WO1998017640A1

WO1998017640A1 - Hydrogen peroxide adducts

Info

Publication number: WO1998017640A1
Application number: PCT/GB1997/002879
Authority: WO
Inventors: Robert Alexander Walker Johnstone; Erzsébet FRANCSICSNÉ-CZINEGE
Original assignee: Solvay Interox Ltd
Current assignee: Solvay Interox Ltd
Priority date: 1996-10-24
Filing date: 1997-10-17
Publication date: 1998-04-30
Anticipated expiration: 1999-04-24
Also published as: GB9622135D0; AU4633897A

Abstract

Hydrogen peroxide adducts of phosphine oxides and equivalents for As, Sb and Bi and or phosphonates and phosphinates. Methods of preparation of said adducts by reaction of hydrogen peroxide on the phosphine oxides, equivalents for As, Sb, and Bi and on phosphonates and phosphinates. Methods of preparation of phosphine oxides and their equivalents for As, Sb and Bi and phosphinates as intermediate products for the preparation of said adducts by five different routes: oxidation of phosphinites or arsinites with hydrogen peroxide; oxidation of phosphines and arsines with hydrogen peroxide; reaction of arsenic or antimony halides with a Grignard reagent; reaction of phosphorus, arsenic or bismuth oxyhalides with a Grignard reagent; esterification of an alcohol with an organo-phosphinic, -arsinic, -stibinic or-bismuthinic halide. Process for performing electrophilic oxidations of organic groups, including in particular alkenes, using catalysed hydrogen peroxide in which said adducts are the catalytic intermediate complexes formed in situ or ex situ.

Description

Hydrogen Peroxide Adducts This invention concerns hydrogen peroxide adducts and, more particularly, adducts of hydrogen peroxide of organic compounds comprising at least one element of group 1 5 of the periodic table of the elements (new IUPAC numbering system), methods for the preparation thereof and processes for the oxidation of organic compounds with hydrogen peroxide in the presence of said adducts as catalytic intermediate complex.

Oxidations in organic chemistry have always represented an important part of the reactions investigated at the laboratory and practised at the industrial scale. During recent years, there has been considerable interest in the design of oxidation systems which achieve good yields while retaining high selectivities, aiming at lowering the costs of the reactants, simplifying industrial equipment and minimising the amount of by-products requiring disposal.

Much interest has been focused on the use of hydrogen peroxide solutions for homogeneous or heterogeneous catalysed oxidations. Although heterogeneous catalysis has appeared most often the solution of choice, there remains a number of situations where the catalyst is soluble in the solvent used for the reaction and therefore, homogeneous catalysis control is still an important issue in a lot of systems, like, for example acid- base and phase-transfer catalysis.

As regards oxidation reactions, the use of diphenylphosphinic anhydride and halides, as well as phosphoryl nalides and propanephosphonic anhydride has been reported to catalyse the epoxidation of alkenes by hydrogen peroxide (A.S. Kende et al., " A New Paradigm For Alkene Epoxidation. Activation Of Hydrogen Peroxide By Organophosphorus Electrophiles" , Tetrahedron Letters, Vol. 35, N° 44, 1994, pages 8123- 8126, Pergamon, London) . Yields reported in this disclosure are mostly high, though rarely above 90 % . Organic phosphine oxides are known as catalysts for the preparation of organic peroxides by reaction of hydrogen peroxide or a hydroperoxide with organic chlorides or alkenes (US-A-3, 458,557) .

Triphenylphosphine oxide and tπphenylarsine oxide have been reported to form adduct complexes with hydrogen peroxide in methanol, even in the presence of a small quantity of water (G.V. Howell et al. , "Tπphenylarsine

Oxide-Hydrogen Peroxide Adduct, Journal of Chemical Society (A), 1968, pages 1 1 7-1 18).

A limited range of phosphine, arsine and antimonine compounds have been suggested by Farbenfabπken Bayer in DE 1 268619 as the substrate for preparing hydrogen peroxide adducts of the corresponding oxides.

It is an object of certain aspects of the present invention to provide new hydrogen peroxide adducts of compounds comprising at least one element of Group 15 of the Periodic Table of the elements which in at least certain embodiments are stable, and in preferred aspects thereof are solid under normal conditions and which in yet furthei preferred aspects thereof melt or decompose only at a high temperature.

It is an object of other aspects of the present invention to provide methods for the preparation of new hydrogen peroxide adducts of compounds comprising at least one element of Group 1 5 of the Periodic Table of the elements which allow their economical preparation on an industrial scale.

It is an object of still further aspects of the present invention to provide a process for the electrophilic oxidation of organic compounds with hydrogen peroxide in which hydrogen peroxide adducts of compounds comprising at least one element of Group 15 of the Periodic Table of the elements may contribute to catalyse the reaction and in advantageous aspects thereof allow the achievement of high conversion rates in moderate reaction times.

According to one aspect of the present invention hydrogen peroxide adducts are provided characterised in that they satisfy the following formula (I) 98/17640

in which,

1.1 n represents a real number such that 0 n„2 1.20 represents the oxygen atom 1.3 the colon ^• represents a free electron pair of said oxygen atom connected to M which is engaged in an adduct link with the hydrogen atoms of the

H₂O₂ molecule

1.4 H₂O₂ represents one molecule of hydrogen peroxide

1.5 M represents any one of phosphorus, arsenic antimony and bismuth atoms

1.6 Rι, R₂ and R₃ each represent a group selected from aliphatic, cycloaliphatic or aromatic groups such that

1.6.1 R_{1 r} R₂ and R₃ are the same as each other and are other than C₂-C₄ alkyl, cyclohexyl, benzyl, phenyl or p-dimethylaminophenyl or 1.6.2 Ri and R₂ are the same as each other and R₃ is different from R, and R₂ and is other than phenyl or isopropyl when M represents P or 1.6.3 R,, R₂ and R₃ are each different Herein, selections of the groups for the adducts themselves, but not their use for oxidation, are in accordance with the restrictions of 1 6 1 1 6 2 and 1.6 3 above unless otherwise stated

In many suitable hydrogen peroxide adducts of the present invention, R R₂ and R₃ in formula S are each selected from the following groups - (i) alkyl, cycloalkyl, alkoxy, aryl, aryloxy and aralkyl groups, (ii) any of the foregoing groups in (i) substituted by at least one halogen atom, (iii) any of the foregoing groups in (i) in which the aryl group or moiety therein is substituted by an alkyl, carboxylic acid, sulphonic acid or amino substituent and (iv) ketal groups.

In such suitable hydrogen peroxide adducts. the alkyl. cycloalkyl and alkoxy groups in (i) preferably contain in the range of 1 to 20 carbons (except to the extent proscribed by 1.6.1 ), and the alkyl moiety can be linear or branched The cycloalkyl can be alkyl substituted. In (n), the number of halogen substituents is often selected in the range of 1 to 15 halogens The halogen is in many instances selected from fluoride, chloride or bromide Within (i) the aryl group or moiety is often phenyl or alkyl-substituted phenyl and a preferred aralkyl group is benzyl again except as constrained by 1 6 1

In a number of embodiments according > ihe invention, in formula I, R_{1 #} R₂ and R₃ are identical and selected frorn:- a linear alkyl group of from 5 to 20 carbon atoms or a phenyl group substituted by a halogen and/or sulphonic acid substituent.

In a number of other embodiments according to the invention, in formula I, Ri and R₂ are identical to each other and R₃ is different from Rt and R₂ and all are selected from - (a) a linear alkyl group of from 1 to 20 carbon atoms

(b) a linear alkoxy group of from 1 to 10 carbon atoms optionally substituted by from 1 to 15 halogen atoms or a phenyl group

(c) a phenyl group, optionally substituted by a halogen atom or sulphonic acid group and R₃ can also be selected from groups satisfying either of the following formulae II and ill

in which n has the same definition as in formula !

