CS255853B2 - Process for preparing alcanoic acids substituted in alpha position by aromatic group - Google Patents

Description

The invention relates to a novel process for the preparation of alkanoic acids substituted in the alpha position by an aromatic group. More particularly, the invention relates to a process for the preparation of alpha-substituted alkanoic acids or aromatic esters thereof, characterized by the general formula I

R ¹ ''

I 2 '

Ar - CH - COOR (I) in which Ar is a (phenyl) group which may be substituted by a halogen atom, an alkyl group, a C 1-8 -alkoxy group, a C 1-8 -alkanoylamino group, a C 1-4 -haloalkyl group, a phenyl group or a 1-oxo-2-isoindolinyl group, a b) naphthyl group which may be substituted by a C 1-4 alkoxy group or a thienyl group,

R ¹ represents a hydrogen atom or a C 1-6 alkyl group, or Ar and R ¹ may form a fused ring with the carbon atom to which they are attached,.

R is hydrogen, C ^ _ ~ ₄ alkyl or C ^ _ ^ - hydroxyalkyl.

Many of the compounds of formula I are commercially valuable. For example, alpha- (4-isobutylphenyl) propionic acid corresponds to a compound of formula I wherein Ar is

2

4-isobutylphenyl, R is methyl and R is hydrogen. This substance is known as Ibuprofen, which is an anti-inflammatory agent. Alpha- (6-methoxy-2-naphthyl) propionic acid, corresponding to a compound of formula I, wherein Ar is 6-methoxy-2-naphthylic

The 2 group, R is methyl and R is hydrogen, is known as Naproxen. Alpha- (4-difluoromethoxyphenyl) isovaleric acid corresponding to the compound of formula (I) ve

Wherein Ar represents a 4-difluoromethoxyphenyl group, R 6 is an isopropyl group and R 8 is a hydrogen atom, is very effective as the acid portion of the pyrethroid insecticides.

Numerous processes have been known for the preparation of alkanoic acids substituted in the alpha position by an aromatic group. These processes are typically described below in connection with the production of alpha- (4-isobutylphenyl) propionic acid (Ibuprofen):

A process comprising reacting a 4-isobutylphenylacetic acid ester produced by a two-step process from 4-isobutylacetophenone with an alkyl carbonate in the presence of a base to give the corresponding malonic ester, methylating the compound with methyl iodide, hydrolyzing the methylation product and then thermal decomposition the desired propionic acid derivative (British Patent No. 97170'C); .

The process of converting 4-isobutylacetophenone to the corresponding hydantoin by treatment with potassium cyanide and ammonium carbonate, hydrolyzing the hydantoin to the alpha amino acid, alkylating it to the dialkylamino compound and reducing it to form alpha- (4-isobutyphenyl) propionic acid / British Patent No. 1 167 192 /. ,

3. A process according to which 4-isobutylacetophenone and a monochloroacetic acid ester are subjected to a Darzens reaction to form the corresponding epoxycarboxylic acid ester, the ester is hydrolyzed, the hydrolysis product is decarboxylated to form alpha-4-isobutylphenyl / propionaldehyde and the aldehyde is oxidized to the desired acid derivative. propionic (British Patent No. 1,160,725).

4. A process comprising 4-isobutylbenzaldehyde with mercaptal-S-formaldehyde oxide to form mercaptal-S-ketene oxide, in reaction with thionyl chloride to form mercaptal-chloroketene, treatment with alcohol to alpha- (4-isobutylphenyl) alkylthioacetate and _in that the ester is subjected to methylation, hydrolysis and reductive desulfurization, respectively, to obtain the desired propionic acid derivative (U.S. Pat. No. 4,242,519).

Processes (1) and (4) involve a number of steps and are not industrially advantageous. Process (2) is industrially disadvantageous because it has a degree in which toxic substances such as potassium cyanide are used.

Processes (1) and (3) are economically disadvantageous because the ethoxycarbonyl group introduced in the initial stage is finally removed by decarboxylation in the final stage.

Therefore, it is clear that the introduction of a novel and industrially advantageous process for the production of the compounds of formula (I) above will contribute significantly to the development of technology in the art.

The purpose of the present invention is to provide a unique and industrially advantageous process for the preparation of the compounds of formula (I) above.

Other features and advantages of the process of the invention will be apparent from the following description.

