FR2651495A1 - Process for the preparation of 1-aminocyclopropanecarboxylic acid and of one of its synthetic intermediates - Google Patents

Abstract

The invention relates to a process for the preparation of 1-aminocyclopropanecarboxylic acid according to which an organic or inorganic base is reacted with a dimethylsulphonium derivative of the following formula (I): and then the compound resulting from this reaction is hydrolysed. The invention also relates to a process for the preparation of an intermediate in the synthesis of 1-aminocyclopropanecarboxylic acid.

Description

PROCESS FOR THE PREPARATION OF AMINO-1 CYCLOPROPANECARBOXYLIC ACID
AND ONE OF ITS SYNTHETIC INTERMEDIARIES
The present invention relates to a new process for the preparation of 1-amino-cyclopropanecarboxylic acid. The invention also relates to a process for the preparation of an intermediate for the synthesis of 1-amino-cyclopropanecarboxylic acid.

 1-Amino cyclopropanecarboxylic acid (ACC) is biosynthesized in various plant systems from (S) adenosylmethionine.

 ACC is present in the tissue of many plants where it plays the role of precursor of ethylene, phtohormone that triggers fruit ripening and regulates plant growth. As a result, ACC is used in agrochemistry as a growth regulator. ACc has recently been incorporated into peptide derivatives, for example in carboxypeptidase irylibitors.

Several methods of synthesis of ACC have already been described
Thus, the method described by I. BREGOUVC et al. in
Monatsh. Chemistry 103 (1972), 288-291, wherein esters of acylaminoacrylic acid are reacted with diazomethane to form pyrazolines which are pyrolyzed to form esters.
N-acylated CCA. ACC is then obtained by saponification of said esters.

There is also known a process for preparing ACc by cyclopropanation of olefins using amino carboxycarbenes, described by U. Sccolloopf et al, Angew. Chem. Int. Ed. English, 1986, 25, 192-193, and a method for cyclization with dibrooethane of a nitril derivative of glycine described by MJ O'Donnell et al. in
Synthesis 1984,127.

 However, the starting compounds used in these processes are generally commercially inaccessible or require several synthesis steps and most importantly, the ACC yields are low and the purifications of the intermediate products are often essential.

 As a result, the ACC synthesis methods described so far are often difficult to apply to the preparation of large amounts of this amino acid which renders them unsuitable for use on an industrial scale.

 The applicant then developed a new process for preparing the ACC overcoming the disadvantages of the prior art and which constitutes a first object of the present invention.

 Another object of the invention is a method for preparing an ACC synthesis intermediate.

dans laquelle : .R est un atone d'hydrogène, un radical aliphatique linéaire ou ramifié, saturé ou insaturé en C1-C20, un radical aryle éventuellement substitué ou un radical aralkyle éventuellement substitué
A A est A1 et/ou A2, A1 et A2 étant identiques ou différents et représentent un atome d'halogène, un reste SO4-CH3, ou un reste S03-R1, R1 étant un radical alkyle, aralkyle ou aryle, de façon à obtenir un dérivé spiro de formule (II), suivante

dans laquelle R à la même signification que celle donnée ci-dessus,
(2) on hydrolyse le dérivé spiro (II). The present invention thus provides a process for the preparation of 1-amino-cyclopropanecarboxylic acid, characterized in that the following steps are carried out:
(1) reacting in at least one organic solvent, an organic or inorganic base with a dimethylsulfonium derivative of formula (I) below

in which: R is a hydrogen atone, a linear or branched, saturated or unsaturated C 1 -C 20 aliphatic radical, an optionally substituted aryl radical or an optionally substituted aralkyl radical;
AA is A1 and / or A2, A1 and A2 are identical or different and represent a halogen atom, a SO4-CH3 residue, or a SO3-R1 residue, where R1 is an alkyl, aralkyl or aryl radical, so as to obtain a spiro derivative of formula (II), following

in which R has the same meaning as that given above,
(2) the spiro derivative (II) is hydrolyzed.