— C_zH_2z— represents a saturated alkylene group in which z represents an integer of from 2 to 5, M has the same definition as above, R₄ and R₅are identical to or different from each other and are selected from aliphatic cycloaliphatic or aromatic groups and can be the same as or different from R, or R₂ and

in which R₄, R₅and — C_zH_2z — have the same definition as in formula (II) and — C_yH₂ +ι represents a linear alkyl group in which y represents an integer of from 1 to 8. it will be recognised that when R₃ is in accordance with formula (IIS), although the presentation indicates two hydrogen peroxide molecules, a single hydrogen peroxide molecule may link simultaneously with both of the O=M moieties in the complex

In a number of further embodiments according to the invention, Rι, R₂ and R₃ are different from each other and selected from - (a) a phenyl group, optionally substituted by a halogen atom or sulphonic acid group,

(b) a linear alkyl group of from 1 to 10 carbon atoms, optionally substituted by a halogen atom

(c) a ketal group

and not more than one of Ri R₂ and R₃ being selected from groups that satisfy either of formulae (II) or (III) as defined above

In yet other embodiments of adducts satisfying formula I at least one of the groups Rt, R₂ and R₃ can be selected from alkenyl groups often containing from 2 to 20 carbons, such as isopropyl, with the remaining groups in R, R₂ and R₃ being selected in accordance with the options and limitations hereinabove for formula I compounds

Adducts in which R₃ is in accordance with formula (II!) that are worthy of note include those in which each of Ri R? R_d and R₅ represents a phenyl group, optionally substituted, z represents 2 and each M represents P Such adducts tend to contain two hydrogen peroxide molecules

It is recognised that the hydrogen peroxide adducts according to the invention encompass products which fall into several different classes of organic chemicals, i e when fvl is a phosphorus atom adducts of H₂O₂ of phosphonates, phosphinates and phosphine oxides are encompassed, when is an arsenic atom adducts of H₂0₂ of arsenates, arsinates and arsine oxides are encompassed and similarly when is an antimony or bismuth atom Adducts of the 1 1 type (H₂O₂ organic compound) and of the 1 2 type as well may be formed between the hydrogen peroxide and the organic compound of the group 15 element, the H₂O molecule having a second H atom capable of establishing a link with a second compound containing an -M=0 moiety

By adducts of phosphonates, it is intended to designate the diesters of the adducts of phosphonic acid, which is itself derived from the inorganic orthophosphoπc acid by replacement of one of its -OH groups by an organic hydrocarbon group, according to the following formula (IV) ^R1

O

^B 3 in which the groups — OR1 and — OR₂ represent two alkoxy or aryloxy groups of the diester and — R₃ is an alkyl aryl or alkaryl group, optionally substituted.

By the adducts of phosphinates. it is intended to designate the monoesters of the adducts of phosphinic acid, which is itself derived from the inorganic orthophosphoric acid by replacement of two of its -OH groups by organic hydrocarbon groups, according to the following formula (V)

^!2 2

■x₃ wherein the — ORi group is the alkoxy group of tne monoester and the —

R₂ and —R₃ groups are hydrocarbon groups, possibly substituted

By the adducts of phosphine oxides, it is intended to designate the products according to formula (I) wherein the three groups — Ri, — R₂ and — R₃ are the organic hydrocarbon groups, optionally substituted, such as indicated above.

In some preferred hydrogen peroxide adducts satisfying formula I, M is selected from any one of phosphorus, arsenic and antimony

According to a first class of hydrogen peroxide adducts according to the invention, Ri, R₂ and R₃ are three identical groups and the adducts are of phosphine oxides.

Within this first class, the three identical groups R_{t l} R₂ and R₃ are selected from alkyl groups, and preferably, linear alkyl groups In most instances, said alkyl groups contain from 5 to 20 carbon atoms and particularly the number is selected in the range of from 6 to 10 carbon atoms Noteworthy examples of adducts in this class contain three identical n-octyl chains, such as the adduct of tris(n-octyl)phosphine oxide with H₂O₃ which has been synthesized and isolated.

Other representative adducts which belong to this first class include those which have three aryl, and particularly, phenyl groups substituted by at least one halogen atom in any one or several of the positions ortho meta and para around the benzene ring

In this latter sub-class of adducts. the halogen atom may be any of chlorine, bromine, iodine or fluorine atoms Fluorine substituted adducts have been found to be particularly interesting A member of this sub-class which has revealed itself to be particularly suitable is the adduct of tris(2, 3,4,5, 6-pentafluorophenyl)phosphιne oxide with H₂O₂.

Two other members of this sub-class of adducts deserving mention are the adducts of trιs(3,5-dιfluorophenyl)phosphιne oxide and of trιs(4- fluorophenyl)phosphιne oxide with H₂0_:

A further interesting member of this sub-class is the adduct of the trιs(4- fluorophenyl)arsine oxide with H₂O₂

Another further member of this sub-class deserving mention is the adduct of tris(phenyl)stibine oxide with H₂O₂ A further valuable sub-class of adducts with three identical R,, R₂ and R₃ groups is the sub-class of the adducts of phosphine oxide which have their three identical phenyl groups substituted by one sulphonic acid group in any one of the ortho, meta or para positions around the benzene ring

According to a second class of hydrogen peroxide adducts according to the invention, Ri and R₂ are identical groups and R₃ is a group which differs from the R, and R₂ groups.

It is recognised that adducts which are within this second class can be any of the three H₂O₂ adducts of phosphonates phosphmate or phosphine oxide types and the corresponding adducts in which M is arsenic antimony or bismuth.

According to this second class, a number of adducts in which M is a phosphorus atom have proven to be valuable

In this second class of adducts containing P, a first subclass of adducts which have two identical ethoxy groups linked to the P atom have revealed themselves' of interest. By way of example, two products, the adducts of diethoxy(phenyl)phosphonate and of dιethoxy(benzyl)-ρhosphonate have been synthesized and identified.

A second desirable subclass of those adducts containing the P atom is the one in which two identical phenyl or substituted phenyl groups are linked to the P atom.

Members of this second subclass include the adducts of ethoxy- (diphenyl)phosphιnate and of 2.2.2-trιfluoro(ethoxyjdιphenylphosphιnate. This second subclass includes as well the adducts of dimeric phosphine oxide with H₂O₂. Also of noteworthy interest in this sub-class are the adduct in which R₃ is a group of formula (II) above in which R, and R₂ are phenyl groups and R₄ and Rs groups are phenyl groups and in which z has the value 2 or 3 and the adduct in which R₃ is a group of formula (III) above in which R,, R₂, R₄ and R₅ are also phenyl groups and in which z has the value 2 and y has the value 1

A third subclass of adducts comprising phosphorus and having two identical R, and R₂ groups is represented by the adducts of bis-

(phenylsulphonic acid)phenylphosphιne oxide with H₂0₂ In those adducts, the sulphonic acid group may variously substitute the phenyl group in any of the ortho, meta or para positions.

According to a third class of hydrogen peroxide adducts according to the invention, the hydrogen peroxide adducts have three different R_u R₂ and R₃ groups

An interesting member of this third class of auduαs is the adduct of the o- bornyl(methyl)phenylphosphιne oxide with H 0₂ By an o-bornyl group, it is intended to designate an alkoxy group derived from bornyl alcohol, also called bicyclo(2.2.1 )heptan-2-ol, 1 ,7,7-trιmethykendo-

It will be recognised that some of the adducts according to the invention are chiral. In the class of chiral adducts. M can be a P atom, or an As, Sb or Bi atom to provide chira ty of the adduct, by ensuring that R,. R₂ and R₃ are different. According to another aspect of the present invention there are provided methods for the preparation of the hydrogen peroxide adducts as described hereabove, and particularly those in accordance with formula I above, wherein a monoester of a phosphinic or arsinic acid or a mono or diester of phosphoπic acid or the equivalent organic acid for arsenic is reacted in a solvent with hydrogen peroxide. By monoesters of a phosphinic or arsinic acid are intended esters which are obtained by esteπfication of a phosphinic or arsinic acid with an alkyl (particularly C1 -C4) or aryl or alkaryl alcohol and which are described by the following formula (VI)

f .

