DE2634663A1 - METHOD OF MANUFACTURING AN OPTICALLY ACTIVE ALKYLCHRYSANTHEMATE - Google Patents

Description

MÜLLER-BORE DETJJS ¹ JEL ÖCHCN HEHTEL

PAT E 3ST TA N WA Ϊ. TE

DR. WOLFGANG MÜL.LER-BOR & (PATENT ADVOCATE FROM 1927 - I97S) DR. PAUL DEUFEl., DIPU-CHEM. DR. ALFRED SCHÖN, DtPU-CHEM. WERNER HERTEL., DIPL ..- PHYS.

p 2921
-2. AUG. 1976

Sumitomo Chemical Company, Limit ed. Osaka, Japan

Process for the production of an optically active
Alkyl chrysanthemates

709811/105

S MtTNCHEN 8 · · SIEBEHTSTR. 4 POST BOX 800720 KABXI .: MtTEBOPAT XXL. (089) 474003 · IXIIX »44883

Process for the preparation of an optically active alkyl chrysanthemum

The invention relates to a process for the preparation of an optically active alkyl chrysanthemate in which 2,5-dimethyl-2,4-hexadiene is reacted with an alkyl diazoacetate in the presence of a copper complex, which with a novel Ship's viewing base is coordinated,

Chrysanthemic acid is known to be an important manufacturing material synthetic pyrethroids that are effective as insecticides. There are four stereoisomers of chrysanthemic acid, namely, two kinds of geometric isomers, i.e. H. cis and trans, each of which has d and 1 optical isomers. The pyrethroids derived from the d-trans and d-cis chrysanthemum acids are known for their particularly high insecticidal activity known. The naturally occurring chrysanthemic acid is known to have a d-trans structure.

Two processes are available for the industrial production of optically active chrysanthemic acid. According to one of these procedures the racemic mixture is first synthesized, whereupon it is subjected to an optical resolution. That the second of these methods is the direct synthesis of the desired asymmetric optical isomer.

A known process for the synthesis of chrysanthemic acid consists in the reaction of a Alkyldiazoacetats with 2,5-dimethyl-2,4-hexadiene in the presence of a copper catalyst (see _"v GB-PS 740 014) and subsequent hydrolysis of the Alkylchrysanthemats formed.

70981 ■ 1 /

The present invention relates to the asymmetric synthesis of alkylohrysanthemates. A method is from BE-PS 787 473 for the production of an optically active alkyl chrysanthemum "known in which an alkyl diazoacetate with 2,5-dimethyl-2,4-hexadiene is reacted in the presence of a copper catalyst which is coordinated with a chiral ligand according to following reaction scheme: COOR

N ₀ CHCOOR ^ % f
_2 ^ v ^ / \, / ^ COOR

Cu (L *) _n

wherein L ^ represents a chiral ligand.

From BE-PS 810 959 it is known the asymmetric synthesis of Alkylchrysanthematen in an advantageous manner with a To catalyze copper complex that is coordinated with a chiral Schiff base of the following formula (I)

(D

where mean:

C * is an asymmetric carbon atom, R is an alkyl radical having 1 to 10 carbon atoms or

an aralkyl radical which optionally has one or more alkoxy substituents carries with a total of 7 to 20 carbon atoms, R aryl radicals which carry one or more alkoxy substituents with a total of 7 to 30 carbon atoms,

709811/1050.

X ¹ and X ² on their own

a) hydrogen atoms,

b) alkyl radicals with 1 to 10 carbon atoms,

c) phenyl residues,

d) alkoxy radicals with 1 "to 10 carbon atoms,

e) halogen atoms or

f) nitro groups, or together a benzo group.

The following is a further explanation of the novel Ghiral copper complexes, which according to BE-PS 81O 959 as Catalysts are usable, given.

Forms the Schiff base of the given formula (l) Metal? J complex with bivalent copper ion, so are three types of chelates possible (for the chemistry of the metal complexes of Schiff bases see e.g. R. H. Holm, G. W. Everett, Jr. and A. Chakravorty "Progress in Inorganic Chemistry" 7, 83-214, (1966), Interscience Publishers, Few York).

One of these chelates has the following dimeric structure (II), where the Schiff base behaves as a tridentate ligand:

(II)

1 ?
wherein R, R and X have the meaning given.

