JPWO2017033813A1 - Process for producing alkenyl halide - Google Patents

Abstract

（Ｒは水素原子またはメチル基を表し、Ｗは炭素数２〜１０の２価の飽和炭化水素基を表す）
で表されるアルケニルアルコールを下記一般式（２）
【化２】

（Ｘは塩素原子、臭素原子またはヨウ素原子を表す）
で表されるハロゲン化チオニルと反応させる、下記一般式（３）
【化３】

（Ｒ、Ｗ、Ｘは前記定義のとおりである）
で表されるアルケニルハライドの製造方法であって、
前記塩基の使用量がアルケニルアルコール（１）１モルに対して０．００１〜０．３モルであり、
前記溶媒が炭化水素および／またはハロゲン化炭化水素であり、
前記反応における反応温度が６０〜１４０℃であることを特徴とする前記アルケニルハライドの製造方法。The following general formula (1) in a solvent in the presence of a base
[Chemical 1]

(R represents a hydrogen atom or a methyl group, and W represents a divalent saturated hydrocarbon group having 2 to 10 carbon atoms)
An alkenyl alcohol represented by the following general formula (2)
[Chemical formula 2]

(X represents a chlorine atom, a bromine atom or an iodine atom)
The following general formula (3) is reacted with thionyl halide represented by
[Chemical 3]

(R, W and X are as defined above)
A process for producing an alkenyl halide represented by:
The amount of the base used is 0.001 to 0.3 mol with respect to 1 mol of alkenyl alcohol (1),
The solvent is a hydrocarbon and / or a halogenated hydrocarbon;
The method for producing the alkenyl halide, wherein a reaction temperature in the reaction is 60 to 140 ° C.

Description

  The present invention relates to a novel method for producing an alkenyl halide having a carbon-carbon double bond at one molecular end and a halogen atom at the other molecular end.

Alkenyl halides having a carbon-carbon double bond at one molecular end and a halogen atom at the other molecular end are useful as raw materials for pharmaceuticals, agricultural chemicals, various chemicals, resins, coupling agents and the like.
Conventionally, as a method for producing the alkenyl halide, for example, (1) a method in which alkenyl alcohol having a carbon-carbon double bond at one molecular end and a hydroxyl group at the other molecular end is chlorinated using thionyl chloride. (See Patent Document 1 and Non-Patent Document 1),
(2) A method of reacting hydrogen chloride with a diene having a carbon-carbon double bond at both ends of the molecule (see Non-Patent Document 2),
(3) A method in which an alkenyl alcohol having a carbon-carbon double bond at one molecular terminal and a hydroxyl group at the other molecular terminal is reacted with paratoluenesulfonyl chloride and then reacted with lithium chloride (Non-patent Document 3) reference),
(4) Gas phase reaction in a catalyst having nickel or copper supported on activated carbon with a dichloro compound having a chlorine atom at one molecular end and a chlorine atom bonded to the carbon atom adjacent to the carbon atom at the other molecular end (See Non-Patent Document 4),
(5) A method of reacting 2-methyl-2-propenyl chloride and diazomethane under a copper chloride catalyst (see Non-Patent Document 5),
Etc. are known.

JP-A-63-112531

Journal of the American Chemical Society, 83, 2719, 1961 Bashkirskii Kimicheskii Zhurnal, Vol. 15, No. 4, p. 54, 2008 Anales de Quimica, Series C: Quimica Organica Bioquimica, 84, 1, 105, 1988 Izvestiya Vysshikh Uchebnykh Zavedenii, Kimiya i Kimicheskaya Teknologya, Vol. 22, No. 142, 1979 Chemische Berichte, 99, 9, 2855, 1966

  However, in any of the above methods (1) to (5), the yield of the target alkenyl halide is low, and many by-products such as structural isomers and dienes having different double bond positions are produced. It interferes with industrial production. In the method (1), which is widely used, an equal amount of tertiary amine is added to capture the generated hydrogen chloride, and a larger amount of waste is generated than the amount of product obtained by the reaction. In order to avoid this, a tertiary amine is used as a catalytic amount. The generated hydrogen chloride further reacts with the target alkenyl halide, and the dichloro compound becomes the main product, which cannot be employed. From the above, in the above methods (1) to (5), it is industrially inexpensive to produce an alkenyl halide having a carbon-carbon double bond at one molecular terminal and a halogen atom at the other molecular terminal. It was difficult.

