JP5189279B2 - Method for producing 2-acyl heteroaromatic compound - Google Patents

Description

  The present invention is a formula (3) useful as an intermediate raw material for medical and agricultural chemicals:

（式中、ＸはＮＨ又は硫黄原子を示し、Ｒ^１は水素原子又は炭素数１〜４のアルキル基を示し、Ｒ^２はアリール基又は炭素数１〜４のアルキル基を示す。）で表される２−アシルヘテロ芳香族化合物（以下、２−アシルヘテロ芳香族化合物（３）という。）の製造方法に関する。

(Wherein, X represents NH or a sulfur atom, R ¹ represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, and R ² represents an aryl group or an alkyl group having 1 to 4 carbon atoms). It is related with the manufacturing method of 2-acyl hetero aromatic compound (henceforth 2-acyl hetero aromatic compound (3)).

  In the presence of a catalyst, the formula (1):

（式中、Ｘ及びＲ^１は前記に同じ。）で表されるヘテロ芳香族化合物（以下、ヘテロ芳香族化合物（１）という。）を式（２）：
（Ｒ^２ＣＯ）_２Ｏ （２）
（式中、Ｒ^２は前記に同じ。）で表される無水カルボン酸化合物（以下、無水カルボン酸化合物（２）という。）と気相接触反応せしめて２−アシルヘテロ芳香族化合物（３）を製造する方法は公知であるが（例えば、特許文献１又は非特許文献１参照）、反応終了後に得られる反応生成ガスから２−アシルヘテロ芳香族化合物（３）を取り出す方法については殆ど開示されておらず、反応終了後に氷冷した水で捕集することが記載されているのみである。
特開昭６２−２９８５８１ Ｃａｔａｌ．Ｌｅｔｔ．，５４，９５−１００（１９９８）

(Wherein X and R ¹ are the same as defined above) a heteroaromatic compound (hereinafter referred to as heteroaromatic compound (1)) represented by formula (2):
(R ² CO) ₂ O (2)
(Wherein R ² is the same as above) and a gas-phase contact reaction with a carboxylic anhydride compound represented by the following formula (hereinafter referred to as carboxylic anhydride compound (2)) to give 2-acyl heteroaromatic compound (3). Although the manufacturing method is well-known (for example, refer patent document 1 or nonpatent literature 1), almost no method is disclosed about taking out 2-acyl heteroaromatic compound (3) from the reaction product gas obtained after completion | finish of reaction. In addition, it is only described that the reaction is collected with ice-cold water after the reaction is completed.
JP-A-62-298581 Catal. Lett. , 54, 95-100 (1998)

  When the present inventors produce 2-acetylpyrrole by subjecting pyrrole, which is a kind of heteroaromatic compound (1), to gas-phase contact reaction with acetic anhydride, it is included in the reaction product gas by ice-cold water as in the conventional method. When 2-acetylpyrrole was collected, the melting point of 2-acetylpyrrole was as high as about 90 ° C., so that the reaction product gas was introduced into the ice-cold water from the reactor through the introduction tube, and at the same time solidified 2-acetylpyrrole. Happened and the inlet tube was blocked. Further, the solubility of 2-acetylpyrrole in 100 g of water is about 0.4 g, and water is not preferable as a collecting solvent, and the conventional method is not yet satisfactory for industrial production.

  Then, after using pyrrole as a collection solvent to obtain a pyrrole solution of the reaction mixture, it was attempted to obtain 2-acetylpyrrole by concentrating and distilling off pyrrole, but pyrrole and / or 2-acetyl was obtained. Polymerization of pyrrole occurred and it was difficult to obtain 2-acetylpyrrole (see Comparative Example 1).

  In producing the 2-acetylheteroaromatic compound (3) by reacting the heteroaromatic compound (1) with the carboxylic anhydride compound (2) in the gas phase, the present invention provides a 2-acylheteroaromatic compound (3). A method for producing a 2-acyl heteroaromatic compound (3) without causing solidification of the polymer and polymerization of the heteroaromatic compound (1) and / or the 2-acyl heteroaromatic compound (3) together Is an issue.

