WO1999032440A1

WO1999032440A1 - Method for preparing aromatic thiols and derivatives, reagents, intermediate products and method for obtaining them

Info

Publication number: WO1999032440A1
Application number: PCT/FR1998/002825
Authority: WO
Inventors: Jean-Francis Spindler; Jean-Roger Desmurs; Pierre Beslin; Yannick Quesnel; Clotilde Mispelaere
Original assignee: Rhodia Chimie
Priority date: 1997-12-22
Filing date: 1998-12-22
Publication date: 1999-07-01
Also published as: JP2002512174A; EP1042282A1; AU1881199A; FR2772757A1; FR2772757B1

Abstract

The invention concerns a method for preparing an aromatic thiol bearing an amino group from a hydroxylated compound bearing an amino group. The invention also concerns the starting reagents, the intermediate products such as an aromatic S-arylthiocarbamate and the method for obtaining them and the derived products such as thioethers. The invention concerns a method for the transposition of an O-arylthiocarbamate compound bearing at least one amino group into a S-arylthiocarbamate compound bearing at least one amino group, characterised in that it consists in heating an O-arylthiocarbamate compound bearing at least one amino group and an electroattractive group. The resulting S-arylthiocarbamate compound is used as intermediate for making an aromatic thiol or thioether.

Description

PROCESS FOR THE PREPARATION OF AROMATIC THIOLS AND DERIVATIVES. RFAOTIFS. INTERMEDIATE PRODUCTS AND THEIR PROCESS

OBTAINING.

The present invention relates to a process for the preparation of an aromatic thiol carrying an amino group from a hydroxylated aromatic compound carrying an amino group. More specifically, the invention relates to the preparation of 5-amino-2-chloro-4-fluoro-thiophenol. The invention also relates to the starting reagents, the intermediate products of the aromatic S-arylthiocarbamate type and their process for obtaining.

The invention also relates to derivatives of aromatic thiols such as thioethers.

In the following description of the present invention, the term "aromatic thiol carrying an amino group" means an aromatic compound in which two hydrogen atoms directly linked to the aromatic ring are replaced, one by an SH group and the other by an NH ₂ or NHR group, R being defined later. By "aromatic compound" is meant the classic notion of aromaticity as defined in the literature, in particular by Jerry MARCH, Advanced Organic Chemistry, 4 ^th edition, John Wiley and Sons, 1992, pp. 40 and following.

In a simplified manner, the expression “aryl” will denote all the aromatic compounds whether they are carbocyclic aromatic compounds or heterocyclic aromatic compounds.

5-amino-2-chloro-4-fluoro-thiophenol is an intermediate for the manufacture of a herbicide of thiadiazabicyclononate type which can be represented by the following formula:

SCH ₂ COOCH ₃

There are numerous access routes to thiophenols in the literature. One is to perform pyrolysis of a di-O-arylthiocarbonate to O-aryl S-arylthiocarbonate [A. Schόnberg et al, Ann., 483. p.107 (1930)]. The yield obtained is low (around 30%) and the conversion of phenol to thiophenol only takes place with a maximum yield of 50%. Melvin S. Newman et al worked on the conversion of phenols to thiophenols via a dialkylthiocarbamate [. Org. Chem., 3J., P.3980 (1966)] according to the following reaction scheme:

ArOH - ”. ArOCSNR ₂ - ArSCONR ₂ - »ArSH The phenolic compound is reacted with a dialkylthiocarbamoyl chloride leading to an O-arylthiocarbamate which rearranges according to the transposition of Newman-Kwart into S-arylthiocarbamate which allows the corresponding thiol to be obtained after hydrolysis basic.

The disadvantage from which the described method suffers is that it cannot be applied to a phenolic compound carrying an amino group because the Newman-Kwart transposition does not take place and the only examples given in the publication relate to a protected amino function in the form of acetamide or substituted by alkyl groups.

It has now been found that it was possible to transpose an O-arylthiocarbamate type compound bearing at least one amino group into an S-arylthiocarbamate type compound insofar as the starting substrate comprises an aromatic ring carrier at least one electro-attracting group.

Thus, one of the objects of the present invention is a method of transposing an O-arylthiocarbamate type compound carrying at least one amino group into an S-arylthiocarbamate type compound carrying at least one amino group characterized by the fact that it consists in heating a compound of the O-arylthiocarbamate type carrying at least one amino group and one electron-withdrawing group. Another subject of the invention is the process for the preparation of an aromatic thiol carrying at least one amino group from a hydroxylated aromatic compound carrying at least one amino group, characterized in that it consists in using a compound of S-arylthiocarbamate type carrying at least one amino group and at least one electron-withdrawing group. More specifically, the method consists in carrying out the transposition of an O-arylthiocarbamate group into an S-arylthiocarbamate group by heating an O-arylthiocarbamate type compound carrying at least one amino group and one electron-withdrawing group, then to hydrolyze the compound of type S- arylthiocarbamate carrying at least one amino group and at least one electron-withdrawing group.

Another subject of the invention also lies in a process for the preparation of an aromatic thioether carrying at least one amino group from a compound of the S-arylthiocarbamate type.

Other objects of the invention specified later relate to the intermediate products and the starting reagents.

In accordance with the process of the invention, it has been found that a compound of the O-arylthiocarbamate type carrying a free amine function could not be rearranged into the compound of the S-arylthiocarbamate type unless the presence of at least one electron-withdrawing group on the aromatic cycle.

The term "electron withdrawing group", a group as defined by HC BROWN in the work by Jerry March - Advanced Organic Chemistry, ^4th Edition, John Wiley and Sons, 1992, Chapter 9, pp. 273 - 292.

The electron-withdrawing group can be at any position of the aromatic cycle but it is preferably in position 2 and / or 4 relative to the amino group.

Preferred starting compounds include at least two electron-withdrawing groups in positions 2 and 4 relative to the amino group.

More precisely, the invention relates to a process for transposing a compound of O-arylthiocarbamate type into S-arylthiocarbamate, characterized in that it consists in heating a compound of O-arylthiocarbamate type carrying at least one amino group and d '' an electro-attractor group corresponding to the general formula (I):

in which :

- A symbolizes the remainder of a cycle forming all or part of a carbocyclic or heterocyclic, aromatic, monocyclic or polycyclic system, - R represents a hydrogen atom or a hydrocarbon group,

- X _] represents an electro-attracting group,

- X ₂ represents a hydrogen atom or a substituent of any kind, Z is a group comprising a doublet donor atom linked to the carbon atom carrying the sulfur atom,

- n represents the number of substituents X ₂ on the cycle.

As stated above, the compound of the invention carries at least one amino group on the aromatic ring. It is a free or substituted amine function, one of the hydrogen atoms being replaced by a hydrocarbon group having from 1 to 20 carbon atoms, such as alkyl, cycloalkyl, aralkyl or heterocyclic radicals.

More particularly, the symbol R represents an alkyl group having 1 to 10 carbon atoms and preferably 1 to 4 carbon atoms or a cyloalkyl group having 3 to 8 carbon atoms, preferably a cyclopentyl or cyclohexyl group; an aryl group having 6 to 12 carbon atoms, preferably a phenyl group; an aralkyl group having 7 to 12 carbon atoms, preferably a benzyl group. The invention applies in particular to aromatic compounds corresponding to formula (I) in which A is the residue of a cyclic compound, preferably having at least 4 atoms in the ring, optionally substituted, and representing at least the one of the following cycles:

. an aromatic, monocyclic or polycyclic carbocycle,. an aromatic, monocyclic or polycyclic heterocycle comprising at least one of the heteroatoms O, N and S,

It will be specified, without however limiting the scope of the invention, that the optionally substituted residue A represents, the rest:

1 ° - of an aromatic, monocyclic or polycyclic carbocyclic compound. By "polycyclic carbocyclic compound" is meant:

. a compound consisting of at least 2 aromatic carbocycles and forming between them ortho- or ortho- and pericondensed systems,. a compound consisting of at least 2 carbocycles of which only one of them is aromatic and forming between them ortho- or ortho- and pericondensed systems.

