EP1042282A1 - Verfahren zur herstellung von aromatischen thiolen und derivaten, reagenzien und zwischenprodukte zu ihrer herstellung - Google Patents

Verfahren zur herstellung von aromatischen thiolen und derivaten, reagenzien und zwischenprodukte zu ihrer herstellung

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Publication number
EP1042282A1
EP1042282A1 EP98963591A EP98963591A EP1042282A1 EP 1042282 A1 EP1042282 A1 EP 1042282A1 EP 98963591 A EP98963591 A EP 98963591A EP 98963591 A EP98963591 A EP 98963591A EP 1042282 A1 EP1042282 A1 EP 1042282A1
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EP
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Prior art keywords
group
formula
compound
carbon atoms
arylthiocarbamate
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EP98963591A
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English (en)
French (fr)
Inventor
Jean-Francis Spindler
Jean-Roger Desmurs
Pierre Beslin
Yannick Quesnel
Clotilde Mispelaere
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Rhodia Chimie SAS
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Rhodia Chimie SAS
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Publication of EP1042282A1 publication Critical patent/EP1042282A1/de
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
    • C07C319/02—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of thiols
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B45/00—Formation or introduction of functional groups containing sulfur
    • C07B45/06—Formation or introduction of functional groups containing sulfur of mercapto or sulfide groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C333/00—Derivatives of thiocarbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
    • C07C333/02—Monothiocarbamic acids; Derivatives thereof
    • C07C333/04—Monothiocarbamic acids; Derivatives thereof having nitrogen atoms of thiocarbamic groups bound to hydrogen atoms or to acyclic carbon atoms

Definitions

  • 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.
  • 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.
  • 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.
  • 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:
  • 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.
  • 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.
  • 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.
  • 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.
  • 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):
  • - 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 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
  • 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.
  • 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,
  • 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.
  • 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,
  • 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-
  • R Q represents a hydrogen atom or an alkyl group having from 1 to 4 carbon atoms, a cyclohexyl or phenyl group.
  • a monocyclic, carbocyclic, aromatic compound such as, for example, benzene, toluene, isobutylbenzene, anisole, phenetole or veratrole, guaiacol, guetol, 4-phenoxypropionic acid,
  • 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.
  • A represents an aromatic nucleus, preferably a benzene nucleus.
  • group Z it is a group comprising a doublet donor atom, in position ⁇ with respect to the carbon carrying the sulfur atom.
  • atom having an available doublet mention may be made of a nitrogen, sulfur or oxygen atom.
  • 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:
  • 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.
  • , 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.
  • and R 2 identical or different, represent a methyl, isopropyl, cyclohexyl or trimethylsilyl group and R-
  • Z represents an amino group in which the groups R -
  • 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.
  • n is advantageously equal to 1 or 2.
  • the electron-withdrawing group is more particularly one of the following atoms or groups:
  • 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;
  • 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:
  • R4 and R5 can take the meanings given above.
  • 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.
  • 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
  • the invention also relates to the use of the compounds of formula (II) for the preparation of aromatic thiols corresponding to formula (III):
  • 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
  • the invention also relates to the use of the compounds of formula (II) for the preparation of aromatic thioethers corresponding to formula (VI):
  • 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,
  • 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.
  • 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).
  • a heteroatom for example, oxygen
  • a functional group for example -CO-
  • 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).
  • acyclic, saturated or unsaturated, linear or branched aliphatic radical may optionally carry a cyclic substituent.
  • 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.
  • R 8 represents a linear or branched alkyl radical having from 1 to 4 carbon atoms or a phenyl radical.
  • R 8 radicals 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
  • 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 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.
  • organic solvent having a high boiling point above the chosen temperature.
  • solvents examples include 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.
  • a first variant of the process of the invention consists in carrying out an acid hydrolysis.
  • 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.
  • sulfuric acid is chosen.
  • concentration of the acid is indifferent.
  • 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.
  • 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.
  • the hydrolysis reaction is carried out in basic medium.
  • 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 .
  • 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.
  • the preparation of an aromatic thioether can be carried out from the compound of the S-arylthiocarbamate type.
  • alkylating agents which are particularly suitable, mention may in particular be made of alkylating agents of the halide, carbonate or sulphate type.
  • 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.
  • 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.
  • Vlla represents a chlorine atom and R 8 represents a linear or branched alkyl radical having from 1 to 4 carbon atoms.
  • halides methyl chloride, chloroethane, methyl bromide are preferred.
  • 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.
  • 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.
  • 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.
  • 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.
  • a basic agent preferably sodium hydroxide or potassium hydroxide
  • S-arylthiocarbamate 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.
  • the thioether preferably corresponding to formulas (VI) and (Via) is recovered according to conventional separation techniques, for example filtration.
  • 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):
  • - 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.
  • the leaving group Y can be defined as a weak base.
  • weak base is meant a base whose pka of the conjugated acid is less than 6.5, preferably less than 5.
  • 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: .
  • the preferred sulfonic ester groups are:
  • 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 ⁇ with respect to the carbon carrying the sulfur atom.
  • Z symbolizes the rest of a possibly silylated amine, an ether or a thioether.
  • 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.
  • 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
  • - 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.
  • 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.
  • 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.
  • 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.
  • Suitable bases are in particular the alkali and alkaline earth metal carbonates and the alkali metal hydroxides, preferably sodium or potassium hydroxide.
  • 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.
  • trialkylbenzylammonium hydroxides and in particular trimethylbenzylammonium 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.
  • 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.
  • 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.
  • an organic solvent preferably an aprotic polar solvent.
  • 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.
  • the reaction is preferably carried out in bulk, in the absence of any aqueous or organic solvent.
  • 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.
  • 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.
  • 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.
  • 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.
  • the reaction mixture is then heated at 50 ° C for 10 hours.
  • the O-arylthiocarbamate is filtered and dried under reduced pressure of 15 mm of mercury.
  • 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.
  • reaction mixture is heated under reflux of ethanol for 2 h 30 then diluted (100 ml of ethanol) and filtered hot on celite.
  • 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.
  • aqueous phases are then basified to pH> 12 with sodium hydroxide and extracted with dichloromethane (4 x 30 ml).
  • the S-arylthiocarbamate is isolated in the form of a white solid which does not require purification.
  • 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%.
  • 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.
  • reaction medium is heated for one hour at 70 ° C.
  • 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.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
EP98963591A 1997-12-22 1998-12-22 Verfahren zur herstellung von aromatischen thiolen und derivaten, reagenzien und zwischenprodukte zu ihrer herstellung Withdrawn EP1042282A1 (de)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
FR9716257 1997-12-22
FR9716257A FR2772757B1 (fr) 1997-12-22 1997-12-22 Procede de preparation de thiols aromatiques, reactifs, produits intermediaires et leur procede d'obtention
PCT/FR1998/002825 WO1999032440A1 (fr) 1997-12-22 1998-12-22 Procede de preparation de thiols aromatiques et derives, reactifs, produits intermediaires et leur procede d'obtention