(VI)

^R3 in which M represents the P or As atom

Especially suitable are the esters in which the R-, group originates from a lower saturated straight chain aliphatic alcohol or from a phenyl substituted straight chain aliphatic alcohol Examples of such alcohols are methanol, ethanol, 1- and 2-propanols and benzyl alcohol Phosphinic acids and arsinic acids which are suitable include those acids in which the two organic substituents R₂ and R₃ are alkyl groups cycloalkyl groups or aryl groups possibly substituted by any one or more of the substituents selected from the following groups alkyl aryl, cycloalkyl halogen sulphonic acid nitro, amine, amide, alcohol, carboxy c acid aldehyde ketone and nitπle By mono or diesters of phosphonic acid or the equivalent acid for arsenic are intended esters which are obtained by esteπfica'ion of a phosphonic or the equivalent acid for arsenic with a lower alkyl or aryl or alkylaryl alcohol and are described by the following formula (VII)

o I

R₂0 — iVt =:0 (VII)

R₃ in which IV! represents the P or As atom

Especially suitable are the esters in which the R, and R₂ groups originate from a lower saturated straight chain aliphatic alcohol or from a phenyl substituted straight chain aliphatic alcohol Examples of such alcohols are methanol, ethanol, 1- and 2-propanols and oenzyi aiconol Phosphonic acids and equivalent acids for arsenic which are suitable include those acids in which the organic substituent R₃ is an alkyl group, a cycloalkyl group or an aryl group possibly substituted by any one or more of the substituents selected from the following groups' alkyl, aryl, cycloalkyl. halogen, sulphonic acid, nitro. amine, amide, alcohol, carboxylic acid, aldehyde, ketone and πitπle

The solvent used in said methods of preparation is selected from the usual organic solvents used in chemical synthesis The choice of the solvent is dictated by its ability to dissolve the esters which are the reagents for the adduct reaction as well as the hydrogen peroxide which is usually supplied in aqueous solution together with the adduct themselves as soon as they are formed Solvents which are well suited for those adducts' preparation exhibit generally a certain polar character in order to dissolve easily the hydrogen peroxide and the adduct They must however never be too polar, as they need as well to dissolve the ester reagents

Solvents which contain heteroatorns o^r a po'a' group in the molecule are generally well suited Aromatic solvents are also used Mixtures of solvents may also be selected if one needs to adjust more easily the polar characteristic of the solvent. Examples of good solvents are dioxane toluene, chloroform and their mixtures, e.g. mixture of chloroform and dioxane

Operating conditions for the reaction are generally at atmospheric pressure, at low temperature and with gentle stirring Temperatures of from 0 °C to 25 °C are suitable Preferred temperatures are generally in the range of from 0 °C to 10 °C Most preferred temperatures are from 0 to 5 °C Concentrated hydrogen peroxide solutions are suitable, as well as more diluted solutions As a general advice, solutions of from 10 to 90 %w/w of H₂O₂ may be used. Preferred solutions are from 30 to 90 % w/w of H₂0₂. Most preferred are the H₂O₂ solutions of from 30 to 80 % w/w H₂0₂ solutions of 70 % w/w have given excellent results The molar ratio of the adduct precursors to hydrogen peroxide is often from 2'1 to 20:1 and, preferably from 3 1 to 15 1 Tne 10 I molar ratio of the esters to hydrogen peroxide has given excellent results

Duration of the reaction to prepare and isolate the adduct depends on the particular nature of the adduct and is generally selected in the range of from a few hours to 3 days, although the actual formation of the adduct may occur quickly within seconds or a few minutes When completed, the reaction may be followed by natural crystallisation of the adducts if the reaction vessel is kept at low temperature, e.g 0 °C to 5 °C A further step of purification of the product by washing or recrystallisation may follow

According to another aspect of the present invention, there are provided methods for the preparation of phosphinates or arsinates as intermediate products for the preparation of hydrogen peroxide adducts in which a phosphinite or an arsmite is reacted in a solvent with hydrogen peroxide.

By the term phosphinite or arsmite is meant products which fall into the following formula(VIII)

^R1 o

(MSI)

*3 in which M represents the P or As atom

The ester group OR,, as well as the organic groups R and R₃ which are suitable are similar as those described above for tne phosphinic or arsinic esters The hydrogen peroxide is introduced in the reaction medium in the form of an aqueous solution

The solvents, concentration and amount of hydrogen peroxide which may be used are the same as those recited previously for the adduct linking reactions The oxidation of the phosphinites or arsinites generally takes place at best under solvent reflux conditions, at atmospheric pressure and with gentle stirring

The phosphinates or arsinates are obtained in the organic phase after a duration of from about 2 to 24 hours after which the phases are separated and the product is further purified by washing and/or any other traditional method and isolated.

The invention concerns as well a method of preparation of hydrogen peroxide adducts as described hereabove in which an oxide of phosphine. arsine or stibine is reacted in a solvent with hydrogen peroxide

By the term "oxide of phosphine. arsine or stibine^' is meant a product satisfying the following formula (IX) Γ

^R3 in which M represents the P, As or Sb atom

Oxides of phosphine arsine or stibine which a< suitable include those in which the organic substituents Ri R and R₃ are alkyl yroups cycloalkyl groups or aryl groups possibly substituted by any one or more of the substituents selected from the following groups alkyl aryl, cycloalkyl halogen sulphonic acid, nitro, amine, amide alcohol carboxylic acid aldehyde ketone and nitrite

The solvent used in said methods of preparation can be selected from those described above for the preparation of the adducts of H₂O₂ of esters of phosphinic and phosphonic acids and the like

Operating conditions for the reaction are generally no different from said adducts of esters of phosphinic and phosphonic acids hereabove

According to another aspect of the present invention there are provided methods for the preparation of phosphine or arsine oxides as intermediate products for the preparation of hydrogen peroxide adducts in which a phosphine or an arsine is reacted in a solvent with hydrogen peroxide

Phosphine or arsine precursors are defined by formula (X) which follows

R, — (λ)

I

^R3 in which M represents the P or As atom and the organic groups R,, R₂ and R₃ have the same meaning as for the phosphine arsine or stibine oxide of formula (IX) above

Reaction conditions are similar to those for the preparation of phosphinates or arsinates above According to another aspect of the present invention there are provided methods for the preparation of arsine or stibine oxides as intermediate products for the preparation of hydrogen peroxide adducts in which, in a first step, an arsenic or antimony halide is reacted with a Grignard reagent and, in a second step, the arsine or stibine obtained from the first step is further oxidised with hydrogen peroxide.

As arsenic or antimony halides, trichlorides of formula AsCI₃ and SbCI₃ may be used.

By Grignard reagent, it is intended an organo-magnesium compound of formula R-Mg-X commonly used in organic syntheses in which X is a halogen atom and R an organic group. Said Grignard reagent is generally prepared at the time it is needed by reaction of an organic halide R-X in solution in dry diethylether with turnings of dry magnesium metal The reaction is generally largely exothermic and necessitates usually cooling to a low temperature of around 0 °C.

It will be recognised that the R group of said Grignard reagent will end up as one of the three identical groups R, R₂ and R_r, in the final adduct of H₂O₂ with arsenic or antimony halide oxide The R group of the R-X halide is accordingly carefully selected in view of the particular organic groups of the adduct it is intended to synthesize in a further reaction

The reaction of the Grignard reagent with AsCI₃ and with SbCI₃ is generally performed by adding the AsCI₃ or the SbCI₃ in solution in anhydrous diethylether,

A convenient way of controlling the temperature during the reaction is to work at reflux of the diethylether solvent After a few hours of stirring at reflux temperature, the reaction may be stopped by quenching with an aqueous solution of ammonium chloride The arsine or stibine obtained can be extracted and purified from the reaction mixture with an appropriate organic solvent. A solvent which has been found to be suitable is chloroform. The second step of the preparation can be performed in a way exactly similar to the one used for the preparation of phosphine and arsine oxide already described above.

According to another aspect of the present invention, there are provided methods for the preparation of phosphine, arsine or bismuthine oxides as intermediate products for the preparation of hydrogen peroxide adducts, in which a phosphorus, arsenic or antimony oxyhalide is reacted with a Grignard reagent.

Said last methods are entirely similar to the fu st step of the methods described hereabove for the oxides of arsines or stibmes and are therefore incorporated here by reference, mutatis mutandis the only differences being the replacement of the arsenic or antimony halides by respectively, phosphorus, arsenic or bismuth oxyhalides.

