CS255851B2 - Process for preparing alcanoic acids substituted in alpha position by aromatic group - Google Patents

Description

The invention relates to a novel process for the production 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

Ar - CH - COOR ² (I) wherein Ar is

a) a phenyl group which may be substituted by halogen, C ₁ _ ^ - alkyl, C _1-6 alkoxy, C - ^ - alkanoylamino, C - ^ - haloalkyl, phenyl or oxo-2-isoindolinyl ,

b) a naphthyl group which may be substituted by C ^^ - alkoxy or C ₁ _ ₆ alkoxy, and halogen or

c) 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 represents a hydrogen atom, a C 1-6 -alkyl group or a C 1-6 -hydroxyalkyl group.

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 ”, an anti-inflammatory agent. Alpha 6 * (6-methoxy-2-naphthyl) propionic acid, corresponding to a compound of formula I, wherein AR is 6-methoxy-2-naphthyl, R is methyl and R is hydrogen, is known as Naproxen. Alpha- (4-difluoromethoxyphenyl) isovaleric acid corresponding to a compound of formula I wherein Ar is

2

4-difluoromethoxyphenyl, R is an isopropyl group and R is a hydrogen atom, is very effective as the acid moiety of pyrethroid insecticides.

Numerous processes have been known for the preparation of alkanoic acids substituted in the alpha position by an aromatic group. These procedures are described below as typical 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 methylacea product then thermal decomposition to yield the desired derivative. propionic acid (British Patent No. 971,700);

A process comprising converting 4-isobutylacetophenone to the corresponding hydantoin by treatment with potassium cyanide and ammonium carbonate, hydrolyzing the hydantoin to an alpha-amino acid, alkylating it to a dialkylamino compound and reducing it to form alpha- (4-isobutylphenyl) propionic acid (British Pat. 1,167,192).

A process according to which 4-isobutylacetophenone and a monochloroacetic acid ester are subjected to a Darzeis reaction to give 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 propionic acid derivative (British Patent No. 1,160,725).

4. A process comprising the condensation of 4-isobutylbenzaldehyde with mercaptal-S-formaldehyde oxide to form mercaptal-S-ketene oxide, in reaction with thionyl chloride to form mercaptal alpha-chloroketene, treatment with alcohol to alpha- (4-isobutylphenyl) -alpha- alkyl thioacetate 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 step in which toxic substances such as potassium cyanide are used.

Processes (1) and (3) are economically disadvantageous since 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, a process for the preparation of the alkanoic acids substituted in the alpha position by an aromatic group or their esters of the above-mentioned general formula I is possible, which is characterized in that acetal-alpha-sulfonyloxy ketone of the general formula II

Ar -

? ^S0 2- ^K ! CH - R (II), in which:

Ar and R ¹ have the abovementioned meaning,

R ⁴ and R ⁴ independently represent C 1-4 alkyl, or together denote a len group,

R represents a C 1-6 alkyl group, a phenyl group which may be substituted by a halogen atom or a C 1-6 alkyl group, or a camphyl group, subjected to analysis.

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.

a) 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 substituents 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 groups, haloalkyl groups such as trifluoroethyl and trifluoropropyl, such as the 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 up to 3, may be attached to the aromatic ring.

Particular examples of phenyl and naphthyl groups having substituents on the aromatic ring include chlorophenyl, fluorophenyl, bromophenyl, iodophenyl, tolyl, ethylphenyl, isopropylphenyl, isobutylphenyl, tert-butylphenyl, methoxyphenyl, ethoxyphenyl, isopropoxyphenyl, trifluoroethylphenyl, oxo-isoindolinylphenyl, oxo-isoindolinylphenyl, , 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.

The camphyl group represented by R ⁵ is D- or L-10-camphyl. .

The process of the invention hydrolyzes the alpha-sulfonyloxy ketone acetal of formula II. '

It has been discovered that the hydrolysis of a compound of formula (II), in particular said acetal compound containing a sulfonyloxy group of the formula OSC (R ⁾ at position 2 and an aromatic group Ar at position 1, results in a single reaction in which the sulfonyloxy group cleaves and the aromatic group position 2 to form an alkanoic acid substituted in the alpha position by an aromatic group of formula I.

The hydrolysis may be carried out in the absence of a solvent, but is desirably carried out in a generally inert solvent under the reaction conditions. Examples of inert solvents are dimethylformamide (DME), dimethylsulfoxide (DMSO), 1,3-dimethyl-2-imidazolidinone (DMI), 1,4-dioxane, tetrahydrofuran (THF), diethylene glycol dimethyl ether (diglyme), hexamethylphosphoric triamide (HMPA) ), 1,2-dimethoxyethane, pyridine, methanol, ethanol, ethylene glycol and acetic acid. These solvents may be used alone or as a mixture of 2 or more substances.

The reaction temperature is not critical and can vary widely depending on the type of starting material of formula (II) and the like. In general, temperatures in the range of about 0 to 250 ° C, preferably between room temperature to 200 ° C, can be used. This reaction is generally carried out at elevated temperature, preferably from about 40 ° C to the reflux temperature of the reaction mixture, particularly preferably from about 50 to 180 ° C, for acceleration. The reaction may be carried out at atmospheric or elevated pressure.

The water required to hydrolyze the compound of formula (II) may be introduced beforehand into a solvent of the type mentioned above by way of example and the compound of formula (II) may be stirred into the solvent to effect the reaction. Alternatively, it is also possible to mix the compound of formula II into a solvent, to add water to the mixture and to react the water with the compound of formula

II.

Alternatively, the compound of formula II may be heated to a temperature in the above range in the above solvent in an anhydrous medium, and then water is added to effect hydrolysis of the compound of formula II (see Examples 11 and 15 below).

