WO2019208355A1 - Procédé de production d'un composé de trifluorométhyle thioalkyle, et composition de composé d'halogénure de trifluorométhyl thioalkyle - Google Patents

Procédé de production d'un composé de trifluorométhyle thioalkyle, et composition de composé d'halogénure de trifluorométhyl thioalkyle Download PDF

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WO2019208355A1
WO2019208355A1 PCT/JP2019/016449 JP2019016449W WO2019208355A1 WO 2019208355 A1 WO2019208355 A1 WO 2019208355A1 JP 2019016449 W JP2019016449 W JP 2019016449W WO 2019208355 A1 WO2019208355 A1 WO 2019208355A1
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trifluoromethylthioalkyl
formula
atom
compound
reaction
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Japanese (ja)
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信吾 安村
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Kumiai Chemical Industry Co Ltd
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Kumiai Chemical Industry Co Ltd
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Priority to IL278051A priority Critical patent/IL278051B2/en
Priority to CN201980012615.7A priority patent/CN111699172B/zh
Priority to JP2019565358A priority patent/JP6660518B1/ja
Publication of WO2019208355A1 publication Critical patent/WO2019208355A1/fr
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
    • C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
    • C07C323/01—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and halogen atoms, or nitro or nitroso groups bound to the same carbon skeleton
    • C07C323/02—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and halogen atoms, or nitro or nitroso groups bound to the same carbon skeleton having sulfur atoms of thio groups bound to acyclic carbon atoms of the carbon skeleton
    • C07C323/03—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and halogen atoms, or nitro or nitroso groups bound to the same carbon skeleton having sulfur atoms of thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated

Definitions

  • the present invention relates to a method for producing a trifluoromethylthioalkyl compound having a trifluoromethylthio group at one end of an alkyl chain and a halogen atom at the other end.
  • the present invention also relates to a composition comprising such a trifluoromethylthioalkyl halide compound.
  • the fluoroalkylthio group is a useful substituent in pharmaceutical and agrochemical compounds.
  • the pest control agent disclosed in Patent Document 1 has a trifluoroethylsulfinyl group and a trifluoromethylthioalkoxy group on the benzene ring, and the fluoroalkylthio group is important in the expression of the pest control activity. Have a role.
  • Patent Document 2 the hydroxy group of bromohexanol, which is a raw material, is acetyl protected, and after reacting a metal thiocyanate to synthesize a thiocyanate compound, the resulting thiocyanate compound is reacted with a trifluoromethylation reagent, The target trifluoromethylthiohexyl bromide is produced through deprotection and bromination of the group ("Reference Example 1" in this document).
  • Non-Patent Document 1 a target trifluoromethylthiohexyl bromide is produced in one step by performing a coupling reaction between a raw material bromohexaneboronic acid and a trifluoromethylthiolation reagent in the presence of a copper catalyst. Yes.
  • Non-Patent Document 2 bromoundecanoic acid as a raw material is reacted with a trifluoromethyl thiolating reagent in the presence of an iridium catalyst to produce the target trifluoromethyl thiodecyl bromide in one step.
  • Patent Document 4 describes a trifluoromethylthiolation reaction in which a raw material alkyl halide compound is reacted with thiophosgene in the presence of a fluorine compound.
  • the method described in Patent Document 4 is a method for producing a trifluoromethylthioalkyl compound from a low-reactivity alkyl halide compound using a single step and a less expensive raw material. It is superior to the conventional technology.
  • Patent Document 4 neither describes nor suggests a method for producing an alkyl compound having a trifluoromethylthio group at one end of an alkyl chain and a halogen atom at the other end.
  • Patent Documents 2 and 3 The method for producing a trifluoromethylthioalkyl halide compound disclosed in Patent Documents 2 and 3 is a very long process that requires 5 steps to produce the target compound, and is costly and labor-intensive, and is improved in terms of industrial production. It was desired.
  • the method for producing a trifluoromethylthioalkyl halide compound disclosed in Non-Patent Documents 1 and 2 can obtain the target compound in one step.
  • this method since it is necessary to use a special catalyst, a special ligand, a special reaction apparatus, etc., it costs.
  • the manufacturing method of these literatures is an excellent method as a laboratory manufacturing method, it cannot be said that it is preferable in terms of industrial manufacturing.
