphthalonitrile and 0.02 g (excess) of zinc acetate in 10 ml of dry butanol were heated to boiling under nitrogen. To the boiling mixture was added 2.3 mL (excess) DBU, and the reaction mixture was heated at reflux for a further 9 hours. The mixture was allowed to cool and the solvent was removed. The oil obtained was purified by column chromatography (eluting with petroleum ether / dichloromethane (DCM) (8: 2)) to first remove the symmetrical product. The eluent composition was slowly changed in favor of dichloromethane (DCM) (i.e. the petroleum ether / dichloromethane (DCM) ratio was gradually changed to 6: 4, 1: 1, 4: 6, 2: 8 and finally pure dichloromethane was used). This gave a green fraction which was purified again by column chromatography (eluting with petroleum ether / dichloromethane (DCM) (8: 2)) to remove traces of symmetrical product.

A light green fraction was eluted with petroleum ether / dichloromethane (DCM) (2: 8), and finally the fraction containing the desired product was isolated with tetrahydrofuran (THF) / petroleum ether (5: 100).

After evaporation of the solvents, the obtained solid residue was recrystallized from tetrahydrofuran (THF) / methanol to give a solid

176

0.03 grams (0.017 millimoles, 3.5 percent) was obtained.

1,4-dibutoxy-2-p-N, N-dimethylaminophenyl) -8,11,15,18,22,25hexakis (decyl) phthalocyaninosin (II) complex.

¹ H NMR (300 MHz, C ₆ D ₅ ) δ 8.29 (d, 2H), 8.01 (s, 4H), 7.97 (s, 2H), 7.87 (s, 1H), 6 , 97 (d, 2H), 5.20 (m, 4H), 4.92-4.90 (rt, 8H), 4.71-4.66 (rt, 4H), 2.98 (m, 4H) 2.64 (s, 6H);

2.51 (m, 10H), -1.87 (m, 8H), 1.50 (t, 8H), 1.40-1.00 (m,

74H), 0.86-0.70 (m, 24H) ppm.

Example 89

Preparation of 1,4-dibutoxy-2- (p-hydroxymethylphenyl) 8,11,15,18,22,25-hexakis (decyl) phthalocyaninosin zinc complex

To a boiling and stirred solution of 40 milligrams (0.025 millimoles) of 1,4-dibutoxy-2- (p-hydroxymethylphenyl) -8, 11,15,18,22,25hexakis (decyl) phthalocyanines in 10 milliliters of butanol was added 22 milligrams (0 , 1 millimol) of zinc acetate dihydrate (99.999 percent pure). The mixture was heated to reflux until completion of the reaction (as evidenced by thin layer chromatography (TLC)). The solvent was removed under reduced pressure and the product was purified by silica gel column chromatography (eluting with toluene). The second blue fraction contained 13 mg (0.022 mmol, 90 percent) of 1,4-dibutoxy-2- (p-hydroxymethylphenyl) -8,11,15,18,22,25-hexacis (decyl) phthalocyaninosin (II) complex.

¹ H NMR (300 MHz, CDCl ₃ ) δ 8.03 (d, 2H, J = 7.8 Hz), 7.82-7.89 (m, 2H), 7.55-7.61 (m, 7H), 4.65-4.76 (m, 6H), 4.23-4.41 (m, 10H), 4.03 (t, 2H, J = 6.2 Hz), 2.25 (qn) (2H, J = 7.4Hz),

0.70-2.17 (m, 120H), 0.61 (t, 3H, J = 7.4 Hz) ppm.

177 · «« «« * * * * * * * * * * * * * * * * * * * *

For C ₁₀₇ Hi ₅₈ N ₈ O ₃ Zn

Found: C 76.85%; H, 9.45%;

Calculated: C 76.96%; H, 9.54%;

MALDI-MS: isotopic cluster 1669 [M ⁺ ].

_Max (abs.) 715.5 nm (THF).

6.55%. 6.71%.

Example 90

Preparation of 1,4-dibutoxy-2-p - [(Q-tyrosinyl-butyl ester) oxymethyl-phenyl-8,11,15,18,22,25-hexakis (decyl) phthalocyaninosin (II) complex

1,442 grams (3,528 millimoles) of 3,6-didecylphthalonitrile, 0.218 grams (0.39-7 millimoles) of 4-p0-tyrosinylmethyl ester) oxymethylphenyl-3,6-dibutoxyphthalonitrile and 0.128 grams (excess) of zinc acetate dihydrate in 30 milliliters of dry butanol were The mixture was heated at reflux for 1 hour. 0.592 mg (excess) of DBU was added to the boiling mixture and the reaction mixture was heated at reflux for 36 h in the dark. The mixture was allowed to cool and the solvent was removed by evaporation under reduced pressure. The residue was washed with methanol and purified by column chromatography (eluting with toluene) to remove symmetrical octadecylzinc phthalocyanine first. The eluent was changed to petroleum ether / tetrahydrofuran (THF) (10: 1) to give a green fraction. Solvents were removed from this fraction and the green-yellow solid obtained was recrystallized from tetrahydrofuran (THF) / methanol to give 6 mg of 1,4-dibutoxy-2β - [(O-tyrosinyl-butyl ester) oxymethyl-phenyl-8,11] , 15,18,22,25hexakis (decyl) phthalocyaninosin (II) complex in the form of a blue-green solid.

178 • 44 4 * 4 · 4 · 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4

MALDI-MS: isotopic cluster centered in 1886 (indicating that the methoxy groups contained in the starting material were transesterified with solvent-derived butoxy groups).

_Max (abs.) 716 nm (THF).

Example 91

Preparation of 1,4-di (butyloxy-2- (4'-butoxy-4'-oxobutyl) 8,11,15,18,22,25-hexakis (decyl) phthalocyaninatosin (II) complex

A mixture of 1,6 g (3,9 millimoles) of 3,6-didecylphthalonitrile,

500 mg (1.3 mmol) of 3,6-bis (butyloxy) -4- (4'-ethyl-4'oxobutyl) phthalonitrile and 370 mg (1.73 mmol) of zinc acetate dihydrate (99.999 percent pure) in 20 milliliters of dry butanol was heated to boiling. A large excess of DBU was added to the boiling mixture and the reaction mixture was heated at reflux for an additional 6 hours. The solvent was removed under reduced pressure and the residue was chromatographed on silica gel (eluting with petroleum ether (40-60 ° C) / tetrahydrofuran (THF) (10: 1)). The first blue fraction contained 1,4,8,11,15,18,22,25-octakis (decyl) phthalocyanine-zinc complex. A second fraction was collected and purified by further silica gel chromatography (with the same eluent). The product obtained was precipitated from tetrahydrofuran (THF) / methanol as an oil. The solvent over the oil was decanted and the green residue was dried under high vacuum to give 18 milligrams (0.01 millimoles, 0.8 percent) of 1,4-di (butyloxy-2- (4'-butoxy-4'oxobutyl). -8,11,15,18,22,25-hexakis (decyl) phthalocyaninosin (II) complex.

179 ································· · · ···· ^X * H NMR (270 MHz, C ₆ D ₆₎ δ 8.00 (m, 4H), 7.92 (s, 2H), 7.6 (s,

1H), 4.6-5.4 (m, 18H), 4.15 (t, 2H), 3.42 (t, 2H), 1.0-2.6 (m, 110H), 0.81 (m, 27H) ppm.

MALDI-MS: cluster 1704.

Λ _max (abs.) 711 nm; _Max (em.) 719 nm (THF).

Example 92

Preparation of 1,4-diphenyl-8,11,15,18,22,25-hexakis (decyl) phthalocyaninatosin (II) complex

To a solution of 0.28 g (1 mmol) of 3,6-didecylphthalonitrile and 0.408 g (1 mmol) of 3,6-didecylphthalonitrile in 8 ml of boiling butanol was added 106 mg (0.7 equivalents) of DBU. The resulting solution was heated to boiling for 1 hour and then 70 mg (0.3 equivalents) of zinc acetate dihydrate (99.999 percent pure) was added. The reaction mixture turned green and was heated at reflux for an additional 24 hours. After cooling, 10 ml of methanol was added to the mixture, the resulting precipitate was filtered off and washed with 3 x 10 ml of methanol. The product was purified by silica gel chromatography (eluting with petroleum ether (40-60 ° C) / dichloromethane (4: 1)) to isolate 0.1 g (6.3 percent) of 1,4,8,11,15, 18,22,25-octocis (decyl) phthalocyanine-zinc complex. The eluent was changed to petroleum ether (40-60 ° C) / dichloromethane (7: 3) to give a second fraction, after evaporation and recrystallization of the solid residue from tetrahydrofuran (THF) / methanol to yield 60 mg (0.04). millimol, percent) of the desired product.

¹ H NMR (270 MHz, CDCl ₃ ) δ 8.02 - 8.08 (m, 4H), 8.01 (s, 2H),

7.75 (d, 2H), 7.6-7.68 (m, 8H), 7.26 (br s, 2H), 4.32 (t,

180 't 4 · 4 00 0 0 00. 044 ·· 00 0 ·· · 0

4 4 · 4,040,040

0004 0 4 43 4-4 4 0 ··· #

4H), 4.08 (t, 4H), 3.11 (t, 4H), 2.07 (qn, 4H), 1.88 (qn, 4H), 1.0-1.6 (m, 88H) 0.7 - 0.9 (m, 18H) ppm.

_Max (THF): Abs. 710 nm.

MALDI-MS: isotopic cluster 1571 [M ⁺ ].

Example 93

Preparation of 1,4-bis (4-methoxyphenyl) -8,11,15,18,22,25hexakis (decyl) phthalocyaninosin zinc complex

To a solution of 342 mg (1 mmol) of 3,6-bis (4-methoxyphenyl) phthalonitrile and 0.816 g (2 mmol) of 3,6-didecylphthalonitrile in 10 ml of boiling butanol was added 0.32 g (0.7 equivalents) of DBU. The resulting solution was heated at reflux for 1 hour and then 0.2 grams (0.3 equivalents) of zinc acetate dihydrate (99.999 percent pure) was added. The reaction mixture turned green and was heated at reflux for an additional 24 hours. After cooling, 10 ml of methanol was added to the mixture, the resulting precipitate was filtered off and washed with 3 x 10 ml of methanol.

The product was purified by silica gel chromatography (eluting with petroleum ether (40-60 ° C) / dichloromethane (4: 1)) to isolate 0.21 g (12.3 percent).