According to another aspect of the present invention, there are provided methods for the preparation of phosphine, arsine. stibine or bismuthme oxides as intermediate products for the preparation of hydrogen peroxide adducts, in which an organo -phosphinic, -arsinic -stibinic or bismuthimc halide is used for esterifying an alcohol

In this last method, the organo -phosphinic. -arsinic -stibinic and - bismuthinic halides are in accordance with the formula (XI) which follows

° 2 in which M represents a P. As, Sb or Bi atom and R₂ and R₃ are alkyl groups, cycloalkyl groups or aryl groups optionally substituted by any one or more of the following substituents selected from alkyl aryl, cycloalkyl, halogen, sulphonic acid, nitro, amine, amide, alcohol carboxylic acid aldenyde. ketone and nitrile substituents.

It will be recognised that the halides according to formula (XI) are members of the class of the halides of phosphinic arsinic. stibinic and bismuthinic acid

The operating conditions for this reaction are usually at above-ambient temperature and atmospheric pressure Temperatures of from 30 °C to 90 °C are generally suitable. Most often a temperature of 50 °C to 85 °C is preferred.

A temperature of 80 "C has given good results

According to a particularly valuable aspect of the present invention, there is provided a process for the oxidation of a substrate containing an electrophilically oxidisable moiety employing hydrogen peroxide as oxidant in the presence of an homogeneous catalyst, characterised in that, at least one of the adducts of hydrogen peroxide of compounds comprising at least one element of Group 15 of the Periodic Table of the elements is employed as the catalytic intermediate complex.

In most embodiments employing the catalytic intermediate complex in the oxidation process of an organic substrate, the complex satisfies formula (I):

wherein, n represents a real number such as 0 n_2

H₂O₂ represents one molecule of hydrogen peroxide O represents an oxygen atom the colon : represents a free electron pair in said oxygen atom which is engaged in an adduct link with a hydrogen atom of the H₂0₂ molecule

M represents any one of phosphorus, arsenic, antimony and bismuth atoms

Ri, R₂ and R₃ each represents an identical or different organic group selected from aliphatic, cycloaliphatic or aromatic groups

In many of the complexes employed advantageously in the oxidation process, R,, R₂ and R₃ are each selected from the following groups

(I) alkyl, cycloalkyl, alkoxy, aryl, and aralkyl groups

(ii) any of the foregoing groups in (I) substituted by at least one halogen atom, (iii) any of the foregoing groups in (I) in which the aryl group or moiety therein is substituted by an alkyl. carboxylic acid sulphonic acid or ammo substituent and

(iv) ketal groups

(v) a group satisfying either formula (II) or formula (III) as described hereinabove In a significant fraction of the above-described complexes employed advantageously in the oxidation process R,, R₂ and R₃ are selected from alkyl, cycloalkyl or alkoxy groups or alkyl substituents which contain from 1 to 10 carbon atoms or which are substituted by halogen atoms selected in the range of 1 to 15, and/or groups in which the aryl group or moiety is phenyl

All the variations of hydrogen peroxide adducts described hereinbefore which satisfy formula I and meet the restrictions of 1 6 1 or 1.6.2 or 1.6.3 described hereinabove are suitable for use in the oxidation process of the present invention, as are the products of the various methods described hereinbefore for the manufacture of such adducts Selection for the groups Ri, R₂ and R₃ in the complexes to be employed can be made in accordance with the selections indicated for the complexes themselves

One class of useable complexes comprises chiral adducts which can be employed to favour the production of certain enantiomers at the expense of others

The electrophilic oxidations which may be catalysed by the adducts according to the inventions are the oxidations of the groups comprising alkene, ketone, aldehyde, nitπles amines, sulphides sulphoxides and thiols Such groups are usually to be found as substituent in aliphatic cycloaliphatic heterocyclic or aromatic compounds and often in those containing from 3 to 25 carbons

The process according to the invention is particularly well suited to the epoxidation of alkenes with gener ally n yh and most often excellent rates of conversion A list of suitable alkenes can be found in WO 93/00338, which is incorporated herein by reference

The electrophilic oxidation reaction of the present invention is generally performed in a two phase reaction medium due to the presence of an organic solvent non miscible with water and an aqueous phase which originates from the hydrogen peroxide which is most often introduced into the medium as an aqueous solution

Concentrated hydrogen peroxide solutions ar e suitable for the oxidation reaction, as well as more dilute solutions As a general guidance solutions of from 10 to 90 %w/w of H₂0₂ may be used Preferred solutions are from 20 to 70

% w/w of H₂O₂ Most preferred are H₂0₂ solutions of from 30 to 60 % w/w and H₂O₂ solutions of 35 % w/w have given excellent results

It will be recognised that the reaction is consistent with the so-called phase transfer mechanism of catalysis the adduct acting as a phase transfer agent capable of extracting the hydrogen perox.de molecules from the water solvent and transferring them to the organic phase in which the organic molecules of substrate to be oxidised aie dissolved and thereby catalyse the actual reaction desired After having delivered their H_:O₂ the adducts regenerate the oxides of phosphine or of the equivalent elements of group 15 which are therefore acting as a ligand A new cycle then takes place again by the spontaneous regeneration of the adduct in the aqueous phase It will be recognised that the catalysts can be produced ex situ and introduced into the reaction medium or generated in situ in the reaction medium The invention process could also be described as phase transfer catalysed catalytic electrophilic oxidation

The reaction period for the oxidation is selected taking into account the substrate, the solvent temperature hydrogen peroxide adduct and the concentration of the reactants and the catalyst it ,s often selected in the range of from 2 to 120 hours

The reaction temperature for the electrophilic oxidations is often selected in the range of temperatures described above within which the hydrogen peroxide adducts can be made, and in many instances in the range of from 50 to 120 °C. Nonetheless, the skilled chemist will usually seek to employ a reaction temperature for the oxidation of a specific oxidisable substituent in the substrate that is within or near the temperature range that has previously been regarded as suitable for employing hydrogen peroxide to oxidise that substituent The mole ratio of adduct to substrate is often from 0 1 1 to 2 1 , and the equivalent mole ratio of H₂O₂ to substrate is often from 0 5 1 to 15 1 and preferably from 1 1 to 3 1

In some instances the adduct will be preformed and introduced as such into the oxidation reaction mixture In other instances the requisite precursor will be introduced into the reaction mixture and will be formed in situ by reaction with hydrogen peroxide An equimolar allowance for the peroxide consumed in the adduct formation may be made ιι desired m determining the amount of peroxide needed to be introduced for the oxidation The precursor can be introduced before the introduction of the substrate or substrate and precursor may be present together

Having described the invention in general terms specific embodiments thereof are described in greater detail by way of example only

In cases where only examples of phosphine oxides and equivalents for As, Sb and Bi are given and no experimental details cf the preparation of such adducts are specified, said adducts were formed and used in situ

In the examples which follow, analysis of the products was performed by

¹H nuclear magnetic resonance spectroscopy (NMR) at 200 MHz in CDCI₃ as solvent with tetramethylsilane as internal standard, by infrared spectroscopy

(IR), gas chromatography (GC) and by thin layer chromatography (TLC) on plates coated with Kieselgel " GF254 (ex Merck company) 0 2 mm thick. In the Examples which follow, all yields are mol % based on the initial amount of substrate and all ratios of H₂0₂ to substrate are given as mol:mol unless otherwise specifically disclosed otherwise Conversion represents the proportion of substrate consumed, in the production of both desired and by- products.

Example 1

Synthesis of dJethyl(benzyl)phosphonate-hydrogen peroxide adduct

a) Synthesis of dιethyl(benzyl)phosρhonate

Freshly distilled benzylchloride (1 1 5 ml or 12 66 g or 0 2 mol) was warmed till reflux at 180 °C in static N₂ atmosphere and stirred

Triethyl phosphite (20 0 ml or 19 20 g or 0 120 mol) was added to it dropwise over a period of 40 minutes After the addition the reaction mixture was refluxed for an hour

The product was purified by vacuum destination at 0 2-0 3 Hg mm, at 110 °C, to give 18.32 g (yield 80 3 %) dιethyl(benzyl)phosphonate

Calculated for C11H17O3P C, 57 9: H 7 5 Found C, 57 6 57 5. H. 7 6, 7.6.