 In the context of the present invention, R is preferably an aliphatic radical, linear or branched, saturated or unsaturated C1-C20, more preferably C1-Cs, such as methyl, or an aryl radical, preferably benzyl. R1 may be more particularly chosen from C1-C20 alkyls, or from aryl radicals such as paratolyl or benzyl.

Preferably A is a SO4CH3 residue.

 As organic solvents, those whose dielectric constant at 250c is greater than 10 are preferred. Among these, preferred are the alcohols, advantageously linear or branched C1-C8 alcohols, and more particularly methanol, or also aprotic solvents. such as dimethylsulfoxide (DMSO), acetonitrile or dimethylformamide (DMF).

 It is also possible to use a mixture of several of said organic solvents.

 The preferred organic bases are the alcoholates, more preferably the linear or branched C 1 -C 4 potassium or sodium hydroxide alcoholates, such as sodium methoxide and sodium n-propylate. The preferred inorganic bases are the alkaline to alkalictic hydroxides. more particularly sodium hydroxide or potassium hydroxide and alkali carbonates, preferably potassium carbonate.

 The reaction of step (1) described above is generally carried out at temperatures between 0 and 1500C, preferably between 40 and 100 C, for about 15 minutes to 36 hours.

 the reaction of step (1) is generally carried out using from 0.01 to 2.5 mol / l, preferably from 0.1 to 1.5 mol / l of compound of formula (I), in the organic solvent or the mixture of organic solvents.

 from 1 to 6 equivalents and preferably from 1 to 3 equivalents, from said inorganic organic bases per mole of compound (I) are generally used.

At the end of step (1), the spiro derivative (II) obtained can, during a second step, be hydrolysed. The hydrolysis can be carried out in an aqueous medium, either from the isolated spiro (II) derivative
reaction crude by conventional extraction and crystallization techniques, either from the crude reaction without it being necessary to isolate the spiro derivative (II).

 In the latter case, the hydrolysis being carried out in an aqueous medium, it is however necessary to remove said organic solvent from the crude reaction before or after addition of water, for example by evaporation.

 The hydrolysis of the spiro derivative (II) can be carried out by means of a mineral acid, preferably sulfuric acid.

 The hydrolysis can also be carried out using a mineral base such as sodium hydroxide, potassium hydroxide, lime or barite.

 However, acid hydrolysis is preferred. The hydrolysis step of the compound (II) is generally carried out at a temperature of 100 to 200 ° C., preferably at a temperature of between 150 and 1900 ° C.

 This hydrolysis step is generally carried out using from 0.2 to 5 moles, preferably from 0.8 to 3 moles of spiro (II) derivative per liter of water and from 0.5 to 10 moles, of preferably from 1.5 to 6 moles of acid or base per liter of water. At the end of step (2) of hydrolysis of the spiro derivative (II), the ACC obtained is recovered according to conventional methods.

 The dimethylsulfonium derivatives (I) can be prepared according to the method described in US Pat. No. 4,093,444.

dans laquelle A2 représente un atane d'halogène, un reste S04CH3 ou un reste S03-R1, R1 étant un radical alkyle, aryle au arakyle tels que définis ci-dessus,
avec (b) un composé RA1, AI ayant la même signification que
A2, A1 et A2 étant identiques ou différents et R ayant la signification donnée cidessus. However, in an advantageous embodiment of the invention, the dimethylsulphonium derivatives of formula (I), for which R is a linear or branched aliphatic radical, saturated or unsaturated C 1 -C 20, preferably C 15 such as methyl or a aralkyl radical such as benzyl, may be prepared by reaction in the presence of a base, (a) a dimethylsulfonium derivative of formula (III) below

in which A2 represents a halogen atane, a SO 4 CH 3 residue or a SO 3 -R 1 residue, R 1 being an alkyl or aryl radical with aralkyl as defined above,
with (b) a compound RA1, AI having the same meaning as
A2, A1 and A2 being identical or different and R having the meaning given above.

 Preferably, A1 is dimethylsulfate.

 Said reaction between the dimethylsulfonium (III) and RA1 derivative is generally carried out in at least one solvent whose dielectric constant at 250c is greater than 10, such as aprotic polar solvents such as acetonitrile, DMSO or DMF or preferably solvents such as water with alcohols.

