Process for preparing one or more thiopyridinone-type compounds

Abstract

The present invention relates to a process for preparing one or more thiopyridinone-type compounds of formula (I) and their optical isomers, geometric isomers, and tautomers, as well as their organic or mineral acid or base salts, and their solvates such as hydrates. The invention also relates to one or more thiopyridinone-type compounds of formula (I'') and a composition incorporating said compounds.

Description

Title of the invention: Process for preparing one or more thiopyridinone-type compounds

[0001] The present invention relates to a process for preparing one or more thiopyridinone-type compounds of formula (I), as described below, and their optical isomers, geometric isomers, and tautomers, as well as their acid or base salts, organic or mineral, and their solvates such as hydrates.

[0002] The invention also relates to one or more thiopyridinone type compounds of formula (I”).

[0003] N-[(2-thioxo-l,2-dihydropyridin-3-yl)carbonyl]glycine, belonging to the thiopyridinone family, is a compound whose properties are generally of interest in the field of cosmetics, in particular for use as a whitening, lightening and / or depigmenting agent for keratinous materials, especially skin.

[0004] N-[(2-thioxo-l,2-dihydropyridin-3-yl)carbonyl]glycine can for example be prepared by means of a synthetic route described in the scientific article entitled "Synthesis of N-(2-mercaptopyridyl-3-formyl)-N-alkyl glycine and the corresponding disulfides" (Luo, YL; Yang, ZX; Peng, SX, Div. Med. Chem.., China Pharm. Univ., Nanjing, 21009, Peop. Rep. China, Yaoxue Xuebao 25(5), 374-8 (1990)).

[0005] More generally, thiopyridinone type compounds corresponding to the following formula (A): O h: (HAS) formula (A) in which: Ra represents a hydrogen atom or a linear saturated alkyl group in CrC6, Rb represents a hydrogen atom, a linear saturated alkyl group in CrC10, a branched saturated alkyl group in C3-C10 or a phenylalkyl group in CrC6; are likely to be prepared using the following synthesis method:

[0006] More particularly, according to such a reaction scheme, the process for preparing thiopyridinone-type compounds of formula (A) comprises at least the following successive steps:

[0007] a) at least one activation step of the carboxylic acid group of 2-chlorotonic acid of the following formula: O 'N-'" 'Cl

[0008] in the presence of at least one carboxylic acid activation agent according to classical acid activation methods (described for example in Comprehensive Organic Transformation by R. LAROCK Wiley VCH Ed. in the chapter Interconversion of nitriles, carboxylic acids and derivatives, 1989) to lead to a compound corresponding to the following formula (W): (W) • formula (W) in which: - X forms an acid halide and a mixed anhydride,

[0009] b) at least one reaction step of the compound of formula (W) with an amine of the following formula (V):

[0010] to lead to a compound of the following formula (Y): O (Y) • formulas (V) and (Y) in which RA and RB have the same meanings as in formula (A); then

[0011] c) at least one exchange step between the chlorine atom and the sulfur atom using reagents such as sodium disulfite, thiourea, sodium thiosulfate or thioacetic acid in a basic medium to lead to one or more compounds of formula (A): (HAS)

[0012] d) and optionally, for compounds of formula (A) in which the radical RB represents a hydrogen atom (i.e., comprising a carboxylic acid group), these can also be obtained through the implementation of at least one additional step of saponification of the corresponding esters using one or more inorganic bases, for example with sodium hydroxide (NaOH) or lithium hydroxide (LiOH), followed by acidification.

[0013] It follows that non-esterified thiopyridinone compounds, i.e. those corresponding to formula (A) in which RB represents a radical other than the alkyl or phenylalkyl groups, can be prepared from such a process, either by carrying out one or more additional saponification steps (optional step d)), or directly from an amine of corresponding formula (V) (step b)).

[0014] However, such a process still has a number of disadvantages (for example, additional saponification step, impurity), particularly when the desired final thiopyridinone compounds are not esterified.

[0015] On the one hand, when the thiopyridinone compound of formula (A), in which the radical RB corresponds to a hydrogen atom, is obtained directly from a corresponding amine of formula (V), i.e. without implementing one or more additional saponification steps, the process thus implemented still too often poses difficulties of feasibility on an industrial scale and requires better optimization.

[0016] On the other hand, when the thiopyridinone compound of formula (A), in which the radical RB corresponds to a hydrogen atom, is obtained by carrying out one or more additional saponification steps, then the process has the disadvantages of increasing energy consumption, increasing the quantity of reagents used, and generating additional effluents. Furthermore, such additional steps can cause a significant decrease in yield.

[0017] It follows that the process for preparing non-esterified thiopyridinone compounds of formula (A) does not lead to fully satisfactory yields and its implementation needs to be further optimized, particularly in terms of the number of steps and / or product quality on an industrial scale.

[0018] In view of the above, there is therefore a real need to propose a new process for preparing thiopyridinone type compounds corresponding to formula (I), as described below, which does not have the disadvantages mentioned above.

[0019] In other words, one of the aims of the present invention is to provide a process for preparing thiopyridinone-type compounds that offers, in particular, a better yield and more optimized implementation, specifically on an industrial scale. Furthermore, the compounds of formula (I) produced by the process of the invention exhibit a purity far superior to that obtained by the saponification of the ester.

[0020] The present invention therefore relates in particular to a process for preparing at least one compound of the following formula (I): (I)

[0021] Formula (I) wherein:

[0022] - A represents a divalent hydrocarbon chain, saturated or unsaturated, of preferably saturated, cyclic or acyclic, preferably acyclic, linear or branched, comprising from 1 to 10 carbon atoms, possibly interrupted by one or more heteroatoms or groups, such as an oxygen atom, a sulfur atom, an NR2 or (thio)carbonyl group, or their associations such as thioester, with R2 representing a hydrogen atom or a Ci-C4 alkyl group; - M represents a hydrogen atom, an alkali or alkaline earth metal, an ammonium group; - R1 represents a hydrogen atom, an alkyl group, linear or branched, in CrCl₂, possibly substituted by an OR3, SR3 group with R3 corresponding to a hydrogen atom or an alkyl group, linear or branched, in CiCl₂,

[0023] as well as one of its optical isomers, geometric isomers, and tautomers, as well as one of its acid or base salts, organic or mineral, and one of its solvates such as hydrates;

[0024] said process taking place according to the following synthesis scheme (1): • in which: - Hal and Hal', whether identical or different, represent a halogen atom, and - M, A and R1 have the same meanings as in formula (I);

[0025] at least step (iii) is at acidic pH i.e. less than 7.

