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WO2002066423A1 - Procede de preparation de composes de polyfluoroalkylsulfenyle - Google Patents

Procede de preparation de composes de polyfluoroalkylsulfenyle Download PDF

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Publication number
WO2002066423A1
WO2002066423A1 PCT/JP2002/001558 JP0201558W WO02066423A1 WO 2002066423 A1 WO2002066423 A1 WO 2002066423A1 JP 0201558 W JP0201558 W JP 0201558W WO 02066423 A1 WO02066423 A1 WO 02066423A1
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group
atom
hydrogen atom
optionally substituted
alkyl
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PCT/JP2002/001558
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English (en)
Japanese (ja)
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Kazuya Okano
Liangyou He
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Nihon Nohyaku Co., Ltd.
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Priority claimed from JP2001046037A external-priority patent/JP2002249485A/ja
Priority claimed from JP2001046036A external-priority patent/JP2002249480A/ja
Priority claimed from JP2001318198A external-priority patent/JP2003128644A/ja
Application filed by Nihon Nohyaku Co., Ltd. filed Critical Nihon Nohyaku Co., Ltd.
Publication of WO2002066423A1 publication Critical patent/WO2002066423A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D231/44—Oxygen and nitrogen or sulfur and nitrogen atoms

Definitions

  • the present invention relates to a method for producing a polyfluoroalkylsulfenyl derivative useful as a medicinal and agricultural chemical.
  • Benzyl useful as a precursor of difluoromethinolesulfenyl chloride used for producing a difluoromethylsulfenyl derivative The present invention relates to a method for producing (difluoromethyl) sulfide, and a 1-arylu 3-cyano 4-trifluoromethylsulfenylvirazole derivative particularly useful as an agricultural or veterinary drug.
  • a bisazole derivative having a trifluoromethylsulfenyl group or a pyrazole derivative having a difluoromethylphenyl group are useful as insecticides and are effective methods for introducing polyfluoroalkylsulfenyl groups, especially trifluoromethylsulfuryl groups and dimethyl groups. There is a need for a method for introducing a fluoromethylphenyl group.
  • sulfides can also be prepared by nucleophilic substitution of thiols with alkyl halides.
  • this nucleophilic substitution reaction is difficult to proceed, and particularly in the case of perfluorinated alkyl halides required for producing a trifluoromethylsulfenyl derivative, various activations are required, which complicates the work. Or toxic substances are used for activation.
  • thiol is liable to be converted to disulfide by air oxidation, which may cause difficulty in industrial handling, and also has a problem of odor. Therefore, it is difficult to industrially produce a trifluoromethylsulfur derivative by this method.
  • thiol When thiol is used as a raw material, the number of steps is increased since thiol is generally produced by reducing an intermediate such as thiocyanatodisulfide.
  • a method of polyfluoroalkylating a thiosiano group to introduce a polyfluoroalkylsulfenyl group For example, a method is known in which trifluoromethyltrimethyl / resilane is allowed to act on a thiocyanate compound (Tetrahedron Lett., 1997, 65), but trifluoromethyltrimethylsilane used as a raw material is expensive. It is difficult to industrially produce a trifluoromethylsulfenyl derivative by the method.
  • the method for producing a trifluoromethylsulfenyl derivative using disulfide as a raw material is effective in view of the ease of producing the raw material.
  • Patent No. 2,746,707 discloses that an excess amount of sodium formate and an excess amount of sulfur dioxide are used to react disulfide with trifluoromethyl halide to obtain the corresponding trifluoromethyl sulfone.
  • a method for producing a fermented body is described.
  • sulfur dioxide is irritating and has a negative impact on the environment, which is problematic for industrial use.
  • Trifluoromethyl bromide has been banned from production because it destroys the ozone layer, and is a raw material that is harmful to the global environment.
  • Trifluoromethyl bromide has been banned from production because it destroys the ozone layer, and is a raw material that is harmful to the global environment.
  • difluoromethylsulfenyl chloride is effective as a method for introducing a polyfluoroanolekylsulfenyl group, for example, a diphnoleolomethinolesnorephenyl group.
  • a polyfluoroanolekylsulfenyl group for example, a diphnoleolomethinolesnorephenyl group.
  • difluoromethylsulfuryl chloride can be synthesized from benzinole (difluoromethyl) sulfide and benzyl (difluoromethyl) sulfide.
  • the present invention relates to a polyfluoroalkylsulfuric acid compound obtained by conducting a polyfluoroalkylation reaction with a halogenated polyfluoroalkyl in the presence of a disulfide as a raw material in the presence of an industrially easy-to-use auxiliary agent. And a method for synthesizing benzyl (difluoromethyl) sulfide in a high yield by using a commercially available solvent.
