Process for preparation of one or more compounds of thiopyridone type

Abstract

A process for the preparation of one or more compounds of the thiopyridone type. The present invention relates to a method for preparing one or more compounds of the thiopyridone type of formula (I) as well as the optical isomers, geometric isomers and tautomers thereof, and also organic or inorganic acid or alkali salts thereof, and solvates such as hydrates thereof. The invention also relates to one or more compounds of the thiopyridone type of formula (I '') and to compositions using said compounds.

Description

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

[0002] The present invention also relates to one or more compounds of the thiopyridone type of formula (I").

[0003] N-[(2-Thioxo-1,2-dihydropyridin-3-yl)carbonyl]glycine (belonging to the thiopyridone family) is the following compound: its properties are generally advantageous in the cosmetic field, in particular for use as a whitening agent, brightening agent and / or depigmenting agent for keratin materials, especially the skin.

[0004] N-[(2-Thioxo-1,2-dihydropyridin-3-yl)carbonyl]glycine can be prepared, for example, by the synthetic route described in the scientific paper entitled "Synthesis of N-(2-mercaptopyridyl-3-formyl)-N-alkyl glycine and the corresponding disulfides" (Luo, Y.L., Yang, Z.X. and Peng, S.X., Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing (Div. Med. Chem., China Pharm. Univ., Nanjing), 21009, China, Acta Pharmaceutica Sinica, 25(5), 374 - 8 (1990)).

[0005] More generally, compounds of the thiopyridone type corresponding to the following formula (A):

[0006]

[0007] ■ In formula (A):

[0008] -R A represents a hydrogen atom or a saturated straight-chain C1-C6 alkyl group,

[0009] -R B represents a hydrogen atom, a saturated straight-chain C1-C 10 alkyl group, a saturated branched-chain C3-C 10 alkyl group or a phenyl(C1-C6)alkyl group;

[0010] can be prepared according to the following synthetic route:

[0011]

[0012] More particularly, according to such reaction schemes, a process for preparing a compound of the thio-pyridone type of formula (A) comprises at least the following successive stages:

[0013] a) Activating the carboxylic acid group of 2-chloronicotinic acid of the following formula in the presence of at least one reagent for activating carboxylic acids, at least according to the conventional methods for acid activation (for example, as described in the chapter Interconversion of Nitriles, Carboxylic Acids and Derivative of R. Larock's Comprehensive Organic Transformations published by Wiley VCH, 1989):

[0014]

[0015] To produce the stage of a compound corresponding to the following formula (W):

[0016]

[0017] ■ In formula (W):

[0018] -X forms an acyl halide and a mixed anhydride,

[0019] b) Reacting at least the compound of formula (W) with an amine of the following formula (V):

[0020]

[0021] To produce the stage of a compound of the following formula (Y):

[0022]

[0023] ■ In formulas (V) and (Y), R A and R B have the same meaning as in formula (A); then

[0024] c) Exchanging the chlorine atom for a sulfur atom using a reagent such as sodium dithionite, thiourea, sodium thiosulfate or thioacetic acid, at least in an alkaline medium, in order to produce one or more compounds of formula (A):

[0025]

[0026] d) And optionally, for those in which the group R BA compound of formula (A) representing a hydrogen atom (i.e., containing a carboxylic acid group), which can also be obtained by means of at least one additional step of saponifying the corresponding ester using one or more inorganic bases, such as sodium hydroxide (NaOH) or lithium hydroxide (LiOH), followed by acidification.

[0027] It follows that the unesterified thiopyridone compounds, i.e., those corresponding to formula (A) (where R B represents a group other than an alkyl or phenylalkyl group), can be prepared by this method by employing one or more additional saponification steps (optional step d)) or directly from the corresponding amine of formula (V) (step b)).

[0028] However, this method still exhibits a certain number of drawbacks (e.g., additional saponification steps, impurities), especially when the desired final thiopyridone compound is unesterified.

[0029] On the one hand, when the thiopyridone compound of formula (A) (where the group R B corresponds to a hydrogen atom) is obtained directly from the corresponding amine of formula (V), i.e., without employing one or more additional saponification steps, the method so implemented still too often causes feasibility difficulties on an industrial scale and requires better optimization.

[0030] On the other hand, when the thiopyridone compound of formula (A) (where the group R B corresponds to a hydrogen atom) is obtained from the implementation of one or more additional saponification steps, then the method particularly exhibits the drawbacks of increased energy consumption, an increase in the amount of reagents used, and the generation of additional effluents. In addition, such additional steps may lead to a significant decrease in yield.

[0031] It follows that the method for preparing the unesterified thiopyridone compound of formula (A) does not yield a completely satisfactory yield, and its implementation requires further optimization, especially in terms of the number of steps and / or product quality on an industrial scale.

[0032] In view of the above, there is thus a practical need to provide a novel method for preparing a thiopyridone-type compound corresponding to formula (I) as described below, which method does not exhibit the above drawbacks.

[0033] In other words, one of the objects of the present invention is to provide a method for preparing a thiopyridone-type compound, which method particularly has a better yield and its implementation is more optimized, especially at the industrial level. In addition, the compound of formula (I) using the method of the present invention exhibits a higher purity than that obtained by saponification of the ester.

[0034] Accordingly, the subject of the present invention is in particular a method for preparing at least one compound of the following formula (I):

[0035]

[0036] In formula (I):

[0037] - A represents a saturated or unsaturated, preferably saturated, cyclic or acyclic, preferably acyclic, straight-chain or branched divalent hydrocarbon chain containing 1 to 10 carbon atoms, which is optionally inserted with one or more heteroatoms or groups such as oxygen atom, sulfur atom, NR2 or (thio)carbonyl, or a combination thereof such as thioester, wherein R2 represents a hydrogen atom or a C1-C4 alkyl group;

[0038] - M represents a hydrogen atom, an alkali metal or an alkaline earth metal, an ammonium group;

[0039] - R 1 represents a hydrogen atom, a straight-chain or branched C1-C 10 alkyl group - which is optionally substituted by OR3, SR3 groups, wherein R3 corresponds to a hydrogen atom or a straight-chain or branched C1-C 10 alkyl group,

[0040] as well as one of its optical isomers, geometric isomers and tautomers, as well as one of its organic or inorganic acid salts or base salts, and its solvate such as hydrate;

[0041] The method takes place according to the following synthesis scheme ( 1 ):

[0042]

[0043] ■ wherein:

[0044] - Hal and Hal' are the same or different and represent halogen atoms, and

[0045] - M, A and R 1 have the same meaning as in formula (I);

[0046] At least stage (iii) is at an acidic pH, i.e., less than 7.

