JP2002512174A - Method for preparing aromatic thiols and derivatives, and reagents, intermediate products and methods for producing them - Google Patents

Abstract

  (57) [Summary] The present invention relates to a method for preparing an amino group-bearing aromatic thiol from an amino group-bearing hydroxylated compound. The invention also relates to starting reagents, intermediate products such as aromatic S-arylthiocarbamates, and methods for their production, and derived products such as thioethers. The present invention relates to a method for rearranging an O-arylthiocarbamate compound carrying at least one amino group into an S-arylthiocarbamate compound carrying at least one amino group, the method comprising: Heating an O-arylthiocarbamate compound carrying two amino groups and an electron withdrawing group. The resulting S-aryl thiocarbamate compound is used as an intermediate to produce an aromatic thiol or thioether.

Description

DETAILED DESCRIPTION OF THE INVENTION

The subject of the present invention is a process for the preparation of aromatic thiols bearing amino groups, starting from hydroxylated aromatic compounds bearing amino groups. More specifically, the present invention relates to the preparation of 5-amino-2-chloro-4-fluoro-thiophenol.

[0002] The invention also relates to starting reagents, intermediate products of the aromatic S-arylthiocarbamate type, and methods for producing them.

[0003] The invention further relates to derivatives of aromatic thiols such as thioethers.

In the following disclosure of the present invention, the term “aromatic thiol bearing an amino group” refers to two hydrogen atoms directly attached to an aromatic ring, one replaced by an SH group and the other NH ₂ Or an aromatic compound substituted with an NHR group, wherein R is defined below.

The term “aromatic compound” is defined in the literature, especially in Advanced Organic Chemistry by Jerry MARCH, 4th edition (John Wiley and Sons, 1992, p. 40 and thereafter). It means the standard concept of aromaticity as it is.

In a simplified manner, the expression “aryl” is used to refer to all aromatic compounds, whether they are carbocyclic or heteroaromatic. used.

[0007] 5-Amino-2-chloro-4-fluoro-thiophenol is an intermediate in the production of herbicides of the thiadiazabicyclononate type and can be represented by the following formula:

[0008]

Embedded image The literature discloses numerous access routes to thiophenol.

One method is by pyrolysis of di-O-arylthiocarbonates to O-aryl S-arylthiocarbonates [A. Schomber
g et al., Ann. 483, p. 107 (1930)]. The yields obtained in this way are low (about 30%) and the conversion of phenol to thiophenol is at most 50%.
It only occurs in% yield.

[0010] Melvin S. Newman et al. Studied a method for converting phenol to thiophenol via a dialkylthiocarbamate according to the following reaction scheme [J. Org. Chem. , 31, p. 3980 (1966)]: ArOH → ArOCSNR ₂ → ArSCONR ₂ → ArSH A phenolic compound is reacted with dialkylthiocarbamoyl chloride to derive an O-arylthiocarbamate. Rearrangement to a carbamate, which material is converted to the corresponding thiol to be obtained by base hydrolysis.

A disadvantage of this method described is that this method cannot be applied to phenolic compounds bearing an amino group, since the Newman-Kwart rearrangement does not take place. Is only for amine functions which are protected in the form of acetamide or substituted by alkyl groups.

In this case, when the starting substrate contains an aromatic ring carrying at least one electron withdrawing group, the compound of the O-arylthiocarbamate type carrying at least one amino group is converted to an S-aryl It has been found that it can be rearranged to a compound of the luthiocarbamate type.

Accordingly, one of the objects of the present invention is to provide compounds of the O-arylthiocarbamate type carrying at least one amino group with a S-type compound bearing at least one amino group.
A method for rearranging to a compound of the arylthiocarbamate type, comprising heating a compound of the O-arylthiocarbamate type carrying at least one amino group and an electron withdrawing group. It is characterized by having.

Another subject of the present invention is a process for the preparation of an aromatic thiol bearing at least one amino group, starting from a hydroxylated aromatic compound bearing at least one amino group, the process comprising: Using an S-arylthiocarbamate-type compound that carries at least one amino group and at least one electron withdrawing group.

More specifically, the method comprises heating an O-arylthiocarbamate type compound bearing at least one amino group and an electron withdrawing group to form the O-arylthiocarbamate group with an S-arylthiocarbamate group. Rearranging to an arylthiocarbamate group and then hydrolyzing a compound of the S-arylthiocarbamate type carrying at least one amino group and at least one electron withdrawing group.

Another subject of the invention also relates to a process for preparing aromatic thioethers bearing at least one amino group, starting from compounds of the S-arylthiocarbamate type.

Another subject of the present invention, which is described in detail below, relates to intermediate products and starting reagents.

According to the method of the present invention, a compound of the O-arylthiocarbamate type bearing a free amine function is converted to the S-arylthiocarbamate type, unless at least one electron withdrawing group is present on the aromatic ring. It was found that the compound could not be rearranged.

The term “electron withdrawing group” is defined by Jerry MARCH, Advanced Organic Chemistry, 4th edition (John).
n Wiley and Sons, 1992, Chapter 9, pages 273-292.
)). C. A group is defined as defined by BROWN.

The electron withdrawing group may be at any position on the aromatic ring, but is preferably at the 2 and 4 positions with respect to the amino group.

Suitable starting compounds contain at least two electron-withdrawing groups at the 2 and / or 4 positions with respect to the amino group.

More specifically, the present invention relates to a method for rearranging a compound of the O-arylthiocarbamate type to an S-arylthiocarbamate, the method comprising the following general formula (I) ), Which comprises heating a compound of the O-arylthiocarbamate type carrying at least one amino group and an electron withdrawing group, corresponding to:

[0023]

Embedded image Wherein: -A is the symbol representing the remainder of the ring that forms all or part of the monocyclic or polycyclic aromatic carbocyclic or heterocyclic system; represents a hydrogen atom or a hydrocarbon group, -X ₁ represents an electron withdrawing group, -X ₂ represents a hydrogen atom or a substituted group of any nature, -Z is a carbon atom bearing the sulfur atom to a group containing a bound doublet donor atoms, -n is the number of the substituents X ₂ present in the ring.

As described above, the compound according to the present invention has at least one amino group on the aromatic ring. It is a free or substituted amine functional group, one of whose hydrogen atoms is a hydrocarbon group having 1 to 20 carbon atoms such as alkyl, cycloalkyl, aryl, aralkyl, or heteroatom. It is substituted by a cyclic radical.

More particularly, the symbol R represents an alkyl group having 1 to 10 carbon atoms, preferably 1 to 4 carbon atoms, or a cycloalkyl having 3 to 8 carbon atoms. A group, 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 present invention especially relates to aromatic compounds corresponding to formula (I), wherein A is at least four optionally substituted cyclic compounds, preferably rings. Monocyclic or polycyclic aromatic carbocycles having atoms and having the following rings: monocyclic or polycyclic aromatic carbocycles; And the remainder of the cyclic compound representing at least one of the heterocycles.

Without thereby limiting the scope of the invention, the optionally substituted remaining moiety A is: 1 は -aromatic mono- or polycyclic carbocyclic compounds, wherein The term "polycyclic carbocyclic compound" refers to a compound composed of at least two aromatic carbocycles forming an ortho- or ortho- and peri-fused system therebetween; Consisting of rings, of which only one is aromatic and represents a compound forming an ortho- or ortho- and peri-condensed system between them] 2 ゜ -monocyclic or polycyclic Aromatic heterocyclic compound [wherein the term “polycyclic heterocyclic compound” is composed of at least two heterocycles containing at least one heteroatom in each ring, and At least one of them Compounds which are aromatic and form an ortho- or ortho- and peri-condensed system between them, comprising at least one hydrocarbon ring and at least one heterocycle, at least one of the rings being One is aromatic and is defined as a compound forming an ortho- or ortho- and peri-condensation system between them] 3'-in paragraphs 1 and / or 2, Compounds composed of ring chains as defined: valence bonds, alkylene or alkylidene groups having 1 to 4 carbon atoms, preferably methylene or isopropylidene groups, of the following groups: One of:

[0028]

Embedded image [Wherein R ₀ represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, a cyclohexyl or a phenyl group].