  • the desired polyfluoroalkylsulfenyl compound can be obtained by performing the reaction in the presence of hydrazine or metal borohydride. And completed the first invention.
  • the desired solvent in the reaction of benzyl mercaptan or a salt thereof with chlorodifluoromethane, the desired solvent can be obtained by using a mixed solvent of alcohol and water as a reaction solvent. It was found that benzyl (difluoromethyl) sulfide was obtained in good yield.
  • a first gist of the present invention is a method for obtaining a polyfluoroalkylsulfenyl compound by reacting disulfide with one or more selected from hydrazine and metal borohydride and a polyfluoroalkyl halide.
  • a second gist of the present invention is to provide a method for producing benzyl (difluoromethyl) sulfide by reacting benzyl mercaptan or a salt thereof with chlorodifluoromethane in the presence of a solvent and a base, wherein a mixed solvent of alcohol and water is used as a solvent.
  • a method for producing benzyl (difluoromethyl) sulfide which is characterized in that it is used.
  • the disulfide used in the first invention is represented by the general formula (1).
  • R 11 and R 12 each independently represent a group bonded to a sulfur atom at a carbon atom, and may be bonded to each other to form a ring.
  • Examples of the group bonded to a sulfur atom at a carbon atom include an alkyl group, an aryl group, and a heteroaryl group. These groups may further have a substituent.
  • R 11 and R 12 specifically, dimethinoresin sulfide, getyl disulfide, g-n-propinoresin sulfide, diisopropyl disulfide, g-n-butyl disulfide, — Sec-Petinoresinolefide, diisobutyl / resinose-renofide, g-tert-ptynoresinose-renofide, di-n-amyl disulfide, diisoamyl-disulfide, g-tert-amino-resin-norfide, G-n-heptino Resin-norebuide, di-tert-octinore di-no-sulfide, di-n-decino-resin-no-resulfide, g-tert-dodecyl-disulphide, aryl-disulfide, 2-hydroxyshetyl, 2-
  • the disulfide is preferably a disulfide which is a heterocyclic ring in which at least one of R 11 and R 12 in the general formula (1) may be substituted.
  • the heterocyclic ring include pyrazole, pyrrole, imidazole, pyridine, thiophene, and furan.
  • the disulfide is more preferably di (birazolyl) disulfide having a substituent. Pyrazol derivatives having a trifluoromethylsnorrefenyl group obtained from di (birazolyl) disnorefedica having a substituent are useful as agricultural and veterinary drugs.
  • a compound represented by the general formula (2) or the general formula (3) is particularly preferable.
  • R 1 represents a hydrogen atom, a C 1 -C 4 alkyl group or a C 2 -C 5 acyl group, and c R 1 specifically represents a hydrogen atom; a methyl group, an ethyl group, an n-propyl group, C such as isopropyl, n-butyl, isopropyl, sec-butyl, t-butyl, etc.
  • a straight-chain or branched-chain alkyl group of 1 to 4 carbon atoms; or a methylcarbonyl group, an ethylcarbonyl group, an n-propylcarbonyl group, an isopropylcarbonyl group, an n-butylcarboninole group, an isobutylcarbonyl group, a sec-butylcarbonyl group, t represents a C1-C4 linear or branched chain acyl group such as a monobutylcarbonyl group.
  • R 2 represents a hydrogen atom, a hydroxyl group or an alkyl group of C 1 through C 4.
  • R 2 is, specifically, a hydrogen atom; a hydroxyl group; or a direct group such as a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a sec-butyl group, and a t-butyl group. It represents a chain or branched alkyl group, preferably a hydrogen atom.
  • R 3 is a hydrogen atom, a hydroxyl group, an alkyl group of C 1 through C 4, a haloalkyl group of C 1 through C 4, C 1 alkoxy group ⁇ C 4, optionally substituted phenoxy group, a C 1 through C 4 Haloalkoxy group, C 1 -C 4 alkylsulfenyl group, C 1 -C 4 alkylsulfininole group, C 1 -C 4 anolequinolenes olefoninole group, optionally substituted aryl Group or a heteroaryl group.
  • R 3 is preferably an optionally substituted aryl group or a heteroaryl group, and particularly preferably an optionally substituted aryl group or a heteroaryl group represented by the following formula.
  • R 4 is an alkyl group of C 1 through C 4, a haloalkyl group of C 1 through C 4, alkoxy group of C 1 through C 4, optionally substituted phenoxy group, Haroarukoki of C 1 through C 4 And a C 1 -C 4 alkylsulfenyl group, a C 1 -C 4 alkylsulfenyl group, a C 1 -C 4 alkylsulfonyl group, a halogen atom, a nitro group or a cyano group.
  • n 0, 1 or 2.