[0047] Thus, the method according to the present invention enables the achievement of the object as described above, that is, it gives a satisfactory yield and shows an optimized implementation at the industrial level, especially compared to the known methods for obtaining thiopyridone compounds. In addition, these compounds are extremely pure (greater than or equal to 99% by HPLC, actually even greater than or equal to 99.0%).

[0048] Advantageously, the method according to the invention makes it possible to reduce the amount of reagents used as well as the effluents generated, and its implementation can lead to energy savings, in particular compared to known methods for obtaining thiopyridone compounds with one or more additional saponification stages.

[0049] Another subject of the invention is a compound of formula (I"):

[0050]

[0051] ● In formula (I"):

[0052] - M, A and R 1 have the same meaning as in formula (I),

[0053] as well as their optical isomers, geometric isomers and tautomers, as well as their organic or inorganic acid salts or base salts, and their solvates such as hydrates,

[0054] with the exception of the following compounds (X) and (XI) and their tautomers (X') and (XI)':

[0055]

[0056] Furthermore, the 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.

[0057] Other subjects, features, aspects and advantages of the invention will become even more clear and apparent after reading the following description and examples.

[0058] In the following and unless otherwise indicated, the limits of the ranges of values are included within these ranges, in particular in the expressions "between... and" and "ranging from... to...".

[0059] Furthermore, the expression "at least one / species" used in the present specification is equivalent to the expression "one / species or more than one / species".

[0060] Furthermore, the expression "at least" used in the present specification is equivalent to the expression "greater than or equal to". Finally, in a manner known per se, the term "C n " compound or group indicates a compound or group containing "n" carbon atoms in its chemical structure.

[0061] The HPLC purity corresponds to the relative purity expressed as a percentage of the area measured at the maximum absorption wavelength (λ 最大 ) of the product being analyzed.

[0062] Depending on the requirements of the stage of the process according to the invention, the reaction medium can be maintained as an acidic or basic medium.

[0063] An acidic pH (i.e. a pH less than 7) can be adjusted by adding an acidifying agent (optionally in aqueous solution), which is organic or inorganic, especially inorganic. Among these acidifying agents, by way of example, mention may be made of inorganic or organic acids such as hydrochloric acid, orthophosphoric acid, sulfuric acid, carboxylic acids such as acetic acid, tartaric acid, citric acid or lactic acid, and sulfonic acids.

[0064] Preferably, the acidifying agent is an inorganic acid, especially hydrochloric acid.

[0065] Preferably, the acidifying agent is introduced in aqueous solution.

[0066] A basic pH (i.e. a pH greater than 7) can be adjusted by adding a base agent (optionally in aqueous solution), said base agent or alkalizing agent being organic or inorganic, preferably inorganic.

[0067] The base agent can be selected from inorganic base agents, organic base agents or hybrid base agents.

[0068] Within the meaning of the present invention, the terms "base agent" and "alkalizing agent" are used interchangeably.

[0069] The alkalizing agent can be an inorganic base agent, preferably selected from the group consisting of alkali metal hydroxides or alkaline earth metal hydroxides such as lithium hydroxide, sodium hydroxide, potassium hydroxide, alkali metal carbonates (hydrogen carbonates) or alkaline earth metal carbonates (hydrogen carbonates) such as sodium carbonate (hydrogen carbonate) or potassium carbonate (hydrogen carbonate), and mixtures thereof. The alkalizing agent can be an organic base agent, preferably selected from the group consisting of mono-(C1-C6)(hydroxy)alkylamines, di-(C1-C6)(hydroxy)alkylamines, tri-(C1-C6)(hydroxy)alkylamines (preferably tri-(C1-C6)(hydroxy)alkylamines), saturated or unsaturated cyclic amines, which are aromatic such as pyridine, or non-aromatic optionally substituted by one or more (C1-C4)alkyl groups such as tetrahydropyridine optionally substituted by one or more (C1-C4)alkyl groups, piperidine optionally substituted by one or more (C1-C4)alkyl groups, or piperazine optionally substituted by one or more (C1-C4)alkyl groups. Preferably, the base agent of the present invention is a tertiary amine.

[0070] Preferably, the alkalizing agent is selected from the group consisting of alkali metal hydroxides or alkaline earth metal hydroxides, especially sodium hydroxide, alkali metal carbonates (hydrogen carbonates) or alkaline earth metal carbonates (hydrogen carbonates), especially sodium carbonate (hydrogen carbonate) or potassium carbonate (hydrogen carbonate), and tri-(C1-C6)(hydroxy)alkylamines, especially tri-(C1-C6)alkylamines, especially triethylamine.

[0071] More preferably, the basifying agent is inorganic and is selected from the group consisting of: alkali metal hydroxides or alkaline earth metal hydroxides, alkali metal carbonates (hydrogen carbonates) or alkaline earth metal carbonates (hydrogen carbonates), and mixtures thereof, especially alkali metal hydroxides or alkaline earth metal hydroxides, especially sodium hydroxide.

[0072] Preferably, the organic solvent used in the method of the present invention is a non-polar aprotic solvent, that is, having a dielectric constant E in the range of 1 to 11 and a dipole moment μ in the range of 0 to 2, and it is particularly selected from the group consisting of: n-hexane, cyclohexane, 1,4-dioxane, carbon tetrachloride (CCl4), benzene, tetrachloroethylene (Cl2C═CCl2), toluene, carbon disulfide (CS2), trichloroethylene (Cl2C═CHCl), diethyl ether (Et2O), chloroform (CHCl3), bromobenzene (PhBr), chlorobenzene (PhCl), ethyl acetate (CH3C(O)OEt or AcOEt), dimethyl ether (DME), tetrahydrofuran (THF), methyltetrahydrofuran (2-MeTHF), dichloromethane (CH2Cl2), dichloroethane (ClCH2CH2Cl), and 1,1-dichloroethane (Cl2CHCH3). Preferably, the organic solvent exhibits a dielectric constant E in the range of 1 to 7 and a dipole moment μ in the range of 0 to 2. More preferably, one or more organic solvents are selected from ethyl acetate, methyltetrahydrofuran, and toluene, more preferably ethyl acetate.

[0073] Preparation method

[0074] As indicated above, the method according to the present invention occurs according to the reaction scheme as described above ( 1 ), and at least stage (iii), that is, the stage of reacting the compound of formula (V) to produce the compound of formula (I) is carried out at a pH strictly less than 7.

[0075] During the stage (stage (iii)) where reacting the compound of formula (V) results in obtaining the compound of formula (I), the pH of the reaction medium is at a value strictly less than 7.

