FR2700164A1 - Hydrolysis of furanose alpha-halo ester(s) - Google Patents

Abstract

Hydrolysis of a furanose alpha-halo ester (I) is effected by treatment with an alkali metal hydroperoxide (II) in an aq. organic medium. The process is esp. useful for preparing (S)-2-chloropropionic acid, which is an intermediate for (R)-2-aryloxypropionic acid herbicides. Hydrolysis is effected rapidly without racemisation, giving high yields (e.g. 63-79%) of alpha-halo acids with high optical purity (e.g. 70-95% ee).

Description

HYDROLYSIS PROCESS FOR CARBOXYL ESTERS
a-SUBSTITUES a-CHIRAUX.

 The present invention relates to a process for the hydrolysis of? -Substituted? -Chiral carboxylic esters for the preparation of? -Substituted? -Substituted carboxylic acids. In particular, the invention relates to the hydrolysis of α-chiral carboxylic esters substituted at the α-position by a halogen atom and derived from a furanose derived from a sugar, in order to obtain α-chiral α-halogenated carboxylic acids. and more preferably, optically active 2-halogenopropionic acids.

For twenty years, we have tried to control the stereochemistry of chemical reactions. Obtaining an enantiomerically pure molecule is motivated by the fact that the biological activity of a compound can be intimately related to its enantiomeric purity. Thus, 2-chloropropionic acid is a key intermediate in the synthesis of important herbicides such as (R) -2aryloxypropionic acids and their derivatives. The interest of selectively preparing the form
R is that said compound is active at doses less than half the corresponding racemic compounds. This gives rise to a major interest in safeguarding the environment.

dans laquelle R représente un radical méthyle, isopropyle, n-butyle ou isobutyle et R* représente le motif suivant:

- puis à saponifier le chloro-2 ester obtenu par l'hydroxyde de lithium, dans un mélange acétonitrile, ligroïne et eau en quantités volumiques égales.L. Duhamel et al have described in Synlett, p.807, November 1991, the preparation of optically enriched 2-chloroalkanoic acids of (S) f configuration by a process which consists of: chlorinating with N-chlorosuccinimide a silylated ketene acetal of formula:

in which R represents a methyl, isopropyl, n-butyl or isobutyl radical and R * represents the following unit:

and then saponifying the chloro-2 ester obtained with lithium hydroxide in an acetonitrile, ligroin and water mixture in equal volume amounts.

avec le chlorure de triméthylsilyle, en présence de diisopropylamidure de lithium.The silylated ketene acetal is obtained by reaction of:

with trimethylsilyl chloride in the presence of lithium diisopropylamide.

 Said process makes it possible to obtain a (S) -2-chloroalkanoic acid with a yield expressed relative to the ester represented above, of 65-72% but the enantiomeric excess caps at 90%.

 It has now been found and this is the object of the present invention, a method of hydrolysis faster than the previous, non-racemizing, with conservation of the configuration.

 The subject of the present invention is therefore a process for the hydrolysis of an α-halogenated ester derived from a furanose derived from a sugar, characterized in that it consists in hydrolysing said ester with an alkali metal hydroperoxide, in the medium hydro-organic.

 This method was used by D.A. EVANS, T.C. BRITTON and J.A.

Ellman (Tetrahedron Letters, 1987, 28, 6141) for the hydrolysis of amides was said to be ineffective for the hydrolysis of normal esters.

dans laquelle les différents symboles représentent:
- R représente un radical hydrocarboné ayant de 1 à 40 atomes de carbone
qui peut être un radical aliphatique, saturé ou insaturé, linéaire ou ramifié
un radical cyclique, saturé, insaturé ou aromatique, monocyclique ou
polycyclique ; un radical cycloaliphatique- ou arylaliphatique, saturé ou
insaturé, linéaire ou ramifié; un atome d'halogène, de préférence un atome
de fluor, de chlore ou de brome,
- R* représente un radical dérivé d'un motif tétrahydrofuranyle,
- X représente un atome d'halogène, de préférence un atome de chlore ou
de brome différent de R, - avec un hydroperoxyde de métal alcalin, en milieu hydro-organique. More specifically, the process of the invention consists in reacting: an α-chiral α-halogenated ester corresponding to the following formula (I):

in which the different symbols represent:
R represents a hydrocarbon radical having from 1 to 40 carbon atoms
which may be an aliphatic radical, saturated or unsaturated, linear or branched
a cyclic radical, saturated, unsaturated or aromatic, monocyclic or
polycyclic; a cycloaliphatic or arylaliphatic radical, saturated or
unsaturated, linear or branched; a halogen atom, preferably an atom
fluorine, chlorine or bromine,
R * represents a radical derived from a tetrahydrofuranyl unit,
X represents a halogen atom, preferably a chlorine atom or
bromine other than R, with an alkali metal hydroperoxide, in a hydro-organic medium.