1,4,8,11,15,18,22,25-octakis (decyl) phthalocyanine zinc complex. The eluent was changed to petroleum ether (40-60 ° C) / dichloromethane (1: 1) to give a second fraction, after evaporation and recrystallization! of solid residue from tetrahydrofuran (THF) / methanol gave 0.21 g (0.13 mmol, 13 percent) of the desired product.

¹ H NMR (300 MHz, CDCl ₃ ) δ 7.94 (m, 6H), 7.74 (d, 2H), 7.62 (d,

2H), 7.44 (s, 2H), 7.12 (d, 4H), 4.35 (t, 4H), 4.2 (t, 4H),

181 • φ «· · · · · · φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ · Φ · φφφφ

3.96 (s, 6Η), 3.2 (t, 4Η), 2.08 (qn, 4Η), 1.95 (qn, 4Η), 1.0 1.6 (m, 88Η), 0, 81 (t, 12Η), 0.74 (t, 6Η) ppm.

_Max (THF): Abs. 713.5 nm.

Example 94

Preparation of 1,4,8,11-tetrakis (decyl) -15,18,22,25-tetrakis (phenyl) phthalocyaninosin zinc complex and 1,4,15,18tetrakis (decyl) -8,11,22,25-tetrakis ( phenyl) phthalocyaninosin (II) complex

To a boiling solution of 0.30 grams (1.07 millimoles) of 3,6-diphenylphthalonitrile and 1.31 grams (3.21 millimoles, 3 equivalents)

Of 3,6-didecylphthalonitrile in 15 ml of dry pentanol was added 0.46 g (3 ml,

0.7 equivalents) DBU. The resulting solution was heated at reflux for 1 hour, and then 0.28 g (1.29 millimoles, 0.3 equivalents) of zinc acetate dihydrate was added. The reaction mixture was heated at reflux for a further 20 hours. The solution was cooled to room temperature and the residue was dissolved in tetrahydrofuran (THF). The solvents were removed under reduced pressure and the residue was washed with cold methanol. The obtained products were purified by silica gel column chromatography (eluting with a mixture of petroleum ether (40-60 ° C) / dichloromethane (9: 1) containing 1% triethylamine). In the first fraction, 90 milligrams (4.3 percent) of 1,4,8,11,15,18,22,25-octakis (decyl) phthalocyanine-zinc complex was isolated. The eluent was changed to petroleum ether (40-60 ° C) / dichloromethane (3: 1) to give a second fraction containing 1,4,8,11,15,18hexakis (decyl) -22,25-diphenylphthalocyaninatosin (II) complex . Change the eluent again to a petroleum ether mixture (40 to 40 ° C)

182 ·· fe * fefe fefe fefe fefe fefe fefe fefe fefe fefe fefe fefe fefe fefe fefe fefe fefe fefe fefe fefe f ° Dichloromethane (1: 3) yielded 40 milligrams (0.03 millimol, 2.6 percent) of 1,4,8,11-tetrakis (decyl) 15,18,22,25-tetrakis (phenyl) phthalocyaninosin (II) complex and 1,4,15,18-tetrakis (decyl) -8,11,22,25-tetrakis (phenyl) phthalocyaninosin zinc complex.

MALDI-MS: cluster 1443.

_Max (abs.) 713.5 nm (THF).

Example 95

Preparation of 1,4-bis (3-methoxyphenyl) -8,11,15,18,22,25hexakis (decyl) phthalocyaninosin zinc complex

To a solution of 0.33 g (0.38 mmol) of 3,6-bis (3-methoxyphenyl) phthalonitrile and 0.94 g (2.29 mmol, 6 equivalents)

Of 3,6-didecylphthalonitrile in 10 ml of boiling pentanol was added 0.30 g (0.7 equivalents) of DBU. The resulting solution was heated at reflux for 1 hour and then treated with 0.18 g (0.3 equivalents) of zinc acetate dihydrate (99.999 percent pure). The reaction mixture turned green and was heated at reflux for an additional 24 hours. After cooling, 10 ml of methanol was added to the mixture, the resulting precipitate was filtered off and washed with 3 x 10 ml of methanol. The product was purified by silica gel chromatography (eluting with petroleum ether (40-60 ° C) / dichloromethane (4: 1)) to remove 1,4,8,11,15,18,22,25-octakis (decyl). phthalocyanine zinc complex. The eluent was changed to petroleum ether (40-60 ° C) / dichloromethane (1: 1) to give a second fraction which, after evaporation, gave 1,4-bis (3-methoxyphenyl) 8,11,15,18, 22,25-hexakis (decyl) phthalocyanine-zinc complex as a green solid which was recrystallized from tetrahydrofuran (THF) / methanol.

183 · 0 0 · 0 00 00 00 00 * * * 00 00

MALDI-MS: cluster 1632.

A _m x (abs.) 710 nm (THF); Λ _max (em.) 722.4 nm (THF).

Example 96

Preparation of 1,4-bis [6'- (imidazol-1-yl) hexyl] 8.11.15.18.22.25-hexakis (decyl) phthalocyaninatosin (II) complex

A mixture of 550 milligrams (1.3 millimoles) of 3,6-bis (6 '- (imidazol-lyl) hexyl) phthalonitrile and 3.14 grams (7.71 millimoles (9 equivalents)) of 3,6-didecylphthalonitrile in 25 milliliters of pentanol was in the presence of 500 mg (2.3 mmol) of zinc acetate dihydrate (99.999 percent pure) was heated to boiling, 10 equivalents of DBU were added to the reaction mixture, and heating was continued for another 24 hours. The dark green solution remaining at the bottom of the flask was purified by silica gel chromatography (eluting with petroleum ether (40-60 ° C) / tetrahydrofuran (THF) (2). : 1)) to yield 2.08 grams (64 percent)

1.4.8.11.15.18.22.25- octakis (decyl) phthalocyaninatosin (II) complex. The eluent was changed to petroleum ether (40 ° C) / tetrahydrofuran (THF) (1: 1) and the green fraction eluted. Subsequently, the column was eluted with tetrahydrofuran alone to give a second green fraction. According to thin layer chromatography (TLC) and NMR spectra, the two fractions were identical and were therefore pooled. After evaporation of the solvent, the green residue was dissolved in hot tetrahydrofuran (THF) / methanol and after cooling 1,4-bis [6 '- (imidazol-1-yl) hexyl] -8,11,15,18,22 was separated, 25-hexakis184 »<* * 99 * 99 99 99 99 99 99 99 99 99 99 99 99 99 99 99 99 99

9 (decyl) phthalocyanine-zinc complex in the form of a green oil, which after drying under high vacuum amounted to 270 milligrams (0.16 millimoles, 12 percent).

¹ H NMR (270 MHz, C ₆ D ₆ with pyridine-d ₅ added) δ 7.95 (s, 2H), 7.91 (s, 4H), 7.82 (s, 2H), 5.65 - 5.81 (m, 6H), 4.7-4.92 (m, 16H), 2.65 (t, 4H), 2.37 (m, 12H), 2.18 (m, 4H), 1 78 (m, 12H), 1.4 (m, 12H), 1.1-1.34 (m, 72H), 0.79 (m, 18H) ppm.

Λ max (abs) 705.0 nm (THF).

MALDI-MS: cluster 1719.

In addition, the following phthalocyanines containing the same substituents on each ring were prepared:

Example 97

Preparation of 2,3,9,10,16,17,23,24-octabrom1,4,8,11,15,18,22,25-octabutoxyphthalocyaninatonicelic complex

0.5 g (1.16 mmol) of 4,5-dibromo-3,6-dibutoxyphthalonitrile was heated to boiling under nitrogen in 6 ml of dry butanol. DBU (0.18 g, 1.2 mmol) was added and the mixture was warmed to room temperature for 1 h. To the reaction mixture was added 0.09 g (0.3 mmol) of nickel acetate acetate hydrate and the resulting mixture was warmed to room temperature for an additional 24 hours. After cooling, the reaction mixture was removed under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluting with dichloromethane (DCM) / triethylamine (99: 1)) to give 2,3,9,10,16,17,23,24-octabromo-1,4, 8,11,15,18,22,25octabutoxyphthalocyaninatonicelic complex, the amount of

185 9 9

9 9 9 9 9 9 9 9 9 9

9 98 9 9 9

9 9 9 9 9 9

The recrystallization from tetrahydrofuran (THF) / methanol was 0.21 g (40.6 percent).

Mp> 250 ° C.

PrO C64H72NgO8BrgNl ·

Found: C 43, 45 O, 0 ; H 4.00 o. · 0 y N 6, 23% • Calculated: C 43.20 0, O ; H 4.08 g, · o r N 6, 30% • ¹ H NMR (270 MHz, CDC1 ₃ , 3 4 mg v 0, 7 ml) δ 4.78 (t, 16H, J = 6.9 Hz), 2, 22 (quint. 16H r J = 7.3 Hz), 1,70 - 1.56 (m, 16H),

1.04 (t, 24H, J = 7.3Hz) ppm.

Example 98

Preparation of 1,4 / 8,11,15,18,22,25-octabutoxy-2,3,9,10,16,17,23,24-octa (tris (isopropyl) silylethinyl) phthalocyaninatonicellate complex

According to the procedure described in Example 98, 0.51 grams (0.81 millimoles) of 4,5- (tris (isopropyl) silylethynyl) -3,6-dibutoxyphthalonitrile was reacted with 0.7 grams (0.5 grams) for 20 hours. 48 millimoles of DBU and 0.07 grams (0.24 millimoles) of nickel acetate tetrahydrate in 6 milliliters of dry butanol. Purification by column chromatography (eluting with dichloromethane (DCM) / petroleum ether (1: 2)) afforded 0.25 g (48 percent) of 1,4,8, 11,15,18,22,25-octabutoxy-2,3 9, 10, 16, 17, 23, 24-octa (tris (isopropyl) silylethynyl) -phthalocyaninatonicellate complex.

For C 15 H 24 O 6 N 8 O 8 SiO 2

Found: C 70.37%; H, 9.26%; N 4.28%.

Calculated: C 70.46%; H, 9.34%; N 4.32%.

MS (MALDI) isotopic cluster 2591 [M ⁺ ].

