Continuous preparation method of 4-methylimidazole

Abstract

The continuous preparation method of 4-methylimidazole comprises the following steps: providing a channel reactor; introducing liquid ammonia into the channel reactor; hydroxyacetone and formamide are introduced into the channel reactor, and the retention time of the reaction mixture in the channel reactor is 3-10 min.

Description

technical field [0001] The invention relates to a continuous preparation method of 4-methylimidazole, which improves the reaction efficiency. The present invention also relates to the use of the channel reactor in the continuous preparation of 4-methylimidazole. Background technique [0002] 4-methyl imidazole (4-methyl imidazole) is an important medical intermediate, mainly used in peptic ulcer drugs (histamine H 2 Synthesis of -receptor antagonist) cimetidine (Cimetidine, also known as cimetidine, trade name Tagamet). Cimetidine was invented and patented by SmithKline Beecham. It entered the British and American markets in 1976 and 1977 respectively, and became the world's first drug with annual sales exceeding one billion US dollars. After the expiration of the patent in 1994, the production of cimetidine expanded to all parts of the world. Currently, although the new generation of histamine H 2 - Receptor antagonists such as ranitidine, famotidine and the latest drug...

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Problems solved by technology

[0004] "Research on the Conversion of Hydroxyacetone into 4-Methylimidazole" by Yang Chunhua et al. ("Applied Chemical Industry" Volume 39 No. 5, May 2010) discloses a hydroxyacetone process, which adopts a traditional kettle reaction. Acetone, formamide, and liquid ammonia are used as raw materials, and 4-methylimidazole can be obtained in a relatively high yield at hydroxyacetone:formamide=1:5, temperature 160°C, and pressure 1.8-2.0MPa, but the reaction time is as long as 5 hours, the conversion rate can only reach 85.8%, and the product selectivity is only 81.6%, which has the problems of low yield and selectivity and high reaction cost

Disclosed in the U.S. Patent Application US07129711 is a process for preparing 4-methylimidazole, which is similar to "Research on the Conversion of Hydroxyacetone into 4-Methylimidazole" by Yang Chunhua et al. Amide and liquid ammonia are used as raw materials, and 4-methylimidazole is obtained by reaction at 100-200°C and pressure of 1-25MPa, but the reaction time is still as long as 0.5-2 hours, the reaction efficiency is low, and the yield is only 81%.

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