 The a-chiral α-halogenated esters which are more particularly involved in the process of the invention correspond to formula (I) in which R represents an aliphatic radical or a cycloaliphatic or arylaliphatic radical.

 More specifically, R may represent an alkyl, alkenyl, alkadienyl or alkynyl radical, linear or branched, preferably having from 1 to 24 carbon atoms.

dans ces formules R5 représente l'hydrogène ou un radical alkyle linéaire ou ramifié ayant de 1 à 4 atomes de carbone, de préférence, un radical méthyle ou éthyle,
- et/ou porteuse de l'un des substituants suivants:

dans ces formules, R5 ayant la signification donnée précédemment.The hydrocarbon chain can be optionally:
- interrupted by one of the following groups:

in these formulas R5 represents hydrogen or a linear or branched alkyl radical having from 1 to 4 carbon atoms, preferably a methyl or ethyl radical,
and / or carrier of one of the following substituents:

in these formulas, R5 having the meaning given above.

 The acyclic aliphatic, saturated or unsaturated, linear or branched may optionally carry a cyclic substituent. By ring is meant a saturated, unsaturated or aromatic carbocyclic ring, for example a cyclohexyl, phenyl or naphthyl radical.

dans ces formules R5 ayant la signification donnée précédemment.The acyclic aliphatic residue may be linked to the ring by a valency bond or by one of the following groups:

in these formulas R5 having the meaning given above.

 Among the aliphatic radicals optionally substituted by a ring, the preferred radicals are the following: a linear or branched alkyl radical having from 1 to 12 carbon atoms, a cycloalkylalkyl radical preferably having from 1 to 4 carbon atoms in the alkyl chain; a phenylalkyl radical having, preferably, from 1 to 4 carbon atoms in the alkyl chain.

 The a-chiral α-halogenated esters which are more particularly involved in the process of the invention correspond to formula (I) in which R represents a cycloaliphatic radical, saturated, unsaturated or aromatic, monocyclic or polycyclic, preferably bicyclic.

 As more specific examples of carbocyclic R radicals, there may be mentioned, inter alia: an optionally substituted cycloalkyl radical preferably having from 5 to 7 carbon atoms, an optionally substituted phenyl radical, an optionally substituted naphthyl radical.

 The present invention does not exclude the presence of substituents on any ring intervening in the radical R, insofar as these do not interfere at the level of the hydrolysis reaction. As examples of substituents which may be carried by the ring, mention may be made, inter alia, of linear or branched alkyl radicals, preferably having from 1 to 4 carbon atoms, the linear or branched alkoxy radicals preferably having from 1 to at 4 carbon atoms.

 As examples of preferred R radicals, mention may be made of the following radicals: the methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl radicals, the cyclohexyl radical, the phenyl or tolyl radicals; , xylyl or naphthyl optionally carrying linear or branched alkyl radicals having 1 to 4 carbon atoms or alkoxy radicals having 1 to 4 carbon atoms, - benzyl or phenylethyl radicals.

 Among all the aforementioned R radicals, the invention is particularly applicable to compounds of formula (I) in which R represents a linear or branched alkyl radical having from 1 to 12 carbon atoms and preferably from 1 to 4 carbon atoms .

dans ladite formule (Il) - R1, R2, identiques ou différents, représentent un radical alkyle linéaire ou ramifié ayant de 1 à 12 atomes de carbone, un radical cyclohexyle, un radical phényle ou un radical benzyle, - R3, R4, identiques ou différents, représentent un radical alkyle linéaire ou ramifié ayant de 1 à 12 atomes de carbone, un radical cyclohexyle, un radical phényle ou un radical benzyle - les radicaux R1 et R2 d'une part, R3 et R4 d'autre part, peuvent former ensemble un cycle à 5 chaînons (dioxolanne) ou à 6 chaînons (1,4-dioxanne).As regards the radical R * involved in α-chiral halogen compounds, it comprises the furanose unit derived from a sugar. II represents more particularly a radical corresponding to the following formula (II):

in said formula (II) - R1, R2, which may be identical or different, represent a linear or branched alkyl radical having from 1 to 12 carbon atoms, a cyclohexyl radical, a phenyl radical or a benzyl radical, - R3, R4, which are identical or different, represent a linear or branched alkyl radical having 1 to 12 carbon atoms, a cyclohexyl radical, a phenyl radical or a benzyl radical - the radicals R1 and R2 on the one hand, R3 and R4 on the other, can form together a 5-membered (dioxolane) or 6-membered (1,4-dioxane) ring.