  • the trifluoromethyl thioating agent used in Non-Patent Documents 1 and 2 a portion not introduced into the product remains as an extra organic compound, which may adversely affect the subsequent reaction.
  • the yield of the target compound is low, and improvement has been desired from this aspect.
  • the present inventor has conducted extensive research on a method for producing a trifluoromethylthioalkyl halide compound.
  • a dihalogenated alkyl compound having halogen atoms at both ends as a raw material and adding thiophosgene while heating in the presence of a fluorine compound
  • the target trifluoromethylthioalkyl halide compound is obtained as follows: It has been found that it can be obtained in one step without using a special catalyst or the like. And based on this knowledge, it came to complete this invention.
  • this invention solves the said subject by providing the invention as described in the following [1] to [11].
  • Formula (1) (In the formula, X 1 represents a halogen atom selected from the group consisting of a fluorine atom, a chlorine atom, a bromine atom and an iodine atom, and n represents an integer in the range of 1 to 10.)
  • a method for producing a trifluoromethylthioalkyl halide compound, comprising adding thiophosgene while heating at 45 ° C. or higher in the presence of a dihalogenated alkyl compound represented by formula (I) and a fluorine compound.
  • X 1 represents a chlorine atom or a bromine atom
  • X 2 represents a bromine atom or an iodine atom
  • n shows 5 or 6
  • X 1 represents a chlorine atom or a bromine atom
  • X 2 represents a bromine atom or an iodine atom
  • n shows the integer of the range of 3 to 8
  • X 1 represents a chlorine atom
  • X 2 represents a bromine atom or an iodine atom
  • n shows 5 or 6
  • X 1 represents a chlorine atom
  • X 2 represents a bromine atom
  • n shows 5 or 6
  • the fluorine compound used in the reaction is tetramethylammonium fluoride, tetrabutylammonium fluoride, sodium fluoride, potassium fluoride, cesium fluoride or a mixture thereof.
  • Formula (1) (In the formula, X 1 represents a halogen atom selected from the group consisting of a fluorine atom, a chlorine atom, a bromine atom and an iodine atom, and n represents an integer in the range of 1 to 10.)
  • a trifluoromethylthioalkyl halide compound having a trifluoromethylthio group at one end of an alkyl chain and a halogen atom at the other end can be produced in a single step using relatively inexpensive raw materials and reagents. It is possible to provide a simple method. Moreover, according to this invention, it becomes possible to provide the composition containing such a trifluoromethylthioalkyl halide compound.
  • the halogen atom is a fluorine atom, a chlorine atom, a bromine atom or an iodine atom.
  • the present invention relates to formula (1): (In the formula, X 1 represents a halogen atom, and n represents an integer in the range of 1 to 10.)
  • a dihalogenated alkyl compound represented by the formula (I) and a fluorine compound thiophosgene is added while heating, a method for producing a trifluoromethylthioalkyl halide compound.
  • the present invention can produce the target trifluoromethylthioalkyl halide compound of the formula (1) in one step according to the following reaction formula. For this reason, as in the prior art, a multi-step process is not necessary for producing a trifluoromethylthioalkyl halide compound, and no special catalyst is required, so that it is an industrially preferred production method in terms of production cost. It is.
  • the compounds and reaction conditions used in the present invention will be described in detail.
  • the raw material used in the present invention is a dihalogenated alkyl compound represented by the formula (2), which is a known compound or can be produced from a known compound by a known method.
  • the dihalogenated alkyl compound of the formula (2) include bromochloromethane, dibromomethane, chloroiodomethane, bromoiodomethane, 1-bromo-2-chloroethane, 1,2-dibromoethane, 1-chloro-2-iodoethane.
  • dihalogenated alkyl compound of formula (2) preferably 1-bromo-3-chloropropane, 1,3-dibromopropane, 1-chloro-3-iodopropane, 1-bromo-4-chlorobutane, 1,4-dibromo Butane, 1-chloro-4-iodobutane, 1-bromo-5-chloropentane, 1,5-dibromopentane, 1-chloro-5-iodopentane, 1-bromo-6-chlorohexane, 1,6-dibromohexane 1-chloro-6-iodohexane, 1-bromo-7-chloroheptane, 1,7-dibromoheptane, 1-chloro-7-iodoheptane, 1-bromo-8-chlorooctane, 1,8-dibromooctane 1-chloro-8-iodooctan
  • X 1 and X 2 may be the same halogen atom or different halogen atoms. From the viewpoint of the yield of the target compound of the formula (1), X 1 and X 2 Are preferably different halogen atoms. Further, also in terms of yield, it is preferred that X 1 atomic number is smaller than the atomic number of the X 2. The reason is as follows.
