WO2013035674A1 - Method for producing 2-halo-1-(1-halocyclopropyl)ethanone - Google Patents

Method for producing 2-halo-1-(1-halocyclopropyl)ethanone Download PDF

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WO2013035674A1
WO2013035674A1 PCT/JP2012/072377 JP2012072377W WO2013035674A1 WO 2013035674 A1 WO2013035674 A1 WO 2013035674A1 JP 2012072377 W JP2012072377 W JP 2012072377W WO 2013035674 A1 WO2013035674 A1 WO 2013035674A1
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ethanone
aliphatic alcohol
compound
halocyclopropyl
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French (fr)
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久 菅野
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株式会社クレハ
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/63—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by introduction of halogen; by substitution of halogen atoms by other halogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/02—Systems containing only non-condensed rings with a three-membered ring

Definitions

  • the present invention relates to a novel process for producing 2-halo-1- (1-halocyclopropyl) ethanone used as an intermediate for agricultural chemicals and the like.
  • Patent Document 1 describes a method for producing these intermediates by reacting a chlorinating agent or brominating agent with 1- (1-halocyclopropyl) ethanone in the presence of a diluent. . Specifically, a method for producing the above intermediate by chlorination or bromination of 1- (1-halocyclopropyl) ethanone in dichloromethane using sulfuryl chloride or sulfuryl bromide is described. Yes.
  • Japanese Patent Publication Japanese Unexamined Patent Publication No. 64-22857” (published on January 25, 1989) Japanese Patent Publication “JP-A-8-277240 (published on Oct. 22, 1996)”
  • the method for producing the intermediate described in Patent Document 1 requires a long reaction time because of poor reactivity. Further, when the reaction is performed for a long time, unnecessary chlorination or bromination occurs, and a non-negligible by-product can be produced. For example, when chlorination is carried out, the main product, 2-chloro-1- (1-chlorocyclopropyl) ethanone, remains even when 1- (1-chlorocyclopropyl) ethanone as the raw material remains. As a result, chlorination further proceeds and a by-product 1- (1-chlorocyclopropyl) -2,2-dichloroethanone is produced in a considerable amount.
  • the present invention has been made in view of such problems and requirements.
  • the object of the present invention is to produce 2-halo-1- (1-halocyclopropyl) ethanone in a shorter reaction time and with higher selectivity. It is to provide a method of manufacturing.
  • the inventor has conducted various studies to solve these problems, and as a result, in the production of 2-halo-1- (1-halocyclopropyl) ethanone, the reaction system can be shortened by coexisting an aliphatic alcohol. It has been found that the conversion rate can be increased even with the reaction time, and the production of 1- (1-halocyclopropyl) -2,2-dihaloethanone as a by-product can be suppressed, and the present invention has been completed.
  • X 1 is the same as X 1 in formula (I)
  • a sulfuryl halide In the presence of an aliphatic alcohol, the compound is reacted with a sulfuryl halide to be halogenated, whereby a method for producing 2-halo-1- (1-halocyclopropyl) ethanone is provided.
  • the halogenation of 1- (1-halocyclopropyl) ethanone is carried out in the presence of an aliphatic alcohol. It is possible to produce 2-halo-1- (1-halocyclopropyl) ethanone with a shorter reaction time than in the past and with high selectivity.
  • X 1 is the same as X 1 in formula (I))
  • 2-halo-1- (1-halocyclopropyl) ethanone represented by the general formula (I) (hereinafter referred to as compound (I)) is a target product in the present invention. Can be used as a body.
  • X 1 and X 2 are the same or different halogen atoms.
  • the halogen atom include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.
  • X 1 and X 2 are preferably bromine atoms or chlorine atoms, and X 1 and X 2 are both Particularly preferred is a chlorine atom.
  • compound (II) 1- (1-halocyclopropyl) ethanone represented by general formula (II) (hereinafter referred to as compound (II)) is a raw material for producing compound (I).
  • X 1 in compound (II) is the same halogen atom as the halogen atom represented by X 1 in compound (I).
  • compound (II) is a well-known compound, and what was manufactured using the prior art can be used.
  • the aliphatic alcohol is not particularly limited as long as it can synthesize compound (I) from compound (II) in a shorter reaction time and with high selectivity.
  • Such an aliphatic alcohol may be either a saturated aliphatic alcohol or an unsaturated aliphatic alcohol, and examples thereof include saturated or unsaturated aliphatic alcohols having 1 to 10 carbon atoms. Examples of more suitable aliphatic alcohols include saturated aliphatic alcohols having 1 to 4 carbon atoms.
  • methanol, ethanol, 1-propanol, 2-propanol, 1-butanol and the like are preferable, and methanol and ethanol are particularly preferable.
  • the sulfuryl halide is a compound represented by the general formula: SO 2 X 2 X 3 .
  • X 2 are the same halogen atom and X 2 in the compound (I), X 3 is the same or as X 2 is a different halogen atom. Of these it is preferred and X 2 and X 3 are identical halogen atoms.
  • the plurality of halogen atoms contained in the halogenated sulfuryl are preferably the same halogen atoms.
  • the halogenated sulfuryl include sulfuryl fluoride, sulfuryl chloride, sulfuryl bromide, and sulfuryl iodide.
  • halogen atoms contained are different from each other, such as sulfuryl chlorofluoride.
  • a method for isolating a compound halogenated by a desired halogen atom when X 2 and X 3 are halogenated using a sulfuryl halide which is a halogen atom different from each other a method such as distillation is used. Can do.
  • This reaction can be advantageously performed in a solvent inert to the reaction.
  • the solvent used in this reaction is not particularly limited, but a solvent that does not react with sulfuryl halide is preferable.