[0026] The process according to the invention thus makes it possible to achieve the objectives described above, that is to say, it leads to a satisfactory yield and offers optimized industrial implementation, particularly compared to known processes for obtaining thiopyridinone compounds. Furthermore, the compounds are extremely pure (greater than or equal to 99% or even greater than or equal to 99.0% by HPLC).

[0027] Advantageously, the process according to the invention makes it possible to reduce the quantities of reagents used as well as the effluents generated, and its implementation can lead to an energy saving, in particular compared to known processes for obtaining thiopyridinone compounds implementing one or more additional saponification steps.

[0028] The present invention also relates to a compound of the following formula (I”):

[0029] (I”) • Formula (I”) in which: - M, A and RI have the same meanings as in formula (I), as well as their optical isomers, geometric isomers, and tautomers, as well as their acid or base salts, organic or mineral, and their solvates such as hydrates, with the exception of compounds (X) and (XI) and their following tautomers (X') and (XI)': (X') (XI) (xr)

[0030] Furthermore, the present invention also relates to a composition comprising, in a physiologically acceptable medium, at least one compound of formula (I”), its salts, and / or isomers and / or solvates, as described above.

[0031] Other objects, features, aspects and advantages of the invention will become even clearer upon reading the description and example that follows.

[0032] In what follows, and unless otherwise indicated, the bounds of a range of values ​​are included in that range, in particular in the expressions "between" and "ranging from ... to ...".

[0033] Furthermore, the expression "at least one" used in this description is equivalent to the expression "one or more".

[0034] Furthermore, the expression "at least" used in this description is equivalent to the expression "greater than or equal to". Finally, in a manner known per se, a compound or group in "Cn" or "Cn" is designated as a compound or group containing "n" carbon atoms in its chemical structure.

[0035] HPLC purity corresponds to the relative purity expressed as a percentage of area, measured at the maximum absorption wavelength (Xmax) of the analyzed product.

[0036] Depending on the needs of the steps of the process of the invention, the reaction media can be maintained in an acidic or basic environment.

[0037] An acidic pH, i.e., less than 7, can be adjusted by adding an acidifying agent, possibly in aqueous solution. The acidifying agent may be organic or mineral, particularly mineral. Examples of acidifying agents include mineral or organic acids such as hydrochloric acid, orthophosphoric acid, sulfuric acid, carboxylic acids such as acetic acid, tartaric acid, citric acid, lactic acid, and sulfonic acids.

[0038] Preferably, the acidifying agent is a mineral acid, in particular hydrochloric acid.

[0039] Preferably, the acidifying agent is introduced in aqueous solution.

[0040] A basic pH, i.e., greater than 7, can be adjusted by adding an agent alkaline, possibly in aqueous solution, said alkaline or alkalizing agent being organic or mineral, preferably mineral.

[0041] The alkali agent(s) may be chosen from mineral, organic or hybrid alkali agents.

[0042] For the purposes of the present invention, the terms "alkaline agent" and "alkalinizing agent" are used interchangeably.

[0043] The alkalizing agent(s) may be mineral alkali metals, preferably selected from the group consisting of alkali metal hydroxides or alkaline earth metal hydroxides, such as lithium hydroxides, sodium hydroxide, potassium hydroxide, alkali or alkaline earth metal (bi)carbonates such as sodium or potassium (bi)carbonates, and mixtures thereof. The alkalizing agent(s) may also be organic alkali metals, preferably selected from the group consisting of Mono(Ci-C6)(hydroxy)alkylamines, di(Ci-C6)(hydroxy)alkylamines, tri(Cr-C6)(hydroxy)alkylamines (preferably tri(Ci-C6)(hydroxy)alkylamines), saturated or unsaturated cyclic amines, aromatic such as pyridine, or non-aromatic, optionally substituted with one or more (Ci-C4)alkyl groups such as tetrahydropyridine optionally substituted with one or more (Cr-C4)alkyl groups, piperidine optionally substituted with one or more (Ci-C4)alkyl groups, or piperazine optionally substituted with one or more (Ci-C4)alkyl groups. Preferably, the alkali agents of the invention are tertiary amines.

[0044] Preferably, the alkalizing agents are chosen from the group consisting of alkali or alkaline-earth metal hydroxides, in particular sodium hydroxide, alkali or alkaline-earth metal (bi)carbonates, in particular sodium or potassium (bi)carbonates and tri(Ci-C6)(hydroxy)alkylamines, in particular tri(Ci-C6)alky lamines, especially triethylamine.

[0045] More preferably, the alkalizing agents are mineral and are chosen from the group consisting of alkali or alkaline-earth metal hydroxides, alkali or alkaline-earth metal (bi)carbonates, and their mixtures, in particular alkali or alkaline-earth metal hydroxides, in particular sodium hydroxide.

[0046] Preferably, the organic solvent(s) used in the process of the invention is / are aprotic and nonpolar, i.e., has a dielectric constant E ranging from 1 to 11 and a dipole moment p ranging from 0 to 2, in particular chosen from the group consisting of n-hexane, cyclohexane, 1,4-dioxane, carbon tetrachloride (CC14), benzene, tetrachloroethylene (C12C=C12C), toluene, carbon disulfide (CS2), trichloroethylene (C12C=CHC1), diethyl ether (Et2O), trichloromethane (CHC13), bromobenzene (PhBr), chlorobenzene (PhCl), ethyl acetate (CH3C(O)OEt or AcOEt), dimethyl ether (DME), tetrahydrofuran (THF), Methyltetrahydrofuran (2-MeTHF), dichloromethane (CH2C12), dichloroethane (C1CH2CH2C1), 1,1-dichloroethane (C12CHCH3). Preferably, the organic solvent(s) have a dielectric constant E ranging from 1 to 7 and a dipole moment p ranging from 0 to 2.Preferably, the organic solvent(s) are chosen from ethyl acetate, methyltetrahydrofuran and toluene, more preferably ethyl acetate. Preparation process

[0047] As previously stated, the process according to the invention takes place according to the reaction scheme (1), as described above, and at least step (iii), i.e. the reaction step of the compound of formula (V) leading to the compound of formula (I), is carried out at pH strictly less than 7.

[0048] The pH of the reaction medium is at a value strictly less than 7 during the reaction step of the compound of formula (V) leading to the obtaining of the compound of formula (I) (step (iii)).

[0049] Preferably, the reaction medium in step (iii) is at a pH less than or equal to 6, more preferably less than or equal to 5, even more preferably less than or equal to 4.

[0050] Preferably, the reaction medium in step (iii) is at pH which varies from 1 to 4, in particular from 2 to 3.