  • X 1 and X 2 are both halogen atoms, both may be substituted with a trifluoromethylthio group by the reaction of a fluorine compound and thiophosgene. For this reason, by making X 1 and X 2 different halogen atoms, the trifluoromethylthio group is preferentially introduced into only one of the X 1 and X 2 with a difference in reactivity. This is because the desired formula (1) can be obtained in a high yield.
  • the atom with the atomic number of X 1 being X 2 It is preferably smaller than the number.
  • X 1 and X 2 are different halogen atoms from the viewpoint of reducing the by-product bis (trifluoromethylthio) alkyl compound (described later) of the formula (3). preferable. When many by-products are generated, the yield of the target compound of the formula (1) is lowered accordingly. Also from this point, it is preferable that X 1 and X 2 are different halogen atoms, and that the atomic number of X 1 is smaller than the atomic number of X 2 .
  • X 1 and X 2 are different halogen atoms from the viewpoint of reducing the unreacted formula (2).
  • the reaction is carried out in the step of producing an alkylphenyl sulfide derivative by reacting the compound of formula (1) (hereinafter sometimes referred to as “post-step”). It becomes a factor to inhibit.
  • post-step the step of producing an alkylphenyl sulfide derivative by reacting the compound of formula (1)
  • reducing unreacted Formula (2) is preferable not only from the viewpoint of the yield of the compound of Formula (1) but also from the viewpoint of reactivity in the subsequent steps.
  • X 1 and X 2 are different halogen atoms, thiophosgene preferentially nucleophilic attacks on one halogen atom, so that the yield increases and the amount of unreacted compound of formula (2) is reduced. Can do. From the same viewpoint, it is preferable X 1 atomic number is smaller than the atomic number of the X 2.
  • X 1 is preferably a chlorine atom or a bromine atom
  • X 2 is preferably a bromine atom or an iodine atom.
  • X 1 is a chlorine atom
  • X 2 is a bromine atom.
  • n in formula (2) is not particularly limited, but n is preferably in the range of 3 to 8, more preferably in the range of 4 to 7, and preferably 5 or 6. Particularly preferred.
  • the fluorine compound used in the present invention may be any fluorine compound as long as the reaction proceeds.
  • the fluorine compound used in the present invention include a tetraalkylammonium fluoride salt (eg, tetramethylammonium fluoride, tetrabutylammonium fluoride), an alkali metal fluoride salt (eg, sodium fluoride, fluoride). Potassium, cesium fluoride, etc.), alkaline earth metal fluoride salts (eg, magnesium fluoride, calcium fluoride, etc.), and mixtures thereof, but are not limited thereto.
  • a tetraalkylammonium fluoride salt eg, tetramethylammonium fluoride, tetrabutylammonium fluoride
  • an alkali metal fluoride salt eg, sodium fluoride, fluoride. Potassium, cesium fluoride, etc.
  • alkaline earth metal fluoride salts e
  • the fluorine compound used in the present invention preferably includes a tetraalkylammonium fluoride salt and an alkali metal fluoride salt, more preferably an alkali metal fluoride salt. It is done.
  • fluorine compound used in the present invention preferably include tetramethylammonium fluoride, tetrabutylammonium fluoride, sodium fluoride, potassium fluoride, cesium fluoride and the like, more preferably fluoride.
  • tetramethylammonium fluoride tetrabutylammonium fluoride
  • sodium fluoride potassium fluoride
  • cesium fluoride cesium fluoride
  • potassium fluoride is mentioned.
  • the form of potassium fluoride used in the present invention may be any form as long as the reaction proceeds, and those skilled in the art can appropriately select it.
  • potassium fluoride commercially available potassium fluoride can be used directly, and it can be used evenly dissolved in a solvent or partially dissolved.
