CN111699172B - Process for producing trifluoromethylsulfanylalkyl compound and trifluoromethylsulfanylalkyl compound composition - Google Patents
Process for producing trifluoromethylsulfanylalkyl compound and trifluoromethylsulfanylalkyl compound composition Download PDFInfo
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- C07—ORGANIC CHEMISTRY
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- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
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- 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
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Abstract
The present invention is a method for producing a trifluoromethylthio haloalkane compound represented by formula (1), wherein thiophosgene is added while heating at 45 ℃ or higher in the presence of a dihaloalkane compound represented by formula (2) and a fluorine compound, and X in formula (1) is 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, n represents an integer in the range of 1 to 10, and X in the formula (2) 2 Represents a halogen atom selected from the group consisting of a fluorine atom, a chlorine atom, a bromine atom and an iodine atom, X 1 And n is as defined above.
Description
Technical Field
The present invention relates to a method for producing a trifluoromethylsulfanyl compound having a trifluoromethylthio group at one end of an alkyl chain and a halogen atom at the other end. In addition, the present invention relates to compositions comprising such trifluoromethylsulfanyl haloalkane compounds.
Background
Fluoroalkylthio groups are useful substituents for pharmaceutical and agrochemical compounds. For example, a pest control agent disclosed in patent document 1 has trifluoroethylsulfinyl group and trifluoromethylsulfanyloxy group on the benzene ring, and fluoroalkylthio group plays an important role in the expression of pest control activity.
In order to produce pharmaceutical and agricultural chemical compounds having a trifluoromethylsulfanyl group, it is indispensable to produce a synthetic equivalent functioning as a trifluoromethylsulfanyl alkylating reagent, and various synthetic methods of trifluoromethylsulfanyl alkyl synthon (synthon) have been studied.
For example, in patent document 2, the hydroxyl group of bromohexanol as a raw material is protected with an acetyl group, a metal thiocyanate is reacted to synthesize a thiocyanate compound, the obtained thiocyanate compound is reacted with a trifluoromethylating agent, and the hydroxyl group is deprotected and brominated to produce the objective trifluoromethylsulfanyl bromohexane ("reference example 1" of this document).
[ solution 1]
For example, in patent document 3, the hydroxyl group of bromopentanol as a raw material is protected with an acetyl group, a metal thiocyanate is reacted to synthesize a thiocyanate compound, the obtained thiocyanate compound is reacted with a trifluoromethylating agent, and the target trifluoromethylthio-bromopentane is produced through deprotection and bromination of the hydroxyl group (examples 122 to 123, reference examples 2 to 3 of this document).
[ solution 2]
For example, in non-patent document 1, bromohexylboronic acid and a trifluoromethylthio reagent, which are raw materials, are subjected to a coupling reaction in the presence of a copper catalyst, thereby producing the objective trifluoromethylthio bromohexane in one step.
[ solution 3]
For example, in non-patent document 2, bromoundecanoic acid and a trifluoromethylthio reagent, which are raw materials, are reacted in the presence of an iridium catalyst to produce a target trifluoromethylthio bromodecane in one step.
[ solution 4]
Patent document 4 describes a trifluoromethylthionation reaction in which a starting haloalkane 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 trifluoromethylsulfanyl alkyl compound from a haloalkane compound having low reactivity by using a one-step (single step) and a lower-cost raw material, and is superior to the prior art known in the past in patent document 4. However, patent document 4 does not describe nor suggest 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.
Prior patent literature
Patent document
Patent document 1: WO2013/157229A1
Patent document 2: WO2015/122396A1
Patent document 3: WO2015/199109A1
Patent document 4: WO2016/076183A1
Non-patent document
Non-patent document 1: organic Letters,16 (18), 4738-4741 (2014)
Non-patent document 2: chemistry A European Journal,22 (14), 4753-4756 (2016)
Disclosure of Invention
Problems to be solved by the invention
In the methods for producing trifluoromethylthio haloalkane compounds disclosed in patent documents 2 and 3, 5 steps are required for producing the target compound, which is very long, and it is required to increase the cost and labor, and improvement in industrial production is desired.
On the other hand, the production methods of trifluoromethylsulfanyl haloalkane compounds disclosed in non-patent documents 1 and 2 can obtain the target compound in one step. However, in the present method, it is necessary to use a special catalyst, a special ligand, a special reaction apparatus, and the like, and therefore, it is costly. Therefore, the production methods of these documents are excellent as laboratory production methods, but are not preferable in terms of industrial production. Further, the trifluoromethylthio reagent used in non-patent documents 1 and 2 may have an adverse effect on the subsequent reaction because the part thereof not introduced into the product remains as an excess organic compound. Further, the present method is also expected to improve the yield of the target compound, because the yield is low.
The present invention aims to provide a method for producing a trifluoromethylthio haloalkane compound having a trifluoromethylthio group at one end of an alkyl chain and a halogen atom at the other end in one step using a relatively low-cost raw material or reagent. In addition, another object of the present invention is to provide a composition comprising such trifluoromethylsulfanyl haloalkane compound.
Means for solving the problems
In view of the above circumstances, the present inventors have made extensive studies on a method for producing a trifluoromethylsulfanyl haloalkane compound. As a result, it has been found that a target trifluoromethylsulfanyl halide compound can be obtained in one step by using a dihaloalkane compound having halogen atoms at both ends as a raw material and adding thiophosgene while heating in the presence of a fluorine compound, and that a special catalyst or the like is not required. Thus, the present invention has been completed based on this technical idea.
That is, the present invention solves the above problems by providing the inventions described in the following items [1] to [11 ].
[1] A process for producing a trifluoromethylthio haloalkane compound represented by the formula (1),
[ solution 5]
(in the formula, X 1 Represents a halogen atom selected from the group consisting of a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, n represents an integer in the range of 1 to 10),
the manufacturing method is characterized in that the manufacturing method,
adding thiophosgene while heating at 45 ℃ or higher in the presence of a dihaloalkane compound represented by the formula (2) and a fluorine compound,
[ solution 6]
(in the formula, X 2 Represents a halogen atom selected from the group consisting of a fluorine atom, a chlorine atom, a bromine atom and an iodine atom, X 1 And n is as defined above).