 The furanose motif can be derived from glucose but also from many other sugars such as allose, altrose, mannose, galactose, talose, gulose, idose, ribose, arabinose, xylose and lyxosis.

 The preferred motif chosen in the process of the invention is derived from glucose.

The preferred radical R * is therefore the following:

par réaction dudit acétal avec un N-halogénosuccinimide (N-bromosuccinimideou N-chlorosuccinimide) dans un solvant organique.Examples of α-chiral α-halogenated esters preferably used in the process of the invention include, in particular, esters derived from a furanose unit bearing a free OH in position 3 and one of the alkanoic acids a. -halogenated compounds: - 2-chloropropionic acid - 2-bromo-propionic acid - 2-chlorobutanoic acid - 2-bromo-butanoic acid - 2-chloro-3-methyl-butanoic acid - I 2-bromo-3-methyl-butanoic acid - 2-chloro-3,3-dimethyl-butanoic acid - 2-bromo-3,3-dimethyl-butanoic acid - 2-chloro hexanoic acid - 2-bromoacid acid hexanoic acid - 2-chloro-4-methylpentanoic acid - 2-bromo-4-methylpentanoic acid
A preferred mode of synthesis of α-chiral α-halogenated esters of formula (I) as starting materials in the process of the invention consists in selectively halogenating an O-silyl ketene acetal corresponding to the following formulas:

by reacting said acetal with N-halosuccinimide (N-bromosuccinimide or N-chlorosuccinimide) in an organic solvent.

 In formulas (III) or (III) 'of said acetals, R and R * have the meaning given above and the different radicals R6, which may be identical or different, represent a hydrocarbon radical. Preferably, R6 represents a linear or branched alkyl radical having 1 to 4 carbon atoms or a phenyl radical.

Preferably, R6 represents a methyl radical.

 The acetal ketene concentration is advantageously between 0.05 and 0.5 M.

 The amount of halogenating agent, expressed as the molar ratio between the halogenating agent and the ketene acetal, may be in the range of from 1 to 3.0, and is preferably in the region of 1.5.

The halogenation reaction is conducted in an organic solvent which preferably does not exhibit too high polarity. Suitable organic solvents are preferably those whose dielectric constant (measured at 25 ° C.) is less than or equal to 10. As examples of solvents, mention may be made, inter alia, of dichloromethane, trichloromethane, carbon tetrachloride, toluene, diethyl ether, tetrahydrofuran,
Ethyl acetate.

 The temperature of the reaction is chosen between -10 ° C and -100 ° C, preferably between -70 ° C and -90 ° C.

 The halogenating agent is preferably introduced in solid form.

 With regard to O-silyl ketene acetals, they are known products described in the literature. They can be synthesized according to the procedure used by L. DUHAMEL et al (loc cit).

 Said method consists in carrying out the following steps: step 1: coupling at 20 ° C. of the carboxylic acid of formula R-CH 2 -COOH with the chiral auxiliary R * OH, with dicyclohexylcarbodiimide (DCC) and in the presence of a catalytic amount (10%) of N, N-dimethylaminopyridine in dichloromethane medium; step 2: reaction of the obtained ester R-CH 2 -COOR * with a silicon compound of formula (R 6) 3 SiCl at -70 ° C. in the presence of a base (a lithium amide and preferably lithium diisopropyl amide) making it possible to obtain the O-silylated ketene acetal corresponding to formulas (III) and (III) '.

 According to the process of the invention, an α-halo a-ch iraI ester is hydrolyzed in the presence of an alkali metal hydroperoxide.

 As regards the alkali metal hydroperoxide, it is preferable to use hydroperoxides of sodium, potassium or lithium. Most preferably, lithium hydroperoxide is selected.

 According to a preferred embodiment of the invention, the alkali metal hydroperoxide is formed in situ from the alkali metal hydroxide and hydrogen peroxide.