  • the potassium fluoride includes potassium fluoride produced by a spray-drying method with a fine powder and a large specific surface area in terms of dissolution and dispersibility in a reaction organic solvent.
  • the amount of the fluorine compound used in the present invention may be any amount as long as the reaction proceeds. From the viewpoints of yield, by-product suppression, economic efficiency, etc., it is usually 3.0 mol or more, preferably 3.0 mol or more and 15.0 mol or less, relative to 1.0 mol of the dihalogenated alkyl compound of formula (2) More preferably, the range is 3.0 mol or more and 12.0 mol or less, more preferably 4.0 mol or more and 9.0 mol or less, and further preferably 4.0 mol or more and 7.0 mol or less.
  • thiophosgene form The form of thiophosgene used in the present invention may be any form as long as the reaction proceeds, and those skilled in the art can appropriately select it.
  • thiophosgene When thiophosgene is added dropwise, thiophosgene may be used directly without a solvent, or may be used in a state dissolved in a solvent.
  • dissolved in the solvent those skilled in the art can select from the solvent mentioned later suitably. However, this is not the case when thiophosgene is obtained as a solution other than the solvent described below.
  • the amount of thiophosgene used in the present invention may be any amount as long as the reaction proceeds. From the viewpoints of yield, by-product suppression, economic efficiency, etc., it is usually 0.9 mol or more and 5.0 mol or less, preferably 1.0 mol or more with respect to 1.0 mol of the dihalogenated alkyl compound of formula (2). Examples include a range of 3.0 mol or less, more preferably 1.0 mol or more and 2.0 mol or less, and still more preferably 1.0 mol or more and 1.5 mol or less.
  • the present invention is preferably carried out using a solvent.
  • the solvent used in the present invention may be any solvent as long as the reaction proceeds.
  • examples of the solvent used in the present invention include nitriles (for example, acetonitrile), ethers (for example, diethyl ether, diisopropyl ether, cyclopentyl methyl ether (CPME), tetrahydrofuran (THF), dioxane, monoglyme, diglyme and the like.
  • Carboxylic acid esters eg, ethyl acetate, butyl acetate, etc.
  • halogenated hydrocarbons eg, dichloromethane, chloroform, carbon tetrachloride, tetrachloroethane, etc.
  • aromatic hydrocarbons eg, benzene, chlorobenzene, Dichlorobenzene, nitrobenzene, toluene, xylene, etc.
  • amides eg, N, N-dimethylformamide (DMF), N, N-dimethylacetamide (DMAC), N-methylpyrrolidone (NMP), etc.
  • Zorinon compound such as 1,3-dimethyl-2-imidazolinone (DMI), etc.
  • sulfoxides e.g., dimethyl sulfoxide (DMSO) etc.
  • DMSO dimethyl sulfoxide
  • the solvent used in the present invention is preferably nitriles, ethers, aromatic hydrocarbons and amides, more preferably nitriles.
  • the solvent used in the present invention are preferably acetonitrile, propionitrile, diethyl ether, diisopropyl ether, cyclopentyl methyl ether (CPME), tetrahydrofuran (THF), 1,4-dioxane, monoglyme, diglyme, Benzene, chlorobenzene, dichlorobenzene, nitrobenzene, toluene, xylene, N, N-dimethylformamide (DMF), N, N-dimethylacetamide (DMAC), N-methylpyrrolidone (NMP) and the like, more preferably acetonitrile, A propionitrile etc. are mentioned, More preferably, acetonitrile is mentioned.
  • the acetonitrile used in the present invention is preferably dehydrated, but a person skilled in the art can appropriately adjust the dehydration method.
  • the amount of the solvent used in the present invention may be any amount as long as the reaction proceeds. From the viewpoints of yield, by-product suppression, economic efficiency, etc., usually 0.01 to 50 L (liter), preferably 0.1 to 15 L, relative to 1.0 mol of the dihalogenated alkyl compound of formula (2), A range of 0.1 to 10 L is more preferable, and a range of 0.1 to 5 L is more preferable.