According to the invention, there is provided a process for the production of alpha-substituted alkanoic acids or aromatic esters thereof of the aforementioned general formula (I), which comprises the formation of an alpha-sulfonyloxy ketone acetal of the general formula (II)

¹ 1 N - C - CH - R in which

Ar and R ¹ have the abovementioned meaning,

R ³ and R ⁴ mutually independently denote C ^^ - alkyl, or together represent ~ ^ ₂ -6 -alkylene,

R ⁵ represents a C 1-6 alkyl group, a phenyl group which may be substituted with a ^- 6 halogen atom or a C 1-6 alkyl group, or a camphoryl group with an oxygen affinity reagent selected from the group consisting of iodotrimethylsilane, trimethylsilylperfluoromethanesulfonate and Lewis of acids.

In said compounds of formulas I and II, Ar in its broadest sense may include groups derived from cyclic compounds having aromatic character. Thus, the groups may generally be categorized as aryl groups, optionally containing at least one substituent and heteroaromatic groups.

and / aryl groups optionally containing at least one substituent

Included within the meaning of Ar are, for example, phenyl, biphenyl, and naphthyl groups. .

The phenyl groups of Ar may be unsubstituted or may contain one or more substituents on the aromatic ring. Particular examples of the substituent include halogen atoms such as chlorine, bromine, fluorine and iodine, alkyl groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl and tert-butyl, alkoxy groups such as methoxy, ethoxy, n-propoxy and isopropoxy, haloalkyl groups such as trifluoroethyl and trifluoropropyl, such as heterocyclic groups oxo-isoindolinyl, alkanoylamino groups such as acetylamino and propionylamino groups.

The naphthyl groups of Ar may be substituted with alkoxy groups, preferably methoxy groups.

Preferably, 1 to 5 of said substituents, especially 1 to 3, may be attached to the aromatic ring.

Specific examples of phenyl and naphthyl groups having substituents on the aromatic ring include chlorophenyl, fluorophenyl, bromophenyl, iodophenyl, tolyl, ethylphenyl, isopropylphenyl, isobutylphenyl, rec.butylphenyl, methoxyphenyl, ethoxyphenyl, isopropoxyphenyl, trifluoroethylindenyl, oxo-isoindolinyl, oxo-isoindolinyl. acetylaminophenyl, fluorobiphenyl, acetylaminobiphenyl and methoxynaphthyl.

b / Heteroaromatic groups

In the meaning of Ar, a heteroaromatic group may be a thienyl group.

The alkyl groups in said compounds of formulas I and II may be straight or branched chain groups.

Examples of such groups include straight or branched alkyl groups having 1 to 6 carbon atoms, in particular methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, isoamyl and n-hexyl.

The alkoxy and alkanoyl groups in said compounds of formulas I and II have no more than 6 carbon atoms, preferably no more than 4 carbon atoms.

The alkylene groups in said compounds of formula II are preferably ethylene, propylene, butylene, trimethylene, or tetramethylene.

A camphyl group within the meaning of a substituent is D- or L-10-camphyl.

The method of the invention treats a compound of formula II with an oxygen affinity reagent selected from the group consisting of iodotrimethylsilane, trimethylsilylperfluoromethane. sulfonate and Lewis acids. It has been found that as a result of this treatment, the sulfonyloxy group of formula -OSC 1 -R ⁵ at position 2 of the compound of formula II cleaves and the aromatic group Ar at position 1 is rearranged to position 2 to give the compound of formula I.

In addition, the reaction of either -OR or -OR of the compound of formula II forms a -OR group of the product of formula I. Therefore, the product of this reaction is an ester of formula I in which R is an alkyl group.

As used herein, an oxygen affinity agent refers to a compound exhibiting the ability to coordinate in such a manner as to the acceptance of a free electron pair of an oxygen atom.

Examples of an oxygen affinity reagent are the following compounds:

a) iodotrimethylsilane, b) trimethylsilylperfluoromethanesulfonates, such as trimethylsilyltrifluoromethanesulfonate, and trimethylsilylpentafluoromethanesulfonate, δ Lewis acids such as aluminum chloride, aluminum bromide, zinc chloride, titanium tetrachloride, tin tetrachloride.

These oxygen affinity agents may be used alone or as a mixture of 2 or more compounds. Particularly preferred oxygen affinity reagents used in the process of the invention are iodotrimethylsilane, trimethylsilyl trifluoromethanesulfonate, ferric chloride, aluminum chloride, and tin tetrachloride.