  • X represents a carbon atom substituted with a nitrogen atom or a halogen atom, preferably a carbon atom substituted with a halogen atom, particularly preferably a carbon atom substituted with a chlorine atom.
  • n 0, 1 or 2, and preferably represents 1.
  • a preferred compound is bis (1-1 (2,6-dichloro-1-41-trifnoroleolomethinolefeninole) _3-canolepo-trinole-1.5_ (pyrazin-12-ylmethylamino) ) Pyrazole (41-yl) is a single disulfide.
  • X represents a carbon atom substituted with a nitrogen atom or a halogen atom, preferably a carbon atom substituted with a halogen atom, particularly preferably a carbon atom substituted with a chlorine atom.
  • the polyfluoroalkyl halide used in the first invention is represented by the general formula (4).
  • R 2 1 — X 2 (4) X 2 represents a chlorine atom, a bromine atom or an iodine atom, preferably a bromine atom or an iodine atom, more preferably an iodine atom.
  • R 2 1 represents a polyfurfuryl O b alkyl group.
  • a polyfluoroalkyl group is an alkyl group substituted by one or more fluorine atoms.
  • the carbon number of the alkyl group of the polyfluoroalkyl group is preferably 1 to 20, more preferably 1 to 10, and particularly preferably 1.
  • R 2 1 may have a substituent other than a fluorine atom, as a substituent other than full Tsu atom, preferably a halogen atom other than fluorine, a substituent having a SansoHara child, having a nitrogen atom Substituents and the like are exemplified, and particularly preferably, a halogen atom other than fluorine is exemplified.
  • R 2 1 is preferably all of the hydrogen atoms are halogen atom (however, the full Tsu atom containing 1 or more) perhaloalkyl group substituted with halogen is part of the hydrogen atoms on the alkyl group on the alkyl group And a polyhaloalkyl group substituted with an atom (including one or more fluorine atoms). More preferably, a perfluoroalkyl group in which all hydrogen atoms on the alkyl group are substituted with fluorine atoms, alkyl Examples thereof include a polyfluoroalkyl group in which a part of hydrogen atoms on the group is substituted with a fluorine atom, and particularly preferably a perfluoroalkyl group.
  • perfluoroalkyl halides include trifluoromethyl chloride, trifluoromethyl bromide, trifluoromethyl iodide, pentafluoroethyl chloride, pentafluoroethyl bromide, Pentaphthalenoyl iodide, heptafluoropropyl chloride, heptafluoropropyl bromide, heptafluoropropyl iodide, heptafluoropropyl iodide, nonafluorobutyl chloride, nonafluorobutyl bromide, nonafluorobutyl iodide Robutyl, perphnoleo chloride pentinole, perphnoleo bromide pentinole, perphnolelopentyl iodide, perfluoro chloride hexyl, perfluoro bromide hexyl, perfluoro
  • Halogenated trifluoromethyls such as trifluoromethyl, trifluoromethyl bromide, and iowidani trifluoromethyl are used, more preferably trifluoromethyl bromide and trifluoromethyl bromide, and particularly preferably trifluoromethyl bromide.
  • Trifluoromethyl iodide is used.
  • the amount of the polyfluoroalkyl nodogen used is usually at least 2 mol equivalent to disulfide (that is, at least 1 mol equivalent to zeo atom), and usually at most 20 mol equivalent, preferably 8 mol equivalent. Less than the equivalent (that is, less than 4 molar equivalents relative to the iodine atom). Unreacted polyfluoroalkyl halide can be recovered by methods such as volatile separation, distillation, and extraction.
  • the first invention is characterized in that the reaction between the disulfide and the polyfluoroalkyl halide is carried out in the presence of hydrazine or metal borohydride.
  • hydrazine anhydrous hydrazine and hydrazine hydrate can be used as the hydrazine, but hydrazine hydrate is preferred for safety. Is used.
  • the amount of hydrazine to be added is generally at least 0.5 molar equivalent, preferably at least 1.5 molar equivalent, and usually at most 10 molar equivalent, preferably at most 4 molar equivalent, based on disulfide. In the case of hydrazine, there is an advantage that it is not necessary to use an electron transfer catalyst together.
  • the reaction between disulfide and polyfluoroalkyl halide, which is carried out in the presence of hydrazine, can be carried out in the absence of a base, but is preferably carried out in the presence of a base.
  • the base include organic bases such as triethylamine, trimethylamine, and pyridine; and inorganic bases such as potassium carbonate, potassium hydrogen carbonate, potassium hydroxide, sodium hydroxide, and dipotassium hydrogen phosphate.
  • the amount of the base is usually at least 1 molar equivalent, preferably at least 2 molar equivalents, and usually at most 10 molar equivalents, preferably at most 3 molar equivalents, based on disulfide.