[0051] According to a particular embodiment of the invention, the pH is between 6 and 2, more particularly between 5 and 3. The method according to the invention preferably comprises successively at least the following steps: - at least one step (i) of preparation of the compound of the following formula (III): • Formula (III) in which: - Hal and Hal' have the same meanings as those described above; preferably, Hal and Hal' are identical and, more preferably, represent a chlorine atom.

[0052] by activation of the carboxylic group of the compound of the following formula (II): m

[0053] in the presence of one or more carboxylic acid activation agents according to classical methods of activating acid functions, in particular using thionyl halide such as thionyl chloride;

[0054] particularly the carboxylic acid activating agent(s) are such as are defined below as "the carboxylic acid activating agent", in particular selected from thionyl halides such as thionyl chloride, which is added dropwise (in particular in an excess of activating agent relative to the carboxylic acid to be activated, preferably between 1 and 2 molar equivalents such that 1.1 molar equivalents with respect to (II)) on the compound of formula (II), preferably the compound (II) is in a nonpolar aprotic solvent as defined above, in particular an ester solvent of (Ci-C6)alkyl acid and (Ci-C6)alkanol such as ethyl acetate or an aromatic solvent such as toluene;

[0055] particularly the reaction of step (i) is carried out under an inert atmosphere of argon or nitrogen (at atmospheric pressure), at a temperature between 25 °C and solvent reflux, preferably between 40 °C and 120 °C such as 77 °C or 110.6 °C,

[0056] particularly the reaction mixture of step (i) is left, preferably under solvent reflux, under mechanical stirring for a period of between 30 minutes and 10 hours, more particularly between 1 hour and 6 hours such as 4 hours;

[0057] preferably then the reaction mixture of step (i) is cooled to room temperature (25 °C) and preferably under an inert atmosphere; - at least one step (ii) of the reaction of the compound of formula (III) with an amine of the following formula (IV): XX R'

[0058] to obtain the compound of the following formula (V): O • Formulas (IV) and (V) in which: - A, M and R1 have the same meanings as those indicated previously for the compound of formula (I);

[0059] particularly step (ii) is carried out with:

[0060] * at least one equivalent of compound (IV) preferably more than one equivalent (particularly between 1.5 and 2.5 equivalents, more particularly 2 equivalents of compound (IV)), preferably in a polar (a)protic solvent, preferably a polar protic solvent such as water, particularly in a volume-to-weight ratio between 1 and 7, preferably between 2 and 5, such as 3.5 relative to the weight of the compound of formula (II), preferably the reaction mixture is left at a temperature between 10 °C and 30 °C, such as 20 °C ± 5 °C, preferably the reaction medium is left under an inert atmosphere, it is then particularly at least one mineral or organic alkali agent, preferably mineral such as sodium hydroxide, is added to the reaction medium to achieve a basic pH.

[0061] * at least one compound of formula (III) in particular in an organic solvent aprotic nonpolar as defined above, in particular ethyl acetate or toluene, with an alkali agent as defined above, said alkali agent preferably being in a polar (a)protic solvent such as water, more particularly a mineral alkali agent such as sodium hydroxide (preferably between 1 and 3 equivalents of alkali agent, such as 1.5 equivalents),

[0062] preferably the compound of formula (III) is added dropwise to the compound of formula (IV) at a temperature between 10 °C and 30 °C such as 20 °C + / - 5 °C and preferably under an inert atmosphere and under mechanical stirring, particularly the reaction is maintained between 1 minute and 6 hours, more particularly between 30 minutes and 2 hours, such as one hour;

[0063] more preferably during the addition of the compound of formula (III) said reaction medium is maintained at a basic pH, more particularly between 7.5 and 10;

[0064] preferably the mixture is left to settle, particularly at a temperature between 10 °C and 30 °C such that at 20 °C + / - 5 °C, the aqueous phase is collected;

[0065] particularly the aqueous phase is cooled to a temperature below 30 °C, preferably between 20 and 30 °C, such as 25 °C + / -5 °C; preferably said phase is acidified with a mineral or organic acid, preferably mineral such as hydrochloric acid, in particular with at least 1 equivalent of acid, preferably between 1 and 3 equivalents such as 1.6 equivalents, the pH of said aqueous phase is preferably between 1 and 5, in particular between 2 and 4 such as 2.5 + / -0.2;

[0066] preferably the aqueous phase is then filtered and the resulting solid is preferably washed with a polar (a)protic solvent, preferably a polar protic solvent such as water; then said solid is optionally dried, preferably at a temperature greater than or equal to 20 °C, more preferably between 30 °C and 60 °C, such as 50 °C + / - 5 °C; to lead to the compound of formula (V);

[0067] The drying step is optional; the wet product can be used directly in the next step. - at least one thionation reaction step (iii) of the compound of formula (V) to lead to the compound of formula (I);

[0068] said reaction step (iii) taking place at a pH less than 7 (the value 7 being excluded), that is to say, said step taking place at an acidic pH (or in an acidic reaction medium) preferably less than or equal to 6, more preferably less than or equal to 5, even more preferably less than or equal to 4, in particular in a pH range from 1 to 4, preferably from 2 to 3; according to a particular embodiment of the invention the pH of step (iii) is between 6 and 2, more particularly between 5 and 3; said thionation reaction of compound (V) is carried out in the presence of a thionation agent preferably with thiosulfate of an alkali or alkaline earth agent such as sodium thiosulfate, preferably in the presence of a polar (a)protic solvent, preferably a polar protic solvent such as water;

[0069] preferably the reaction medium in step iii) is maintained under an inert atmosphere, in particular at a temperature less than or equal to the reflux of the solvent, preferably at a temperature between 50 °C and 110 °C, more particularly between 60 °C and 100 °C, preferably between 70 °C and 90 °C such as 80 °C + / - 3 °C; preferably for between 30 minutes and 24 hours, more preferably between 1 hour and 10 hours, better between 4 and 8 hours such as 6 hours; preferably the reaction mixture is cooled to a temperature between 10 °C and 30 °C such as 20 °C + / - 5 °C;

[0070] iiil) the reaction mixture is then adjusted preferably to a pH between 7 and 8, in particular using at least one alkaline agent as defined above, preferably a mineral alkaline agent such as sodium hydroxide; preferably the reaction mixture is then left under mechanical stirring at a temperature between 10 °C and 30 °C such as 20 °C + / - 5 °C in particular for one minute to one hour such as 15 minutes; preferably the reaction mixture is filtered and the solid is washed with particularly a polar (a)protic solvent, preferably a polar protic solvent such as water;