  • reaction temperature The reaction temperature in the present invention may be any temperature as long as the reaction proceeds. From the viewpoint of yield, suppression of by-products and economic efficiency, the reaction temperature is usually 50 ° C. or higher and below the boiling point of the solvent used, preferably 50 ° C. or higher and 110 ° C. or lower, more preferably 60 ° C. or higher and 100 ° C. or lower. More preferably, a range of 70 ° C. or higher and 90 ° C. or lower can be exemplified.
  • reaction time The reaction time in the present invention is not particularly limited.
  • the reaction time in this invention can adjust the reaction time of this invention suitably for those skilled in the art. From the viewpoint of yield, by-product suppression, economic efficiency, etc., a range of usually 0.5 hours to 48 hours, preferably 1 hour to 36 hours, more preferably 1 hour to 24 hours can be exemplified.
  • reaction time means the time from immediately after the addition of the entire amount of thiophosgene to the end of the reaction.
  • the reaction time in the present invention is an aging period for consuming unreacted raw materials, and is distinguished from the addition time of thiophosgene.
  • the product produced by the present invention is a trifluoromethylthioalkyl halide compound represented by the formula (1).
  • the trifluoromethylthioalkyl halide compound of the formula (1) include chloromethyl (trifluoromethyl) sulfide, bromomethyl (trifluoromethyl) sulfide, chloroethyl (trifluoromethyl) sulfide, bromoethyl (trifluoromethyl) sulfide, and chloropropyl.
  • Trifluoromethyl sulfide bromopropyl (trifluoromethyl) sulfide, chlorobutyl (trifluoromethyl) sulfide, bromobutyl (trifluoromethyl) sulfide, chloropentyl (trifluoromethyl) sulfide, bromopentyl (trifluoromethyl) sulfide, Chlorohexyl (trifluoromethyl) sulfide, bromohexyl (trifluoromethyl) sulfide, chloroheptyl (trifluoromethyl) ) Sulfide, bromoheptyl (trifluoromethyl) sulfide, chlorooctyl (trifluoromethyl) sulfide, bromooctyl (trifluoromethyl) sulfide, chlorononyl (trifluoromethyl) sulfide, bromononyl (trifluorofluor
  • the trifluoromethylthioalkyl halide compound of formula (1) is preferably chloropropyl (trifluoromethyl) sulfide, bromopropyl (trifluoromethyl) sulfide, chlorobutyl (trifluoromethyl) sulfide, bromobutyl (trifluoromethyl) sulfide, chloro Pentyl (trifluoromethyl) sulfide, bromopentyl (trifluoromethyl) sulfide, chlorohexyl (trifluoromethyl) sulfide, bromohexyl (trifluoromethyl) sulfide, chloroheptyl (trifluoromethyl) sulfide, bromoheptyl (trifluoromethyl) ) Sulfide, chlorooctyl (trifluoromethyl) sulfide, bromooctyl (trifluoromethyl) sulfide, etc
  • Examples thereof include chloropentyl (trifluoromethyl) sulfide, bromopentyl (trifluoromethyl) sulfide, chlorohexyl (trifluoromethyl) sulfide, bromohexyl (trifluoromethyl) sulfide, and more preferably chloropentyl (trifluoromethyl).
  • a by-product In the production method of the present invention, a by-product may be generated depending on conditions.
  • a bis (trifluoromethylthio) alkyl compound represented by the following formula (3) can be exemplified.
  • the bis (trifluoromethylthio) alkyl compound of the formula (3) does not inhibit the reaction in the production of the alkylphenyl sulfide derivative, which is a subsequent step of the formula (1).
  • the compound of the formula (1) is a raw material for producing the alkylphenyl sulfide derivative and reacts with a trifluoroalkylthiophenol derivative in a later step (described later). In this step, the compound of the formula (3) inhibits the reaction. There is nothing to do. Therefore, even if the by-product of formula (3) remains, the production method of the present invention does not lower the reactivity in the subsequent step.
  • Addition conditions of thiophosgene The present invention is characterized in that thiophosgene is added to a raw material mixture containing the raw material compound of general formula (2) and a fluorine compound at an addition temperature of 45 ° C. or more and an addition time of 0.25 hours or more. .
  • thiophosgene is added to a raw material mixture containing the raw material compound of general formula (2) and a fluorine compound at an addition temperature of 45 ° C. or more and an addition time of 0.25 hours or more.