 The amount employed of the alkali metal hydroperoxide expressed relative to the bonded ester of formula (I) is generally at least equal to the stoichiometry of the reaction.

 When it is expressed by the molar ratio between the alkali metal hydroperoxide and the bonded ester of formula (I), it may vary between 2 and 8.

 The hydrogen peroxide used according to the invention is a commercial aqueous solution.

 The concentration of the hydrogen peroxide solution is not critical in itself. An aqueous solution of hydrogen peroxide having a weight concentration ranging from 20% to 50% and preferably to 30% is generally used.

 The amount of hydrogen peroxide expressed by the molar ratio between the hydrogen peroxide and the bonded ester of formula (I) can vary between 4 and 8.

 The reaction is advantageously carried out in a hydro-organic medium.

 The volume ratio between water and the organic solvent may vary, for example, from 0.3 to 3.0.

 The choice of the organic solvent and the water / organic solvent ratio is determined in such a way that the reaction medium obtained is homogeneous.

 It is preferable to use a polar organic solvent.

As examples of organic solvents that are suitable for the present invention, mention may be made more particularly of: oxygenated heterocyclic solvents, such as, in particular, dioxane, tetrahydrofuran, dioxolane, aliphatic alcohols such as methanol, propanol, butanol, pentanol,
Ethylene glycol.

ketones such as acetone, methyl ethyl ketone, diethyl ketone, tetramethylene sulfone (sulfolane), ethers and more particularly dimethyl ethers derived from ethylene oxide or propylene oxide, such as 1,2-dimethoxyethane, 1,5-dimethoxy-3-oxa-pentane, 1,8-dimethoxy-3,6-dioxa-octane, 1,1-dimethoxy-3,6,9-trioxetecane.

monomethyl, monoethyl, monopropylic and monobutyl ethers of ethylene glycol sold under the trade name Cellosolves,
It is possible to use a mixture of organic solvents.

 The concentration of the ester of formula (I) in the reaction solvent (water + organic solvent) is such that it varies between 0.001 and 1 mole / liter, preferably between 0.01 and 0.1 mole / liter.

 As for the temperature of the hydrolysis reaction, it is advantageously chosen between -10 ° C. and 25 ° C.

According to a practical embodiment of the invention, the ester is introduced into the reaction solvent (water + organic solvent). The reaction medium is brought to the chosen temperature, then the hydrogen peroxide is introduced and, finally,
The alkali metal hydroxide.

 It is essential that, at the end of the reaction, the excess of alkali metal hydroperoxide be destroyed by reaction with a reducing agent. Examples of reducing agents that may be mentioned include sodium sulfite, sodium thiosulfate, sodium dithionite, etc. The amount of reducing agent introduced is preferably used in excess, for example at 20% relative to the amount of hydrogen peroxide engaged.

 At the end of the reaction, the α-halogenated α-halogen carboxylic acid is recovered by any known means.

 A mode of separation used preferably consists in recovering in the aqueous phase, the α-halogenated a-chiral carboxylic acid, in salified form, and in the organic phase, the chiral acid R * OH. For this purpose, the reaction medium is treated with a basic agent, preferably an aqueous solution of a base such as sodium hydrogencarbonate, sodium carbonate, sodium hydroxide, potassium hydroxide, etc.

 The amount of basic agent used is such that the pH of the reaction medium is greater than 7, preferably between 9 and 10.

 The aqueous phase is then washed with an organic solvent such that the chiral auxiliary is recovered in the organic phase. Examples of organic washing solvents that may be mentioned include: aliphatic or aromatic halogenated hydrocarbons, and there may be mentioned: perchlorinated hydrocarbons such as in particular carbon tetrachloride, tetrachlorethylene, hexachloroethane, hexachloropropene, and hexachlorobutadiene, partially chlorinated hydrocarbons such as methylene chloride, dichloroethane, tetrachloroethane, trichlorethylene, 1-chlorobutane, 1,2-dichlorobutane; monochlorobenzene, 1,2-dichlorobenzene, 1,3-dichlorobenzene, 1,4-dichlorobenzene or mixtures of different chlorobenzenes; monobromobenzene or mixtures of monobromobenzene with one or more dibromobenzenes, aliphatic or aromatic ether-oxides and, more particularly, diethylether, dipropylether, diisopropylether, dibutylether, methyltertiobutylether, dipentylether, diisopentylether, oxide methyl and tert-butyl, ethyl tert-butyl ether, diphenyl ether; Petroleum ether; dibenzyl ether, anisole, phenetole, dimethoxybenzene, veratrole, aliphatic esters such as, in particular, methyl acetate, ethyl acetate and propyl acetate.