[0076] Preferably, during stage (iii), the reaction medium 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.

[0077] Preferably, during stage (iii), the reaction medium is at a pH varying from 1 to 4, especially in the range of 2 to 3.

[0078] According to a specific embodiment of the present invention, the pH is between 6 and 2, more particularly between 5 and 3. The method according to the present invention preferably sequentially includes at least the following stages:

[0079] - Step (i) of preparing a compound of formula (III) by activating the carboxyl group of a compound of formula (II) at least by a conventional method for activating acid functional groups in the presence of one or more reagents for activating carboxylic acids, in particular using thionyl halides such as thionyl chloride:

[0080]

[0081] ■ In formula (III):

[0082] - Hal and Hal' have the same meanings as those described above; preferably, Hal and Hal' are the same and more preferably represent a chlorine atom;

[0083]

[0084] In particular, the reagent for activating carboxylic acids is a "reagent for activating carboxylic acids" as defined below, particularly selected from thionyl halides such as thionyl chloride, which is added dropwise (particularly in an amount in excess relative to the carboxylic acid to be activated, preferably between 1 and 2 molar equivalents relative to (II), such as 1.1 molar equivalents of the activator) to the compound of formula (II); preferably, the compound (II) is in a non-polar aprotic solvent as defined above, particularly a solvent which is an ester of a (C1-C6) alkyl acid and a (C1-C6) alkanol, such as ethyl acetate, or an aromatic solvent, such as toluene;

[0085] In particular, 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 the reflux temperature of the solvent, preferably between 40°C and 120°C, such as 77°C or 110.6°C,

[0086] In particular, the reaction mixture of step (i) is preferably continuously stirred mechanically under reflux of the solvent for a period between 30 minutes and 10 hours, more particularly between 1 hour and 6 hours, such as 4 hours;

[0087] Preferably, subsequently, the reaction mixture of step (i) is cooled to ambient temperature (25°C) and preferably under an inert atmosphere;

[0088] - Reacting at least the compound of formula (III) with an amine of formula (IV):

[0089]

[0090] To obtain step (ii) of a compound of formula (V):

[0091]

[0092] ■ In formula (IV) and (V):

[0093] -A, M and R 1 have the same meanings as those indicated above for the compounds of formula (I);

[0094] In particular, stage (ii) is carried out as follows:

[0095] * At least one equivalent of compound (IV), preferably more than one equivalent (in particular between 1.5 equivalents and 2.5 equivalents, more particularly 2 equivalents of compound (IV)), preferably in a polar (aprotic) solvent, preferably a polar protic solvent such as water, in particular with a weight / volume ratio between 1 and 7, still better between 2 and 5, such as 3.5, relative to the weight of the compound of formula (II); preferably, the reaction mixture is at a temperature between 10 °C and 30 °C, such as 20 °C ± 5 °C; preferably, the reaction medium is under an inert atmosphere; subsequently, in particular, at least one inorganic base or organic base, preferably an inorganic base such as sodium hydroxide, is added; at least one equivalent of the base is added to the reaction medium in order to reach an alkaline pH of the medium,

[0096] * At least one compound of formula (III), in particular in a non-polar aprotic organic solvent as defined above, in particular ethyl acetate or toluene, and a base as defined above, which base may preferably be in a polar (aprotic) solvent such as water, more particularly an inorganic base such as sodium hydroxide (preferably between 1 and 3 equivalents of the base, such as 1.5 equivalents),

[0097] Preferably, at a temperature between 10 °C and 30 °C, such as 20 °C ± 5 °C, and preferably under an inert atmosphere and with mechanical stirring, the compound of formula (III) is added dropwise to the compound of formula (IV); in particular, the reaction is maintained between 1 minute and 6 hours, more particularly between 30 minutes and 2 hours, such as one hour;

[0098] More preferably, during the addition of the compound of formula (III), the reaction medium is maintained at an alkaline pH, more particularly between 7.5 and 10;

[0099] Preferably, in particular at a temperature between 10 °C and 30 °C, such as 20 °C ± 5 °C, the mixture is separated by sedimentation and the aqueous phase is collected;

[0100] In particular, the aqueous phase is cooled to a temperature below 30 °C, preferably between 20 °C and 30 °C, such as 25 °C ± 5 °C; preferably, the phase is acidified with an inorganic or organic acid, preferably an inorganic acid 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 the aqueous phase is preferably between 1 and 5, particularly between 2 and 4, such as 2.5 ± 0.2;

[0101] Preferably, the aqueous phase is then filtered, and the obtained solid is preferably washed with a polar (aprotic) solvent, preferably a polar protic solvent such as water; then the solid is preferably dried at a temperature of greater than or equal to 20 °C, more preferably between 30 °C and 60 °C, such as 50 °C ± 5 °C, to produce the compound of formula (V);

[0102] The drying step is optional; the wet product can be directly used in the subsequent step;

[0103] - at least one step (iii) of sulfiding the compound of formula (V) to produce the compound of formula (I);

[0104] The reaction step (iii) occurs at a pH less than 7 (excluding the value 7), i.e., the step occurs 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, still more preferably less than or equal to 4, particularly in the pH range extending from 1 to 4, preferably from 2 to 3; according to a specific embodiment of the present invention, the pH of step (iii) is between 6 and 2, more particularly between 5 and 3;

[0105] The sulfidation reaction of the compound (V) is carried out in the presence of a sulfiding agent, preferably with an alkali metal thiosulfate or an alkaline earth metal thiosulfate such as sodium thiosulfate, preferably in the presence of a polar (aprotic) solvent, preferably a polar protic solvent such as water;

[0106] Preferably, the reaction medium in step iii) is maintained under an inert atmosphere, particularly at a temperature less than or equal to the reflux temperature of the solvent, preferably 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 a period between 30 minutes and 24 hours, more preferably between 1 hour and 10 hours, still better between 4 hours 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;

[0107] iii1) Subsequently, the reaction mixture is preferably adjusted to a pH between 7 and 8, particularly using at least one basic agent as defined above, preferably an inorganic basic agent such as sodium hydroxide; preferably, the reaction mixture is then maintained at a temperature between 10 °C and 30 °C, such as 20 °C ± 5 °C, under mechanical stirring for a period particularly between one minute and 1 hour, such as 15 minutes; preferably, the reaction mixture is filtered, and the solid is particularly washed with a polar (aprotic) solvent, preferably a polar protic solvent such as water;

[0108] iii2) Subsequently, the filtrate is preferably acidified with an organic acid or an inorganic acid, preferably an inorganic acid such as hydrochloric acid, at a temperature of greater than or equal to 40 °C, such as 60 °C ± 5 °C, until a pH between 1 and 5, preferably between 1.5 and 3, such as 2 ± 0.5, is obtained; subsequently, the temperature is preferably maintained at 60 °C ± 5 °C for a period of time, particularly between 1 minute and 30 minutes, such as 15 minutes.