Examples of rings from 1 ゜ to 3 ゜ include: 1 ゜ -benzene, toluene, xylene, naphthalene, anthracene 2 ゜ -furan, pyrrole, thiophene, isoxazole, furazane, Isothiazole, imidazole, pyrazole, pyridine, pyridazine, pyrimidine, quinoline, naphthyridine, benzofuran, indole 3'-biphenyl, 1,1'-methylenebiphenyl, 1,1'-isopropylidenebiphenyl, 1,1'-oxybiphenyl, 1,1'-Iminobiphenyl.

More particularly, the optionally substituted remaining moiety A is:-aromatics such as, for example, benzene, toluene, isobutylbenzene, anisole, phenetole or veratrol, guaiacol, guetol, 4-phenoxypropionic acid Carbocyclic monocyclic compounds,-for example, aromatic condensed polycyclic compounds such as naphthalene, 2-methoxynaphthalene,-aromatic carbocyclic non-condensed polycyclic compounds such as phenoxybenzene,-for example, tetrahydronaphthalene A carbocyclic fused polycyclic partially aromatic compound such as 1,2-methylenedioxybenzene, -a carbocyclic non-fused polycyclic partially aromatic compound such as cyclohexylbenzene, -For example, aromatic heterocyclic monocyclic compounds such as pyridine, furan, thiophene, etc.- for example quinoline, Aromatic condensed polycyclic partially heterocyclic compounds such as indole or benzofuran;-for example, aromatic non-condensed polycyclic partially heterocyclic compounds such as phenylpyridine and naphthylpyridine; Fused polycyclic partially aromatic and partially heterocyclic compounds such as, for example, tetrahydroquinoline; non-fused polycyclic partially aromatic and partially heterocyclic compounds such as for example cyclohexylpyridine Represents the rest of the compound.

In the process according to the invention, the compounds of the formula (I) are preferably used, wherein A represents an aromatic ring, preferably a benzene ring.

Referring to the definition of the group Z, Z is α with respect to the carbon bearing the sulfur atom.
A group containing a doublet donor atom at the position.

The atoms with available doublets can include nitrogen, sulfur, or oxygen atoms.

Thus, Z encodes the remainder of the optionally silylated amine, ether, or thioether.

Thus, the group —O—CS—Z is, inter alia, a thiocarbamate group of the formula —O—CS—N (R ₁ ) (R ₂ ); thiocarbonate group represented by CS-OR _3; - wherein, be a dithiocarbonate group represented by -O-CS-SR _3.

For the purposes of understanding the present invention, compounds of formula (I) are commonly referred to as O-arylthiocarbamates, but thiocarbonate and dithiocarbonate-type compounds, as well as other equivalents, are also contemplated. It should be noted that it includes.

In these different formulas, R may be the same or different₁, R₂,
R₃Is more particularly 1 to 12 carbon atoms, preferably 1 to 4 carbon atoms.
Alkyl groups having elemental atoms, cycloalkyl groups having 3 to 8 carbon atoms
Preferably a cyclohexyl group, an alkyl group having 1 to 12 carbon atoms.
Si with the radical "R", which may be the same or different and represent ("R") ₃ Represents a type group.

Also, two to three groups R ₁ and R ₂ together with a nitrogen atom, optionally containing another heteroatom such as an oxygen or nitrogen atom, from 3 to 8 atoms, preferably 4
A heterocycle having from 1 to 5 atoms may be formed.

As a more specific example, R ₁ and R ₂ , which may be the same or different, represent a methyl, isopropyl, cyclohexyl, or trimethylsilyl group, wherein R ₁ and R ₂ together form the following ring

[0040]

Embedded image Can be formed.

Preferred compounds corresponding to formula (I) are those in which Z represents an amino group, wherein the radicals R ₁ , R ₂ , which may be the same or different, have 1 to 4 atoms. Is a compound representing an alkyl group having the formula, preferably a methyl or trimethylsilyl group.

As mentioned above, the hydroxylated aromatic compound of formula (I) also contains an electron withdrawing group X ₁ and optionally another substituent X ₂ in its ring.

The number of substituents present on a ring depends on the degree of carbon condensation of the ring and whether there is unsaturation on the ring.

The maximum number of substituents that can be included in a ring can be easily determined by those skilled in the art.

As used herein, the term “some” generally means that the number of substituents present on the aromatic ring is less than 5. 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 represented by —R₄-X-R₄-CF₃  -R₄-COOR₅  -R₄-CHO -R₄-SO-R₅  -R₄-SO₂-R₅  -R₄-S-CF₃  -R₄-NO₂  -R₄-CN-R₄−N = C (R₅)₂  -R₄-NH-CO-R₅  -R₄-N⁺(R₅)₃  -R₄-Si (R₅)₃  [In these formulas, R₄Is a valence bond or, for example, methylene, ethylene,
Straight or branched chains such as pyrene, isopropylene, isopropylidene, etc.
Represents an unsaturated divalent hydrocarbon radical having 1 to 4 carbon atoms;
Is a radical R which may be different₅Is a hydrogen atom or a straight or branched chain
Represents a saturated or unsaturated alkyl group having 1 to 20 carbon atoms
X represents a halogen atom, preferably chlorine, bromine or fluorine
Is].

The aromatic ring may have other substituents X of any nature₂Can be carried. these
The substituent is X₁Or an electron-withdrawing group such as
May be present, in particular: methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-
One to six carbon atoms, preferably one to four, such as butyl, tert-butyl, etc.
A straight or branched alkyl group having 2 carbon atoms, 2 to 6 carbon atoms, preferably 2 to 4 carbon atoms, such as vinyl, allyl, etc.
Linear or branched alkenyl groups having a hydrogen atom, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy radical, etc.
A straight chain having 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms;
Is a branched alkoxy group, a 2-oxypropionic acid group, a cycloalkyl group having 3 to 8 carbon atoms, preferably cyclohexyl
Benzyl group, phenyl group, group represented by the following formula: -R₄−N (R₅)₂  -R₄-CO-N (R₅)₂  [In these formulas, R₄And R₅Can have the meaning given so far
].

Among the different substituents mentioned above, the formula (I) which is optionally used in the process according to the invention
The compound of the above) has two electron-withdrawing groups, more specifically, two halogen atoms.

The process according to the invention is perfectly suitable for preparing thiophenols bearing amine functions, starting from O-phenylthiocarbamate.

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

[0051]

Embedded image Wherein R, X ₁ , X ₂ , Z and n have the previously given meanings.

Even more preferred compounds are those corresponding to the following general formula (Ia ₁ ):

[0053]

Embedded image Wherein X ₁ , X ₂ , R, R ₁ , R ₂ , and n have the previously given meanings.

Another subject of the invention is the novel compounds obtained, ie of the S-arylthiocarbamate type, which can be represented by the following formula (II):

[0055]

Embedded image Wherein A, R, X ₁ , X ₂ , Z, and n have the previously given meanings.

Suitable compounds correspond more particularly to the following formula (IIa):

[0057]

Embedded image Wherein R, X ₁ , X ₂ , Z and n have the previously given meanings.

As a new product, the following formula (IIa)₁), In particular X in the formula ₁ And X₂There may be mentioned compounds wherein represents a halogen atom:

[0059]

Embedded image Wherein X ₁ , X ₂ , R, R ₁ , R ₂ , and n have the previously given meanings.