 As alcohol, mention may be made of methanol, ethanol, and iso-propanol.

 Said reaction can be carried out in the presence of a mineral base such as sodium hydroxide and potassium hydroxide, with an organic base such as alcoholates, preferably sodium or potassium alcoholates, linear or branched C1-C4, such as methylate of sodium, sodium n-propoxide to potassium t-butoxide.

Said reaction can be carried out with varying concentrations of dimethylsulfonium (III) derivative and RA1 compound.

Generally, from 0.5 to 4 moles, preferably from 0.8 to 3 moles of dimethylsulfonium (III) derivative per liter of solvent, from 1 to 1.2 equivalents of compound RA1 per mole of dimethylsulfonium (III) derivative are used. and from 1 to 1.2 equivalents of base per mole of dimethylsulfonium derivative (III).

The reaction temperature is generally between 0 and 1000C, more generally between 20 and 700C.

 At the end of the reaction between the dimethylsulfonium (III) derivative and RA1, the resulting reaction crude may be stripped of said solvent according to conventional methods, for example by evaporation.

However, if the solvent is not water, it may not be necessary to remove it.

 The dimethylsulfonium derivative (I) obtained can be used directly in step (1) of the ACC preparation process as described above, this after optional elimination, for example by filtration, of the salts formed during the reaction between the dimethylsulfonium (III) derivative and RA1.

avec un agent méthylant de formule A2-CH3 dans laquelle A2 a la signification donnée cidessus. The dimethylsulfonium (III) derivative can in turn be obtained by a process according to which the hydantoin is reacted with the methionine of the following formula (IV)

with a methylating agent of formula A2-CH3 in which A2 has the meaning given above.

 Preferably, A2-CH3 is dimethylsulfate.

This type of reaction can be done according to the method described by
RO ATKINSON et al, J. cnem. Soc., 1951, p. 1378, which also describes the process for preparing hydantoin of methionine (IV) from methionine.

 In general, the dimethylsulfonium (III) derivative is prepared by reacting 1 to 5 moles of hydantoin with methionine (IV) per liter of a solvent such as those mentioned above for the synthesis of the dimethylsulfonium derivative (I). ).

 From 1 to 1.2 moles of A2-CH3 compound are used per mole of hydantoin of methionine (IV).

 The dimethylsulfonium (III) derivative thus prepared can then be isolated from the reaction crude according to conventional techniques, for example by crystallization or be directly involved in the process for the preparation of the dimethylsulfonium derivative (I), as described above, in the crude oil. reaction.

The dimethylsulfonium derivatives of formula (I) for which R is a linear or branched, saturated or unsaturated C 1 -C 20, preferably C 1 -C 8, aliphatic radical such as methyl, or an aryl radical such as benzyl may also be prepared from hydantoin of methionine (IV) on which the compound RA1 is first reacted in the presence of a base, and then the methylating agent
A2-CH3
The conditions of use of RA1 and A2-CH3 are identical to those described above for the preparation of the dimethylsulfonium derivative (I) from the hydantoin of methionine (IV) on which the reaction is first reacted. methylating agent A2-CH3 then the compound RA1 in the presence of a base.

When R is a methyl radical, the dimethylsulfonium derivative (I) may be advantageously prepared in a single step by reacting in the presence of a base, the hydantoin of methionine (IV) with the methylating agent of formula A2-CH3 . In this case too,
A2-CH3 is advantageously dimethylsulphate.

 The reaction between the hydantoin of methionine (IV) and A2-CH3 is generally carried out in at least one solvent of the same nature as the solvents used for the synthesis of the dimethylsulfonium derivative (I) from the dimethylsulfonium derivative (III). ).

 The base used is of the same nature as that used to prepare the dimethylsulfonium derivative (I) from the dimethylsulfonium (III) derivative.

 The hydantoin concentration of the methionine (r7) in said solvent is generally between 0.05 and 4 mol / l and preferably between 0.1 and 3 mol / l.