  • Specific examples of the solvent include, for example, halogenated hydrocarbons such as dichloromethane, trichloromethane and dichloroethane, aromatic hydrocarbons such as benzene, toluene and xylene, and aliphatic hydrocarbons such as petroleum ether, hexane and methylcyclohexane. Among them, halogenated hydrocarbons are preferable. Moreover, you may use these solvents in mixture of 2 or more types.
  • the amount of the sulfuryl halide used relative to compound (II) is, for example, 0.5 to 10 times mol, preferably 0.8 to 5 times mol.
  • the amount of the aliphatic alcohol used relative to compound (II) is, for example, 0.01 to 20 times mol, preferably 0.1 to 20 times mol, more preferably 0.5 to 10 times mol. .
  • the reaction temperature and reaction time can be appropriately set depending on the type of solvent and aliphatic alcohol used.
  • the reaction temperature is preferably ⁇ 100 ° C. to 100 ° C., more preferably 0 ° C. to 80 ° C.
  • the reaction time is preferably 0.01 to 48 hours, more preferably 0.1 to 24 hours, and further preferably 0.1 to 12 hours.
  • reaction time When the reaction time is increased, the produced compound (I) is further halogenated with sulfuryl halide, and 1- (1-halocyclopropyl) -2 represented by the following general formula (III), which is a byproduct. , 2-dihaloethanone (hereinafter referred to as compound (III)) is produced. Therefore, it is preferable that the reaction time is shorter.
  • X 1 and X 2 are the same as X 1 and X 2 in General Formula (I), respectively, and X 3 is the same as X 3 in the sulfuryl halide.
  • Example 1 In a 100 ml three-necked flask, 1- (1-chlorocyclopropyl) ethanone (compound (V)) (5 g) and 2 equivalents of methanol to compound (V) were dissolved in dichloromethane (20 ml). Next, under cooling with ice water (reaction temperature 20 ° C.), sulfuryl chloride (11.38 g) was added dropwise over 10 minutes. After completion of the dropwise addition, in order to calculate the conversion rate and the selectivity due to the difference in reaction time, the reaction solution was collected after 0.25 hours and 1 hour and analyzed. Specifically, the collected reaction solution was dissolved in deuterated chloroform, and a 1 H-NMR spectrum was measured. And the ratio of compound (IV), (V) and (VI) was computed from the integrated value. The results are shown in Table 1.
  • Example 2 Synthesis of 2-chloro-1- (1-chlorocyclopropyl) ethanone and the same procedure as in Example 1 except that the reaction was performed using 1 equivalent of ethanol with respect to compound (V) instead of methanol. Analysis was carried out. The results are shown in Table 1.
  • the conversion rate (%) represents the ratio of the reacted compound (V) in the starting compound (V). Therefore, when the value of conversion rate is high, it shows that many reaction products are produced
  • the selectivity (%) represents the ratio of the compound (IV) in the reaction product.
  • the amount of aliphatic alcohol is the amount used relative to the amount of compound (V) used in the reaction.
  • the conversion rate was low in the short-time reaction (for example, 4% conversion rate in the 1-hour reaction). That is, almost no compound (IV) is produced, indicating that the reactivity is poor. Further, it was shown that the selectivity is about 77% although the conversion rate is increased to 99% or more by carrying out the reaction for a long time (68 hours). That is, it is shown that the ratio of the compound (VI) as a by-product is increased while the ratio of the reaction product is increased by performing the reaction for a long time.
  • the present invention can be suitably used for production of industrially important agricultural chemicals and intermediates thereof.

Abstract

The present invention provides a method for producing a 2-halo-1-(1-halocyclopropyl)ethanone represented by general formula (I), wherein a compound represented by general formula (II) is halogenated by being reacted with a sulfuryl halide in the presence of an aliphatic alcohol. (In the formulae, X1 and X2 respectively represent the same or different halogen atoms.)

Description

２－ハロ－１－（１－ハロシクロプロピル）エタノンの製造方法Process for producing 2-halo-1- (1-halocyclopropyl) ethanone
　本発明は、農薬等の中間体として使用される２－ハロ－１－（１－ハロシクロプロピル）エタノンの新規な製造方法に関する。 The present invention relates to a novel process for producing 2-halo-1- (1-halocyclopropyl) ethanone used as an intermediate for agricultural chemicals and the like.
　２－クロロ－１－（１－ハロシクロプロピル）エタノンおよび２－ブロモ－１－（１－ハロシクロプロピル）エタノンは、殺菌および殺カビ活性ならびに植物成長調節活性を有する化合物の中間体として知られている（例えば、特許文献１参照）。また、特許文献１には、希釈剤の存在下において、塩素化剤または臭素化剤を１－（１－ハロシクロプロピル）エタノンと反応させることによりこれら中間体を製造する方法が記載されている。具体的には、１－（１－ハロシクロプロピル）エタノンをジクロロメタン中において、塩化スルフリルまたは臭化スルフリルを用いて、塩素化または臭素化を行うことにより上記中間体を製造する方法が記載されている。 2-Chloro-1- (1-halocyclopropyl) ethanone and 2-bromo-1- (1-halocyclopropyl) ethanone are known as intermediates for compounds having fungicidal and fungicidal and plant growth-regulating activities. (For example, refer to Patent Document 1). Patent Document 1 describes a method for producing these intermediates by reacting a chlorinating agent or brominating agent with 1- (1-halocyclopropyl) ethanone in the presence of a diluent. . Specifically, a method for producing the above intermediate by chlorination or bromination of 1- (1-halocyclopropyl) ethanone in dichloromethane using sulfuryl chloride or sulfuryl bromide is described. Yes.