¹H-NMR (CDCI₃) 8=1 20 (t. 6H), 3 20 (d 2H) 3 68-4 07 (m 4H) 7.20-7 29 (m,

5H)

b) Synthesis of dιethyl(benzyl)phosρhonate-hydιogen peroxide adduct Diethyl(benzyl)phosphonate (1 14 g or 5 mmol) was dissolved in dioxane (6ml) Aqueous hydrogen peroxide (70 % 2 42 g or 0 05 mmol) was added to it dropwise at 0-5 °C The reaction mixtui e was stn red at 0-5 °C for a further 2 hours, then left in the refrigerator for 48 hours After evaporating the solvent the residue was dried in vacuo over sodium hydroxide pellets. The oily residue was 1 2 g of dιethyl(benzyl)phosphonate- hydrogen peroxide adduct (yield 83 %)

The analysis showed an amount of H₂0₂ (as active oxygen) of 8 52 w/w %; corresponding to a 1 2 mole ratio of H₂0 phosphonate TLC (EtOAc water: AcOH = 18:1 -1 ) ¹H-NMR (CDCI3) 8=1 20 (t 12H 3 15 (d. 4H) 3 68-4.07 (m, 8H), 7.20-7.29 (m, 10H), 7.5-9 0 (br s. 2H) Example 2

Synthesis of ethyl(diphenyl)phosphinate-hydrogen peroxide adduct

To a solution of ethyl(dιphenyl)phosphιnate (2 g or 4 3 mol) in dioxane (5ml), aqueous hydrogen peroxide was added dropwise at 0 °C The reaction mixture was stirred at 0-10 °C for 5 hours and was put in the refrigerator for one day After having been dried in vacuum over sodium hydroxide pellets, the resulting oily residue was 1 02 g (yield 95 %) of ethyl(dιphenyl)phosphιnate-hydrogen peroxide adduct

The analysis showed an amount of H₂O₂ (as active oxygen) of 6 64 w/w %, corresponding to the 1 2 molar ratio of H₂O₂ phosphinate The product decomposed at 60 °C Calculated as C:aH₃₂O₆p₂ requires C 63 9 % H, 6 1 % Found C, 62 5 %, 62 4 %, H 6 2 % 6 2 % ¹H-NMR (CDCI₃) o=1 18-1 25 (t 6H), 3 85-3 99 (d 4H) 6 12 (s 2H) 7 41 -7 76 (m 20H) In solvent dimethylsulphoxide (d6-DMSO) =10 19 s 2H)

Example s

lesis of trioctylphosphine oxide-hydrogen peroxide adduct Tπoctylphosphine oxide (1 94 g or 5 0 mmol) was dissolved in dioxane (5 ml) and chloroform (2 ml) Aqueous 70 w/w % hydrogen peroxide (2 43 g or 0 05 mol) was added to it dropwise at 0 °C The reaction mixture was stirred at room temperature overnight

After evaporating the solvents the oily residue was dried over sodium hydroxide pellets under vacuum and was crystallised in petroleum ether at 40- 60 °C The resulting product was collected on a filter washed with petroleum ether to give 1 44 g (yield 68 6 %) tπoctylphosphine oxide-hydogen peroxide adduct

The analysis of the product gave a melting point of 49-52 °C and showed an H₂O₂ content expressed as active oxygen of 4 29 % corresponding to the 1 2 molar ratio of H₂0₂ phosphine oxide (4 21 % expected) Calculated as C₄8H₁₀₄O₄P₂ requires C 71 4 % H 1 3 0 % Found C 73 2 % 73 1 %, H, 13 0 %, 13 0 % ¹H-NMR (CDCI₃) 8=0 69-75 (t 18H) 1 1 1 -1 60 (m 84H), 8 78 (s, 2H) Example 4

Synthesis of ethylene-1 ,2-bis(diphenylphosphine oxide)-hydrogen peroxide adduct

5 To a solution of ethylene-1 ,2-bιs(dιphenylphosphιne) (0 48 g or 3 7 mmol) in dioxane (12 ml) and chloroform (12 ml) aqueous 35 w/w % hydrogen peroxide (3.5 ml or 0.04 mol) was added dropwise at 0 °C The reaction mixture was stirred for 30 min, during which period crystals formed and was thereafter stored in the refrigerator overnight 0 The resulting crystals were filtered off. washed with petroleum ether at 40-60°C and dried under vacuum to give 1.29 g (yield 70 4 %) of ethylene-1 ,2- bis(diphenylphosphine oxide)-hydrogen peroxide adduct

The analysis of the product gave a melting point of 140°C (decomposition), then the resulting compound solidified and melted again at

1 5 258-260°C, which is the melting pom* o^f the ethylene-1 ,2- bis(diphenylphosphιne oxide)

The compound showed an H₂0₂ content expi essed as active oxygen of 14.07 %, corresponding to the 2 1 molar ratio of H_>0₂ phosphine oxide (13.65 % expected). Calculated as C₂₆H_2SO_GP₂ requires C 62 7 %, H 5 6 % Found C,

20 62.8 %, 62 8 %; H, 5 6 %. 5 6 % Η-NMR (CDCI₃) o=2 50 (s 4H). 7 23-7 74 (m, 20H),.8.9 (s 4H) IR (KBr). 3446 3055 2942 291 1 2286 1637 1591 , 1485, 1439, 1421 , 1409, 1319, 1188 1 176 1 123 1089 998 928, 764. 742, 731 , 695, 533, 512 IR (CHCI₃ solution) H-bonding 3856 3753 3737 3713, 3691 , 3678. 3651 , 3234, 3058, 2913, 2257

25 Example 5

Synthesis of propylene-1 ,2-bis(diphenylphosphine oxide)-hydrogen peroxide adduct

To a solution of propane-1 .3-bιs(dιphenylphosphιne) (1 24 g or 3 0 mmol) in 30 chloroform (3.0 ml) and dioxane (3 0 ml) aqueous 70 w/w % hydrogen peroxide (1.45 g or 0.03 mol) was added dropwise at 0 C Tne reaction mixture was stirred for 3 hours and stored in the refπgeratoi to crystallise As no crystals were formed, the product was precipitated by addition of petroleum ether at 40- 60 °C. The product was filtered off. washed with petroleum ether at 40-60 °C and dried under vacuum to give 1.2 g (yield 83 9 % of propylene-1 ,3- bis(diphenylphosphine oxιde)-hydrogen peroxide adduct

The analysis of the product gave a melting point of 98-100 °C (decomposition at 110-130 °C) The compound showed an H₂0₂ content, expressed as active oxygen of 7.30 %, corresponding to the 1.1 molar ratio of H₂O₂:phosphine oxide (7 11 % expected) Calculated as C₂₇H₂₈O₄P₂ requires: C, 67.7 %; H, 5.9 % Found C, 67 6 % 67 6 %. H 5 9 %. 5 9 % Η-NMR (CDCI₃): 5=1.44-1.46 (m, 2H), 2 32-2 45 (m 4H ^{^} 26-^" 59 (m 20H 8 5-9 5 (br. s. 2H). In de-DMSO, 8=10.07 (s 2H)

Example β

Synthesis of R,R-trans-4,5-bis(diphenylphosphinomethyl)-2,2-dimethyl-1,3- diαxolan-hydrogen peroxide adduct R,R-trans-4,5-bis(dιphenylphosphιnomethyl)-2 2-dιmethyl-1 3-dιoxolan (1.0 g or 2.0 mmol) was dissolved in chloroform (4ml) and αioxane (2 ml) The solution was cooled to 0 °C and aqueous 70 w/w % hydrogen peroxide (1.32 g or 0.027 mol) was added to it dropwise The reaction mixture was stirred for 1 hour and it was put to the refrigerator overnight As no crystals were formed the product was precipitated by addition of 20 ml of petroleum ether at 40-60 °C

The resulting crystals were collected on a filter were washed with petroleum ether at 40-60 °C and dried under vacuum to give 1 06 g (yield 93 8 %) of R,R-trans-4.5-bιs(dιphenylρhosphιπomethyl)-2 2-dιmethyl-1 3-dιoxolan- hydrogen peroxide adduct The analysis of the product gave a melting point of 200-204 °C