[0109] Preferably, the reaction mixture is then allowed to stir mechanically at a temperature between 10 °C and 30 °C, such as 20 °C ± 5 °C, for a period of time, particularly between one minute and 1 hour, such as 15 minutes; preferably, the reaction mixture is filtered, and the solid is washed particularly with a polar (aprotic) 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, particularly under vacuum.

[0110] iii3) The solid can be purified by dissolving it in a polar (aprotic) solvent, preferably a polar protic solvent such as water, and adjusting the pH between 7 and 8 by particularly using a base agent as defined above, preferably an inorganic base agent such as sodium hydroxide; subsequently, the mixture is preferably maintained under mechanical stirring at a temperature particularly between 10 °C and 30 °C, such as 20 °C ± 5 °C, for a period between 1 minute and 30 minutes, such as 5 minutes; subsequently, the mixture is preferably filtered, and the solid is washed with a polar (aprotic) solvent, preferably a polar protic solvent such as water.

[0111] iii4) Subsequently, the filtrate is optionally acidified (depending on the nature of M) with an inorganic acid or an organic acid, preferably an inorganic acid such as hydrochloric acid, at a temperature of 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 maintained at a temperature of greater than or equal to 40 °C, such as 60 °C ± 5 °C, for a period particularly between 1 minute and 60 minutes, such as 15 minutes; subsequently, the solid is filtered out and washed with a polar (aprotic) solvent, preferably a polar protic solvent such as water, and then particularly dried at a temperature of greater than or equal to 20 °C, more particularly between 40 °C and 60 °C, such as 50 °C, preferably under vacuum.

[0112] According to the general features of the present invention, stage (i), i.e., the stage of preparing the compound of formula (III) by activating the carboxyl group of the compound of formula (II), is preferably carried out in an organic solvent in the presence of one or more reagents for activating carboxylic acids.

[0113] The reagent for activating carboxylic acids can be selected from the group consisting of thionyl halides such as thionyl chloride, oxalyl halides such as oxalyl chloride, and mixtures thereof, preferably thionyl chloride (SOCl2).

[0114] Preferably, the activator is thionyl chloride (SOCl2), and the organic solvent exhibits a dielectric constant E in the range of 1 to 7 and a dipole moment μ in the range of 0 to 2.

[0115] Again preferably, the activator is thionyl chloride (SOCl2), and the organic solvent is selected from the group consisting of ethyl acetate, methyl tetrahydrofuran, and toluene, more preferably ethyl acetate.

[0116] Stage (ii), i.e., the stage of reacting the compound of formula (III) with the amine of formula (IV) to produce the 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, with an aqueous composition comprising at least the amine of formula (IV) in the presence of one or more base agents.

[0117] Advantageously, stage (ii) is thus carried out in a reaction medium whose pH is strictly greater than 7, i.e., thus at an alkaline pH.

[0118] In other words, the stage of reacting the compound of formula (III) with the amine of formula (IV) to produce the compound of formula (V) takes place in an alkaline medium.

[0119] In this way, according to the synthesis scheme ( 1 ), the halogenated derivative of the general formula HHal’ (Hal' as defined above), especially hydrochloric acid, produced during stage (ii) is effectively neutralized during stage (ii).

[0120] Stage (ii) is preferably carried out in a reaction medium whose pH varies from 7.5 to 10.

[0121] Stage (ii) advantageously comprises adding 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 base agents.

[0122] In this case, the base agent can be added to the composition comprising at least the amine of formula (IV) before carrying out stage (ii).

[0123] Alternatively, stage (ii) advantageously comprises simultaneously adding 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 base agents to an aqueous composition comprising at least one amine of formula (IV).

[0124] Thus, when the composition comprising at least the compound of formula (III) and the aqueous composition comprising one or more basic agents are added simultaneously to the aqueous composition comprising at least one amine of formula (IV), the yield of the process according to the invention is advantageously improved.

[0125] According to this alternative, the aqueous composition comprising at least the amine of formula (IV) may additionally comprise one or more basic agents.

[0126] In this case, the basic agent can be added to the composition comprising at least the amine of formula (IV) before carrying out step (ii).

[0127] The content of the basic agent can 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).

[0128] The content of the amine of formula (IV) can vary from 1.5 to 3 molar equivalents, preferably from 1.8 to 2.5 molar equivalents, relative to the number of moles of the compound of formula (III).

[0129] Preferably, the organic solvent is the same as the organic solvent used during step (i) and particularly exhibits a dielectric constant E in the range of 1 to 7 and a dipole moment μ in the range of 0 to 2.

[0130] More preferably, the organic solvent is selected from the group consisting of ethyl acetate, methyltetrahydrofuran and toluene, more preferably ethyl acetate.

[0131] Relative to the total weight of the composition comprising at least the compound of formula (III), the organic solvent can be present in a content in the range of 70% to 90% by weight, preferably in a content in the range of 75% to 85% by weight.

[0132] Relative to the total weight of the composition comprising at least the amine of formula (IV), water can be present in a content in the range of 60% to 90% by weight, preferably in a content in the range of 70% to 80% by weight.

[0133] The volume ratio of the organic solvent to water can vary from 3 to 1, preferably equal to 2 / 1.

[0134] The reaction temperature can vary from 10 °C to 45 °C, preferably from 15 °C to 25 °C.

[0135] The duration of the reaction can vary from 10 to 120 minutes, preferably from 30 to 60 minutes.

[0136] After completion of the reaction, the reaction medium can be acidified with an organic or inorganic acid, preferably an aqueous solution of an inorganic acid.

[0137] Among these acidifying agents, mention may be made, by way of example, of inorganic or organic acids such as hydrochloric acid, orthophosphoric acid, sulfuric acid, carboxylic acids such as acetic acid, tartaric acid, citric acid or lactic acid, and sulfonic acids.

[0138] Preferably, the acidifying agent is an inorganic acid, in particular hydrochloric acid.

[0139] The desired product of formula (V) precipitates from the medium and is filtered off and washed with water for subsequent use in stage (iii).

[0140] As indicated above, stage (iii) is the stage in which the compound of formula (V) is reacted to form the compound of formula (I).

[0141] Stage (iii) is an exchange reaction between a halogen atom and a mercapto - SH group or a sulfur atom to form the compound of formula (I).