  • Addition of thiophosgene to the raw material mixture can be performed by a known method. For example, the method etc. which are dripped at a reaction system using a separating funnel, a dropping funnel, a burette, a syringe, etc. can be mentioned.
  • a small amount of thiophosgene is added over time, it is preferable to use a combination of a syringe and a syringe pump.
  • a method of dropping it into the reaction system using a metering pump, a dropping tank or the like can be mentioned.
  • the addition temperature of thiophosgene in the present invention can be appropriately adjusted by those skilled in the art if it is 45 ° C. or higher. From the viewpoints of yield, by-product suppression, economic efficiency, etc., the addition temperature is usually in the range of 45 ° C. or higher and the boiling point of the solvent used, preferably 50 ° C. or higher and 110 ° C. or lower. More preferably, the range of 60 degreeC or more and 100 degrees C or less can be illustrated, More preferably, the range of 70 degreeC or more and 90 degrees C or less can be illustrated.
  • “addition temperature” means the temperature of the reaction system immediately after the addition of thiophosgene.
  • the temperature of the thiophosgene is considered to have little effect on the reaction system, so the temperature of the raw material mixture at the time of addition should be the addition temperature. You can also.
  • the addition time of thiophosgene in the present invention can be appropriately adjusted by those skilled in the art as long as it is 0.25 hours (that is, 15 minutes) or longer.
  • the lower limit of the addition time in the present invention is preferably 0.5 hours or more, more preferably 1.0 hours or more, still more preferably 2.0 hours or more, and particularly preferably 3.5 hours. The above can be illustrated.
  • the upper limit of the addition time in the present invention is preferably 48 hours or less, more preferably 36 hours or less, still more preferably 24 hours or less, and particularly preferably 12 hours. The following can be illustrated.
  • the range of addition time in the present invention can be appropriately adjusted by those skilled in the art by combining the above lower limit and upper limit.
  • the combination of the upper limit and the lower limit of the addition time is, for example, preferably 0.5 hours to 48 hours, more preferably 1.0 hours to 36 hours, still more preferably 2.0 hours to 24 hours, and particularly preferably 3. Examples are 5 hours to 12 hours.
  • the “addition time” means the time from the start of adding thiophosgene to the reaction system until the completion of the addition of the entire amount to the reaction system.
  • the addition rate of thiophosgene with respect to 1 mol of dihalogenated alkyl compounds of Formula (2) is 10 mol / hour or less.
  • the composition of the trifluoromethylthioalkyl halide compound of the present invention will be described.
  • the composition of the trifluoromethylthioalkyl halide compound of the present invention comprises a trifluoromethylthioalkyl halide compound represented by the above formula (1), a bis (trifluoromethylthio) alkyl compound represented by the above formula (3), and Containing.
  • the bis (trifluoromethylthio) alkyl compound of the formula (3) is a by-product in the production method of the present invention, but does not inhibit the reaction in the production of the alkylphenyl sulfide derivative, which is a subsequent step of the formula (1). Therefore, there is no problem even if the expression (3) is included.
  • the composition of the present invention can be used as a raw material in an alkylphenyl sulfide derivative.
  • the content of the compound of the formula (3) is usually not more than 1 time, preferably not more than 0.1 times, based on the weight with respect to the content of the compound of the formula (1). More preferably, it is 0.01 times or less.
  • the ratio of the compound of the formula (3) to the compound of the formula (1) exceeds 1 time, the ratio of the by-product becomes too high, and the ratio of the compound of the formula (1) becomes low in the post-process. It is easy to deteriorate.
  • alkylphenyl sulfide derivative (post-process) will be described.
  • the trifluoromethylthioalkyl halide compound of formula 1 can be used for the production of alkylphenyl sulfide derivatives.
  • Alkylphenyl sulfide derivatives are useful as pest control agents or intermediates thereof.
  • the alkylphenyl sulfide derivative can be produced by the following formula.
  • m represents an integer of 0, 1, 2;
  • R 1 is a C1-C6 haloalkyl group (excluding 2-bromoethyl group), C2-C8 alkenyl group (excluding allyl group), C2-C8 haloalkenyl group, C2-C6 alkynyl group, C2-C6 halo An alkynyl group, a branched C4-C6 alkyl group (excluding an isobutyl group), a C3-C6 cycloalkyl C1-C6 alkyl group or a C3-C6 halocycloalkyl C1-C6 alkyl group,
  • R 2 represents a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C3-C6 cycloalkyl group, a C3-C6 halocycloalkyl group, a C1-C6 alkoxy group, a
  • the above reaction is performed in the presence of a base.