(decomposition at 205-220 °C with vigorous effervescence) The compound had an H₂0₂ content, expressed as active oxygen of 6 12 %. corresponding to the 1 :1 molar ratio of H₂O₂:phosphιne oxide (6.03 % expected). Calculated as C₃ιH₃₄O₆P₂ requires. C, 65.9 %; H. 6 1 % Found: C. 65 7 %, 65.8 %; H, 6.1 %, 6.1 %. ¹H-NMR (CDCI₃)' 8=1.17 (s, 6H). 2 58 (m 2H), 2 90 (m. 2H), 4.14 (m, 2H), 7.23-7.81 (m, 20H). 9 43 (s 2H) In d₆-DMSO 8=10 00 (s. 2H) Example 7

Synthesis of tris(4-fiuorophenyl)phosρhine oxide-hydrogen peroxide adduct

To a solution of tris(4-fluorophenyl)phosphιne oxide (0 66 g or 2.0 mmol) in chloroform (3 ml) and dioxane (2 ml), aqueous hydrogen peroxide 70 w/w % (0.97 g or 0.02 mol) was added dropwise at 0 °C The reaction mixture was stirred at room temperature overnight As no crystallisation was observed, the solvents were evaporated and the oily residue was dried in a vacuum dessicator over sodium hydroxide to give 0 52 q ' yelπ 7^ 5 %) of trιs(4- fluoropheny phosphme oxide-hydrogen peroxide adduct as white solid material The analysis of the product gave a melting point of 86-89 °C (decomposition at 170-200 °C) The compound had an H 0₂ content, expressed as active oxygen of 4 07 %, corresponding to the 1 2 molar ratio of H₂O₂. phosphine oxide (4 86 % expected) Calculated as

requires C, 61.9 %, H. 3 8 % Found C 62 4 % 62 3 H 3 8 % 3 8 % ¹H-NMR (CDCI₃) 8=7 06-7 63 (m, 24H), 8 39 (s 2H)

sβεis of tris 4-fSuorophenyl)arsine oxide a) Synthesis of trιs(4-fluorophenyl)arsιne To dry magnesium turnings (2 8 g or 0 116 mol) activated by iodine crystals was added 10 % a total quantity of 13 4 ml or 0 1 16 mol of fluoroiodobenzene in anhydrous diethyl ether (75 ml) After the reaction has started, the remainder of the fluoroiodobenzene was added dropwise over a period of 30 mm, so as to maintain gentle reflux of the diethyl ethei The soution -,vas refluxed for 1 hour and 20 ml of anhydrous toluene was then added After cooling it to 0 °C, a solution of arsenic trichloride (2 6 ml or 0 03 mol) in anhydrous toluene (25 ml) was added dropwise over 30 mm The reaction mixture was refluxed for 4 hours and then at room temperature overnight

An aqueous solution of 15 % w/v NH₄CI (150 ml) was added to the reaction mixture and the resultant mixture was stirred for 1 hour. After separating the phases, the organic phase was washed 4 times with 250 ml distilled water. The resulting yellow solution was dried over magnesium sulphate. Filtration and removal of the solvents gave 1 1 g of a yellow oil Chromatography was carried out using silica and DCM/petroleum ether (40/60 °C b.p ) as eluent The product was collected and left in the refrigerator over the weekend after initial concentration of the soiutiec The white solid that precipitated out was filtered off and recrystalliseo from a mixture of DCM/petroleum ether (40/60 °C b p ) to give colourless crystals in 43 % yield (6 g). Found: C, 60.16 %; H. 3.32 %. Cι₈H₁₂F₃As requires C, 60.02 %, H. 3.36 %. Melting point was 80-81 ° C Mass spectrometry with electr ionization: m/z [M+H 361. b) Synthesis of tris(4-fluorophenyl)arsιne oxide Tris(4-fluorophenyl)arsιne (3 96 g or 1 1 38 mmol obtained in step a) was dissolved in chloroform (7 ml) Aqueous 70 w/w % hydrogen peroxide (0 56 g, 11.38 mmol) was added dropwise at 0 °C to the chloroform solution The reaction was stirred for 3 hours at room temperature Petroleum ether (40/60 °C b.p.; 20 ml) was added and the reaction mixture was then left in the refrigerator for 4 hours

The resulting crystals were collected and recrystallised from DCM/petroleum ether (40/60 °C b p ) to give 2 4 g (yield 58 %) of colourless crystals. Found C 56 92 % H 3 24 % C,sH . F ,AsO requires C 57 45 %, H, 3.19 %; melting point 156-160 °C mass sp^ctrorn try with electron ionization m/z [M 376

Example 9

Synthesis of triphenylstibine oxide a) Synthesis of triphenylstibine oxide

To a solution of triphenylstibine (1 77 g 5 0 mmol) in chloroform (4 ml), 70 w/w % aqueous hydrogen peroxide (0 29 g or 6 0 mmol) was added dropwise at 0 °C The thick white suspension which was formed was then stirred for 2 hours after which it was stored in the refrigerator overnight The resulting crystals were filtered off, washed with cold chloroform and dried under vacuum at 60 °C to give triphenylstibine oxide in 71 % yield (1 3 g) Melting point of the crystals was 260-280 °C. Cι₈H₁₅SbO requires C. 58 6 % H 4 1 % Found C, 57 4 %, 57.5 %; H, 3.9 %, 3 9 % Example 10

Synthesis of tris(3,5-difluorαphenyl)phosphme oxide

To dry magnesium turnings (2 43 g or 0 1 mol) activated by iodine crystals 10 % of the total quantity of 1 -bromo-3 5-dιfluorober.zene (20 0 g. 0 102 mol) in anhydrous diethyl ether (60 ml) was added After the reaction had started, the remainder of the 1 -bromo-3,5-dιfluorobenzene was added dropwise over a period of 40 mm, so as to maintain gentle reflux of the diethyl ether The brown, opaque solution was refluxed for 1 hour and cooled to 0 °C A solution of phosphorus oxychloπde (2 82 ml or 4 65 g or 0 03 moi) in anhydrous diethyl ether (30 ml) was then added dropwise ovei 40 mir. The reaction mixture was stirred at room temperature for 2 hours ana then u was quenched with a 15 % aqueous ammonium chloride solution (150 ml) Chloroform (300 ml) was added to it and shaken After separating the phases the upper aqueous phase was extracted 2 times with chloroform (100 ml) The combined chloroform phase was washed 3 times with water ( 150 ml) and dried (sodium sulphate) The chloroform was removed under reduced pressure to give an oily residue (7 5 g) The product was crystallised from acetone to give tπs(3,5- difluorophenyl)phosphιne oxide in 34 5 % yie'd (4 0 g)

The melting point of the product v/as 194-196 °C Calculated for Cι₈H₉OF₆P C, 55 9 %, H 2 3 % Found C 55 8 % 55 8 % H 2 4 %, 2 3 % ¹H-NMR (CDCI₃) 8=7 00-7 06 (m 3H) 7 08-7 24 i n 6H) mass spectrometry with electron ionization M^*, m/z=386

Example 11

Synthesis of tris(pentafiuorophenyl)phosphine oxidea) Synthesis of trιs(pentafluorophenyl)phosphιne

To dry magnesium turnings (1 46 g or 0 06 inou activated oy iodine crystals, 10 % of the total quantity of pentafluoro-iodobenzene (7 9 ml or 17 6 g or 0 06 mol) in anhydrous diethyl ether (50 ml) was added After the reaction had started, the remainder of the pentafluoro-iodobenzene was added dropwise over a period of 40 min, so as to maintain gentle reflux of the diethyl ether The brown, opaque solution was refluxed for 1 5 hours After cooling it to 0 °C, a solution of phosphorus oxychloπde (1 67 ml or 2 75 g or 0 018 mol) in anhydrous diethyl ether (20 ml) was added dropwise over 40 mm The reaction mixture was stirred at room temperature for 2 hours and then it was quenched with a 5 % aqueous hydrochloric acid solution (80 ml) Chloroform (200 ml) was added to it and shaken. After separating the phases, the upper aqueous phase was extracted 2 times with chloroform (70 ml). The combined chloroform solutions were washed 3 times with water (150 ml), dried (sodium sulphate) and concentrated in vacuo to give 9.4 g of dark brown oily residue