 The chiral auxiliary is thus recovered in said organic solvent.

 The aqueous phase is then acidified by the addition of an acid, preferably a mineral acid such as hydrochloric, nitric or sulfuric acid, generally from 5 to 10 N.

 The amount of acid added is such that the aqueous phase has a pH of less than or equal to 1.

 The α-chiral α-halogen carboxylic acid is extracted using an organic solvent which may be selected from the list of organic washing solvents given above.

 The α-halogenated a-chiral carboxylic acid can be separated by any known means, in particular by distillation under reduced pressure.

 The process of the invention makes it possible to conduct the hydrolysis of the ahalogenated ester without racemization.

 Another advantage of the method of the invention is that it allows the recycling of the chiral auxiliary because it can be easily recovered with preservation of its initial rotatory power.

 The following examples illustrate the invention without limiting it.

In the examples, the different symbols have the following meaning:
number of moles of α-halogenated carboxylic acid obtained
Halogenated acid yield = V
number of moles of 1,2,5,6-di-O- (1-methylethylidene) -α-D-ester
introduced glucofuranosyl
nb of moles of (S) - nb of moles of (R)
Energetic excess ee = ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
nb of moles of (S) + nb of moles of (R)
Nb of moles of (S) means number of moles of α-halogenated carboxylic acid of (S) configuration.

Nb of moles of (R) means number of moles of α-halogenated carboxylic acid of (R) configuration.

nb of moles of (S) - nb of moles of (R)
Diastereomeric excess ed = ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
nb of moles of (S) + nb of moles of (R)
Nb of moles of (S) means number of moles of α-halogenated ester (I) of (S) configuration for the carbon carrying the halogen.

Nb of moles of (R) means number of moles of α-halogenated ester (I) of (R) configuration for the carbon carrying the halogen.

 In the following examples, the α-halogenated carboxylic acid is an alkanoic acid.

EXAMPLES
The following is the operating protocol which is used in the examples.

 In the examples, the various analyzes are carried out by gas chromatography carried out on Hewlett-Packard 5890 series II gas chromatograph, provided with an HP 3396 series Il integrator printer with a column A: HP1, 1 = 5 m, O = 0.53 mm, stationary phase = methylsilicone, Tnj = Tdet = 200 C, flow rate in He = 10 ml / min.

For the determination of "ed", the column used is the following: - column B: HPl, I = 25 m, = 0.25 mm, stationary phase = methylsilicone, Tnj = Tdet = 210 C, flow rate in He = 1 ml / min with split = 1/15
For the determination of "ee", the column used is the following: - column C: Chirasil-L-Val, I = 25 m, = 0.25 mm, Tjnj = Tdet = 2Oooc flow in He = 1 ml / min with split = 1/15
Rotational powers were measured using a Perkin polarimeter
Elmer 241.

The ee are determined by polarimetry and GPC of the corresponding N-butyl amide (column C), prepared as follows according to the procedure of K. Watabe et al. (Synthesis 1987, 225). 10 mg of ahalogenated acid are placed in an excess of thionyl chloride (1 ml) at room temperature overnight or at 40 ° C. for 2 hours. The excess thionyl chloride is then evaporated and the residue taken up in 0.5 ml of anhydrous ether. The solution is cooled to 0.degree. C. and 1.2 ml of a 2% solution of tert-butylamine in dry ether are added dropwise thereto. After 30 minutes, the solvent is evaporated and the residue is taken up in a small amount of ether, filtered and evaporated. The tert-butylamide formed is dissolved in CH 2 Cl 2 and injected into CPG (column
C).

I) Synthesis of 1, 2, 5, 6-di-O- (1-methylethylidene) -α-D-glucofuranosyl alkanoates
Starting from an alkanoic acid of formula R - CH 2 --COOH, the nature of the radical R is specified in the summary table (Table I).

 To 60 mmol of alkanoic acid dissolved in 50 ml of dry dichloromethane, 5 mmol of 4-N, N-dimethylaminopyridine and 50 mmol of 1,2,5,6-di-O- (1-methylethylidene) are added successively. aD-glucofuranose. After having cooled to 0 ° C., 60 mmol of dicyclohexylcarbodiimide in solution in 60 ml of dry dichloromethane are added.