The present inventor has intensively studied to solve the above-mentioned problems. As a result, the 2-acyl heteroaromatic compound (3) in the reaction product gas is easily solidified by using a hydrophobic organic solvent instead of the conventional water. That the by-product carboxylic acid contained in the obtained collected liquid contributes to the polymerization of the heteroaromatic compound (1) and / or the 2-acyl heteroaromatic compound (3). Obtained knowledge. Therefore, if the by-product carboxylic acid is removed, the 2-acyl heteroaromatic compound (3) can be produced without causing polymerization of the heteroaromatic compound (1) and / or the 2-acyl heteroaromatic compound (3). As a result, the present invention has been completed.
That is, the present invention provides a method for producing a 2-acyl heteroaromatic compound (3) by reacting a heteroaromatic compound (1) with a carboxylic anhydride compound (2) in a gas phase contact reaction. The 2-acyl heteroaromatic compound (3) is dissolved and collected in a hydrophobic organic solvent by contacting with a hydrophobic organic solvent, and then the by-product carboxylic acid contained in the obtained collected liquid is removed. To a method for producing a 2-acetylheteroaromatic compound.

  According to the production method of the present invention, compared with the conventional method, the solidification of the 2-acyl heteroaromatic compound (3) and the polymerization of the heteroaromatic compound (1) and / or the 2-acyl heteroaromatic compound (3) are performed. Since the 2-acyl heteroaromatic compound (3) can be produced without producing both, the production method of the present invention has high industrial utility value.

The present invention is described in detail below.
In Formula (1) and Formula (3), R ¹ is a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, preferably a hydrogen atom. Examples of the alkyl group having 1 to 4 carbon atoms include linear or branched alkyl groups having 1 to 4 carbon atoms, specifically, methyl group, ethyl group, propyl group, isopropyl group, butyl group, An isobutyl group, a sec-butyl group, and a tert-butyl group are mentioned.

In formula (2) and formula (3), R ² is an aryl group or an alkyl group having 1 to 4 carbon atoms, preferably an alkyl group having 1 to 4 carbon atoms. As an aryl group, the aryl group which may be substituted by the above-mentioned alkyl group is mentioned, Specifically, a phenyl group, 2-tolyl group, 3-tolyl group, 4-tolyl group etc. are mentioned, for example. Examples of the alkyl group having 1 to 4 carbon atoms include the above-described alkyl groups.

  Specific examples of the heteroaromatic compound (1) include pyrrole, 2-methylpyrrole, 3-methylpyrrole, 2-ethylpyrrole, 3-ethylpyrrole, 2-propylpyrrole, 3-propylpyrrole, 2-isopropylpyrrole, 3-isopropylpyrrole, 2-butylpyrrole, 3-butylpyrrole, 2-isobutylpyrrole, 3-isobutylpyrrole, 2-sec-butylpyrrole, 3-sec-butylpyrrole, 2-tert-butylpyrrole, 3-tert- Butylpyrrole, thiophene, 2-methylthiophene, 3-methylthiophene, 2-ethylthiophene, 3-ethylthiophene, 2-propylthiophene, 3-propylthiophene, 2-isopropylthiophene, 3-isopropylthiophene, 2-butylthiophene, 3-Buchi Thiophene, 2-isobutyl-thiophene, 3-isobutyl-thiophene, 2-sec-butyl-thiophene, 3-sec-butyl-thiophene, 2-tert-butyl-thiophene and 3-tert-butyl-thiophene.

  Specific examples of the carboxylic anhydride compound (2) include acetic anhydride, propionic anhydride, butyric anhydride, isobutyric anhydride, valeric anhydride, isovaleric anhydride, pivalic anhydride, caproic anhydride, benzoic anhydride, and toluyl anhydride. An acid etc. are mentioned.