  Therefore, the object of the present invention is to produce an alkenyl halide having a carbon-carbon double bond at one molecular terminal and a halogen atom at the other molecular terminal, in a favorable yield and at low cost, and advantageously industrially. It is to provide a method.

  As a result of intensive studies, the present inventors have reacted an alkenyl alcohol having a carbon-carbon double bond at one molecular end and a hydroxyl group at the other molecular end with thionyl halide in a hydrocarbon at 60 to 140 ° C. Even when the amount of base used is reduced to a catalytic amount, dichloro compounds in which hydrogen chloride is added to the terminal double bond of alkenyl alcohol and structural isomers with different positions of the double bond are greatly generated. It was found that an alkenyl halide having a carbon-carbon double bond at one molecular terminal and a halogen atom at the other molecular terminal was obtained in a high yield. .

That is, the present invention
[1] The following general formula (1) in a solvent in the presence of a base

(R represents a hydrogen atom or a methyl group, and W represents a divalent saturated hydrocarbon group having 2 to 10 carbon atoms)
An alkenyl alcohol represented by the following general formula (2)

(X represents a chlorine atom, a bromine atom or an iodine atom)
The following general formula (3) is reacted with thionyl halide represented by

(R, W and X are as defined above)
A process for producing an alkenyl halide represented by:
The amount of the base used is 0.001 to 0.3 mol with respect to 1 mol of alkenyl alcohol (1),
The solvent is a hydrocarbon and / or a halogenated hydrocarbon;
The method for producing the alkenyl halide, wherein a reaction temperature in the reaction is 60 to 140 ° C.
[2] The production method of [1], wherein the base is selected from a tertiary amine or a nitrogen-containing aromatic compound.
[3] The production method of [1] or [2], wherein the amount of the base used is 0.01 to 0.1 mol with respect to 1 mol of the alkenyl alcohol.
I will provide a.

  According to the present invention, an alkenyl halide having a carbon-carbon double bond at one molecular end and a halogen atom at the other molecular end can be produced industrially advantageously at a good yield and at a low cost. .

  The production method of the present invention comprises the following general formula (1) in a solvent in the presence of a base.

(R represents a hydrogen atom or a methyl group, and W represents a divalent saturated hydrocarbon group having 2 to 10 carbon atoms)
(Hereinafter referred to as alkenyl alcohol (1)) represented by the following general formula (2)

(X represents a chlorine atom, a bromine atom or an iodine atom)
The following general formula (3) is reacted with thionyl halide represented by the formula (hereinafter referred to as thionyl halide (2)).

(R, W and X are as defined above)
A method for producing an alkenyl halide represented by the following (hereinafter referred to as alkenyl halide (3)),
The amount of the base used is 0.001 to 0.3 mol with respect to 1 mol of alkenyl alcohol (1), the solvent is a hydrocarbon and / or a halogenated hydrocarbon, and the reaction temperature in the reaction is 60 to 140 ° C.

In the general formulas (1) and (3), W represents a divalent saturated hydrocarbon group having 2 to 10 carbon atoms. Here, the divalent saturated hydrocarbon group refers to a divalent hydrocarbon group having no double bond or triple bond.
W may be linear, branched or cyclic, and is preferably linear or branched, more preferably linear.
Examples of W include ethane-1,1-diyl group, ethane-1,2-diyl group, propane-1,1-diyl group, propane-1,2-diyl group, propane-1,3-diyl group , Pentane-1,5-diyl group, hexane-1,6-diyl group, cyclohexane-1,4-diyl group and the like.
W is preferably a saturated hydrocarbon group having 2 to 10 carbon atoms, more preferably a saturated hydrocarbon group having 2 to 6 carbon atoms, still more preferably a saturated hydrocarbon group having 2 carbon atoms, and an ethane-1,2-diyl group. Is most preferred.

  In the general formulas (2) and (3), X is preferably a chlorine atom.

  Among them, alkenyl alcohol (1) is 3-methyl-3-buten-1-ol (hereinafter referred to as IPEA), thionyl halide (2) is thionyl chloride, and alkenyl halide (3) is 3-methyl. It is preferably -3-butenyl chloride (hereinafter referred to as IPEC).