  • the base used in the above reaction may be any base as long as the reaction proceeds.
  • examples of the base include alkali metal hydroxides, alkali metal carbonates, and alkali metal hydrogen carbonates.
  • Preferable specific examples of the base for the above reaction include sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogen carbonate and potassium hydrogen carbonate, more preferably sodium carbonate. You may use the base in the said reaction individually or in combination of 2 or more types of arbitrary ratios.
  • the amount of the base used in the above reaction may be any amount as long as the reaction proceeds.
  • the above reaction may be performed in the presence of a catalytic amount of iodides.
  • iodides include sodium iodide and potassium iodide, and preferably sodium iodide.
  • the amount of iodide used may be any amount as long as the reaction proceeds.
  • the above reaction is preferably performed using a solvent. Any solvent may be used as long as the reaction proceeds.
  • the solvent preferably includes nitriles, ethers, aromatic hydrocarbons, and amides, and more preferably aromatic hydrocarbons and amides.
  • the solvent used in the above reaction preferably acetonitrile, propionitrile, diethyl ether, diisopropyl ether, cyclopentyl methyl ether (CPME), tetrahydrofuran (THF), 1,4-dioxane, chlorobenzene, dichlorobenzene , Toluene, xylene, N, N-dimethylformamide (DMF), N, N-dimethylacetamide (DMAC), N-methylpyrrolidone (NMP), etc., more preferably chlorobenzene, dichlorobenzene, toluene, xylene, N , N-dimethylformamide (DMF), N, N-dimethylacetamide (DMAC), N-methylpyrrolidone (NMP) and the like.
  • solvents can be used alone or as a mixed solvent having an arbitrary mixing ratio.
  • the amount of solvent used may be any amount as long as the reaction proceeds. Further, the ratio of the mixed solvent may be any ratio as long as the reaction proceeds.
  • the reaction temperature in the above reaction is not particularly limited as long as the reaction proceeds. From the viewpoint of yield, suppression of by-products and economic efficiency, the reaction temperature is usually 50 ° C. or higher and below the boiling point of the solvent used, preferably 50 ° C. or higher and 110 ° C. or lower, more preferably 60 ° C. or higher and 100 ° C. or lower. More preferably, a range from 70 ° C. to 90 ° C. can be exemplified.
  • the reaction time in the above reaction is not particularly limited as long as the reaction proceeds. From the viewpoint of yield, by-product suppression, economic efficiency, etc., a range of usually 0.5 hours to 48 hours, preferably 1 hour to 36 hours, more preferably 1 hour to 24 hours can be exemplified.
  • the alkylphenyl sulfide derivative Needless to say, it may be used for manufacturing.
  • Example 3 Production of (5-chloropentyl) trifluoromethyl sulfide
  • a stirrer, reflux condenser, thermometer and dropping funnel 5.57 g (30 mmol) of 1-bromo-5-chloropentane, 6.97 g (120 mmol) of potassium fluoride (spray-dried product), 12 mL o-xylene and 30 mL acetonitrile were added.
  • the components other than the solvent and the like in the reaction solution were 9-0.1% (6-chlorohexyl) trifluoromethyl sulfide, 1,6-bis ((tri Fluoromethyl) thio) hexane was 3.0%, and unreacted starting material 1-bromo-6-chlorohexane was 4.3%.
  • a part of the obtained reaction solution was isolated and purified by a method well known to those skilled in the art, and subjected to NMR measurement to confirm the following spectrum.
  • Example 6 Example 7 Except having changed the usage-amount of potassium fluoride and thiophosgene, operation similar to Example 5 was performed and Example 6 and Example 7 were implemented. The results are summarized in Table 1.
  • Example 5 shows that when the reaction was carried out using 1,5-dibromopentane having bromine atoms at both ends of the alkyl chain as a raw material, the target compound (5-bromopentyl) trifluoromethyl sulfide, This shows that a mixture of 1,5-bis ((trifluoromethyl) thio) pentane having both ends trifluoromethylthiolated and 1,5-dibromopentane, which is an unreacted raw material, is obtained.