 Generally 1 to 1.1 equivalents of base per mole hydantoin of methionine (IV) is used. The concentration of methylating agent A2-CH3 in said solvent is generally between 2 and 2.5 mol / l and preferably between 2 and 2.2 mol.

 At the end of the reaction between the hydantoin of methionine (r7) and the compound A2-CH3, the dimethylsulfonium derivative (I) obtained can be engaged in said step (1) of the ACC preparation process, in as the same conditions as those described when the dimethylsulfonium derivative (I) is prepared from the compound (III) according to the method described above.

 The use of the hydantoin of methionine (IV) for the preparation of the dimethylsulfonium derivative (I) is particularly advantageous in the context of the invention.

 Indeed, the hydantoin of methionine (IV) can be easily prepared from methionine in one step.

 In addition, the use of this compound as a starting material for the preparation of ACC according to the method described above may allow a sequence of steps which does not require isolation of intermediates. In the case where ACC is prepared from the hydantoin of methionine (IV) in such a sequence, methanol is preferably used in each of the steps as organic solvent.

dans laquelle R représente un atome d'hydrogène, un radical aliphatique, linéaire ou ramifié, saturé ou insaturé en C1-C20 un radicale aryle éventuellement substitué ou un radical aralkyle éventuellement substitué, ledit procédé étant caractérisé en ce qu'on fait réagir dans au moins un solvant organique, une base organique ou minérale avec un dérivé diméthylsulfonium de formule (I) suivante:

dans laquelle : .R a la même signification que celle donnée cidessus,
A A est A1 et/ou A2, A1 et A2 étant identiques au différents et représentent un atome d'halogène, un reste S03-R1, R1 étant un radical alkyle, aryle ou aryle ou un reste SO4-CH3. The present invention also relates to a process for preparing a synthesis intermediate of the AOC of the following formula (II)

in which R represents a hydrogen atom, a linear or branched, saturated or unsaturated C 1 -C 20 aliphatic radical, an optionally substituted aryl radical or an optionally substituted aralkyl radical, said process being characterized in that it is reacted in at least one organic solvent, an organic or inorganic base with a dimethylsulfonium derivative of formula (I) below:

where: .R has the same meaning as given above,
AA is A1 and / or A2, A1 and A2 are identical to the different and represent a halogen atom, a SO3-R1 residue, R1 being an alkyl, aryl or aryl radical or a SO4-CH3 residue.

 The particular embodiments of this process are identical to those described for the preparation of the spiro derivative (II) described above and obtained at the end of step (1) of the process for preparing the ACC according to the present invention.

 The following examples are intended to illustrate the present invention.

Example 1
Synthesis of [(dioxo-2,5-imidazolidin-4-yl) -ethyl-2-dimethylsulfonium methylsulfate (Compound (III)).

 In a 0.25 l three-neck flask equipped with a condenser and a dropping funnel, containing a suspension of 40.1 g (0.23 mol) of [(methylthio) -ethyl-2 -] - 5- imidazolidine-2,4-dione (compound (IV)), in water (118 ml) is poured in 5 minutes 20 ml of dimethylsulfate. The reaction medium is heated at 800 ° C. for 45 minutes with magnetic stirring. After cooling, the product of the reaction is precipitated with ethanol (1000 ml), filtered and then recrystallized from 550 ml of a 90/10 (v / v) ethanol / water mixture.

 69.13 g of compound (III) are thus obtained, ie a yield of 85% relative to the compound (IV) introduced.

 The compound (III) obtained has a melting point of 169-171 ° C.

Cumulative analysis for C8 H16 N2 O6 S2
C% H% N% S%
Calculated 31.99 5.37 9.33 21.35
Found 31.68 5.27 9.28 21.21
Example 2
Synthesis of [(dioxo-2,5-methyl-1-imidazolidin-4-yl) -ethyl-2-dimethylsulfonium methylsulfate (compound I)) from compound (III).