2 ° - of an aromatic, monocyclic or polycyclic heterocyclic compound. By "polycyclic heterocyclic compound", we define:. a compound consisting of at least 2 heterocycles containing at least one heteroatom in each cycle of which at least one of the two cycles is aromatic and forming between them ortho- or ortho- and pericondensed systems, . a compound consisting of at least one hydrocarbon ring and at least one heterocycle of which at least one of the rings is aromatic and forming between them ortho- or ortho- and pericondensed systems. 3 ° - of a compound constituted by a chain of cycles, as defined in paragraphs 1 and / or 2 linked together:. by a valential link,

. by an alkylene or alkylidene group having from 1 to 4 carbon atoms, preferably a methylene or isopropylidene group,. by one of the following groups: -O-, -CO-, -COO-, -OCOO-

-S-, -SO-, -SO 2 ^"

-N-, -CO-N-, I I

^R o ^R 0 in these formulas, R _Q represents a hydrogen atom or an alkyl group having from 1 to 4 carbon atoms, a cyclohexyl or phenyl group. As examples of cycles under 1 ° to 3 °, we can cite:

1 ° - benzene, toluene, xylene, naphthalene, anthracene,

2 ° - furan, pyrrole, thiophene, isoxazole, furazanne, isothiazole, imidazole, pyrazole, pyridine, pyridazine, pyrimidine, quinoline, naphthyridine, benzofuran, indole, 3 ° - biphenyl, 1,1'-methyienebiphenyl, 1, 1 '-isopropyiidenebiphenyl, 1,1'-oxybiphenyl, 1, 1'-iminobiphenyl.

More particularly, the optionally substituted residue A represents, the remainder:

a monocyclic, carbocyclic, aromatic compound, such as, for example, benzene, toluene, isobutylbenzene, anisole, phenetole or veratrole, guaiacol, guetol, 4-phenoxypropionic acid,

- a polycyclic, condensed, aromatic compound, such as, for example, naphthalene, 2-methoxynaphthalene,

- a polycyclic, non-condensed, carbocyclic, aromatic compound, such as, for example, phenoxybenzene,

a polycyclic, condensed, carbocyclic, partially aromatic compound, such as, for example, tetrahydronaphthalene, 1,2-methylene dioxybenzene, - a polycyclic, non-condensed, carbocyclic, partially aromatic compound, such as, for example, cyclohexylbenzene,

- a monocyclic, heterocyclic, aromatic compound, such as, for example, pyridine, furan, thiophene, - a polycyclic, condensed, aromatic, partially heterocyclic compound, such as, for example, quinoline, indole or benzofuran,

- a polycyclic, non-condensed, aromatic, partially heterocyclic compound, such as, for example, phenylpyridines, naphthylpyridines,

- a polycyclic, condensed, partially aromatic, partially heterocyclic compound, such as, for example, tetrahydroquinoline,

- a polycylic compound, non-condensed, partially aromatic, partially heterocyclic, such as, for example, cyclohexylpyridine. In the process of the invention, use is preferably made of a compound of formula (I) in which A represents an aromatic nucleus, preferably a benzene nucleus.

As regards the definition of group Z, it is a group comprising a doublet donor atom, in position α with respect to the carbon carrying the sulfur atom.

As an atom having an available doublet, mention may be made of a nitrogen, sulfur or oxygen atom.

Thus, Z symbolizes the rest of a possibly silylated amine, an ether or a thioether. The group -O-CS- Z can therefore be, among others, a group:

- thiocarbamate symbolized by the formula -0-CS-N (R- |) (R2);

- thiocarbonate represented by the formula -O-CS-OR3;

- dithiocarbonate represented by the formula -O-CS-SR3.

It should be noted that for the understanding of the invention, the compound of formula (I) is generically called compound O-arylthiocarbamate but it also includes the compounds of thiocarbonate and dithiocarbonate type and other equivalent.

In the different formulas, R- |, R2, R3, identical or different, represent more particularly an alkyl group having from 1 to 12 carbon atoms, preferably from 1 to 4; a cycloalkyl group having 3 to 8 carbon atoms, preferably a cyclohexyl group; an Si type group (^ 3, with the same or different% radicals, which represent an alkyl group having from 1 to 12 carbon atoms. It is also possible that the two groups Ri and R ₂ , can form together and with the nitrogen atom a heterocycle having 3 to 8 atoms, preferably 4 to 5 atoms and optionally comprising another heteroatom such as an atom oxygen or nitrogen.

As more specific examples, R- | and R ₂ , identical or different, represent a methyl, isopropyl, cyclohexyl or trimethylsilyl group and R- _| and R ₂ can together form one of the following cycles:

The preferred compounds corresponding to formula (I) are those in which

Z represents an amino group in which the groups R - |, R ₂ , identical or different, represent an alkyl group having from 1 to 4 atoms, preferably methyl or a trimethylsilyl group.

As mentioned previously, the hydroxylated aromatic compound of formula (I) also comprises an electron-withdrawing group X and optionally other substituents X ₂ on the ring.

The number of substituents present on the cycle depends on the carbon condensation of the cycle and on the presence or not of unsaturations on the cycle.

The maximum number of substituents likely to be carried by a cycle, is easily determined by a person skilled in the art.

In the present text, the term "several" is generally understood to mean less than 5 substituents on an aromatic ring. Thus, n is advantageously equal to 1 or 2.

The electron-withdrawing group is more particularly one of the following atoms or groups:

. an acyl group having 2 to 20 carbon atoms, preferably acetyl. a group of formula:

-R ₄ -X -R4-CF ₃ -R4-COOR5

-R4-CHO -R4-SO-R5 -R4-SO2-R5 -R4-S-CF ₃ -R4-N0 ₂

-R4-CN -R ₄ -N = C (R ₅ ) ₂ -R4-NH-CO-R5

-R ₄ -N + (R ₅ ) ₃

-R4-Si (Rδ) 3 in said formulas, R4 represents a valential bond or a divalent, linear or branched, saturated or unsaturated hydrocarbon group having from 1 to 4 carbon atoms such as, for example, methylene, ethylene, propylene , isopropylene, isopropylidene; the identical or different radicals R5 represent a hydrogen atom or a linear or branched, saturated or unsaturated alkyl group having from 1 to 20 carbon atoms; X symbolizes a halogen atom, preferably a chlorine, bromine or fluorine atom.

The aromatic nucleus may carry other substituents X ₂ of any kind. It can be either an electron-withdrawing group such as X ^ or an electron-donor type group and in particular:

. an alkyl group, linear or branched, having from 1 to 6 carbon atoms, preferably from 1 to 4 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl,. a linear or branched alkenyl group having from 2 to 6 carbon atoms, preferably from 2 to 4 carbon atoms, such as vinyl, allyl,. a linear or branched alkoxy group having from 1 to 6 carbon atoms, preferably from 1 to 4 carbon atoms such as the methoxy, ethoxy, propoxy, isopropoxy, butoxy radicals, a 2-oxy propionic group,. a cycloalkyl group having 3 to 8 carbon atoms, preferably a cyclohexyl group,. a benzyl group,. a phenyl group,

. a group of formula:

-R4-N (Rδ) 2 -R ₄ -CO-N (R ₅ ) ₂ in said formulas, R4 and R5 can take the meanings given above.