To facilitate the process, it is convenient to introduce the compound of formula (II) into a mixture of water and the above polar solvent.

The amount of water required for the hydrolysis is not critical and may vary widely depending upon the type of compound of formula (II) used, reaction conditions and the like. Generally, it is used in an amount of at least 1 mol, preferably at least 5 mol, per 1 mol of the compound of the formula (II). If too much water is used, the solubility of the compound of formula II is reduced. It is therefore preferable not to use too much water.

In order to prevent the unwanted cleavage of the acetal moiety from the compound of formula (II) by acid, the hydrolysis of usually 2a neutral or basic conditions (at a pH of about 7 to 14) is preferably performed.

Because the sulfonyloxy group of formula -OSO _? The -R at the 2-position is cleaved off as the ^2- sulfonic acid of the formula RSO4H during hydrolysis, it is advisable to arrange for a base to be present in the reaction system to maintain the reaction system under neutral to basic conditions during the reaction. Examples of the base that can be used for this purpose include alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, alkaline earth metal hydroxides such as magnesium hydroxide and calcium hydroxide, alkali metal carbonates such as potassium carbonate and sodium carbonate, alkaline earth metal carbonates , such as magnesium carbonate and calcium carbonate, alkali metal bicarbonates such as sodium bicarbonate and potassium bicarbonate, alkali metal salts of carboxylic acids such as sodium formate, sodium acetate, potassium acetate and sodium propionate, alkali metal phosphates such as sodium phosphate and potassium phosphate and organic tertiary amines such as pyridine, triethylamine and tributylamine. These inorganic or organic bases are usually used in an amount of at least 1 equivalent, preferably 1 to 10 equivalents, per 1 mol of the compound of the formula II.

Hydrolysis can usually be completed in about 1 to 250 hours, although there is dependence on the type of starting compound of formula (II) and reaction conditions.

When the above hydrolysis is cleaved sulphonyloxy group of the formula -OSO ^ -R ^{5 is} in position 2 of the compound of formula II and the aromatic group Ar in the 1-position, rearranges to position 2. Simultaneously cleaves one of the acetal groups -OR ^ -OR ^ and the remaining one acetal

2 is a group of formula -OR in a compound of formula I wherein R is alkyl. Depending on the conditions used in the hydrolysis, particularly under strongly basic conditions, the resulting ester of formula I (a compound of formula I in which R is an alkyl group) is further hydrolyzed to a compound of formula I in which R is a hydrogen atom.

4

When hydrolyzing a compound of formula II in which R and R together form an alkylene group, the corresponding compound of formula I in which R is a hydroxyalkyl group is obtained.

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 for Ar are those of the formula R ¹ -Ar ¹ , in which Ar ¹ is a phenylene or naphthylene group and R 1 is a hydrogen atom, a halogen atom, a C 1-6 -alkyl group, a C 1-6 -alkoxy group, a C 1-6 -alkoxy group ₆ -haloalkyl, C 1-8 -alkanoylamino, oxoisoindolinyl or phenyl. Another preferred example of the aromatic group Ar is thienyl.

Suitable R ³ groups are C 1-6 -alkyl groups such as methyl, ethyl, n-propyl, iso -propyl or butyl. A preferred set of meanings for R ¹ are hydrogen C ₁ а _G-alkyl groups.

4

C 1-6 -alkyl groups are suitable as the alkyl groups represented by R and R respectively. l ”b o 4

Suitable alkylene groups formed by R and R together are a C 1-4 alkylene group such as ethylene, propylene and trimethylene.

Examples of preferred alkyl groups represented by R ⁵ include unsubstituted C 1-8 -alkyl groups such as methyl, ethyl, butyl, and further preferably D- or L-10-camphyl is preferred as R ⁵ . Substituted or unsubstituted phenyl are preferred as aromatic R groups

groups of the general formula _7 where 7 R represents a hydrogen atom, an atom halogen or C 1-6 -alkyl.

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

OR ³ OSO-R ⁵

I 1 ² 1 'hr - C - CH - R ¹ 4'

OR (1-1) in which

Ar ² represents a group of the formula R 1 -Ar ³ - or a thienyl group,

R ¹ 'is hydrogen or C ^ _G-alkyl,

R ³ a

R ⁴ 'independently represent C ^ g alkyl group or together represent a _C2 _22 ^"and lkylenovou group,

R ⁵ 'represents a C 1-8 -alkyl group of the general formula, a D- or L-10-camphoryl group or a C 1-6 -alkyl group;

and Ar 1, R and R ⁷ are as defined above.

In the compound of formula (II), Ar and R may form a fused ring together with the carbon atom to which they are attached. A particular example of compounds of formula II in which Ar and R ³ together form a fused ring is a compound of formula

Hydrolysis of these compounds by the method of the invention provides the following compound

of the general formula Ccr- ^C00R!

Compounds of formula Τ ': е can be prepared by synthesis from alpha-haloketones of formula V (J X

II. >

Ar - C - CH - R), in which:

X represents a halogen atom г ».

Ar and R are as described above, as shown in the following reaction scheme:

X ^OR3

II i i i <он 'i 1

Ar-C-CH-R------- ------ Ar-C-CH-R

R ⁵ -SO ² Hal or (R ⁵ SO ₂ ) ₂ O

Ar-C - CH-R ¹

X /

AND

OR (VI)

OM (VII)

In the above reaction scheme

M is an alkali metal,

Hal denotes a halogen atom, in particular a chlorine atom, and

3 4 5 г

Ar, R, R, R, R, and X have the above-mentioned knowledge.

Compounds of formula (V) may be readily prepared by providing a compound of formula (VIII)

X

R ¹ - TLI - COC1 (VIII), wherein

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

Ar - H where

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

I »J

Ar-C-CH ₂ -R where

Ar and R ^J Mejia as defined hereinbefore, which prov / Measuring known manner.