  Specific examples of the 2-acyl heteroaromatic compound (3) include 2-acetylpyrrole, 2-acetyl-3-methylpyrrole, 2-acetyl-4-methylpyrrole, 2-acetyl-5-methylpyrrole, and 2-acetyl. -3-ethylpyrrole, 2-acetyl-4-ethylpyrrole, 2-acetyl-5-ethylpyrrole, 2-acetyl-3-propylpyrrole, 2-acetyl-4-propylpyrrole, 2-acetyl-5-propylpyrrole 2-acetyl-3-isopropylpyrrole, 2-acetyl-4-isopropylpyrrole, 2-acetyl-5-isopropylpyrrole, 2-acetyl-3-butylpyrrole, 2-acetyl-4-butylpyrrole, 2-acetyl- 5-butylpyrrole, 2-acetyl-3-isobutylpyrrole, 2-acetyl-4-y Butylpyrrole, 2-acetyl-5-isobutylpyrrole, 2-acetyl-3-sec-butylpyrrole, 2-acetyl-4-sec-butylpyrrole, 2-acetyl-5-sec-butylpyrrole, 2-acetyl-3 -Tert-butylpyrrole, 2-acetyl-4-tert-butylpyrrole, 2-acetyl-5-tert-butylpyrrole, 2-acetylthiophene, 2-acetyl-3-methylthiophene, 2-acetyl-4-methylthiophene 2-acetyl-5-methylthiophene, 2-acetyl-3-ethylthiophene, 2-acetyl-4-ethylthiophene, 2-acetyl-5-ethylthiophene, 2-acetyl-3-propylthiophene, 2-acetyl- 4-propylthiophene, 2-acetyl-5-propylthiophene 2-acetyl-3-isopropylthiophene, 2-acetyl-4-isopropylthiophene, 2-acetyl-5-isopropylthiophene, 2-acetyl-3-butylthiophene, 2-acetyl-4-butylthiophene, 2-acetyl-5 -Butylthiophene, 2-acetyl-3-isobutylthiophene, 2-acetyl-4-isobutylthiophene, 2-acetyl-5-isobutylthiophene, 2-acetyl-3-sec-butylthiophene, 2-acetyl-4-sec- Butylthiophene, 2-acetyl-5-sec-butylthiophene, 2-acetyl-3-tert-butylthiophene, 2-acetyl-4-tert-butylthiophene, 2-acetyl-5-tert-butylthiophene,

  2-propionylpyrrole, 2-propionyl-3-methylpyrrole, 2-propionyl-4-methylpyrrole, 2-propionyl-5-methylpyrrole, 2-propionyl-3-ethylpyrrole, 2-propionyl-4-ethylpyrrole, 2-propionyl-5-ethylpyrrole, 2-propionyl-3-propylpyrrole, 2-propionyl-4-propylpyrrole, 2-propionyl-5-propylpyrrole, 2-propionyl-3-isopropylpyrrole, 2-propionyl-4 -Isopropylpyrrole, 2-propionyl-5-isopropylpyrrole, 2-propionyl-3-butylpyrrole, 2-propionyl-4-butylpyrrole, 2-propionyl-5-butylpyrrole, 2-propionyl-3-isobutylpyrrole, 2 − Lopionyl-4-isobutylpyrrole, 2-propionyl-5-isobutylpyrrole, 2-propionyl-3-sec-butylpyrrole, 2-propionyl-4-sec-butylpyrrole, 2-propionyl-5-sec-butylpyrrole, 2 -Propionyl-3-tert-butylpyrrole, 2-propionyl-4-tert-butylpyrrole, 2-propionyl-5-tert-butylpyrrole, 2-propionyl-thiophene, 2-propionyl-3-methylthiophene, 2-propionyl -4-methylthiophene, 2-propionyl-5-methylthiophene, 2-propionyl-3-ethylthiophene, 2-propionyl-4-ethylthiophene, 2-propionyl-5-ethylthiophene, 2-propionyl-3-propylthio , 2-propionyl-4-propylthiophene, 2-propionyl-5-propylthiophene, 2-propionyl-3-isopropylthiophene, 2-propionyl-4-isopropylthiophene, 2-propionyl-5-isopropylthiophene, 2- Propionyl-3-butylthiophene, 2-propionyl-4-butylthiophene, 2-propionyl-5-butylthiophene, 2-propionyl-3-isobutylthiophene, 2-propionyl-4-isobutylthiophene, 2-propionyl-5-isobutyl Thiophene, 2-propionyl-3-sec-butylthiophene, 2-propionyl-4-sec-butylthiophene, 2-propionyl-5-sec-butylthiophene, 2-propionyl-3-tert-butylthio Phen, 2-propionyl-4-tert-butylthiophene, 2-propionyl-5-tert-butylthiophene,