Among the various aforementioned substituents, the compounds of formula (I) preferably used in the process of the invention have two electron-attracting groups and more particularly two halogen atoms.

The process of the invention is entirely suitable for the preparation of thiophenols carrying an amine function from an O-phenylthiocarbamate.

They can be represented more particularly by the formula (la):

in which R, X ^, X ₂ , Z and n have the meaning given above.

Even more preferred compounds correspond to the general formula

in which X _{1 f} X ₂ , R, Rj, R and n have the meaning given above.

Another subject of the invention resides in the new compounds obtained, namely compounds of the S-arylthiocarbamate type, which can be symbolized by the formula

in which A, R, X ^ X ₂ , Z and n have the meaning given above.

The preferred compounds correspond more particularly to the formula (IIa):

in which R, X ^ X ₂ , Z and n have the meaning given above.

As new products, mention may be made of the compounds corresponding to the formula (IIa ₎ ) and in particular those in which Xi and X ₂ represent a halogen atom:

in which X ^ X, R, Rj, R ₂ and n have the meaning given above.

The invention also relates to the use of the compounds of formula (II) for the preparation of aromatic thiols corresponding to formula (III):

in which A, R, X ^ X ₂ and n have the meaning given above, which consists in carrying out the hydrolysis of a compound of the S-arylthiocarbamate type preferably corresponding to formula (II) and more preferably to the formula

(lia) and (lia-,). The process of the invention allows easy access to the compounds corresponding to the formula

in which R, X- _| , X ₂ and n have the meaning given above.

The invention also relates to the use of the compounds of formula (II) for the preparation of aromatic thioethers corresponding to formula (VI):

in which A, R, X- |, X ₂ and n have the meaning given above and R ₈ represents a hydrocarbon radical having from 1 to 24 carbon atoms, which can be a saturated or unsaturated, linear or branched acyclic aliphatic radical ; a saturated, unsaturated or aromatic, monocyclic or polycyclic cycloaliphatic radical; a saturated or unsaturated, linear or branched aliphatic radical, carrying a cyclic substituent,

In the present text, we designate, in a simplified manner, by "thioether groups", groups of the type -S-Rβ in which RQ has the given meaning. previously. R ₈ therefore represents both an acyclic or cycloaliphatic, saturated, unsaturated or aromatic aliphatic radical as a saturated or unsaturated aliphatic radical carrying a cyclic substituent.

The aromatic thioether capable of being obtained according to the process of the invention corresponds to formula (VI) in which R ₈ represents an acyclic aliphatic radical, saturated or unsaturated, linear or branched.

More preferably, R ₈ represents a linear or branched alkyl radical having from 1 to 12 carbon atoms, preferably from 1 to 6 carbon atoms: the hydrocarbon chain can possibly be interrupted by a heteroatom (for example, oxygen), by a functional group (for example -CO-) and / or carrying a substituent (for example, a halogen, an ester function, preferably methyl or ethyl).

The acyclic, saturated or unsaturated, linear or branched aliphatic radical may optionally carry a cyclic substituent. The term “ring” is preferably understood to mean a saturated, unsaturated or aromatic carbocyclic ring, preferably cycloaliphatic or aromatic, in particular cycloaliphatic ring comprising 6 carbon atoms in the ring or benzene.

The acyclic aliphatic radical can be linked to the ring by a valential bond, a heteroatom or a functional group and examples are given above.

The cycle can be optionally substituted and, as examples of cyclic substituents, it is possible, among others, to consider the substituents such as alkyl, alkoxy groups, halogen atom, trifluoromethyl group, etc.

R ₈ may also represent a carbocyclic radical saturated or comprising 1 or 2 unsaturations in the ring, generally having from 3 to 8 carbon atoms, preferably 6 carbon atoms in the ring; said cycle can be substituted.

R ₈ may also represent an aromatic carbocyclic radical, preferably a monocyclic radical generally having at least 4 carbon atoms, preferably 6 carbon atoms in the ring; said cycle can be substituted.

The process of the invention applies very particularly to aromatic thioethers of formula (VI) in which R ₈ represents a linear or branched alkyl radical having from 1 to 4 carbon atoms or a phenyl radical. As examples of preferred R ₈ radicals according to the invention, mention may be made of methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl or phenyl radicals. The process for the preparation of said thioether consists in carrying out the hydrolysis of a compound of S-arylthiocarbamate type preferably corresponding to formula (II) and more preferably to formula (IIa) and (IIa |) and S-alkylation or S-arylation using an alkylating or arylating agent.

The term "alkylating agent" is generic and designates the replacement of the hydrogen atom by any hydrocarbon group, in particular alkyl, cycloalkyl, aryl, arylalkyl groups, etc.

The process of the invention allows easy access to the compounds corresponding to the formula

in which R, R ₈ , Xj, X2 and n have the meaning given above.

In accordance with the process of the invention, the thermal rearrangement of the O-arylthiocarbamate into S-arylthiocarbamate is carried out. The transformation is obtained by heating the reaction mixture to a temperature varying for example between 140 ° C and 400 ° C and, preferably, from 150 ° C to 300 ° C.

Heating of the reaction mixture may be carried out in fusion or in an organic solvent having a high boiling point above the chosen temperature. As examples of more specific solvents, mention may be made of the following solvents: glycerol, biphenyl oxide, eutectic mixture of biphenyl and biphenyl oxide referenced under the trade names of Dowtherm® or Gilotherm®.

The heating is carried out in a conventional manner, for example by induction or by means of heat transfer fluids, molten salt baths in particular calcium chloride or organic solvents having a high boiling point and in particular those mentioned above.

At the end of the reaction, the product obtained is subjected to a hydrolysis operation in order to release the SH function. A first variant of the process of the invention consists in carrying out an acid hydrolysis.

For this purpose, use may be made of a protonic acid of mineral origin, preferably hydrochloric acid, sulfuric acid phosphoric acid or an organic acid such as, for example, trifluromethanesulfonic acid or the acid methanesulfonic. Preferably sulfuric acid is chosen. The concentration of the acid is indifferent. Preferably, a diluted acid solution of 1 to 2 N is used.

The amount of acid used, expressed by the ratio between the number of H + ions and the number of moles of S-arylthiocarbamate is preferably chosen between 0.1 and 2.

The amount of acid used is preferably catalytic and more preferably between 0.1 and 0.25.

The hydrolysis reaction is carried out at a temperature which is not critical and which can vary from room temperature (generally 15 ° C and 25 ° C) to the reflux temperature of the reaction mixture.

At the end of the reaction, the desired product is preferably obtained corresponding to formula (III) either by decantation or by extraction using an organic solvent having a lipophilic character. Mention may in particular be made of halogenated or non-halogenated aromatic hydrocarbons, for example toluene and halogenated or non-halogenated aliphatic hydrocarbons, preferably dichloromethane, aliphatic or aromatic ethers-oxides, such as for example ethyl oxide or oxide isopropyl.

According to another variant of the process of the invention, the hydrolysis reaction is carried out in basic medium. To do this, use is made of a strong base, preferably an inorganic base such as an alkali and alkaline earth metal carbonate, an alkali metal hydroxide or an organic base, preferably sodium methylate. Mention may more particularly be made of soda, potash and sodium or potassium carbonate. The base is generally used in the form of a solution, the concentration of which can vary widely between 1 and 12 N.

The amount of base used expressed by the ratio between the number of OH ions ^" and the number of moles of S-arylthiocarbamate is preferably chosen between 1 and 2. The amount of base is preferably greater than the stoichiometry of the reaction .