Further, the present invention provides the following formula (III):

[0061]

Embedded image A compound of formula (II) for preparing an aromatic thiol corresponding to A, R, X ₁ , X ₂ , Z and n have the meanings given above The use also hydrolyzes compounds of the S-arylthiocarbamate type, preferably compounds of formula (II), more preferably compounds of formula (IIa) and (IIa ₁ ) Including.

The method according to the invention allows easy access to compounds corresponding to the following formula (IIIa):

[0063]

Embedded image Wherein R, X ₁ , X ₂ , and n have the previously given meanings.
.

The invention furthermore relates to the use of a compound of formula (II) for preparing an aromatic thioether corresponding to formula (VI):

[0065]

Embedded image Wherein A, R, X ₁ , X ₂ , and n have the previously given meanings, and R ₈ represents a hydrocarbon radical having 1 to 24 carbon atoms, wherein the radical is , Straight or branched, saturated or unsaturated, acyclic aliphatic radical; monocyclic or polycyclic, saturated, unsaturated, or aromatic, alicyclic radical; Linear or branched, saturated or unsaturated aliphatic radicals].

The term “thioether group” as used herein, in a simplified manner, means a group of the type —S—R ₈ , wherein R ₈ is as previously given. Has the meaning, and thus R ₈ represents both a saturated, unsaturated or aromatic, acyclic or alicyclic radical and a saturated or unsaturated aliphatic radical bearing a cyclic substituent .

The aromatic thioether obtained by the process of the present invention corresponds to formula (VI), wherein R ₈ represents a linear or branched, saturated or unsaturated acyclic aliphatic radical. .

More preferably, R ₈ represents a straight-chain or branched alkyl radical having 1 to 12 carbon atoms, preferably 1 to 6 carbon atoms: Is optionally interrupted with a group bearing a heteroatom (eg, oxygen), a functional group (eg, —CO—), and / or a substituent (eg, a halogen, ester function, preferably methyl or ethyl). May have been.

The straight or branched, saturated or unsaturated, acyclic aliphatic radical can optionally carry a cyclic substituent. The term ring is preferably saturated, unsaturated,
Alternatively, it is meant an aromatic carbocyclic ring, preferably an alicyclic or aromatic ring, especially an alicyclic ring containing 6 carbon atoms in the ring, or benzene.

The acyclic aliphatic radical may be attached to the ring by a valence bond, a heteroatom, or a functional group, examples of which are given below.

The ring may be optionally substituted, for example, it may be substituted with a cyclic substituent, and such substituents include, inter alia, an alkyl group, an alkoxy group, a halogen atom, a trifluoromethyl group and the like. Can be envisaged.

Also, R ₈ typically has from 3 to 8 carbon atoms in the ring, preferably has 6 carbon atoms, is saturated, or has one or two unsubstituted rings. It may represent a carbocyclic radical, including saturation; the ring may be substituted.

Further, R ₈ may represent an aromatic carbocyclic radical, wherein the ring generally has at least 4 carbon atoms, preferably a monocyclic having 6 carbon atoms. Preferably, the ring may be substituted.

The process according to the invention relates very particularly to the aromatic thioethers of the formula (VI), wherein R ₈ is a straight-chain or branched chain having 1 to 4 carbon atoms. Represents a branched alkyl radical or a phenyl radical.

Examples of suitable R ₈ radicals according to the invention include the following radicals: methyl, ethyl, propyl, isopropyl, butyl, isobutyl, se
c-butyl, tert-butyl, or phenyl.

The method for preparing the thioether comprises the step of preparing a compound of the S-arylthiocarbamate type, preferably a compound corresponding to formula (II), more preferably a compound corresponding to formulas (IIa) and (IIa ₁ ). Hydrolysis and S using alkylating or arylating agents
-Alkylation or S-arylation.

The term “alkylating agent” is generic and indicates the replacement of a hydrogen atom with any hydrocarbon group, particularly an alkyl, cycloalkyl, aryl, arylalkyl group, and the like.

The method according to the invention allows easy access to compounds corresponding to formula (VIa):

[0079]

Embedded image Wherein R, R ₈ , X ₁ , X ₂ , and n have the previously given meanings.

According to the method of the present invention, a thermal rearrangement of an O-arylthiocarbamate to an S-arylthiocarbamate is performed.

This transformation involves the reaction medium being, for example, between 140 ° C. and 400 ° C., preferably 150 ° C.
It is obtained by heating to a temperature that varies between 300C and 300C.

The heating of the reaction medium can be carried out in the melt or in an organic solvent having a boiling point above the selected temperature. Examples of more specific solvents include the following solvents: glycerol, diphenyl oxide, a eutectic mixture of diphenyl oxide and diphenyl under the trade name Dotherm® or Gilotherm®.

The heating is carried out in a standard manner, for example by means of an induction or heat exchanger or a molten salt bath, in particular calcium chloride or a high-boiling organic solvent, in particular a molten salt bath of the organic solvents mentioned above.

At the end of the reaction, the product obtained is subjected to a hydrolysis step in order to release the SH function.

A first variant of the process according to the invention consists in carrying out an acid hydrolysis.

For this purpose, inorganic protonic acids, preferably hydrochloric acid, sulfuric acid, phosphoric acid or organic acids such as, for example, trifluoromethanesulfonic acid and methanesulfonic acid are used. Preferably, sulfuric acid is selected.

The concentration of the acid is not critical. Preferably, a 1 to 2N dilute acid solution is used.

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

The amount of acid used is preferably a catalytic amount, more preferably the ratio is between 0.1 and 0
. It is used in an amount such that it is between 25.

The temperature at which the hydrolysis reaction is carried out is not critical and depends on the ambient temperature (generally 15
C. to 25 ° C.) to the reflux temperature of the reaction mixture.

At the end of the reaction, the desired product, preferably the product corresponding to formula (III), is obtained by either decantation or extraction with an organic solvent having lipophilicity. In particular, halogenated or non-halogenated aromatic hydrocarbons, such as toluene, and halogenated or non-halogenated aliphatic hydrocarbons, preferably dichloromethane, aliphatic or aromatic ether oxides, such as ethyl oxide or oxide Isopropyl and the like can be mentioned.

According to another variant of the method of the invention, the hydrolysis is performed in a basic medium.

To this end, strong bases, preferably inorganic bases such as alkali metal or alkaline earth metal carbonates and alkali metal hydroxides, or organic bases, preferably sodium methylate, are used. More preferably, mention may be made of soda, potash and sodium or potassium carbonate.

The bases are generally used in the form of a solution, and the concentration of the solution is from 1 to 1
It may vary over a wide range between 2N.

[0095] OH ^- The amount of base used, expressed in number of moles of ion counts and S- arylthio carbamate is suitable for being selected between 1 and 2. The amount of base is preferably greater than the stoichiometry of the reaction.

The base hydrolysis can also be carried out in the presence of an alcohol used in such an amount that the reaction mixture can be easily stirred, preferably in the presence of methanol.

The salified thiol functionality is neutralized with a strong acid as described above,
It may be desirable to release. The amount of acid used is preferably that corresponding to stoichiometry.

Next, the obtained product is separated as described above, for example, by extraction or decantation.

The product thus obtained is of high purity, which means that no further purification steps are required. However, if necessary, for example, alcohol,
More specifically, purification may be performed by recrystallization from a solvent such as ethanol.

According to another variant of the process of the invention, the preparation of the aromatic thioethers can be carried out starting from compounds of the S-arylthiocarbamate type.

More precisely, the base hydrolysis of the compounds of the S-arylthiocarbamate type is carried out as described above, followed by a thioalkylation using standard alkylating agents.

Particularly suitable alkylating agents include, in particular, alkylating agents of the halide, carbonate or sulfate type.