The amount of oxygen affinity reagent used is not strictly limited and can vary widely depending on the type of compound of Formula II and / or the type of reagent. Generally, the reagents are used in an amount of at least 0.1 mol, preferably 0.2 to 5.0 mol, particularly preferably 1.0 to 2.0 mol, per 1 mol of the compound of formula (II).

Treatment of the compound of formula (11) with an oxygen affinity reagent may be carried out in the absence of a solvent. Usually, however, the treatment is conveniently carried out in a solvent, in particular an aprotic solvent. For example, when using Lewis acid or iodotrimethylsilane as said reagent, particularly good results are obtained with halogenated hydrocarbons such as methylene chloride, chloroform and 1,2-dichloroethane. When trimethylsilyl trifluoromethanesulfonar is used as an oxygen affinity reagent, preferred solvents are halogenated hydrocarbons, acetonitrile and orthoformates.

The reaction proceeds very smoothly under mild conditions. The processing temperature is about -40 to 150 ° C, preferably about -20 to 100 ° C, and particularly preferably -10 to 90 ° C.

Treatment of a compound of formula (II) with an oxygen affinity reagent produces a compound of formula (I) under these conditions. If the reagent is a Lewis acid, the product and the reagent may in some cases form a complex. In this case, the product can be isolated by adding water to the reaction mixture to decompose the complex and then the substance is subjected to the usual isolation operation.

The compound of formula (I) produced by the process of the invention can be isolated from the reaction mixture by methods known per se, such as extraction, chromatography, distillation and crystallization.

The compounds of formula (II) used as starting materials in the process according to the invention are novel compounds which have not been previously described in the literature.

Various groups of compounds of formula II are exemplified below.

Preferred aromatic groups Ar are those of the formula R @ ¹ --Ar @ ¹ represents a phenylene or naphthylene group and R @ ^b represents a hydrogen atom, a halogen atom, a C8-6 -alkoxy group, a C8-6 -haloalkyl group, a C8-6-alkanoylamino group, an oxoisoinfolinyl group. or a phenyl group. Another preferred example of the aromatic group Ar is thienyl.

Suitable R ¹ groups are C 6 -C 6 -alkyl groups such as methyl, ethyl, n-propyl, isopropyl or butyl. A preferred set of meanings for R ¹ are hydrogen and alkyl groups Cg_ _g ..

'3

C.-alkyl groups are suitable as the alkyl groups represented by the individual R a

34

R. As the alkylene group formed by R and R together are C ₂ _ suitable -aikylenová ₁₂ group such as ethylene, propylene and trimethylene.

Examples of suitable alkyl groups represented by R ~ include unsubstituted C C.-alkyl groups such as methyl, ethyl, butyl and further preferably D- or ^1-6 5 is preferred as R ³

L-10-Camphoryl. As aromatic R groups, substituted or unsubstituted phenyl groups of the general formula are preferred

where

R ⁷ represents a hydrogen atom, a halogen atom or a _C 6-6 -alkyl group.

Of the compounds of Formula II, those of Formula I-1 below are preferred

OR ³ OS0 ₂ -R ⁵ * 1

Ar - C - CH - R i) R ⁴ (1-1) in which

Ar 1 represents a group of the formula R ¹ -Ar ¹ - or a thienyl group,

R ¹ represents hydrogen or alkyl group Cji _A * л '

R and R independently represent С ^ _ ^ - а1куlovou group or together represent a ^C 2-12 ^{_alícylenOVOU sku} P ^inu '

R ⁵ represents a C 1-4 alkyl group, a D- or L-10-camphoryl group or a group of the general formula

and Ar ¹ , r6 and R? are as defined above.

In the compound of formula (II), Ar and R @ ^{1 may} form a fused ring together with the atom bonded to these groups. A particular example of compounds of formula II, a fused ring, is a compound of formula carbon to which Ar and R ¹ form

Treatment of these compounds with an oxygen affinity reagent according to the present invention yields the following compound of formula

COOR ²

Compounds of formula (II) may be prepared by synthesis from alpha-haloketones of formula (V) in which:

X represents a halogen atom and Ar a

R ¹ is as defined above, as shown in the following reaction scheme:

/IN/

X I ř

Ar-C-CH-R

Ar-C ^ -H-R (VII)

R ⁵ -SO 2 -Hal ³ or OSO2-R ⁵ and / or _R 5 _S Q _2/2 Q-Ar-C = CH-R ¹

AB ⁴ / VI / / II /

In the above reaction scheme

M is an alkali metal,

Hal denotes a halogen atom, 2 especially a chlorine atom, and

3 4 5,,

Ar, R, R, R, R and X are as defined above.

