JP5189278B2 - Method for collecting 2-acyl heteroaromatic compounds - 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。）の捕集方法に関する。

(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). The present invention relates to a method for collecting 2-acyl heteroaromatic compound (hereinafter referred to as 2-acyl heteroaromatic 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)

  In the production of 2-acetylpyrrole by subjecting pyrrole, which is a kind of heteroaromatic compound (1), to gas-phase contact reaction with acetic anhydride, production of 2-acetylpyrrole by ice-cold water as in the conventional method is performed. Since the melting point of 2-acetylpyrrole was as high as about 90 ° C. when collection was attempted, solidification of 2-acetylpyrrole occurred simultaneously with the introduction of the reaction product gas from the reactor to the ice-cold water through the introduction tube. A blockage occurred. 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.

  In addition, since the heteroaromatic compound (1) forms an azeotrope with many solvents (see, for example, VCH verlagsgesellschaft mbH, Azeotropic Data, pages 656 to 664 (1994)), it is usually a common trap. When a solvent-collecting solvent such as an alcohol solvent or an aromatic hydrocarbon solvent is used as a collection solvent, it becomes difficult to recover the unreacted heteroaromatic compound (1) by distillation, which increases production costs. This is not desirable because it causes

  In the production of a 2-acyl heteroaromatic compound (3) by reacting a heteroaromatic compound (1) with a carboxylic anhydride compound (2) in a gas phase, the present invention is compared with the conventional method by 2-acetylpyrrole. An industrially advantageous method for collecting 2-acyl heteroaromatic compound (3) that can easily recover unreacted heteroaromatic compound (1) without causing solidification of Is an issue.

  In the present invention, a reaction gas containing a 2-acyl heteroaromatic compound (3) produced by reacting a heteroaromatic compound (1) with a carboxylic anhydride compound (2) in a gas phase contact is produced as a heteroaromatic compound (1). The 2-acyl heteroaromatic compound is collected by dissolving the 2-acyl heteroaromatic compound (3) in the heteroaromatic compound (1).

  According to the collection method of the present invention, unreacted heteroaromatic compound (1) can be easily recovered without solidifying 2-acylheteroaromatic compound (3) as compared with the conventional method. Therefore, since the production efficiency of the 2-acyl heteroaromatic compound (3) can be improved, the collection method of the present invention has a 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 present invention, the method of reacting the heteroaromatic compound (1) with the carboxylic anhydride compound (2) in a gas phase contact 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.

  In the present invention, the reaction product gas containing the 2-acyl heteroaromatic compound (3) obtained by the above-described reaction is brought into contact with the heteroaromatic compound (1) as a collection solvent to obtain a 2-acyl heteroaromatic compound ( 3) is dissolved in the collection solvent and collected. By using the heteroaromatic compound (1) as a collection solvent, the 2-acylheteroaromatic compound (3) is dissolved in the heteroaromatic compound (1) without solidifying, and further, an unreacted heteroaromatic compound ( 1) can be easily recovered by distillation. The heteroaromatic compound (1) used is preferably the same type as the raw material used. Although the usage-amount of heteroaromatic compound (1) will not be specifically limited if it is the quantity which can fully melt | dissolve 2-acylheteroaromatic compound (3), It is with respect to 1 weight part of 2-acylheteroaromatic compound (3). The amount is usually 0.5 to 99 parts by weight, preferably 10 to 90 parts by weight.

  Next, the resulting heteroaromatic compound (1) solution of the reaction product gas is mixed with a basic aqueous solution, and then separated to obtain an organic layer. When the organic layer is concentrated, the heteroaromatic compound (1) is obtained. At the same time it can be recovered as a distillate, 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
2-acetylpyrrole was obtained as follows.
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. Using 1548 g of ice-cooled pyrrole as a collection solvent, the product contained in the reaction product gas flowing out from the reaction tube through the introduction tube from the start of the supply of pyrrole and acetic anhydride to 6 hours was collected. 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

Comparative Example 1
The reaction was carried out in the same manner as in Example 1 except that 1500 g of ice-cold water was used instead of the collection solvent pyrrole of Example 1 and the gaseous reaction product gas flowing out from the reaction tube was dissolved and cooled through the introduction tube. . As a result, the product contained in the obtained reaction product gas was deposited in the vicinity of the inlet of the introduction pipe at the same time as contacted with ice-cold water, and the introduction pipe was blocked in 1 hour from the start of the reaction, making it difficult to continue the reaction. .

Reference example 1
2573 g of the collected liquid obtained in Example 1 was added to 1290 g of water, and 1576 g of a 20% by weight aqueous sodium hydroxide solution was added dropwise over 90 minutes at a liquid temperature of 20 to 30 ° C. with stirring. Got.
Using 1876 g of the organic layer, distillation was performed by 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 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%.

Claims (3)

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) Formula (3) produced by a gas phase contact reaction with a carboxylic anhydride compound represented by:

(Wherein X, R ¹ and R ² are the same as above), the reaction product gas containing a 2-acyl heteroaromatic compound represented by formula (3) is brought into contact with the heteroaromatic compound (1). A method for collecting 2-acyl heteroaromatic compounds, wherein the 2-acyl heteroaromatic compounds represented by the formula (1) are dissolved in the heteroaromatic compound (1) and collected.   The collection method according to claim 1, wherein the heteroaromatic compound (1) is pyrrole or thiophene. The collection method according to claim 1 or 2, wherein R ² is an alkyl group having 1 to 4 carbon atoms.