186 • 44 • 4 4 4

4 44

4 49 49 • 4 4 4

4 4

4 4 4 »

4444 44 <4 4 <

4

4 • ^X 444 H NMR (270 MHz, CDCl 3, 3.0 mg in 0.7 ml) δ 4.80 (t, 16H, J = 7.7 Hz), 2.13 (quint, 16H, J = 7 6 Hz), 1.36-1.25 (br s, 168H), 0.83 (t, 24H, J = 7.4 Hz) ppm.

Example 99

Preparation of 1,4,8,11,15,18,22,25-octakis (butoxy) 2,3,9,10,16,17,23,24-octakis (ethinyl) phthalocyaninatonicellate complex

130 mg (0.05 mmol) of the compound prepared in Example 98 was stirred under argon in 5 mL of tetrahydrofuran (THF) at -78 ° C. To this solution was added dropwise 1 ml of a 1.0 molar solution of TBAF in tetrahydrofuran (THF) (excess). The reaction mixture was allowed to warm to room temperature, stirred for an additional 12 hours and then poured into 20 mL of 5% hydrochloric acid. The resulting solution was extracted with 2 x 20 mL diethyl ether. The combined organics were washed with saturated sodium bicarbonate solution, water, brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was chromatographed on silica gel (eluting with petroether (40-60 ° C) / dichloromethane (DCM) (2: 1 to 1: 1)) to give 42 mg (0.03 mmol, 60 percent) of the solvents. 4,8,11,15,18,22,25-octakis (butoxy) -2,3,9,10,16,17,23,24-octakis (ethinyl) phthalocyaninatonicellate complex as a green solid.

¹ H NMR (270 MHz, C ₆ D ₆ ) δ 5.11 (t, 16H), 3.5 (s, 8H), 2.35 (p, 16H), 1.75 (m, 16H), 1 1.1 (t, 24H) ppm.

¹³ C NMR (270 MHz, C ₆ D ₆ ) δ 155.24, 145.41, 129, 62, 123.42, 88.04,

79.73, 77.31, 33.09, 19.89, 14.39 ppm. Λ max (abs.) Δ 62.0 nm (THF).

Fcfc fcfc fcfc fcfc fcfc fcfc fcfc fcfc fcfc fcfc fcfc fcfc fcfc fcfc fcfc fcfc fcfc fcfc fcfc fcfc fcfc fcfc fcfc fcfc fcfc fcfc fcfc fcfc fcfc fcfc ··

Example 100

Preparation of 1,4,8,11,15,18,22,25-octa (butoxy) 2,9 / 10,16 / 17,23 / 24-tetrabromophthalocyanine-zinc complex

A mixture of 0.5 g (1.42 mmol) of 4-bromo-3,6-dibutoxyphthalonitrile, 0.5 g (3.28 mmol) of 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU) and 71 mg (0.39 millimoles) of zinc acetate in 20 milliliters of dry butanol was heated to boiling under nitrogen for 2 days in the dark. The solution was cooled and the solvent was evaporated under reduced pressure. The crude product was washed with 3 x 50 mL methanol. The obtained green solid was purified by preparative thin layer chromatography (TLC) of silica gel. This chromatography did not completely separate all four of the possible structural isomers, and these were contained in the two green-colored fractions which were separated. Based on ^Χ Η NMR spectra measurements, it was determined that the first fraction, which was 30 milligrams, was composed of a mixture whose main component (> 70 percent) was 1,4,8,11,15,18,22,25-octa (butoxy) -2,9,16,23-tetrabromophthalocyanine zinc complex.

¹ H NMR (300 MHz, C ₆ D ₆ ) δ 7.95 (s, 2H), 7.85 (s, 2H), 5.43 5.20 (m, 8H), 4.64 (br s, 4H), 4.45 (br s, 4H), 2.46 (m, 4H), 2.30 (m, 8H), 2.03 (m, 4H), 1.8-1.5 (m, 16H), 1.3-1.2 (m, 12H), 1.2-0.8 (m, 12H).

_Max (abs.) 733 nm (THF).

· 4 ·

188

0 «00 0 0 ·

0 0 0 0 0 0 0000

Description of biological experiments

Using cell deactivation studies

To demonstrate that the study compounds of the invention also have the ability to function as an effective photosensitizer of biological systems, cells were incubated with the study compound, formulated in a liposome suspension, and then exposed to radiation of appropriate wavelength and energy. The number of viable cells that survived the irradiation was recorded.

The HT 1080 fibrosarcoma cell line was selected for this study [ATCC Registration Number: CCL-1212 (see S Rasheed, WA Nelson-Rees, EM Toth, P. Arnstein, B. B. Gardner, "Characterization of a newly derived human sarcoma cell line (HT-1080), Cancer, 1974, 33, 1027)]. This cell line represents cells with very fast growth and thus serves as a good model of the fast cell cycle that occurs in psoriasis.

Preparation of liposomes

See. publications: G. Valduga, G. Bianco, G. Csik, E. Reddi,

L. Masiero, S. Garbisa, G. Jori, "Interaction of Hydro- or Lipophilic Phthalocyanines with Cells of Different Metastatic Potential, Biochem. Pharmacol., 51, 585 (1996).

The compounds were formulated into monoellular liposomes from L-α-dioleoylphosphatidylcholine (DOPC). The procedure developed can be schematically described in the following points:

189

• 9 9

9 *

• 9

9

9

1. A DOPC stock solution of 20 mg / ml in chloroform was prepared.

2. 4 milliliters of this solution were added to a 250 milliliter glass flask which was attached to a rotary evaporator and mixed with an appropriate volume of a tetrahydrofuran (THF) solution of the compound of the invention to achieve a final molar ratio between the phthalocyanine and said phospholipid 1: 200. The flask was wrapped in aluminum foil.

3. The flask was saturated with nitrogen and held at room temperature for 5 minutes.

4. The evaporator was then connected to a water pump to reduce the pressure and the solvent was evaporated from the solution at room temperature.

5. The flask was saturated with nitrogen and milliliters of nitrogen saturated phosphate buffered saline (PBS) were added. The lipid film containing said phthalocyanine was resuspended by gentle agitation in the presence of glass beads.

The thus formed aqueous suspension was sonicated (at a frequency of 10 hertz) for approximately 30 minutes. The flask was again saturated with nitrogen and stored in an ice bath. Finally, the resulting liposomes were stored overnight at room temperature.

190 · 0 · 90 · 9 · 9 * 9 · 9 · 9 · 9 · 9

The shelf life of said liposomes was at least three months when stored at 4 ° C. Prior to use, the liposomes were filtered through a 0.2 micron filter and the phthalocyanine concentration was measured by diluting a small amount of said suspension in a known excess of tetrahydrofuran (THF) and determining the absorbance of the solution thus formed.

Cellular studies

Cells were routinely cultured in DMEM (which was Eagles modified Dulbecco medium to which 100 units per milliliter of penicillin, 10 micrograms / milliliter of streptomycin, 0.25 µm / milliliter of anphotericin and 2mM glutamine was added) containing 10% FCS (fetal calf) serum), wherein the cultivation was carried out in a humidified atmosphere containing 5 percent carbon dioxide and at 37 ° C. Said cells were usually separated using a solution of 0.05% trypsin - 0.02% EDTA in phosphate buffered saline. The effect of trypsin was blocked by the addition of FCS. The cell pellet, which was obtained by centrifugation at 1000 rpm for 8 minutes, was resuspended in DMEM medium and 10% FCS and then inoculated into a 75 cm ² tissue culture flask.

Consumption of phthalocyanines by cells

In a typical experiment, 6 x 10 ⁵ cells were suspended in DMEM (which was Dulbecco's Eagles Modified Medium) containing 10% FCS and incubated in a 25 cm ² tissue culture flask. After 24 hours, the culture medium was removed and replaced with 5 ml of DMEM (enriched with 3% FCS) containing either 5 μΜ

191 t · ·· · 4 · · 4 4 4 4 9 · 9999 • 99 94 99 «4 9

948 99 94 999 4 4

4,999,994

4494 49 49 49 · * 4999 or 10 μΜ phthalocyanine according to the invention. The phthalocyanine was added in an aqueous suspension of DOPC liposomes. After 1 hour incubation, the medium was removed and the cells were washed with 2x4 milliliters of PBS containing no calcium and magnesium ions.

The obtained cell pellet was homogenized with 2 ml of a 2% aqueous sodium dodecyl sulfate (SDS) solution and the suspension thus obtained was divided into two parts:

(a) 1 milliliter was diluted with a known volume of tetrahydrofuran (THF) to determine the phthalocyanine concentration by spectrophotometric analysis (excitation by radiation at a wavelength of 650 nanometers, measured in the wavelength range from 660 nanometers to 780 nanometers) performed on a Perkin spectrophotofluorimeter -Elmer LS50B.

b) 0.5 ml was used to determine the protein content, which was carried out by standard bicinchoninic acid assay.

In this context, reference may be made to P.K.

Smith, "Measurement of protein using bicinchoninic acid,

Anal. Bloch., 1985, 150, 76.

The amount of recovered phthalocyanine was calculated by interpolation of the calibration curve and the consumption was expressed in nanomoles of phthalocyanine / milligram of cell protein.

192 • · *

Cell irradiation studies

For irradiation studies, 1.8 χ 10 ⁵ cells were seeded in 7 cm diameter Petri dishes and incubated for 24 hours in DMEM containing 10% FCS in a humidified atmosphere containing 5% carbon dioxide and incubated for 5 hours. temperature 37 ° C. Said medium was removed and replaced with 1 milliliter DMEM medium containing from 2.5 μΜ to 10 μΜ phthalocyanine, which was added to the medium in the DOPC liposome suspension. After 1 hour incubation, the cells were washed twice with PBS containing calcium (0.9 mM CaCl 2 2H ₂ O) and magnesium (0.5 mM MgCl ₂ .2H ₂ O) ions.

Radiation source

The radiation source - Waldmann PDT 1200 (from Waldmann Medical Division, Villingen-Schwenningen, Germany) - was an incoherent radiation source equipped with a filter that allowed the passage of light with a wavelength from 600 nanometers to 730 nanometers. A built-in power meter was used to monitor radiation doses. The lamp was operated at an output of 100 mW / cm ² .

Cells in Petri dishes were irradiated (at 100 mW / cm ² ) for 1, 5, 10, 15 minutes (corresponding to 6 to 90 J / cm ² ) in the presence of 1 milliliters of PBS containing calcium and magnesium ions.

The irradiated cells were mixed with 2 ml of DMEM medium containing 10% FCS and incubated overnight. The photosensitized cells were examined by an assay in which 4449

193

Uses trypan blue (see C. Milanesi, F.)