[0071] iii2) the filtrate is then acidified, preferably at a temperature greater than or equal to 40 °C, such as 60 °C + / - 5 °C, using an organic or mineral acid, preferably mineral such as hydrochloric acid, until a pH between 1 and 5, preferably between 1.5 and 3, such as 2 + / - 0.5, is obtained; the temperature is then preferably maintained at 60 °C + / - 5 °C for a period particularly between 1 minute and 30 minutes, such as 15 minutes; preferably the reaction mixture is then left under mechanical stirring at a temperature between 10 °C and 30 °C such as 20 °C + / - 5 °C in particular for one minute to one hour such as 15 minutes; preferably the reaction mixture is filtered and the solid is washed with particularly a polar (a)protic solvent, preferably a polar protic solvent such as water; preferably the solid is dried at a temperature between 20 °C and 60 °C such as 50 °C in particular under vacuum;

[0072] iii3) the solid can be purified by solubilizing it in a (a)polar protic solvent, preferably a polar protic solvent such as water, adjusting the pH between 7 and 8 using, in particular, an alkali agent as defined above, preferably a mineral such as the soda, the mixture is then preferably kept under mechanical stirring, in particular between 10 °C and 30 °C such as 20 °C + / - 5 °C for between 1 minute and 30 minutes, such as 5 minutes; the mixture is then preferably filtered and the solid washed with a polar (a)protic solvent, preferably a polar protic solvent such as water;

[0073] iii4) the filtrate is then optionally acidified (depending on the nature of M) using mineral or organic acid, preferably mineral such as hydrochloric acid, in particular at a temperature greater than or equal to 40 °C, such as 60 °C + / - 5 °C, preferably the pH is maintained between 1 and 4, more preferably between 1.5 and 3 such as 2 + / - 0.5; preferably the mixture is then left at a temperature greater than or equal to 40 °C, such as 60 °C + / - 5 °C, for in particular between 1 and 60 minutes such as 15 minutes, the solid is then filtered and washed with a polar (a)protic solvent, preferably polar protic such as water, followed in particular by drying at a temperature greater than or equal to 20 °C, more particularly at a temperature between 40 °C and 60 °C such as 50 °C, preferably under vacuum.

[0074] In accordance with a general feature of the invention, step (i), i.e. the step of preparing the compound of formula (III) by activating the carboxylic group of the compound of formula (II), is preferably carried out in the presence of one or more activating agents of carboxylic acids, in an organic solvent.

[0075] The carboxylic acid activating agent(s) may be chosen from the group consisting of thionyl halides such as thionyl chloride, oxalyl halides such as oxalyl chloride, and mixtures thereof, preferably thionyl chloride (SOC12).

[0076] Preferably, the activating agent is thionyl chloride (SOC12) and the organic solvent has a dielectric constant E ranging from 1 to 7 and a dipole moment p ranging from 0 to 2.

[0077] Preferably, the activating agent is thionyl chloride (SOC12) and the organic solvent is chosen from the group consisting of ethyl acetate, methyltetrahydrofuran and toluene, more preferably ethyl acetate.

[0078] Step (ii), i.e. the step of reacting the compound of formula (III) with an amine of formula (IV) to lead to a compound of formula (V), is preferably carried out by contacting a composition comprising at least the compound of formula (III) and at least one organic solvent, preferably an aprotic organic solvent as described above, and an aqueous composition comprising at least the amine of formula (IV), in the presence of one or more alkali agents.

[0079] Advantageously, step (ii) is thus implemented in a reaction medium whose pH is strictly greater than 7, i.e. therefore at basic pH.

[0080] In other words, the reaction step of the compound of formula (III) with an amine of formula (IV) to lead to a compound of formula (V) takes place in a basic medium.

[0081] In this way, according to the synthesis scheme (1), the halogenated derivatives of general formula HHal' (Hal' as defined above), in particular hydrochloric acid, generated during step (ii), are efficiently neutralized during step (ii).

[0082] Step (ii) is preferably carried out in a reaction medium with a pH ranging from 7.5 to 10.

[0083] Step (ii) advantageously comprises the addition of a composition comprising at least the compound of formula (III) and at least one organic solvent, preferably an aprotic organic solvent as described above, to a composition comprising at least one amine of formula (IV) and one or more alkali agents.

[0084] In this case, the alkali agent(s) may be added to a composition comprising at least the amine of formula (IV) before the implementation of step (ii).

[0085] Alternatively, step (ii) advantageously comprises the simultaneous addition of a composition comprising at least the compound of formula (III) and at least one organic solvent, preferably an aprotic organic solvent as described above, and an aqueous composition comprising one or more alkali agents to an aqueous composition comprising at least one amine of formula (IV).

[0086] The yield of the process according to the invention is thus advantageously improved when said composition comprising at least the compound of formula (III) and said aqueous composition comprising one or more alkali agents are added simultaneously to said aqueous composition comprising at least one amine of formula (IV).

[0087] According to this alternative, the aqueous composition comprising at least the amine of formula (IV) may further comprise one or more alkali agents.

[0088] In this case, the alkali agent(s) may be added to a composition comprising at least the amine of formula (IV) before the implementation of step (ii).

[0089] The alkali agent content may vary from 2 to 4 molar equivalents, preferably from 2.5 to 3.5 molar equivalents, relative to the number of moles of the compound of formula (III).

[0090] The amine content of formula (IV) can vary from 1.5 to 3 molar equivalents, preferably from 1.8 to 2.5 equivalents, relative to the number of moles of the compound of formula (III).

[0091] Preferably, the organic solvent is identical to the organic solvent used in step i) and has in particular a dielectric constant E ranging from 1 to 7 and a dipole moment p ranging from 0 to 2.

[0092] More preferably, the organic solvent is chosen from the group consisting of ethyl acetate, methyltetrahydrofuran and toluene, more preferably ethyl acetate.

[0093] The organic solvent may be present in a content ranging from 70 to 90% by weight, preferably in a content ranging from 75 to 85% by weight, relative to the total weight of the composition comprising at least the compound of formula (III).

[0094] Water may be present in a content ranging from 60 to 90% by weight, preferably in a content ranging from 70 to 80% by weight, relative to the total weight of the composition comprising at least the amine of formula (IV).

[0095] The volume ratio between the organic solvent and water can vary from 3 to 1, preferably is equal to 2 / 1.

[0096] The reaction temperature can vary from 10 to 45 °C, preferably varies from 15 to 25 °C.

[0097] The duration of the reaction can vary from 10 to 120 minutes, preferably varies from 30 to 60 minutes.

[0098] Once the reaction is complete, the reaction medium can be acidified with an aqueous solution of organic or mineral acid, preferably mineral.