  The amount of thionyl halide (2) used is preferably in the range of usually 0.8 to 5 mol times relative to alkenyl alcohol (1), and from the viewpoint of economy and ease of post-treatment, it is 1 to 3 mol times. A range is more preferred.

The production method of the present invention is carried out in the presence of a base. Examples of the base include tertiary amines such as triethylamine, tributylamine, trioctylamine, triallylamine, diisopropylethylamine, 1,4-diazabicyclo [2.2.2] octane; pyridine, 2-picoline, 2,6 -Nitrogen-containing heterocyclic aromatic compounds such as lutidine. Of these, tertiary amines are preferable, and triethylamine is more preferable.
The amount of the base used is preferably in the range of usually 0.001 to 0.3 mol times the alkenyl alcohol (1), and 0.01 to 0.1 mol times from the viewpoint of economy and ease of post-treatment. The range of is more preferable.

The solvent used in the production method of the present invention is a hydrocarbon and / or a halogenated hydrocarbon. By using hydrocarbons and / or halogenated hydrocarbons as the solvent, the solubility of the hydrogen halide generated in the reaction can be lowered, quickly removed from the reaction system, and the formation of by-products can be suppressed.
The hydrocarbon and / or halogenated hydrocarbon is not particularly limited as long as it does not participate in the reaction.
Examples of the hydrocarbon include aliphatic hydrocarbons such as n-pentane, n-hexane, n-heptane, n-octane and cyclohexane; and aromatic hydrocarbons such as benzene, toluene, xylene and mesitylene.
Examples of the halogenated hydrocarbon include halogenated aromatic hydrocarbons such as chlorobenzene and fluorobenzene; halogenated aliphatic hydrocarbons such as dichloromethane, chloroform and 1,2-dichloroethane.
The said solvent may be used individually by 1 type, and may mix and use 2 or more types.
Although there is no restriction | limiting in particular in the usage-amount of a solvent, It is preferable that it is 0.1-100 mass times normally with respect to alkenyl alcohol (1), and it is more preferable that it is 0.5-50 mass times, More preferably, it is 35 mass times.

  The reaction temperature in the manufacturing method of this invention is 60-140 degreeC, and it is preferable that it is 70-100 degreeC. When the temperature is lower than 60 ° C., the reaction rate from the reaction intermediate halosulfite ester to the target product becomes very slow, and the hydrogen halide is not quickly excluded from the reaction system. There is a tendency that the amount of by-products produced by the addition of hydrogen halides to the product increases. When the temperature is higher than 140 ° C., there is a problem in the stability of the product, and diene polymerization and isomerization generated by decomposition tend to occur. In addition, decomposition of thionyl halide (2) is promoted, and the intended reaction may not proceed. While the reaction time varies depending on the type and amount of alkenyl alcohol (1), base, thionyl halide (2) and solvent used, it is usually in the range of 5 minutes to 48 hours.

In the production method of the present invention, for example, an alkenyl alcohol (1), a base, and a solvent are mixed with cooling in a batch reactor, and after thionyl halide (2) is added, the mixture is stirred at a predetermined temperature. The remaining alkenyl alcohol (1) and thionyl halide (2) can be dropped simultaneously while stirring a part of the alkenyl alcohol (1), a base, and a solvent at the reaction temperature. . Moreover, it can also carry out by the method of dripping alkenyl alcohol (1), stirring halogenated thionyl (2), a base, and a solvent at reaction temperature.
Although there is no restriction | limiting in particular in reaction pressure, From a viewpoint of making easy to exclude hydrogen halide, sulfurous acid gas, etc. which generate | occur | produce by reaction, it is preferable to carry out under reduced pressure or atmospheric pressure. In order to exclude hydrogen halide and sulfurous acid gas generated by the reaction, an inert gas such as nitrogen may be passed through the reaction solution.

  The alkenyl halide (3) obtained after completion of the reaction can be isolated by a method usually used in the isolation and purification of organic compounds. For example, the target alkenyl halide (3) can be obtained by neutralizing the reaction mixture and washing with water, followed by purification by distillation under reduced pressure or silica gel chromatography. Further, the organic phase obtained by neutralizing and washing the reaction mixture can be used as it is or after dehydration without purification.