70981 1/1050

-X-

The other chelate has the following monomeric structures (Hl) or (IV), in which the Schiff base turns out to be bidentate "tew. tridentate ligand behaves

- σ * Η - σ - oh

(III)

(IV)

1 2

where R, R and X have the meaning given and L is a neutral monodentate ligand (with regard to the copper complexes of H-salicylidene-2-aminoethanol cf., for example, RP Houghton and DJ Pointer, ^T. Chem. Soc. (1965) , 4214)

The alkyl diazoacetate, which serves as the substrate in this asymmetric synthesis, was also investigated. It showed it is that the alkyl diazoacetate of the general formula (V)

N ₂ CHCOOR

(V)

where R means:

70981 1/1056

a) a cycloalkyl radical, which optionally has one or more alkyl substituents carries with a total of 5 "to 20 carbon atoms,

b) a tertiary aralkyl radical with 9 to 20 carbon atoms, or

c) a tertiary alkyl radical, which optionally bears one or more alkoxy substituents with a total of 4 to 20 carbon atoms

is particularly effective in achieving the alkyl- chrysanthemates of excellent optical purity and a high trans isomer content. This finding is great Surprisingly because of the results of reactions in which a primary diazoate of a short-chain aliphatic Alcohol having 1 to 8 carbon atoms, e.g. B. the ethyl ester is used.

The present invention is based on this new finding. According to the invention, there is a method for production an optically active alkyl chrysanthemum created that is characterized by the reaction of an alkyl diazoacetate of the general formula (V) given with 2,5-dimethyl-2,4-hexadiene catalytically using a chiral copper complex, which can be seen from the optically active ship Base of the specified type derives, e.g. B. one with a monomeric structure according to the general formulas (III) or (IV) or one with a dimeric structure according to the general formula (II).

The radical R of the diazoacetate of the given general formula (V) can be, for. B. are the following residues:

(a) Typical suitable cycloalkyl radicals are e.g. B. Cyelopentyl, 2-BIethylcyclopentyl, cyclohexyl, 2-methylcyclohexyl, 2,2-, 2,5- or 2,6-dimethylcyclohexyl, 2,2,6-trimethylcyclohexyl, Cyclooctyl or cyclododecyl.

709811/1056

Cyeloalkyl radicals of natural, occurring or non-natural alicyclic alcohols are also suitable, e.g. B. menthyl, isoinenthyl ', beomenthyl, neoisomenthyl, carbomenthyl, Bornyl, isobornyl, 2-norbornyl, or 1- and 2-adamantyl.

(b) Typical suitable tertiary aralkyl radicals are e.g. B.

α, α-dimethylbenzyl, triphenylmethyl, α, α-diphenylethyl and 2-phenyl-2-butyl.

(c) Typical suitable tertiary alkyl radicals are e.g. B. t-butyl, t-amyl, 2,3-dimethyl-2-butyl, 2,3,4-trimethyl-3-pentyl, and α, α-dimethyl-ß-menthoxyethyl.

The diazoacetates of the given general formula (V) can have either achiral or chiral structure. In in the latter case, any form of enantiomeric or racemic modification can be used to carry out the process according to the invention be used. If an alkyl chrysanthemum produced according to the invention shows some insecticidal action, see above it can be used as such as an insecticide.

Although regarding the methods of synthesis of the alkyl diazoacetates the general formula (V) are not subject to any restrictions, the following procedures should be mentioned as examples:

(I) A process for the diazotization of the corresponding ester of glycine with nitrous acid or a nitrous acid ester, see e.g. B. Organic Syntheses, Coll. Vol. 4, 424 and N. Takamura, T. Mizoguchi, K. Koga and S. Yamada, Tetrahedron 31 , 227 (1975). The ester of glycine can be synthesized by reacting glycine with the corresponding alcohol or the corresponding olefin.

709811 / 10B8

-V

(II) A process by Regitz: P-toluenesulfonyl azide is made reacted with the corresponding acetoacetate and the 2 ~ diazoacetoacetate formed is deacetylated with a base Obtaining diazoacetate, see Organic Syntheses, Coll. VoI 5, p. 179.

(ill) A process by House: The acid chloride of p-toluene— sulfonylhydrazone of glyoxylic acid chloride is reacted with the corresponding alcohol in the presence of a base, cf. B. Organic Syntheses, Coll. Vol. 5, p. 258.