[0099] Examples of acidifying agents include mineral or organic acids such as hydrochloric acid, orthophosphoric acid, sulfuric acid, carboxylic acids such as acetic acid, tartaric acid, citric acid, lactic acid, and sulfonic acids.

[0100] Preferably, the acidifying agent is a mineral acid, in particular hydrochloric acid.

[0101] The desired product of formula (V) precipitates from the medium and is filtered and washed with water before being engaged in step (iii).

[0102] As previously stated, step iii) is a reaction step of the compound of formula (V) to form a compound of formula (I).

[0103] Step iii) is an exchange reaction between the halogen atom and the thiol group -SH or the sulfur atom to form a compound of formula (I).

[0104] Preferably, step iii) is carried out using one or more reagents such as alkali metal (dis)sulfites, in particular sodium disulfite, alkali metal thiosulfates, in particular sodium thiosulfate, thiosulfate, thiourea, or thioacetic acid, and mixtures thereof.

[0105] More preferably, step iii) is carried out using alkali metal thiosulfates, in particular sodium thiosulfate.

[0106] The quantity of reactants may vary from 1.2 to 3 molar equivalents, preferably from 1.4 to 2 molar equivalents, relative to the number of moles of the compound of formula (V).

[0107] The reaction temperature can vary from 60 °C to 110 °C, preferably from 70 °C to 100 °C, more preferably between 75 °C and 90 °C such as 80 °C.

[0108] The reaction temperature advantageously allows limiting the formation of impurities while ensuring a complete reaction.

[0109] The duration of reaction iii) may vary from 3 to 10 hours, preferably from 4 to 8 hours, such as 6 hours

[0110] During reaction iii), the pH of the reaction medium is at a pH less than 7, preferably less than or equal to 6, more preferably less than or equal to 5, even more preferably less than or equal to 4, in particular in a pH range from 1 to 4, preferably 2 and 3.

[0111] According to a particular embodiment of the invention, the pH is between 6 and 2, more particularly between 5 and 3.

[0112] The compound of formula (V) can then be filtered, washed once or several times, preferably with water.

[0113] The process according to the invention thus makes it possible to prepare one or more compounds of formula (I) as well as their optical isomers, geometric isomers, and tautomers, as well as their acid or base salts, organic or mineral, and their solvates such as hydrates.

[0114] Salts of compounds of formula (I) include conventional non-toxic salts of said compounds such as those formed from acid or base.

[0115] As examples of salts of compounds of formula (I), the following may be cited in particular:

[0116] - the salts obtained by adding the compound of formula (I) with a base mineral, such as soda, potash, calcium hydroxide, ammonium hydroxide, magnesium hydroxide, lithium hydroxide, and carbonates or hydrogen carbonates of sodium, potassium or calcium for example;

[0117] - the salts obtained by adding the compound of formula (I) with an organic base such as a primary, secondary or tertiary alkylamine, for example triethylamine or butylamine. This primary, secondary or tertiary alkylamine may contain one or more nitrogen and / or oxygen atoms and may therefore contain, for example, one or more alcohol functions; examples include 2-amino-2-methyl-2-propanol, ethanolamine, triethanolamine, dimethylamino-2-propanol, 2-amino-2-(hydroxymethyl)-1,3-propanediol, 3-(dimethylamino)propylamine.

[0118] We can also mention amino acid salts such as, for example, lysine, arginine, guanidine, glutamic acid, aspartic acid.

[0119] Advantageously, the salts of the compounds of formula (I) can be chosen from alkali or alkaline earth salts such as sodium, potassium, calcium, magnesium; ammonium salts.

[0120] Acceptable solvates of compounds of formula (I) include conventional solvates such as those formed during the preparation of said compounds due to the presence of solvents.

[0121] By way of example, we can cite the solvates due to the presence of water or linear or branched alcohols such as ethanol or isopropanol.

[0122] Optical isomers include enantiomers and diastereomers.

[0123] For the purposes of this invention, the term tautomer refers to the following two forms:

[0124] Preferably, in formulas (I), (IV) and (V), A represents a divalent hydrocarbon chain, saturated or unsaturated, preferably saturated, cyclic or acyclic, preferably acyclic, linear or branched, comprising from 1 to 10 carbon atoms, not interrupted by one or more heteroatoms or groups as described above.

[0125] Preferably, in formulas (I), (IV) and (V), A represents a (Cr C6)alkylene group, more preferably a (Ci-C4)alkylene group, in particular methylene.

[0126] Preferably, in formulas (I), (IV) and (V), R1 represents a hydrogen atom.

[0127] In formulas (I), (IV) and (V), where M represents an alkali or alkaline earth metal, M is preferably a sodium atom or a potassium atom, more preferably sodium.

[0128] According to a preferred feature of the invention, in formulas (I), (IV) and (V), R1 represents a hydrogen atom, A represents a (Ci-C6)alkylene group, more preferably a (Ci-C4)alkylene group, in particular methylene, M represents a hydrogen atom, an alkali or alkaline earth metal, or an ammonium group.

[0129] Advantageously, the process according to the invention makes it possible to prepare one or more compounds of formula (I) chosen from the group consisting of compounds corresponding to the following formula (I'):

[0130] Formula (!') in which:

[0131] M represents a hydrogen atom, an alkali or alkaline earth metal, such as a sodium atom or a potassium atom, an ammonium group, more preferably sodium;

[0132] as well as their optical isomers, geometric isomers, and tautomers, as well as their acid or base salts, organic or mineral, and their solvates such as hydrates.

[0133] Preferably, in formulas (I) and (I'), M represents a hydrogen atom.

[0134] The process according to the invention thus makes it possible to prepare the compound(s) of formula (!') preferably according to the following synthesis scheme (1'): G

[0135] In formulas (III'), (IV'), (V') and (I'), M represents a hydrogen atom, an alkali or alkaline earth metal, such as a sodium atom or a potassium atom, an ammonium group.

[0136] Preferably, M represents a hydrogen atom. Compounds (I”)

[0137] The present invention also relates to a compound of the following formula (I”): (I”)

[0138]

[0139]

[0140]

[0141] • Formula (I”) in which: - M, A and R1 have the same meanings as in formula (I), as well as their optical isomers, geometric isomers, and tautomers, as well as their acid or base salts, organic or mineral, and their solvates such as hydrates, with the exception of compounds (X) and (XI) and their tautomers (X') and (XI)' following: (X) ,Q UH (X') ,0 OH (XI) .0 ûH (xr) ...,,0 GH ''SH Optical isomers, acid or base salts, solvates, and tautomers have the same definitions as those mentioned previously. Composition The invention also relates to a composition, preferably cosmetic, comprising at least one compound of formula (I”) and their optical isomers, geometric isomers, and tautomers, as well as their acid or base salts, organic or mineral, and their solvates such as hydrates.