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 the oxidation of 1-acetoxy-1-alkene substituted in the 1-position by an aromatic group of the general formula XI wherein:

Ar, R 1 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, the process comprising acetalizing the corresponding alpha-sulfonyloxy ketone to a compound of formula II, and a method of reducing the alpha-oxoketone acetal of formula XII

(XII), where

Ar, R ¹ ,

4

R and R 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, alpha- (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 more detail.

Example 1

0.526 g of alpha- (p-toluenesulfonyloxy) propiophenone dimethylacetal and 0.150 g of calcium carbonate were heated under reflux for 72 hours in 10 ml of a 3: 7 mixture of methanol water. To the mixture was added 10 mL of water and extracted three times with 10 mL of diethyl ether. The extracts were washed with 10 ml of water and dried over anhydrous magnesium sulfate. Quantitative analysis of the product by gas chromatography (internal standard method) revealed that it contained 0.162 g of methyl 1-alpha-phenylpropionate.

Yield: 66%.

Example 2

1.75 g of .alpha .- (p-toluenesulfonyloxy) dimethyl acetal pr of iophenone and 0.500 g of calcium carbonate were refluxed in 33 ml of water / methanol (3: 7) for 72 hours. To the mixture was added 50 ml of water and extracted three times with 30 ml of diethyl ether. The extracts are washed with 30 ml of water and evaporated under reduced pressure to a volume of about 5 ml. 12 ml of methanol, 5 ml of water, 7 ml of 10% aqueous potassium hydroxide solution were added to the residue, and the mixture was heated under reflux for 5 hours. To the mixture was added 30 mL of water and washed 5 times with 20 mL of diethyl ether. The aqueous layer was adjusted to pH 1 with concentrated hydrochloric acid and extracted four times with 20 ml of diethyl ether. The extracts are washed with 20 ml of water, dried over anhydrous magnesium sulphate and evaporated under reduced pressure. 0.358 g of alpha-phenylpropionic acid is obtained in the form of a colorless oil. Yield 48%. This product fully agrees with the authentic sample in IC and NMR spectral data.

Examples 3 to 15

0.526 g of alpha- (p-toluenesulfonyloxy) propiophenone dimethylacetal and equimolar amounts of the individual bases listed in Table 1 are heated in an oil bath in 10 ml of each of the solvents listed in Table 1. 10 ml of water are added to the mixture and extracted 3 times with 10 ml of diethyl ether. . The extracts were washed with 10 ml of water and dried over anhydrous magnesium sulfate.

The product was analyzed for methyl alpha-phenylpropionate content by gas chromatography as in Example 1. &lt; tb &gt;

The results are shown in Table 1:

Example Solvent (ratio in mixture) Base Bath temperature (° C) Reaction time (h) Methyl alpha-phenylpropionate yield (%) 3 Dioxane: water (9: 1) с ₃ соок ¹¹⁰ 216 54.3 4 Dioxane: water (6: 4) CaCO ₃ 110 64 56.6 5 DMF: water (9: 1) * CH ₃ COOK 150 14 40.3 6 DMF: water (6: 4) CH ₃ COOK 150 14 55.6 7 DMF: water (6: 4) CaCO ₃ 100 ALIGN! 94 54.6 8 DMF: water (6: 4) CaCO ₃ 100 ALIGN! 72. 54.4 9 DMSO: water (6: 4) CaCO ₃ 100 ALIGN! 94 54.3 10 DMSO: water (4: 6) CaCO ₃ 100 ALIGN! 72 58.5 11 Anhydrous methanol - 15O ^(X) 7 34.2 12 Methanol: water (7: 3) CH ₃ COOK 110 72 60.8 13 Methanol: water (6: 4) CaCO ₃ 110 . ⁶⁴ 63.0 1 14 Methanol: water (4: 6) CaCO ₃ 110 72 33.3 15 Dec Acetic acid с ₃ соок 130 14 39.0

(x) heated in a 30 ml sealed tube.

Example 16

0.410 g of alpha- (p-toluenesulfonyloxy) -p-isobutylpropiophenone dimethyl acetal and 0.100 g of calcium carbonate were heated under reflux in a 3: 7 mixture of water and methanol for 22 hours. Water (15 ml) was added and the mixture was extracted with diethyl ether (3 x 10 ml). The extracts were washed with 10 ml of water, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The oily residue was purified by column chromatography (silica gel, methylene chloride) to give 0.180 g of methyl alpha- (4-isobutylphenyl) propionate as a colorless oil. Yield 81%. This product fully agrees with the authentic sample in IR and NMR spectral data.

Example 17

0.910 g of alpha- (p-toluenesulfonyloxy) -β-isobutylpropiophenone dimethylacetal and 1.25 g of potassium carbonate were refluxed in 26 ml of a 3: 7 mixture of water and methanol for 20 hours. Water (30 ml) was added and the mixture was washed with methylene chloride (4 x 10 ml). The aqueous layer was adjusted to pH 2 with dilute hydrochloric acid and extracted 4 times with 20 mL methylene chloride. The extracts were washed with 30 ml of water and dried over anhydrous magnesium sulfate. 0.335 g of alpha- (4-isobutylphenyl) propionic acid is obtained in the form of colorless crystals having a melting point of 71-75 ° C. Yield 7-3%. This product fully agrees with the authentic sample in IC and NMR spectral data.