The Chiral-Schiff base of the given formula (I) is synthesized by reacting a chiral amino alcohol of the following formula (VI) with a salicylaldehyde derivative of following formula (VIl)

- C * H - C - OH I Io

(VI)

(VII)

wherein R ^, R, X and X have the meaning given.

70981 1/1058

In the amino alcohol of the formula VI, typical suitable radicals R ¹ and R ^{2 are} e.g. B. methyl, ethyl, propyl, isopropyl, butyl, isobutyl, 2-butyl, t-butyl, hexyl, octyl, cyclohexylmethyl, benzyl, benzhydryl and 2,2-biphenylethyl.

Preferred radicals R are z, -B. Methyl, isopropyl, isobutyl, Cyelohexylmethyl, benzyl and a benzyl radical with a substituent in the 4-position of the aromatic nucleus, where as a substituent z. B. methoxy, ethoxy, propoxy, isopropoxy, Butoxy or hexyloxy can be present.

ρ
A preferred radical R in the specified amino alcohol is a phenyl radical with a substituent in the 2-position or with substituents in the 2,5-positions. Typical suitable 2-substituted phenyl radicals are e.g. B. 2-methoxyphenyl, 2-ethoxyphenyl, 2-propoxyphenyl, 2-isopropoxyphenyl, 2-butoxyphenyl, 2-t-butoxyphenyl, 2-hexyloxyphenyl and 2- octyloxyphenyl. Typical suitable 2,5-substituted phenyl radicals are e.g. B. 2-methoxy-5-methylphenyl, 2-butoxy-5-methylphenyl, 5-methyl-2-octyloxyphenyl, 2-benzyloxy-5-methylphenyl, 5-t-butyl-2-methoxyphenyl, 2-butoxy-5- t-butylphenyl, 5-t-butyl-2-octyloxyphenyl, 4-methoxybiphenyl-3-yl, 4-butoxybiphenyl-3-yl, 4-octyloxybiphenyl-3-yl, 2,5-dimethoxyphenyl, 2,5-butoxyphenyl and 2,5-dioctyloxyphenyl.

The optically active amino alcohols which can be used according to the invention the given formula (VI) can be prepared by one of the following two methods, namely either by the fact that a racemic mixture of the corresponding amino alcohols is separated with a suitable resolving agent, or thereby, that the amino alcohol is obtained from the reaction of an optically active precursor compound. So z. B. an optically active amino ester of the following formula (VHI) with a Grignard reagent of the following formula (IX) an optically active amino alcohol of the formula (Vl) while maintaining the configuration:

70981 1/1058

E ² E ¹ - C * H - COOR ³ + R ² MgZ> R ¹ - C * H - C - OH

III ₂

HH ₂ m ₂ έγ

(VIII) (IX) (VI)

1 2

where R is an alkyl or aralkyl radical, R is an aryl radical,

R ^ is an alkyl radical having 1 to 10 carbon atoms or a benzyl radical and Z is a chlorine, bromine or iodine atom.

Regarding the addition reaction of phenyl magnesium bromide

for L-alanine ethyl ester cf. BA McKenzie, R. Roger,

G. 0. Willis, J. Chem. Soc, 779, (1926) and B. M. Benjamin,

H.J. Schaefer, C.J. Collins, J. Am. Chem. Soc, 7-9, 616O,

(1957).

Typical suitable salicylaldehyde derivatives of the given formula (VII) are, for. B. salicylaldehyde, 3-hyd Äthoxysalicylalde-, o-vanillin, 3,5-Dibromosalicylaldehyd, 5-Chlorosalicyl- aldehyde, 5-ITitrosalicylaldehyd, B-isopropyl-ö-methylsalicylal- dehyd, 2-hydroxy-naphthaldehyde, and 1-hydroxy -2-naphth.aldeh.yd,

With regard to the chiral copper complexes which can be used as catalysts according to the invention, typical suitable copper complexes of the formulas (II), (III) and (IV) are those which are derived from the following chiral Schiff bases:

(a) H-salicylidene-2-amino-1,1-di (2-methoxyphenyl) -3 ~ phenyl-1-propanol,

(b) H "-Salicylidene-2-amino-1,1-di (2-isopropoxyphenyl) -3- phenyl-1- propanol,

(c) S-salicylidene-2-amino-1,1-di (5-t-butyl-2-isopropoxy phenyl ) -3-phenyl-1-propanol,