The product was crystallised from petroleum ether (40-60 °C) The resulting crystals were collected on a filter to give tris(pentafluorophenyl)ρhosphine in 23 3 % yield (2 30 g) The melting point of the product was 110-113 °C

b) Synthesis of trιs(pentafluorophenyi)phosphιne oxide

To the solution of trιs(pentafluorophenyl)phosnhιn^ρ (0 8g or 1 5 mmol) in chloroform (4 ml) a 70 % aqueous hydrogen peroxide [ 73 g or 15 mmol) was added at room temperature The reaction mixuirp was refluxed for 20 hours After separating the phases, the chloroform solution was concentrated in vacuo and the product was crystallised from petroleum ether (40-60 °C) The resulting crystals were filtered off dried under vacuum to give tris(pentafluorophenyl)phosphιne oxide in 85 4 % yield (0 7 g) Melting point of the product is 167-169 °C Mass spectrometry with electron ionization' M⁺, m/z=548

Example 12

Synthesis of 1,1,1-trifluoroethyldiphenylphosphinate

To diphenylphosphmic chloride (3 8 ml or 4 73 g or 0 02 mol), 1 ,1 ,1trifluoroethanol was added dropwise The reaction mixture was refluxed at 80 °C for 3 hours The excess of 1 1 1 -tπfluoroethanol was removed under reduced pressure to give an oily residue in 100 % yield (6 g) Calculated for Cι₄H₁₂O₂F₃P requires C 56 0 % H 0 °Λ Fo-:v C 55 9 % H 4 0 % ¹H- NMR (CHCI₃). 8=4.21-4 31 (m, 2H) 7 39-7 85 (m 10H)

Example 13 to 31

Epoxidation of cyclooctene in the presence of various catalysts Cyclooctene (0 11g or 1 0 mmol) was dissolved in the chosen solvent (5ml). After addition of the compound to be tested as a homogeneous catalyst (z mmol), 35 %w/w aqueous hydrogen peroxide solution (x equivalents) was added dropwise at room temperature The reaction mixture was then stirred at the required temperature and the progress of the reaction was monitored by gas chromatography. The products were identified by gas chromatography coupled with mass spectrometry (GC-MS)

The results are summarised in Table 1 which follows.

Table 1

The catalysts used were as follows XA: diethylbenzyl-phosphonate XB: ethyl(diphenyl)ρhosρhinate XC: 1 ,1 ,1 -trifluoroethyldiphenylphosphinate XD: trioctylphosphine oxide

XE: ethylene-1 ,2-bis(diphenylphosρhine oxide) XF: tris(4-fluorophenyl)phosphine oxide XG: tris(3,5-difluorophenyl)phosphine oxide XH: tris(pentafluorophenyl)phosphιne oxide XI: triphenylarsine oxide XJ: triphenylstibine oxide

The results with triphenylarsine oxide (catalyst "XI") show that 2 to 3 equivalents of H₂O₂ are just as effective as a larger excess

Examples 32 to 38

Epoxidation of alkenes in the presence of various catalysts

To a solution of alkene (1 0 mmol) in toluene (5ml) was added the catalyst (1.0 mmol) and, to the mixture, 35 %w/w aqueous hydrogen peroxide (x equivalents) was added over a period of 5 minutes The reaction mixture was stirred at the required temperature and was monitored by gas chromatography The products were identified by gas chromatography coupled with mass spectrometry.

XF and XI have the same signification as in Examples 13 to 31 and AK, AL, and

AN represent respectively

AK: cyclooctene AL: 1-methylcyclohexene

AM: cyclohexene

AN: 1-octene

AO: styrene

The results are summarised in Table 2 which follows

Example 39

Oxidative cleavage of 1,2-cyclαhexanediol

To a solution of trans-1 2-cyclohexanedιol (0 12 g or 1 0 mmol) in toluene (5.0 ml), triphenylarsine oxide (0 32 g or 1 0 mmol) wcs ndded at room temperature To the suspension. 35 w/w % aqueous hydrogen peroxide (0 58 g or 6 mmol) was added dropwise The reaction mixture was stirred at 70 °C meanwhile the triphenylarsine oxide dissolved The reaction was monitored by gas chromatography In 40 hours, the reaction is complete After cooling it to room temperature distilled water (5 ml) was added to the solution and the phases were separated The aqueous phase was concentrated in vacuo the crystalline residue is adipic acid (yield 0 12 g) Its melting point was 146-150 °C IR (KBr disc) 2934, 1700 1440 1066 856 1AA 692

Oxidation of thβoanisole in the presence of phosphine and arsine oxides To a solution (5 0 ml or 1 0 mmol) of thioanisole in chloroform was added the oxide (1 0 mmol) and 2 mmol of 35 w/w % aqueous H₂0₂ The reaction mixture was stirred at the required temperature and was monitored by gas chromatography The results obtained are summarised in Table 3 wnich follows

Table 3

wherein XB and XE have the same signification as in Example 13 to 31 and XP and XQ represent

XP: R, R-trans-4 5-bιs(dιphenylphosρhιnomethyl)-2 2-dιmethyl-1 ,3-dιoxolan- hydrogen peroxide adduct XQ: o-bomyl-methyl-phenyl-phosphine oxide-hydrogen peroxide adduct

Examples 45 to 48

Chiral oxidation of pro-chiral sulphides

To a solution in 5.0 ml of solvent of 1 5 mmol (+)DIOP-bιs-oxιde-H₂O₂ adduct (DIOP representing for R.R-trans-4.5-bιs(dιphenylphosphinomethyl)-2,2- dimethyl-1 ,3-dioxolan), the sulphide (1 0 mmol) was added The reaction mixture was stirred at the required temperature and was monitored by GC or TLC. The sulphoxide was isolated by column chromatography and the enantiomeric excess was calculated from the optical rotation of the product. The results are summarised in Table 4 which follows

Table 4

Optical rotation of the pure enantiomers of the products are (+)-methylphenylsulphoxide' +149 ° (-)-ethylphenylsulphoxιde. -180 ° (-)-benzylphenylsulphoxιde: -252 ° (-)-methyl-p-tolylsulphoxide. -141 °

Claims

1 Hydrogen peroxide adducts. characterised in that they satisfy the following formula (I) .

in which,

1.1 n represents a real number such as 0 n_2

1.2 O represents the oxygen atom

1.3 the colon represents a free electron pair of said oxygen atom connected to M which is engaged in an adduct link with the hydrogen atoms of the H₂0₂ molecule

1 4 H₂O₂ represents one molecule of hvdrcyen peroxide

1 5 M represents any one of phosphorus arsenic antimony and bismuth atoms 1 6 Ri, R₂ and R₃ represent selected from aliphatic cycloaliphatic or aromatic groups further characterised in that

1 6 1 Ri, R₂ and R₃ are the same as each other and are other than C₂-C₄ alkyl cyclohexyl benzyl phenyl or p- dimethylaminopheni ! 01 1 6 2 Ri and R₂ are the same as eacn other and R₃ is different from Ri and R₂ and is other than phenyl or isopropyl when M represents P or 1.6 3 Ri, R₂ and R₃ are each different

An adduct according to claim 1 characterised in that in formula S, R_{1 t} R₂ and R₃ are each selected from the following groups - alkyl, cycloalkyl alkoxy, aryl aryloxy and aralkyi groups and from any of the foregoing substituted by at least one halogen atom and from any of the foregoing groups in which the aryl moiety is substituted by an alkyl, carboxy c acid, sulphonic acid or ammo substituent and from ketal groups.