Compounds of formula (V) may be readily prepared by treating compounds of formula (VIII).

X

AND

R - CH - COCl (VIII), where

R ¹ а X have the above meanings, is subjected to Friedel-Crafts reaction with a compound of formula IX

Ar-H (IX), where

Ar is as defined above, or by halogenation of a compound of formula X ¹¹ 1

Ar - C - CH ₂ - R (X) where

Ar and R ¹ are as defined above, which is carried out by known methods.

As described above, the compound of formula (II) used as starting material for the process of the invention can be prepared in two stages from the alpha-haloketone of formula (V). This compound can also be produced by other methods. Such methods include oxidation of the 1-acetoxy-1-alkene substituted in the 1-position with an aromatic group of formula XI

OR ³

I i

Ar = C = CH-R (XI), where

Ar, R ¹ , R ³ are as defined above, to form an epoxy compound of formula VII, production of an alpha-hydroxyketone acetal of formula VI from the epoxy compound above and a further embodiment of step VI-11, which process comprises acetalizing the corresponding alpha-sulfonyloxy ketone to a compound of formula II, and a method of reducing the alpha-oxoketone acetal of formula XII

OR ³ O

I il i

Ar-C-CR / XII /,

where

Ar, R ¹ , R ³ and R 6 are as defined above to form the alpha-hydroxyketone acetal of formula VI and its treatment in step VI → 11.

The starting material for the process according to the invention, the alpha-sulfonyloxy-ketone acetal of the general formula II, can be produced by a variety of easy methods in a smaller number of steps.

The compounds of formula (I) which can be prepared by the process of the invention include a number of compounds suitable in the pharmaceutical field and as agricultural chemicals. Typical examples of such suitable compounds are Ibuprofen, Naproxen and alpha- [4- (1-oxo-2-isoindolinyl) phenyl] propionic acid (anti-inflammatory agent, Indoprofen). Typical examples also include alpha- (2-thienyl) propionic acid, methyl- [alpha] - (4-acetylaminophenyl) propionate, alpha- (4- (tert-butyl) phenyl) isovaleric acid, methyl-alpha- (4-alkoxyphenyl) isovalerates, afla- (4-biphenylyl) propionic acid, methyl alpha- (4-difluoromethoxyphenyl) isovalerate and methyl alpha- (4-alkoxyphenyl) propionates, which are known as important synthetic intermediates for anti-inflammatory agents and insecticides.

The following examples illustrate the invention in detail.

Example 1

0.31 ml (0.44 g) of iodotrimethylsilane and 2 drops of cyclohexene are stirred in 5 ml of anhydrous methylene chloride at room temperature under an argon atmosphere. 4 ml of a solution of 529 mg of 1-phenyl-2- (p-toluenesulfonyloxy) -1-oxopropane dimethylacetal in anhydrous methylene chloride are added dropwise. The mixture was stirred at room temperature for 3 hours and then 5 mL of saturated aqueous sodium bicarbonate solution was added. The organic layer was washed successively with 5 mL of 10% aqueous sodium thiosulfate, 5 mL of water, 5 mL of 10% aqueous sodium bicarbonate, and 5 mL of water, and then dried over anhydrous magnesium sulfate.

Quantitative gas chromatography analysis (internal standard method) revealed that the product contained 226.4 mg of methyl alpha-phenylpropionate. Yield 91.9%.

t

Examples 2 to 6

176 mg of 1-phenyl-2- (p-tolenesulfonyloxy) -1-oxopropane dimethylacetal and each oxygen affinity reagent listed in Table 1 in a given amount are stirred in 4 ml of anhydrous methylene chloride at a temperature indicated in Table 4 each. To the mixture was added 5 ml of water and then extracted 4 times with 5 ml of methylene chloride. The extracts were washed with 10 ml of water and dried over anhydrous magnesium sulfate.

The product * was analyzed for methyl-aflaphenylpropionate content by gas chromatography in the same manner as in Example 1.