( d) N-Salicylidene -2-amino-1,1-di (2-butoxy-5-t-butylphenyl) -3-phenyl-1-propanol, ^

70981 1/10 5 6

(e) TT-salicylidene-2-amino-i, 1-di (5-t-butyl-2-heptyloxyphenyl) -3 - (phenyl) -1-propanol,

(f) K-salicylidene-2-amino-i, 1-di (5-t-butyl-2-isopropoxyphenyl) -1-propanol,

(g) lT-salieylidene-2-araino-1,1-di (2-butoxy-5-t-butylphenyl) -1-propanol,

(h) N-Salicylidene-2-amino-i, 1-di (5-t-butyl-2-oetylosyphenyl) ~

1-propanol,
(i) N- (3-methoxysalicylidene) -2-amino-1,1-di (5-t-butyl-2-

octyloxyphenyl) -1-propanol,
( 3 ) Π- (3,5-dibromosalicylidene) -2-amino-1,1-di (2-isopropoxy-

phenyl) -3-phenyl-i-propanol,
(k) IT- (3-ethoxysalicylidene) -2-araino-1,1-di (2-isopropoxy-

phenyl) -3-phenyl-1-propanol,
(l) IT- (2-hydroxy-1-naphthylmethylene) -2-amino-1,1-di {2-

i sopropoxyphenyl) -3-phenyl-1-propanol _t (m) IT-salicylidene-2-amino-1, 1-di (4- "butoxybiphenyl-3-yl) -3-

phenyl-1-propanol,
(n) N-salicylidene-2-amino-1,1-di (2,5-dit> utoxyphenyl) -3-phenyl-

1-propanol,
(ο) n-salicylidene-2-amino-1,1-di (2-butoxyphenyl) -3-methyl-1-

butanol, or
(ρ) N-salicylidene-2-amino-i, 1-di (2-benzyloxy-5-t-butylphenyl) -

4-inethyl-1-pentanol.

As copper complexes of the optically active Schiff base of the Formula (I) are copper complexes of the specified compounds of the formulas (II), (III) and (IV) effective, the complex the compound having the dimeric structure of the formula (II) can be used in a particularly advantageous manner. The complex of general formula (II) is synthesized by reacting a Schiff base of the general formula (I) with a Copper (II) salt, e.g. B, - copper (II) acetate.

70981 1/1056

The complex of the compound having the monomeric structure of the formula (IV) is synthesized by reacting the dimeric one Complex of formula (II) with a neutral monodentate ligand, e.g. B. pyridine, picoline, or lutidine. The complex the compound having the monomeric structure of the formula (III) is synthesized by reacting a copper complex of the salicylaldehyde derivative of the formula (VII) with an amino alcohol of the formula (VI).

In the practical implementation of the process according to the invention, the implementation can take place regardless of whether the Chiral copper catalyst is soluble or insoluble in the reaction system.

The catalyst can be isolated and purified in a suitable manner for repeated use.

The molar ratio of copper complex to alkyl diazoacetate of the formula (V) is preferably in the range from 0.001 to 0.1.

Although the reaction temperature is not particularly restricted, a temperature between -50 and 150 ^° C. has proven to be suitable as a rule. In the special cases where the reaction takes place at a temperature below the melting point of 2,5-dimethyl-2,4-hexadiene (15 ⁰ G), the addition of a suitable solvent to the reaction system may prove to be desirable. In these cases z. B. aromatic hydrocarbons, such as benzene, toluene and xylene, suitable as solvents.

The following examples are intended to explain the invention in more detail without restricting it.