3. An adduct according to claim 2 characterised in that in formula 1 R,, R₂ and R₃ are selected from alkyl, cycloalkyl or alkoxy groups or alkyl substituents which contain from 1 to 20 carbon atoms or which are substituted by halogen atoms selected in the range of 1 to 15. and/or groups in which the aryl group or moiety is phenyl

4. An adduct according to claim 2 characterised in that that in formula I, R-i, R₂ and R₃ are identical and selected from -

4.1 a linear alkyl saturated chain of from 5 to 20 carbon atoms or

4.2 a phenyl group substituted by a halogen or sulphonic acid substituent

5. An adduct according to claim 2 characterised in that that in formula I, R and R₂ are identical to each other and R_., is different from R, and R₂ and all are selected from -

5.1. a linear alkyl saturated chain of from 1 to 20 carbon atoms

5.2 a linear alkoxy group of from 1 to 10 carbon atoms optionally substituted by from 1 to 15 halogen atoms or a phenyl group

5.3 a phenyl group, optionally substituted by a halogen atom or sulphonic acid group

5 4 and R₃ can be selected from groups satisfying either of the following formulae II and HI

in which n has the same definition as in formula I, — C_zH_2z — represents a saturated alkylene group in which z represents an integer of from 2 to 5, M has the same definition as above, R₄ and R₅ are identical to or different from each other and are selected from aliphatic, cycloaliphatic or aromatic groups and can be the same as or different from R, or R₂ and:

in which R₄, R5 and — C₂H₂, — have the same definition as in formula (II) and — C_yH_2y,ι represents a linear alkyl group in which y represents an integer of from 1 to 8

6. An adduct according to claim 2 characterised in that R,, R₂ and R₃ are different from each other and selected from -

6 1 a phenyl group, optionally substituted by a one halogen atom or sulphonic acid group 6.2 a linear alkyl group of from 1 to 10 ca^rbcn atoms optionally substituted by a halogen atom 6.3. a ketal group 6.4 and not more than one of R 1 R and R₃ being selected from groups that satisfies either of fomulae (15) or (SI!) as defined in 13 7

7. Hydrogen peroxide adducts according to any preceding claim, characterised in that M is selected from P As and Sb

8 Hydrogen peroxide adducts according to

, 4 characterised in that R_{1 (}

R₂ and R₃ are linear alkyl groups containing from 6 to 10 carbon atoms

9. Hydrogen peroxide adducts according to claim 4, characterised in that M is a phosphorus atom, and R,. R₃ and R₃ are n-octyl groups

10. Hydrogen peroxide adducts according to claim 4 characterised in that Ri, R₂ and R₃ are phenyl groups substituted by at least one halogen atom.

11. Hydrogen peroxide adducts according to claim 4 characterised in that M is a phosphorus atom, and R,. R₂ and R₃ are 2 3 4 5.6-pentafluorophenyl groups.

12 Hydrogen peroxide adducts according to c.a r. 4. characterised in that M is a phosphorus atom, and R, R₂ and R~, are 3,5-dιfluorophenyl groups.

13. Hydrogen peroxide adducts according to claim 4. characterised in that M is a phosphorus atom, and R,. R₂ and R₃ are 4-fluorophenyl groups.

14. Hydrogen peroxide adducts according to claim 4. characterised in that M is a phosphorus atom and R, R_: and R_Λ are nenyl groups substituted by a sulphonic acid group in the ortho mera oι para position

15. Hydrogen peroxide adducts according to claim 4, characterised in that M is an arsenic atom, and R, R₂ and R₃ are 4-fluorophenyl groups.

16. Hydrogen peroxide adducts according to claim 4 characterised in that M is an antimony atom and R, R₂ and R₃ are phenyl groups

17. Hydrogen peroxide adducts according to c:~ιn 5 characterised in that fvl is a phosphorus atom R, and R- ?se i entical ethoxv groups and R₃ is a phenyl group

18 Hydrogen peroxide adducts according to claim 5 characterised in that M is a phosphorus atom, Ri and R₂ are identical ethoxy groups and R₃ is a -benzyl group

19. Hydrogen peroxide adducts accoiumg to uann 5 characterised in that M is a phosphorus atom, Ri and R₂ are pheny! groups and R is an ethoxy group.

20. Hydrogen peroxide adducts according to claim 5 characterised in that M is a phosphorus atom, Ri and R₂ are identical phenyl groups substituted by a sulphonic acid group in the ortho meta or para position and R₃ is a phenyl group

21. Hydrogen peroxide adducts according to claim 5. characterised in that M is a phosphorus atom. R, and R are phenyl groups and R₃ is a 2.2,2- trifluoroethoxy group

22. Hydrogen peroxide adducts according to claim 5 characterised in that M is a phosphorus atom, R,, R₂ R_< and R₅ are phenyl groups and R₃ is the group defined by formula II in which z has the value 2

23. Hydrogen peroxide adducts according to claim 5. characterised in that M is a phosphorus atom. Ri. R₂ R^ and R are phenyl groups and R₃ is the group defined by formula II in wh"~h z

3

24. Hydrogen peroxide adducts according to claim 5 characterised in that M is a phosphorus atom, Ri, R₂ R and R₅ are phenyl groups and R₃ is the group defined by formula ill in which z has the value 2 and y has the value 1

25. Hydrogen peroxide adducts according to claim 6, characterised in that Ri is a phenyl group R₂ is a methyl group and R , is an o-bornyl group

26. Hydrogen peroxide adducts according to any of claims 2 to 25 characterised in that n represents a real number such that 0 n_1

27. Method of preparation of hydrogen peroxide adducts as described in claim 1. characterised in that a mcnoester of a phosphinic or arsinic acid or a diester of phosphonic or arsenic acid is reacted in a solvent with hydrogen peroxide

28 Method of preparation of hydrogen peroxide adducts as described in claim 1 , characterised in that an oxide of phosphine. arsine or stibine is reacted in a solvent with hydrogen peroxide

29. Method of preparation of phosphinates or arsinates as intermediate products for the preparation of hydrogen peroxide adducts as described in claim 1 , characterised in that a phosphinite or an ars ite is reacted in a solvent with hydrogen peroxide

Method of preparation of phosphine or arsine oxides as intermediate products for the preparation of hydrogen n- ox' e adducts as described in claim 1 , characterised in that a phosμh " c an arsine is reacted in a solvent with hydrogen peroxide

Method of preparation of arsine or stibine oxides as intermediate products for the preparation of hydrogen peroxide adducts as described in claim 1 , characterised in that in a first step an arsenic or antimony halide is reacted with a Grignard reactant and in a second step, the arsine or stibine obtained from the first step is further ox'dised with hydrogen peroxide in an oi ganic solvent

Method of preparation of phosphine ar sine oι bismuthme oxides as intermediate products for the preparation of hydrogen peroxide adducts as described in claim 1 characterised in that a phosphorus arsenic or bismuth oxyha de is reacted with a Grignard reactant

Method of preparation of phosphine ai bnit shome or bismuthme oxides as intermediate products for the preparation of hydrogen peroxide adducts as described in claim 1 characterised in that an organo - phosphinic, -arsinic -stibinic or -bismuthinic halide is used for esterifying an alcohol

Process for the oxidation of a substrate containing an electrophilically oxidisable moiety employing hydi ogen peroxide as oxidant in the presence of a homogeneous catalyst chai

in that at least one of the adducts of hydrogen peroxide of compounαs comprising at least one element of Group 15 of tne Periodic T nle of the elements is employed as the catalytic intermediate complex

Process acordmg to claim 34 characterised in that the catalytic intermediate complex satisfies formula (I)

wherein. n represents a real number such as 0 n 1^: H₂O₂ represents one molecule of hydrogen peroxide O represents an oxygen atom the colon : represents a free electron pair in said oxygen atom which is engaged in an adduct link with a hydrogen atom of the H_;O₂ molecule M represents any one of phosphorus arsenic antimony and bismuth atoms

6 A process according to claim 35 characterised in that in formula I, R_{1 t} R₂ and R₃ are each selected from the following groups - alkyl, cycloalkyl, alkoxy, aryl, and aralkyi groups and from any of the foregoing substituted by at least one halogen atom, and from any of the foregoing groups in which the aryl moiety is substituted by an alkyl, carboxylic acid sulphonic acid or ammo si

and from ketal groups

7 A process according to claim 36 characterised in that in formula S R_{1 t} R₂ and R₃ are selected from alkyl cycloalkyl or alkoxy groups or alkyl substituents which contain from 1 to 10 carbon atoms or which are substituted by halogen atoms selected in the range of 1 to 15, and/or groups in which the aryl group or moiety is phenyl

38 A process according to any of claims 34 to 37 characterised in that in formula S M is selected from P As and Sb

39. A process according to any of claims 34 to 38 characterised in that the hydrogen peroxide adduct is generated in situ in the reaction mixture which contains hydrogen peroxide and a precursor material in which M and the groups R ,. R₂ and R- are as defined in the respective claim

40. An oxidation process according to any of claims 34 to 39 characterised by employing a hydrogen peroxide adduct as described in any of claims 1 to 26 or produced by a method according to any of claims 27 to 33.

41. A process according to any of claims 34 to 40 characterised in that the substrate is selected from alkenes, ketcnes. aldehydes, nithles, amines, sulphides, sulphoxides and thiols