[0142] The invention also relates to a composition, preferably cosmetic, comprising a) at least one compound of formula (I”) and their optical isomers, geometric isomers, and tautomers, as well as their acid or base salts, organic or mineral, and their solvates such as hydrates and b) at least one compound of formula (I) and their optical isomers, geometric isomers, and tautomers, as well as their acid or base salts, organic or mineral, and their solvates such as hydrates preferably at least one compound of formula (!') and their optical isomers, geometric isomers, and tautomers, as well as their acid or base salts, organic or mineral, and their solvates such as hydrates, it being understood that said compound of formula (I) or (!') differs from the compounds of formula (I”) by the nature of the divalent radical A and / or by the nature of the radical RI.

[0143] Preferably, the compound of formula (I”) may be present in the composition in a content ranging from 0.01 to 10% by weight, preferably in a content ranging from 0.1 to 5% by weight, more preferably in a content ranging from 0.5 to 3% by weight, relative to the total weight of the composition.

[0144] The composition according to the invention preferably comprises a physiologically acceptable medium, in particular a medium compatible with human keratinous materials, such as body or face skin, lips, mucous membranes, eyelashes, nails, scalp and / or hair.

[0145] The composition may further include at least one adjuvant commonly used in the cosmetic field.

[0146] By way of example, one can cite cosmetic adjuvants chosen from the group consisting of organic solvents, in particular alcohols in C1-C6, more preferably in C2-C6 and carboxylic acid esters in C2-C10; oils, in particular hydrocarbon oils and / or silicone oils of mineral, animal and / or vegetable origin; waxes, pigments, fillers, colorants, surfactants, emulsifiers; cosmetic or dermatological actives, UV filters, polymers, hydrophilic or lipophilic gelling agents, thickeners, preservatives, perfumes, bactericides, ceramides, odor absorbers, antioxidants.

[0147] These possible cosmetic adjuvants may be present in the composition at a rate of 0.001 to 80% by weight, in particular 0.1 to 40% by weight, relative to the total weight of the composition.

[0148] The invention is illustrated in more detail in the following non-limiting examples. Example :

[0149] Step 1: Preparation of the acyl halide (acyl chloride) O QH 1 js O c F, n J e Q i AcQt t sWi rstux. «h 2JD:¥:iOf: ZV EtOAc at 5Ô = £ (Zi

[0150] In a 1 L reactor equipped with a thermometer, a condensation column and a mechanical stirrer, compound 2-chloroonicotinic acid (Z) (70 g, 0.444 mol) and ethyl acetate (280 ml, 4.0 v / w) are introduced.

[0151] The resulting white suspension is heated under reflux in solvent under an inert atmosphere (nitrogen). Thionyl chloride (35.4 mL, 0.489 mol, 1.1 eq.) is added dropwise. The mixture is maintained under reflux with mechanical stirring for an additional 4 hours.

[0152] Once the reaction is complete, the mixture is cooled to a temperature of 50 °C. Ethyl acetate (140 ml, 2.0 v / w) is then added and cooled to a temperature of 25 °C and left to stand under an inert atmosphere (nitrogen). Step 2: amide formation Glycine (IV') (66.7 g, 0.890 mol, 2.0 eq.) and water (259 ml, 3.7 v / w) are introduced into a 1 L reactor equipped with a thermometer, a pH probe and a mechanical stirrer.

[0154] The suspension is cooled to a temperature of 20 ± 5 °C under an inert atmosphere (nitrogen) and 25% aqueous sodium hydroxide NaOHaq (~ 56 ml, 1.0 eq.) is added until a basic pH (> 7) is obtained.

[0155] A solution of acyl(III') chloride in ethyl acetate and a 25% NaOH(aq) solution (~84 mL, 1.5 eq.) are introduced into two separate stopcocks. The acyl chloride solution is added dropwise to the reactor at a temperature of 20 ± 5 °C. During the addition, the pH is maintained at a basic level, preferably between 7.5 and 10, by adding the 25% NaOH(aq) solution.

[0156] Once the addition is complete, the solution is stirred at a temperature of 20 ± 5 °C for a further hour. The mixture is then allowed to settle for a The mixture is left for 30 minutes and the aqueous phase containing compound (V'a) is collected. The ethyl acetate phase is removed.

[0157] The aqueous phase is acidified at a temperature of 25 ± 5 °C with a mineral or organic acid, preferably mineral such as hydrochloric acid, preferably HCl 37% (~ 58.4 ml, 1.6 eq.) up to pH 2.5 ± 0.2. The resulting suspension is left under stirring at a temperature of 25 °C ± 5 °C for about 1 hour.

[0158] The medium is then filtered and the resulting solid is washed with water (140 ml, 2.0 v / w), then dried at a temperature of 50 °C overnight under vacuum to produce the compound (V'b) with a yield of 89% (85.3 g, white powder). Step 3: thionation

[0160] In an IL reactor equipped with a thermometer, a condensation column, a pH probe, and a mechanical stirrer, the compound of formula (V'b) (80 g, 0.373 mol), sodium thiosulfate pentahydrate (185 g, 0.746 mol, 2.0 eq relative to (V'b)), and water (400 mL, 5 v / w) are introduced. The resulting white suspension is heated under an inert atmosphere (nitrogen) to a temperature of 80 °C ± 3 °C and maintained under stirring for several hours (e.g., between 3 and 6 hours).

[0161] The reaction mixture is then cooled to room temperature (20 °C ± 5 °C).

[0162] It should be noted that the thionation reaction is carried out at an acidic pH preferably between 2 and 6 such that 5. Isolation:

[0163] At the end of the reaction, the pH of the reaction mixture is adjusted to a pH between 7 and 8 using a 50% NaOH(aq) solution (-35.8 g, 0.447 mol, 1.20 eq.). The mixture is stirred at room temperature (20 °C ± 5 °C) until the pH stabilizes (e.g., 5 minutes). The mixture is filtered to remove elemental sulfur. The solid is rinsed with water (80 mL, 1 v / w), and the combined filtrates containing the compound of formula (l) are transferred to a 1 L vacuum reactor equipped with a thermometer, a condensation column, a pH probe, and a mechanical stirrer. The solution is heated to a temperature of 60 °C ± 5 °C, acidified by the addition of an organic or mineral acid, preferably a mineral acid such as hydrochloric acid, in particular 34% HCl, until an acidic pH is obtained (e.g., 2.0 ± 0.5). The suspension is kept under stirring at a temperature of 60 °C for 15 minutes before being cooled and maintained at a temperature of 20 °C ± 5 °C and left under stirring for an additional 15 minutes. The solid is filtered and washed with water (2 x 80 mL, 2 x 1 v / w) and then dried at a temperature of 50 °C under vacuum. Compound (I'b) is obtained with a yield of 93% (73.4 g, HPLC purity 99.5%) as a yellow solid. Step 4: Purification (optional)

[0164] In a 1 L reactor equipped with a thermometer, a condensation column, a pH probe and a mechanical stirrer, the compound prepared in the previous step 3 is introduced: compound (I'b) (70 g, 0.330 mol) and water (280 ml, 4 v / w).