[0142] Preferably, stage (iii) is carried out using one or more reagents such as alkali metal (di) sulfites, in particular sodium dithionite, alkali metal thiosulfates, in particular sodium thiosulfate, thiosulfates, thiourea or thioacetic acid, and mixtures thereof.

[0143] More preferably, stage (iii) is carried out using an alkali metal thiosulfate, in particular sodium thiosulfate.

[0144] The amount of the reagent can 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).

[0145] The reaction temperature can vary from 60 °C to 110 °C, preferably in the range of 70 °C to 100 °C, more preferably between 75 °C and 90 °C, such as 80 °C.

[0146] The reaction temperature advantageously makes it possible to limit the formation of impurities while ensuring complete reaction.

[0147] The duration of reaction (iii) can vary from 3 to 10 hours, preferably from 4 to 8 hours, such as 6 hours.

[0148] During reaction (iii), the pH of the reaction medium is a pH less than 7, preferably less than or equal to 6, more preferably less than or equal to 5, still more preferably less than or equal to 4, in particular in a pH range extending from 1 to 4, preferably from 2 to 3.

[0149] According to a particular embodiment of the invention, the pH is between 6 and 2, more particularly between 5 and 3.

[0150] Subsequently, the compound of formula (V) can be filtered off and washed one or more times, preferably with water.

[0151] Thus, the process according to the invention 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 organic or inorganic acid or base salts, and their solvates such as hydrates.

[0152] The salts of the compounds of formula (I) include the conventional non-toxic salts of said compounds, such as those formed by an acid or a base.

[0153] Among the salts of the compounds of formula (I), mention may be made in particular of:

[0154] - salts obtained by addition of a compound of formula (I) with an inorganic base, which inorganic base is, for example, sodium hydroxide, potassium hydroxide, calcium hydroxide, ammonium hydroxide, magnesium hydroxide, lithium hydroxide, and, for example, sodium carbonate, potassium carbonate, or calcium carbonate, or sodium bicarbonate, potassium bicarbonate, or calcium bicarbonate;

[0155] - salts obtained by addition of a compound of formula (I) with an organic base, which organic base is, for example, a primary, secondary or tertiary alkylamine, such as triethylamine or butylamine. Such primary, secondary or tertiary alkylamines may contain one or more nitrogen and / or oxygen atoms and may thus contain, for example, one or more alcohol functional groups; mention may be made in particular of 2-amino-2-methylpropanol, ethanolamine, triethanolamine, 2-(dimethylamino)propanol, 2-amino-2-hydroxymethyl-1,3-propanediol or 3-(dimethylamino)propylamine.

[0156] Also mention may be made of salts of amino acids such as lysine, arginine, guanidine, glutamic acid or aspartic acid.

[0157] Advantageously, the salts of the compounds of formula (I) may be selected from alkali metal salts or alkaline earth metal salts, such as sodium salts, potassium salts, calcium salts or magnesium salts, or ammonium salts.

[0158] The acceptable solvates of the compounds of formula (I) include the conventional solvates, such as those formed during the preparation of said compounds due to the presence of a solvent.

[0159] By way of example, mention may be made of solvates resulting from the presence of water or a straight-chain or branched alcohol such as ethanol or isopropanol.

[0160] Optical isomers are in particular enantiomers and diastereoisomers.

[0161] Within the meaning of the present invention, the term "tautomer" should be understood to mean the following two forms:

[0162]

[0163] As indicated previously, A represents a saturated or unsaturated, preferably saturated, cyclic or acyclic, preferably acyclic, straight-chain or branched divalent hydrocarbon chain containing 1 to 10 carbon atoms, which is optionally interrupted by one or more heteroatoms or groups such as an oxygen atom, a sulfur atom, NR2 or (thio)carbonyl, or a combination thereof such as a thioester, where R2 represents a hydrogen atom or a C1-C4 alkyl group.

[0164] In other words, A represents a saturated or unsaturated, preferably saturated, cyclic or acyclic, preferably acyclic, straight-chain or branched divalent hydrocarbon chain containing 1 to 10 carbon atoms, which is optionally interrupted by one or more heteroatoms such as an oxygen atom or a sulfur atom, or a group selected from NR2 or (thio)carbonyl, or a combination thereof such as a thioester, where R2 represents a hydrogen atom or a C1-C4 alkyl group.

[0165] Still in other words, A represents a saturated or unsaturated, preferably saturated, cyclic or acyclic, preferably acyclic, straight-chain or branched divalent hydrocarbon chain containing 1 to 10 carbon atoms, which is optionally interrupted by one or more heteroatoms such as an oxygen atom or a sulfur atom, or is optionally interrupted by one or more groups selected from NR2 or (thio)carbonyl, or is optionally interrupted by one or more combinations of heteroatoms and groups as defined previously such as a thioester, where R2 represents a hydrogen atom or a C1-C4 alkyl group.

[0166] Preferably, in formulas (I), (IV) and (V), A represents a saturated or unsaturated, preferably saturated, cyclic or acyclic, preferably acyclic, straight-chain or branched divalent hydrocarbon chain containing 1 to 10 carbon atoms, which is not interrupted by one or more heteroatoms or groups as described above.

[0167] Preferably, in formulas (I), (IV) and (V), A represents a (C1-C6)alkylene group, more preferably a (C1-C4)alkylene group, especially a methylene group.

[0168] Preferably, in formulas (I), (IV) and (V), R 1 represents a hydrogen atom.

[0169] In formulas (I), (IV) and (V), when M represents an alkali metal or an alkaline earth metal, M is preferably a sodium atom or a potassium atom, more preferably sodium.

[0170] According to a preferred feature of the present invention, in formulas (I), (IV) and (V), R 1 represents a hydrogen atom, A represents a (C1-C6)alkylene group, more preferably a (C1-C4)alkylene group, especially a methylene group, and M represents a hydrogen atom, an alkali metal or an alkaline earth metal or an ammonium group.

[0171] 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 the compounds corresponding to formula (I'):

[0172]

[0173] In formula (I'):

[0174] M represents a hydrogen atom, an alkali metal or an alkaline earth metal such as a sodium atom or a potassium atom, or an ammonium group, more preferably sodium;

[0175] as well as their optical isomers, geometric isomers and tautomers, as well as their organic or inorganic acid salts or base salts, and their solvates such as hydrates.

[0176] Preferably, in formulae (I) and (I'), M represents a hydrogen atom.

[0177] Thus, the process according to the invention makes it possible to preferably prepare the compound of formula (I') according to the following synthesis scheme (1'):

[0178]

[0179] In formulae (III'), (IV'), (V') and (I'), M represents a hydrogen atom, an alkali metal or an alkaline earth metal such as a sodium atom or a potassium atom, or an ammonium group.