Sorgato, G. Jori, "Photokinetic and ultrastructural studies on porphyrin photosensitization of HeLa cells, Int. J. Radiat. Biol., 1989, 55, 59) and the number of surviving cells was expressed as a percentage of the number of cells that usually survive under the same conditions except for exposure. Preliminary studies have shown that irradiation of cells in the absence of the photosensitizer of the invention and incubation of said cells in the dark in the presence of phthalocyanines have no effect on the number of surviving cells.

Photosensitized deactivation of human fibroblasts by phthalocyanines

Table 3 summarizes the results obtained in the experiments described above. The position of substituents e, f, g and h is shown in formula VIII (VIII)

194 • 9 ··

9 · 9 9

99 * 9

98 99 «9

9 9 9 9 9 9 • • · ·· 9 9 t

9 · 9 9 9 · · · ·

9 10 · 99 «

9 · 99

Table 3

M E F G h Percentage of survivors cells given irradiation time 5 min 10 min 15 min Zn C10H21 C 10 H ₂ i H H 45 3 1 Zn c ₁₂ h ₂₅ C ₁₂ H ₂₅ H H 62 3 0.5 Zn C 10 H ₂ i OBu p-HOCH ₂ C ₆ H ₄ H 91 42 23 Zn C10H21 OBu 2-thiophen-yl H 88 3 0.5 Zn C 10 H ₂ i OBu - (CH ₂ ) ₃ CO ₂ Bu H 90 77 44 Zn C 10 H ₂ i m-MeOC ₆ H ₄ H H 76 . 2 <0.1 Zn c ₁₀ h ₂₁ OBu 4-pyridyl H 61 4 1 Zn Or ₀ H ₂₁ (CH ₂ ) ₄ oh H H 91  52 40 Zn _{0 21} C H (CH ₂ ) ₉ oh H H 69 2 0.3

Photophysical experiments

UV-Vis spe.kter measurement

Ultraviolet to visible spectrum (UVVis spectra) spectra were measured using a Hitachi U-3000 spectrophotometer. Unless otherwise stated, phthalocyanine samples were dissolved in tetrahydrofuran (THF) and filled into a 1 cm x 1 cm quartz cuvette. The measurements were carried out at room temperature, i.e. at a temperature ranging from 20 ° C to 23 ° C.

Measurement of fluorescence spectra

195 a * · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · ·

Fluorescence spectra were measured using a Hitachi U-4500 spectrophotometer. Phthalocyanine samples were dissolved in tetrahydrofuran (THF) and filled into a 1 cm x 1 cm quartz cuvette. The measurements were carried out at room temperature, i.e. at a temperature ranging from 20 ° C to 23 ° C.

Quantum yields of singlet oxygen, Φ _Δ

Quantitative yields of singlet oxygen were determined by direct measurement of singlet oxygen phosphorescence at 1270 nanometers using the method described in S. Nonell and S. Braslavzky, "Time Resolved Singlet Oxygen Detection," Singlet Oxygen, UV-A and Ozone, Methods in Enzymology, vol. 319, Academic Press, 2000. The samples were excited using the harmonic third of the radiation produced by a controlled Nd: YAG laser, λ _ex = 355 nanometers (Spectra Physics GCR-150-10). A small portion of the radiation emanating from the laser was passed through a filter containing an aqueous solution of cobalt sulphate to remove residual radiation at wavelengths of 532 'and 1064 nanometers, and then to the holder in which the sample was placed. The samples were filled into a 1 cm x 1 cm fluorescent cuvette (Hellma). During the measurement, the energy of the incident laser beam was determined by means of a pyroelectric detector placed downstream of the sample. The laser beam energy was adjusted so that cells containing an aqueous sodium nitrite solution were placed between said CO 2 SO 4 filter and the light guide. The energy pulses were typically in the range of 25 to 500 microjoules / pulse, measured by the second pulse. , calibrated pyroelectric detector (Gentec ED-100). It was estimated that

196 • an inter-pulse noise value was less than 10 percent, and an average inter-pulse noise value of less than 3 percent was obtained at 20 exposures.

The phosphorescent radiation of the sample was captured and passed through a 1270 nanometer center interference filter (Infra Red Engineering) and then focused on the active surface of a liquid nitrogen cooled germanium photodiode (North Coast EO-817P). The signal from the detector was transmitted as an AC current to a digital oscilloscope (Tektronix TDS-320), which digitized and calculated the average transient current values. Typically, each sample was irradiated 32 times. The obtained average values were transferred to a personal computer where they were stored and further analyzed.

Stock solutions of these materials were prepared by taking a small sample of the materials and dissolving them in toluene (obtained from Fischer Scientific, analytical purity) containing 1 volume percent pyridine. Pyridine was added to toluene to ensure that the sample did not aggregate. The exact concentrations of these solutions have not been determined. The working solutions were then prepared by diluting the stock solution with toluene such that the absorbance of the resulting solution at a wavelength of 355 nanometers was in the range of 0.01 to 0.100, measured by placing the sample solution in a UV-Vis spectrometer (ATI (Jnicam UV-2). ) and were measured against a blank sample that was solvent alone, and cells with a path length of 2 centimeters were used to measure UV-Vis spectra, ensuring greater measurement accuracy

197 · · · · · · · · · · · · · · · · · · · · · · · · · · · · · ·

absorbance. Particular care has been taken to avoid high sample absorbance in the Q-band region (i.e., in the wavelength range of 600-750 nanometers), since in this case the back-absorption of sample fluorescence radiation could lead to a distortion of the measured values.

The data was recorded at room temperature, ie. at 20 to 23 ° C and the solutions were aerated. The singlet oxygen decay was recorded for each sample at 5 different laser energies, and the measurement data was fed into an exponential decay equation whose shape was I (t) = A.exp (-t / x), using a sedimentation function, which optimized A and τ. A typical course of the decay curve is shown in the attached Figure 1. For each solution, a plot of plot A of the incident laser energy was plotted and the slope of the line connecting the points was determined. The slope value is proportional to the singlet oxygen quantum yield and the amount of light absorbed by the sample. The values of the slopes, which were obtained from the graphs for individual samples, were plotted against values (1-10- ^A ), where A is the absorbance values of the individual samples at the excitation wavelength.

Experimental errors

The main sources of error in the above experiments were laser fluctuations between sample irradiations and sample absorbance measurements. For these reasons, the reported values are subject to an error of ± 10 percent.

• ·

198 • 04 * · 4 · · · ·

4 · 4444

444 · · · · 444 · ·

4 · 4 4 · 4 ··

4 ··· · * · * ·· · * ····

Standard reference materials

The values reported herein (see Figures 1 to 3) are measured compared to perinaphtenone, which is known to have a quantum yield of 0.97 (see S. Nonell and S. Braslavzky, "Time Resolved Singlet Oxygen Detection, in Singlet Oxygen, UV-A and Ozone, Methods in Enzymology, vol. 319,

Academic Press, 2000; and F. Wilkinson, W. P. Helman, and A. B. Ross, "Quantum yields for photosensitized production of the lowest excited singlet of molecular oxygen in solution, J. Phys. Chem. Ref. Data, 1993, 22, 113). The article by Wilkinson et al. Summarizing the singlet oxygen quantum yields contains many different values ranging from 0.95 to 0.97. For this reason, the absolute value may be affected by a small error, but the trends in the recorded results are clearly evident.

Quantum yields of singlet oxygen: results

The determined values are related to said standard, which was perinaftenon whose quantum yield _Φ Δ is equal to 0.97 (see. S. Nonell and S. Braslavzky "Time Resolved Singlet Oxygen Detection in the publication Singlet Oxygen, UV A and Ozone, Methods in Enzymology, vol. 319, Academic Press, 2000). As noted above, the recorded values are loaded with an error of ± 10 percent.

Duration of fluorescence

The duration of fluorescence was determined using the time - correlated single proton counting method (see.

199 ·· ·· · 4 · 4 ·

9 9 • 9 9 9 9 publication Principles of Fluorescence Spectroscopy 2 ^nd Ed. , edited by J. Lakowicz, Kluwer Academic / Plenum Press). The samples were excited by pulsed diode laser (IBH NanoLed) radiation, which produced 635 nanometer wavelength radiation. This laser produced an Imegahertz chain of pulses whose FWHM was 200 picoseconds. Fluorescent radiation was captured at 90 ° to said excitation source, the wavelength of the emitted radiation was selected by a monochromator (Jobin-YAvon Triax 190) and detected by a cooled red-light photomultiplier / discriminator (IBH TXB-04). The signal coming out of the detector was. used as the start signal for time measurement with an amplitude converter (Ortec 567) and the stop signal was derived from the laser driver / feeder. The output TAC signal was processed by a pulse height analyzer (Ortec Trump 8K). The decay curves were usually obtained using a 1024 channel record with a time window of 55 picoseconds / channel. The response functions of the measuring instruments were measured using a radiation scattering suspension and typically these response functions were 450 picoseconds of FWHM. The decay curves were analyzed by the iterative reconvolution of a given response function using the sum of exponentials and least squares optimization (see Principles of Fluorescence Spectroscopy 2 ^nd Ed., Edited by J. Lakowicz, Kluwer).

Academic / Plenum Press).

Quantum yields of fluorescence

Quantum fluorescence yields were determined by the comparative method. Spectra were measured using a JobinYvon Fluoromax-2 spectrofluorometer and were corrected for background and

200 • · ·· · 0 0 0 0 · · · 0 0 0 0 ··

000 0 · 0 ·

0 0 ® · 000 000 0 * ··

00 0 0 0 ·

The spectral response of said device. The samples were compared to the following standard materials: quinine sulfate in 1 molar sulfuric acid, of Φ _£ = 0.55, and rhodamine 101 in acidified ethanol, of Φ _£ = 1.00.