Thus, the alkylating agents respectively correspond to the following formula: R ₈ -X (VIIa), R ₈ -O-SO ₂ -OR ₈ (VIIb), R ₈ -O-
CO-OR ₈ (VIIc) wherein R ₈ has the previously given meaning, X is a halogen atom,
Preferably represents a fluorine, chlorine, bromine or iodine atom].

Preferred among the alkylating agents of the halide type are those corresponding to formula (VIIa), wherein X represents a fluorine, chlorine or bromine atom and R ₈ is 1 Represents a straight-chain or branched alkyl radical having 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms, or a phenyl radical.

Preference is given to those of the formula (VIIa) in which X represents a chlorine atom and R ₈ represents a straight-chain or branched alkyl radical having 1 to 4 carbon atoms. It is equivalent.

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

Because of the relatively low cost, methyl chloride and chloroethane are preferably used.

In the case of sulfate or carbonate type alkylating agents, the compounds of formulas (VIIb) and (VI
Preference is given to using those corresponding to Ic), wherein R ₈ is a straight-chain or branched chain having 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms. Represents a chain alkyl radical or phenyl radical.

Among the above-mentioned alkylating agents, dimethyl sulfate and dimethyl carbonate are preferred.

The amount of alkylating agent, expressed in terms of the amount of S-arylthiocarbamate, is preferably equal to the stoichiometric equivalent and may reach an excess of up to 200%.

Since the hydrolysis reaction is performed in the presence of water, water exists in the reaction medium. Organic solvents can also be used, which may be miscible or immiscible with water. The solvent can be chosen from halogenated or non-halogenated, aliphatic, cycloaliphatic or aromatic hydrocarbons. As examples of solvents, mention may especially be made of dichloroethane, toluene and xylene.

The S-alkylation reaction is carried out by combining the S-arylthiocarbamate and the alkylating agent, regardless of how it is performed.

In general, prior to adding the alkylating agent, an amount of the basic agent ranging from a stoichiometric amount of the S-arylthiocarbamate to an excess, for example, which can reach 100%. , Preferably soda or potash.

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

At the end of the reaction, the thioether, preferably corresponding to formulas (VI) and (VIa), is recovered by standard separation methods, for example by filtration.

In the process according to the invention, the process starts with a compound of formula (I), more preferably a compound of formula (Ia).

These compounds are new products.

One way to obtain them is by hydroxylated, preferably carrying at least one amino or nitro group corresponding to formula (IV)
The aromatic compound is reacted with a sulfur-containing reagent, preferably in accordance with formula (V), optionally in the presence of a base.

More particularly, the starting aromatic substrate corresponds to the following formula (IV):

[0120]

Embedded image Wherein -A, X ₁ , X ₂ and n have the previously given meanings; -W is H ₂ , O ₂ or HR encoding; R is Represents a hydrogen atom or a hydrocarbon group].

Referring to the sulfur-containing reagent, this reagent is more particularly described by the following formula (V
Equivalent to:

[0122]

Embedded image Wherein -Y is a group leaving in the presence of a nucleophile and -Z is a group containing a doublet donor atom in the α-position with respect to the carbon bearing the sulfur atom.

A first variant of the process according to the invention provides compounds of formula (IV) bearing an amino group, ie meaning that W contains at least one hydrogen atom,
It is to react with a sulfur-containing reagent of formula (V) for the purpose of forming an O-arylthiocarbamate type compound of I).

Another variation of the present invention is to first produce a compound of the O-arylthiocarbamate type bearing a nitrated group, and then reduce the nitrated group to an amino group. As a result, an O-arylthiocarbamate type compound of the formula (I) is obtained. Thus, after reacting a compound of formula (IV) bearing a nitrated group, ie, W representing two oxygen atoms, with a sulfur-containing reagent (V), the resulting product is subjected to a reduction step. Can be

Among the compounds of formula (IV) used among others are more particularly those corresponding to the following formula:

[0126]

Embedded image Wherein -X ₁ , X ₂ , and n have the previously given meanings; -W is H ₂ , HR, or O ₂ encoding; R is Represents a hydrogen atom or a hydrocarbon group as described above].

Referring to the sulfur-containing reagents suitably corresponding to formula (V), the leaving group Y is
It can be defined as a weak base.

The term “weak base” means a base whose conjugate acid has a pKa of less than 6.5, preferably less than 5.

The leaving groups Y include the following: halogen atoms (chlorine, bromine, iodine) and hydrocarbon groups in which R ₆ has 1 to 20 carbon atoms;
Sulfonic acid ester group and more representative of the following:, -OSO ₂ R _6: · optionally halogen atom, CF ₃ group or an ammonium group _{N (R 7) 4 (wherein,, R 7} are the same or Alkyl groups having 1 to 10 carbon atoms, preferably 1 to 4 carbon atoms, which can be different and represent alkyl groups having 1 to 4 carbon atoms) More preferably a methyl or ethyl group, a cycloalkyl group having 3 to 8 carbon atoms, preferably a cyclohexyl group, optionally 1 to 10 carbon atoms, preferably 1 to An alkyl group having 4 carbon atoms, more preferably a methyl or ethyl group, an aryl group having 6 to 12 carbon atoms, carrying a halogen atom, a CF ₃ group, or a NO ₂ group;
Preferably the phenyl group, · CX ₃ group (wherein, X represents fluorine, chlorine or bromine atom,), _· CF 2 -CF ₃ group.

Suitable sulphonate groups are: tosylate (p-toluenesulphonate), —OSO₂-C₆H₄−
CH₃・ Brosylate (p-bromobenzenesulfonic acid ester), —OSO₂-C ₆ H₄-Br, -nosylate (p-nitrobenzenesulfonic acid ester), -OSO₂-C₆ H₄-NO₂・ Mesylate (methanesulfonic acid ester), -OSO₂-CH₃・ Betyrate (ammonioalkanesulfonic acid ester), -OSO₂− (C
H₂)_nNMe₃ ⁺(Where n represents a number from 0 to 6), triflate (trifluoromethanesulfonic acid ester), -OSO₂-C
F₃Nonaflate (nonafluorobutanesulfonic acid ester), -OSO₂-C ₄ F₉-Tosylate (2,2,2-trifluoroethanesulfonic acid ester)-
OSO₂-CH₂-CF₃.

A halogen atom is selected as a suitable leaving group.

The leaving group can be displaced by the action of the anion ArO ⁻ , where Ar is phenolate or another chlorinated compound of formula (IV), and It goes without saying that the nature of the leaving group is not fundamental to the present invention.

Referring to the definition of the group Z, Z is α with respect to the carbon bearing the sulfur atom.
A group containing a doublet donor atom at the position.

The available doublet-bearing atoms can include nitrogen, sulfur, or oxygen atoms.

Accordingly, Z is a symbol of the remainder of the optionally silylated amine, ether, or thioether.

The group —O—CS—Z is therefore, inter alia, a thiocarbamate group of the formula —O—CS—N (R ₁ ) (R ₂ ); thiocarbonate represented by CS-OR _3; - wherein, be a dithiocarbonate group represented by -O-CS-SR _3.

In these different formulas, R ₁ , R ₂ , R ₃ , which may be the same or different, are more particularly 1 to 12 carbon atoms, preferably 1 to 4 carbon atoms An alkyl group having 3 to 8 carbon atoms, preferably a cyclohexyl group; an alkyl group having 1 to 12 carbon atoms, the same or different, Si (“R”) with good radical “R”
) Represents a type ₃ group.

Also, the two radicals R ₁ and R ₂ are joined together with a nitrogen atom and have 3 to 8 atoms, preferably 4 to 5 atoms, and an oxygen or nitrogen atom And the like, which may optionally contain another heteroatom.