  In the alkenyl alcohol (1) used in the present invention, for example, a diol having a hydroxyl group at one molecular terminal and having a hydroxyl group bonded to the carbon atom adjacent to the carbon atom at the other molecular terminal is used in the liquid phase. It can be easily obtained by a method of reacting with γ-alumina in the range of 130 to 250 ° C. and reacting while distilling off the product (see JP-A No. 02-196743).

  EXAMPLES Hereinafter, although an Example demonstrates this invention concretely, this invention is not limited to these Examples.

<Example 1>
IPEA 4.34 g (0.05 mol), triethylamine 0.25 g (2.5 mmol), and toluene 125 g were charged into a 300 ml reactor equipped with a stirrer, a condenser, a thermometer, and a dropping funnel, and the temperature of the internal mixture was stirred. The solution was cooled to 5 ° C. Next, 6.54 g (0.055 mol) of thionyl chloride was added dropwise over 10 minutes while maintaining the internal temperature at 10 ° C. or lower. After completion of dropping, the internal temperature was heated to 80 to 85 ° C., and the mixture was heated and stirred for 2 hours. Subsequently, after cooling, 20 g of water was added and stirred, and then allowed to stand. The aqueous phase was then separated and the organic phase was washed with 100 g of 5% aqueous sodium bicarbonate. The organic phase obtained by separation was 128.0 g. As a result of analyzing the organic phase by gas chromatography, the IPEC was 4.71 g (0.045 mol; yield 90%), 3-methyl-2-butenyl chloride. Was found to be 0.02 g (0.2 mmol; yield 0.4%) and 1,3-dichloro-3-methylbutane was 0.17 g (1.2 mmol; yield 2.3%). .

<Example 2>
In Example 1, it carried out similarly except having made reaction temperature 90-95 degreeC, As a result, 4.71 g (0.045 mol; yield 90%) of IPEC and 0.01 g (3-methyl-2-butenyl chloride) were obtained. 0.1 mmol; yield 0.2%) and 0.13 g (0.9 mmol; yield 1.8%) of 1,3-dichloro-3-methylbutane was obtained.

<Example 3>
In Example 1, it carried out similarly except having made reaction temperature 60-65 degreeC, As a result, IPEC was 3.82g (0.037 mol; yield 73%), 3-methyl-2-butenyl chloride was 0.10g ( 1.0 mmol; yield 2.0%) and 0.33 g (2.4 mmol; yield 4.7%) of 1,3-dichloro-3-methylbutane were obtained.

<Example 4>
IPEA 4.31 g (0.05 mol), triethylamine 0.13 g (1.3 mmol), and toluene 62.5 g were added to a 200 ml reactor equipped with a stirrer, a condenser, a thermometer, and a dropping funnel, and the temperature of the internal mixture was adjusted. Cool to 5 ° C. with stirring. Next, 6.54 g (0.055 mol) of thionyl chloride was added dropwise over 10 minutes while maintaining the internal temperature at 10 ° C. or lower. After completion of the dropping, the internal temperature was heated to 80 to 85 ° C., and the mixture was heated and stirred for 1.5 hours. Subsequently, after cooling, 20 g of water was added and stirred, and then allowed to stand. The aqueous phase was then separated and the organic phase was washed with 105 g of 5% aqueous sodium bicarbonate. The organic phase obtained by separation was 66.0 g. As a result of analyzing the organic phase by gas chromatography, the IPEC was 4.20 g (0.040 mol; yield 80%), 3-methyl-2-butenyl chloride. Was found to be 0.01 g (0.1 mmol; yield 0.2%) and 1,3-dichloro-3-methylbutane was produced 0.60 g (4.3 mmol; yield 8.5%). .