Publications (1)

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EP1042282A1 true EP1042282A1 (de) 2000-10-11

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EP98963591A Withdrawn EP1042282A1 (de) 1997-12-22 1998-12-22 Verfahren zur herstellung von aromatischen thiolen und derivaten, reagenzien und zwischenprodukte zu ihrer herstellung

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EP (1) EP1042282A1 (de)
JP (1) JP2002512174A (de)
AU (1) AU1881199A (de)
FR (1) FR2772757B1 (de)
WO (1) WO1999032440A1 (de)

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US3476791A (en) * 1966-05-04 1969-11-04 Trustees Of Ohio State Univ Th O-thiocarbamoyl benzoic acid esters
DE3275295D1 (en) * 1981-11-12 1987-03-05 Fisons Plc Anti-srs-a carboxylic acid derivatives, processes for their production, and pharmaceutical formulation containing them
JPS60166665A (ja) * 1984-02-10 1985-08-29 Sumitomo Chem Co Ltd テトラヒドロ−２ｈ−インダゾ−ル誘導体、その製造法およびそれを有効成分とする除草剤
US4613675A (en) * 1984-11-30 1986-09-23 Sandoz Ltd. Phosphorus containing 1-cyclohexene-1,2-dicarboxamides
CA2085311A1 (en) * 1991-12-16 1993-06-17 Adolf Hubele Microbicides

Non-Patent Citations (1)

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Title
See references of WO9932440A1 *

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AU1881199A (en) 1999-07-12
JP2002512174A (ja) 2002-04-23
FR2772757B1 (fr) 2001-05-25
FR2772757A1 (fr) 1999-06-25
WO1999032440A1 (fr) 1999-07-01

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