Example 18

0.991 g of alpha- (methanesulfonyloxy) -β-isobutylpropiophenone dimethyl acetal and 0.300 g of calcium carbonate are heated under reflux for 72 hours in 10 ml of a 3: 7 mixture of water and methanol. Conventional work-up followed by alkaline hydrolysis of the crude product as in Example 2 afforded 0.519 g of alpha- (4-isobutylphenyl) propionic acid as colorless crystals with a melting point of 73-75 ° C. Yield 84%. This product fully agrees with the authentic sample in IR and NMR spectral data.

Example 19

2.12 g of alpha- (p-toluenesulfonyloxy) -p-methoxypropiophenone dimethyl acetal and 0.560 g of calcium carbonate were heated under reflux for 13 hours in 20 ml of a 3: 7 mixture of water and methanol. Conventional work-up followed by alkaline hydrolysis of the crude product as in Example 2 afforded 0.714 g of alpha- (4-methoxyphenyl) propionic acid as pale yellow crystals having a melting point of 47-50 ° C. Yield: 57%.

Example 20

0.735 g of alpha- (methanesulfonyloxy) -p- (tert-butyl) isovalerophenone dimethylacetal and 0.200 g of calcium carbonate are heated under reflux for 72 hours in 10 ml of a 3: 7 mixture of water and methanol. Conventional work-up as in Example 16 and purification by column chromatography (silica gel, methylene chloride) affords methyl alpha- (4- (tert-butyl) phenyl) isovalerate as a colorless oil.

IR (neat): 2965, 1745, 1165, 1025 cm ^-1 .

NMR (CDCl ₃ ): δ 0.71 (3H, d, J = 7Hz), 1.02 (3H, d, J = 7Hz, 1.32 (9H, s), 2.1-2.6) (1H, m), 3.10 (1H, d, J = 11Hz), 3.60 (3H, s), 7.1-7.4 (4H, m).

Analysis for ^C 24 ^H i6 ° ^2: 'Calculated: 77.37% C 9.74% H Found: 77.26% C, 9.62% H.

Example 21

0.668 g of alpha- (p-toluenesulfonyloxy) acetophenone ethylene acetal are dissolved in 8 ml of 1,3-dimethyl-2-imidazolidinone (DMI) and 200 mg of calcium carbonate and 0.2 ml of water are added. The mixture was heated to 180 ° C with stirring for 22 hours. After cooling, 30 ml of water are added and the mixture is extracted 3 times with 20 ml of diethyl ether. The extracts were washed twice with 10 ml of water and dried over anhydrous magnesium sulfate. The aqueous layers were combined and 4 mL of concentrated hydrochloric acid was added. The mixture was extracted three times with 20 ml diethyl ether, the extracts were washed twice with 10 ml water and dried over anhydrous magnesium sulfate. The evaporation residue under reduced pressure and the extracts obtained during neutralization and acidification are combined and 400 ml of potassium hydroxide are added. The mixture was refluxed for 16 hours in a mixture of 6 ml of methanol and 2 ml of water. After cooling, 30 ml of water are added and the mixture is washed 3 times with 20 ml of diethyl ether. The aqueous layer was acidified to about pH 2 with about 7 mL of 3.5% hydrochloric acid and extracted three times with 20 mL of diethyl ether. The extracts were washed with 10 ml of water, dried over anhydrous magnesium sulfate and evaporated under reduced pressure to give 92 mg of a residue. As found, this residue is a mixture of benzoic acid and phenylacetic acid, according to NMR and gas-liquid chromatography (GLC) of their methyl ester formed by treatment with diazomethane. NMR spectral data show that the mixture contains 65 mg (27% yield) of benzoic acid and 27 mg (10% yield) of phenylacetic acid.

Example 22

0.798 g of alpha- (p-bromobenzenesulfonyloxy) acetophenone ethylene acetal is dissolved in 8 ml of DM1 and 200 mg of calcium carbonate and 0.5 ml of water are added. The mixture was heated to 160 ° C with stirring for 18 hours. The reaction mixture was worked up in the same manner as in Example 21 and the crude product was subjected to alkaline hydrolysis. 84 mg of a semi-solid are obtained, which, according to NMR, is a mixture of benzoic acid and phenylacetic acid in a molar ratio of 7.0: 4.5. Accordingly, the mixture was determined to contain 49 mg (20% yield) of benzoic acid and 35 mg (13% yield) of phenylacetic acid.

Example 23

0.560 g of 1- (2-thienyl) -2- (methanesulfonyloxy) -1-oxopropane dimethylacetal and 0.200 g of calcium carbonate were refluxed for 42 hours in a 3: 7 mixture of water and methanol. Water (30 ml) was added and the mixture was extracted with diethyl ether (3 x 30 ml). The extracts were washed twice with 10 ml of water, dried over magnesium sulphate and evaporated under reduced pressure to give 316 mg of methyl (alpha- (2-thienyl) propionate) as a colorless oil. This product fully agrees with the authentic sample in IR and NMR spectral data. The yield is 93% (in crude form).

The crude oil is subjected to a single distillation at a temperature of 130 ° C (bath temperature) and at a pressure of 2 266 Pa. 279 mg of pure product are obtained. The yield is 82% (after purification).

The aqueous layers obtained by extraction were combined and 6 ml of concentrated hydrochloric acid were added. The mixture is extracted 3 times with 15 ml of diethyl ether, the extracts are washed twice with 10 ml of water, dried over anhydrous magnesium sulphate and evaporated under reduced pressure. 20 mg of alpha- (2-thienyl) -propionic acid are obtained as a colorless oil. Yield 6%. This product fully agrees with the authentic sample in IR and NMR spectral data.