 6 g (20 mmol) of the compound (III) obtained according to the method of Example 1 are dissolved in 20 ml of a 1N sodium hydroxide solution. 2.51 g of dimethylsulphate are added with stirring at room temperature. After stirring for 4 hours, 2 ml of 1N sodium hydroxide solution and then, after 20 minutes, 0.25 g of dimethylsulphate are added to the reaction medium. Stirring at room temperature is maintained overnight. The solution is neutralized to remove the excess of base by adding a solution of sulfuric acid IN, then concentrated to dryness.

 The crude product is then stirred in 88 ml of acetonitrile and the precipitated salts are filtered. The filtrate is concentrated to dryness and dried under vacuum.

 There is thus obtained 6.84 g of compound (I) in the form of a colorless and viscous product.

 H-NMR analysis (360 MHz) shows that the isolated product consists mainly of the desired product and a small amount of acetonitrile.

 The 1 H-NMR spectrum of the desired product is as follows (analysis in DMSO).

Δ (ppm) = 8.13 (s, 1H); 4.18 (t, 1H, J = 6Hz); 3.32 (s, 3H); 3.26 (m, 2H); 2.83 (s, 3H); 2.82 (s, 3H); 2.78 (s, 3H); 2.11-s, 00 (m, 2H).

Example 3 Synthesis of methyl-6-diaza-4,6-spiro- [2,4] heptane-dione-5,7 (compound (II)) from compound (I)
6.7 g of the compound (I) obtained according to Example 2 are solubilized in 13 ml of acetonitrile and 50 ml of propanol and then heated to 700C.

 23.49 ml of a 1.01 M solution of sodium n-propylate in propanol are poured into the reaction mixture whose temperature is maintained at 70-770C for 1h30.

 After cooling, the excess base is neutralized by addition of a 10% sulfuric acid solution in propanol.

 After concentration to dryness and dissolution in water, the product is extracted with ethyl acetate.

 After recrystallization from a 4/1 (v / v) isopropyl ether / isopropanol mixture, a first fraction of 1.84 g of the compound (II) (mp = 129-131 ° C.) is obtained, followed by a second fraction of 0.24. g of the compound (II) (title = 87%). The yield of C (II) is 74.5% relative to the compound (III) as prepared in Example 1.

Centesimal analysis for C6 H8 N2 O2 (first fraction):
C% H% N%
Calculated 51.52 5.75 19.99
Found 51.32 5.79 19.95
Example 4
Process for the synthesis of amino-1-cyclopropane carboxylic acid (ACC) from the compound (II)

Charge in a 50 ml Teflon reactor (reactor
Berghof system DB 2), 2.8 g of compound (II), prepared according to Example 3 as well as 17.47 ml of an aqueous solution of sulfuric acid 2.29 M. The reaction mixture is heated at 1800C for 3 hours. After cooling and degassing the solution, the latter is diluted with one volume of water and brought to pH 5.4 by addition of a calcium hydroxide solution. The famous salts are removed by filtration. The measured yield of ACC obtained relative to the compound (II) introduced is then 72%.

 The filtrate is passed through an Amberlite IRN-77 resin and the ACC is eluted with 1N ammonia solution. After concentration to dryness, 1.35 g of ACC are obtained, which is then recrystallized from an acetone / water 50/50 (v / v) mixture.

 The melting point of the final product is 252 C.

Centesis analysis for C4 H7 N02 1/2 H20 C% H% N% 0%
Calculated 43.63 7.32 12.72 36.32
Found 43.09 7.39 12.65 36.48
Example 5
"Co-ordinated" preparation of ACC from hydantoin of methionine (IV).

In a 250 ml three-necked bale surmounted by a distillation column and a dropping funnel are introduced 17.39 g of compound (IV0 and 32.75 ml of MeONa / MeOH solution 3.11M
20.81 ml of dimethyl sulphate are added dropwise to the suspension obtained after stirring for 10 minutes at room temperature.

During the addition of dimethylsulfate, the flask is cooled to maintain the temperature of the mass below 25-300C
The reaction mixture is stirred for 20-22 hours at room temperature.

 The reaction mixture is refluxed and then 38.23 ml of 3.11M MeONa / MeOH solution are introduced over 20 minutes. The heating is maintained for 6 hours during which the MeOH / Me 2 S mixture is distilled to remove the dimethylsulfide formed during the reaction. After cooling, the excess of base is neutralized by the addition of 30% sulfuric acid in methanol.