Photophysical data of examples of octa-, nona- and decasubstituted phthalocyanines

Table 4 summarizes the results obtained in the experiments described above. The position of the substituents e, f, g and h is shown in formula VIII e e

h

201 ♦ · »201 * * * *

Table

dP Η +1 1.44 r ~ CD i — 1 her rt 03 / rt rt rt <rt rtí rt her 1.39 1,64 l 1.54 1.50 her her her 1.37 rt her dP jw O Φ H +1 WHAT CN with, O CD CN X O rt rt rt rt rt rt rt rt rt rt rt Γ- whose O rt rt rt rt rt rt rt rt dP Φ H +1 what t— O CD <D O < <D O O O CD r ~ O CN <D O Γ CD O what it O rt O CD what her what CD O CD CD with. O what <0 O λ max em. nm (THF) í — i what r- O i — 1 [> Γ— O 00 Cs] O 00 O 00 O 00 what <7i r- cn r- UO CD CD what CD Γ- CN CN Γ • xP CN Γ- O C \ | Γ- CN WHAT r- 10 CN r- what CN C- < WHAT CN Γ '' N ¹ CN CN r- cn: —1 r- M • 9 δ X nt fi | r < what co cn cn O <o O O CN WHAT r- CN WHAT r- ~ l — 1 what , —1 00 Γ- what H- r ~ - Γ- CN > Γ- CD > Γ ~ O CN 00 CN WHAT WHAT LO CD \ -1 lD lT) , —1 Γ- CN i — 1 r- LO CN CN 00 1—1 00 5-1 O and- C- what i — 1 r ' O i — 1 r ~ τ—! : —1 Γ Λ X X X X X X X X X X X X X X X X X X X X X X & X X X X X X X X X X X X S-1 X in X <0 O CM X O O X 1 O, Cxj 2-thiophenyl 1 i — I Ό • H > 1 and 1 šT X > sO at OJ here WITH 2 1 and X X X 3 X cj O at 1 m OJ X O 1 Ή CM X O f-4 at i — 1 04 / X O (—1 O n X YEAH υ X Ch, -1 X <h O WHAT c4 04 / X O c-4 O ω ro 04 / X t * 4 i-4 O Hive ΡΊ X YEAH O x r- r4 X what at WHAT σ> X Ch O x T ^- 4 OJ X o o x rn X Sat O WHAT n X YEAH O ca 3 X O 3 X O 3 X O 3 X O 3 X O 3 X O ΙΌ X kO υ X O O Φ with 1 and <r X Ό O O Φ with 1 £ 3 X O W 04 / X O i— | O 04 / X O O fU X > x> O what Ch i — 1 X <h O what 04 / X O i — 1 O WHAT m 04 / X i — 1 i — 1 O what rn r4 X SD O x θ ' i — 1 X what O what Ch X <h O WHAT t-4 CM X O 1—1 O what cn X O WHAT 0Ί r4 X \ D O what 04 / X O O CM X O i — 1 O 04 / X O r4 O t — 1 04 / X O r4 O 04 / X O c4 O 04 / X O υ 04 / X O i — 1 υ t-4 04 / X O t-4 O Ol X O O Γ4 X O 1-4 O with 04 / X £ £ CN £ CN £ CN £ CN with σ> X σ> WITH σ with Λ X r ~ 1 at C FH £ CN £ CN £ LN £ LN £ LN £ IN £ LN £ CN £ CN £ ! N

• · · ·

A. ·

202 · · f f f f f

Table 4 - Completion

dP here, _ H 10 +1 (0 03 / 03 / 03 / 03 / 03 / 03 / 03 / 03 / dP e 3 +1 fO oj 03 / 03 / 03 / 03 / 03 / 03 / 03 / dP <O θ H +1 00 LO O ω 03 / 03 / 03 / 03 / (0 03 / 03 / λ max em. nm (THF) what CM Γ- λ max abs. nm (THF) m O rH CM CM O r- r- LT) O r- 732 702 (toluene) 729 698 (toluene) 722 700 (toluene) 721 701 (toluene) 716 698 (toluene) 714 700 (s) (toluene) Λ X x X Φ 2 Ή it O lil O X O III at X X 3 X X tP X x O Cst n X O 1 O at III O X <D 2 -H ω at III at X at III O WHAT 0) 2 H cn O III O X O III O 3 X 3 X 6- (imid- azol-1-yl) - hexyl 2 X O 6- (imid- azol-1- yl) hexyl 3 X O 3 X O 3 X O 3 X O 3 X O 3 X O w i — 1 CN X O O i — 1 CN X O O 6- (imid- azol-1- yl) hexyl * —1 CN X O O CN X O O i — l CN X O O 1—1 CN X O O * —1 CN £ O 1—1 o CN X O rH O £ C N £ CM £ CM Ή 2 Ή 2 • H 2 • H 2 • H 2 • H 2

value not measured

Claims (30)