Example 24

0.565 g of 1- (2-thienyl) -2- (methanesulfonyloxy) -1-oxopropane dimethyl acetal and 0.202 g of calcium carbonate were heated under reflux for 21 hours in 6 ml of a 3: 7 mixture of water and methanol. Sodium hydroxide (0.420 g) was added to the reaction mixture, and the mixture was stirred at room temperature for 15 hours and then heated under reflux for 2 hours. To the mixture was added 30 mL of water and washed with 20 mL of diethyl ether. 4 ml of concentrated hydrochloric acid are added to the aqueous layer and the mixture is extracted 3 times with 20 ml of diethyl ether. The extracts were washed with 10 ml of water, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. 0.299 g of alpha- (2-thienyl) propionic acid is obtained in the form of a colorless oil. Yield 95%.

Example 25

0.420 g of sodium hydroxide was dissolved in 6 ml of a 3: 7 mixture of water and methanol and 0.574 g of 1- (2-thienyl) -2- (methanesulfonyloxy) -1-oxopropane dimethylacetal was added. The mixture was heated to reflux for 21 hours. 40 ml of water are then added and the mixture is washed with 20 ml of diethyl ether. 3 ml of concentrated hydrochloric acid are added to the aqueous layer and the mixture is extracted 3 times with 20 ml of diethyl ether. The extracts were washed with 5 ml of water, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. 0.291 g of alpha- (2-thienyl) propionic acid is obtained as a colorless oil. Yield 91%.

Example 26

0.674 g of 1- (2-thienyl) -2- (p-toluenesulfonyloxy) -1-oxopropane dimethyl acetal and 0.200 g of calcium carbonate were heated under reflux for 12 hours in 10 ml of a 3: 7 mixture of water and methanol. Conventional work-up as in Example 16 yields an oily crude product which is subjected to a single distillation at a temperature of 110 to 120 ° C (bath temperature) and at a pressure of 50 psig. 0.253 g of methyl .alpha .- (2-thienyl) propionate is obtained as a colorless oil. Yield 79%.

Example 27

0.684 g of 1- (2-thienyl) -2- (benzenesulfonyloxy) -1-oxopropane dimethylacetal and 0.200 g of calcium carbonate were heated under reflux for 8 hours in 10 ml of a 3: 7 mixture of water and methanol. The usual work-up as in Example 16 yields an oily crude product which is subjected to a single distillation at 110 ° C (bath temperature) and 2 kPa. 0.277 g of methyl alpha- (2-thienyl) propionate is obtained. Yield 81%.

Example 28

0.299 g of alpha - (methanesulfonyloxy) -? - acetylaminopropiophenone dimethylacetal and 0.090 g of calcium carbonate were heated under reflux for 3 hours in 3 ml of a 3: 7 mixture of water and methanol. Water (30 ml) was added and the mixture was extracted with methylene chloride (3 x 20 ml). The extracts were washed with 10 ml of water, dried over magnesium sulphate and evaporated under reduced pressure to a crystalline residue which was purified by column chromatography (silica gel, methylene chloride-diethyl ether). 0.186 g of methyl .alpha .- (4-acetylaminophenyl) propionate is obtained in the form of colorless crystals. Yield 93%.

Melting point: 107 to 109 ° C (from ethanol and hexane).

IC (KBr): 1740, 1665, 1610, 1555, 1515, 1415, 1330, 1160, 860, 840 cm ^-1 .

NMR (CDCl ₃ ): δ 1.46 (3H, d, J = 7Hz), 2.11 (3H, s), 3.64 (3H, s), 3.67 (1H, q, J). = 7 Hz), 7.17 (2H, d, J = 8 Hz), 7.53 (2H, d, J = 8 Hz), 8.17 (1H, broad s).

Analysis for ^C 15 ^H I2 ^NO3: Calculated: 65.14% C 6.83% H 6.33% N Found: 64.94% C, 7.00% H, 6.27% N.

Example 29

0.329 g of alpha- (benzenesulfonyloxy) -p-isobutylpropiophenone dimethyl acetal and 0.10 g of calcium carbonate are heated under reflux for 10 hours in 10 ml of a mixture of water and methanol.

3 in a weight ratio of 3: 7. Working up analogously to Example 28 and purification by column chromatography (silica gel, methylene chloride) afforded C, 181 g of methyl alpha- (4-isobutylphenyl) propionate as a colorless oil. Yield: 82%.

Example 30

0.392 g of .alpha .- (benzenesulfonyloxy) -. Beta.-isobutylpropiophenone dimethyl acetal are heated in 4 ml of a 1: 3 mixture of water and pyridine in an oil bath at 100 DEG C. for 19 hours. Work-up as in Example 28 and purification by column chromatography (silica gel, methylene chloride) gave 0.164 g of methyl alpha- (4-isobutylphenyl) propionate as a colorless oil. Yield 74%.

Example 31

0.392 g of alpha- (benzenesulfonyloxy) -p-isobutylpropiophenone dimethyleacetal is mixed with 10 ml of a 3: 7 mixture of water and methanol and 2 ml of a 10% aqueous potassium hydroxide solution and refluxed for 9 hours. To the mixture was added 30 mL of water and washed 4 times with 15 mL of methylene chloride. The aqueous layer was adjusted to pH &lt; 1 with concentrated hydrochloric acid and extracted 4 times with 15 ml of methylene chloride. The extracts were dried over anhydrous magnesium sulphate and evaporated under reduced pressure. 0.138 g of alpha- (4-isobutylphenyl) propionic acid is obtained in the form of colorless crystals, m.p. 73-75 ° C. Yield 67%.

Example 32

Alpha (p-toluenesulfonyloxy) propiophenone diethyl acetal (0.150 g) and calcium carbonate (0.05 g) were heated under reflux in water (3: 7, 10 ml) for 72 hours. 20 ml of water are added and the mixture is extracted 4 times with 5 ml of diethyl ether and dried over anhydrous magnesium sulfate. Quantitative analysis by gas chromatography (internal standard method) showed that the product contained 23 mg of ethyl alpha-phenylpropionate. Yield 32%.