  • hydrazine is considered to have the function of generating a polyfluoroalkyl anion radical by one-electron reduction of the halogenated polyfluoroalkyl, and further generating a polyfluoroalkyl radical by cleavage.
  • the resulting polyfluoroalkyl radical acts on the disulfide to form a polyfluorosulfur compound.
  • the metal borohydride when the reaction between the disulfide and the halogenated polyfluoroalkyl is carried out in the coexistence of a metal borohydride, the metal borohydride may be lithium borohydride, sodium borohydride, or potassium borohydride.
  • Alkali earth metal borohydride such as calcium borohydride, magnesium borohydride, etc.
  • Typical metal borohydride such as zinc borohydride, zinc borohydride, lithium cyano borohydride Examples thereof include silane and sodium borohydride such as sodium borohydride, and preferably include alkali metal borohydride, and more preferably sodium borohydride.
  • the amount of the metal borohydride to be used is generally at least 0.5 molar equivalent, preferably at least 1.5 molar equivalent, and usually at most 10 molar equivalent, preferably at most 4 molar equivalent, based on disulfide.
  • the reaction between disulfide and halogenated polyfluoroalkyl, which is carried out in the presence of a metal borohydride, is preferably carried out in the presence of a bividinium salt derivative.
  • a bividinium salt derivative examples include those known as electron-transfer catalysts described in J. Org. Chem., 1990, 55, 4127 and the like.
  • viologen Dimethyl-4,4'-biviridinium dichloride (methyl viologen) and other 1,1,1-dialkyl-1,4, —biviridinium salts, 1,1,1-ethylene-1,2,2'-biviridylium
  • biviridem salt derivatives such as 1,1 ′ dialkyl 1,2,2,1 viridylium salts such as dibromide
  • viologen dyes that are 1,1′-dimethyl 4,4,1 viridinium salts. Particularly preferred is methyl viologen.
  • the amount of Bibirijiniumu salt derivative, with respect to disulfide usually 0.0 to 1 mole 0/0 or more, preferably 1 mol% or more, usually 9 9 mole 0/0 or less, preferably 2 0 mol% or less It is.
  • the vibidium salt is present in the aqueous layer after oil-water separation at the end of the reaction, and can be recycled.
  • the reaction between the disulfide and the halogenated polyfluoroalkyl which is carried out in the presence of a metal borohydride, can be carried out in the absence of a base, but is preferably carried out in the presence of a base.
  • a base examples include organic bases such as triethylamine, trimethylamine, and pyridine; and inorganic bases such as potassium carbonate, potassium hydrogencarbonate, potassium hydroxide, sodium hydroxide, and dipotassium hydrogenphosphate.
  • Organic bases, more preferably, triethylamine are exemplified.
  • the amount of the base is preferably a large excess with respect to the disulfide, more preferably at least 10 molar equivalents and at most 100 molar equivalents.
  • the metal borohydride has the function of reducing disulfide to a thiol group.
  • thiol groups become thiolatwaeons in the presence of a base.
  • Thiolato anion is capable of one-electron reduction of coexisting methyl viologen.
  • thiolate anion acts on halogenated polyfluoroalkyl to generate polyfluoroalkyl radical, and induces disulfide to polyfluorosulfur compound. It is presumed that you are.
  • the reaction between the disulfide and the polyfluoroalkyl halide is usually carried out in the presence of a solvent.
  • the solvent is not particularly limited, but preferably DMF, dimethylacetamide, N-methyl-12-pyrrolidone, DMI (1,3-dimethyl-12-imidazolidinone), HMPA (hexamethylphosphoramide), DMSO (Dimethyl sulfoxide), aprotic polar solvents such as sulfolane, and the like, particularly preferably polar solvents having an amide group such as DMF, dimethylacetamide, and N-methyl-1-pyrrolidone.
  • the amount of the solvent used is usually at least 1 fold, preferably at least 2 fold, particularly preferably at least 5 fold, and usually at most 100 fold, preferably at most 1 fold, in terms of volume Z weight ratio to the substrate (disulfide).
  • the range is 100 times or less, particularly preferably 20 times or less.
  • the reaction method is as follows: 1) a method of dissolving a halogenated polyfluoroalkyl under normal pressure, 2) a blowing method, and 3) in a reaction vessel charged with disulfide, a solvent, hydrazine or metal borohydride, and, if necessary, a base. ) A method of charging and reacting a polyfluoroalkyl halide in a closed vessel such as an autoclave.
  • the reaction temperature is usually ⁇ 20 ° C. or higher, preferably 0 ° C. or higher, and is usually selected from a range of 120 ° C. or lower and room temperature or lower.
  • the reaction time is generally 1 hour or longer, preferably 10 hours or longer, and usually 120 hours or shorter, preferably 48 hours or shorter.