Z preferably represents an amino group, wherein the radicals R ₁ and R ₂ , which may be the same or different, are an alkyl group having 1 to 4 carbon atoms, preferably Represents a methyl or trimethylsilyl group.

Suitable sulfur-containing reagents correspond to the following formula (Va):

[0141]

Embedded image Wherein -Y represents a leaving group, preferably a halogen atom; -R ₁ and R ₂ , which may be the same or different, are from 1 to 12 carbon atoms, preferably 1 Alkyl groups having from 3 to 8 carbon atoms; cycloalkyl groups having from 3 to 8 carbon atoms, preferably cyclohexyl groups; alkyl groups having from 1 to 12 carbon atoms, being the same or different Represents a group of type Si (“R”) ₃ with a radical “R” which may be

According to the process of the present invention, a hydroxylated aromatic compound, preferably corresponding to formula (IV), is reacted with a sulfur-containing reagent, preferably corresponding to formula (V).

The amount of sulfur-containing reagent used, expressed as the sulfur-containing reagent / hydroxylated aromatic compound molar ratio, can vary between 1 and 1.2, and is preferably about 1.

The hydroxylated aromatic compound used may be in a salified form.

The hydroxylated aromatic compound in salified form formulated according to the prescription can also be used, or it can be prepared in situ by reacting it with a base.

Accordingly, bases which can be inorganic or organic are involved in the method according to the invention.

The base used at this stage may be phenol or formula (IV) or (IVa
)), The formation of the corresponding anion ArO ⁻ in the reaction medium, starting from another hydroxylated aromatic compound. Therefore, the base must be strong enough to release the hydroxyl proton of ArOH sufficiently.

In general, the base has a pKa higher than 9.0.

When water is used as the solvent, pKa is defined as the ion / base pair ion dissociation constant.

For the selection of bases having a pKa as defined in the present invention, inter alia, the Handbook of Chemistry and Physics (HANDBOOK OF CHEMISTRY)
AND PHYSICS), 66th edition, pages D-161 and D-162.

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

[0152] It is also possible to use quaternary ammonium hydroxide.

As an example of quaternary ammonium hydroxide, the same or different alkyl radicals are straight-chain or branched alkyl having 1 to 12 carbon atoms, preferably 1 to 6 carbon atoms. A tetraalkylammonium hydroxide or a trialkylbenzyl hydroxide representing a chain is preferably used.

Suitably, tetramethylammonium hydroxide, tetraethylammonium hydroxide or tetrabutylammonium hydroxide is selected.

According to the invention, it is also possible to use trialkylbenzylammonium hydroxides, in particular trimethylbenzylammonium hydroxide.

In consideration of economic conditions, sodium hydroxide or potassium hydroxide is suitably selected from all bases.

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

The amount of base introduced into the reaction medium takes into account the amount required to salify the hydroxyl function of the aromatic compound.

Therefore, when the compound has a salifiable functional group other than the hydroxyl group, an amount of a base necessary to salify all the salifiable functional groups is introduced.

In general, the amount of base expressed with respect to the aromatic compound is a stoichiometric amount of 10
It varies between 0 and 120%.

[0161] The base is generally introduced with other reagents.

The reaction can be carried out in a number of different ways. Thus, the reaction can be carried out in batch form in the absence of any solvent, in an aqueous medium, in an organic medium, or in a water-organic medium.

When the reaction is carried out in an aqueous medium, water is generally supplied by means of a base which is introduced in the form of an aqueous solution. The amount of water is selected so that the reaction medium can be easily stirred.

The reaction can also be carried out in an organic solvent, preferably an aprotic polar solvent. In particular, there may be mentioned: halogenated hydrocarbons such as, for example, dichloromethane, dichloroethane, chlorobenzene; especially alcohols such as methanol, isopropanol and ethylene glycol; esters or ethers of polyols such as tetraethylene glycol diacetate. Isopropyl oxide, methyl oxide and tert-butyl oxide, ethylene glycol dimethyl ether (or 1,2-dimethoxyethane) (1,2-dimethoxyethane)
ne, f), linear or cyclic aliphatic ethers such as diethylene glycol dimethyl ether (or 1,5-dimethoxy-3-oxapentane); phenyl oxide, tetrahydrofuran, or dioxane; nitriles such as acetonitrile.

There is no problem if the reaction is carried out in a water-organic medium using water and an organic solvent, preferably a polar solvent, in particular, the above-mentioned organic solvent.

The reaction is suitably carried out in bulk form in the absence of any aqueous or organic solvents.

Although it is advantageous to use solvents when it comes to stirring issues, it is always desirable to minimize the amount of solvent used.

The amount of solvent (including water) is added in such an amount that the medium can be easily stirred. Generally, hydroxylated aromatics represent 5 to 40% of the weight of the solvent. The numerical values are given by way of example and are not limiting.

The process according to the invention is advantageously carried out at a temperature comprised between ambient temperature (typically 15 ° C. to 25 ° C.) and the reflux temperature of the reaction mixture. The reaction temperature is preferably 6
The temperature is selected between 0 ° C and 90 ° C.

The various reagents, bases, and solvents can be used in any order.

At the end of the reaction, the product which can be separated from the medium by standard separation methods, ie, the O-arylthiocarbamate, is recovered. The products can be isolated by filtration or by extraction with a suitable solvent such as toluene or dichloromethane.

The obtained compound may be subjected to a hydrogenation step according to the nature of the nitrogen-containing group carried by the compound.

This can be done in a standard manner using 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 [HOUBEN-WEYL, Organic Chemistry (Methoden). d
er organischen Chemie), Vol. IV / 1C, p. 48
7 and 506 (1980)].

A compound of the O-arylthiocarbamate type, preferably a compound corresponding to formula (I) used in the method according to the invention is obtained.

The following are examples of practical embodiments of the present invention.

These examples are given by way of non-limiting illustration.

Example Synthesis of O-Arylthiocarbamates 5-Nitro-2-chloro-4-fluorophenol (15 mmol) is added at ambient temperature with stirring to a 1N aqueous soda solution (15 mmol, 15 ml).

After 5 minutes, thiocarbamoyl chloride (16.5 mmol, 2.038 g) was added,
Mix.

Next, the reaction mixture is heated to 50 ° C. for 10 hours.

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

Thereafter, the obtained carbamate is purified by recrystallization from ethanol.

A 90% pure product corresponding to the following formula is obtained:

[0183]

Embedded image The properties of this product are as follows (NMR measurements are carried out in the solvent CDCl ₃ ): melting point = 141 ° C.

[0184] ^{-NMR 1 H: 3.41 (3H,} s); 3.47 (3H, s); 7.41 (
1H _arom , d, J = 7), 7.92 (1H _arom , d, J = 7).

-NMR ¹³ C: 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 nitro group to amino Thiocarbamate (10 mmol) and iron (powder, 30 mmol, 1.675 g)
) Is suspended in 100 ml of an ethanol / water solution (1/1 by mass), then acetic acid (11 mmol, 0.661 g, 0.63 ml) is added dropwise.

The reaction mixture was heated under reflux of ethanol for 2.5 hours and then diluted (
100 ml of ethanol) and filtered through celite.
).

The aqueous phase was washed with dichloromethane (2 × 50 ml), then basified to pH> 12 with 5N aqueous soda, extracted with dichloromethane (4 × 50 ml), dried over magnesium sulfate and dried over The solvent is evaporated, recovering 2.48 g of a yellow solid which does not require purification.

A compound of 99% purity corresponding to the following formula is obtained:

[0190]

Embedded image The properties of this compound are as follows: Melting point = 154 ° C.

[0191] ^{-NMR 1 H: 3.35 (3H,} s); 3.45 (3H, s); 6.57 (
1H _arom , d, J = 7), 7.06 (1H _arom , d, J = 10.3).