Example 33

0.978 g of alpha- (methanesulfonyloxy) -p-fluoropropiophenone dimethyl acetal and 0.33 g of calcium carbonate are heated under reflux for 24 hours in 15 ml of a 3: 7 mixture of water and methanol. Work-up and purification as in Example 29 gave 0.454 g of methyl alpha- (4-fluorophenyl) propionate as a colorless oil. Yield 76%.

IC (neat): 1744, 1 607, 1 513, 1 460, 1 439/1 340, 1 230, 1 210, 1 170, 1 160, 840, 796 cm 1.

NMR (CDCl ₃ ): δ 1.46 (3H, d, J = 7 Hz), 3.60 (3H, s,), 3.67 (1H, q, J = 7 Hz), 6.8 to 7 4 (4H, m).

Example 34

0.490 g of 1- (6-methoxy-2-naphthyl) -2- (methanesulfonyloxy) -1-oxopropane dimethylacetal and 0.140 g of calcium carbonate were heated under reflux for 5 hours in 10 ml of a 1: 4 mixture of water and dimethylformamide. . 20 ml of water are added and extracted 4 times with 7 ml of methylene chloride. The extracts were washed 4x with 10 ml of water, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The residue was purified by column chromatography (silica gel, methylene chloride). 0.323 g of methyl alpha- (6-methoxy-2-naphthyl) propionate is obtained in the form of colorless crystals, m.p. 65-68 ° C. Yield 94%. This product fully agrees with the authentic sample in IC and NMR spectral data.

Example 35

0.354 g of 1- (6-methoxy-2-naphthyl) -2-methanesulfonyloxy-1-oxopropane dimethyl acetal and 0.10 g of calcium carbonate were heated under reflux for 28 hours in 8 ml of a 3: 7 mixture of water and methanol. 20 ml of water are added and the mixture is extracted 3 times with 10 ml of methylene chloride. The extracts were washed with 20 ml of water, dried over anhydrous magnesium sulphate and evaporated under reduced pressure. 0.178 g of methyl .alpha .- (6-methoxy-2-naphthyl) propionate is obtained as colorless crystals. Yield 73%.

Example 36> One of two possible diastereomers of 1- (6-methoxy-2-naphthyl) -2- (D-10-camphorsulfonyloxy) -1-oxopropane dimethyl acetal (m.p. 102-105 ° C, = +32.5) was prepared. 170 mg of this diastereomer and 40 mg of calcium carbonate are heated in a 110 DEG C. bath for 14 hours in 5 ml of a 1: 4 mixture of water and dimethylformamide, and 20 ml of water are added. The extracts were washed with water (4.times.10 ml), dried over anhydrous magnesium sulphate and evaporated under reduced pressure to give a residue which was purified by column chromatography (silica gel, methylene chloride) to obtain 68 mg of methyl - (-) - .alpha. (6-methoxy-2-naphthyl) propionate as colorless crystals in 80.2% yield.

Melting point: 94.5 to 95 ° C, [α] 2 D = -78.2 °, c = 1, chloroform).

IC (KBr): 2970, 1739, 1660, 1450, 1334, 1270, 1231, 1 205, 1172, 1158, 1028, 893, 856, 823 cm ^-1 .

The NMR spectral data of the product was consistent with the methyl alpha- (6-methoxy-2-naphthyl) propionate obtained in Example 34,

Example 37

1.007 g (3.308 mmol) of 1- (4-methoxyphenyl) -2-methanesulfonyloxy-1-oxopropane dimethylacetal and 330 mg (3.30 mmol) of calcium carbonate were refluxed in 10 ml of a mixture of water and methanol for 20 hours 3: 7. Work-up and purification as in Example 29 afforded 597 mg of methyl alpha- (4-methoxyphenyl) propionate as a colorless oil. Yield 92.9%.

NMR (CDCl ₃ ): δ 1.47 (3H, d, J = 7Hz, 3.61 (3H, s), 3.67 (1H, q, J = 7Hz), 3.73 (3H, s) 6.83 (2H, d, J = 9Hz), 7.19 (2H, d, J = 9Hz).

Example 38

1,922 (5,000 mmol) of 1- (4-chlorophenyl) -2- (p-toluenesulfonyloxy) -1-oxopropane dimethylacetal and 500 mg (5.00 mmol) of calcium carbonate are heated to 110 ° C (bath temperature) with stirring 3 days in a 4: 1 mixture of dimethylformamide and water. The usual work-up as in Example 16 gave 337 mg of a colorless oil. The oil was found to contain 238 mg of methyl .alpha .- (4-chlorophenyl) propionate by NMR spectroscopy. Yield 12%.

Example 39

In the same manner as in Example 28, 1- (4-) 1-oxo-2-isoindolinyl (phenyl) -2-methanesulfonyloxy-1-oxopropane methyl alpha- (4 -) - 1-oxo-2-isoindolinyl was prepared from dimethyl acetal (phenyl) propionate as colorless crystals. Yield 86%.

Example 1 a d 40

From 1- (4-biphenylyl) -2-methanesulfonyloxy-1-oxopropane dimethyl acetal, methyl alpha- (4-biphenylyl) propionate was prepared as a colorless oil in a similar manner to Example 1. The yield is 80.5% (calculated on 1- (4-biphenylyl) -2-hydroxy-1-oxopropane diniethylacetal).

NMR (CDCl ₃ ): δ 1.47 (3H, d, J = 7 Hz), 3.55 (3H, s), 3.68 (1H, q, J = 7 Hz), 7.1 to 7, 56 (9 H, m).

IC (neat): 1741, 1490, 1215, 1167, 765, 701 cm ^-1 .