　一方、アリールケトン誘導体の塩素化を行う方法として、塩化スルフリルを用いて脂肪族アルコールの存在下に反応を行う方法が知られている（例えば、特許文献２参照）。 On the other hand, as a method of chlorinating an aryl ketone derivative, a method of performing a reaction in the presence of an aliphatic alcohol using sulfuryl chloride is known (for example, see Patent Document 2).
日本国公開特許公報「特開昭６４－２２８５７号公報（１９８９年１月２５日公開）」Japanese Patent Publication “Japanese Unexamined Patent Publication No. 64-22857” (published on January 25, 1989) 日本国公開特許公報「特開平８－２７７２４０号公報（１９９６年１０月２２日公開）」Japanese Patent Publication “JP-A-8-277240 (published on Oct. 22, 1996)”
　しかしながら、特許文献１に記載された上記中間体の製造方法では、反応性に乏しいため、長時間の反応が必要である。また、長時間の反応を行った場合には、不要な塩素化または臭素化が生じてしまい、無視できない量の副生成物が製造され得る。例えば、塩素化を行った場合に、原料である１－（１－クロロシクロプロピル）エタノンが残存する状態でも、主生成物である２－クロロ－１－（１－クロロシクロプロピル）エタノンに対して塩素化がさらに進行し、副生成物である１－（１－クロロシクロプロピル）－２，２－ジクロロエタノンが相当量において生成される。そのため、主生成物の収率の低下を引き起こすという問題がある。また、副生成物が生成されると、分離、および精製等の操作が必要となるが、上記の主生成物と副生成物とを分離することは一般的に困難である。そのため、工業的観点から、製造方法の改良が求められている。 However, the method for producing the intermediate described in Patent Document 1 requires a long reaction time because of poor reactivity. Further, when the reaction is performed for a long time, unnecessary chlorination or bromination occurs, and a non-negligible by-product can be produced. For example, when chlorination is carried out, the main product, 2-chloro-1- (1-chlorocyclopropyl) ethanone, remains even when 1- (1-chlorocyclopropyl) ethanone as the raw material remains. As a result, chlorination further proceeds and a by-product 1- (1-chlorocyclopropyl) -2,2-dichloroethanone is produced in a considerable amount. Therefore, there exists a problem of causing the fall of the yield of a main product. In addition, when a by-product is generated, operations such as separation and purification are required, but it is generally difficult to separate the main product and the by-product. Therefore, improvement of a manufacturing method is calculated | required from an industrial viewpoint.
　なお、特許文献２に記載のアリールケトン誘導体の塩素化を行う反応では、脂肪族アルコールを添加することにより変換率が低下することが示唆されている。 In addition, in the reaction for chlorinating an aryl ketone derivative described in Patent Document 2, it is suggested that the conversion rate is reduced by adding an aliphatic alcohol.
　本発明は、このような問題点および要求に鑑みてなされたものであり、その目的は、より短い反応時間で、かつ高選択的に２－ハロ－１－（１－ハロシクロプロピル）エタノンを製造する方法を提供することにある。 The present invention has been made in view of such problems and requirements. The object of the present invention is to produce 2-halo-1- (1-halocyclopropyl) ethanone in a shorter reaction time and with higher selectivity. It is to provide a method of manufacturing.
　発明者は、これらの問題点を解決すべく種々検討を重ねた結果、２－ハロ－１－（１－ハロシクロプロピル）エタノンの製造において、反応系内に脂肪族アルコールを共存させることにより短い反応時間でも変換率を高めることができ、また、副生成物である１－（１－ハロシクロプロピル）－２，２－ジハロエタノンの生成を抑制できることを見出し、本発明を完成するに至った。 The inventor has conducted various studies to solve these problems, and as a result, in the production of 2-halo-1- (1-halocyclopropyl) ethanone, the reaction system can be shortened by coexisting an aliphatic alcohol. It has been found that the conversion rate can be increased even with the reaction time, and the production of 1- (1-halocyclopropyl) -2,2-dihaloethanone as a by-product can be suppressed, and the present invention has been completed.
　すなわち、本発明に係る２－ハロ－１－（１－ハロシクロプロピル）エタノンの製造方法は、一般式（Ｉ） That is, the method for producing 2-halo-1- (1-halocyclopropyl) ethanone according to the present invention is represented by the general formula (I)
Figure JPOXMLDOC01-appb-C000003
Figure JPOXMLDOC01-appb-C000003
（式（Ｉ）中、Ｘ１およびＸ２は、それぞれ同じかまたは異なるハロゲン原子を表す）
で示される２－ハロ－１－（１－ハロシクロプロピル）エタノンの製造方法であって、
　一般式（ＩＩ） (In formula (I), X 1 and X 2 each represent the same or different halogen atoms)
A process for producing 2-halo-1- (1-halocyclopropyl) ethanone represented by
Formula (II)
Figure JPOXMLDOC01-appb-C000004
Figure JPOXMLDOC01-appb-C000004
（式（ＩＩ）中、Ｘ１は、式（Ｉ）におけるＸ１と同じである）
で示される化合物を脂肪族アルコール存在下において、ハロゲン化スルフリルと反応させてハロゲン化することを特徴とする２－ハロ－１－（１－ハロシクロプロピル）エタノンの製造方法である。 (In formula (II), X 1 is the same as X 1 in formula (I))
In the presence of an aliphatic alcohol, the compound is reacted with a sulfuryl halide to be halogenated, whereby a method for producing 2-halo-1- (1-halocyclopropyl) ethanone is provided.