-NMR ¹³ C: 38.9; 43.6; 112.6-116.4-116.
7-14.14.1 (d, J = 14.3); 146.5 (d, J = 36.6); 15
0.8; 186.6.

Neumann-Kwart rearrangement O-arylthiocarbamate (0.5 mmol) and diphenyl ether (5
g, ie about 10 ml / mmol thiocarbamate), is heated under reflux of diphenyl ether (259 ° C.) for 1 hour 30 minutes.

After cooling, the crude product is diluted with 30 ml of ethyl ether and the S-arylthiocarbamate is extracted with 4 × 30 ml of 6N aqueous hydrochloric acid.

The aqueous phase was then basified with soda to pH> 12 and dichloromethane (4
× 30 ml).

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

A product with a purity of 91% is obtained, corresponding to the following formula:

[0198]

Embedded image The properties of the product are as follows: Melting point = 151 ° C.

[0199] ^{_{-NMR 1 H: 3.03 (3H,}} s broad); 3.11 (3H, s br oad); 3.82 (NH, s broad); 6.99 (1H arom, d, J
= 5.8); 7.13 (1H _arom , d, J = 6.6).

-NMR ¹³ C: 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.

[0201] -NMR ¹⁹ F: 130.7.

Hydrolysis of S-arylthiocarbamate to thiophenol S-arylthiocarbamate (5 mmol) was placed in a 20 ml methanol solution, and then a 1 molar solution of soda (10 ml) was added. Is refluxed for 12 hours.

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

An 85% pure product corresponding to the following formula is obtained:

[0205]

Embedded image The properties of the product are as follows: melting point = 58 ° C.

[0206] _{^{-NMR 1 H: 3.08 (NH2,}} s broad); 3.77 (SH, s)
6.79 (1H _arom , d, J = 3.2); 7.01 (1H _arom , d,
J = 2.2).

Synthesis of thioether from S-arylthiocarbamate 0.25 mol of S-arylthiocarbamate, 75 g of water and 75 g
Of methanol into a reaction vessel.

The reaction medium is heated to 70 ° C. under stirring and a 0.50 mol aqueous soda solution (40% by weight) is added over 30 minutes.

Stirring is performed for 30 minutes at 70 ° C. so that the S-arylthiocarbamate can be hydrolyzed with a conversion of more than 95%.

The reaction medium is cooled to 25 ° C., a 0.25 mol aqueous soda solution (40% by weight) is added over 10 minutes, and then 0.27 mol dimethyl sulfate is added over 30 minutes.

To terminate the methylation (thiophenol conversion (CR)> 99%), the reaction medium is heated to 70 ° C. for 1 hour.

[0212] The reaction mixture is cooled to 10 ° C and the crude thioether is recovered by filtration.

The cake is washed with a 10% soda solution and then with water.

The product is recrystallized from methanol.

A product of the following formula with a purity of 84% is obtained:

[0216]

Embedded image

──────────────────────────────────────────────────続 き Continuation of front page (81) Designated country EP (AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IT, LU, MC, NL, PT, SE ), OA (BF, BJ, CF, CG, CI, CM, GA, GN, GW, ML, MR, NE, SN, TD, TG), AP (GH, GM, KE, LS, MW, SD, SZ, UG, ZW), EA (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), AL, AM, AT, AU, AZ, BA, BB, BG, BR, BY, CA, CH, CN, CU, CZ, DE, DK, EE, ES, FI, GB, GE, GH, GM, HR, HU, ID, IL, IN, IS, JP, KE, KG , KP, KR, KZ, LC, LK, LR, LS, LT, LU, LV, MD, MG, MK, MN, MW, MX, NO, NZ, PL, PT, RO, RU, SD, SE, SG, SI, SK, SL, TJ, TM, TR, TT, UA, UG, US, UZ, VN, YU, ZW (72) Inventor Bezlan, Pierre France, F-14920 Mathieu, Arele De Platanu, 48 (72) Inventor Kesner, Janitsk France, F-76000 Luang, Boulevard-de-la-Marne, 17 (72) Inventor Mizpellaère, Clotild France, F-14000 Can, Rille・ Dou La Day Brand, 172, Le Huaquiyurte F-term (reference) 4H006 AA02 AC56 AC63 BA19 BA28 BA35 BA36 BA37 BB12 BB14 BB15 BC10

Claims (59)