The results are shown in Table 1: Table Example Affinity / molar reagent manifesting to oxygen ratio r / Reaction conditions Yield of methyl alpha-phenyl propionate (%) Temperature / ° с / Time / h / 2 A1C1 ₃ / 0,6 / 0 1 52.5 3 ^A1C1 3 / 0,7 / The flow temperature reverse- 1 63.6 4 ^A1C1 3 / 1,0 / The flow temperature reverse- 0.7 69.3 5 A1C1 ₃ / 1,4 / 0 1 68.0 6 TiCl ₄ / 3,0 / The flow temperature return- 10 16.8

Example 7

3.849 g of 1- (4-chlorophenyl) -2- (p-toluenesulfonyloxy) -1-oxopropane dimethyl acetal are stirred in 10 ml of anhydrous methylene chloride at room temperature under an argon armosphere. The solution obtained by dissolving 1.71 ml (2.40 g) of iodotrimethylsilane and 2 drops of cyclohexene in 2 ml of anhydrous methylene chloride was added dropwise at room temperature and the mixture was stirred for 30 minutes. The same treatment as in Example 1 yielded an oily crude product which, according to its NMR spectrum, contained 1.61 g of methyl alpha- [p-chlorophenyl] propionate. the yield is 81.0%.

Example 8

0.20 ml (0.28 g) of iodotrimethylsilane and one drop of cyclohexene are stirred in 8 ml of anhydrous methylene chloride at room temperature under an argon atmosphere. To the mixture was added dropwise 6 ml of a 490 mg / 1.00 mmol / L dimethylacetal / 6-methoxy-2-naphthyl / -2- / 10-D-kamforsulfonyloxy / -l-oxopropan whose / alpha /? ⁵ = + 32.5 ° (δ = 1.00, chloroform), in anhydrous methylene chloride, and the mixture was stirred at room temperature for 1 hour, and then 10 mL of saturated aqueous sodium bicarbonate was added.

Work-up as in Example 1 followed by column chromatography (silica gel, methylene chloride) gave 230 mg of methyl (R) - (-) - alpha - (6-methoxy-2-naphthyl) propionate as colorless crystals, m.p. 85 to 92 ° C. Yield 94.2%. This product was found to be optically pure by NMR spectroscopy using an optically active shift-inducing agent, Eu (TFC).

Example 9

In a similar manner to Example 1, methyl alpha- [4-biphenylyl] propionate was prepared from 1- (4-biphenylyl) -2-methanesulfonyloxy-1-oxopropane dimethylacetal. The yield is 68% (calculated on 1- (4-biphenylyl) -2-hydroxy-1-oxopropane dimethylacetal).

Example 10

In a similar manner to Example 2, methyl alpha-phenylpropionate was prepared from 1-phenyl-2- (p-toluenesulfonyloxy) -1-oxopropane dimethylacetal and tin tetrachloride. Yield 51.4%.

Example 11

350 mg of 1-phenyl-2- (p-toluenesulfonyloxy) -1-oxopropane dimethyl acetal and 0.20 ml of triethylsilyl trifluoromethanesulfonate were stirred in 1 ml of trimethyl orthoformate at 65 ° C for 9 hours. After the usual work-up, methyl-alpha-phenylpropionate was obtained in 50.5% yield according to gas-liquid chromatographic analysis as in Example 1.

Example 12

In a similar manufacturing process to Example 2, methyl alpha-phenylpropionate was obtained from 1-phenyl-2- (p-toluenesulfonyloxy) -1-oxopropane dimethyl acetal and ferric chloride. Yield 80%.

Example 13.

To 10 ml of methylene chloride was added 0.53 ml (0.75 g) of iodotrimethylsilane under argon and the mixture was stirred at room temperature. To the solution was added 1.074 g of 1- (6-methoxy-2-naphthyl) -2- (p-toluenesulfonyloxy) -1-oxopropane dimethylacetal dissolved in 10 ml of anhydrous methylene chloride over 20 minutes, and the mixture was stirred at the same temperature for 40 minutes. . 20 ml of a 20% aqueous sodium thiosulfate solution was then added and the mixture was stirred overnight. The organic layer was washed successively 5 times with 20 mL of the same sodium thiosulfate solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, chloroform) to give 495 mg of methyl alpha- [6-methoxy-2-naphthyl] propionate in 81% yield. The NMR spectral data of the product were in full agreement with the product obtained according to Example 3 of Patent No. 255,851.