[2]Such as [1]]The process for producing a trifluoromethylsulfanyl halide compound, wherein X is 1 And X 2 Are halogen atoms, X, different from each other 1 Has an atomic number less than X 2 The atomic number of (2).
[3] The process for producing a trifluoromethylsulfanyl haloalkane compound according to [1], which comprises reacting a trifluoromethylsulfanyl halide compound,
X 1 represents a chlorine atom or a bromine atom,
X 2 represents a bromine atom or an iodine atom,
n represents 5 or 6.
[3' ] the process for producing a trifluoromethylsulfanyl haloalkane compound according to [1],
X 1 represents a chlorine atom or a bromine atom,
X 2 represents a bromine atom or an iodine atom,
n represents an integer ranging from 3 to 8.
[3"] the process for producing a trifluoromethylsulfanyl haloalkane compound according to [3],
X 1 represents a chlorine atom, and is a halogen atom,
X 2 represents a bromine atom or an iodine atom,
n represents 5 or 6.
[4] The process for producing a trifluoromethylsulfanyl haloalkane compound according to [1], which comprises reacting a trifluoromethylsulfanyl halide compound,
X 1 represents a chlorine atom, and represents a chlorine atom,
X 2 represents a bromine atom, and is represented by,
n represents 5 or 6.
[5] The process for producing a trifluoromethylsulfanyl haloalkane compound according to [1], which comprises reacting a trifluoromethylsulfanyl halide compound,
the addition of thiophosgene is carried out at a temperature in the range of 60 ℃ to 100 ℃.
[5' ] the process for producing a trifluoromethylsulfanyl haloalkane compound according to [5],
the addition of thiophosgene is carried out at a temperature in the range of 70 ℃ to 90 ℃.
[6] The process for producing a trifluoromethylsulfanyl haloalkane compound according to [1], which comprises reacting a trifluoromethylsulfanyl halide compound,
the fluorine compound used in the reaction is a tetraalkylammonium fluoride salt, an alkali metal fluoride salt or a mixture thereof.
[6' ] the process for producing a trifluoromethylsulfanyl haloalkane compound according to [6],
the fluorine compound used in the reaction is tetramethylammonium fluoride, tetrabutylammonium fluoride, sodium fluoride, potassium fluoride, cesium fluoride or a mixture thereof.
[6"] the process for producing a trifluoromethylsulfanyl haloalkane compound according to [6], wherein the fluorine compound used in the reaction is a fluorinated alkali metal salt.
[6' ] the process for producing a trifluoromethylsulfanyl haloalkane compound according to [6],
the fluorine compound used in the reaction is potassium fluoride.
[7] The process for producing a trifluoromethylsulfanyl haloalkane compound according to [1], which comprises reacting a trifluoromethylsulfanyl halide compound,
the fluorine compound is used in a range of 3.0 mol to 12.0 mol based on 1.0 mol of the compound of the formula (2).
[7' ] the process for producing a trifluoromethylsulfanylhaloalkane compound according to [7],
the fluorine compound is used in a range of 4.0 mol to 9.0 mol based on 1.0 mol of the compound of the formula (2).
[8] The process for producing a trifluoromethylsulfanyl haloalkane compound according to [1], which comprises reacting a trifluoromethylsulfanyl halide compound,
thiophosgene is used in an amount of 1.0 to 3.0 moles based on 1.0 mole of the compound of the formula (2).
[8' ] the process for producing a trifluoromethylsulfanyl haloalkane compound according to [8],
thiophosgene is used in an amount of 1.0 to 2.0 moles based on 1.0 mole of the compound of the formula (2).
[9] The process for producing a trifluoromethylsulfanyl haloalkane compound according to [1], which comprises reacting a trifluoromethylsulfanyl halide compound,
the reaction is carried out at a temperature in the range of 60 ℃ to 100 ℃.
[9' ] the process for producing a trifluoromethylsulfanylhaloalkane compound according to [9],
the reaction is carried out at a temperature in the range of 70 ℃ to 90 ℃.
[10] The production method according to [1], characterized in that,
the solvent used in the reaction is a nitrile, an ether, an amide, an aromatic hydrocarbon or a mixture thereof.
[10' ] the process for producing a trifluoromethylsulfanylhaloalkane compound according to [10],
the solvent used in the reaction is a nitrile.
[10"] the process for producing a trifluoromethylsulfanyl haloalkane compound according to [10],
the solvent used in the reaction was acetonitrile.
[11] A composition of trifluoromethylsulfanyl haloalkane compounds, which is characterized in that,
it comprises the following components: a trifluoromethylthio haloalkane compound represented by the formula (1); and a bis (trifluoromethylthio) alkyl compound represented by the formula (3),
[ solution 7]
(in the formula, X 1 Represents a halogen atom selected from the group consisting of a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, n represents an integer in the range of 1 to 10),
[ solution 8]
Effects of the invention
According to the present invention, a method for producing a trifluoromethylthio haloalkane compound having a trifluoromethylthio group at one end of an alkyl chain and a halogen atom at the other end in one step can be provided using a relatively low-cost raw material or reagent. In addition, according to the present invention, a composition comprising such a trifluoromethylsulfanyl haloalkane compound can be provided.
Detailed Description
1. The symbols and terms described in the present specification will be described.
The halogen atom means a fluorine atom, a chlorine atom, a bromine atom or an iodine atom.
2. The process for producing a trifluoromethylsulfanyl haloalkane compound of the present invention will be described.
The present invention is a method for producing a trifluoromethylthio haloalkane compound represented by the formula (1),
[ solution 9]
(in the formula, X 1 Represents a halogen atom, n representsAn integer in the range of 1 to 10),
the manufacturing method is characterized in that the manufacturing method comprises the following steps,
adding thiophosgene while heating in the presence of a dihaloalkane compound represented by the formula (2) and a fluorine compound,
[ solution 10]
(in the formula, X 2 Represents a halogen atom, X 1 And n is as defined above).
That is, the present invention can produce the target trifluoromethylsulfanyl halide compound of formula (1) in one step by the following reaction formula.
[ solution 11]
Therefore, since it is not necessary to perform a multi-step process for producing the trifluoromethylsulfanyl haloalkane compound as in the conventional art, and a special catalyst or the like is not necessary, it is an industrially preferable production method in terms of production cost or the like. Hereinafter, the compounds, reaction conditions, and the like used in the present invention will be described in detail.