[Claims] 1. A method for rearranging an O-arylthiocarbamate-type compound carrying at least one amino group into an S-arylthiocarbamate-type compound carrying at least one amino group, comprising: A rearrangement method comprising heating a compound of the O-arylthiocarbamate type carrying at least one amino group and an electron withdrawing group. 2. The method according to claim 1, wherein the compound has the following general formula (I): Wherein: -A is a symbol representing the remainder of the ring that forms all or part of the monocyclic or polycyclic aromatic carbocyclic or heterocyclic system; represents a hydrogen atom or a hydrocarbon group, -X ₁ represents an electron withdrawing group, -X ₂ represents a hydrogen atom or a substituted group of any nature, -Z is a carbon atom bearing the sulfur atom a group containing a bound doublet donor atoms, -n corresponds to] represents the number of substituents X ₂ present on the ring, bearing at least one amino group and an electron withdrawing group O- Ally Heating a compound of the luthiocarbamate type,
The method of claim 1. 3. The compound of the O-arylthiocarbamate type has the formula (I)
a): embedded image _{Wherein, R 1, X 1, X} 2, Z, and n are the same definition as in claim 2, characterized in that corresponding to the method of claim 2. 4. The compound of formula (I) of the O-arylthiocarbamate type
An aromatic ring bearing at least one amino group in the form of a free or substituted amine function, wherein one of the hydrogen atoms is a hydrocarbon group having 1 to 20 carbon atoms, preferably Is substituted with an alkyl, cycloalkyl, aryl, aralkyl, or heterocyclic radical. 5. The compound of formula (I) wherein the O-arylthiocarbamate type is an alkyl group having 1 to 10 carbon atoms, preferably having 1 to 4 carbon atoms. Or a cycloalkyl 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; 5. The process according to claim 2, wherein the at least one aralkyl group has an atom. 6. The compound of the O-arylthiocarbamate type of formula (I) wherein A is a cyclic compound, preferably having at least 4 atoms optionally substituted on the ring. And the following rings: an aromatic monocyclic or polycyclic carbocycle; an aromatic monocyclic or polycyclic heterocycle containing at least one of the heteroatoms O, N and S The method according to any one of claims 2, 4 and 5, characterized in that it is the remaining part of a cyclic compound representing at least one of the rings. 7. The method according to claim 6, wherein said A is the remaining portion of the benzene compound. 8. The compound of the O-arylthiocarbamate type corresponding to formula (I) wherein Z is a group containing a nitrogen, sulfur or oxygen atom. A method according to any one of claims 2 and 3. 9. The compound of the O-arylthiocarbamate type having the formula (I) wherein the —O—CS—Z group is: —Formula —O—CS—N (R ₁ ) (R ₂ ) in thiocarbamate group is encoded; - wherein thiocarbonate group represented by -O-CS-OR _3; - wherein dithiocarbonato group [these represented by -O-CS-SR ₃ Wherein R ₁ , R ₂ , R ₃ , which may be the same or different, are more particularly alkyl groups having 1 to 12 carbon atoms, preferably 1 to 4 carbon atoms A cycloalkyl group having 3 to 8 carbon atoms, preferably a cyclohexyl group, and an alkyl group having 1 to 12 carbon atoms,
Represents a group of type Si (“R”) ₃ with a radical “R” which may be the same or different; and the two groups R ₁ and R ₂ are taken together with a nitrogen atom, 3 to 8 atoms containing another heteroatom, such as an oxygen or nitrogen atom,
A heterocyclic ring having preferably 4 to 5 atoms can be formed.] The method according to any one of claims 2, 3 and 8, characterized in that: . 10. The compound of the O-arylthiocarbamate type has the formula (I)
Wherein Z represents an amino group, wherein the radicals R ₁ and R ₂ , which may be the same or different, represent an alkyl group having 1 to 4 atoms, preferably a methyl or trimethylsilyl group 10. The method according to any one of claims 8 and 9, characterized in that: 11. The compound of the O-arylthiocarbamate type has the formula (I)
Where X₁Is an acyl group having 2 to 20 carbon atoms, preferably acetyl; a group represented by the following formula: -R₄-X-R₄-CF₃  -R₄-COOR₅  -R₄-CHO -R₄-SO-R₅  -R₄-SO₂-R₅  -R₄-S-CF₃  -R₄-NO₂  -R₄-CN-R₄−N = C (R₅)₂  -R₄-NH-CO-R₅  -R₄-N⁺(R₅)₃  -R₄-Si (R₅)₃  [In these formulas, R₄Is a valence bond or, for example, methylene, ethylene,
Straight or branched chains such as pyrene, isopropylene, isopropylidene, etc.
Represents an unsaturated divalent hydrocarbon radical having 1 to 4 carbon atoms;
Is a radical R which may be different₅Is a hydrogen atom or a straight or branched chain
Represents a saturated or unsaturated alkyl group having 1 to 20 carbon atoms
X represents a halogen atom, preferably chlorine, bromine or fluorine
Which represents an electron-withdrawing group).
The method according to claim 1. 12. The compound of the O-arylthiocarbamate type has the formula (I)
Where X₂Is X₁Or an electron withdrawing group such as: or-methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-
One to six carbon atoms, preferably one to four, such as butyl, tert-butyl, etc.
A straight or branched alkyl group having 2 carbon atoms, 2 to 6 carbon atoms, preferably 2 to 4 carbon atoms, such as vinyl, allyl, etc.
Linear or branched alkenyl groups having a hydrogen atom, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy radical, etc.
A straight chain having 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms;
Is a branched alkoxy group, a 2-oxypropionic acid group, a cycloalkyl group having 3 to 8 carbon atoms, preferably cyclohexyl
Benzyl group, phenyl group, group represented by the following formula: -R₄−N (R₅)₂  -R₄-CO-N (R₅)₂  [In these formulas, R₄And R₅Is the same as the definition in claim 12.], and represents an electrodonor-type group).
12. The method according to any one of claims 1 to 11. 13. A compound of the formula (I) (O-arylthiocarbamate)
Wherein n is equal to 1 or 2).
13. The method according to any one of claims 12 and 12. 14. The compound according to claim 1, wherein the compound of the O-arylthiocarbamate type contains at least two electron withdrawing groups at positions 2 and 4 with respect to the amino group. Method. 15. The compound of the O-arylthiocarbamate type has the formula (I)
13. The method according to claim 2, wherein X ₁ and X ₂ represent a halogen atom. 16. The thermal rearrangement of the O-arylthiocarbamate to the S-arylthiocarbamate can be effected by changing the reaction medium, for example, between 140 and 400 ° C., preferably between 150 and 300 ° C. The method according to claim 1, wherein the method is performed by heating to a varying temperature. 17. The method according to claim 17, wherein the heating of the reaction medium is carried out by melting or in an organic solvent having a boiling point above the selected temperature. 18. The organic solvent is selected from the following solvents: glycerol, diphenyl oxide, a eutectic mixture of diphenyl oxide and diphenyl, referred to by the trade name Dotherm® or Gilotherm®. The method of claim 17, wherein 19. A compound of the S-arylthiocarbamate type containing at least one amino group and at least one electron withdrawing group. 20. The following formula (II): _{Wherein, A, R, X 1,} X 2, Z, and n are the same definition as in claims 2 15] corresponds to the compound according to claim 19. 21. The following formula (IIa): Wherein R, X ₁ , X ₂ , Z, and n are the same as defined in claims 2 to 5 and in claims 8 to 15. A compound according to claim 1. 22. The following formula (IIa ₁ ): Wherein X ₁ , X ₂ , R, R ₁ , R ₂ and n are the same as defined in claims 2 to 5 and in claims 8 to 15. 22. The compound according to any one of claims 1 to 21. 23. The compound according to claim 22, wherein said compound corresponds to formula (IIa ₁ ) wherein X ₁ and X ₂ represent a halogen atom. 24. A process for the preparation of aromatic thiols and derivatives bearing at least one amino group, the process comprising the steps of claim 19 and at least one amino group. A process comprising the step of using a compound of the S-arylthiocarbamate type containing at least one electron withdrawing group. 25. The method according to claim 19, wherein the compound of the type O-arylthiocarbamate bearing at least one amino group and an electron withdrawing group according to claim 19 is heated. , An O-arylthiocarbamate group by S
Rearranging to an arylthiocarbamate group and then hydrolyzing the resulting S-arylthiocarbamate-type compound bearing at least one amino group and at least one electron-withdrawing group. 25. The method according to claim 24, wherein
The method described in. 26. The method according to claim 24, wherein the transposition step is performed according to a method according to any one of claims 1 to 18. 27. An acid or base hydrolysis of said S-arylthiocarbamate-type compound bearing at least one amino group and at least one electron withdrawing group obtained. The method according to any one of items 24 to 26. 28. The aromatic thiol has the following formula (III): [Wherein, A, R, X ₁ , X ₂ , and n represent claims 2 to 7 and claim 11