<Example 5>
Into a 500 ml reactor equipped with a stirrer, a condenser, a thermometer and a dropping funnel, 1.09 g (12.5 mmol) of IPEA, 1.26 g (12.5 mmol) of triethylamine and 156.38 g of toluene were added, and the temperature of the internal mixture was adjusted. Heat to 80-85 ° C. with stirring. Next, 20.74 g (0.24 mol) of IPEA and 32.81 g (0.275 mol) of thionyl chloride were separately added dropwise over 2 hours while maintaining the internal temperature of 85 to 90 ° C. After completion of the dropwise addition, the mixture was heated and stirred at an internal temperature of 85 to 90 ° C. for 0.5 hour. Subsequently, after cooling, 100 g of water was added and stirred, and then allowed to stand. The aqueous phase was then separated and the organic phase was washed with 140 g of 5% aqueous sodium bicarbonate. The organic phase obtained by separation was 179.00 g. As a result of analyzing the organic phase by gas chromatography, the IPEC was 21.64 g (0.207 mol; yield 82%), 3-methyl-2-butenyl chloride. Of 0.18 g (1.8 mmol; yield 0.7%) and 3.38 g (24.0 mmol; yield 9.5%) of 1,3-dichloro-3-methylbutane were produced. .

<Example 6>
A 500 ml reactor equipped with a stirrer, a condenser, a thermometer and a dropping funnel was charged with 1.26 g (12.5 mmol) of triethylamine, 156.5 g of toluene, and 32.7 g (0.275 mol) of thionyl chloride. The temperature of was heated to 80-85 ° C. with stirring. Next, 21.6 g (0.25 mol) of IPEA was added dropwise over 2 hours while maintaining the internal temperature at 80 to 85 ° C. After completion of dropping, the mixture was heated and stirred at an internal temperature of 80 to 85 ° C. for 0.5 hour. Subsequently, after cooling, 100 g of water was added and stirred, and then allowed to stand. The aqueous phase was then separated and the organic phase was washed with 140 g of 5% aqueous sodium bicarbonate. The organic phase obtained by separation was 182.49 g. As a result of analyzing the organic phase by gas chromatography, IPEC was 23.01 g (0.220 mol; yield 88%), 3-methyl-2-butenyl chloride. It was found that 0.09 g (0.9 mmol; yield 0.35%, 1,3-dichloro-3-methylbutane 1.35 g (9.6 mmol; yield 3.8%) was produced.

<Example 7>
Into a 200 ml reactor equipped with a stirrer, a condenser, a thermometer, and a dropping funnel, 4.31 g (0.05 mol) of IPEA, 0.20 g (2.5 mmol) of pyridine and 62.6 g of toluene were added, and the temperature of the internal mixture was adjusted. Cool to 5 ° C. with stirring. Next, 6.54 g (0.055 mol) of thionyl chloride was added dropwise over 10 minutes while maintaining the internal temperature at 10 ° C. or lower. After completion of dropping, the internal temperature was heated to 80 to 85 ° C., and the mixture was heated and stirred for 2 hours. Subsequently, after cooling, 20 g of water was added and stirred, and then allowed to stand. The aqueous phase was then separated and the organic phase was washed with 100 g of 5% aqueous sodium bicarbonate. The organic phase obtained by separation was 66.5 g. As a result of analyzing the organic phase by gas chromatography, the IPEC was 3.66 g (0.035 mol; yield 70%), 3-methyl-2-butenyl chloride. Was found to be 0.02 g (0.2 mmol; yield 0.4%) and 1,3-dichloro-3-methylbutane was 0.44 g (3.2 mmol; yield 6.3%). .

<Comparative Example 1>
IPEA 4.31 g (0.05 mol), triethylamine 0.26 g (2.5 mmol), and toluene 62.5 g were put into a 200 ml reactor equipped with a stirrer, a condenser, a thermometer, and a dropping funnel, and the temperature of the internal mixture was adjusted. Cool to 5 ° C. with stirring. Next, 6.54 g (0.055 mol) of thionyl chloride was added dropwise over 10 minutes while maintaining the internal temperature at 10 ° C. or lower. After completion of the dropping, the internal temperature was heated to 50 to 55 ° C., and the mixture was heated and stirred for 7 hours. Subsequently, after cooling, 20 g of water was added and stirred, and then allowed to stand. The aqueous phase was then separated and the organic phase was washed with 100 g of 5% aqueous sodium bicarbonate. The organic phase obtained by separation was 66.0 g. As a result of analyzing the organic phase by gas chromatography, IPEC was 3.03 g (0.029 mol; yield 58%), 3-methyl-2-butenyl chloride. It was found that 0.25 g (2.4 mmol; yield 4.8%) and 1.34 g (9.5 mmol; yield 19%) of 1,3-dichloro-3-methylbutane were produced.