　本発明に係る２－ハロ－１－（１－ハロシクロプロピル）エタノンの製造方法によれば、１－（１－ハロシクロプロピル）エタノンのハロゲン化を脂肪族アルコールの存在下に実施することによって、従来よりも短い反応時間で、かつ高選択的に２－ハロ－１－（１－ハロシクロプロピル）エタノンを製造することが可能である。 According to the method for producing 2-halo-1- (1-halocyclopropyl) ethanone according to the present invention, the halogenation of 1- (1-halocyclopropyl) ethanone is carried out in the presence of an aliphatic alcohol. It is possible to produce 2-halo-1- (1-halocyclopropyl) ethanone with a shorter reaction time than in the past and with high selectivity.
　以下、本発明に係る２－ハロ－１－（１－ハロシクロプロピル）エタノンの製造方法の一実施形態について説明する。 Hereinafter, an embodiment of a method for producing 2-halo-1- (1-halocyclopropyl) ethanone according to the present invention will be described.
　本実施形態における２－ハロ－１－（１－ハロシクロプロピル）エタノンの製造方法は、一般式（Ｉ） The production method of 2-halo-1- (1-halocyclopropyl) ethanone in the present embodiment is represented by the general formula (I)
Figure JPOXMLDOC01-appb-C000005
Figure JPOXMLDOC01-appb-C000005
（式（Ｉ）中、Ｘ１およびＸ２は、それぞれ同じかまたは異なるハロゲン原子を表す）
で示される２－ハロ－１－（１－ハロシクロプロピル）エタノンの製造方法であって、一般式（ＩＩ） (In formula (I), X 1 and X 2 each represent the same or different halogen atoms)
A method for producing 2-halo-1- (1-halocyclopropyl) ethanone represented by the general formula (II):
Figure JPOXMLDOC01-appb-C000006
Figure JPOXMLDOC01-appb-C000006
（式（ＩＩ）中、Ｘ１は、式（Ｉ）におけるＸ１と同じである）
で示される化合物を脂肪族アルコール存在下において、ハロゲン化スルフリルと反応させてハロゲン化を行う製造法である。 (In formula (II), X 1 is the same as X 1 in formula (I))
Is a production method in which halogenation is carried out by reacting with a sulfuryl halide in the presence of an aliphatic alcohol.
　一般式（Ｉ）で表される２－ハロ－１－（１－ハロシクロプロピル）エタノン（以下、化合物（Ｉ）とする）は、本発明において目的となる生成物であり、農薬等の中間体として使用され得る。 2-halo-1- (1-halocyclopropyl) ethanone represented by the general formula (I) (hereinafter referred to as compound (I)) is a target product in the present invention. Can be used as a body.
　Ｘ１およびＸ２は、それぞれ同じかまたは異なるハロゲン原子である。ハロゲン原子としては、フッ素原子、塩素原子、臭素原子およびヨウ素原子が挙げられ、なかでも、Ｘ１およびＸ２が何れも臭素原子または塩素原子であることが好ましく、Ｘ１およびＸ２が何れも塩素原子であることが特に好ましい。 X 1 and X 2 are the same or different halogen atoms. Examples of the halogen atom include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom. Among them, X 1 and X 2 are preferably bromine atoms or chlorine atoms, and X 1 and X 2 are both Particularly preferred is a chlorine atom.
　一般式（ＩＩ）で表される１－（１－ハロシクロプロピル）エタノン（以下、化合物（ＩＩ）とする）は、化合物（Ｉ）を製造するための原料である。化合物（ＩＩ）におけるＸ１は、化合物（Ｉ）におけるＸ１で表されるハロゲン原子と同一のハロゲン原子である。なお、化合物（ＩＩ）は公知の化合物であり、従来技術を用いて製造したものを使用することができる。 1- (1-halocyclopropyl) ethanone represented by general formula (II) (hereinafter referred to as compound (II)) is a raw material for producing compound (I). X 1 in compound (II) is the same halogen atom as the halogen atom represented by X 1 in compound (I). In addition, compound (II) is a well-known compound, and what was manufactured using the prior art can be used.
　脂肪族アルコールは、化合物（ＩＩ）から化合物（Ｉ）をより短い反応時間で、かつ、高選択的に合成することができるものであれば特に限定はされない。このような脂肪族アルコールとしては、飽和脂肪族アルコールおよび不飽和脂肪族アルコールの何れであってもよく、例えば、炭素原子数１～１０の飽和または不飽和の脂肪族アルコールが挙げられる。より好適な脂肪族アルコールの例としては、炭素原子数１～４の飽和脂肪族アルコールが挙げられる。具体的にはメタノール、エタノール、１－プロパノール、２－プロパノールおよび１－ブタノール等が好ましく、メタノールおよびエタノールが特に好ましい。 The aliphatic alcohol is not particularly limited as long as it can synthesize compound (I) from compound (II) in a shorter reaction time and with high selectivity. Such an aliphatic alcohol may be either a saturated aliphatic alcohol or an unsaturated aliphatic alcohol, and examples thereof include saturated or unsaturated aliphatic alcohols having 1 to 10 carbon atoms. Examples of more suitable aliphatic alcohols include saturated aliphatic alcohols having 1 to 4 carbon atoms. Specifically, methanol, ethanol, 1-propanol, 2-propanol, 1-butanol and the like are preferable, and methanol and ethanol are particularly preferable.