  • Example 6 when the reaction was carried out using twice the amount of thiophosgene and potassium fluoride used in Example 5, the reaction proceeded rapidly and 1,5-bis ((trifluoromethyl) thio) Pentane was obtained quantitatively.
  • Example 7 the reaction was carried out using half the amount of thiophosgene and potassium fluoride used in Example 5 to obtain (5-bromopentyl) trifluoromethyl sulfide in a yield of 73%. It was. The result of Example 7 is better than that of Example 5, but 51% of unreacted raw material remains.
  • the starting material 1,5-dibromopentane is a known substance, and 1,5-dibromopentane can be found in literature (for example, the Journal of Organic Chemistry, 51 (12), 2206-2210, (1986)) and reagent catalogs. It is described that the boiling point of pentane is 111-112 ° C / 15 mmHg and 221 ° C / 760 mmHg. On the other hand, when the boiling point of (5-bromopentyl) trifluoromethyl sulfide was measured, they were 90 ° C./15 mmHg (actual measured value) and 210 ° C./760 mmHg (calculated value).
  • an industrially preferable method for producing an alkyl compound having a trifluoromethylthio group at one end of an alkyl chain and a halogen atom at the other end is provided.
  • an industrially preferable production method of an alkyl compound having a trifluoromethylthio group at one end of an alkyl chain and a halogen atom at the other end which does not require many steps until the production of the target compound. Is done.
  • an alkyl compound having a trifluoromethylthio group at one end of an alkyl chain and a halogen atom at the other end which does not require a special catalyst, a special ligand, a special reaction apparatus or the like.
  • a preferred manufacturing method is provided.
  • trifluoromethylthioalkyl halide compounds useful as medical pesticides and intermediates thereof can be produced on an industrial scale.
  • (5-chloropentyl) trifluoromethyl sulfide produced in Example 1 was prepared according to the method described in Reference Production Example 1, and 5-trifluoromethylthiopentyl [4-chloro-2-fluoro-5- (2,2 , 2-trifluoroethylthio) phenyl] ether and then an oxidation reaction disclosed in International Publication No. 2013/157229 can be derived into a compound having excellent pest control activity. Therefore, the present invention has a high industrial utility value.

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Abstract

L'invention concerne un procédé de production d'un composé d'halogénure de trifluorométhyl thioalkyle représenté par la formule (1) (dans laquelle X1 représente un atome d'halogène choisi dans le groupe constitué par un atome de fluor, un atome de chlore, un atome de brome et un atome d'iode ; et n représente un nombre entier de 1 à 10), le procédé étant caractérisé en ce qu'il comprend l'ajout de thiophosgène tout en chauffant à 45 °C ou plus en présence d'un composé alkyle dihalogéné représenté par la formule (2) (dans laquelle X2 représente un atome d'halogène choisi dans le groupe constitué par un atome de fluor, un atome de chlore, un atome de brome et un atome d'iode ; et X1 et n sont tels que définis ci-dessus) et un composé fluoré.
PCT/JP2019/016449 2018-04-25 2019-04-17 Procédé de production d'un composé de trifluorométhyle thioalkyle, et composition de composé d'halogénure de trifluorométhyl thioalkyle Ceased WO2019208355A1 (fr)

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IL278051A IL278051B2 (en) 2018-04-25 2019-04-17 A method for producing a thioalkyl trifluoromethyl compound and a thioalkyl trifluoromethyl halide compound
CN201980012615.7A CN111699172B (zh) 2018-04-25 2019-04-17 三氟甲硫基烷基化合物的制造方法和三氟甲硫基卤烷化合物的组合物
JP2019565358A JP6660518B1 (ja) 2018-04-25 2019-04-17 トリフルオロメチルチオアルキル化合物の製造方法及びトリフルオロメチルチオアルキルハライド化合物の組成物

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MUNA VALLI, S. ET AL.: "1-(Trimethylsilyl)-1, 2, 4- triazene: A novel free radical initiator", PHOSPHORUS, SULFUR AND SILICON AND THE RELATED ELEMENTS, vol. 177, no. 5, May 2002 (2002-05-01), pages 1109 - 1116, XP055649864 *

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