PATENT CLAIMS 203 »· ^r 9i 0 · · · 0 0 · A process for the preparation of a substituted phthalocyanine of the general formula I wherein m independently of one another have the values 0,1, 2, 3 or 4, provided that all four m cannot simultaneously be 0; R ¹ are independently selected from the group consisting of optionally substituted alkyl having from 1 to 20 carbon atoms; an optionally substituted alkenyl group containing from 2 to 20 carbon atoms; an optionally substituted alkynyl group containing from 2 to 20 carbon atoms; -R ⁴ -OR ⁵ ; -R ⁴ -SR ⁵ ; ^-R4 -SC>3H; -R ⁴ -SO ² R ⁵ ; -R ⁴ -SO ² N (R ⁵ ) 2; -R ⁴ -N- (R ⁵ ) 2; -R ⁴ -P- (R ⁵ ) 2; -R ⁴ -P (O) (OR ⁵ ) 2; an optionally substituted -R ⁴ -aryl group; eventual • · · · • · · · • · 204 substituted -R ⁴ -heteroaryl; -R ⁴ -COR ⁵ ; -R ⁴ -COOR ⁵ and -R ⁴ -CON (R ⁵ ) ₂ ; wherein R ⁴ are independently selected from the group consisting of chemical bond, - '(CH ₂ ) _q -, wherein q is an integer from 1 to 20, and - (CH ₂ ) _and CH = CH (CH ₂ ) b ^- where a and b are integers from 0 to 20, wherein the sum of a and b is from 0 to 20; and R ⁵ are independently selected from the group consisting of alkyl of 1 to 20 carbon atoms, alkenyl of 2 to 20 carbon atoms, optionally substituted aryl, optionally substituted heteroaryl, hydrogen, or two R ⁵ groups may be together form a saturated or unsaturated ring; R ² are independently selected from the group consisting of p are independently 0, 1, 2 or 3; R ³ are independently selected from fluoro, chloro, bromo and iodo; and M is a metal atom in the oxidation state of M ²⁺ , metal chloride, metal bromide, metal oxide, silicon with two axial substituents or two hydrogen atoms, wherein 205 • ·· 9 · 9 9 9 9 94,999 9 9 9 9 9 9 9 9 99 49 99 9909 one of the two hydrogen atoms is bound to each of the two bonding nitrogen atoms; characterized in that it comprises the following steps: (a) converting of formula II ftalonitrilalkoholu (H0) _m to a sulfonate ester of formula III (R ⁶ SO ₂ O) _m wherein R ⁶ is either an alkyl group containing from 1 to 12 carbon atoms which may be optionally substituted by one or more fluorine and / or chlorine atoms, or an aryl group which may be optionally substituted by one or more substituents selected from the group consisting of methyl, nitro , methoxy, fluoro, chloro and / or bromo; wherein when m is 2, 3 or 4, the R ⁶ groups may be the same or different from each other; • • • (B) converting a sulfonate ester of formula III to a substituted phthalonitrile of formula IV; (c) cyclizing the substituted phthalonitrile of formula III; formulas others IV, either alone or together with any phthalonitrile of formula IV. 2. Way production of substituted phthalonitriles common of formula IV Λχ CN ^r (IV) χ ^X CN R ³ / where R ¹ , R ² , R ³ and ρ have the same meaning as in claim 1; and m is the number 1, 2, 3 or 4, characterized in that it comprises the following steps: (a) converting a phthalonitrile alcohol of formula II CN • · Fefe fefe fefe fefe fefe fefe fefe fefe fefe fefe fefe fefe fefe fefe fefe fefe fefe fefe fefe fefe fefe fefe fefe fefe fefe fefe fefe fefe fefe fefe fefe fefe fefe fefe to the sulfonate ester of formula III CN R (III) CN kde R ⁶ has the same meaning as in claim 1; and (b) converting the sulfonate ester of formula III to a substituted phthalonitrile of formula IV. A process according to claim 1 or 2, wherein the conversion of the sulfonate ester of formula III to a substituted phthalonitrile of formula IV comprises the cross-addition of said sulfonate ester of formula III with an organosinc reagent of formula R ¹ ZnX or an organo-copper reagent of formula of formula R ^x CuX which is catalyzed by palladium or nickel, wherein in the above formulas R ^{1 has the} same meaning as in claim 1 and X represents a halogen atom. A process according to claim 1 or 2, wherein the conversion of the sulfonate ester of formula III to a substituted phthalonitrile of formula IV comprises the cross-addition of a sulfonate ester of formula III with a trialkylborane of formula B (R ^X ) 3 under palladium catalysis, 208 4 4444 444 4444 ·· 44 ·· 44 445 4 R ¹ are independently selected from the group consisting of optionally substituted alkyl having from 1 to 20 carbon atoms; -R ⁴ -OR ⁵ ; -R ⁴ -SR ⁵ ; -R ⁴ -N (R ⁵ ) 2; -R ⁴ -P- (R ⁵ ) 2; an optionally substituted -R ⁴ -aryl group; an optionally substituted -R ⁴ -heteroaryl group; -R ⁴ -COR ⁵ ; -R ⁴ -COOR ⁵ and -R ⁴ -CON (R ⁵ ) 2; where R ⁴ are independently selected from the group consisting of - (CH ₂ ) q -, wherein c [is an integer from 1 to 20, and - (CH ₂ ) _and CH = CH (CH ₂ ) _b -, wherein a and b are integers from 0 to 20, wherein the sum of a and b is from 0 to 20; and R ⁵ are independently selected from the group consisting of alkyl of 1 to 20 carbon atoms, alkenyl of 2 to 20 carbon atoms, aryl, heteroaryl, hydrogen, or two R ⁵ groups may be taken together to form a saturated or unsaturated ring. A process according to claim 1 or 2, wherein the conversion of the sulfonate ester of formula III to a substituted phthalonitrile of formula IV comprises cross-linking the sulfonate ester of formula III with a boronic acid of formula R ¹ B (OH) 2 or a boronic acid ester. R ¹ B (OR ⁷ ) 2 with palladium or nickel catalysis, wherein: R ¹ is selected from the group consisting of alkenyl of 2 to 20 carbon atoms; eventual 209 9 9 9 «9 • 9 · · · · · 9,999,999 9 9 9 9 9 9 9 9 9 9 9 9 9 9999 substituted aryl and optionally substituted heteroaryl; and R ⁷ independently represent an alkyl group containing from 1 to 10 carbon atoms and both R ⁷ together with the -OBO- group form a ring. A process according to claim 1 or 2, wherein the conversion of the sulfonate ester of formula III to a substituted phthalonitrile of formula IV comprises S _N Ar reaction of the sulfonate ester of formula III with a nucleophile of formula HO-R ⁵ , HS-R ⁵ or HN (R ⁵ ) 2, HP (R ⁵ ) 2, or with an iodide anion, wherein R ⁵ are independently selected from the group consisting of alkyl of 1 to 20 carbon atoms, alkenyl of 2 to 20 carbon atoms, aryl, heteroaryl, hydrogen, or two R ⁵ groups may be taken together to form a saturated or unsaturated ring. A process according to claim 1 or 2 wherein the conversion of the sulfonate ester of formula III to a substituted phthalonitrile of formula IV comprises a palladium catalyzed addition of a sulfonate ester of formula III with an addition partner of formula R ¹ H, wherein R ¹ represents an optionally substituted terminal alkenyl group containing from 2 to 3 Or an optionally substituted terminal alkynyl group containing from 2 to 20 carbon atoms. • 0 210 000 0 A process for the preparation of a substituted phthalocyanine of the formula Va wherein m independently of one another are 0, 1, 2, 3 or 4; R ¹ are independently selected from the group consisting of optionally substituted alkyl having from 1 to 20 carbon atoms; an optionally substituted alkenyl group containing from 2 to 20 carbon atoms; an optionally substituted alkynyl group containing from 2 to 20 carbon atoms; -R ⁴ -OR ⁵ ; -R ⁴ -SR ⁵ ; -R ⁴ -SO 3 H; -R ⁴ -SO ² R ⁵ ; -R ⁴ -SO ² N (R ⁵ ) 2; -R ⁴ -N- (R ⁵ ) 2; -R ⁴ -P- (R ⁵ ) 2; -R ⁴ -P (O) (OR ⁵ ) 2; an optionally substituted -R ⁴ -aryl group; an optionally substituted -R ⁴ -heteroaryl group; -R ⁴ -COR ⁵ ; -R ⁴ -COOR ⁵ and -R ⁴ -CON (R ⁵ ) 2; wherein R ⁴ are independently selected from the group consisting of a chemical bond, - (CH ₂ ) _q -, wherein: 211 ·· · · · ♦ · 9 9 9 9 99 9 9 9 9 9 9 9 9 9 9 9 9 9 99 ·· 99 9 9 q is an integer from 1 to 20, and a group - (CH ₂ ) _and CH = CH (CH ₂ ) b - r wherein a and b are integers from 0 to 20, wherein the sum of a and b is from 0 to 20; and R ⁵ are independently selected from the group consisting of alkyl of 1 to 20 carbon atoms, alkenyl of 2 to 20 carbon atoms, optionally substituted aryl, optionally substituted heteroaryl, hydrogen, or two R ⁵ groups may together to form a saturated or unsaturated ring; R ² are independently selected from the group consisting of p are independently 0, 1, 2 or 3; R ³ are independently selected from fluoro, chloro, bromo and iodo; and R ⁸ are independently selected from the group consisting of optionally substituted alkyl groups containing from 1 to 20 carbon atoms; R ⁹ is the same as R ¹⁰ or R ¹¹ ; R ¹⁰ is iodine or bromine; • ·· · · 212 99 99 99 99 9 9 9 9 9 9 9 99 99 9 9 9 9 9 9 9 9 9 9 9 9 99 99 99 9999 R ^u is selected from the group consisting of optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl and optionally substituted heteroaryl; and M is a metal atom in the oxidation state of M ²⁺ , metal chloride, metal bromide, metal oxide, silicon having two axial substituents or two hydrogen atoms, each of which is bound by one of these hydrogen atoms; characterized by the following steps: (a) alkylating a 5,6-dihalogenated 2,3-dicyanohydroquinone in which the R ¹⁰ groups are the same or different and each of the R ¹⁰ groups represents a bromine atom or an iodine atom to form an alkylated monohalogenated product of the formula VIa in which R ⁸ groups are the same or different and each R ⁸ represents an optionally substituted alkyl group containing from 1 to 20 carbon atoms, and the R ¹⁰ group represents a bromine atom or an iodine atom OH 213 • fc ·· fcfc ·· fc * ·· • * «· · fcfcfc fcfcfc · • fcfc fcfcfcfc fcfc · • fcfcfc · · fcfcfc · · fc fcfcfcfc fcfcfc · fcfcfc · fcfcfc · fcfcfc a phthalonitrile monohalide of formula VIa to a substituted phthalonitrile of formula VIIa in which R ¹¹ represents an optionally substituted alkyl group, an optionally substituted alkenyl group, an optionally substituted alkynyl group, an optionally substituted aryl group, an optionally substituted heteroaryl group (VIa) CN CN (Villa) c) cyclizing the substituted phthalonitrile of formula VIIa, either alone or together with another phthalonitrile of formula IV (IV) to give a substituted phthalocyanine of formula Va, wherein the R ⁹ groups are identical to the R ¹¹ groups; or which alternatively comprises the following steps: (a) alkylation of 5,6-dihalogenated 2,3-dicyanohydroquinone in which the R ¹⁰ groups are the same or 214 • 9 9 • * «· • * · • ··· • · 9494 99 99 94 94 94 9 4 9 and 9499 are different and each of the R ¹⁰ groups represents a bromine atom or an iodine atom to form an alkylated monohalogenated product of formula (VIa) wherein R ^{8 are the} same or different and each R ⁸ represents an optionally substituted alkyl group containing from 1 to 20 carbon atoms, and R ¹⁰ represents bromo or an iodine atom (b) cyclizing said phthalonitrile monohalide of formula (VIa), either alone or together with another phthalonitrile of formula (IV) to give a substituted phthalocyanine of