It is also possible to conduct basic hydrolysis, in the presence of an alcohol, preferably, the methanol used in an amount such that the reaction mixture can be easily stirred.

The thiol function being salified, it may be desirable to release it by carrying out a neutralization using a strong acid as mentioned above. The amount of acid corresponding to the stoichiometry is used.

The product obtained is then separated as described above, for example by extraction or decantation. The product obtained has good purity, which means that it is not necessary to carry out further purifications. If necessary, purification can be carried out, for example, by recrystallization from a solvent such as an alcohol and more particularly ethanol. According to another variant of the process of the invention, the preparation of an aromatic thioether can be carried out from the compound of the S-arylthiocarbamate type.

More specifically, a basic hydrolysis of the S-arylthiocarbamate type compound is carried out as previously described, then the thioalkylation using a conventional alkylating agent.

As alkylating agents which are particularly suitable, mention may in particular be made of alkylating agents of the halide, carbonate or sulphate type.

Thus, said agents correspond respectively to the following formulas: R ₈ - X (Vlla) R ₈ - O - S0 ₂ - O - R ₈ (Vllb) R ₈ - O - CO - O - R ₈ (Vile) in said formulas, R ₈ has the meaning given above and X represents a halogen atom, preferably a fluorine, chlorine, bromine or iodine atom.

Among the halide-type alkylating agents, those which are preferred correspond to the formula (Vlla) in which X represents a fluorine, chlorine or bromine atom and R ₈ represents a linear or branched alkyl radical having from 1 to 6 carbon atoms, and preferably from 1 to 4 carbon atoms or a phenyl radical.

Preferably, those corresponding to the formula (Vlla) are used in which X represents a chlorine atom and R ₈ represents a linear or branched alkyl radical having from 1 to 4 carbon atoms.

Among the halides, methyl chloride, chloroethane, methyl bromide are preferred.

Due to their lower cost, it is preferred to use methyl chloride and chloroethane. In the case of alkylating agents of the sulfate or carbonate type, it is preferred to use those corresponding to the formulas (Vllb) and (Vile) in which R ₈ represents a linear or branched alkyl radical having from 1 to 6 carbon atoms and preferably from 1 to 4 carbon atoms or a phenyl radical. Among the abovementioned alkylating agents, dimethylsulfate and dimethylearbonate are preferred. The amount of alkylating agent expressed relative to the amount of S-arylthiocarbamate is preferably equal to the stoichiometry up to an excess of up to 200%.

The hydrolysis reaction being carried out in the presence of water, there is therefore water in the reaction medium. It is possible to use an organic solvent which may or may not be miscible with water. The solvent can be chosen from aliphatic, cycloaliphatic or aromatic hydrocarbons, halogenated or not. Examples of solvents that may be mentioned include dichloroethane, toluene and xylenes. The S-alkylation reaction is carried out by bringing the S-arylthiocarbamate and the alkylating agent in any manner.

Before adding the alkylating agent, generally, a basic agent, preferably sodium hydroxide or potassium hydroxide, is added in an amount ranging from the stoichiometric amount of S-arylthiocarbamate in an excess which can reach, for example, 100%.

The temperature at which the reaction is carried out advantageously varies between 20 and 150 ° C., preferably between 40 and 100 ° C.

At the end of the reaction, the thioether preferably corresponding to formulas (VI) and (Via) is recovered according to conventional separation techniques, for example filtration.

In the process of the invention, one starts from a compound of formula (I) and more preferably of formula (la).

These compounds are new products. One mode of production consists in reacting a hydroxylated aromatic compound carrying at least one amino or nitro group preferentially corresponding to formula (IV) and a sulfur-containing reagent preferentially corresponding to formula (V), optionally in the presence of a based. The starting aromatic substrate more particularly corresponds to formula (IV):

in said formula,

- A, Xi, X2 and n have the meaning given above,

- W symbolizes H2 _. O2 or HR; R representing a hydrogen atom or a hydrocarbon group. As regards the sulfur-containing reagent, it more particularly corresponds to formula (V):

in which: - Y is a group leaving in the presence of a nucleophile,

- Z is a group comprising a doublet donor atom in position relative to the carbon carrying the sulfur atom.

A first variant of the process of the invention consists in reacting a compound of formula (IV) carrying an amino group, which means that W comprises at least one hydrogen atom with the sulfur-containing reagent of formula (V) in the aim of forming an O-arylthiocarbamate type compound of formula (I).

Another variant of the invention consists in obtaining a compound of the type

O-arylthiocarbamate of formula (I) by first making an O-arylthiocarbonate type compound carrying a nitro group and then reducing the nitro group to the amino group. Thus, one reacts with the sulfur-containing reagent (V), a compound of formula (IV) carrying a nitro group, that is to say W represents two oxygen atoms, then the product obtained is subjected to an operation of reduction.

Among the compounds of formula (IV), use is more particularly made of those corresponding to the following formula:

in said formula,

- Xi, X2 and n have the meaning given above,

- W symbolizes H ₂ , HR or O2; R representing a hydrogen atom or a hydrocarbon group as defined.

As regards the sulfur-containing reagent which preferably corresponds to formula (V), the leaving group Y can be defined as a weak base.

By "weak base" is meant a base whose pka of the conjugated acid is less than 6.5, preferably less than 5. As leaving group Y, there may be mentioned the halogen atoms (chlorine, bromine, iodine), the sulfonic ester group -OS0 ₂ R6 in which R ₈ represents a hydrocarbon group having from 1 to 20 carbon atoms and more particularly: . an alkyl group having from 1 to 10 carbon atoms, preferably 1 to 4 carbon atoms and more preferably a methyl or ethyl group, optionally bearing a halogen atom, a CF ₃ group or a ammonium group N (Ry) 4, R, identical or different, representing an alkyl group having from 1 to 4 carbon atoms,

. a cycloalkyl group having 3 to 8 carbon atoms, preferably a cyclohexyl group,. an aryl group having from 6 to 12 carbon atoms, preferably a phenyl group optionally carrying an alkyl group having from 1 to 10 carbon atoms, preferably 1 to 4 carbon atoms and more preferably a methyl group or ethyl, a halogen atom, a CF3 group or a NO2 group,

. a CX3 group in which X represents a fluorine, chlorine or bromine atom,. a group CF ₂ - CF3.

The preferred sulfonic ester groups are:

- tosylates (p-toluenesulfonates) -OSO2-C5H4-CH3

- brosylates (p-bromobenzenesulfonates) -OS0 ₂ -C ₈ H4-Br

- nosylates (p-nitrobenzenesulfonates) -OSO2-C6H4-NO2 - mesylates (methanesulfonates) -OSO2-CH3

- betylates (ammonioalkanesulfonates) -OSθ2- (CH2) _n NMe3 ⁺ with n between 0 and 6,

- triflates (trifluoromethanesulfonates) -OSO2-CF3

- nonaflates (nonafluorobutanesulfonates) -OSO2-C4F9 - tresylates (2,2,2-trifluroethanesulfonates) .- OSθ2-CH ₂ -CF ₃

As the preferred leaving group, a halogen atom is chosen. It goes without saying that the nature of the leaving group is not fundamental according to the invention since it can be displaced by the action of an anion ArO ^" , Ar symbolizing the phenolate or other salified compound of formula (IV) As regards the definition of group Z, it is a group comprising a doublet donor atom, in position α with respect to the carbon carrying the sulfur atom.

As an atom having an available doublet, mention may be made of a nitrogen, sulfur or oxygen atom. Thus, Z symbolizes the rest of a possibly silylated amine, an ether or a thioether.