<Comparative example 2>
IPEA 4.31 g (0.05 mol) and triethylamine 0.20 g (2.0 mmol) were added to a 50 ml reactor equipped with a stirrer, a condenser, a thermometer, and a dropping funnel, and the temperature of the internal mixture was kept at 5 ° C. with stirring. Until cooled. Next, 6.54 g (0.055 mol) of thionyl chloride was added dropwise over 10 minutes while maintaining the internal temperature at 10 ° C. or lower. After completion of dropping, the internal temperature was heated to 50 to 55 ° C., and the mixture was heated and stirred for 2.5 hours. Subsequently, after cooling, 62.5 g of toluene and 20 g of water were added and stirred, and then allowed to stand. The aqueous phase was then separated and the organic phase was washed with 100 g of 5% aqueous sodium bicarbonate. The organic phase obtained by separation was 68.3 g. As a result of analyzing the organic phase by gas chromatography, the IPEC was 0.46 g (4.4 mmol; yield 8.8%), 3-methyl-2 It was found that 0.14 g (1.3 mmol; yield 2.6%) of -butenyl chloride and 4.80 g (0.034 mol; yield 68%) of 1,3-dichloro-3-methylbutane were produced. .

<Comparative Example 3>
A 200 ml reactor equipped with a stirrer, a condenser, a thermometer, and a dropping funnel was charged with IPEA (4.36 g, 0.05 mol), triethylamine (0.26 g, 2.5 mmol), and diethylene glycol dibutyl ether (62.5 g). The temperature was cooled to 10 ° C. with stirring. Next, 6.54 g (0.055 mol) of thionyl chloride was added dropwise over 10 minutes while maintaining the internal temperature at 15 ° C. or lower. After completion of the dropping, the internal temperature was heated to 60 to 65 ° C., and the mixture was heated and stirred for 7 hours. Subsequently, after cooling, 20 g of water was added and stirred, and then allowed to stand. The aqueous phase was then separated and the organic phase was washed with 100 g of 5% aqueous sodium bicarbonate. The organic phase obtained by separation was 67.2 g. As a result of analyzing the organic phase by gas chromatography, the IPEC was 2.72 g (0.026 mol; yield 52%), 3-methyl-2-butenyl chloride. Of 0.12 g (1.15 mmol; yield 2.3%) and 1.47 g (17.5 mmol; yield 35%) of 1,3-dichloro-3-methylbutane were produced.

<Comparative Example 4>
In Comparative Example 3, the organic phase obtained as a result of separation was 66.8 g, except that the internal temperature at the time of heating and stirring after the completion of the dropwise addition of thionyl chloride was 80 to 85 ° C. As a result of analyzing the organic phase by gas chromatography, IPEC was 2.98 g (0.029 mol; yield 57%), and 3-methyl-2-butenyl chloride was 0.10 g (1.00 mmol; yield 2.0%). 1,3-dichloro-3-methylbutane was found to be produced in an amount of 2.05 g (14.5 mmol; yield 29%).

  The alkenyl halide obtained by the method of the present invention has a highly reactive terminal vinyl group and primary halogen group, and thus is an industrially extremely useful compound, and is a pharmaceutical, agricultural chemical, various chemicals, and resin. It is useful as a raw material for coupling agents and the like.

Claims (3)

The following general formula (1) in a solvent in the presence of a base

(R represents a hydrogen atom or a methyl group, and W represents a divalent saturated hydrocarbon group having 2 to 10 carbon atoms)
An alkenyl alcohol represented by the following general formula (2)

(X represents a chlorine atom, a bromine atom or an iodine atom)
The following general formula (3) is reacted with thionyl halide represented by

(R, W and X are as defined above)
A process for producing an alkenyl halide represented by:
The amount of the base used is 0.001 to 0.3 mol with respect to 1 mol of alkenyl alcohol (1),
The solvent is a hydrocarbon and / or a halogenated hydrocarbon;
The method for producing the alkenyl halide, wherein a reaction temperature in the reaction is 60 to 140 ° C. The production method according to claim 1, wherein the base is selected from a tertiary amine or a nitrogen-containing aromatic compound. The manufacturing method of Claim 1 or 2 whose usage-amount of the said base is 0.01-0.1 mol with respect to 1 mol of said alkenyl alcohols.