formula (Va) wherein the R ⁹ groups are identical to the R ¹⁰ groups; and c) optionally converting a group R ⁹ which is identical to a group R ¹⁰ which represents a bromine atom or an iodine atom into a group R ⁹ which is identical to a group R ¹¹ which represents an optionally substituted alkyl group, an optionally substituted alkenyl group, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl. 215 · · ** ** ** ** ** ** ** ** to to to to to to to to to to ······· · · ··· · «·· · * ···· A process for the preparation of a substituted phthalocyanine of the general formula Vb wherein m independently of one another are 0, 1, 2, 3 or 4; R ¹ are independently selected from the group consisting of optionally substituted alkyl having from 1 to 20 carbon atoms; an optionally substituted alkenyl group containing from 2 to 20 carbon atoms; an optionally substituted alkynyl group containing from 2 to 20 carbon atoms; -R ⁴ -OR ⁵ ; -R ⁴ -SR ⁵ ; -R ⁴ -SO 3 H; -R ⁴ -SO ² R ⁵ ; -R ⁴ -SO ² N (R ⁵ ) 2; -R ⁴ -N- (R ⁵ ) 2; -R ⁴ -P- (R ⁵ ) 2; -R ⁴ -P (O) (OR ⁵ ) 2; an optionally substituted -R ⁴ -aryl group; an optionally substituted -R ⁴ -heteroaryl group; -R ⁴ -COR ⁵ ; -R ⁴ -COOR ⁵ and -R ⁴ -CON (R ⁵ ) 2; wherein R ⁴ are independently selected from the group consisting of chemical bond, - (CH ₂ ) _q -, wherein 216 «« »* ·· ** φ φ φ ♦ · · · · · · φ φ φ φ φ · · φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ q is an integer from 1 to 20, and - (CH ₂ ) _and CH = CH (CH ₂ ) b ^- <wherein a and b are integers from 0 to 20, wherein the sum of a and b is from 0 to 20; and R ⁵ are independently selected from the group consisting of alkyl of 1 to 20 carbon atoms, alkenyl of 2 to 20 carbon atoms, optionally substituted aryl, optionally substituted heteroaryl, hydrogen, or two R ⁵ groups may together to form a saturated or unsaturated ring; R ² are independently selected from the group consisting of p are independently 0, 1, 2 or 3; R ³ are independently selected from fluoro, chloro, bromo and iodo; R ⁸ are independently selected from the group consisting of optionally substituted alkyl groups containing from 1 to 20 carbon atoms; R ¹¹ is selected from the group consisting of optionally substituted alkyl, optionally substituted alkenyl, optionally 99 99 • * · * 9 9 999 999 217 9 * «V 9 9 9 9 9 · 4 9 9 9 9 9 9 9 · 9 99 9999 substituted alkynyl, optionally substituted aryl, and optionally substituted heteroaryl; and M is a metal atom in the oxidation state of M ²⁺ , metal chloride, metal bromide, metal oxide, silicon with two axial substituents or two hydrogen atoms, each of which is bound by one of these hydrogen atoms; characterized by the following steps: (a) conversion of a phthalonitrile dihalide of formula VIb wherein R ^{8 are the} same or different and each R ⁸ represents an optionally substituted alkyl group containing from 1 to 20 carbon atoms, and R ¹⁰ are the same or different, each the groups R ¹⁰ represents chlorine, bromine or iodine atom, the substituted phthalonitrile of formula VIIb, in which the groups ^R11 are the same or different and each of R ¹¹ is optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl I g OR ° (VIb) CN CN (VI Ib) 218 b) cyclizing the substituted phthalonitrile of formula VIIb, either alone or together with another phthalonitrile of formula IV CN CN (IV) to form a substituted phthalocyanine of formula Vb; or which alternatively comprises the following steps: (a) cyclizing the phthalonitrile dihalide of formula VIb, either alone or together with another phthalonitrile of formula IV, to form a substituted phthalocyanine of formula Vb; and (b) converting the group R ¹⁰ , which represents chlorine, bromine or iodine, into the group R ¹¹ , which represents an optionally substituted alkyl group, an optionally substituted alkenyl group, an optionally substituted alkynyl group, an optionally substituted aryl group, an optionally substituted heteroaryl group group. Process according to claim 8 or 9, characterized in that the conversion of halides of the formula VIa or VIb into the substituted phthalonitrile of the formulas VIIa or VIIb or the conversion of the halides of the formulas Va or Vb, wherein: « -.--. ·········· 219 / ^M ! * ί ίί ί * ί J · * ··················· 11. R ⁹ is the same as R ¹⁰ , to a substituted phthalocyanine of formula Va or Vb, wherein R ⁹ is the same as R ¹¹ , includes the cross-addition of a halinide of formula VIa, VIb, Va or Vb with an organo-zinc reagent of formula R ^{1: L} ZnX or organocopper reagent of the formula R ⁿ CuX which is catalysed by palladium or nickel, wherein in these formulas, the R ¹¹ as defined in claim 8 or 9, and X represents a halogen atom. Process according to claim 8 or 9, characterized in that the conversion of the halide of the formula VIa or VIb into the substituted phthalonitrile of the formulas VIIa or VIIb or the conversion of the halide of the formulas Va or Vb, where the R ⁹ group is the same as the R ¹⁰ group of formula Va or Vb, wherein R ⁹ is the same as R ¹¹ , comprises the cross-addition of a halinide of formula VIa, VIb, Va or Vb with a trialkylborane of formula (R ¹¹ ) B (R ¹ ) ₂ to catalyze palladium, R ¹ are independently selected from the group consisting of optionally substituted alkyl having from 1 to 20 carbon atoms; -R ⁴ -OR ⁵ ; -R ⁴ -SR ⁵ ; -R ⁴ -N (R ⁵ ) 2; -R ⁴ -P- (R ⁵ ) 2; an optionally substituted -R ⁴ -aryl group; an optionally substituted -R ⁴ -heteroaryl group; -R ⁴ -COR ⁵ ; -R ⁴ -COOR ⁵ and -R ⁴ -CON (R ⁵ ) ₂ ; where R ⁴ are independently selected from the group consisting of - (CH ₂ ) _q -, wherein q is an integer 9 9 · · · · · 9 9 9 9 9 • 9 · 9 9 9 9 •• 99 99 99 220 12. from 1 to 20, and - (CH ₂ ) _and CH = CH (CH ₂ ) _b wherein a and b are integers from 0 to 20, wherein the sum of a and b is from 0 to 20; and R ⁵ are independently selected from the group consisting of alkyl of 1 to 20 carbon atoms, alkenyl of 2 to 20 carbon atoms, aryl, heteroaryl, hydrogen, or two R ⁵ groups may be taken together to form a saturated or unsaturated ring; and R ¹¹ is selected from the group consisting of optionally substituted alkyl, optionally substituted aryl, and optionally substituted heteroaryl. Process according to claim 8 or 9, characterized in that the conversion of the halide of the formula VIa or VIb into the substituted phthalonitrile of the formulas VIIa or VIIb or the conversion of the halide of the formulas Va or Vb, where the R ⁹ group is the same as the R ¹⁰ group of formula Va or Vb where R ⁹ is identical to the group R ¹¹ comprises a cross- coupling of the halide of the formula VIa, VIb, Va, or Vb with a boronic acid of the formula R ¹¹ B (OH) 2 or a boronic ester of formula R ^U B (OR ⁷ ) 2 with palladium or nickel catalysis, wherein: R ¹¹ is selected from the group consisting of optionally substituted alkenyl; eventual 221 • »· · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · fefefe · 13. 14. substituted aryl and optionally substituted heteroaryl; and R ⁷ independently represent an alkyl group containing from 1 to 10 carbon atoms and both R 'together with the -OBO- group form a ring. Process according to claim 8 or 9, characterized in that the conversion of the halide of the formula VIa or VIb into the substituted phthalonitrile of the formulas VIIa or VIIb or the conversion of the halide of the formulas Va or Vb, where the R ⁹ group is the same as the R ¹⁰ group into a substituted phthalocyanine Va or Vb, wherein R ⁹ is the same as R ¹¹ , includes a palladium catalyzed cross-addition of a halide of formula VIa, VIb, Va or Vb with an R ^{1: L} H addition partner, wherein R ¹¹ is optionally substituted alkenyl or optionally substituted alkynyl. Process according to claim 8 or 9, characterized in that the conversion of the halide of the formula VIa or VIb into the substituted phthalonitrile of the formulas VIIa or VIIb or the conversion of the halide of the formulas Va or Vb, where the R ⁹ group is the same as the R ¹⁰ group of formula Va or Vb, wherein R ⁹ is identical to R ¹¹ , includes a palladium catalyzed cross-addition of a halide of formula VIa, VIb, Va or Vb with an organosilicon reagent of formula (R ¹¹ ) Si (alkyl) 3 or an organotin reagent reagent of formula (R ^u) Sn (alkyl) 3, where 222 · «# # # # # # # # # # # # # # # # # # # # # # # # # # # # # ··········································· 15 Dec 16. R ¹¹ represents an optionally substituted alkynyl group. The method of any one of claims 1 to 14, wherein the substituted phthalocyanine of formula I, Va or Vb and / or the substituted phthalocyanine of formula IV is substituted or bonded to an amino acid, fatty acid, nucleic acid, di-, tri- or to a decapeptide, polypeptide, protein, carbohydrate, polysaccharide or polymer. A process for preparing phthalonitrile halides of the formula VIa 0R ^S where R ⁸ are independently selected from the group consisting of alkyl groups having from 1 to 20 carbon atoms which are optionally substituted; R ¹⁰ is selected from the group consisting of bromine and iodine; characterized by the following steps: (a) alkylation of 5,6-dihalogenated 2,3-dicyanohydroquinone in which the R ¹⁰ groups are the same or 223 • · 9 9 9 9 • 999 · 99 are different and each of R ¹⁰ is bromine or iodine, to form the alkylated monohalogenated product of Formula VIa 17. A process for the preparation of a phthalonitrile halide of the formula VIIb of the general formula wherein R ⁸ are independently selected from the group consisting of alkyl groups having from 1 to 20 carbon atoms which are optionally substituted; R ¹¹ is selected from the group consisting of optionally substituted alkyl, optionally substituted alkenyl; optionally substituted alkynyl, optionally substituted aryl, and optionally substituted heteroaryl; • · • · 224 · 0 · 0 0 0 0 0 · · · 0 · ···· characterized by the following stages: (a) alkylating a 5,6-dihalogenated 2,3-dicyanohydroquinone in which the R ¹⁰ groups are the same or different and each of the R ¹⁰ groups represents a chlorine atom, a bromine atom or an iodine atom to form an alkylated dihalogenated product of formula VIb, wherein R ^{8 are the} same or different and each R ⁸ represents an optionally substituted alkyl group containing from 1 to 20 carbon atoms, and R ¹⁰ represents chlorine, bromine or iodine (b) conversion of said alkylated dihalogenated product of formula VIb to a substituted phthalonitrile of formula VIIIb CN CN (VIb) (VI Ib) 9 225 • * 9 9 9 9 9 9 9 9 9 9999 99 99 «9 9 · Substituted phthalonitrile of the formula VIa or OR ^S 'IF x ^{CN r11} \ OR ⁸ CN _R -n / \ Λ ^X CN r11 / T CN OR ⁸ (Fairy) OR ⁸ (Vllb) wherein the R ⁸ groups are the same or different and each R ⁸ represents an optionally substituted alkyl