The group -O-CS- Z can therefore be, among others, a group:

- thiocarbamate symbolized by the formula -0-CS-N (R ₁ ) (R2); - thiocarbonate represented by the formula -O-CS-OR3;

- dithiocarbonate represented by the formula -O-CS-SR3.

In the different formulas, Rj, R2, R3, identical or different, represent more particularly an alkyl group having from 1 to 12 carbon atoms, preferably from 1 to 4; a cycloalkyl group having 3 to 8 carbon atoms, preferably a cyclohexyl group; an Si type group (^ ₃ , with the same or different% radicals, which represent an alkyl group having from 1 to 12 carbon atoms.

It is also possible that the two groups R 1 and R ₂ , together form and with the nitrogen atom a heterocycle having 3 to 8 atoms, preferably 4 to 5 atoms and optionally comprising another hetero atom such as an atom oxygen or nitrogen.

Z preferably represents an amino group in which the groups R 1, R ₂ , which are identical or different, represent an alkyl group having from 1 to 4 atoms, preferably methyl or a trimethylsilyl group.

The sulfur reagent preferably used corresponds to the formula

in said formula: - Y represents a group leaving, preferably, a halogen atom,

- Ri and R2, identical or different, represent an alkyl group having from 1 to 12 carbon atoms, preferably from 1 to 4; a cycloalkyl group having 3 to 8 carbon atoms, preferably a cyclohexyl group; a group of type S ^, with the radicals% identical or different, which represent an alkyl group having from 1 to 12 carbon atoms.

In accordance with the process of the invention, the hydroxylated aromatic compound reacting preferentially with formula (IV) and the sulfur-containing reactant reacting preferentially with formula (V) are reacted.

The quantity of sulfur-containing reagent used, expressed by the molar ratio of sulfur-containing reagent to hydroxylated aromatic compound, can vary between 1 and 1.2, and is preferably around 1.

The reacted hydroxylated aromatic compound can be in salified form. It is possible to use a salified form of a hydroxylated aromatic compound prepared extemporaneously but it is also possible to prepare it in situ by reacting it with a base.

A base which can be mineral or organic therefore intervenes in the process of the invention.

The base used in this step allows the formation, from phenol or other hydroxylated aromatic compound of formula (IV) or (IVa), the corresponding anion ArO "in the reaction medium. Thus, the base must be strong enough to tear off the proton of the hydroxyl of ArOH. The base generally has a pKa greater than 9.0.

PKa is defined as the ionic dissociation constant of the acid / base couple, when water is used as a solvent.

For the choice of a base having a pKa as defined by the invention, reference may be made, inter alia, to the HANDBOOK OF CHEMISTRY AND PHYSICS, 66 ^th edition, p. D-161 AND D-162.

Suitable bases are in particular the alkali and alkaline earth metal carbonates and the alkali metal hydroxides, preferably sodium or potassium hydroxide.

It is also possible to use a quaternary ammonium hydroxide.

As examples of quaternary ammonium hydroxide, use is preferably made of tetralkylammonium or trialkylbenzylammonium hydroxides in which the identical or different alkyl radicals represent a linear or branched alkyl chain having from 1 to 12 carbon atoms, preferably from 1 to 6 carbon atoms.

Tetramethylammonium hydroxide, tetraethylammonium hydroxide or tetrabutylammonium hydroxide is preferably chosen.

It is also possible according to the invention to use trialkylbenzylammonium hydroxides and in particular trimethylbenzylammonium hydroxide.

For economic considerations, one chooses from all the bases, preferably sodium or potassium hydroxide.

The concentration of the basic starting solution is not critical. The alkali metal hydroxide solution used has a concentration generally between 10 and 50% by weight.

The amount of base introduced into the reaction medium takes account of the amount necessary to salify the hydroxylated function of the aromatic compound. If the said compound has salifiable functions other than the hydroxyl group, the quantity of base necessary to salify all the salifiable functions is therefore introduced.

Generally, the amount of base expressed relative to the aromatic compound varies between 100 and 120% of the stoichiometric amount.

The base is generally introduced with the other reagents.

The reaction can be carried out according to numerous variants. Thus, it can be carried out in bulk in the absence of any solvent, in an aqueous medium, in an organic medium or in a hydro-organic medium. When the reaction is carried out in an aqueous medium, water is generally provided by the base which is introduced in the form of an aqueous solution. The amount of water is adjusted so that the reaction medium can be easily stirred.

It is also possible to carry out the reaction in an organic solvent, preferably an aprotic polar solvent. Mention may in particular be made of halogenated hydrocarbons such as, for example, dichloromethane, dichloroethane, chlorobenzenes; alcohols such as in particular methanol, isopropanol and ethylene glycol; polyol esters or ethers such as tetraethylene glycol diacetate; aliphatic ethers, linear or cyclic such as isopropyl ether, methyl and tert-butyl ether, ethylene glycol dimethyl ether (or 1, 2-dimethoxyethane), diethylene glycol dimethyl ether (or 1, 5-dimethoxy 3-oxapentane); phenyl oxide, tetrahydrofuran or dioxane; nitriles such as acetonitrile.

There is no drawback in carrying out the reaction in a hydro-organic medium, therefore using water and an organic, preferably polar, solvent, and in particular those mentioned above.

The reaction is preferably carried out in bulk, in the absence of any aqueous or organic solvent.

For agitation reasons, it may be advantageous to use a solvent, but it is always desirable to minimize its quantity.

The amount of solvent (which includes water) is added so that the medium is easily stirred. The hydroxylated aromatic compound generally represents from 5 to 40% of the weight of solvent. Its values are given for information only and are not limiting. The process of the invention is advantageously carried out at a temperature between room temperature (generally 15 ° C to 25 ° C) and the reflux temperature of the reaction mixture. The reaction temperature is preferably chosen between 60 ° C and 90 ° C. The different reagents, base and solvent can be used in any order.

At the end of the reaction, a product is recovered, namely an O-arylthiocarbamate which can be separated from the medium according to conventional separation techniques. It can be separated by filtration or else by extraction using an appropriate solvent, for example toluene or dichloromethane.

The compound obtained, depending on the nature of the nitrogen group which it carries, can be subjected to a hydrogenation step.

This can be carried out in a conventional manner by iron, in the presence of hydrochloric acid or by catalytic reduction with hydrogen in the presence of palladium deposited on carbon black or Raney nickel [cf. HOUBEN- WEYL Methoden der organischen Chemie Band IV / 1c p. 487 and 506 (1980)].

A compound of O-arylthiocarbamate type is obtained which preferably corresponds to formula (I) which is used in the process of the invention. Examples of practical embodiments of the invention are given below.

The examples are given by way of illustration, without limitation.

EXAMPLES

Synthesis of O-arvIthiocarbamate

5-nitro-2-chloro-4-fluorophenol (15 mmol) is added to a 1N aqueous sodium hydroxide solution (15 mmol, 15 ml) at room temperature and with stirring.

Thiocarbamoyl chloride (16.5 mmol, 2.038 g) is added, 5 min later, in one go.

The reaction mixture is then heated at 50 ° C for 10 hours.

After cooling, the O-arylthiocarbamate is filtered and dried under reduced pressure of 15 mm of mercury.

The carbamate obtained is then purified by recrystallization from ethanol. 90% of a product corresponding to the following formula is obtained:

Its characteristics are as follows (the NMR measurements are carried out in the CDCI3 solvent): - melting point = 141 ° C

- 1 H NMR: 3.41 (3H, s); 3.47 (3H, s); 7.41 O Harom, d, J = 7); 7.92 (I Harom. D, J ≈ 7).

- 13c NMR: 39.1; 43.8; 119.9 (d, J = 25.2); 122.9 135.5 (d, J = 9.9); 146.1-150.8-155.0; 185.2.