[0180] Preferably, M represents a hydrogen atom.

[0181] Compound (I ” )

[0182] The invention also relates to a compound of formula (I”):

[0183]

[0184] ● In formula (I”):

[0185] - M, A and R 1 have the same meanings as in formula (I),

[0186] as well as their optical isomers, geometric isomers and tautomers, as well as their organic or inorganic acid salts or base salts, and their solvates such as hydrates,

[0187] with the exception of the following compounds (X) and (XI) and their tautomers (X') and (XI'):

[0188]

[0189] Optical isomers, acid salts or base salts, solvates and also tautomers have the same definitions as those mentioned above.

[0190] Preferably, in formula (I"), R 1 represents a hydrogen atom.

[0191] Composition

[0192] The subject of the present invention is also a composition, preferably a cosmetic composition, which comprises at least one compound of formula (I") and also its optical isomers, geometric isomers and tautomers, and also its organic or inorganic acid salts or base salts, and its solvates such as hydrates.

[0193] Another subject of the present invention is a composition, preferably a cosmetic composition, which comprises a) at least one compound of formula (I") and also its optical isomers, geometric isomers and tautomers, and also its organic or inorganic acid salts or base salts, and its solvates such as hydrates, and b) at least one compound of formula (I) and also its optical isomers, geometric isomers and tautomers, and also its organic or inorganic acid salts or base salts, and its solvates such as hydrates, preferably at least one compound of formula (I') and also its optical isomers, geometric isomers and tautomers, and also its organic or inorganic acid salts or base salts, and its solvates such as hydrates, it being understood that the compounds of formula (I) or (I') differ from the compounds of formula (I") in terms of the nature of the divalent group A and / or the nature of the group R 1 of the compound.

[0194] Preferably, relative to the total weight of the composition, the compound of formula (I") may be present in the composition in an amount ranging from 0.01% to 10% by weight, preferably in an amount ranging from 0.1% to 5% by weight, more preferably in an amount ranging from 0.5% to 3% by weight.

[0195] The composition according to the invention preferably comprises a physiologically acceptable medium, in particular a medium compatible with human keratin materials such as the skin of the body or face, lips, mucous membranes, eyelashes, nails, scalp and / or hair.

[0196] The composition may additionally comprise at least one adjuvant commonly used in the cosmetic field.

[0197] By way of example, cosmetic adjuvants that may be mentioned are selected from the group consisting of: organic solvents, in particular C1-C6 alcohols, more preferably C2-C6 alcohols and C2-C 10Carboxylic acid esters; oils, especially hydrocarbon oils and / or silicone oils of mineral, animal and / or vegetable origin; waxes, pigments, fillers, dyes, surfactants, emulsifiers; cosmetic or dermatological active agents, UV screening agents, polymers, hydrophilic or lipophilic gelling agents, thickeners, preservatives, fragrances, bactericides, ceramides, odor absorbers and antioxidants.

[0198] These optional cosmetic adjuvants may be present in the composition in proportions of from 0.001% to 80% by weight, particularly from 0.1% to 40% by weight, relative to the total weight of the composition.

[0199] The invention is illustrated in more detail in the following non-limiting examples.

[0200] Examples:

[0201] Stage 1: Preparation of acyl halide (acyl chloride)

[0202]

[0203] The 2-chloronicotinic acid compound (Z) (70 g, 0.444 mol) and ethyl acetate (280 ml, 4.0 v / w) were introduced into a 1-litre reactor equipped with a thermometer, a condenser column and a mechanical stirrer.

[0204] The resulting white suspension was heated to the reflux of the solvent under an inert atmosphere (nitrogen). Thionyl chloride (35.4 ml, 0.489 mol, 1.1 equivalents) was added dropwise. The mixture was maintained under mechanical stirring at reflux for an additional period of 4 hours.

[0205] Once the reaction was complete, the mixture was cooled to a temperature of 50 °C. Then ethyl acetate (140 ml, 2.0 v / w) was added and then the mixture was cooled to a temperature of 25 °C and left to stand under an inert atmosphere (nitrogen).

[0206] Stage 2: Amide formation

[0207]

[0208] Glycine (IV') (66.7 g, 0.890 mol, 2.0 equivalents) and water (259 ml, 3.7 v / w) were introduced into a 1-litre reactor equipped with a thermometer, a pH probe and a mechanical stirrer.

[0209] The suspension was cooled to a temperature of 20 °C ± 5 °C under an inert atmosphere (nitrogen) and 25% aqueous sodium hydroxide solution NaOH aq (approx. 56 ml, 1.0 equivalent) was added until an alkaline pH (> 7) was obtained.

[0210] A solution of the acyl chloride (III') in ethyl acetate and 25% NaOH aq solution (about 84 ml, 1.5 equivalents) were introduced into two separate dropping funnels. The acyl chloride solution was added dropwise to the reactor at a temperature of 20 °C ± 5 °C. During the addition, the pH was maintained alkaline, preferably between 7.5 and 10, by adding 25% NaOH aq solution.

[0211] Once the addition was complete, the solution was stirred for an additional one-hour period at a temperature of 20 °C ± 5 °C. The mixture was separated by sedimentation for a period of 30 minutes, and the aqueous phase containing the compound (V′ a ) was collected. The ethyl acetate phase was discarded.

[0212] The aqueous phase was acidified at a temperature of 25 °C ± 5 °C with an inorganic or organic acid, preferably an inorganic acid such as hydrochloric acid, preferably 37% HCl (about 58.4 ml, 1.6 equivalents), to a pH of 2.5 ± 0.2. The resulting suspension was stirred at a temperature of 25 °C ± 5 °C for approximately 1 hour.

[0213] Subsequently, the medium was filtered, and the obtained solid was washed with water (140 ml, 2.0 v / w), and then dried overnight under vacuum at a temperature of 50 °C to yield the compound (V′ b ) (85.3 g, white powder) with a productivity of 89%.

[0214] Stage 3: Sulfurization

[0215]

[0216] The compound of formula (V′ b ) (80 g, 0.373 mol), sodium thiosulfate pentahydrate (185 g, 0.746 mol, 2.0 equivalents relative to (V′ b )) and water (400 ml, 5 v / w) were introduced into a 1-liter reactor equipped with a thermometer, a condenser column, a pH probe and a mechanical stirrer. The resulting white suspension was heated to a temperature of 80 °C ± 3 °C under an inert atmosphere (nitrogen) and maintained with stirring for several hours (e.g., between 3 and 6 hours).

[0217] Subsequently, the reaction mixture was cooled to ambient temperature (20 °C ± 5 °C).