group containing from 1 to 20 carbon atoms; and R ¹¹ are the same or different and each R ¹¹ represents an optionally substituted alkyl group, an optionally substituted alkenyl group; optionally substituted alkynyl, optionally substituted aryl, and optionally substituted heteroaryl. Substituted phthalonitrile of formula IV (IV) ^R p where is 1, 2, 3 or 4; 226 # 9 # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # ······························ R ¹ are independently selected from the group consisting of C 1 -C 20 alkyl optionally substituted by one or more substituents selected from F, Cl, B, I, OH, -R ⁴ -OR ⁵ , -R ⁴ -SR ⁵ , amino, -NHR ⁵ , -N (R ⁵ ) 2, -N (R ⁵ ) ^3+, and / or -R ⁴ -N- (R ⁵⁾ ) 2; an alkenyl group having from 2 to 20 carbon atoms optionally substituted by one or more substituents selected from the group consisting of fluorine, chlorine, bromine, iodine, hydroxy, -R ⁴ -O-R ⁵ , -R ⁴ -SR ⁵ , amino, -NHR ⁵ , -N (R ⁵ ) 2, -N (R ⁵ ) ^3+, and / or -R ⁴ -N- (R ⁵ ) 2; an alkynyl group containing from 2 to 20 carbon atoms optionally substituted by one or more substituents selected from the group consisting of fluorine, chlorine, bromine, iodine, hydroxy, -R ⁴ -OR ⁵ , -R ⁴ -SR ⁵ , amino, -NHR ⁵ , -N (R ⁵ ) 2, -N (R ⁵ ) ³⁺ , -R ⁴ -N- (R ⁵ ) 2, -Si (R ⁵ ) 3, group -C5H4N, -C4H3S and / or -C6H5 · ^-R4 -OR ^5; -R ⁴ -SR ⁵ ; -R ⁴ -SO 3 H; -R ⁴ -SO ₂ R ⁵ ; -R ⁴ -SO ² N (R ⁵ ) 2; -R ⁴ -N- (R ⁵ ) 2; -R ⁴ -P- (R ⁵ ) 2; ^-R4 -P (O) ^(OR5) _2; -R ⁴ -aryl which is optionally substituted by one or more substituents selected from the group consisting of alkyl of 1 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, nitro, methoxy, fluoro, 227 fcfc fc · fcfc · fc fcfc · • fcfc fcfc ·· fcfc fc fc ···· «fcfc fc ·· · · fcfcfc ··· fcfc · ·« fc · · fcfcfcfc chlorine, bromine atom , hydroxy, amino, -NHR ⁵ , -N (R ⁵ ) 2, -N (R ⁵ ) ³⁺ , -NHCOR ⁵ , -COR ⁵ , -COOR ^5, and / or -CON ( R ⁵ ) 2; -R ⁴ -heteroaryl which is optionally substituted with one or more substituents selected from the group consisting of alkyl of 1 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, nitro, methoxy, fluoro, chloro, atom bromo, hydroxy, amino, -NHR ⁵ , -N (R ⁵ ) 2, -N (R ⁵ ) 3 ⁺ f -NHCOR ⁵ , -COR ⁵ , -COOR ⁵ and / or -CON ^(R5) 2; -R ⁴ -COR ⁵ ; -R ⁴ -COOR ⁵ and -R ⁴ -CON (R ⁵ ) ₂ ; wherein R ⁴ are independently selected from the group consisting of a chemical bond, - (CH ₂ ) _q -, wherein q is an integer from 1 to 20, and - (CH ₂ ) _and CH = CH (CH ₂ ) _b - wherein a and b are integers from 0 to 20, wherein the sum of a and b is from 0 to 20; and R ⁵ are independently selected from the group consisting of alkyl of 1 to 20 carbon atoms, alkenyl of 2 to 20 carbon atoms, aryl, heteroaryl, hydrogen, or two R ⁵ groups may be taken together to form a saturated or unsaturated ring; 228 • 44 4 4 4 · · · · · 4 4 4 · · · · · · · 4,444 44 44 4 · 4 · 4 4 4 4 4 4 445 44 4 · 44 · · 4 · 4 4 4 R ² is selected from the group consisting of p being 0, 1, 2 or 3; R ³ are independently selected from fluoro, chloro, bromo and iodo; with the proviso that at least one R ¹ is an alkyl group containing from 1 to 20 carbon atoms which is substituted by one or more substituents selected from the group consisting of chlorine, bromine, amino, -NHR ⁵ , -N (R ⁵ ) 2 and / or -R ⁴ -N- (R ⁵ ) 2; an alkenyl group containing from 2 to 20 carbon atoms optionally substituted by one or more substituents selected from the group consisting of fluorine atom, chlorine atom, bromine atom, iodine atom, hydroxy group, -R ⁴ -OR ⁵ , -R ⁴ -SR ⁵ , amino, -NHR ⁵ , -N (R ⁵ ) 2, -N (R ⁵ ) ^3+, and / or -R ⁴ -N- (R ⁵ ) 2; or an alkynyl group containing from 2 to 20 carbon atoms optionally substituted by one or more substituents selected from the group consisting of fluorine, chlorine, bromine, iodine, hydroxy, -R ⁴ -OR ⁵ , -R ⁴ - S-R ⁵ , amino, -NHR ⁵ , -N (R ⁵ ) 2, -N (R ⁵ ) ³⁺ , -R ⁴ -N- (R ⁵ ) 2, -Si (R ⁵⁾ ₁₃ , -C5H4N, -C4H3S, and / or -C ₆ H ₅ . 229 9 9 9 9 999 * 999 9 · 9 9 9 9 · 99 9 9,999 · 9,999 · 9 9 9 9,999,999 9999 99 99 99 99 20 May A substituted phthalocyanine of the formula I wherein m are independently 0, 1, 2, 3 or 4; R ¹ are independently selected from the group consisting of C 1 -C 20 alkyl optionally substituted by one or more substituents selected from F, Cl, B, I, OH, -R ⁴ -OR ⁵ , -R ⁴ -SR ⁵ , amino, -NHR ⁵ , -N (R ⁵ ) 2, -N (R ⁵ ) ^3+, and / or -R ⁴ -N- (R ⁵⁾ ) ₂ ; an alkenyl group containing from 2 to 20 carbon atoms optionally substituted by one or more substituents selected from the group consisting of fluorine atom, chlorine atom, bromine atom, iodine atom, hydroxy group, -R ⁴ -OR ⁵ , -R ⁴ -SR ⁵ , amino, -NHR ⁵ , -N (R ⁵ ) 2, -N (R ⁵ ) ^3+, and / or 230 φ · φ «·· ♦ · · · · · · · · · 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 99 9 9 -R ⁴ -N- (R ⁵ ) 2; an alkynyl group containing from 2 to 20 carbon atoms optionally substituted by one or more substituents selected from the group consisting of fluorine, chlorine, bromine, iodine, hydroxy, -R ⁴ -OR ⁵ , -R ⁴ -SR ⁵ , amino, -NHR ⁵ , -N (R ⁵ ) 2, -N (R ⁵ ) ³⁺ , -R ⁴ -N- (R ⁵ ) 2, -Si (R ⁵ ) 3, -C5H4N, -C4H3S, and / or -C6H5; -R ⁴ -OR ⁵ ; -R ⁴ -SR ⁵ ; -R ⁴ -SO 3 H; -R ⁴ -SO ₂ R ⁵ ; -R ⁴ -SO ² N (R ⁵ ) 2; -R ⁴ -N- (R ⁵ ) 2; -R ⁴ -P- (R ⁵ ) 2; ^-R4 -P (O). (OR ⁵⁾ _2; -R ⁴ -aryl, which is optionally substituted with one or more substituents selected from the group consisting of alkyl of 1 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, nitro, methoxy, fluoro, chloro, atom bromo, hydroxy, -OR ⁵ , -SO 3 H, amino, -NHR ⁵ , -N (R ⁵ ) 2, -N (R ⁵ ) ³⁺ , -NHCOR ⁵ , -COR ⁵ , -COOR ⁵ and / or -CON (R ⁵ ) 2; -R ⁴ -heteroaryl which is optionally substituted with one or more substituents selected from the group consisting of alkyl of 1 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, nitro, methoxy, fluoro, chloro, atom bromo, hydroxy, amino, -NHR ⁵ , -N (R ⁵ ) 2, -N (R ⁵ ) ³⁺ , -NHCOR ⁵ , -COR ⁵ , -COOR ^5, and / or -CON ^(R5) 2; • 000 231 0 0 00 0 · * 0 · 0 00 0000 0000 00 ·· 00 00 · ··· 00 00 000 0 0 0 0 ·· · 000 00 00 0 · 0000 -R ⁴ -COR ⁵ ; -R ⁴ -COOR ⁵ ; -R ⁴ -CON (R ⁵ ) ₂ ; where R ⁴ are independently selected from the group consisting of chemical bond, - (CH ₂ ) _q -, wherein q is an integer from 1 to 20, and - (CH ₂ ) _and CH = CH (CH ₂ ) _b -, wherein a and b are integers from 0 to 20, wherein the sum of a and b is from 0 to 20; and R ⁵ are independently selected from the group consisting of alkyl of 1 to 20 carbon atoms, alkenyl of 2 to 20 carbon atoms, optionally substituted aryl, optionally substituted heteroaryl, hydrogen, or two R ⁵ groups may be together form a saturated or unsaturated ring; R ² is selected from the group consisting of p independently of 0, 1, 2 or 3, with the proviso that all indices m and all indices p cannot simultaneously be 0; R ³ are independently selected from fluoro, chloro, bromo and iodo; 232 4 4 4 4 4 4 4 4 4 4 4 4,444 · ♦ · 4,444 · · 4 4 · * ···· * 4 ··· ·· ·· ·· ·· 44 ·· 21. M is a metal atom in the oxidation state of M ²⁺ , metal chloride, metal bromide, metal oxide, silicon with two axial substituents or two hydrogen atoms, each of which is bound by one of these hydrogen atoms; with the proviso that at least one R ¹ is an alkyl group containing from 1 to 20 carbon atoms which is substituted by one or more substituents selected from the group consisting of chlorine, bromine, amino, -NHR ⁵ , -N (R 1) ⁵ ) 2 and / or -R ⁴ -N- (R ⁵ ) 2; an alkenyl group containing from 2 to 20 carbon atoms optionally substituted by one or more substituents selected from the group consisting of fluorine atom, chlorine atom, bromine atom, iodine atom, hydroxy group, -R ⁴ -OR ⁵ , -R ⁴ -SR ⁵ , amino, -NHR ⁵ , -N (R ⁵ ) 2, -N (R ⁵ ) ^3+, and / or -R ⁴ -N- (R ⁵ ) 2; or an alkynyl group containing from 2 to 20 carbon atoms optionally substituted by one or more substituents selected from the group consisting of fluorine, chlorine, bromine, iodine, hydroxy, -R ⁴ -OR ⁵ , -R ⁴ - SR ⁵ , amino, -NHR ⁵ , -N (R ⁵ ) 2 / -N (R ⁵ ) ³⁺ , -R ⁴ -N- (R ⁵ ) 2, -Si (R ⁵ ) ₃ , -C ₅ H ₄ N, -C ₄ H ₃ S, and / or -c _s h ₅ . The substituted phthalocyanine of the formula I according to claim 20 which is substituted or linked to an amino acid, a fatty acid, a nucleic acid, a di-, 233 ΦΦ * φ • • • φ «φ φ φ φ φ φ φ • • • φ polypept polypept polypept polypept polypept polypept polypept polypept polypept polypept polypept polypept polypept , a protein, a carbohydrate, a polysaccharide, or a polymer. The substituted phthalocyanine according to claim 20 or 21, wherein the M group is an isotope of zinc, aluminum, magnesium, palladium, platinum, silicon with two axial substituents or two hydrogen atoms. A substituted phthalocyanine according to any one of claims 20 to 22, which forms a sandwich complex or multimer. A substituted phthalocyanine according to any one of claims 20 to 23, which is bound to a carrier or trapped or incorporated into a macromolecular carrier. A substituted phthalocyanine according to any one of claims 20 to 24 for use as a medicament. The substituted phthalocyanine of claim 25 for use in photodynamic therapy of a human or animal disease. A pharmaceutical composition comprising the substituted phthalocyanine of any one of claims 20 to 26, or a pharmaceutically acceptable salt thereof, in admixture or in association with a pharmaceutically acceptable carrier, diluent or excipient. The pharmaceutical composition of claim 27 for use in the photodynamic therapy of a human or animal disease. Μ · 234 * · t t t t 1 1 1 1 1 1 1 1 1 · 1 1 1 1 1 1 1 1 1 1 1 ♦ • • • «« · · · The pharmaceutical composition of claim 28, wherein the radiation source is a laser or an incoherent radiation source emitting light of optimal wavelength. Use of a substituted phthalocyanine according to any one of claims 20 to 26 for the manufacture of a phototherapeutic agent for use in photodynamic therapy. The use of claim 30, wherein said phototherapeutic agent is used to treat a disease characterized by benign or malignant cell proliferation. The use of claim 30, wherein said phototherapeutic agent is used to treat a viral, fungal, bacterial or prion-induced disease. The use of claim 30, wherein said phototherapeutic agent is used to treat a disease such as a tumor, rheumatoid arthritis, inflammatory arthritis, hemophilia, osteoarthritis, vascular stenosis, vascular restinosis, atheromas, hyperplasia, hyperplasia of the inner wall of the vessel, benign prostatic hyperplasia , psoriasis, mycosis fungoides, eczema, keratosis from radiation or lichen. Use of a substituted phthalocyanine according to any one of claims 20 to 26 for the production of a photodiagnostic agent for identifying areas that are pathologically infected by cell proliferation.