(starting Compound)
The starting material used in the present invention is a dihaloalkane compound represented by the formula (2), and may be a known compound or may be produced from a known compound by a known method. <xnotran> (2) , , , , , 1- -2- ,1,2- , 1- -2- , 1- -2- , 1- -3- ,1,3- , 1- -3- , 1- -3- , 1- -4- ,1,4- , 1- -4- , 1- -4- , 1- -5- ,1,5- , 1- -5- , 1- -5- , 1- -6- ,1,6- , 1- -6- , 1- -6- , 1- -7- ,1,7- , 1- -7- , 1- -7- , 1- -8- ,1,8- , 1- -8- , 1- -8- , 1- -9- ,1,9- , 1- -9- , 1- -9- , 1- -10- , </xnotran> 1, 10-dibromodecane, 1-chloro-10-iododecane, 1-bromo-10-iododecane, and the like, but are not limited thereto.
The dihaloalkane compound of the formula (2) preferably includes 1-bromo-3-chloropropane, 1, 3-dibromopropane, 1-chloro-3-iodopropane, 1-bromo-4-chlorobutane, 1, 4-dibromobutane, 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-iodooctane and the like, more preferably includes 1-bromo-5-chloropentane, 1, 5-dibromopentane, 1-chloro-5-iodopentane, 1-bromo-6-chlorohexane, 1, 6-dibromohexane, 1-chloro-6-iodohexane and the like, and further preferably includes 1-bromo-6-chlorohexane, 1-bromohexane, 1-chloro-5-iodohexane, 1-bromohexane, 1-chloro-6-iodohexane and the like.
In the formula (2), X 1 And X 2 May be the same halogen atom or different halogen atoms, but X is preferably X from the viewpoint of the yield of the target compound represented by the formula (1) 1 And X 2 Are halogen atoms different from each other. Further, from the viewpoint of yield, X is preferred in the same manner 1 Has an atomic number less than X 2 The atomic number of (2). The reason is as follows.
X 1 And X 2 Since both are halogen atoms, both may be substituted with trifluoromethylthio group by the reaction of the fluorine compound with thiophosgene. Thus, by making X 1 And X 2 Being different halogen atoms, having reactivity at X 1 And X 2 With the difference therebetween, the target formula (1) can be obtained in a high yield by preferentially introducing trifluoromethylthio group into only one of them. Here, the reactivity of the halogen atom is F<Cl<Br<Order of I, so that X is preferentially substituted for trifluoromethylthio 2 Preferably X 1 Has an atomic number smaller than X 2 The atomic number of (2).
In addition, in the formula (2), X is also preferably X from the viewpoint of reducing the bis (trifluoromethylthio) alkyl compound of the formula (3) (described later) as a by-product 1 And X 2 Are halogen atoms different from each other. If a large amount of by-products are produced, the yield of the target compound of formula (1) is correspondingly reduced. From this point of view, X is also preferable 1 And X 2 Are halogen atoms different from each other, and X is more preferred 1 Has an atomic number less than X 2 The atomic number of (2).
Further, in the formula (2), X is also preferable from the viewpoint of reducing the amount of unreacted formula (2) 1 And X 2 Are halogen atoms different from each other. When the dihalogenated alkyl group of the formula (2) remains without being reacted, it becomes a factor of inhibiting the reaction in the subsequent step of producing the alkylphenyl sulfide derivative by reacting the compound of the formula (1) (hereinafter, may be referred to as "subsequent step"). Therefore, it is preferable to reduce the unreacted formula (2) not only in terms of the yield of the compound of formula (1), but also in terms of reactivity in the subsequent step. X 1 And X 2 When the halogen atoms are different from each other, thiophosgene preferentially attacks one halogen atom, so that the yield can be improved and the unreacted compound of formula (2) can be reduced. From the same viewpoint, X is preferred 1 Has an atomic number less than X 2 The atomic number of (2).
As X 1 And X 2 In combination of (1), preferably X 1 Is a chlorine atom or a bromine atom, X 2 Is a bromine atom or an iodine atom. In particular, X is preferably X from the viewpoint of the yield of the objective trifluoromethylthio-haloalkane compound of formula (1) 1 Is a chlorine atom, X 2 Is a bromine atom.
The value of n in formula (2) is not particularly limited, and n is preferably in the range of 3 to 8, more preferably in the range of 4 to 7, and particularly preferably 5 or 6.
(fluorine Compound)
The fluorine compound used in the present invention may be any fluorine compound as long as the reaction can be performed. Examples of the fluorine compound used in the present invention include, but are not limited to, tetraalkylammonium fluoride (e.g., tetramethylammonium fluoride, tetrabutylammonium fluoride, etc.), alkali metal fluoride (e.g., sodium fluoride, potassium fluoride, cesium fluoride, etc.), alkaline earth metal fluoride (e.g., magnesium fluoride, calcium fluoride, etc.), and mixtures thereof.
In view of reactivity, yield, economic efficiency and the like, the fluorine compound used in the present invention preferably includes tetraalkylammonium fluoride and alkali metal fluoride, and more preferably includes alkali metal fluoride.
Specific examples of the fluorine compound used in the present invention include tetramethylammonium fluoride, tetrabutylammonium fluoride, sodium fluoride, potassium fluoride, cesium fluoride, and the like, more preferably sodium fluoride, potassium fluoride, cesium fluoride, and the like, and further preferably potassium fluoride.
(form of potassium fluoride)
The form of potassium fluoride used in the present invention may be any form as long as the reaction can proceed, and can be appropriately selected by those skilled in the art. The potassium fluoride may be potassium fluoride which is generally commercially available as it is, or may be used in a state of being uniformly dissolved in a solvent or in a state of being partially dissolved. The potassium fluoride includes potassium fluoride produced by a spray drying method, and is a fine powder having a large specific surface area from the viewpoint of dissolution and dispersibility in a reaction organic solvent.
(amount of fluorine Compound)
The amount of the fluorine compound used in the present invention may be any amount as long as the reaction can be carried out. From the viewpoints of yield, by-product inhibition, economic efficiency, and the like, the following can be exemplified: the amount of the alkyl halide compound of the formula (2) is usually 3.0 mol or more, preferably 3.0 mol or more and 15.0 mol or less, more preferably 3.0 mol or more and 12.0 mol or less, still more preferably 4.0 mol or more and 9.0 mol or less, and still more preferably 4.0 mol or more and 7.0 mol or less based on 1.0 mol of the alkyl halide compound.