Reduction of the nitro group to amino

The thiocarbamate (10 mmol) and iron (powder, 30 mmol, 1.675 g) are placed in suspension in 100 ml of an ethanol / water solution (1/1 by mass) then the acetic acid (11 mmol, 0.661 g , 0.63 ml) is added dropwise.

The reaction mixture is heated under reflux of ethanol for 2 h 30 then diluted (100 ml of ethanol) and filtered hot on celite.

After washing the aqueous phase with dichloromethane (2 x 50 ml), basification to pH> 12 using a 5N aqueous sodium hydroxide solution, extraction with dichloromethane (4 x 50 ml), drying over sodium sulfate. magnesium and evaporation of the organic solvents, 2.48 g of a yellow solid are collected which does not require purification.

We get 99% of a co the formula:

Its characteristics are as follows:

- melting point = 154 ° C.

- 1 H NMR: 3.35 (3H, s); 3.45 (3H, s); 6.57 (1 H _arom , d, J = 8.25); 7.06 O Harom. α, J = 10.3). - ¹³ C NMR: 38.9; 43.6; 112.6-116.4-116.7-134.1 (dJ = 14.3); 146.5 (d, J = 36.6); 150.8; 186.6.

Neumann-Kwart transposition

The O-arylthiocarbamate (0.5 mmol) and diphenyl ether (5 g or about 10 ml / mmol of thiocarbamate) are heated at the reflux of the diphenyl ether (259 ° C) for 1 hour 30 minutes. After cooling, the crude is diluted with 30 ml of ethyl ether and the S-arylthiocarbamate is extracted with 4 x 30 ml of an aqueous solution of 6N hydrochloric acid.

The aqueous phases are then basified to pH> 12 with sodium hydroxide and extracted with dichloromethane (4 x 30 ml).

After drying over magnesium sulfate and evaporation of the dichloromethane phases, the S-arylthiocarbamate is isolated in the form of a white solid which does not require purification.

We get 91% of a pro formula:

Its characteristics are as follows:

- melting point = 151 ° C.

- 1 H NMR: 3.03 (3H, S | _ar ) \ 3.11 (3H, S | _arge ); 3.82 (NH, S | _arge ); 6.99 d Harom. <W = 5.8); 7.13 (1 Harom, d, J = 6.6). - 13c NMR: 37.0; 117.0 (d, J = 22.54); 125.4 (d, J ≈ 4.4); 128.0 (d, J = 9.4); 133.8 (d, J = 13.1); 151.0 (d, J = 245); 165.4.

- 9F NMR = 130.7.

Hvdrolvse of S-arvIthiocarbamates to Thiophenols S-arylthiocarmabate (5 mmol) is placed in solution in 20 ml of methanol then a molar solution of sodium hydroxide is added (10 ml) and the reaction mixture is brought to reflux of methanol for 12 hours.

After cooling, the aqueous phase is washed with dichloromethane (2 x 30 ml) then acidified to pH 1 with 6N hydrochloric acid and extracted with dichloromethane (4 x 30 ml), after drying over sodium sulfate. magnesium and evaporation of the solvent the thiophenol is recovered which does not require purification.

85% of a product corresponding to the formula is obtained:

Its characteristics are as follows:

- melting point = 58 ° C

- 1 H NMR: 3.08 (NH2, S | _argθ ); 3.77 (SH, s); 6.79 (1H _arom , d, J = 3.2); 7.01 (Harom »dJ = 2.2).

Synthesis of a thioether from an S-arvlthiocarbamate.

0.25 mol of S-arylthiocarbamate, 75 g of water and 75 g of methanol are loaded into the reactor.

The mixture is heated to 70 ° C. with stirring and 0.50 mol of a 40% by weight aqueous sodium hydroxide solution are added over 30 minutes.

The mixture is stirred at 70 ° C. for 3 hours so as to hydrolyze the S-arylthiocarbamate with a conversion rate greater than 95%.

The reaction medium is cooled to 25 ° C. and 0.25 mol of an aqueous sodium hydroxide solution at 40% by weight is added over ten minutes, then 0.27 mol of dimethylsulphate in 30 minutes.

To complete the methylation (TT thiophenol> 99%), the reaction medium is heated for one hour at 70 ° C.

The reaction mixture is cooled to 10 ° C. and the crude thioether is recovered by filtration. The cake is washed with a 10% sodium hydroxide solution and then with water.

The product is recrystallized from methanol. 84% of the product of the following formula is obtained:

Claims

1 - Process for transposing a compound of O-arylthiocarbamate type carrying at least one amino group into a compound of S-arylthiocarbamate type carrying at least one amino group characterized in that it consists in heating a compound of O-arylthiocarbamate type carrying at least one amino group and one electron-withdrawing group.

2 - Process according to claim 1 characterized in that it consists in heating a compound of the O-arylthiocarbamate type carrying at least one amino group and of an electro-attractor group corresponding to the general formula

in which: - A symbolizes the rest of a cycle forming all or part of a carbocyclic or heterocyclic, aromatic, monocyclic or polycyclic system,

- R represents a hydrogen atom or a hydrocarbon group,

- Xi represents an electro-attractor group,

- X2 represents a hydrogen atom or a substituent of any kind,

Z is a group comprising a doublet donor atom linked to the carbon atom carrying the sulfur atom,

- n represents the number of substituents X2 on the cycle.

3 - Process according to claim 2 characterized in that the compound of O-arylthiocarbamate type corresponds to formula (la):

in which R, X ^, X2, Z and n have the meaning given in claim 2.

4 - Method according to one of claims 2 and 3 characterized in that the O-arylthiocarbamate type compound of formula (I) carries at least one amino group on the aromatic ring in the form of a free or substituted amine function, one of the hydrogen atoms being replaced by a hydrocarbon group having from 1 to 20 carbon atoms, preferably alkyl, cycloalkyl, aryl aralkyl or heterocyclic radicals.

5 - Method according to one of claims 2 to 4 characterized in that the compound of O-arylthiocarbamate type corresponds to formula (I) in which R represents an alkyl group having 1 to 10 carbon atoms and preferably 1 to 4 carbon atoms or a cyloalkyl group having 3 to 8 carbon atoms, preferably a cyclopentyl or cyclohexyl group; an aryl group having 6 to 12 carbon atoms, preferably a phenyl group; an aralkyl group having 7 to 12 carbon atoms, preferably a benzyl group.

6 - Method according to one of claims 2, 4 and 5 characterized in that the compound of O-arylthiocarbamate type corresponds to formula (I) in which A is the remainder of a cyclic compound, preferably having, at at least 4 atoms in the ring, optionally substituted, and representing at least one of the following rings:. an aromatic, monocyclic or polycyclic carbocycle,

. an aromatic, monocyclic or polycyclic heterocycle comprising at least one of the heteroatoms O, N and S.

7 - Process according to claim 6 characterized in that A is the remainder of a benzene compound.

8 - Method according to one of claims 2 and 3 characterized in that the compound of O-arylthiocarbamate type corresponds to formula (I) in which Z is a group comprising a nitrogen, sulfur or oxygen atom .

9 - Method according to one of claims 2, 3 and 8 characterized in that the compound of O-arylthiocarbamate type corresponds to formula (I) in which the group -O-CS- Z is a group: - thiocarbamate symbolized by the formula -0-CS-N (R ₁ ) (R ₂ );

- thiocarbonate represented by the formula -O-CS-OR3;

- dithiocarbonate represented by the formula -O-CS-SR3. in the formulas, R ^, R2, R3, identical or different, represent more particularly an alkyl group having from 1 to 12 carbon atoms, preferably from 1 to 4; a cycloalkyl group having 3 to 8 carbon atoms, preferably a cyclohexyl group; a group of type Si (φ ₃ , with the same or different% radicals, which represent an alkyl group having from 1 to 12 carbon atoms; and two groups R 1 and R 2, can form together and with the nitrogen atom a heterocycle having 3 to 8 atoms, preferably 4 to 5 atoms and optionally comprising another heteroatom such as an oxygen or nitrogen atom.