　ハロゲン化スルフリルは、一般式：ＳＯ２Ｘ２Ｘ３によって表される化合物である。ここで、Ｘ２は化合物（Ｉ）中のＸ２と同一のハロゲン原子であり、Ｘ３はＸ２と同じかまたは異なるハロゲン原子である。なかでもＸ２とＸ３とが同一のハロゲン原子であることが好ましい。換言すれば、ハロゲン化スルフリルに含まれる複数のハロゲン原子は互いに同一のハロゲン原子であることが好ましい。ハロゲン化スルフリルとしては、例えば、フッ化スルフリル、塩化スルフリル、臭化スルフリルおよびヨウ化スルフリル等が挙げられる。また、塩化フッ化スルフリル等、含まれるハロゲン原子が互いに異なるハロゲン原子である化合物を使用することも可能である。Ｘ２とＸ３とが互いに異なるハロゲン原子であるハロゲン化スルフリルを用いてハロゲン化した場合に、所望のハロゲン原子によってハロゲン化された化合物を単離する方法としては、蒸留等の方法を用いることができる。 The sulfuryl halide is a compound represented by the general formula: SO 2 X 2 X 3 . Here, X 2 are the same halogen atom and X 2 in the compound (I), X 3 is the same or as X 2 is a different halogen atom. Of these it is preferred and X 2 and X 3 are identical halogen atoms. In other words, the plurality of halogen atoms contained in the halogenated sulfuryl are preferably the same halogen atoms. Examples of the halogenated sulfuryl include sulfuryl fluoride, sulfuryl chloride, sulfuryl bromide, and sulfuryl iodide. It is also possible to use compounds in which the halogen atoms contained are different from each other, such as sulfuryl chlorofluoride. As a method for isolating a compound halogenated by a desired halogen atom when X 2 and X 3 are halogenated using a sulfuryl halide which is a halogen atom different from each other, a method such as distillation is used. Can do.
　本反応は、反応に不活性な溶媒中において有利に行うことができる。本反応において使用される溶媒は特に限定されないが、ハロゲン化スルフリルと反応しない溶媒が好ましい。溶媒の具体例としては、例えば、ジクロロメタン、トリクロロメタンおよびジクロロエタン等のハロゲン化炭化水素類、ベンゼン、トルエンおよびキシレン等の芳香族炭化水素類、ならびに石油エーテル、ヘキサンおよびメチルシクロヘキサン等の脂肪族炭化水素類が挙げられ、なかでもハロゲン化炭化水素類が好ましい。また、これらの溶媒は、２種類以上を混合して用いてもよい。 This reaction can be advantageously performed in a solvent inert to the reaction. The solvent used in this reaction is not particularly limited, but a solvent that does not react with sulfuryl halide is preferable. Specific examples of the solvent include, for example, halogenated hydrocarbons such as dichloromethane, trichloromethane and dichloroethane, aromatic hydrocarbons such as benzene, toluene and xylene, and aliphatic hydrocarbons such as petroleum ether, hexane and methylcyclohexane. Among them, halogenated hydrocarbons are preferable. Moreover, you may use these solvents in mixture of 2 or more types.
　化合物（ＩＩ）に対するハロゲン化スルフリルの使用量は、例えば０．５～１０倍モルであり、好ましくは０．８～５倍モルである。また、化合物（ＩＩ）に対する脂肪族アルコールの使用量は、例えば０．０１～２０倍モルであり、好ましくは０．１～２０倍モルであり、より好ましくは０．５～１０倍モルである。 The amount of the sulfuryl halide used relative to compound (II) is, for example, 0.5 to 10 times mol, preferably 0.8 to 5 times mol. The amount of the aliphatic alcohol used relative to compound (II) is, for example, 0.01 to 20 times mol, preferably 0.1 to 20 times mol, more preferably 0.5 to 10 times mol. .
　反応温度および反応時間は、用いられる溶媒および脂肪族アルコールの種類等によって適宜設定することができる。反応温度は、好適には－１００℃～１００℃であり、より好適には０℃～８０℃である。また、反応時間は、好適には０．０１～４８時間、より好適には０．１～２４時間であり、さらに好適には０．１～１２時間である。 The reaction temperature and reaction time can be appropriately set depending on the type of solvent and aliphatic alcohol used. The reaction temperature is preferably −100 ° C. to 100 ° C., more preferably 0 ° C. to 80 ° C. The reaction time is preferably 0.01 to 48 hours, more preferably 0.1 to 24 hours, and further preferably 0.1 to 12 hours.
　なお、反応時間が長くなると、生成した化合物（Ｉ）がハロゲン化スルフリルによってさらにハロゲン化され、副生成物である下記一般式（ＩＩＩ）で表される１-（１－ハロシクロプロピル）-２,２－ジハロエタノン（以下、化合物（ＩＩＩ）とする）が生成される。そのため、反応時間はより短いほうが好ましい。 When the reaction time is increased, the produced compound (I) is further halogenated with sulfuryl halide, and 1- (1-halocyclopropyl) -2 represented by the following general formula (III), which is a byproduct. , 2-dihaloethanone (hereinafter referred to as compound (III)) is produced. Therefore, it is preferable that the reaction time is shorter.
Figure JPOXMLDOC01-appb-C000007
Figure JPOXMLDOC01-appb-C000007
　一般式（ＩＩＩ）中、Ｘ１およびＸ２は、それぞれ上記一般式（Ｉ）におけるＸ１およびＸ２と同じであり、Ｘ３は、上記ハロゲン化スルフリル中のＸ３と同じである。 In General Formula (III), X 1 and X 2 are the same as X 1 and X 2 in General Formula (I), respectively, and X 3 is the same as X 3 in the sulfuryl halide.