[0165] The pH of the mixture is adjusted to pH between 7 and 8 using 50% NaOHaq (-29.0 g, 0.363 mol, 1.10 eq.).

[0166] The mixture is left under agitation at room temperature (20 ± 5 °C) until the pH stabilizes (for example 5 minutes).

[0167] The mixture is then filtered to remove any residual elemental sulfur. The filter is rinsed with water (70 mL, 1 v / w). The filtrate is transferred to an empty 1 L reactor equipped with a thermometer, a pH probe, and a mechanical stirrer. The solution is heated to a temperature above 60°C and acidified by the addition of a mineral or organic acid, preferably a mineral acid such as 34% HCl, to, for example, pH 2.0 ± 0.5 (~42.5 g, 0.396 mol, 1.20 eq.).

[0168] The suspension is stirred at a temperature above 40 °C, for example 60 °C or higher, for several minutes, for example 15 minutes. The suspension is cooled to room temperature (such as 20 °C ± 5 °C) and stirred again for several more minutes (such as 15 minutes). The resulting solid is filtered and washed with water (2 x 70 mL, 2 x 1 w / w).

[0169] The solid obtained was dried at 50 °C under vacuum to give the purified compound (I'b) with a yield of 98% (68.30 g, HPLC purity 99.55%) in the form of a yellow solid.

[0170] The purity of compounds (l'a) and (L'b) is measured on an HPLC system (WATERS Alliance 2695 type or equivalent) equipped with a column oven and a dual-wavelength UV detector or a photodiode array detector. Detection is performed at 300 nm. The mobile phase consists of a pH 3 buffered ammonium acetate solution and methanol. The column used is a Gemini C18 5µm - 250 x 4.6 mm.

Claims

Demands

1. A process for preparing at least one compound of the following formula (I): Formula (I) in which: - A represents a divalent hydrocarbon chain, saturated or unsaturated, preferably saturated, cyclic or acyclic, preferably acyclic, linear or branched, comprising from 1 to 10 carbon atoms, optionally interrupted by one or more heteroatoms, such as an oxygen atom, a sulfur atom, or groups selected from an NR2 or (thio)carbonyl group, or their associations such as thioester, with R2 representing a hydrogen atom or a Ci-C4 alkyl group; - M represents a hydrogen atom, an alkali or alkaline earth metal, an ammonium group; - R1 represents a hydrogen atom, an alkyl group, linear or branched, in Ci-Cio, possibly substituted by an OR3, SR3 group with R3 corresponding to a hydrogen atom or an alkyl group, linear or branched, in Ci-Ci0, as well as one of its optical isomers, geometric isomers, and tautomers, as well as one of its acid or base salts, organic or mineral, and one of its solvates such as hydrates; said process taking place according to the following synthesis scheme (1): • in which: - Hal and Hal', identical or different, represent a halogen atom, and - M, A and R1 have the same meanings as in formula (I); at least step (iii) is at acidic pH i.e. less than 7.

2. A process according to claim 1, characterized in that step (iii) takes place at a pH less than or equal to 6, more preferably less than or equal to 5, even more preferably less than or equal to 4, in particular in a pH range from 1 to 4, preferably 2 and 3.

3. A process according to claim 1 or 2, characterized in that step (iii) takes place at a pH between 6 and 2, more particularly between 5 and 3.

4. A method according to any one of the preceding claims, characterized in that step (ii) is carried out by contacting a composition comprising at least the compound of formula (III) and at least one organic solvent, and a composition aqueous comprising at least the amine of formula (IV), in the presence of one or more alkaline agents.

5. A process according to any one of the preceding claims, characterized in that step (ii) comprises the addition of a composition comprising at least the compound of formula (III) and at least one organic solvent, to a composition comprising at least the amine of formula (IV) and at least one alkali agent.

6. A process according to any one of the preceding claims, characterized in that step (ii) comprises the simultaneous addition of a composition comprising at least the compound of formula (III) and at least one organic solvent, and of an aqueous composition comprising one or more alkali agents to an aqueous composition comprising at least the amine of formula (IV).

7. A process according to any one of the preceding claims, characterized in that step (ii) is carried out in a reaction medium having a pH strictly greater than 7, preferably having a pH ranging from 7.5 to 10.

8. A process according to any one of the preceding claims, characterized in that step (ii) is carried out with: * at least one equivalent of compound (IV), preferably more than one equivalent, in particular between 1.5 and 2.5 equivalents, more particularly 2 equivalents of compound (IV), preferably in a polar (a)protic solvent, preferably a polar protic solvent such as water, in particular in a volume-weight ratio of between 1 and 7, preferably between 2 and 5, such as 3.5 relative to the weight of the compound of formula (II), preferably the reaction mixture is left at a temperature of between 10 °C and 30 °C, such as 20 °C + / - 5 °C, preferably the reaction medium is left under an inert atmosphere, then particularly at least one mineral or organic alkali agent, preferably a mineral one such as sodium hydroxide, is added, at least one equivalent of the alkali agent is added to the reaction medium to achieve a basic pH of said medium,* at least one compound of formula (III) in particular in a nonpolar aprotic organic solvent, in particular ethyl acetate or toluene, with an alkali agent, said alkali agent preferably being in a polar (a)protic solvent such as water, more particularly a mineral alkali agent such as sodium hydroxide,