Claims (14)

SUBJECT OF THE INVENTION A process for producing alkanoic acids substituted in the alpha position by an aromatic group or esters thereof of the general formula I R ¹ - I 2 Ar - CH - COOR (I) wherein Ar is a) a phenyl group optionally substituted by a halogen atom, a C 1-8 -alkyl group, a C 1-8 -alkoxy group, a C 1-8 -alkonylamino group, a C 1-8 -haloalkylsupinone , phenyl or oxo-2-isoindolinyl group, and b / a naphthyl group which is optionally substituted C ^ _ ~ ₆ alkoxy or с / thienyl, R ¹ is hydrogen or C ₁ _ ₆ -alkyl group. or Ar and R ¹ optionally form a fused ring with the carbon atom to which they are attached, R is hydrogen, С ^ _д-а1куlovou group or a C ₁ _ ₄ -hydroxyalkylovou group, characterized in that the acetal-.alpha Sulphonyloxy formula II OR ³ 0S0 _o -R ⁵ . 1 í 1 Ar - C - CH - R ./II/, in which ' Ar and R ¹ are as defined above .. R ³ and R independently are C ^ _ ^ - alkyl group or together represent С _ ^ ₂ - а1куlenovou group .. R represents a C 1-6 alkyl group, a phenyl group optionally substituted by a halogen atom or a C 1-6 alkyl group, or a camphoryl group with an oxygen affinity reagent selected from the group consisting of iodotrimethylsilane, trimethylsilylperfluoromethanesulfonate and Lewis acids. 2. A process according to claim 1, wherein the Lewis acid is selected from the group consisting of aluminum chloride, tin tetrachloride and ferric chloride. _ 3. The process according to claim 1, wherein the oxygen affinity reagent is used in an amount of 0.1 mol, preferably 0.2 to 5.0 mol, based on 1 mol of the compound of formula II. 4. The method of claim 1 wherein the oxygen affinity agent is treated at a temperature of -40 to 150 ° C, preferably at -20 to 100 ° C. 5. Method according to claim 1, characterized in that the acetal is used alpha-Sulphonyloxy of formula II wherein Ar is 6-methoxy-2-naphthyl group, R ¹ represents methyl and R ^3, R and R5 are defined referred to in point 1. 6. Method according to claim 1, characterized in that the acetal is used alpha-Sulphonyloxy of formula II wherein Ar is 4-isobutylphenyl group, R ¹ represents a methyl group And R, R and R have the meaning given in point 1. 7. A process according to claim 1, wherein the alpha-sulfonyloxy ketone acetal of formula (II) wherein Ar is 4-C. .-alkoxyphenyl group, R ¹ represents an isopropyl And R, R and R are as defined in point 1. 8. A process according to claim 1, wherein the alpha-sulfonyloxy-ketone acetal of formula (II) wherein Ar is 4-C.alpha.-alkoxyphenyl is methyl. 3 4 5 1 and R, R and R are as defined in point 1. 9. The method according to claim 1, characterized in that the acetal .alpha.-Sulphonyloxy of formula II wherein Ar is 4-difluoromethoxy, R ¹ is isopropyl, And R, R and R are as defined in point 1. 10. A process according to claim 1, wherein the acetal of an alpha-sulfonyloxy ketone of formula II wherein Ar is a 2-thienyl group, R is a methyl group And 45, R, R 'and R have the meaning given in point 1. 11. A process according to claim 2, wherein the acetal of an alpha-sulfonyloxy ketone of formula II wherein Ar is a 4-acetylaminophenyl group is methyl. And R, R and R are as defined in point 1. 12. A process according to claim 1, wherein the acetal of an alpha-sulfonyloxy ketone of formula II wherein Ar is 4- (1-oxo-2-isoindolinyl) phenyl is R is The methyl group and R, R and R are as defined in point 1. 13. The process of claim 1, wherein the alpha-sulfonyloxy ketone acetal of formula (II) wherein Ar is a 4-biphenylyl group, k is methyl and R and R are as defined in point 1. 14. A method according to a point of formula (II) in which the group 3 and R, R and R are each 1, characterized in that alpha-sulphonyloxy-ketone Ar acetal used is the 4- (tertiary) acetal. butyl / phenyl group, R ¹ is isopropyl as defined in point 1.