As a rule, there is an unambiguous relationship between the absolute configuration of that substance, the asymmetry

70981 1/1056

induced, and the absolute configuration of the substance which induces the asymmetry. It is therefore superfluous to say in the context of the present invention that if a copper complex of an enantiomeric structure opposite to that described in the following Examples " is also used as a catalyst, the formed alkyl chrysanthemum and the corresponding chrysanthemic acid have the opposite enantiomeric structure in question.

example 1

0.03 g (0.2 mmol) of the dimeric copper complex of (R) -F-salicylidene-2-amino-1,1-di (5-t-butyl-2-octyloxy) propanol (corresponding to the formula given ( II), where R = methyl, R ² = 5-t-butyl-2-octyloxyphenyl and X ¹ = X ² = hydrogen) were in 17.6 g (160 mmol) of 2,5-dimethyl-2,4-hexadiene solved. A mixture of 4 »4 S (40 mmol) of the specified diene and 4.5 g (20 mmol) of 1-menthyl diazoacetate was added dropwise to the resulting solution over the course of 7 hours with stirring. At the beginning of the addition, the catalyst solution was heated to 75 ⁰ G again, to initiate the decomposition of the diazoacetate, and the mixture was kept at 40 C. By the end of the addition, an almost quantitative amount of nitrogen gas had evolved.

The reaction mixture was to isolate the excess unreacted diene (boiling point 45 ° C / 20 mmHg) under reduced Pressure distilled and there were 4.7 g of 1-menthyl chrysanthemate obtained in the form of an oil which had a boiling point of 123 ° C / 0.2 mmHg. The yield was $ 76, based on the diazo compound.

70981 1/1056

The 1-menthyl ester was on a gas chromatography apparatus, which was equipped with a glass capillary column (liquid phase QF-1) analyzed to determine the Composition of the optical isomers of chrysanthemate, the following results being obtained:

d-trans form 89.9 ^,
1-trans form 2.7 %,

Total amount of d-cis and l ~ cis forms (separation was not possible) 7.4 ^

The calculation showed that the percentage of trans isomer in the ester was 93 % and the optical purity of the trans isomers was 92%.

A mixture of 4.2 g of 1-menthyl ester, 1.8 g Kaiiumhydroxid, 1.5 ml of water and 11 ml of ethanol was heated 7.5 hours at 100 ⁰ C with stirring. When the ethanol was distilled off from the reaction mixture, the residue was diluted with water and extracted with ether. The aqueous alkaline solution was acidified with dilute sulfuric acid and then extracted with toluene. After the organic layer was washed with water and dried, the toluene was distilled off under reduced pressure, whereby chrysanthemic acid (2.4 g, yield 90 %) was obtained.

The chrysanthemic acid was reacted with d-2-octanol and the obtained diastereomers were analyzed by gas chromatography for determining the optical isomers of chrysanthemic acid, the following results being obtained:

d-trans-form 90.4 %, 1-trans-form 4.7 f ° d-cis-form 3.6 %, 1-cis-form 1.3 ^

7 0 9 8 11/10 5 6

The calculation showed that the optical purity of the trans isomers was 90% and that of the cis isomers was 50 % .

With regard to the analysis of chrysanthemic acid, see e.g. B. referred to A. Murano, Agr. Biol. Chem. 3J5, 2203 (1972).

Examples 2 "to 6

Experiments similar to those in Example 1 "were described carried out using the dimeric chiral copper complexes given in Table I and 1-menthyl diazoate. The results obtained are shown in Table I as well.

The content of trans isomer in 1-menthyl chrysanthemate was determined by gas chromatography. The optical purity of the Chrysanthemic acid obtained after hydrolysis was determined by gas clock ο graphic analysis of the corresponding (S) -1-jienthyl— heptylesters determined.

It deserves to be emphasized that when using a Catalyst of (R) configuration dextrorotatory chrysanthemic acid and when using a catalyst of (S) configuration levorotatory chrysanthemic acid is the preferred product,

Comparative example A.

In the reaction between 1-menthyl diazoacetate and 2,5-dimethyl-2,4-hexadiene copper powder was used as a catalyst instead of the chiral copper complex. The received Results are also shown in Table I below.

70981 1/1056

Table I (Synthesis of 1-menthyl chrysanthemate)

Ghiral copper complex (II) Ohrysanthemat

Optical purity of the acid

E.g.
Mr. Configu- ₁
ration R *
A. methyl ρ
Tv Reacti
temper methyl ( ⁰ C) -J
O 2 (S) methyl 5-t-butyl-2-
octyloxyphenyl 40 981 3 (S) Benzyl 5-t-butyl-2-
isopropoxyphenyl 40 ■ ^. 4th (R) Benzyl 5_t-butyl-2-
butoxyphenyl 60 ο
cn 5 (R) Copper powder 5-t-butyl ~ 2-
heptyloxyphenyl 40 6th (S) 5_t-butyl-2-
heptyloxyphenyl 40 Cf.
E.g. 123

temperature yield trans trans ice

(f) (fo)

69 76

64 72 90 59 69 70 88 60 67 89 87 25th 42 91 86 22nd 36 75 86 5

0.7

Examples 7 "to 16

Experiments similar to those described in Example 1 were carried out using the diazoacetates given in Table II and a chiral copper complex (of the formula (II) with (R) configuration, in which R ¹ = methyl, R ² = 5-t-butyl -2-octyloxyphenyl). The results obtained are shown in Table II below.