  • the product is isolated by the usual post-treatment method, ie, extraction by oil-water separation, oil-water separation or crystallization by adding water, or distillation, or used in the next step without isolation.
  • a polyfluorinated alkylsulfenyl compound corresponding to the disulfide used as a raw material can be obtained.
  • pyrazole derivatives represented by general formulas (5) and (6) can be obtained.
  • R ⁇ R 2 , R 3 , X, n are as defined in general formula (2).
  • R 5 is R 2 1 the same meaning in the general formula (4).
  • Specific examples of the compound represented by the general formula (5) include: 1,1- (2,6-dichloro-41-trifnoreo methinolefeninole) 1,4-trifleuromethinoles / refenisle- 5-(pyrazine-1 -ylmethylamino) pyrazole-3 -capillonitrile, 1-(2,6 dichloro-1 4-1tri phenolic methinolepheninole) _ 4 -diphnoreomethyl sulphenyl 5-(pyridine 1 -2-) (Methylmethylamino) pyrazole-3 carbonitrile.
  • X has the same meaning as in general formula (2).
  • R 5 has the same meaning as R 21 in formula (4).
  • the pyrazole derivative represented by the general formulas (5) and (6) obtained by the first invention is used as a raw material, and is represented by the general formula (7) by a route such as the reaction formulas 1 and 2. Can be obtained.
  • RR ⁇ R 3 , X and n have the same meanings as in the general formula (2).
  • R 5 has the same meaning as R 21 in formula (4).
  • p represents 1 or 2, and preferably 1.
  • Specific examples of the compound represented by the general formula (7) include 1- (2,6-dichloro-opening—4-trifluoromethylphenyl) -14-trifluoromethylsulfiel-15-1 ( Pyrazine-1-ylmethylamino) pyrazole-13-potunitrile.
  • X has the same meaning as in the general formula (2).
  • R 5 has the same meaning as R 21 in formula (4).
  • p represents 1 or 2, and preferably 1.
  • Specific examples of the compound represented by the general formula (8) include 1- (2,6-dichloro-4-trifluoromethyl-phenol) -141-trifnoroleolomethinoresnorefininole-51-aminopyrazo 1-ru 3-carbonitrile.
  • Examples of the method of oxidizing the sulfur atom in Reaction Formulas 1 and 2 include a chemical oxidation method using an oxidizing agent and a biochemical oxidation method using enzymes, bacteria, etc., but the chemical oxidation method is generally used. Used. In chemical oxidation, it is usually at least 0.2 molar equivalent, preferably at least 0.25 molar equivalent, and usually at most 5.0 molar equivalent, based on the compound of the general formula (5) or (6).
  • the oxidizing agent is preferably added in an amount of 2.0 molar equivalents or less in the presence or absence of a solvent.
  • the reaction is carried out at a temperature of 120 ° C. or less, usually for 1 hour or more, usually for 48 hours or less, preferably for 6 hours or less.
  • Examples of the oxidizing agent used in this reaction include hydrogen peroxide, oxone, m-chloroperbenzoic acid, peracetic acid, sodium periodate, ruthenium tetroxide, ozone, t-butyl hydroperoxide, nitric acid, and the like. And preferably hydrogen peroxide.
  • Hydrogen peroxide is usually used as a hydrogen peroxide solution, and the concentration of the hydrogen peroxide in the hydrogen peroxide solution is usually 10 weight. /. As described above, it is preferably at least 30% by weight, usually at most 70% by weight, and preferably at most 60% by weight.
  • an organic solvent generally used for an oxidation reaction can be used, and a hydrocarbon solvent such as toluene and hexane, and a halogenated hydrocarbon solvent such as dichloromethane and chloroform are used.
  • an acid examples include a protonic acid and a Lewis acid, and a protonic acid is preferred.
  • the protic acid include inorganic acids such as sulfuric acid, hydrochloric acid, nitric acid, and phosphoric acid, and organic acids such as acetic acid, formic acid, and trifluoroacetic acid.
  • sulfuric acid is more preferable.
  • sulfuric acid having a concentration of 60 to 90% by weight is generally used, and sulfuric acid having a concentration of 75 to 85% by weight is preferably used.
  • a preferred combination of the oxidizing agent and the solvent is a combination of hydrogen peroxide and sulfuric acid.
  • a catalyst that assists oxidation may be added as needed.
  • a catalyst that assists oxidation of sulfide can be generally used as the catalyst.
  • a ruthenium compound, a tungsten compound, a vanadium compound, These include molybdenum compounds, titanium compounds, and more preferably ruthenium compounds.
  • the ruthenium compound include ruthenium trichloride and ruthenium oxide.