　本実施の形態における化合物（Ｉ）の製造方法の具体例としては、例えば、上記一般式（Ｉ）および上記一般式（ＩＩ）におけるＸ１は塩素原子であり、上記一般式（Ｉ）におけるＸ２は塩素原子であり、上記ハロゲン化スルフリルは塩化スルフリルである場合が挙げられる。すなわち、下記反応式（１）に示す２－クロロ－１－（１－クロロシクロプロピル）エタノンの製造方法が挙げられる。
（反応式１） Specific examples of the preparation of compounds according to the present embodiment (I) are, for example, X 1 in the general formula (I) and the general formula (II) is chlorine atom, X in the general formula (I) 2 is a chlorine atom, and the sulfuryl halide is sulfuryl chloride. That is, a method for producing 2-chloro-1- (1-chlorocyclopropyl) ethanone represented by the following reaction formula (1) can be mentioned.
(Reaction Formula 1)
Figure JPOXMLDOC01-appb-C000008
Figure JPOXMLDOC01-appb-C000008
　上記の反応式（１）は、脂肪族アルコール中において、上記化学式（Ｖ）で表される１－（１－クロロシクロプロピル）エタノン（以下、化合物（Ｖ）とする）を脂肪族アルコール存在下で塩化スルフリルと反応させることによって、上記化学式（ＩＶ）で表される２－クロロ－１－（１－クロロシクロプロピル）エタノン（以下、化合物（ＩＶ）とする）が得られることを表す反応式である。 In the above reaction formula (1), 1- (1-chlorocyclopropyl) ethanone represented by the above chemical formula (V) (hereinafter referred to as compound (V)) in an aliphatic alcohol is present in the presence of the aliphatic alcohol. A reaction formula showing that 2-chloro-1- (1-chlorocyclopropyl) ethanone represented by the above chemical formula (IV) (hereinafter referred to as compound (IV)) can be obtained by reacting with sulfuryl chloride in It is.
　なお、生成した化合物（ＩＶ）が塩化スルフリルによってさらに塩素化されると、下記反応式に示すように、副生成物である１-（１－クロロシクロプロピル）-２,２－ジクロロエタノン（以下、化合物（ＶＩ）とする）が生成される。 When the produced compound (IV) is further chlorinated with sulfuryl chloride, as shown in the following reaction formula, 1- (1-chlorocyclopropyl) -2,2-dichloroethanone (hereinafter referred to as by-product) , Referred to as compound (VI)).
Figure JPOXMLDOC01-appb-C000009
Figure JPOXMLDOC01-appb-C000009
　脂肪族アルコールを反応系中に含んでいない従来の２－クロロ－１－（１－ハロシクロプロピル）エタノンおよび２－ブロモ－１－（１－ハロシクロプロピル）エタノンの製造方法では、長時間の反応が必要である。しかしながら、本実施の形態に係る製造方法によれば、従来の反応と比較して極めて短い時間で多くの化合物（ＩＩ）を反応させることができ、反応時間を大幅に短縮することができる。すなわち、短い反応時間でも変換率を高めることができる。また、従来の製造方法では、無視できない量の副生成物が製造されてしまうが、本実施の形態に係る製造方法によれば、副生成物である化合物（ＩＩＩ）の生成が抑えられ、その結果、反応生成物における化合物（Ｉ）の割合を増加させることができる。 In the conventional method for producing 2-chloro-1- (1-halocyclopropyl) ethanone and 2-bromo-1- (1-halocyclopropyl) ethanone which does not contain an aliphatic alcohol in the reaction system, A reaction is required. However, according to the production method according to the present embodiment, a large amount of compound (II) can be reacted in a very short time compared to the conventional reaction, and the reaction time can be greatly shortened. That is, the conversion rate can be increased even with a short reaction time. Further, in the conventional production method, a by-product in a non-negligible amount is produced, but according to the production method according to the present embodiment, the production of the by-product compound (III) is suppressed, As a result, the proportion of compound (I) in the reaction product can be increased.
　以下に実施例を示し、本発明の実施の形態についてさらに詳しく説明する。もちろん、本発明は以下の実施例に限定されるものではなく、細部については様々な態様が可能であることはいうまでもない。さらに、本発明は上述した実施形態に限定されるものではなく、請求項に示した範囲で種々の変更が可能であり、それぞれ開示された技術的手段を適宜組み合わせて得られる実施形態についても本発明の技術的範囲に含まれる。また、本明細書中に記載された文献の全てが参考として援用される。 Examples will be shown below, and the embodiments of the present invention will be described in more detail. Of course, the present invention is not limited to the following examples, and it goes without saying that various aspects are possible in detail. Further, the present invention is not limited to the above-described embodiments, and various modifications can be made within the scope shown in the claims, and the present invention is also applied to the embodiments obtained by appropriately combining the disclosed technical means. It is included in the technical scope of the invention. Moreover, all the literatures described in this specification are used as reference.
　（実施例１）
　１００ｍｌの三口フラスコにおいて、１－（１－クロロシクロプロピル）エタノン（化合物（Ｖ））（５ｇ）と、化合物（Ｖ）に対して２当量のメタノールとを、ジクロロメタン（２０ｍｌ）に溶解させた。次に氷水冷下（反応温度２０℃）において、塩化スルフリル（１１．３８ｇ）を１０分かけて滴下した。滴下終了後、反応時間の相違による変換率および選択率を算出するために、０．２５時間および１時間経過後に反応液を採取し、分析を行った。具体的には、採取した反応液を、重水素化クロロホルム中に溶解させ、１Ｈ－ＮＭＲスペクトルを測定した。そして、その積分値から化合物（ＩＶ）、（Ｖ）および（ＶＩ）の割合を算出した。結果を表１に示す。 Example 1
In a 100 ml three-necked flask, 1- (1-chlorocyclopropyl) ethanone (compound (V)) (5 g) and 2 equivalents of methanol to compound (V) were dissolved in dichloromethane (20 ml). Next, under cooling with ice water (reaction temperature 20 ° C.), sulfuryl chloride (11.38 g) was added dropwise over 10 minutes. After completion of the dropwise addition, in order to calculate the conversion rate and the selectivity due to the difference in reaction time, the reaction solution was collected after 0.25 hours and 1 hour and analyzed. Specifically, the collected reaction solution was dissolved in deuterated chloroform, and a 1 H-NMR spectrum was measured. And the ratio of compound (IV), (V) and (VI) was computed from the integrated value. The results are shown in Table 1.