The content of trans isomer in the alkyl chrysanthemates was determined by gas chromatography. The optical purity of the chrysanthemic acid obtained after hydrolysis of the ester was by gas chromatography of the corresponding (S) -I-menthyl-1-heptyl ester certainly.

The diazoacetates used in the examples were determined by one of the methods (A) or (B) given below.

According to method (A) a corresponding glycine ester with iso- amyl nitrite diazotized. The process can be carried out by the following reaction scheme be reproduced:

ROH> H ₂ UGH ₂ COOR> IT

A typical example of this procedure is the manufacture of 1-menthyl diazoacetate described in Example 17.

According to method (B), the reaction takes place according to the following reaction scheme:

70981 1/1056

-V At

Diketones

corresp.
alcohol

CH ₃ CCH ₂ COOR
Acetoacetate

Toluenesulfonyl azide

CH ^ CCCOOR j tt

Efa — methoxide

α-diazoacetoaetate

U ₂ CHCOOR diazoate acetate

A typical example of this procedure is production of Z ^^ - trimethyl-S-pentyl-diazoacetate in example 18 described.

Comparative Free Example B

Using the same copper catalyst as in the Examples 6 to 16 were the reaction between ethyl diazoacetate and 2,5-dimethyl-2,4-hexadiene. The received Results are also shown in Table II below.

70981 1/1056

Table II (Synthesis of alkyl chryaanthemates)

CO OO

cn cn

Diazoacetates synthesis
method React
functional Chrysanthemum
mate trans
W. Optical purity of the
Chrysanthemums, $ ice cream E.g.
No. R. A. temp. Yield 81 trans 75 7th dl-menthyl A. 40 67 89 90 8th d-neomenthyl A. 65 77 68 87 74 9 dl-Bornyl A. 40 74 84 70 46 10 1-adamantyl B. 23 82 58 85 ■ 58 11 Cyclohexyl A. 40 71 79 70 45 12th α, α-dimethyl-ß-
(1-menthoxy) ethyl B. 40 80 75 86 46 13th t-butyl B. 60 74 78 75 43 14th 2, 3-dimethyl-2-butyl B. 40 71 92 85 - 15th 2,3,4-trimethyl-3-
pentyl B. 40 64 56 88 - 16 α, α-dimethyl-benzyl - 40 60 51 71 62 Cf.
E.g. _B ethyl 40 54 68

to cn Ck)

CO cn co

Example 17

A mixture of 1-menthylglycine (19.7 g; 0.092 mol), isoamyl nitrite (12.0 g; 0.10 mol) and acetic acid (1.6 g; 0.027 mol) in chloroform (400 ml) was added for 25 minutes Stirring heated to reflux temperature. The reaction mixture was washed with 1N sulfuric acid, then with a saturated aqueous solution of sodium bicarbonate and then with water / water. After the organic phase had been dried, the residue obtained by condensation (21 g) was purified by column chromatography (silica gel 160 g, methylene chloride), 1-menthyl diazoacetate (15.0 g, 73 %) being obtained:

. yellow crystals, [a] _D = -86.8 ° (chloroform, c = 1.0), IR (film) <? 2125 cm " ¹
MR (chloroform, TMS) £ 5.29 ppm

With regard to 1-menthylglycine, see e.g. B. referred to K. Harada, T. Hayakawa, Bull. Chem. Soc. Japan, 3-7, 191 (1964).

Example 18

(0.186 mole, 15.7 g) was added to a mixture of 2,3,4-trimethyl-3-pentanol (24.3 g '0.18 mole) and triethylamine (0.1 g) was added dropwise diketene was stirred at 70 ⁰ C . After the reaction mixture had been stirred for 1.5 hours at 110 ° C., it was distilled under reduced pressure, the corresponding acetoacetate (boiling point 84 ° C./0.6 mm; 35.3 g >> 88 fo) being obtained.