 The dicyclohexylurea is filtered and the filtrate is concentrated. The residue taken up in 60 ml of ethyl acetate is filtered again. The filtrate is washed with 50 ml of water, three times 50 ml of a saturated solution of NaHCO 3, and 50 ml of a saturated solution of NaCl. The organic phase is dried over MgSO4. It is concentrated and purified by chromatography, the residue on silica (eluent = ethyl acetate / petroleum ether: 10/90).

 The synthesized esters are characterized in IR by a band (c = 0) at 1740 cm -1.

Infra-red spectra were recorded on the Perkin spectrometer
Elmer 16PC FTIR.

II) Synthesis of ketene acetals
7.5 mmol of diisopropylamine are placed in 15 ml of anhydrous tetrahydrofuran (THF) at 0 ° C. 7.5 mmol of n-butyllithium (2.5 M in hexane) are added and the mixture is stirred for 15 minutes at 0 ° C. The mixture is cooled to -70 ° C. and 7.5 mmol of ClSiMe3 and then 5 mmol of ester in solution in 2 ml of THF are added successively in the course of 6 minutes (with the syringe pump). After addition, the mixture is kept at -70 ° C. for 3 hours, before the reaction medium is allowed to slowly return to room temperature (3 h to pass from 70 ° C. to 0 ° C.) The THF is evaporated. The residue is taken up in 40 ml of pentane. The supernatant is centrifuged, sampled and concentrated to isolate the crude ketene acetal after evaporation.

 The ketene acetals synthesized are characterized in IR by a band Y (c = c) at 1680cm-1.

111) Access to α-halogenated esters by halogenation of ketene acetals
5 mmol of crude ketene acetal are dissolved in 50 ml of dry THF and cooled to -70 ° C. 1.5 equivalents of halogenating agent (N-bromosuccinimide or N) are then added in one go. -chlorosuccinim ide) in solid form by means of a bubble to solid. It is maintained at -70 ° C. for 1 hour, and 50 ml of a 0.4 M solution of sodium thiosulphate are then added at this temperature, and then the reaction medium is taken up in 80 ml of ether and washed with a solution of thiosulphate. then three times 50 ml of water. It is dried over MgSO 4. A filter is obtained, the residue is evaporated and the residue is analyzed by gas chromatography on HP1 column 25 m long (column B).

 The synthesized halogenated esters are characterized in IR by a Y (c = o) band at 1745 cm -1.

IV) Hydrolysis of the α-halogenated esters
The crude α-halogenated ester (5 mmol) in solution (0.05M solution) is placed in a mixture of 75 ml of THF and 25 ml of water, and the solution is cooled to 0.degree. 4 equivalents (1.8 ml) of a 30% aqueous solution of hydrogen peroxide and then 2 equivalents of LiOH. The solution is stirred at 0 ° C. until the ester has completely disappeared (followed by GC) (column A). Excess lithium hydroperoxide is destroyed at 0 C with 10% excess of a 1.5N solution of Na2SO3 (21 ml); this reaction is exothermic. Its total destruction is checked using a starchy potassium iodide paper. If necessary, the pH of the solution is adjusted with a saturated solution of NaHCO 3 up to pH 9 or 10. The aqueous solution is extracted twice with 50 ml of ether. The chiral alcohol is then recovered. The aqueous phase is acidified with concentrated HCl to pH = 1 and extracted with 3 times 50 ml of ether. The organic phase is dried over Na 2 SO 4, concentrated, and the residue is distilled under reduced pressure to yield α-halogenated acids.

The halogenated acids synthesized are characterized in IR by a band Y (c = o) at 1710 cm-1
Examples 1 to 8:
In the various examples, starting from an alkanoic acid of formula
R - CH 2 --COOH in which R represents a methyl radical (Examples 1 and 5), an isopropyl radical (Examples 2 and 6), a t-butyl radical (Examples 3 and 7) and an n-butyl radical (Examples 4 and 4); 8).

 The halogenating agent used is respectively N-chlorosuccinimide in Examples 1 to 4 and N-bromosuccinimide in Examples 5 to 8.