28. The method according to any one of claims 24 to 27, characterized in that: 29. The aromatic thiol has the following formula (IIIa): Wherein R, X ₁ , X ₂ , and n are the same as defined in claims 2 to 7 and in claims 11 to 15. The described method. 30. An O-arylthiocarbamate type compound containing at least one amino group and at least one electron withdrawing group. 31. The following formula (I): _{Wherein, A, R, X 1,} X 2, Z, and n are the same definition as in claims 2 15] corresponds to the compound according to claim 30. 32. The following formula (Ia): Wherein R, X ₁ , X ₂ , Z, and n are the same as defined in claims 2 to 5 and in claims 8 to 15. A compound according to claim 1. 33. The following formula (Ia ₁ ): 31 wherein X ₁ , X ₂ , R, R ₁ , R ₂ and n are the same as defined in claims 2 to 5 and in claims 8 to 15. 33. The compound according to any one of claims 1 to 32. 34. The compound according to claim 33, wherein said compound corresponds to formula (Ia ₁ ) wherein X ₁ and X ₂ represent a halogen atom. 35. A method for preparing an O-arylthiocarbamate compound containing at least one amino group and at least one electron withdrawing group according to any one of claims 30 to 34, The method comprises converting a hydroxylated aromatic compound bearing at least one amino or nitro group to the following formula (V): Wherein -Y is a group leaving in the presence of a nucleophile and -Z is a group containing a doublet donor atom in the α-position with respect to the carbon carrying the sulfur atom. A preparation method, comprising a step of reacting with a contained reagent. 36. The method according to claim 35, wherein the reaction is performed in the presence of a base. 37. The starting aromatic substrate has the following formula (IV): [Wherein -A, X ₁ , X ₂ , and n represent claims 2 to 7 and claims 11 to 15
And -W is an encoding of H ₂ , O ₂ , or HR; R represents a hydrogen atom or a hydrocarbon group]. The method according to any one of 35 and 36. 38. The starting aromatic substrate has the following formula (IVa): [Wherein -X ₁ , X ₂ , and n are the same as defined in claims 2 to 7 and claims 11 to 15, and -W represents H ₂ , HR, or O ₂ . R represents a hydrogen atom or a hydrocarbon group, as defined]. 39. The method according to claim 15, wherein the compound of formula (IV) or (IVa) bearing an amino group
39. A method according to any one of claims 35 to 38, comprising reacting a compound of formula (I) with a sulfur-containing compound of formula (V). 40. The method according to claim 15, wherein the method is a compound of formula (IV) or (IVa) bearing a nitro group.
39. The method according to claim 35, comprising reacting the compound of formula (I) with a sulfur-containing compound (V), and then subjecting the resulting product to a reduction step. the method of. 41. The method according to claim 35, wherein the sulfur-containing compound corresponds to formula (V), wherein the leaving group Y is a weak base. the method of. 42. The leaving group Y is a halogen atom (preferably chlorine, bromine or iodine) and a sulfonate group, —OSO ₂ R _{6 wherein} R ₆ is 1 to 20 And more preferably: a halogen atom, a CF ₃ group, or an ammonium group N (R ₇ ) ₄ , wherein R ₇ may be the same or different Represents an alkyl group having 1 to 4 carbon atoms) and has 1 to 10 carbon atoms, preferably an alkyl group having 1 to 4 carbon atoms, more preferably methyl Or an ethyl group,-a cycloalkyl group having 3 to 8 carbon atoms, preferably a cyclohexyl group,-optionally 1 to 10 carbon atoms, preferably 1 to 4 carbon atoms. Alkyl group, more preferably methyl or Ethyl group, a halogen atom, CF ₃ group, or carries a NO ₂ group, an aryl group having from 6 to 12 carbon atoms,
Preferably wherein the phenyl group, · CX ₃ group (wherein, X is fluorine, chlorine or bromine atom), a represents a _· CF 2 -CF ₃ group, according to claim 41 the method of. 43. The leaving group Y is: tosylate (p-toluenesulfonic acid ester), —OSO₂-C₆H₄−
CH₃・ Brosylate (p-bromobenzenesulfonic acid ester), —OSO₂-C ₆ H₄-Br, -nosylate (p-nitrobenzenesulfonic acid ester), -OSO₂-C₆ H₄-NO₂・ Mesylate (methanesulfonic acid ester), -OSO₂-CH₃・ Betyrate (ammonioalkanesulfonic acid ester), -OSO₂− (C
H₂)_nNMe₃ ⁺(Where n represents a number from 0 to 6), triflate (trifluoromethanesulfonic acid ester), -OSO₂-C
F₃Nonaflate (nonafluorobutanesulfonic acid ester), -OSO₂-C ₄ F₉-Tosylate (2,2,2-trifluoroethanesulfonic acid ester)-
OSO₂-CH₂-CF₃  43. The method according to claim 41, wherein
Method. 44. The method according to claim 41, wherein the leaving group Y is a halogen atom. 45. The method according to claim 8, wherein the sulfur-containing reagent is represented by the formula (V):
45. The method according to any one of claims 41 to 44, characterized in that: 46. The sulfur-containing reagent used has the following formula (Va): Wherein: -Y represents a leaving group, preferably a halogen atom; -R ₁ and R ₂ , which may be the same or different, are from 1 to 12 carbon atoms, preferably 1 An alkyl group having 3 to 8 carbon atoms; a cycloalkyl group having 3 to 8 carbon atoms, preferably a cyclohexyl group; and an alkyl group having 1 to 12 carbon atoms, which is the same or 47 (represents a group of the type Si ("R") ₃ with a radical "R" which may be different]. 45. A process according to any one of claims 41 to 45, characterized in that: 47. A compound of formula (IV) or (IVa) and a sulfur-containing reagent (
The reactions of V) and (Va) are characterized in that they are carried out in batch form in the absence of any solvent, in an aqueous medium, in an organic medium or in a water-organic medium. 47. The method according to any one of claims 41 to 46. 48. The process according to claim 41, wherein the reaction is carried out at a temperature comprised between ambient temperature and the reflux temperature of the reaction mixture, preferably between 60 ° C. and 90 ° C. 48. The method according to any one of the preceding claims. 49. A process for the preparation of aromatic thioethers and derivatives bearing at least one amino group, the method comprising the steps of: adding at least one amino group according to claim 19 to at least one amino group. A process comprising the step of using a compound of the S-arylthiocarbamate type containing one electron withdrawing group. 50. The method according to claim 19, wherein the compound of the type O-arylthiocarbamate bearing at least one amino group and an electron withdrawing group according to any one of claims 19 to 23 is heated. , An O-arylthiocarbamate group by S
Rearrangement to an arylthiocarbamate group and then hydrolyzing the resulting S-arylthiocarbamate type compound bearing at least one amino group and at least one electron withdrawing group, followed by an alkylating agent 50. The method of claim 49, comprising performing S-alkylation by the reaction of 51. The aromatic thioether has the following formula (VI): [Wherein, A, R, X ₁ , X ₂ , and n represent claims 2 to 7 and claim 11
And R ₈ represents a hydrocarbon radical having 1 to 24 carbon atoms, which is a straight-chain or branched, saturated or unsaturated acyclic fatty acid. Aromatic radicals; monocyclic or polycyclic, saturated, unsaturated, or aromatic, alicyclic radicals; linear or branched, saturated or unsaturated, aliphatic radicals bearing cyclic substituents The method according to any one of claims 49 and 50, characterized in that: 52. The aromatic thioether has the following formula (VIa): Wherein R, X ₁ , X ₂ and n are the same as defined in claims 2 to 7 and 11 to 15 and R ₈ is the same as defined in claim 51 A method according to claim 51, characterized in that: 53. The thioether of the formula (VI) or (IVa) wherein R
₈Are: linear or branched, saturated or unsaturated, acyclic aliphatic radicals;-optionally substituted cyclic substituents, optionally bearing a benzene ring;
A straight chain that can be attached to the ring by a valence bond, a heteroatom, or a functional group.
Or branched, saturated or unsaturated, acyclic aliphatic radical; -saturated, or containing one or two unsaturations in the ring,
Carbocyclic radicals having 3 to 8 carbon atoms, preferably 6 carbon atoms (
The ring may be substituted), the ring generally has at least 4 carbon atoms, preferably 6 carbon atoms
An aromatic carbocyclic radical, preferably a monocyclic radical having the formula
53). The method according to any one of claims 51 and 52, wherein
The method described. 54. The thioether of the formula (VI) or (IVa) wherein R ₈ Is a straight chain having 1 to 12 carbon atoms, preferably 1 to 6 carbon atoms.
Refers to a chain or branched alkyl radical: the hydrocarbon chain is a heteroatom (eg,
Oxygen), a functional group (preferably —CO—), and / or a substituent (preferably
A group bearing a halogen, ester function, preferably methyl or ethyl)
54. The method according to claim 51, wherein
The method according to claim 1. 55. A method according to any one of claims 49 to 54, characterized in that said dislocation is performed according to a method according to any one of claims 1 to 18. 56. The base hydrolysis of the resulting compound of the S-arylthiocarbamate type carrying at least one amino group and at least one electron withdrawing group is carried out. 56. The method according to any one of the preceding claims. 57. The process according to claim 49, wherein an alkylating agent of the halide, sulfate or carbonate type is used. 58. The alkylating agent used is represented by the following formula: R ₈ —X (VIIa), R ₈ —O—SO ₂ —O—R ₈ (VIIb), R ₈ —O—
CO-OR ₈ (VIIc) wherein R ₈ is the same as defined in claims 53 and 54, and X represents a halogen atom, preferably a fluorine, chlorine, bromine, or iodine atom. 58. The method according to claim 57, wherein the method corresponds to one of the following: 59. The method according to claim 58, wherein said alkylating agent is methyl chloride, dimethyl sulfate, and dimethyl carbonate.