 After filtration of the salts, then addition of 90 ml of water, the reaction mixture is concentrated to 90 ml.

 The compound (II) obtained is then determined by HPLC.

 The yield of compound (II) relative to the starting compound (rV) is 73%.

 21.48 g of the concentrated reaction mixture and 2.22 ml of a 95% sulfuric acid solution are charged into a 50 ml Teflon reactor and heated at 1800 ° C. for 3 hours.

The measured yield (CERP assay by the orthophthaldehyde derivatization method) at AOC is 52% relative to the starting compound (IV).

Example 6
Preparation of the compound (II) from the compound (I)

 The compound (I) obtained according to the method of Example 2 is solubilized in different organic solvents at varying concentrations in the presence of different bases and the resulting reaction mixture is heated to different temperatures.

The starting compounds (I) and (II) are determined by
The results obtained as well as the different parameters of the tests carried out are shown in Table I below.
TABLE I

<tb><SEP> Test <SEP> Base <SEP> Number <SEP> Solvent <SEP> Concentration <SEP> Temp. <SEP> Time <SEP> of <SEP> Results
<tb><SEP> equivalent. <SEP> in <SEP> compound <SEP> (I) <SEP> reection <SEP> TT <SEP> RR
<tb> of <SEP> base <SEP> in <SEP> the <SEP> solvent <SEP> (%) <SEP> (%)
<tb><SEP> 1 <SEP> K2CO3 <SEP> 1 <SEP> CH3ON <SEP> 0.03 <SEP> M <SEP> reflux <SEP> 16 <SEP> H. <SEP> 100 <SEP> 67
<tb><SEP> 2 <SEP> KOH <SEP> 1 <SEP> CH3ON <SEP> 0.31 <SEP> M <SEP> reflux <SEP> 17 <SEP> H. <SEP> 66 <SEP> 43
<tb><SEP> 3 <SEP> PrONa <SEP> 5.7 <SEP> PrOH / CH3ON <SEP> 0.1 <SEP> M <SEP> TA <SEP> 7 <SEP> H. <SEP> 100 <SEP> 62
<tb><SEP> (9/1, <SEP> v / v)
<tb><SEP> 4 <SEP> PrONa <SEP> 1 <SEP>"<SEP> 0.1 <SEP> M <SEP> 70 <SEP> 45 <SEP> min. <SEP> 80 <SEP> 69
<tb><SEP> 5 <SEP> PrONa <SEP> 1.2 <SEP> 0.1 <SEP> M <SEP> 70 <SEP> 90 <SEP> min. <SEP> 100 <SEP> 81
<Tb>
In this table
- PrONa is sodium n-propylate
- CH3 CN is acetonitrile
- reflux is the reflux temperature of the solvent
- TA is the ambient temperature
Tr is the conversion rate of the compound (I) involved in
the reaction.

RR is the yield of compound (II) obtained with respect to
number of moles of compound (I) engaged
- The number of basic equivalents is given in relation to a
mole of compound (I) engaged.

Claims (19)

1. Process for the preparation of 1-amino-cyclopropane  carboxylic acid, characterized in that the  following steps:  (1) In at least one organic solvent, a  organic or mineral base with a dimethylsulfonium derivative  of formula (I) below

 in which R is a hydrogen atom, a linear or branched, saturated or unsaturated C 1 -C 20 aliphatic radical, an optionally substituted aryl radical or an optionally substituted aralkyl radical, AA is A1 and / or A2, A1 and A2 being identical or different and representing a halogen atom, a SO4-CH3 residue or a SO3-R1 residue, where R1 is an alkyl, araikyl or aryl radical so as to obtain a derivative; spiro of the following formula (II)