To a mixture of the above ester (35.3 gj 0.164 mol), Triethylamine (17 g; 0.168 mol) and acetonitrile (200 ml) were added dropwise to p-toluenesulfonyl azide (38 g; 0.164 mol) was added. After the reaction mixture was stirred for 1.5 hours, it became under reduced pressure concentrated. The residue obtained was washed with ether (200 ml)

70981 1/1056

extracted and the organic phase was twice with a aqueous solution of potassium hydroxide (12.6 g). The organic phase was then dried and concentrated, the corresponding oc-diazoacetoacetate (40 g) was obtained.

^{A sodium methoxide solution which had been prepared from sodium (4.2 g) and methanol (65 ml) at 0 °} C. was added to a solution of the above ester (40 g) in methanol (65 ml). After a further 1 hour stirring of the reaction mixture "at 0 ⁰ C ice-water (300 ml) was filled, whereupon sodium chloride was added and the mixture extracted with ether (4OO ml, total) was extracted. After the organic phase had been washed with water and dried, it was concentrated and distilled, with 2,3> 4-trimethyl-3-pentyl-diazoacetate (boiling point 59 ° C / 0.2 mm; 20 g; 64 °) was obtained:

yellow oil, IR (film) 2125 cm " ¹ NMR (chloroform,! EMS) I 5.40 ppm

70981 1/1056

Claims (15)