　（実施例２）
　メタノールの代わりに、化合物（Ｖ）に対して１当量のエタノールを用いて反応を行った以外は実施例１と同様にして、２－クロロ－１－（１－クロロシクロプロピル）エタノンの合成および分析を行った。結果を表１に示す。 (Example 2)
Synthesis of 2-chloro-1- (1-chlorocyclopropyl) ethanone and the same procedure as in Example 1 except that the reaction was performed using 1 equivalent of ethanol with respect to compound (V) instead of methanol. Analysis was carried out. The results are shown in Table 1.
　（比較例１）
　反応系中にメタノールを添加せず、反応液を採取する時間を０．２５時間、１時間、２０時間および６８時間とした以外は実施例１と同様にして、２－クロロ－１－（１－クロロシクロプロピル）エタノンの合成および分析を行った。ただし、反応時間２時間後以降の反応は室温にて行った。結果を表１に示す。 (Comparative Example 1)
In the same manner as in Example 1, except that methanol was not added to the reaction system and the time for collecting the reaction solution was 0.25 hours, 1 hour, 20 hours and 68 hours, 2-chloro-1- (1 -Chlorocyclopropyl) ethanone was synthesized and analyzed. However, the reaction after 2 hours of reaction time was performed at room temperature. The results are shown in Table 1.
Figure JPOXMLDOC01-appb-T000010
Figure JPOXMLDOC01-appb-T000010
　表１中、変換率（％）は、原料となる化合物（Ｖ）のうちの反応した化合物（Ｖ）の割合を表す。そのため、変換率の値が高い場合には、反応生成物が多く生成されていることを示す。また、選択率（％）は、反応生成物中の化合物（ＩＶ）の割合を表す。脂肪族アルコールの量は、反応に用いた化合物（Ｖ）の量に対する使用量である。 In Table 1, the conversion rate (%) represents the ratio of the reacted compound (V) in the starting compound (V). Therefore, when the value of conversion rate is high, it shows that many reaction products are produced | generated. The selectivity (%) represents the ratio of the compound (IV) in the reaction product. The amount of aliphatic alcohol is the amount used relative to the amount of compound (V) used in the reaction.
　比較例において示されるように、脂肪族アルコールが無添加である場合には、短時間の反応では変換率が低かった（例えば、１時間の反応で、４％の変換率）。すなわち、化合物（ＩＶ）がほとんど生成しておらず、反応性に乏しいことを示している。また、長時間（６８時間）の反応をさせることによって、変換率が９９％以上に上昇するものの、選択率が７７％程度であることが示された。すなわち、長時間の反応をさせることによって、反応生成物の割合は上昇するものの、副生成物である化合物（ＶＩ）の割合が上昇していることを示している。 As shown in the comparative example, when no aliphatic alcohol was added, the conversion rate was low in the short-time reaction (for example, 4% conversion rate in the 1-hour reaction). That is, almost no compound (IV) is produced, indicating that the reactivity is poor. Further, it was shown that the selectivity is about 77% although the conversion rate is increased to 99% or more by carrying out the reaction for a long time (68 hours). That is, it is shown that the ratio of the compound (VI) as a by-product is increased while the ratio of the reaction product is increased by performing the reaction for a long time.
　一方、実施例１および２において示されるように脂肪族アルコールを添加した場合には、０．２５または１時間という短い時間において、９４％または９９％を超える高い変換率を示した。さらに、脂肪族アルコールを添加した場合には、９５％を超える高い選択率を示した。すなわち、脂肪族アルコールを添加した場合には、極めて短時間で反応を終了させることができるとともに、副生成物である化合物（ＶＩ）の生成を抑え、目的物である化合物（ＩＶ）の生成量を高めることができることを示している。 On the other hand, when the aliphatic alcohol was added as shown in Examples 1 and 2, a high conversion rate exceeding 94% or 99% was shown in a short time of 0.25 or 1 hour. Further, when an aliphatic alcohol was added, a high selectivity exceeding 95% was shown. That is, when the aliphatic alcohol is added, the reaction can be completed in a very short time, and the production of the compound (VI) as a by-product is suppressed, and the amount of the compound (IV) as the target product produced. It can be increased.
　本発明は、産業上重要な農薬の製造およびその中間体の製造に好適に利用可能である。 The present invention can be suitably used for production of industrially important agricultural chemicals and intermediates thereof.

Claims (7)

  1. 　一般式（Ｉ）
    Figure JPOXMLDOC01-appb-C000001
     （式（Ｉ）中、Ｘ１およびＸ２は、それぞれ同じかまたは異なるハロゲン原子を表す）
    で示される２－ハロ－１－（１－ハロシクロプロピル）エタノンの製造方法であって、
    　一般式（ＩＩ）
    Figure JPOXMLDOC01-appb-C000002
     （式（ＩＩ）中、Ｘ１は、式（Ｉ）におけるＸ１と同じである）
    で示される化合物を脂肪族アルコール存在下において、ハロゲン化スルフリルと反応させてハロゲン化することを特徴とする２－ハロ－１－（１－ハロシクロプロピル）エタノンの製造方法。     Formula (I)
    Figure JPOXMLDOC01-appb-C000001
     (In formula (I), X 1 and X 2 each represent the same or different halogen atoms)
    A process for producing 2-halo-1- (1-halocyclopropyl) ethanone represented by
    Formula (II)
    Figure JPOXMLDOC01-appb-C000002
     (In formula (II), X 1 is the same as X 1 in formula (I))
    A process for producing 2-halo-1- (1-halocyclopropyl) ethanone, characterized by reacting with a halogenated sulfuryl compound in the presence of an aliphatic alcohol.