  2-butyrylpyrrole, 2-butyryl-3-methylpyrrole, 2-butyryl-4-methylpyrrole, 2-butyryl-5-methylpyrrole, 2-butyryl-3-ethylpyrrole, 2-butyryl-4-ethylpyrrole 2-butyryl-5-ethylpyrrole, 2-butyryl-3-propylpyrrole, 2-butyryl-4-propylpyrrole, 2-butyryl-5-propylpyrrole, 2-butyryl-3-isopropylpyrrole, 2-butyryl- 4-isopropylpyrrole, 2-butyryl-5-isopropylpyrrole, 2-butyryl-3-butylpyrrole, 2-butyryl-4-butylpyrrole, 2-butyryl-5-butylpyrrole, 2-butyryl-3-isobutylpyrrole, 2-butyryl-4-isobutylpyrrole, 2-butyryl-5-isobutyl pillow 2-butyryl-3-sec-butylpyrrole, 2-butyryl-4-sec-butylpyrrole, 2-butyryl-5-sec-butylpyrrole, 2-butyryl-3-tert-butylpyrrole, 2-butyryl-4 -Tert-butylpyrrole, 2-butyryl-5-tert-butylpyrrole, 2-butyryl-thiophene, 2-butyryl-3-methylthiophene, 2-butyryl-4-methylthiophene, 2-butyryl-5-methylthiophene, 2-butyryl-3-ethylthiophene, 2-butyryl-4-ethylthiophene, 2-butyryl-5-ethylthiophene, 2-butyryl-3-propylthiophene, 2-butyryl-4-propylthiophene, 2-butyryl-5 -Propylthiophene, 2-butyryl-3-isopropylthiophene, 2-butyl Ryl-4-isopropylthiophene, 2-butyryl-5-isopropylthiophene, 2-butyryl-3-butylthiophene, 2-butyryl-4-butylthiophene, 2-butyryl-5-butylthiophene, 2-butyryl-3-isobutyl Thiophene, 2-butyryl-4-isobutylthiophene, 2-butyryl-5-isobutylthiophene, 2-butyryl-3-sec-butylthiophene, 2-butyryl-4-sec-butylthiophene, 2-butyryl-5-sec- Butylthiophene, 2-butyryl-3-tert-butylthiophene, 2-butyryl-4-tert-butylthiophene, 2-butyryl-5-tert-butylthiophene,

  2-benzoylpyrrole, 2-benzoyl-3-methylpyrrole, 2-benzoyl-4-methylpyrrole, 2-benzoyl-5-methylpyrrole, 2-benzoyl-3-ethylpyrrole, 2-benzoyl-4-ethylpyrrole, 2-benzoyl-5-ethylpyrrole, 2-benzoyl-3-propylpyrrole, 2-benzoyl-4-propylpyrrole, 2-benzoyl-5-propylpyrrole, 2-benzoyl-3-isopropylpyrrole, 2-benzoyl-4 -Isopropylpyrrole, 2-benzoyl-5-isopropylpyrrole, 2-benzoyl-3-butylpyrrole, 2-benzoyl-4-butylpyrrole, 2-benzoyl-5-butylpyrrole, 2-benzoyl-3-isobutylpyrrole, 2 -Benzoyl-4-isobutylpyrrole 2-benzoyl-5-isobutylpyrrole, 2-benzoyl-3-sec-butylpyrrole, 2-benzoyl-4-sec-butylpyrrole, 2-benzoyl-5-sec-butylpyrrole, 2-benzoyl-3-tert- Butylpyrrole, 2-benzoyl-4-tert-butylpyrrole, 2-benzoyl-5-tert-butylpyrrole, 2-benzoyl-thiophene, 2-benzoyl-3-methylthiophene, 2-benzoyl-4-methylthiophene, 2 -Benzoyl-5-methylthiophene, 2-benzoyl-3-ethylthiophene, 2-benzoyl-4-ethylthiophene, 2-benzoyl-5-ethylthiophene, 2-benzoyl-3-propylthiophene, 2-benzoyl-4- Propylthiophene, 2-benzoyl-5 Propylthiophene, 2-benzoyl-3-isopropylthiophene, 2-benzoyl-4-isopropylthiophene, 2-benzoyl-5-isopropylthiophene, 2-benzoyl-3-butylthiophene, 2-benzoyl-4-butylthiophene, 2- Benzoyl-5-butylthiophene, 2-benzoyl-3-isobutylthiophene, 2-benzoyl-4-isobutylthiophene, 2-benzoyl-5-isobutylthiophene, 2-benzoyl-3-sec-butylthiophene, 2-benzoyl-4 -Sec-butylthiophene, 2-benzoyl-5-sec-butylthiophene, 2-benzoyl-3-tert-butylthiophene, 2-benzoyl-4-tert-butylthiophene, 2-benzoyl-5-tert-butylthio Examples include phen.

