Synthesis process of 2-thiopheneacetic acid

Abstract

The invention discloses a synthesis process of 2-thiopheneacetic acid, which comprises the following steps: enabling thiophene as a raw material and formaldehyde react with hydrochloric acid gas to produce 2-chloromethyl thiophene in the presence of an organic solvent; enabling 2-chloromethyl thiophene to react with trimethylsilyl cyanide to generate 2-thiophene acetonitrile in a catalyst condition in the presence of an organic solvent; and generating the thiopheneacetic acid from 2-thiophene acetonitrile in an alkaline condition. The process disclosed by the invention has the positive effects that (1) the required raw materials are relatively simple, and the reaction residues thiophene, an organic solvent, ethanol and dichloromethane can be recycled, thereby greatly reducing the production cost; (2) 2-chloromethyl thiophene reacts in the organic solvent so that chloromethyl thiophene can be stored stably and the danger of explosion is avoided; (3) since trimethylsilyl cyanide is adopted as a cyaniding reagent, the use of highly-toxic substance sodium cyanide is avoided, the reaction yield is increased, the product quality and the safety performance are relatively high, and the industrial production is facilitated; and (4) the reaction conditions are mild, a small quantity of catalyst is used, and the process is simple; and compared with the existing synthesis process, the process disclosed by the invention has obvious economic benefits and environmental benefits.

Description

technical field [0001] The invention relates to a synthesis process of 2-thiopheneacetic acid, which belongs to the technical field of fine chemicals. Background technique [0002] 2-thiopheneacetic acid is an important intermediate in organic synthesis, widely used in the synthesis of medicines, especially cephalosporins, such as the synthesis of spectrum antibacterial drugs cephalothin, cefotaxime, and cefoxitin. Structural modification of cephalosporin core 7-aminocephalosporanic acid can improve the antibacterial activity of the drug. In recent years, many new cephalosporin antibiotics have been developed with 2-thiopheneacetic acid abroad, including ceftriazole, cefniterol, and furonicazone. At the same time, 2-thiopheneacetic acid is also widely used in the fields of pesticides, dyes and other fine chemicals [0003] At present, there are mainly the following methods for the synthesis of 2-thiopheneacetic acid: (1) thiophene is obtained by acetylation reaction to o...

AI Technical Summary

Problems solved by technology

This synthesis reaction needs to be carried out under high pressure, the resulting product is difficult to separate, and the yield of the target product is only 20.9%.

(2) Chinese patent application 200510047449 discloses a method for synthesizing 2-thiopheneacetic acid from thiophene and glyoxylic acid. Although the method is simple, the cost of raw materials is high, the reaction yield is low and the post-treatment is complicated, so it is not easy to produce industrially

This synthetic method requires high-pressure reaction and noble metal catalyst, and there is highly toxic sodium cyanide in the reactant, which is dangerous in production and is not conducive to industrial production.

(5) Chloromethylation of thiophene to obtain 2-chloromethylthiophene, and then pressurize with carbon monoxide, methanol, and potassium hydroxide under cobalt salt catalysis to generate 2-thiophene acetate, and then hydrolyze to obtain 2-thiopheneacetic acid, This synthesis method also requires high-pressure reaction and noble metal catalyst, and the intermediate product 2-chloromethylthiophene is a kind of tear gas substance, which is unstable and has the risk of explosion when it is airtight.