(forms of thiophosgene)
The form of the thiophosgene used in the present invention may be any form as long as the reaction can proceed, and can be appropriately selected by those skilled in the art. When thiophosgene is added dropwise, thiophosgene may be used as it is without a solvent, or may be used in a state of being dissolved in a solvent. When thiophosgene is used in a state of being dissolved in a solvent, a person skilled in the art can appropriately select from the solvents described later. However, the thiophosgene is not limited to the one obtained as a solution other than the solvent described later.
(amount of thiophosgene)
The amount of thiophosgene used in the present invention may be any amount as long as the reaction can be carried out. From the viewpoints of yield, by-product inhibition, economic efficiency, and the like, the following can be exemplified: the amount of the alkyl halide compound of the formula (2) is usually in the range of 0.9 to 5.0 moles, preferably 1.0 to 3.0 moles, more preferably 1.0 to 2.0 moles, and still more preferably 1.0 to 1.5 moles, based on 1.0 mole of the alkyl halide compound.
(solvent)
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 can be carried out. Examples of the solvent used in the present invention include, but are not limited to, nitriles (e.g., acetonitrile), ethers (e.g., diethyl ether, diisopropyl ether, cyclopentyl methyl ether (CPME), tetrahydrofuran (THF), dioxane, ethylene glycol dimethyl ether (Monoglyme), diethylene glycol dimethyl ether, etc.), carboxylic acid esters (e.g., ethyl acetate, butyl acetate, etc.), halogenated hydrocarbons (e.g., dichloromethane, chloroform, carbon tetrachloride, tetrachloroethane, etc.), aromatic hydrocarbons (e.g., benzene, chlorobenzene, dichlorobenzene, nitrobenzene, toluene, xylene, etc.), amides (e.g., N-Dimethylformamide (DMF), N-Dimethylacetamide (DMAC), N-methylpyrrolidone (NMP), etc.), imidazolinones (e.g., 1, 3-dimethyl-2-imidazolidinone (DMI), etc.), sulfoxides (e.g., dimethyl sulfoxide (DMSO), etc.), and the like. These solvents may be used alone or as a mixed solvent at an arbitrary mixing ratio.
From the viewpoints of reactivity, yield, economic efficiency, and the like, the solvent used in the present invention preferably includes nitriles, ethers, aromatic hydrocarbons, and amides, and more preferably includes nitriles.
Specific examples of the solvent used in the present invention include acetonitrile, propionitrile, diethyl ether, diisopropyl ether, cyclopentyl methyl ether (CPME), tetrahydrofuran (THF), 1, 4-dioxane, ethylene glycol dimethyl ether (Monoglyme), diglyme, benzene, chlorobenzene, dichlorobenzene, nitrobenzene, toluene, xylene, N-Dimethylformamide (DMF), N-Dimethylacetamide (DMAC), N-methylpyrrolidone (NMP), etc., more preferably include acetonitrile, propionitrile, etc., and still more preferably include acetonitrile.
The acetonitrile used in the present invention is preferably dehydrated, and the dehydration method can be appropriately adjusted by those skilled in the art.
(amount of solvent)
The amount of the solvent used in the present invention may be any amount as long as the reaction can be carried out. From the viewpoints of yield, by-product inhibition, economic efficiency, and the like, the following can be exemplified: the amount of the dihaloalkane compound of the formula (2) is usually in the range of 0.01 to 50L (liter), preferably 0.1 to 15L, more preferably 0.1 to 10L, and still more preferably 0.1 to 5L, relative to 1.0 mol of the dihaloalkane compound.
(reaction temperature)
The reaction temperature in the present invention may be any temperature as long as the reaction can be carried out. From the viewpoints of yield, by-product inhibition, economic efficiency, and the like, the reaction temperature may be, for example: usually 50 ℃ or higher and is a range of the boiling point of the solvent used or lower, preferably 50 ℃ or higher and 110 ℃ or lower, more preferably 60 ℃ or higher and 100 ℃ or lower, and further preferably 70 ℃ or higher and 90 ℃ or lower.
(reaction time)
The reaction time in the present invention is not particularly limited. With respect to the reaction time in the present invention, the reaction time in the present invention can be appropriately adjusted by those skilled in the art. From the viewpoints of yield, by-product inhibition, economic efficiency, and the like, the following can be exemplified: usually, it is in the range of 0.5 to 48 hours, preferably 1 to 36 hours, and more preferably 1 to 24 hours. The "reaction time" herein means a time from immediately after the addition of the total amount of thiophosgene to completion of the reaction. The reaction time in the present invention is a period of aging for consuming unreacted raw materials, which is different from the addition time of thiophosgene.
(Main product)
The product produced by the present invention is a trifluoromethylsulfanyl haloalkane compound represented by formula (1). Examples of the trifluoromethylthio-haloalkane compound of formula (1) include chloromethyl (trifluoromethyl) sulfide, bromomethyl (trifluoromethyl) sulfide, chloroethyl (trifluoromethyl) sulfide, bromoethyl (trifluoromethyl) sulfide, 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 (trifluoromethyl) sulfide, chlorodecyl (trifluoromethyl) sulfide, bromodecyl (trifluoromethyl) sulfide, and the like, but are not limited thereto.
The trifluoromethylthio haloalkane compound of the formula (1) preferably includes 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 and the like, more preferably includes chloropentyl (trifluoromethyl) sulfide, bromopentyl (trifluoromethyl) sulfide, chlorohexyl (trifluoromethyl) sulfide, bromohexyl (trifluoromethyl) sulfide and the like, and further preferably includes chloropentyl (trifluoromethyl) sulfide, chlorohexyl (trifluoromethyl) sulfide and the like.
(by-products)
In the production method of the present invention, by-products may be generated depending on conditions. Examples of the by-product include a bis (trifluoromethylthio) alkyl compound represented by the following formula (3).