Patent claims -f \\ Process for the preparation of an optically active alkyl- ^v - ^ chrysantnemats, characterized in that 2,5-dimethyl-2,4-hexadiene with a diazoacetate of the formula H ₂ CH-COOR wherein R is a) a cycloalkyl radical, which may contain one or more alkyl substituents with a total of 5 to 20 carbon atoms, h) a tertiary aralkyl radical with 9 to 20 carbon atoms, or c) a tertiary alkyl radical, which may contain one or more Alkoxy substituents have a total of 4 "to 20 carbon atoms reacts in the presence of a copper complex coordinated with a chiral Schiff base of the formula R ² - C - OH where mean: C * is an asymmetric carbon atom, R is an alkyl radical with 1 to 10 carbon atoms or 70981 1/1056 an aralkyl radical which optionally bears one or more alkoxy substituents with a total of 7 "to 20 carbon atoms
2
R aryl radicals which have one or more alkoxy substituents carry with a total of 7 to 30 carbon atoms, X ¹ and X ² for themselves
a) hydrogen atoms,
"b) alkyl radicals with 1 to 10 carbon atoms, c) phenyl residues, d) alkoxy radicals with 1 to 10 carbon atoms, e) halogen atoms or f) nitro groups, or
together a benzo group. 2. The method according to claim 1, characterized in that one of the following formula is used as the copper complex wherein R ¹ , R ² , X ¹ and X ^{2 have} the meaning given in claim 1, is used. 3. The method according to claim 1, characterized in that there is used as a chiral Schiff base before those obtained is by reaction of a chiral amino alcohol of the general formula 70981 1/1056 s ² R ¹ - C * H - C - OH t I ₂ 1 2 wherein C *, R ¹ and R are those in claim. 1 have the meaning given with a salicylaldehyde derivative of the general formula OH 1 2 wherein X and X are those in claim. 1 have given meaning 4. Procedure according to. Claim 2, characterized in that one the copper complex used is one which is obtained by reacting a chiral Schiff base according to claim 3 with a copper (II) salt. · 5. The method according to claim 1, characterized in that one a diazoacetate of the formula given is used in which R is (a) menthyl, (b) neomenthyl, (c) 1-adamantyl, (d) α, α-dimethyl-ß (menthoxy) ethyl, (e) 2,3-dimeth.yl-2-butyl, (f) 2,3,4-trimethyl-3-pentyl, (g) bornyl, (h) cyclohexyl, (i) t-butyl or Cj) α, α-dimethylbenzyl. 6. The method according to claim 1, characterized in that one the diazoacetate used is one which is obtained by diazotizing a g-lycin ester of the formula 7098 11/1056 in which R denotes a cycloalkyl radical, which optionally has a or carries more than one alkyl substituent with a total of 5 to 20 carbon atoms. j 7. The method according to claim 1, characterized in that there is a copper complex with a chiral Schiff's base given formula is used in which R is (a) benzyl, (b) methyl, (c) isopropyl or (d) isobutyl. 8. The method according to claim 1, characterized in that one a copper complex with a Chiral-Schiff base of the ο used formula, in which R mean: (a) 2-methoxyphenyl, (b) 2-ethoxyphenyl, (c) 2-isopropoxyphenyl, (d) 5-t-butyl-2-isopropoxyphenyl, (e) 5-t-butyl-2-heptyloxyphenyl, (f) 2-butoxy-5-t-butylphenyl, (g) 5-t-butyl-2-octyloxyphenyl, (h) 4-butoxybiphenyl-3-yl, or (i) 2,5-dibutoxyphenyl. 9. The method according to claim 3 »characterized in that one uses a Chiral-Schiff base which is obtained below Using a salicylaldehyde derivative (a) salicylaldehyde, (b) o-vanillin, (c) 3-ethoxysalicylaldehyde, (d) 3,5-di "bromosalieylaldehyde, (e) 5-chlorosalieylaldehyde, (f) 3-hitrosalicylaldehyde, (g) 3-isopropyl- 6-methylsalicylaldehyde, (h) 2-hydroxy-1-naphthaldehyde, or (i) 1-hydroxy-2-naphthaldehyde. 709811/1056 10. Procedure according to. Claim 2, characterized in that one used a copper complex with a chiral marine base, which is either an (R) - or (S) -enantiomer of the following compounds: (a) Ή— SaIicyliden-2-amino-1,1-di (2-methoxyphenyl) -3-phenyl-1-propanol, (b) H-salieylidene-2-amino-1,1-di (2-isopropoxyphenyl) -3-phenyl-1-propanol, (c) N-salieylidene-2-amino-i, 1-di (5-t-butyl-2-isopropoxyphenyl) -3-phenyl-1-propanol, (d) N-salicylidene-2-amino-1,1-di (2-butoxy-5-t-butylphenyl) -3-phenyl-1-propanol, (e) IT-salieylidene-2-amino-i, 1-di (5-t-butyl-2-heptyloxyphenyl) -3-phenyl-1-propanol, (f) ΪΓ-salicylidene-2-amino-1,1-di (5-t-butyl-2-isopropoxyphenyl) -1-propanol, (g) H-salicylidene-2-amino-1,1-di (2-butoxy-5-t-butylphenyl) - 1-propanol,
(h) N-salicylidene-2-amino-i, 1-di (5-t-butyl-2-octyloxy- phenyl) -1-propanol,
(i) N- (3-methoxysalicylidene) -2-amino-1,1-di (5-t-butyl-2- octyloxyphenyl) -1-propanol,
(j) N- (3,5-dibromosalicylidene) -2-amino-1,1-di (2-isopropoxy- phenyl) -3-phenyl-1-propanol,
(k) W- (3-ethoxysalicylidene) -2-amino-1,1-di (2-isopropoxy- phenyl) -3-phenyl-1-propanol,
(1) F- (2-Hydroxy-1-naphthylmethylene) -2-amino-1,1-di (2- isopropoxyphenyl) -3-phenyl-1-propanol, (m) N-salicylidene-2-amino-i, 1-di (4-butoxybiphenyl-3-yl) -3- ph.enyl-1-propanol,
(n) F-salicylidene-2-amino-1,1-di (2,5-dibutoxyphenyl) -3- phenyl-1-propanol,
(o) IT-salicylidene-2-amino-i, 1 -di (2-butoxyphenyl) -3-methyl- 1-butanol, or
(p) N-salieylidene-2-amino-1,1-di (2-butoxy-5-t-butylphenyl) - 4-methyl-t-pentanol. 709811/1056 11. The method according to .Anspruch 1, characterized in that carries out the reaction in the absence of a solvent. 12. The method according to claim 1, characterized in that one the reaction is carried out in the presence of a solvent. 13. The method according to claim 12, characterized in that one used an aromatic hydrocarbon as a solvent. 14. The method according to claim 1, characterized in that one is a Re
turns. a reaction temperature in the range of -50 to 150 ^{0 C} 15. The method according to claim 1, characterized in that, the molar ratio of Zupfer complex: alkyl diazoacetate selects in the range of 0.001: 0.1. 709811 / ΐσ56