  2. 　上記ハロゲン化スルフリルに含まれる複数のハロゲン原子は互いに同一のハロゲン原子である、請求項１に記載の製造方法。 The production method according to claim 1, wherein the plurality of halogen atoms contained in the sulfuryl halide are the same halogen atoms.
  3. 　上記一般式（Ｉ）および上記一般式（ＩＩ）におけるＸ１は塩素原子であり、上記一般式（Ｉ）におけるＸ２は塩素原子であり、上記ハロゲン化スルフリルは塩化スルフリルである、請求項１または２に記載の製造方法。 X 1 in the general formula (I) and the general formula (II) is a chlorine atom, X 2 in the general formula (I) is a chlorine atom, and the sulfuryl halide is sulfuryl chloride. Or the manufacturing method of 2.
  4. 　上記脂肪族アルコールは炭素原子数１～１０の飽和または不飽和の脂肪族アルコールである、請求項１～３のいずれか１項に記載の製造方法。 The production method according to any one of claims 1 to 3, wherein the aliphatic alcohol is a saturated or unsaturated aliphatic alcohol having 1 to 10 carbon atoms.
  5. 　上記脂肪族アルコールは炭素原子数１～４の飽和脂肪族アルコールである、請求項４に記載の製造方法。 The production method according to claim 4, wherein the aliphatic alcohol is a saturated aliphatic alcohol having 1 to 4 carbon atoms.
  6. 　上記脂肪族アルコールの使用量は上記一般式（ＩＩ）で示される化合物に対して０．０１～２０倍モルである、請求項１～５のいずれか１項に記載の製造方法。 The production method according to any one of claims 1 to 5, wherein the amount of the aliphatic alcohol used is 0.01 to 20-fold mol relative to the compound represented by the general formula (II).
  7. 　上記ハロゲン化スルフリルの使用量は上記一般式（ＩＩ）で示される化合物に対して０．５～１０倍モルである、請求項１～６のいずれか１項に記載の製造方法。 The production method according to any one of claims 1 to 6, wherein the amount of the sulfuryl halide used is 0.5 to 10 moles compared to the compound represented by the general formula (II).
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* Cited by examiner, † Cited by third party
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CN104292089A (en) * 2014-09-30 2015-01-21 大连九信生物化工科技有限公司 Synthetic process of 1-chloro-cyclopropanecarbonyl chloride
CN104447262A (en) * 2014-12-17 2015-03-25 上海生农生化制品有限公司 Method for synthesizing 1-chloro-1-chloroacetyl-cyclopropane by adopting one-pot reaction
CN107602365A (en) * 2017-09-27 2018-01-19 长治市晋宁化工有限公司 A kind of preparation method of 2 chlorine 1 (1 chlorine cyclopropyl) ethyl ketones
WO2018060093A1 (en) 2016-09-29 2018-04-05 Bayer Cropscience Aktiengesellschaft 1,5-substituted imidazole derivatives as fungicides for crop protection.
CN108586220A (en) * 2018-06-27 2018-09-28 安徽国星生物化学有限公司 A kind of synthetic method of the chloro- 1- of 2- (1- chlorine cyclopropyl) ethyl ketone
CN111675608A (en) * 2020-05-26 2020-09-18 安徽久易农业股份有限公司 Process for producing 1-chloro-1' -chloroacetyl-cyclopropane

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Publication number Priority date Publication date Assignee Title
CN104292089A (en) * 2014-09-30 2015-01-21 大连九信生物化工科技有限公司 Synthetic process of 1-chloro-cyclopropanecarbonyl chloride
CN104292089B (en) * 2014-09-30 2016-01-13 大连九信生物化工科技有限公司 The synthesis technique of the chloro-1 '-chloracetyl cyclopropane of a kind of 1-
CN104447262A (en) * 2014-12-17 2015-03-25 上海生农生化制品有限公司 Method for synthesizing 1-chloro-1-chloroacetyl-cyclopropane by adopting one-pot reaction
CN104447262B (en) * 2014-12-17 2021-05-11 上海生农生化制品股份有限公司 Method for synthesizing 1-chloro-1-chloroacetyl-cyclopropane by one-pot method
WO2018060093A1 (en) 2016-09-29 2018-04-05 Bayer Cropscience Aktiengesellschaft 1,5-substituted imidazole derivatives as fungicides for crop protection.
CN107602365A (en) * 2017-09-27 2018-01-19 长治市晋宁化工有限公司 A kind of preparation method of 2 chlorine 1 (1 chlorine cyclopropyl) ethyl ketones
CN108586220A (en) * 2018-06-27 2018-09-28 安徽国星生物化学有限公司 A kind of synthetic method of the chloro- 1- of 2- (1- chlorine cyclopropyl) ethyl ketone
CN111675608A (en) * 2020-05-26 2020-09-18 安徽久易农业股份有限公司 Process for producing 1-chloro-1' -chloroacetyl-cyclopropane
CN111675608B (en) * 2020-05-26 2023-12-15 安徽久易农业股份有限公司 Process for producing 1-chloro-1' -chloroacetyl-cyclopropane

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