[0218] It should be noted that the sulfidation reaction is carried out at an acidic pH preferably between 2 and 6 such as 5.

[0219] Separation:

[0220] At the end of the reaction, 50% NaOH was usedaq The solution (about 35.8 g, 0.447 mol, 1.20 equivalents) adjusts the pH of the reaction mixture to a pH between 7 and 8. The mixture is stirred at ambient temperature (20 °C ± 5 °C) until the pH stabilizes (e.g., for 5 minutes). The mixture is filtered to remove elemental sulfur. The solid is rinsed with water (80 ml, 1 v / w), and the combined filtrate containing the compound of formula (I′ a ) is transferred to an empty 1-liter reactor equipped with a thermometer, a condenser column, a pH probe, and a mechanical stirrer. The solution is heated to a temperature of 60 °C ± 5 °C and acidified by adding an organic acid or an inorganic acid, preferably an inorganic acid such as hydrochloric acid, especially 34% HCl, until an acidic pH (e.g., 2.0 ± 0.5) is obtained. The suspension is maintained at a temperature of 60 °C with stirring for a period of 15 minutes, then cooled and maintained at a temperature of 20 °C ± 5 °C, and stirred for an additional 15 minutes. The solid is filtered out and washed with water (2 × 80 ml, 2 × 1 v / w), and then dried under vacuum at a temperature of 50 °C. A compound of formula (I′ b ) in the form of a yellow solid (73.4 g, HPLC purity 99.5%) with a yield of 93% is obtained.

[0221] Stage 4: Purification (optional)

[0222] The compound prepared during the previous stage 3: compound (I′ b ) (70 g, 0.330 mol) and water (280 ml, 4 v / w) are introduced into a 1-liter reactor equipped with a thermometer, a condenser column, a pH probe, and a mechanical stirrer.

[0223] The pH of the mixture is adjusted to a pH between 7 and 8 using 50% NaOH aq (about 29.0 g, 0.363 mol, 1.10 equivalents).

[0224] The mixture is stirred at ambient temperature (20 °C ± 5 °C) until the pH stabilizes (e.g., for 5 minutes).

[0225] Subsequently, the mixture is 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-liter reactor equipped with a thermometer, a pH probe, and a mechanical stirrer. The solution is heated to a temperature greater than 60 °C and acidified by adding an inorganic acid or an organic acid, preferably an inorganic acid such as 34% HCl, to a pH of, for example, 2.0 ± 0.5 (about 42.5 g, 0.396 mol, 1.20 equivalents).

[0226] Stir the suspension at a temperature greater than 40 °C, for example greater than or equal to 60 °C, for a few minutes, for example 15 minutes. Cool the suspension to ambient temperature (such as 20 °C ± 5 °C) and stir for an additional few minutes (such as 15 minutes). Filter out the obtained solid and wash it with water (2 × 70 ml, 2 × 1 v / w).

[0227] Dry the obtained solid under vacuum at 50 °C to obtain the purified compound (I′ b )(68.30 g, HPLC purity 99.55%) in the form of a yellow solid with a yield of 98%.

[0228] Compound (I′ a ) and (I′ b ) purity was 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 was carried out at 300 nm. The mobile phase consisted of an ammonium acetate solution buffered at pH 3 and methanol. The column used was Gemini C18 5μm - 250x 4.6 mm.

Claims

1. A method for preparing: at least one compound of formula (I): In formula (I): - A represents a saturated or unsaturated, preferably saturated, cyclic or acyclic, preferably acyclic, straight-chain or branched divalent hydrocarbon chain containing 1 to 10 carbon atoms, which is optionally inserted with one or more heteroatoms such as oxygen atoms or sulfur atoms, or a group selected from NR2 or (thio)carbonyl, or a combination thereof such as a thioester, where R2 represents a hydrogen atom or a C1-C4 alkyl group; - M represents a hydrogen atom, an alkali metal or an alkaline earth metal, an ammonium group; -R 1 represents a hydrogen atom, a straight-chain or branched C1-C 10 alkyl group - which is optionally substituted by an OR3 or SR3 group, where R3 corresponds to a hydrogen atom or a straight-chain or branched C1-C 10 alkyl group, as well as one of its optical isomers, geometric isomers and tautomers, as well as one of its organic or inorganic acid salts or base salts, and one of its solvates such as a hydrate; The method occurs according to the following synthetic scheme ( 1 ): ■ wherein: - Hal and Hal' are the same or different and represent halogen atoms, and -M, A and R 1 have the same meanings as in formula (I); at least step (iii) is at an acidic pH, i.e., less than 7.

2. The method according to claim 1, wherein Step (iii) occurs 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, particularly in a pH range extending from 1 to 4, preferably from 2 to 3.

3. The method according to claim 1 or 2, characterized in that, Step (iii) occurs at a pH between 6 and 2, more particularly between 5 and 3.

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

5. The method according to any one of the preceding claims, characterized in that, Step (ii) comprises adding a composition comprising at least a compound of formula (III) and at least one organic solvent to a composition comprising at least an amine of formula (IV) and at least one base agent.

6. The method according to any one of the preceding claims, characterized in that Step (ii) comprises simultaneously adding a composition comprising at least a compound of formula (III) and at least one organic solvent and an aqueous composition comprising one or more base agents to an aqueous composition comprising at least an amine of formula (IV).

7. The method according to any one of the preceding claims, characterized in that, Step (ii) is carried out in a reaction medium, the pH of which is strictly greater than 7, preferably the pH of the reaction medium varies from 7.5 to 10.