  • the amount of these catalysts for Surufui de of starting material usually 0.0 to 1 mol% or more, or preferably 0.1 mole 0/0 or more, usually 1 0 0 mol% or less, preferably 2 0 mode % Or less.
  • the reaction is usually carried out at a temperature of at least 30 ° C, preferably at least 10 ° C, usually at a temperature of 120 ° C or less, preferably at a temperature of room temperature (25 ° C) or less. It is usually performed for 1 hour or more, usually for 48 hours or less, preferably for 6 hours or less.
  • benzyl mercaptan or a salt thereof is used.
  • Benzyl mercaptan is a compound having a structure of Ph CH 2 SH (wherein, Ph represents a phenyl group).
  • the salt of benzyl mercaptan include an alkali metal salt of benzyl mercaptan, an alkaline earth metal salt of benzyl mercaptan, and the like, and an alkali metal salt of benzyl mercaptan is preferably used.
  • the amount of benzyl mercaptan or a salt thereof added is usually 5% or more, preferably 10% or more, when the weight of benzyl mercaptan is expressed as a percentage (%) based on the volume of a mixed solvent of water and alcohol. 0% or less, preferably 50% or less Below.
  • the chlorodifluoromethane used in the second invention is a compound having a structure of CHF 2 C 1.
  • the amount of difluoromethane added is usually 1 mole or more, usually 5 moles or less, and preferably 3 moles or less, in molar ratio to benzyl mercaptan.
  • the base used in the second invention generally includes an alkali metal hydroxide, an alkaline earth metal hydroxide, ammonia, an organic amine, and the like.
  • an alkali metal hydroxide is used, More preferably, sodium hydroxide or hydroxide hydrate is used.
  • the amount of the base to be added is usually 1 mole or more, usually 5 moles or less, preferably 2 moles or less in molar ratio to benzyl mercaptan.
  • the second invention is characterized in that a water / alcohol mixture is used as a solvent.
  • the alcohol used for the mixed solvent is preferably an alcohol compatible with water, particularly preferably an alcohol having 1 to 3 carbon atoms. Specifically, methanol, ethanol and isopropanol are used, and preferably isopropanol is used.
  • the alcohol and the mixing ratio (volume ratio) of the mixed solvent differ depending on the type of alcohol.
  • Alcohol: water 1: 100 or more, preferably 50: 50 or more, usually 100: 1 or less , Preferably in the range of 95: 5 or less.
  • each component to the reactor and the reaction method are not particularly limited, but a preferable example is that a mixed solvent of alcohol and water is first prepared, and benzyl mercaptan or a salt thereof is added thereto. And then add a base to dissolve. Next, the reaction is carried out by introducing chlorodifluoromethane into the mixture, and benzinole (difluoromethyl) sulfide represented by the following formula (CHF 2 SCH 2 Ph (where Ph represents a fuel group))
  • the reaction temperature is usually at least 20 ° C, preferably at least 10 ° C, and usually at most 120 ° C, preferably at most 70 ° C.
  • the reaction time is generally 1 hour or longer, usually 120 hours or shorter, preferably 5 hours or shorter.
  • the reaction atmosphere is preferably replaced with an inert gas such as nitrogen or argon, and the solvent used in the reaction is preferably degassed to remove oxygen.
  • reaction product After completion of the reaction, extraction is performed according to a conventional method. Thereafter, the reaction product may be used in another reaction without isolation or purified by distillation or the like to isolate the reaction product.
  • the reaction temperature is usually 150 ° C. or higher, preferably 110 ° C. or higher, and usually 150 ° C. or lower, preferably 100 ° C. or lower.
  • the reaction time is generally 10 minutes or longer, preferably 30 minutes or longer, and usually 24 hours or shorter, preferably 10 hours or shorter.
  • a difluoromethylsulfenyl group By reacting the thus obtained difuromethylsulfenyl chloride with the pyrazole compound, a difluoromethylsulfenyl group can be introduced into the pyrazole compound.
  • the pyrazole compound to be reacted with difluoromethylsulfuryl chloride include a compound represented by the general formula (10).
  • R ⁇ R 2 s R 3 , X and n are as defined in general formula (2).
  • Difluoromethylsulfenyl chloride and a compound represented by the general formula (10) The compound represented by the general formula (9) can be produced by reacting
  • R ⁇ RR 3 , X, n have the same meaning as in general formula (2).
  • the compound represented by the general formula (9) is preferably, for example, methylphenyl) -1,4-difluoromethylsulfenyl-5- (pyridine-12-ylmethinoleamino) pyrazole-3-caprolpo-tolyl. No.
  • difluoromethylsulfuryl chloride reacts with the compound represented by the general formula (10). It is usually at least 0.5 molar equivalent, preferably at least 0.8 molar equivalent, and usually at most 10 molar equivalent, preferably at least 5 molar equivalent.