Example 41.

Methyl (indane-1-carboxylate) was prepared from 1,1-dimethoxy-2-methanesulfonyloxy-1,2,3,4-tetrahydronaphthalene in a similar manner to Example 34. Yield 4%.

Example 42

In a similar manner to Example 34, methyl alpha- (4-difluoromethoxyphenyl) propionate was prepared from 1- (4-difluoromethoxyphenyl) -2-methanesulfonyloxy-1-oxopropane dimethyl acetal in 51% yield.

IC (neat): 1,745, 1,515, 1,385, 1,230, 1,160, 1,130, 1,050 cm ^-1 .

NMR (CDCl ₃ ): δ 1.46 (3H, d, J = 7Hz), 3.61 (3H, s), 3.67 (1H, q, J = 7Hz), 6.43 (1H, t, J = 74 Hz), 7.02 (2H, J = 9Hz), 7.26 (2H, J = 9Hz).

Example 43

0.368 g of 1- (4-difluoromethoxyphenyl) -2-methanesulfonyloxy-3-methyl-1-oxobutane dimethylacetal and 0.100 g of calcium carbonate are heated under reflux in 3 ml of a 3: 7 mixture of water and methanol for 18 hours. days. Conventional work-up followed by chromatography affords 0.132 mg of methyl alpha- (4-difluoromethoxyphenyl) isovalerate as a colorless oil. Yield 51%.

NMR (CDCl 3: δ 0.71 (3H, d, J = 7Hz), 1.02 (3H, d, J = 7Hz), 2.0-2.5 (1H, m),

3.14 (1H, d, J = 11Hz), 3.63 (3H, s,), 6.47 (1H, t, J = 74Hz), 7.02 (2H, d, J = 9Hz) 7.31 (2H, d, J = 9Hz).

Example 44

0.368 g of 1- (4-difluoromethoxyphenyl) -2-methanesulfonyloxy-3-methyl-1-oxobutane and 0.100 g of calcium carbonate are heated to 110 DEG C. in a 3 ml solvent mixture consisting of water and dimethylformamide (1: 4 by weight). for 12 days and then refluxed for 3 days. After customary working-up and separation, 78 mg of methyl .alpha .- (4-difluoromethoxyphenyl) isovalerate is obtained. Yield 30%.

Example 45 _t ¹

In 7 ml of a 3: 7 mixture of water and methanol, 724 mg of 1- (4-ethoxyphenyl) -2-methanesulfonyloxy-3-methyl-1-oxobutane dimethylacetal and 200 mg of calcium carbonate are refluxed for 11 hours. After usual work-up and purification, 467 mg of methyl alpha- (4-ethoxyphenyl) isovalerate is obtained as a colorless oil. Yield 99%.

Boiling point: 160 ° C (bath temperature) / 2.266 kPa.

NMR (CDCl ₃ ): δ 0.70 (3H, d, J = 6Hz), 1.01 (3H, d, J = 6Hz), 1.38 (3H, t, J = 7Hz) 1), 2.0-2.6 (1H, m), 3.07 (1H, d, J = 10Hz), 3.30 (3H, s), 3.97 (2H, q, J = 7Hz) 6.80 (2H, d, J = 9Hz), 7.20 (2H, d, J = 9Hz).

Analysis for ^C 20 ^H I4 ° ^3: calculated: 71.16% C, 8.53 '% H Found: 70.93% C, 8.52% H.

Example 46

In a similar manner to Example 45, 1- (4-methoxyphenyl) -2-methanesulfonyloxy-3-methyl-1-oxobutane dimethyl acetal gave methyl alpha- (4-methoxyphenyl) isovalerate as a colorless oil. Yield 94%.

IR (neat): 1,740, 1,515, 1,255, 1,160, 1,040, 830 cm ^-1 .

NMR (CDCl ₃ ): δ 0.70 (3H, d, J = 6Hz), 1.00 (3H, d, J = 6Hz), 2.0-2.6 (1H, m),

3.08 (1H, d, J = 10Hz), 3.63 (3H, s), 3.78 (3H, s), 6.80 (2H, d, J = 9Hz), 7.21 (3H, s) 2H, d, J = 9Hz).

Example 1 a d 47 ’

In 5 ml of a 3: 7 mixture of water and methanol, the mixture was heated to reflux

495 mg of 1- (4-methoxyphenyl) -2-methanesulfonyloxy-3-methyl-1-oxobutane ethylene acetal and 150 mg of calcium carbonate for 148 hours. The usual work-up followed by column chromatography purification gave 307 mg of 2-hydroxyethyl-alpha- (4-methoxyphenyl) isovalerate as a colorless oil. Yield 81%.

IR (neat): 3,600-3,200, 1,735, 1,610, 1,510, 1,255, 1,170, 1,160, 1,035, 830 cm ^-1 .

NMR (CDCl ₃ ): δ 0.70 (3H, d, J = 7Hz), 1.03 (3H, d, J = 7Hz), 2.0-2.5 (1H, m),

2.27 (1H, broad s), 3.13 (1H, d, J = 10 Hz), 3.5-3.8 (2H, m), 3.76 (3H, s), 4.0- 4.3 (2H, m), 6.81 (2H, d, J = 9Hz), 7.21 (2H, d, J = 9Hz).

Example 48

555 mg of 1- (6-methoxy-2-naphthyl) -2- (L-10-camphorsulfonyloxy) -1-oxopropane dimethyl acetal diastereomer was reacted in the same manner as in Example 36 to give 249 mg of methyl (+) - alpha - (6-methoxy-2-naphthyl) propionate.

Yield: 90%, [.alpha.] D = + 75.0 DEG (c = 0.949, chloroform).