8. The method 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, particularly between 1.5 equivalents and 2.5 equivalents, more particularly 2 equivalents of compound (IV), preferably in a polar (aprotic) solvent, preferably a polar protic solvent such as water, particularly with a weight / volume ratio between 1 and 7, even better between 2 and 5, such as 3.5, relative to the weight of the compound of formula (II); preferably, the reaction mixture is at a temperature between 10°C and 30°C, such as 20°C ± 5°C; preferably, the reaction medium is under an inert atmosphere; subsequently, particularly adding at least one inorganic base agent or organic base agent, preferably an inorganic base agent, such as sodium hydroxide; adding at least one equivalent of the base agent to the reaction medium to achieve the basic pH of the medium, *At least one compound of formula (III), particularly in a non-polar aprotic organic solvent, especially ethyl acetate or toluene, and a base agent, which can preferably be in a polar (non)-protic solvent such as water, more particularly an inorganic base agent such as sodium hydroxide, preferably a base agent between 1 and 3 equivalents, such as 1.5 equivalents, Preferably, at a temperature between 10 °C and 30 °C such as 20 °C + / - 5 °C, and preferably under an inert atmosphere and with mechanical stirring, the compound of formula (III) is added dropwise to the compound of formula (IV); in particular, 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), the reaction medium is maintained at an alkaline pH, more particularly between 7.5 and 10; Preferably, at a temperature between 10 °C and 30 °C such as 20 °C + / - 5 °C, the mixture is separated by sedimentation, and the aqueous phase is collected; In particular, the aqueous phase is cooled to below 30 °C, preferably at a temperature between 20 °C and 30 °C such as 25 °C + / - 5 °C; preferably, the phase is acidified with an inorganic or organic acid, preferably an inorganic acid such as hydrochloric acid, particularly with at least 1 equivalent of acid, preferably between 1 and 3 equivalents such as 1.6 equivalents of acid; the pH of the aqueous phase is preferably between 1 and 5, particularly between 2 and 4, such as 2.5 + / - 0.2; Preferably, the aqueous phase is then filtered, and the obtained solid is preferably washed with a polar (non)-protic solvent, preferably a polar protic solvent such as water; then the solid is preferably dried 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 produce the compound of formula (V); The drying stage is optional; the wet product can be directly used in the subsequent stage.

9. The method according to any one of claims 2 to 6, characterized in that, The base agent can be an organic base agent or an inorganic base agent, preferably selected from the group consisting of: alkali metal hydroxides or alkaline earth metal hydroxides, especially sodium hydroxide, alkali metal carbonates (hydrogencarbonates) or alkaline earth metal carbonates (hydrogencarbonates), especially sodium (hydrogen) carbonate or potassium (hydrogen) carbonate, and tris(C1-C6)(hydroxy)alkylamines, especially tris(C1-C6)alkylamines, especially triethylamine.

10. The method according to any one of the preceding claims, characterized in that, In stage (iii), the sulfidation reaction of the compound (V) is carried out in the presence of a sulfidation reagent, preferably with an alkali metal thiosulfate or an alkaline earth metal thiosulfate such as sodium thiosulfate, preferably in the presence of a polar (non)-protic solvent, preferably a polar protic solvent such as water; Preferably, the reaction medium in step (iii) is maintained under an inert atmosphere, particularly at a temperature less than or equal to the reflux temperature of the solvent, preferably 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 a duration between 30 minutes and 24 hours, more preferably between 1 hour and 10 hours, still more preferably between 4 hours 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.

11. The method according to the preceding claim, characterized in that, After said vulcanization step (iii): iii1) The reaction mixture is preferably adjusted to a pH between 7 and 8 using at least one basic agent as defined above, preferably an inorganic basic agent such as sodium hydroxide; preferably, the reaction mixture is then maintained under mechanical stirring at a temperature between 10 °C and 30 °C, such as 20 °C ± 5 °C, for a duration particularly between one minute and 1 hour, such as 15 minutes; preferably, the reaction mixture is filtered, and the solid is washed particularly with a polar (aprotic) solvent, preferably a polar protic solvent such as water. iii2) Subsequently, the filtrate is acidified preferably at a temperature greater than or equal to 40 °C, such as 60 °C ± 5 °C, using an organic acid or an inorganic acid, preferably an inorganic acid such as hydrochloric acid, until a pH between 1 and 5, preferably between 1.5 and 3, such as 2 ± 0.5, is obtained; subsequently, the temperature is 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 maintained under mechanical stirring at a temperature between 10 °C and 30 °C, such as 20 °C ± 5 °C, for a duration particularly between one minute and 1 hour, such as 15 minutes; preferably, the reaction mixture is filtered, and the solid is washed particularly with a polar (aprotic) 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, particularly under vacuum. iii3) The solid can be purified by dissolving it in a polar (aprotic) solvent, preferably a polar protic solvent such as water, and adjusting the pH between 7 and 8 using a basic agent, preferably an inorganic basic agent such as sodium hydroxide; subsequently, the mixture is preferably maintained under mechanical stirring particularly at a temperature between 10 °C and 30 °C, such as 20 °C ± 5 °C, for a duration between 1 minute and 30 minutes, such as 5 minutes; subsequently, the mixture is preferably filtered, and the solid is washed with a polar (aprotic) solvent, preferably a polar protic solvent such as water. iii4) Subsequently, depending on the nature of M, the filtrate is optionally acidified using an inorganic or organic acid, preferably an inorganic acid such as hydrochloric acid, particularly at a temperature of 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 kept at a temperature of greater than or equal to 40 °C, such as 60 °C + / - 5 °C, for a period particularly between 1 minute and 60 minutes, such as 15 minutes. The solid is then filtered off and washed with a polar (aprotic) solvent, preferably a polar protic solvent such as water, and then dried preferably under vacuum at a temperature of greater than or equal to 20 °C, more particularly between 40 °C and 60 °C, such as 50 °C.

12. The method according to any one of claims 4 to 11, characterized in that, The volume ratio of the organic solvent to the water can vary from 3 to 1, preferably equal to 2 / 1.

13. The method according to any one of the preceding claims, characterized in that: ● A represents an (C1-C6)alkylene group, more preferably an (C1-C4)alkylene group, particularly a methylene group; and / or ●R 1 represents a hydrogen atom.

14. The method according to any one of the preceding claims, characterized in that, The compound of formula (I) is selected from the group consisting of compounds corresponding to the following formula (I'): In the formula (I'), M represents a hydrogen atom, an alkali metal or an alkaline earth metal such as a sodium atom or a potassium atom, or an ammonium group; preferably, M represents a hydrogen atom.

15. A compound of the following formula (I”): ● In the formula (I”): - A represents a saturated or unsaturated, preferably saturated, cyclic or acyclic, preferably acyclic, straight-chain or branched divalent hydrocarbon chain containing 1 to 10 carbon atoms, which is optionally interrupted by one or more heteroatoms such as an oxygen atom or a sulfur atom, or a group selected from NR2 or (thio)carbonyl, or a combination thereof such as a thioester, where R2 represents a hydrogen atom or a C1-C4 alkyl group; - M represents a hydrogen atom, an alkali metal or an alkaline earth metal, or an ammonium group; -R 1 represents a hydrogen atom, as well as its optical isomers, geometric isomers and tautomers, as well as its organic or inorganic acid salts or base salts, and its solvates such as hydrates, with the exception of the following compounds (X) and (XI) and their tautomers (X') and (XI'):

16. A composition, preferably a cosmetic composition, comprising one or more compounds of formula (I”) as described in the previous claim, as well as its optical isomers, geometric isomers and tautomers, as well as its organic or inorganic acid salts or base salts, and its solvates such as hydrates.

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