  In the production method of the present invention, the method of reacting the heteroaromatic compound (1) with the carboxylic anhydride compound (2) in a gas phase contact reaction is described in, for example, JP-A-62-298581, Catal. Lett. , 54, 95-100 (1998) or the like can be used. Specific examples include a method in which a zeolite catalyst is used as the catalyst and the heteroaromatic compound (1) is subjected to a gas phase contact reaction with the carboxylic anhydride compound (2) in a temperature range of 100 to 300 ° C.

  The 2-acyl heteroaromatic compound (3) obtained by the above-mentioned method is dissolved and collected in the hydrophobic organic solvent by bringing the reaction product gas containing this into contact with the hydrophobic organic solvent as the collecting solvent. . In this way, by using a hydrophobic organic solvent as the collection solvent, the reaction mixture can be collected without solidifying the reaction mixture. The hydrophobic organic solvent is not particularly limited as long as it dissolves the 2-acyl heteroaromatic compound (3). For example, a hydrophobic alcohol solvent such as butanol or hexanol, for example, aliphatic carbonization such as hexane, cyclohexane or octane. Examples include hydrogen solvents such as aromatic hydrocarbon solvents such as toluene and xylene, and hydrophobic heteroaromatic compound solvents such as pyrrole, preferably hydrophobic heteroaromatic compound solvents, and heteroaromatics of the same type as the raw materials used. The group compound (1) is particularly preferred. This is because if the heteroaromatic compound (1) is used as a collection solvent, the unreacted heteroaromatic compound (1) can be easily recovered by distillation. These may be used alone or in admixture of two or more. The amount of the organic solvent to be used is not particularly limited as long as it can dissolve the 2-acyl heteroaromatic compound (3) sufficiently, but is usually 0.5 with respect to 1 part by weight of the 2-acyl heteroaromatic compound (3). It is -99 weight part, Preferably it is 10-90 weight part.

  Next, by-product carboxylic acid is removed from the obtained collected liquid. Examples of the method for removing the carboxylic acid include 1) a method of mixing with the water, 2) a method of mixing with the basic aqueous solution, and the like, and a method of mixing with the basic aqueous solution is preferable. After mixing with a basic aqueous solution, the organic layer may be obtained by liquid separation. If it does in this way, carboxylic acid byproduced can be removed to a water layer as carboxylate. Examples of basic aqueous solutions include aqueous solutions of alkali metal hydroxides such as lithium hydroxide, potassium hydroxide, and sodium hydroxide, such as methylamine, dimethylamine, trimethylamine, ethylamine, diethylamine, triethylamine, propylamine, dipropylamine, Examples include aqueous solutions of hydrophilic amines such as tripropylamine and isopropylamine, for example, aqueous solutions of hydrophilic heteroaromatic hydrocarbon compounds such as pyridine, picoline, lutidine, collidine, and the like. The amount of the basic aqueous solution used is not particularly limited as long as it can sufficiently neutralize the carboxylic acid contained in the collected liquid, and as a base contained in the basic aqueous solution with respect to 1 mol of carboxylic acid. The amount is usually 1 mol or more, preferably 1.5 to 5 mol.

  If the organic layer is concentrated after separation, the 2-acyl heteroaromatic compound (3) can be obtained as a concentrated residue. The 2-acyl heteroaromatic compound (3) may be further purified by a desired purification operation such as distillation.