[ solution 12]
The bis (trifluoromethylthio) alkyl compound of formula (3) does not inhibit the reaction in the production of the alkylphenyl sulfide derivative as the subsequent step of formula (1). The compound of formula (1) is a raw material for producing an alkylphenyl sulfide derivative, and is reacted with a trifluoroalkylthiophenol derivative in a subsequent step (described later), but in this step, the compound of formula (3) does not inhibit the reaction. Therefore, in the production method of the present invention, even if the by-product of formula (3) remains, the reactivity does not decrease in the subsequent step, and therefore, the reaction can be carried out more easily without removing the compound of formula (3) or purifying the compound of formula (1). Further, in the present invention, since only thiophosgene and potassium fluoride are used as raw materials, the remaining portion that is not introduced into the product becomes an inorganic salt and is easily removed by a washing operation with water. Therefore, the following advantages are also provided: there is little possibility that an excessive organic compound does not remain and an adverse effect is exerted in the subsequent step as in non-patent documents 1 and 2.
3. Thiophosgene addition conditions
The present invention is characterized in that thiophosgene is added to a raw material mixture containing a raw material compound of the general formula (2) and a fluorine compound at an addition temperature of 45 ℃ or higher for an addition time of 0.25 hours or longer. Hereinafter, the conditions for adding thiophosgene will be described in detail.
(method of addition)
The addition of thiophosgene to the raw material mixture can be carried out by a known method. For example, a method of adding dropwise to the reaction system using a separatory funnel, a dropping funnel, a burette, a syringe, or the like can be mentioned. In the case where it takes time to add a small amount of thiophosgene, it is preferable to use a syringe and a syringe pump in combination. When it takes time to add a large amount of thiophosgene to a reaction tank or the like, a method of dropping it into the reaction system using a metering pump, a dropping tank, or the like may be mentioned. When thiophosgene is added, it is preferable to stir the raw material mixture with a stirrer or the like for the purpose of carrying out the reaction.
(addition temperature)
The addition temperature of thiophosgene in the present invention may be appropriately adjusted by those skilled in the art as long as it is 45 ℃ or higher. From the viewpoints of yield, by-product inhibition, economic efficiency, and the like, the addition temperature may be, for example: usually 45 ℃ or higher and not higher than the boiling point of the solvent used, preferably 50 ℃ or higher and not higher than 110 ℃, more preferably 60 ℃ or higher and not higher than 100 ℃, and still more preferably 70 ℃ or higher and not higher than 90 ℃. Here, the "addition temperature" refers to the temperature of the reaction system immediately after the addition of thiophosgene. It is considered that if the amount of thiophosgene added to the raw material mixture at one time is relatively small, the influence of the thiophosgene temperature on the reaction system is small, and therefore the temperature of the raw material mixture at the time of addition may be set to the addition temperature.
(addition time)
The time for adding thiophosgene in the present invention is appropriately adjusted by those skilled in the art as long as it is 0.25 hours (i.e., 15 minutes) or more. In particular, from the viewpoint of improving the yield, the lower limit of the addition time in the present invention is as follows: preferably 0.5 hours or more, more preferably 1.0 hours or more, further preferably 2.0 hours or more, and particularly preferably 3.5 hours or more. In particular, from the viewpoints of byproduct suppression, economic efficiency, and the like, the upper limit of the addition time in the present invention may be, for example: preferably 48 hours or less, more preferably 36 hours or less, further preferably 24 hours or less, and particularly preferably 12 hours or less. The range of the addition time in the present invention can be appropriately adjusted by a person skilled in the art by combining the above-mentioned lower limit and upper limit. As a combination of the upper limit and the lower limit of the addition time, for example, there can be exemplified: preferably 0.5 to 48 hours, more preferably 1.0 to 36 hours, further preferably 2.0 to 24 hours, and particularly preferably 3.5 to 12 hours. However, the present invention is not limited to these combinations. Here, the "addition time" refers to a time from the start of the addition of thiophosgene to the reaction system to the end of the addition of the total amount to the reaction system.
The following conditions are particularly preferred as the time for adding thiophosgene.
The addition time (h) x (addition temperature (DEG C) -45) is not less than 10
Further, the addition rate of thiophosgene is preferably 10 mol/hr or less based on 1 mol of the dihaloalkane compound of the formula (2).
Further, thiophosgene is preferably added under the following conditions.
1 or more than the above-mentioned addition rate (mol/hr) × (the above-mentioned addition temperature (. Degree.C.) -45) or more than 400
4. The composition of the trifluoromethylsulfanyl haloalkane compound of the present invention will be described.
The trifluoromethylthio haloalkane composition of the present invention contains a trifluoromethylthio haloalkane compound represented by the above formula (1) and a bis (trifluoromethylthio) alkyl compound represented by the above formula (3).
The bis (trifluoromethylthio) alkyl compound of formula (3) is a by-product in the production process of the present invention, but does not inhibit the reaction in the production of the alkylphenyl sulfide derivative of formula (1) in the subsequent step, and therefore there is no problem even if formula (3) is contained. The composition of the present invention can be used as a raw material in an alkylphenyl sulfide derivative.
In the composition of the present invention, the content of the compound of formula (3) is usually 1 time or less, preferably 0.1 time or less, more preferably 0.01 time or less on a weight basis with respect to the content of the compound of formula (1). When the ratio of the compound of formula (3) to the compound of formula (1) exceeds 1 time, the ratio of by-products becomes too high, and the ratio of the compound of formula (1) becomes low in the subsequent step, so that the reactivity tends to be lowered.
5. The method for producing an alkylphenyl sulfide derivative (subsequent step) will be described.
The trifluoromethylsulfanyl haloalkane compound of formula 1 can be used for the production of an alkylphenyl sulfide derivative. The alkylphenyl sulfide derivative is useful as a pest control agent or an intermediate thereof. The alkyl phenyl sulfide derivative can be produced by the following formula.
[ solution 13]
(wherein m represents an integer of 0, 1 or 2,
R 1 represents a C1-C6 haloalkyl group (excluding 2-bromoethyl group), a C2-C8 alkenyl group (excluding allyl group), a C2-C8 haloalkenyl group, a C2-C6 alkynyl group, a C2-C6 haloalkynyl group, a branched C4-C6 alkyl group (excluding 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 C1-C6 haloalkoxy group, a cyano group or a nitro group,
R 3 represents a hydrogen atom, a halogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group).