  • the reaction temperature is usually 0 ° C. or higher, usually 150 ° C. or lower, preferably 100 ° C. or lower.
  • the reaction time is usually 1 hour or longer, usually within 24 hours, preferably within 4 hours.
  • Solvents used in the reaction between difluoromethylsulfenyl chloride and the compound represented by the general formula (10) include aromatic hydrocarbons such as benzene, toluene and xylene; acetone, methylethylketone and the like. Ketones; halogenated hydrocarbons such as chloroform or methylene chloride; ether solvents such as ether, diisopropyl ether, and tetrahydrofuran; non-protonic polar solvents such as DMF and dimethyl sulfoxide; Of these, toluene and chloromethane are preferred.
  • the reaction is preferably performed in the presence of a base, and the base may be pyridine, Amines such as luminin are used. Examples>
  • the obtained crystals were dissolved in 130 OmL of ethyl acetate, dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the resulting crystals were collected by filtration.
  • the obtained crystals are washed with 10 OmL of hexane, and
  • the autoclave was cooled to 180 ° C and 2.
  • OmL of trifluoromethyl iodide (4.0 Og, 20.4 mM) was introduced into the reaction solution from a compressed cylinder.
  • the temperature of the reaction solution was returned to room temperature while stirring, and further stirred for one day.
  • 15 OmL of distilled water was poured into the solution while stirring, and extracted with ethyl acetate (200 mL ⁇ 3 times).
  • the combined ethyl acetate extracts were washed with distilled water (12 OmL) and dried over anhydrous magnesium sulfate.
  • the autoclave was cooled to -80 ° C, and 0.5 mL of trifluoromethyl iodide (1.0 Og, 5.1 OmM) was introduced into the reaction mixture from a compression pom- bane.
  • the temperature of the reaction solution was returned to room temperature while stirring, and further stirred for one day. Thereafter, the solution was poured into 20 mL of distilled water while stirring, and extracted with ethyl acetate (3 OmL ⁇ 3 times). The ethyl acetate extracts were combined, washed with distilled water (10 mL), and dried over anhydrous magnesium sulfate.
  • Diooyl disulfide OlOO g (0.916 mM) and DMF (4. OmL) were charged into a nitrogen-substituted 30 mL SUS autocrepe. While stirring, an aqueous solution (0.6 mL) containing potassium carbonate (0.253 g, 1.83 mM) and hydrazine monohydrate (0.185 g, 3.66 mM) was added. The autoclave was cooled to 180, and 0.5 mL of trifluoromethyl iodide (1. 00 g, 5.1 Omm o 1). The temperature of the reaction solution was returned to room temperature with stirring, and the mixture was further stirred for 2 days.
  • the autoclave was cooled to 180 ° C, and after introducing 0.18 g (0.92 mM, 4.1 eq) of trifluoromethylinochloride into the reaction solution, the autoclave was sealed. The temperature of the reaction solution was returned to room temperature with stirring, and the mixture was further stirred for 24 hours. The autoclave was opened, the reaction solution was poured into 2 OmL of water, and extracted with getileruthere (2 OmL X 3). The combined ether extracts were washed with distilled water and dried over anhydrous magnesium sulfate.
  • Example 8 5-amino-1,1- (2,6-dichloro-1,4-trifluoromethylphenyl) obtained in Example 8—4-trifluoromethylinoresolefinino-levirazonone-l-carbotrile 200 g, To a mixture of 56.2 g of formylpyrazine and 800 ml of toluene was added 6.0 g of pyridinum p-toluenesulfonate, and the mixture was heated under reflux for 27 hours while removing generated water. Further, 6.0 g of pyridium-p-toluenesulfonate was added, and the mixture was further heated under reflux for 10 hours, cooled with ice, and the generated crystals were filtered.
  • Example 10 8.25 g of benzinole (chlorodifluoromethinole) sulfy obtained in Example 10 was cooled to 0 ° C., and 4.2 g of chlorine gas was blown thereinto over 30 minutes while stirring. After stirring at the same temperature for 1 hour, a distillation apparatus was installed and heated to an internal temperature of 65 ° C to obtain 4.3 g of difluoromethylsulfuryl chloride (77% yield) as a fraction.
  • benzinole (chlorodifluoromethinole) sulfy obtained in Example 10 was cooled to 0 ° C., and 4.2 g of chlorine gas was blown thereinto over 30 minutes while stirring. After stirring at the same temperature for 1 hour, a distillation apparatus was installed and heated to an internal temperature of 65 ° C to obtain 4.3 g of difluoromethylsulfuryl chloride (77% yield) as a fraction.