10 - Method according to one of claims 8 and 9 characterized in that the compound of type O-ary .thiocarbamate corresponds to formula (I) in which Z represents an amino group in which the groups R- |, R ₂ , identical or different, represent an alkyl group having from 1 to 4 atoms, preferably methyl or a trimethylsilyl group.

11 - Method according to one of claims 2 and 3 characterized in that the compound of the O-arylthiocarbamate type corresponds to formula (I) in which Xi represents an electro-attractor group such as:

. an acyl group having 2 to 20 carbon atoms, preferably acetyl. a group of formula: -R4-X

-R4-CF ₃ -R4-COOR5 -R4-CHO -R4-SO-R5 -R4-SO2-R5

-R4-S-CF ₃ -R4-N0 ₂ -R4-CN

-R ₄ .N = C (R ₅ ) 2 -R4-NH-CO-R5

-R ₄ -N + (R ₅ ) ₃

-R4-Si (Rδ) 3 in said formulas, R4 represents a valence bond or a divalent, linear or branched, saturated or unsaturated hydrocarbon group having from 1 to 4 carbon atoms such as, for example, methylene, ethylene, propylene, isopropylene, isopropylidene; the identical or different radicals R5 represent a hydrogen atom or a linear or branched, saturated or unsaturated alkyl group having from 1 to 20 carbon atoms; X symbolizes a halogen atom, preferably a chlorine, bromine or fluorine atom.

12 - Method according to one of claims 2, 3 and 11 characterized in that the compound of the O-arylthiocarbamate type corresponds to formula (I) in which X2 represents an electron-attracting group such as X ^ or a group of electro-donor type such as:

. an alkyl group, linear or branched, having from 1 to 6 carbon atoms, preferably from 1 to 4 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl,

. a linear or branched alkenyl group having from 2 to 6 carbon atoms, preferably from 2 to 4 carbon atoms, such as vinyl, allyl,. a linear or branched alkoxy group having from 1 to 6 carbon atoms, preferably from 1 to 4 carbon atoms such as the methoxy, ethoxy, propoxy, isopropoxy, butoxy radicals, a 2-oxy propionic group,

. a cycloalkyl group having 3 to 8 carbon atoms, preferably a cyclohexyl group,. a benzyl group,. a phenyl group,. a group of formula:

-R4-N (Rδ) 2 -R ₄ -CO-N (R ₅ ) ₂ in said formulas, R4 and R5 may take the meanings given in claim 12.

13 - Method according to one of claims 2, 3 and 12 characterized in that the compound of O-arylthiocarbamate type corresponds to formula (I) in which n is equal to 1 or 2.

14 - Process according to claim 1 characterized in that the compound of the O-arylthiocarbamate type comprises at least two electron-withdrawing groups in position 2 and 4 relative to the amino group. 15 - Method according to one of claims 2, 3, 11 and 12 characterized in that the compound of O-arylthiocarbamate type corresponds to formula (I) in which Xi and X2 represent a halogen atom.

16 - Method according to one of claims 1 to 15 characterized in that one carries out the thermal rearrangement of O-arylthiocarbamate to S-arylthiocarbamate, by heating the reaction mixture at a temperature varying for example between 140 ° C and 400 ° C and preferably 150 ° C and 300 ° C.

17 - Process according to claim 17 characterized in that one carries out the heating of the reaction mixture in fusion or in an organic solvent having a high boiling point above the chosen temperature.

18 - Process according to claim 18 characterized in that the organic solvent is chosen from the following solvents: glycerol, biphenyl oxide, eutectic mixture of biphenyl oxide and biphenyl referenced under the trade names of Dowtherm® or Gilotherm®.

19 - Compound of S-arylthiocarbamate type comprising at least one amino group and at least one electron-withdrawing group.

20 - Compound according to the following formula (II):

in which A, R, X ^, X2, Z and n have the meaning given in claims 2 to 15.

21 - Compound according to either of Claims 19 and 20 corresponding to the following formula (IIa):

in which R, X ^, X2, Z and n have the meaning given in claims 2 to 5, 8 to 15.

22 - Compound according to one of claims 19 to 21 corresponding to the formula

in which X- |, X2, R, Ri, R2 and n have the meaning given in claims 2 to 5, 8 to 15.

23 - Compound according to claim 22 characterized in that it corresponds to the formula (lia-]) in which] and X ₂ represent a halogen atom.

24 - Process for the preparation of an aromatic thiol carrying at least one amino group and derivative characterized in that it consists in using a compound of S-arylthiocarbamate type comprising at least one amino group and at least one electro-attractor group described in one of claims 19 to 23.

25 - Process according to claim 24 characterized in that it consists in carrying out the transposition of an O-arylthiocarbamate group into an S-arylthiocarbamate group by heating an O-arylthiocarbamate type compound carrying at least one amino group and an electron-withdrawing group described in one of claims 19 to 23, then in hydrolyzing the compound obtained of S-arylthiocarbamate type carrying at least one amino group and at least one electro-attractive group. 26 - Method according to one of claims 24 and 25 characterized in that the transposition is carried out according to the method described in one of claims 1 to 18.

27 - Method according to one of claims 24 to 26 characterized in that one carries out an acid or basic hydrolysis of the compound obtained of S-arylthiocarbamate type carrying at least one amino group and at least one electro group -attractor.

28 - Method according to one of claims 24 to 27 characterized in that the aromatic thiol corresponds to formula (III):

in which A, R, X- \, X2 and n have the meaning given in claims 2 to 7, 11 to 15.

29 - Process according to claim 28 characterized in that the aromatic thiol corresponds to the formula (IIIa):

in which R, X- _| , X2 and n have the meaning given in claims 2 to 7, 11 to 15.

30 - Compound of O-arylthiocarbamate type comprising at least one amino group and at least one electron-withdrawing group.

31 - Composed according to the following formula (I):

in which A, R, Xi, X2, Z and n have the meaning given in claims 2 to 15.

32 - Compound according to one of claims 30 and 31 corresponding to the following formula (la):

in which R, X- |, X ₂ , Z and n have the meaning given in claims 2 to 5, 8 to 15.

33 - Compound according to one of claims 30 to 32 corresponding to the formula

in which X _{1 f} X, R, Ri, R ₂ and n have the meaning given in claims 2 to 5, 8 to 15.

34 - Compound according to claim 33 characterized in that it corresponds to the formula (la ^) in which X and X ₂ represent a halogen atom.

35 - Process for the preparation of an O-arylthiocarbamate compound comprising at least one amino group and one electro-attractor group according to one of claims 30 to 34 characterized in that it consists in reacting a hydroxylated aromatic compound carrying d '' at least one amino or nitro group and a sulfur-containing reagent corresponding to the

in which :

- Y is a group leaving in the presence of a nucleophile, - Z is a group comprising a doublet donor atom in position α with respect to the carbon carrying the sulfur atom.

36 - Process according to claim 35 characterized in that the reaction is carried out in the presence of a base.

37 - Method according to one of claims 35 and 36 characterized in that the starting aromatic substrate corresponds to formula (IV):

in said formula,

- A, Xi, X ₂ and n have the meaning given in claims 2 to 7, 11 to 15,

- W symbolizes H ₂ , 0 ₂ or HR; R representing a hydrogen atom or a hydrocarbon group.