The above reaction is carried out in the presence of a base. The base used in the above reaction may be any base as long as the reaction can be carried out. Examples of the base include alkali metal hydroxides, alkali metal carbonates, and alkali metal bicarbonates from the viewpoints of reactivity, yield, economic efficiency, and the like. Preferable specific examples of the base used in the above reaction include sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogencarbonate and potassium hydrogencarbonate, and more preferable examples include sodium carbonate. The base used in the above reaction may be used alone or in combination of 2 or more kinds in an arbitrary ratio. The amount of the base used in the above reaction may be any amount as long as the reaction can be carried out.
To promote the reaction, the reaction may be carried out in the presence of a catalytic amount of an iodide species. Examples of the iodide include sodium iodide and potassium iodide, and sodium iodide is preferably used. The iodide may be used in any amount as long as the reaction proceeds.
The above reaction is preferably carried out using a solvent. Any solvent may be used as long as the reaction can be carried out. From the viewpoints of reactivity, yield, economic efficiency, and the like, the solvent preferably includes nitriles, ethers, aromatic hydrocarbons, amides, and more preferably includes aromatic hydrocarbons and amides. Specific examples of the solvent used in the above reaction include acetonitrile, propionitrile, diethyl ether, diisopropyl ether, cyclopentyl methyl ether (CPME), tetrahydrofuran (THF), 1, 4-dioxane, chlorobenzene, dichlorobenzene, toluene, xylene, N-Dimethylformamide (DMF), N-Dimethylacetamide (DMAC), N-methylpyrrolidone (NMP), and the like, and more preferably include chlorobenzene, dichlorobenzene, toluene, xylene, N-Dimethylformamide (DMF), N-Dimethylacetamide (DMAC), N-methylpyrrolidone (NMP), and the like. These solvents may be used alone or as a mixed solvent at an arbitrary mixing ratio.
The solvent may be used in any amount as long as the reaction can be carried out. 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 can be carried out. From the viewpoints of yield, by-product inhibition, economic efficiency, and the like, the reaction temperature may be, for example: usually 50 ℃ or higher and is a range of the boiling point of the solvent used or lower, preferably 50 ℃ or higher and 110 ℃ or lower, more preferably 60 ℃ or higher and 100 ℃ or lower, and further preferably 70 ℃ or higher and 90 ℃ or lower. The reaction time in the above reaction is not particularly limited as long as the reaction proceeds. From the viewpoints of yield, by-product inhibition, economic efficiency, and the like, the following can be exemplified: usually, it is in the range of 0.5 to 48 hours, preferably 1 to 36 hours, and more preferably 1 to 24 hours.
In the above-mentioned method for producing an alkylphenyl sulfide derivative, even when the bis (trifluoromethylthio) alkyl compound of the formula (3) is present in a mixed state, the reaction is not inhibited or the like. Therefore, even if the bis (trifluoromethylthio) alkyl compound produced as a by-product in the method for producing a trifluoromethylthio haloalkane compound of the present invention is present in a mixed state, it can be used as it is for producing an alkylphenyl sulfide derivative. It is needless to say that the method for producing a trifluoromethylsulfanyl haloalkane compound of the present invention may be followed by producing a trifluoromethylsulfanyl haloalkane compound, removing a bis (trifluoromethylsulfanyl) alkyl compound as a by-product, and then using the resulting product in the production of an alkylphenyl sulfide derivative.
Examples
The production method of the present invention will be specifically described below with reference to examples, but the present invention is not limited to these examples.
In the present specification, the following apparatuses were used for the measurement of the physical properties in examples and reference production examples.
( 1 H nuclear magnetic resonance spectrum ( 1 H-NMR))
Varian Mercury-300, internal standard: tetramethylsilane (TMS)
(gas chromatography (GC) analysis method)
GC-2010 (manufactured by Shimadzu corporation) and a detection method: FID
For the GC analysis method, the following documents can be referred to as necessary.
(a) The method comprises the following steps (Co., ltd.) compiled by the society of Japan, "New Experimental chemistry lecture 9 analytical chemistry II", pp.60 to 86 (1977), the issuer Hoffy Uighur, and the pill Co., ltd. (for example, regarding the stationary phase liquid which can be used in the column, see pp.66)
(b) The method comprises the following steps The "Experimental chemistry lecture 20-1" 5 th edition, pages 121 to 129 (2007), the issuer Toyota Cheng Silang, the Boshan Kabushiki Kaisha (for example, as to a specific method of using a hollow capillary separation column, refer to pages 124 to 125)
(example 1)
Production of (5-chloropentyl) trifluoromethylsulfide
[ solution 14]
1.85g (10 mmol) of 1-bromo-5-chloropentane, 2.32g (40 mmol) of potassium fluoride (spray-dried product) and 20mL of acetonitrile were charged into a reaction flask equipped with magnetic stirring. While the mixture was stirred under heating reflux (temperature in the reaction system: 82 ℃ C.), 1.38g (12 mmol) of thiophosgene was added dropwise over 1 hour, and then the reaction mixture was stirred under heating reflux for 1 hour. The obtained reaction solution was analyzed by GC internal standard method using biphenyl as an internal standard substance, and as a result, the yield of (5-chloropentyl) trifluoromethylsulfide was 90.0%, the yield of 1, 5-bis ((trifluoromethyl) thio) pentane was 6.0%, and the recovery of 1-bromo-5-chloropentane as an unreacted raw material was 0.5%. A part of the obtained reaction solution was separated and purified by a method known to those skilled in the art, and NMR measurement was performed to confirm the following spectrum.
1 H-NMR(300MHz,CDCl3)δ(ppm)：
3.55(t,J＝6.6Hz,2H),2.90(t,J＝7.2Hz,2H),1.86-1.69(m,4H),1.62-1.54(m,2H)
(example 2)
Production of (5-chloropentyl) trifluoromethylsulfide
[ chemical 15]
To a reaction flask equipped with magnetic stirring were added 3.71g (20 mmol) of 1-bromo-5-chloropentane, 4.65g (80 mmol) of potassium fluoride (spray-dried product), and 30mL of acetonitrile. While the mixture was stirred under heating reflux (temperature in the reaction system was 82 ℃), 9.20g (24 mmol) of a 30% o-xylene solution of thiophosgene was added dropwise over 3 hours, and then the reaction mixture was stirred under heating reflux for 1 hour. The obtained reaction solution was analyzed by GC internal standard method using biphenyl as an internal standard substance, and as a result, the yield of (5-chloropentyl) trifluoromethylsulfide was 89.5%, the yield of 1, 5-bis ((trifluoromethyl) thio) pentane was 4.7%, and the recovery of 1-bromo-5-chloropentane as an unreacted raw material was 0.6%.