 in which R has the same meaning as that given above (2) the spiro derivative (II) is hydrolyzed.  aryl radical, preferably benzyl.  C 1 -C 20, preferentially C 1 -C 8 such as methyl, or a  a linear or branched, saturated or unsaturated aliphatic radical  2. Method according to claim 1 characterized in that R is 3. Method according to one of claims 1 or 2 characterized in  that said organic solvent is an organic solvent of which  the dielectric constant at 250c is greater than 10,  preferably an alcohol and more preferably an alcohol  linear or branched C1-C8, to a polar aprotic solvent  such as dimethylsulfoxide, acetonitrile or  dimethylformamide. 4. Method according to claim 3 characterized in that said  organic solvent is methanol. 5. Method according to one of claims 1 to 4 characterized in  that said organic base is an alcoholate, preferably a  Sodium or potassium alkoxide, linear C14 branched. 6. Method according to one of claims 1 to 4 characterized in that  that the mineral base is an alkaline hydroxide or  alkaline earth, preferably soda or potash to one  alkali carbonate, preferably potassium carbonate. 7. Method according to one of claims 1 to 6 characterized in that  the hydrolysis step (2) of the spiro (II) derivative is carried out in  aqueous medium. 8. Process according to claim 7, characterized in that  performs said hydrolysis by means of a mineral acid,  preferably sulfuric acid. 9. Process according to claim 7, characterized in that  performs said hydrolysis by means of a mineral base such  soda, potash, lime or barite. 10. Method according to one of claims 1 to 9 characterized in that  the dimethylsulfonium derivative (I) for which  R is a linear or branched aliphatic radical, saturated or  unsaturated C1-C20, preferably C1-C5, such as methyl, or  an aryl radical such as benzoyl, by reaction in the presence  of a base, (a) a dimethylsulfonium derivative of the formula  (III) next

 and R has the meaning given above.  meaning that A2, A1 and A2 are identical or different  or aralkyl, with (b) a compound RA1, A1 having the same  S04CH3 or a residue S03-R1, where R1 is an alkyl or aryl radical  in which A2 represents a halogen atom, a remainder 11. Process according to claim 10, characterized in that RA1  is dimethylsulfate. 12. Method according to one of claims 10 and 11 characterized in  said reaction is carried out between the dimethylsulphonyl  fonium (III) and RA1 in at least one solvent whose constant  dielectric at 250c is greater than 10, such as solvents  aprotic polar or preferably solvents such as water  or alcohols. 13. Method according to one of claims 10 and 12 characterized in  what is done said reaction between the derivative of  dimethylsulfonium (III) and RAI in the presence of a mineral base  such as soda and potash or an organic base such as  alcoholates, preferably sodium alcoholates or  potassium, linear or branched C1-C4. 14. Method according to one of claims 10 and 13 characterized in  what is prepared the dimethylsulfonium derivative (III) in  reacting hydantoin with methionine of formula (IV)  next

 is dimethylsulfate.  with a methylating agent of formula A2-CH3 15. Process according to claim 14, characterized in that A2-CH3 16. Method according to one of claims 1 to 9 characterized in oe  the dimethylsulfonium derivative (I) for which R is prepared  is a saturated linear or branched aliphatic radical  unsaturated C1-C20, preferably C1-C5, such as methyl or  an aralkyl radical such as benzoyl, by first reacting  hydantoin of methionine (w) with an RAI compound in  presence of a base, then with the methylating agent A2-CH3. 17. Process according to one of Claims 1 to 9, characterized in oe  the dimethylsulfonium derivative (I) for which R is prepared  is a methyl radical by reacting in the presence of a  base, hydantoin of methionine (EV) with the agent  methylating A2-CH3 18. Process according to claim 17, characterized in that A2-CH3  is dimethylsulfate. 19. Process for preparing a CCA synthesis intermediate  of formula (II) below,

 in which R represents a hydrogen atom, an aliphatic radical, linear or branched, saturated or unsaturated in C1-C20, an optionally substituted aryl radical, an optionally substituted aralkyl radical, said process being characterized in that at least one organic solvent, an organic or inorganic base, is reacted with a dimethylsulfonium derivative of formula (I) next

 in which R R has the same meaning as given above A A is A1 and / or A2, A1 and A2 are the same or different and represent a halogen atom, a SO4-CH3 residue or a SO3-R1 residue, R1 being an alkyl, aralkyl or aryl radical.