38 - Method according to claim 37 characterized in that the starting aromatic substrate corresponds to the formula (IVa):

in said formula,

- Xi, X ₂ and n have the meaning given in claims 2 to 7, 11 to 15,

- W symbolizes H2, HR or O2; R representing a hydrogen atom or a hydrocarbon group as defined.

39 - Method according to one of claims 35 to 38 characterized in that it consists in reacting a compound of formula (IV) or (IVa) carrying an amino group with the sulfur reagent of formula (V).

40 - Method according to one of claims 35 to 38 characterized in that it consists in reacting a compound of formula (IV) or (IVa) carrying a nitro group with the sulfur-containing reagent (V), then subjecting the product obtained to a reduction operation.

41 - Method according to one of claims 35 to 40 characterized in that the sulfur-containing reagent corresponds to formula (V) in which the leaving group Y is a weak base.

42 - Process according to claim 41 characterized in that the leaving group Y is a halogen atom (preferably chlorine, bromine, iodine), a sulfonic ester group -OS0 ₂ R6 in which R ₈ represents a hydrocarbon group having from 1 to 20 carbon atoms and more preferably:

. an alkyl group having from 1 to 10 carbon atoms, preferably 1 to 4 carbon atoms and more preferably a methyl or ethyl group, optionally bearing a halogen atom, a CF ₃ group or a ammonium group N (R ₇ ), R ₇ , identical or different, representing an alkyl group having from 1 to 4 carbon atoms,

. a cycloalkyl group having 3 to 8 carbon atoms, preferably a cyclohexyl group,

. an aryl group having from 6 to 12 carbon atoms, preferably a phenyl group optionally carrying an alkyl group having from 1 to 10 carbon atoms, preferably 1 to 4 carbon atoms and more preferably a methyl group or ethyl, a halogen atom, a CF ₃ group or a NO2 group,

. a CX3 group in which X represents a fluorine, chlorine or bromine atom,

. a group CF2 - CF3.

43 - Method according to one of claims 41 and 42 characterized in that the leaving group Y is chosen from: - tosylates (p-toluenesulfonates) -OSθ2-C ₆ H ₄ -CH ₃

- brosylates (p-bromobenzenesulfonates) -OSθ2-CeH ₄ -Br

- nosylates (p-nitrobenzenesulfonates) -OSθ2-C ₆ H -N0 ₂

- mesylates (methanesulfonates) -OSO2-CH3

- triflates (trifluoromethanesulfonates) -OS0 ₂ -CF ₃

- nonaflates (nonafluorobutanesulfonates) -OSθ2-C ₄ F ₉

- the tresylates (2,2,2-trifluroéthanesulfonates) .- OS0 ₂ -CH ₂ -CF3 44 - Method according to one of claims 41 to 43 characterized in that the leaving group Y is a halogen atom.

45 - Method according to one of claims 41 to 44 characterized in that the sulfur-containing reagent corresponds to formula (V) in which Z has the meaning given in claims 8 to 10.

46 - Method according to one of claims 41 to 45 characterized in that the sulfur reagent used corresponds to the formula (Va):

in said formula:

- Y represents a leaving group, preferably a halogen atom,

- R and R2, identical or different, represent an alkyl group having from 1 to 12 carbon atoms, preferably from 1 to 4; a cycloalkyl group having 3 to 8 carbon atoms, preferably a cyclohexyl group; a group of type S ^, with the radicals% identical or different, which represent an alkyl group having from 1 to 12 carbon atoms.

47 - Method according to one of claims 41 to 46 characterized in that the reaction of the compounds of formula (IV) or (IVa) and the sulfur-containing reagent (V) and (Va) is carried out in bulk in the absence of any solvent, in aqueous medium, in organic medium or in hydro-organic medium.

48 - Method according to one of claims 41 to 47 characterized in that the reaction is carried out at a temperature between room temperature and the reflux temperature of the reaction mixture, preferably between 60 ° C and 90 ° C.

49 - Process for the preparation of an aromatic thioether carrying at least one amino group and derivative characterized in that it consists in using a compound of S-arylthiocarbamate type comprising at least one amino group and at least one electro-attractor group described in one of claims 19 to 23. 50 - Process according to claim 49 characterized in that it consists in carrying out the transposition of an O-arylthiocarbamate group into an S-arylthiocarbamate group by heating an O-arylthiocarbamate type compound carrying at least one amino group and an electro-attractor group described in one of claims 19 to 23, then hydrolyzing the compound obtained of the S-arylthiocarbamate type carrying at least one amino group and at least one electro-attractor group and then carrying out the S-alkylation by reaction with an alkylating agent.

51 - Method according to one of claims 49 and 50 characterized in that the aromatic thioether corresponds to formula (VI):

in which A, R, Xi, X2 and n have the meaning given in claims 2 to 7, 11 to 15 and R ₈ represents a hydrocarbon radical having from 1 to 24 carbon atoms, which may be a saturated acyclic aliphatic radical or unsaturated, linear or branched; a saturated, unsaturated or aromatic, monocyclic or polycyclic cycloaliphatic radical; a saturated or unsaturated, linear or branched aliphatic radical, carrying a cyclic substituent.

52 - Process according to claim 51 characterized in that the aromatic thioether responds to

in which R, X, X2 and n have the meaning given in the claims

2 to 7, 11 to 15 and R ₈ , in claim 51.

53 - Method according to one of claims 51 and 52 characterized in that the thioether corresponds to the formula (VI) or (Via) in which R ₈ represents:

- an acyclic aliphatic radical, saturated or unsaturated, linear or branched.

an acyclic, saturated or unsaturated, linear or branched aliphatic radical optionally carrying a cyclic substituent, optionally substituted, preferably, a benzene ring, which can be linked to the ring by a valential bond, a heteroatom or a functional group, - a saturated carbocyclic radical or comprising 1 or 2 unsaturations in the ring, generally having 3 to 8 carbon atoms, preferably 6 carbon atoms in the ring; said cycle being able to be substituted,

- an aromatic carbocyclic radical, preferably monocyclic generally having at least 4 carbon atoms, preferably 6 carbon atoms in the ring; said cycle can be substituted.

54 - Method according to one of claims 51 to 53 characterized in that the thioether corresponds to the formula (VI) or (Via) in which R ₈ represents a linear or branched alkyl radical having from 1 to 12 carbon atoms, preferably from 1 to 6 carbon atoms: the hydrocarbon chain can possibly be interrupted by a heteroatom (for example, oxygen), by a functional group (preferably -CO-) and / or carrying a substituent (of preferably a halogen, an ester function, preferably methyl or ethyl),

55 - Method according to one of claims 49 to 54 characterized in that the transposition is carried out according to the method described in one of claims 1 to 18.

56 - Method according to one of claims 49 to 55 characterized in that one carries out a basic hydrolysis of the compound obtained of S-arylthiocarbamate type carrying at least one amino group and at least one electro-attracting group .

57 - Method according to one of claims 49 to 56 characterized in that one implements an alkylating agent of halide, sulfate or carbonate type.

58 - Process according to claim 57, characterized in that an alkylating agent corresponding to one of the formulas is used:

R ₈ - X (Vlla) R ₈ - O - S0 ₂ - O - R ₈ (Vllb) R ₈ - O - CO - O - R ₈ (Vile) in said formulas, R ₈ has the meaning given in claims 53 and 54 and X represents a halogen atom, preferably a fluorine, chlorine, bromine or iodine atom.

60 - Process according to claim 58 characterized in that the alkylating agent is methyl chloride, dimethylsulfate and dimethylearbonate.