  • a polyfluoroalkylation reaction with a polyfluoroalkyl halide is carried out in the presence of a disulfide as a raw material in the presence of an industrially easy-to-use auxiliary agent, to give a polyfluoroalkylsulfuel compound.
  • a disulfide as a raw material in the presence of an industrially easy-to-use auxiliary agent.
  • an industrially easy-to-use auxiliary agent to give a polyfluoroalkylsulfuel compound.

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Abstract

L'invention concerne un procédé de préparation de composés de polyfluoroalkylsulfényle par polyfluoroalkylation d'un disulfure avec un halogénure de polyfluoroalkyle en présence d'un assistant simple à utiliser industriellement, ainsi qu'un procédé de synthèse de sulfure de benzyl-difluorométhyle à rendement élevé au moyen d'un solvant simple à utiliser industriellement. L'invention concerne en particulier un procédé de préparation de composés de polyfluoroalkylsulfényle consistant à faire réagir un disulfure avec au moins un élément choisi parmi l'hydrazine et les borohydrures métalliques et un halogénure de polyfluoroalkyle.
PCT/JP2002/001558 2001-02-22 2002-02-21 Procede de preparation de composes de polyfluoroalkylsulfenyle WO2002066423A1 (fr)

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
JP2001046037A JP2002249485A (ja) 2001-02-22 2001-02-22 ポリフルオロアルキルスルフェニル化合物の製造方法
JP2001-46036 2001-02-22
JP2001-46037 2001-02-22
JP2001046036A JP2002249480A (ja) 2001-02-22 2001-02-22 ポリフルオロアルキルスルフェニル化合物の製造法
JP2001-318198 2001-10-16
JP2001318198A JP2003128644A (ja) 2001-10-16 2001-10-16 ベンジル（ジフルオロメチル）スルフィドの製造方法

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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005023776A1 (fr) 2003-09-04 2005-03-17 Bayer Cropscience S.A. Derives pesticides d'oxyalkylamino-1-arylpyrazole substitues en 5
US7371768B2 (en) * 2000-07-31 2008-05-13 Nihon Nohyaku Co., Ltd. Pyrazol derivatives, pest control agent comprising the same as active ingredient, and process for producing the same
US7517877B2 (en) 2002-03-05 2009-04-14 Merial Limited 5-substituted-alkylaminopyrazole derivatives as pesticides
US7569516B2 (en) 2003-12-24 2009-08-04 Bayer Cropscience Ag Plant growth regulation
WO2023056319A1 (fr) * 2021-09-28 2023-04-06 Northwestern University Minéralisation à basse température d'une substance perfluoroalkyle et polyfluoroalkyle dans des solvants aprotiques polaires

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EP0976737A1 (fr) * 1997-04-07 2000-02-02 Mitsubishi Chemical Corporation Derives de pyrazole, leur procede de preparation, intermediaires et pesticide comprenant ces derives comme composant actif

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EP0976737A1 (fr) * 1997-04-07 2000-02-02 Mitsubishi Chemical Corporation Derives de pyrazole, leur procede de preparation, intermediaires et pesticide comprenant ces derives comme composant actif

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CLAUDE WAKSELMAN ET AL.: "Reactions of bromotrifluoromethane and related halides: synthesis of trifluoromethyl sulfides from disulfides", J. CHEM. SOC., CHEM. COMMUN., no. 15, 1991, pages 993 - 994, XP002952299 *
GEORGE G.I. MOORE: "Fluoroalkanesulfonyl chlorides", J. ORG. CHEM., vol. 44, no. 10, 1979, pages 1708 - 1711, XP002952300 *

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7371768B2 (en) * 2000-07-31 2008-05-13 Nihon Nohyaku Co., Ltd. Pyrazol derivatives, pest control agent comprising the same as active ingredient, and process for producing the same
US7517877B2 (en) 2002-03-05 2009-04-14 Merial Limited 5-substituted-alkylaminopyrazole derivatives as pesticides
US7576107B2 (en) 2002-03-05 2009-08-18 Merial Limited 5-substituted-alkylaminopyrazole derivatives as pesticides
WO2005023776A1 (fr) 2003-09-04 2005-03-17 Bayer Cropscience S.A. Derives pesticides d'oxyalkylamino-1-arylpyrazole substitues en 5
US7879897B2 (en) 2003-09-04 2011-02-01 Merial Limited Pesticidal 5-substituted-oxyalkylamino-1-arylpyrazole derivatives
US7569516B2 (en) 2003-12-24 2009-08-04 Bayer Cropscience Ag Plant growth regulation
WO2023056319A1 (fr) * 2021-09-28 2023-04-06 Northwestern University Minéralisation à basse température d'une substance perfluoroalkyle et polyfluoroalkyle dans des solvants aprotiques polaires

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