(example 3)
Production of (5-chloropentyl) trifluoromethylsulfide
[ solution 16]
5.57g (30 mmol) of 1-bromo-5-chloropentane, 6.97g (120 mmol) of potassium fluoride (spray-dried product), 12mL of o-xylene and 30mL of acetonitrile were charged into a four-necked flask equipped with a stirrer, a reflux condenser, a thermometer and a dropping funnel. While the mixture was stirred under heating reflux (temperature in the reaction system: 90 ℃ C.), 4.14g (36 mmol) of thiophosgene was added dropwise over 3 hours, and then the reaction mixture was stirred under heating reflux for 1 hour. As a result of analysis of the obtained reaction solution by GC area percentage method, regarding the components other than the solvent and the like in the reaction solution, 92.0% was obtained for (5-chloropentyl) trifluoromethylsulfide, 1.0% was obtained for 1, 5-bis ((trifluoromethyl) thio) pentane, and 3.0% was obtained for 1-bromo-5-chloropentane as an unreacted raw material.
Comparative example 1
Production of (5-chloropentyl) trifluoromethylsulfide
[ solution 17]
3.99g (20 mmol) of 1-bromo-5-chloropentane, 4.65g (80 mmol) of potassium fluoride (spray-dried product), and 40mL of acetonitrile were charged into a four-necked reaction flask equipped with a stirrer, a reflux condenser, a thermometer, and a dropping funnel. While the mixture was stirred at an internal temperature of 35 ℃ 2.76g (24 mmol) of thiophosgene was added dropwise over 3 hours, and then the reaction mixture was stirred at an internal temperature of 35 ℃ for 1 hour. As a result of analysis of the obtained reaction solution by GC area percentage method, with respect to the components other than the solvent and the like in the reaction solution, 9.9% of (5-chloropentyl) trifluoromethylsulfide, 0% of 1, 5-bis ((trifluoromethyl) thio) pentane, and 88.6% of 1-bromo-5-chloropentane as an unreacted raw material were obtained.
(example 4)
Production of (6-chlorohexyl) trifluoromethylthioether
[ solution 18]
To a reaction flask equipped with magnetic stirring were added 2.00g (10 mmol) of 1-bromo-6-chlorohexane, 2.32g (40 mmol) of potassium fluoride (spray-dried product), and 20mL of acetonitrile. While the mixture was stirred under heating reflux (temperature in the reaction system: 82 ℃ C.), 1.38g (12 mmol) of thiophosgene was added dropwise over 1 hour, and then the reaction mixture was stirred under heating reflux for 1 hour. The obtained reaction solution was analyzed by a GC area percentage method, and as a result, with respect to components other than the solvent and the like in the reaction solution, 90.1% of (6-chlorohexyl) trifluoromethylsulfide, 3.0% of 1, 6-bis ((trifluoromethyl) thio) hexane, and 4.3% of 1-bromo-6-chlorohexane as an unreacted raw material were obtained. A part of the obtained reaction solution was separated and purified by a method known to those skilled in the art, and NMR measurement was performed to confirm the following spectrum.
1 H-NMR(300MHz,CDCl3)δ(ppm)：
3.54(t,J＝6.6Hz,2H),2.89(t,J＝7.2Hz,2H),1.75(m,4H),1.47(m,4H)
(example 5)
Production of (5-bromopentyl) trifluoromethylthioether
[ solution 19]
To a reaction flask equipped with magnetic stirring were added 2.30g (10 mmol) of 1, 5-dibromopentane, 2.32g (40 mmol) of potassium fluoride (spray-dried product), and 20mL of acetonitrile. While the mixture was stirred under heating reflux (temperature in the reaction system: 82 ℃ C.), 1.38g (12 mmol) of thiophosgene was added dropwise over 1 hour, and then the reaction mixture was stirred under heating reflux for 1 hour. As a result of analysis of the obtained reaction mixture by a GC internal standard method using biphenyl as an internal standard substance, the yield of (5-bromopentyl) trifluoromethylsulfide was 45.2%, the yield of 1, 5-bis ((trifluoromethyl) thio) pentane was 26.5%, and the yield of 1, 5-dibromopentane as an unreacted raw material was 22.4%. A part of the obtained reaction solution was separated and purified by a method known to those skilled in the art, and NMR measurement was performed to confirm the following spectrum.
Process for preparation of (5-bromopentyl) trifluoromethylthioether 1 H-NMR Displacement)
1 H-NMR(300MHz,CDCl3)δ(ppm)：
3.39(t,J＝6.6Hz,2H),2.90(t,J＝7.2Hz,2H),1.90(m,2H),1.74(m,2H),1.57(m,2H)
Process for preparing (1, 5-bis ((trifluoromethyl) thio) pentane 1 H-NMR Displacement)
1 H-NMR(300MHz,CDCl3)δ(ppm)：
2.89(t,J＝7.2Hz,4H),1.74(quin,J＝7.2Hz,4H),1.55(m,2H)
(example 6, example 7)
The same operations as in example 5 were carried out except that the amounts of potassium fluoride and thiophosgene were changed, and example 6 and example 7 were carried out. The results are summarized in Table 1.
[ Table 1]
The results of example 5 show that, when 1, 5-dibromopentane having bromine atoms at both ends of the alkyl chain is reacted as a raw material, a mixture of (5-bromopentyl) trifluoromethylsulfide as a target compound, 1, 5-bis ((trifluoromethyl) thio) pentane having trifluoromethylthio) groups at both ends of the alkyl chain, and 1, 5-dibromopentane as an unreacted raw material is obtained.
In example 6, thiophosgene and potassium fluoride in an amount 2 times that used in example 5 were used to conduct the reaction, and as a result, the reaction rapidly proceeded to quantitatively obtain 1, 5-bis ((trifluoromethyl) thio) pentane.
In example 7, a reaction was carried out using 1 in 2 out of the amount used in example 5 of thiophosgene and potassium fluoride, and as a result, (5-bromopentyl) trifluoromethylsulfide was obtained in a yield of 73%. The result of example 7 was better than that of example 5, but 51% of the unreacted raw material remained.