The results obtained are recorded in the summary table:
Table I

<tb><SEP> X <SEP> X
<tb><SEP> 4 <SEP> OR * <SEP> XOH
<tb><SEP> O <SEP> O
<tb> N <SEP> Example <SEP> | <SEP> R <SEP> | <SEP> X <SEP> 0 <SEP> ed (%) <SEP> rdt <SEP> | <SEP> ee (%)
<tb><SEP> 1 <SEP> | <SEP> Me <SEP> | <SEP> Cl <SEP> 0 <SEP> 90 <SEP> 64 <SEP> | <SEP> 90
<tb><SEP> 2 <SEP> iPr <SEP> Cl <SEP> 96 <SEP> 79 <SEP> 95
<tb><SEP> 3 <SEP> tBu <SEP> Cl <SEP> 90 <SEP> 72 <SEP> 90
<tb><SEP> 4 <SEP> nBu <SEP> Cl <SEP> (a) <SEP> 65 <SEP> 80
<tb><SEP> 5 <SEP> Me <SEP> Br <SEP> 75 <SEP> 69 <SEP> 75
<tb><SEP> 6 <SEP> iPr <SEP> Br <SEP> (a) <SEP> 75 <SEP> 84
<tb><SEP> 7 <SEP> tBu <SEP> Br <SEP> (a) <SEP> 71 <SEP> 85
<tb><SEP> 8 <SEP> nBu <SEP> Br <SEP> (a) <SEP> 63 <SEP> 70
<tb> (a) - not totally separated

Claims (18)

1 - A hydrolysis process of an α-halogenated ester derived from a furanose derived from a sugar characterized in that it consists in hydrolyzing said ester with an alkali metal hydroperoxide in a hydro-organic medium. 2 - Process according to claim 1 characterized in that the alkali metal hydroperoxide is a hydroperoxide of sodium, potassium or lithium, preferably lithium hydroperoxide. 3- Method according to one of claims 1 and 2 characterized in that the alkali metal hydroperoxide is formed in situ from the alkali metal hydroxide and hydrogen peroxide. 4- Method according to one of claims 1 to 3 characterized in that the amount of the implementation of the alkali metal hydroperoxide expressed by the molar ratio between the alkali metal hydroperoxide and the ester of formula (I) ) varies between 2 and 8. 5- Method according to one of claims 1 to 4 characterized in that the amount of hydrogen peroxide expressed by the molar ratio between the hydrogen peroxide and the bonded ester of formula (I) varies between 4 and 8 . 6. Process according to one of claims 1 to 5 characterized in that the volume ratio between water and the organic solvent varies between 0.3 and 3.0. 7- Method according to one of claims 1 to 6 characterized in that the organic solvent is selected from: - oxygenated heterocyclic solvents such as in particular, dioxane, tetrahydrofuran, dioxolane, - aliphatic alcohols such as ethanol, propanol, butanol, pentanol. ketones, such as acetone, methyl ethyl ketone and diethyl ketone. tetramethylene sulfone (sulfolane), propylene carbonate, ethers and more particularly dimethyl ethers derived from ethylene oxide or propylene oxide, such as dimethoxy-1,2-ethane or dimethoxy; -1,5 oxa-3-pentane, 1,8-dimethoxy-3,6-dioxa-octane, 1,1-dimethoxy-3,6,5-trioxa undecane, -monomethyl, monoethyl, monopropylic, monobutyl, ethylene ethers glycol. 8- Method according to one of claims 1 to 7, characterized in that the concentration of the ester of formula (I) in the reaction solvent (water + organic solvent) varies between 0.001 and 1 mol / liter, preferably between 0.01 and 0.1 mole / liter. 9 - Process according to one of claims 1 to 8 characterized in that the temperature of the hydrolysis reaction is chosen between -10 C and 25 C. 10- Method according to one of claims 1 to 9, characterized in that the α-chiral α-halogenated ester corresponds to the following formula (I):

 in which the different symbols represent:  R represents a hydrocarbon radical having from 1 to 40 carbon atoms  which may be an aliphatic radical, saturated or unsaturated, linear or branched  a cycloaliphatic radical, saturated, unsaturated or aromatic, monocyclic or  polycyclic; a cycloaliphatic or arylaliphatic radical, saturated or  unsaturated, linear or branched, a halogen atom, preferably an atom  fluorine, chlorine or bromine,  R * represents a radical derived from a tetrahydrofuranyl unit,  X represents a halogen atom, preferably a chlorine atom or  bromine, different from R.  1 1 - Process according to one of claims 1 to 10, characterized in that the α-chiral α-halogenated ester corresponds to formula (I) in which R represents an alkyl, alkenyl, alkadienyl, alkynyl, linear or branched having preferably from 1 to 24 carbon atoms: the hydrocarbon chain possibly being:  - interrupted by one of the following groups:

  in these formulas R5 represents hydrogen or a linear or branched alkyl radical having from 1 to 4 carbon atoms, preferably a methyl or ethyl radical,  and / or carrier of one of the following substituents:

 in these formulas, R5 having the meaning given above. 12 - Process according to claim 1 I characterized in that said radical R is carrying a cyclic substituent connected by a valency bond or by one of the following groups:

 in these formulas R5 having the meaning given above. 13- Method according to one of claims 1 to 12 characterized in that the α-chiral α-halogenated ester corresponds to formula (I) wherein R represents: - a linear or branched alkyl radical having from 1 to 12 carbon atoms; - a cycloalkylalkyl radical preferably having 1 to 4 carbon atoms in the alkyl chain; - a phenylalkyl radical having preferably 1 to 4 carbon atoms in the alkyl chain; - a cycloalkyl radical; optionally substituted having, preferably, from 5 to 7 carbon atoms, - an optionally substituted phenyl radical, - an optionally substituted naphthyl radical. 14- Method according to one of claims 1 to 13 characterized in that the α-chiral α-halogenated ester corresponds to formula (I) wherein R represents: - methyl, ethyl, propyl, isopropyl, n butyl, isobutyl, sec-butyl or tert-butyl, the cyclohexyl radical, the phenyl, tolyl, xylyl or naphthyl radicals optionally bearing linear or branched alkyl radicals having from 1 to 4 carbon atoms or alkoxy radicals having 1 to 4 carbon atoms, benzyl or phenylethyl radicals. 15- Method according to one of claims 1 to 14 characterized in that the α-chiral α-halogenated ester corresponding to formula (I) wherein R represents a linear or branched alkyl radical having from 1 to 12 atoms of carbon and preferably from 1 to 4 carbon atoms. 16- Method according to one of claims 1 to 15, characterized in that the α-chiral α-halogenated ester corresponds to the formula (I) in which R * represents a unit corresponding to the following formula (II):

 in said formula (II), R 1, R 2, which are identical or different, represent a linear or branched alkyl radical having from 1 to 12 carbon atoms, a cyclohexyl radical, a phenyl radical or a benzyl radical, R 3, R 4, which are identical; or different, represent a linear or branched alkyl radical having 1 to 12 carbon atoms, a cyclohexyl radical, a phenyl radical or a benzyl radical, - the radicals R1 and R2 on the one hand, and R3 and R4 on the other hand can together form a 5-membered (dioxolan) or 6-membered (1,4-dioxane) ring. 17- Method according to one of claims 1 to 16, characterized in that the α-chiral α-halogenated ester corresponds to formula (I) wherein R * represents a furanose unit derived from the following sugars: glucose, I allose, altrose, mannose, galactose, talose, gulose, idose, ribose, arabinose, xylose and lyxose. 18- Method according to one of claims 1 to 17, characterized in that the α-chiral α-halogenated ester corresponding to formula (I) wherein R * represents the following radical:

 19- Method according to one of claims 1 to 18, characterized in that the α-chiral α-halogenated ester corresponding to formula (I) is an ester derived from a furanose unit bearing an OH in the 3-position and one of the following halogenated alkanoic acids: - 2-chloropropionic acid - 2-bromo-propionic acid - 2-chlorobutanoic acid - 2-bromo-butanoic acid - 2-chloro-methyl acid 3-butanoic acid - 2-bromo-3-methyl-butanoic acid - 2-chloro-3,3-dimethyl-butanoic acid - 2-bromo-3,3-dimethyl-butanoic acid - 2-chloro hexanoic acid - I - 2-bromo-hexanoic acid - 2-chloro-4-methylpentanoic acid - 2-bromo-4-methylpentanoic acid 20 - Method according to one of claims 1 to 19, characterized in that the α-halogenated ester a-chiral compound corresponding to formula (I) is prepared by reacting an N-halosuccinimide (N-bromosuccinimide or N-chlorosuccinimide) in an organic solvent and a keten acetal O-silylated compound corresponding to the following formulas:

 in said formulas (III) or (III) ': - R * has the meaning given above in one of claims 10, 16 to 18, - the radicals R6, identical or different, represent a linear or branched alkyl radical having 1 to 4 carbon atoms or a phenyl radical, preferably a methyl radical, - R has the meaning given above in one of claims 10 to 15. 21 - Use of the process of the invention described in claims 1 to 20 to the preparation of (S) -2-chloropropionic acid.