9. preferably between 1 and 3 equivalents of alkaline agent, such as 1.5 equivalents, preferably the compound of formula (III) is added dropwise to the compound of formula (IV) at a temperature between 10 °C and 30 °C such as 20 °C + / - 5 °C and preferably under an inert atmosphere and under mechanical stirring, particularly the reaction is maintained between 1 minute and 6 hours, more particularly between 30 minutes and 2 hours, such as one hour; more preferably during the addition of the compound of formula (III) said reaction medium is maintained at a basic pH, more particularly between 7.5 and 10; preferably the mixture is left to settle, particularly at a temperature between 10 °C and 30 °C such that at 20 °C + / - 5 °C, the aqueous phase is collected; particularly the aqueous phase is cooled to a temperature below 30 °C, preferably between 20 and 30 °C, such as 25 °C + / -5 °C; preferably said phase is acidified with a mineral or organic acid, preferably mineral such as hydrochloric acid, in particular with at least 1 equivalent of acid, preferably between 1 and 3 equivalents such as 1.6 equivalents, the pH of said aqueous phase is preferably between 1 and 5, in particular between 2 and 4 such as 2.5 + / -0.2; preferably the aqueous phase is then filtered and the resulting solid is preferably washed with a polar (a)protic solvent, preferably a polar protic solvent such as water; then said solid is optionally dried, preferably at a temperature greater than or equal to 20 °C, more preferably between 30 °C and 60 °C, such as 50 °C + / - 5 °C; to give the compound of formula (V); The drying step is optional; the wet product can be used directly in the next step. A process according to any one of claims 2 to 6, characterized in that the alkali agent(s) may be organic or mineral alkali agents, preferably selected from the group consisting of alkali or alkaline earth metal hydroxides, in particular sodium hydroxide, alkali or alkaline earth metal (bi)carbonates, in particular sodium or potassium (bi)carbonates and tri(Ci-C6)(hydroxy)alkylamines, in particular tri(Ci-C6)alkylamines, in particular triethylamine.

10.

11. A process according to any one of the preceding claims, characterized in that in step (iii) the thionation reaction of compound (V) is carried out in the presence of a thionation agent, preferably with an alkali or alkaline earth thiosulfate such as sodium thiosulfate, preferably in the presence of a polar protic solvent, preferably a polar protic solvent such as water; preferably the reaction medium in step (iii) is maintained under an inert atmosphere, in particular at a temperature less than or equal to the reflux of the solvent, preferably at a temperature between 50 °C and 110 °C, more particularly between 60 °C and 100 °C, preferably between 70 °C and 90 °C such as 80 °C + / - 3 °C; preferably for between 30 minutes and 24 hours, more preferably between 1 hour and 10 hours, preferably between 4 and 8 hours such as 6 hours;Preferably the reaction mixture is cooled to a temperature between 10 °C and 30 °C such that 20 °C + / - 5 °C. A process according to the preceding claim, characterized in that after step (iii) of thionation: iül) the reaction mixture is adjusted preferably to a pH between 7 and 8, in particular using at least one alkaline agent as defined above, preferably a mineral alkaline agent such as sodium hydroxide; preferably the reaction mixture is then left under mechanical stirring at a temperature between 10 °C and 30 °C such as 20 °C + / - 5 °C in particular for one minute to one hour such as 15 minutes; preferably the reaction mixture is filtered and the solid is washed with particularly a polar (a)protic solvent, preferably a polar protic solvent such as water; iii2) the filtrate is then acidified, preferably at a temperature greater than or equal to 40 °C, such as 60 °C + / - 5 °C, using an organic or mineral acid, preferably mineral such as hydrochloric acid, until a pH between 1 and 5 is obtained, preferably between 1.5 and 3, such as 2 + / - 0.5; the temperature is then preferably maintained at 60 °C + / - 5 °C for a period particularly between 1 minute and 30 minutes, such as 15 minutes; Preferably, the reaction mixture is then left under mechanical stirring at a temperature between 10 °C and 30 °C, such as 20 °C + / - 5 °C, in particular for one minute to one hour.

12.

13. such as 15 minutes; preferably the reaction mixture is filtered and the solid is washed with particularly a polar (a)protic solvent, preferably polar protic such as water; preferably the solid is dried at a temperature between 20 °C and 60 °C such as 50 °C especially under vacuum; iii3) the solid can be purified by solubilizing it in a polar (a)protic solvent, preferably a polar protic solvent such as water, adjusting the pH between 7 and 8 using, in particular, an alkaline agent, preferably a mineral one such as soda, the mixture is then preferably kept under mechanical stirring, in particular between 10 °C and 30 °C such as 20 °C + / - 5 °C for between 1 minute and 30 minutes, such as 5 minutes; the mixture is then preferably filtered and the solid washed with a polar (a)protic solvent, preferably a polar protic solvent such as water; iii4) the filtrate is then optionally acidified, according to the nature of M, with mineral or organic acid, preferably mineral such as hydrochloric acid, in particular at a temperature greater than or equal to 40 °C, such as 60 °C + / - 5 °C, preferably the pH is maintained between 1 and 4, more preferably between 1.5 and 3 such as 2 + / - 0.5; preferably the mixture is then left at a temperature greater than or equal to 40 °C, such as 60 °C + / - 5 °C, for in particular between 1 and 60 minutes such as 15 minutes, the solid is then filtered and washed with a polar (a)protic solvent, preferably polar protic such as water, followed in particular by drying at a temperature greater than or equal to 20 °C, more particularly at a temperature between 40 °C and 60 °C such as 50 °C, preferably under vacuum. A process according to any one of claims 4 to 11, characterized in that the volume ratio between the organic solvent and water can vary from 3 to 1, preferably is equal to 2 / 1. A method according to any one of the preceding claims, characterized in that: • A represents a (Ci-C6)alkylene group, more preferably a (Ci-C4)alkylene group, notably methylene; and / or • R1 represents a hydrogen atom.

14. A process according to any one of the preceding claims, characterized in that the compound(s) of formula (I) is or are chosen from the group consisting of compounds corresponding to the following formula (F): p (D / X, ,„ <P £ X, GM

15. Formula (F) in which M represents a hydrogen atom, an alkali or alkaline earth metal, such as a sodium atom or a potassium atom, an ammonium group; preferably M represents a hydrogen atom. Composed of the following formula (I"): • Formula (I' ') in which: - A represents a divalent hydrocarbon chain, saturated or unsaturated, preferably saturated, cyclic or acyclic, preferably acyclic, linear or branched, comprising from 1 to 10 carbon atoms, optionally interrupted by one or more heteroatoms, such as an oxygen atom, a sulfur atom, or groups selected from an NR2 or (thio)carbonyl group, or their associations such as thioester, with R2 representing a hydrogen atom or a Ci-C4 alkyl group; - M represents a hydrogen atom, an alkali or alkaline earth metal, an ammonium group; - R1 represents a hydrogen atom, as well as their optical isomers, geometric isomers, and tautomers, as well as their acid or base salts, organic or mineral, and their solvates such as hydrates, with the exception of compounds (X) and (XI) and their following tautomers (X') and (XI)':

16. Composition, preferably cosmetic, comprising one or more compounds of formula (I”), as described in the preceding claim, as well as their optical isomers, geometric isomers, and tautomers, as well as their acid or base salts, organic or mineral, and their solvates such as hydrates.