  In order to describe the present invention in more detail, specific examples are given below, but the present invention is not limited thereto. The analysis used gas chromatography.

Example 1
500 ml of zeolite catalyst was filled in a stainless steel reaction tube having an inner diameter of 20 mm. After the zeolite catalyst packed part of the reaction tube was heated to 300 ° C., pyrrole and acetic anhydride were supplied at the same temperature to carry out the reaction. The supply amount of pyrrole was 99.1 g / hr, and the supply amount of acetic anhydride was 150.9 g / hr. The product contained in the reaction product gas flowing out of the reaction tube from the start of the supply of pyrrole and acetic anhydride was collected using 1548 g of chilled pyrrole as the collection solvent. 2-Acetylpyrrole did not solidify during trapping. The composition of the obtained collected liquid was as follows.
2-Acetylpyrrole 14.3 parts by weight Pyrrole 58.9 parts by weight Acetic acid 18.8 parts by weight To 1290 g of water, 2573 g of the collected liquid was added, and 1576 g of a 20% by weight aqueous sodium hydroxide solution was stirred and the liquid temperature 20 It was added dropwise at -30 ° C over 90 minutes. The PH at that time was 6.98. After completion of dropping, liquid separation was performed to obtain an organic layer. The composition of the obtained organic layer was as follows.
2-Acetylpyrrole 17.1 parts by weight Pyrrole 71.1 parts by weight Acetic acid 0 parts by weight Using 1876 g of the organic layer, a glass distillation tower having a tower diameter of 20 mm and a theoretical plate number of 12 and using a glass distillation column under a reduced pressure of 18 to 2 kPa, Distillation was performed by distillation to distill pyrrole. Distillation of pyrrole required 3.5 hours, and the liquid temperature in the distillation pot during this distillation was 69 to 132 ° C. As a result, first, a fraction which was pyrrole having a purity of 99% was obtained with a yield of 98%.
Subsequently, 2-acetylpyrrole was distilled at a reflux ratio of 5 under a reduced pressure of 2 to 0.3 kPa. At this time, the liquid temperature of the distillation column condenser was kept at 100 ° C. to prevent the solidification of 2-acetylpyrrole. As a result, a fraction which was 2-acetylpyrrole having a purity of 98% was obtained with a yield of 75%.

Comparative Example 1
The collected liquid obtained in the same manner as in Example 1 was distilled in a total distillation under reduced pressure of 18 to 2 kPa using a glass distillation tower having a tower diameter of 20 mm and a theoretical plate number of 12 to distill acetic acid and pyrrole. I made it come out. The distillation of acetic acid and pyrrole required 7.5 hours, and the liquid temperature in the distillation kettle during this distillation was 105 to 176 ° C. As a result, when a fraction of 90% purity pyrrole was obtained at a yield of 80%, the distillate became highly viscous and difficult to distill. The distillation kettle residue was black tar.

Claims (5)

Formula (1):

(Wherein, X represents NH or a sulfur atom, and R ¹ represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms) (hereinafter referred to as a heteroaromatic compound (1)). .) To formula (2):
(R ² CO) ₂ O (2)
(Wherein R ² represents an aryl group or an alkyl group having 1 to 4 carbon atoms) and a vapor-phase contact reaction with a carboxylic anhydride compound represented by formula (3):

In the method for producing a 2-acyl heteroaromatic compound represented by the formula (wherein X, R ¹ and R ² are the same as above), the obtained reaction product gas is contacted with a hydrophobic organic solvent to formula ( 2-acetyl heteroaromatic compound represented by 3) is dissolved and collected in a hydrophobic organic solvent, and then by-product carboxylic acid contained in the obtained collected liquid is removed. 2-acetyl A method for producing a heteroaromatic compound.   The method according to claim 1, wherein the reaction mixture solution is mixed with a basic aqueous solution in removing the carboxylic acid.   The production method according to claim 1 or 2, wherein the hydrophobic organic solvent is a heteroaromatic compound (1).   The manufacturing method in any one of Claims 1-3 whose heteroaromatic compound (1) is pyrrole or thiophene. R ² is an alkyl group having 1 to 4 carbon atoms, The process according to any one of claims 1 to 4.