In IR and NMR spectral data, the product obtained is consistent with the product obtained in Example 36.

Example 49

Br ^H ₂ ^SO 4

1- (5-bromo-6-methoxy-2-naphthyl) -2-methylsulfonyloxy-1-oxopropane neopentene acetal (14.8 mmol) and basic IRC-50 wet resin (4 g) were charged to a pressure reactor. 144 ml of acetone and 48 ml of water are added, the reaction mixture is heated to 120 ° C, under a pressure of 50 psi for 8 h. Thin layer chromatography showed approximately 95% conversion to 2-hydroxymethyl-2-methylpropyl-2- (5-bromo-6-methoxy-2-naphthyl) propionate. Acetone was removed and the resulting slurry was charged to a pressure reactor. The solvent ratio is adjusted to 48 ml water / 150 ml acetone. 7 ml of concentrated sulfuric acid are added and the mixture is stirred at 80 DEG C., at a pressure of 20 psig for 20 h. The aqueous solution was separated and 2- (5-bromo-6-methoxy-2-naphthyl) propionic acid was precipitated with concentrated hydrochloric acid to give 3.35 g of the acid.

2- (5-bromo-6-methoxy-2-naphthyl) propionic acid, m.p. Mp 167-170 ° C.

Recrystallization of the acetone / water fraction (residue) yielded a white crystalline product of neopentylene acetal-1- (5-bromo-6-methoxy-2-naphthyl) -2-methylsulfonyloxy-1-oxopropane in 57.6% yield.

Claims (16)

SUBJECT OF THE INVENTION A process for producing alkanoic acids substituted in the alpha position by an aromatic group or esters thereof, having the general formula I Ar-1h-COOR ² wherein Ar is a 1-oxo-2-isoindolinyl group, b) a naphthyl group optionally substituted by a C 1-8 alkoxy group; or -alkoxy and halogen; or c) a thienyl group, R ¹ represents a hydrogen atom or a 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 ² is hydrogen, C - ^ - alkyl or C₁₋₄ -hydróxyalkylovou group, characterized in that the alpha-Sulphonyloxy acetal of the formula II (II) in which Ar and R ¹ have the abovementioned meaning, R ³ and R ⁴ independently represent a C - ^ - alkyl, or together represent C ₂ _ ₆ ~ -alkylene R represents a C _1-6 -alkyl group, a phenyl group which is optionally substituted by a halogen atom or a C 1-6 -alkyl group, or a camphoryl group, subjected to hydrolysis. 2. Process according to claim 1, characterized in that the hydrolysis is carried out at a temperature of 0 to 10 ° C 250 ° C, preferably at 50 to 180 ° C. 3. The process according to claim 1, wherein the hydrolysis is carried out in an inert solvent such as dimethylformamide, dimethylsulfoxide, 1,3-dimethyl-2-imidazolidinone. 1,4-dioxane, tetrahydrofuran, diethylene glycol dimethyl ether, hexamethylphosphoric triamide, 1,2-dimethoxyethane, pyridine, methanol, ethanol, ethylene glycol and acetic acid. 4. A method according to claim 1, characterized in that the basic medium is used. 5. The method of claim 1, 6. A process according to claim 5, characterized in that it is equivalent to 1 mole of the compound of formula II. 7. A process according to claim 1, wherein Ar is 6-methoxy-: And the groups R, R and R are as defined in the point that the hydrolysis is carried out in neutral or That the hydrolysis is carried out in the presence of a base. that the base is used in an amount of at least 1 By using alpha-sulfonyloxy ketone acetal: -naphthyl, R * is methyl 1. 8. A process according to claim 1, wherein the acetal of an alpha-sulfonyloxy ketone of the formula II wherein Ar is a 4-isobutylphenyl group, R1 is a methyl group And R, R and R are as defined in point 1. 9. A method according to claim 1, wherein the acetal of the 1α-sulfonyloxy ketone of formula (II) wherein Ar is a 4-C1-alkoxyphenyl group, R1 is isopropyl The groups aR, R and R are as defined in point 1. 10. The method of claim 1, wherein the acetal-alpha Sulphonyloxy of formula II wherein Ar is 4-C ₁ _ _{4-alkoxyphenyl} group, R ¹ represents methyl and R ^3, R ⁴ and R ^S have the meaning given in point 1. 11. The method according to claim 1, characterized in that the acetal .alpha.-Sulphonyloxy of formula II wherein Ar is 4-difluoromethoxy, R ¹ represents an isopropyl group and R ^3, R ⁴ and R ⁵ are as defined in point 1. * 12. The method according to claim 1, characterized in that the acetal used ве alpha Sulphonyloxy of formula II wherein Ar is 2-thienyl group, R ¹ represents a methyl group And R, R and R are as defined in point 1. 13. The method according to claim 1, characterized in that the acetal .alpha.-Sulphonyloxy formula II in which Ar represents a 4-acetylaminophenyl group, R₁ represents methyl and R ^3, R ⁴ and R ⁵ are as defined in point 1. 14. The method according to claim 1, characterized in that the acetal .alpha.-Sulphonyloxy of formula II wherein Ar is 4- (l-oxo-2-isoindolinyl) phenyl group, R ¹ represents methyl and R ^3, R ⁴ and R ⁵ have the meaning given in point 1. 15. The method according to claim 1, characterized in that the acetal .alpha.-Sulphonyloxy of formula II wherein Ar is 4-biphenylyl, R ¹ <= methyl and R ^3, R ⁴ and R ⁵ are as defined in 1. 16. A process according to claim 1, wherein the alpha-sulfonyloxy ketone of formula (II) wherein Ar is a 4- (tert-butyl) phenyl group, R &lt; 1 &gt; is isopropyl And R, R and R are as defined in point 1.