1, 5-dibromopentane as a raw material is a known substance, and it is described in the literature (for example, the Journal of Organic Chemistry,51 (12), 2206-2210 (1986), etc.) or in the catalogues of reagents, etc. that 1, 5-dibromopentane has a boiling point of 111 to 112 ℃/15mmHg and 221 ℃/760mmHg. On the other hand, the boiling point of (5-bromopentyl) trifluoromethylsulfide was measured, and the results were 90 ℃/15mmHg (measured value) and 210 ℃/760mmHg (calculated value).
As described above, 1, 5-dibromopentane and (5-bromopentyl) trifluoromethylsulfide have boiling points very close to each other, and separation and purification based on a distillation operation are difficult. Therefore, from the viewpoint of industrial production, it is preferable to reduce the unreacted raw materials as in examples 1 to 4.
(reference production example 1)
Preparation of 5-trifluoromethylsulfanyl pentyl [ 4-chloro-2-fluoro-5- (2, 2-trifluoroethylthio) phenyl ] ether
[ solution 20]
To a reaction vessel equipped with magnetic stirring were added 10.1g (30 mmol) of 4-chloro-2-fluoro-5- (2, 2-trifluoroethylthio) phenol having a purity of 77.1%, 7.7g (33 mmol) of (5-chloropentyl) trifluoromethylsulfide having a purity of 88.2%, 3.5g (33 mmol) of sodium carbonate, 0.45g (3 mmol) of sodium iodide and 15mL of N, N-dimethylformamide, and the mixture was stirred at 90 ℃ for 8 hours. After completion of the reaction, the reaction mixture was cooled, and 4.8g of a 25% aqueous sodium hydroxide solution and 30mL of water were added to conduct extraction with 15mL of dichloromethane. The organic layer and water were partitioned, and 5-trifluoromethylsulfanylpentyl [ 4-chloro-2-fluoro-5- (2, 2-trifluoroethylthio) phenyl ] ether was obtained as a dichloromethane solution (31.9 g). The obtained methylene chloride solution was analyzed by an LC absolute calibration curve method, and the purity was 36.6% and the yield was 90.3%. A part of the obtained methylene chloride solution was separated and purified by a method known to those skilled in the art, and NMR measurement was performed to confirm the following spectrum.
1 H-NMR(300MHz,CDCl3)δ(ppm)：
7.23(d,J＝3.9Hz,1H),7.20(d,J＝6.0Hz,1H),4.03(t,J＝6.3Hz,2H),3.41(q,J＝9.9Hz,2H),2.92(t,J＝7.2Hz,2H),1.90-1.74(m,4H),1.66-1.58(m,2H)
Reference production examples 2, 3, 4 and 5 were carried out in the same manner as in reference production example 1 except that the kind and amount of the solvent were changed. The results are summarized in Table 2.
[ Table 2]
Industrial applicability
According to the present invention, there 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.
According to the present invention, there 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 before the production of the target compound.
According to the present invention, there 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, without requiring a special catalyst, a special ligand, a special reaction apparatus, or the like.
According to the present invention, there 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 can yield a target compound in high yield.
Further, according to the present invention, trifluoromethylsulfanyl halide compounds useful as pharmaceutical and agricultural chemicals and intermediates thereof can be produced on an industrial scale.
For example, a compound having excellent pest control activity can be derived from (5-chloropentyl) trifluoromethylsulfide produced in example 1 by preparing 5-trifluoromethylsulfanyl-pentyl [ 4-chloro-2-fluoro-5- (2, 2-trifluoroethylthio) phenyl ] ether by the method described in reference production example 1 and then subjecting the ether to an oxidation reaction disclosed in, for example, international publication No. 2013/157229.
Therefore, the invention has high industrial utilization value.
Claims (7)
1. A process for producing a trifluoromethylthio haloalkane compound represented by the formula (1),
[ solution 1]
In the formula, X 1 Represents a chlorine atom, n represents 5 or 6,
the manufacturing method is characterized in that the manufacturing method comprises the following steps,
adding thiophosgene while heating at 45 ℃ or higher in the presence of a dihaloalkane compound represented by the formula (2) and a fluorine compound,
[ solution 2]
In the formula, X 1 Represents a chlorine atom, X 2 Represents a bromine atom, n represents 5 or 6,
the product of the production process has a content of the compound of formula (3) of 0.1 times or less by weight relative to the content of the compound of formula (1),
wherein n represents 5 or 6.
2. A process for producing a trifluoromethylsulfanyl haloalkane compound according to claim 1, wherein,
the addition of thiophosgene is carried out at a temperature in the range of 60 ℃ to 100 ℃.
3. A process for producing a trifluoromethylsulfanyl haloalkane compound according to claim 1, wherein,
the fluorine compound used in the reaction is a tetraalkylammonium fluoride salt, an alkali metal fluoride salt or a mixture thereof.
4. A process for producing a trifluoromethylsulfanyl haloalkane compound according to claim 1, wherein,
the fluorine compound is used in a range of 3.0 mol to 12.0 mol based on 1.0 mol of the compound of the formula (2).
5. A process for producing a trifluoromethylsulfanyl haloalkane compound according to claim 1, wherein,
thiophosgene is used in a range of 1.0 mol to 3.0 mol with respect to 1.0 mol of the compound of the formula (2).
6. A process for producing a trifluoromethylsulfanyl haloalkane compound according to claim 1, wherein,
the reaction is carried out at a temperature in the range of 60 ℃ to 100 ℃.
7. A process for producing a trifluoromethylsulfanyl haloalkane compound according to claim 1, wherein,
the solvent used in the reaction is a nitrile, an ether, an amide, an aromatic hydrocarbon or a mixture thereof.
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| Publication number | Publication date |
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| TWI719457B (en) | 2021-02-21 |
| IL278051B1 (en) | 2023-08-01 |
| IL278051A (en) | 2020-11-30 |
| TW201945335A (en) | 2019-12-01 |
| JP6660518B1 (en) | 2020-03-11 |
| WO2019208355A1 (en) | 2019-10-31 |
| IL278051B2 (en) | 2023-12-01 |
| JPWO2019208355A1 (en) | 2020-04-30 |
| CN111699172A (en) | 2020-09-22 |
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