Process for producing cis-1.3 disubstituted benzyl imidazoline-2-ketone-2H-furo[3.4-d]imidazole-2,4,6- trione

Abstract

The invention belongs to the technical field of organic chemistry, and more particularly relates to a preparation method of cis-1.3-disubstituted benzyl imidazoline-2-ketone-2H-furo (3.4-d) imidazole-2, 4, 6-triketone (cyclic anhydride, I). The prior art has the disadvantages of high unit consumption of acetic anhydride, incomplete reaction and poor product quality, etc. In the preparation method, 1, 3-disubstituted benzyl imidazoline-2-ketone-cis-4, 5-dicarboxylic acid and various acyl halide are subject to dehydration / ring closure in an organic solvent or in a solvent-free way so as to obtain the cis-1.3-disubstituted benzyl imidazoline-2-ketone-2H-furo (3.4-d) imidazole-2, 4, 6-triketone (cyclic anhydride, I). The method can avoid the adoption of a great deal of acetic anhydride, and has mild reaction condition, product purity of more than 99 percent, low cost and less pollution to the environment, thus being suitable for industrial production.

Description

technical field [0001] The invention belongs to the technical field of organic chemistry, in particular to a cis-1.3-disubstituted benzyl imidazolin-2-ketone-2H-furo[3.4-d]imidazole-2,4,6-triketone (cyclic anhydride , 1) preparation method. [0002] [0003] where R 1 for hydrogen, C 1 ~C 6 Alkyl, phenyl, p-tolyl, p-methoxyphenyl, 3,4-dimethylphenyl, 3,4-dimethoxyphenyl, 3,4,5-trimethylphenyl, 3,4,5-trimethoxyphenyl or p-chlorophenyl, Ar is phenyl, p-tolyl, p-methoxyphenyl, 3,4-dimethylphenyl, 3,4-dimethoxy phenyl, 3,4,5-trimethylphenyl, 3,4,5-trimethoxyphenyl, p-chlorophenyl, thienyl, furyl or naphthyl. Background technique [0004] (3aS, 6aR)-1,3-disubstituted benzyl-tetrahydro-4H-furo[3,4-d]imidazole-2,4(1H)-dione (I) is a synthetic d-biotin ( d-Biotin, vitamin H, key intermediate of coenzyme R). U.S. Patent 2489232 describes 1,3-dibenzyl imidazolin-2-one-cis-4,5-dicarboxylic acid and acetic anhydride dehydration ring closure to prepare cis-1.3-dibenzyl imidazol...

AI Technical Summary

Problems solved by technology

U.S. Patent 2489232 describes 1,3-dibenzyl imidazolin-2-one-cis-4,5-dicarboxylic acid and acetic anhydride dehydration ring closure to prepare cis-1.3-dibenzyl imidazolin-2-one-2H - The preparation method of furo[3.4-d]imidazole-2,4,6-trione (cyclic acid anhydride, I), but the reaction conditions and yield are not disclosed, in our research process (Chemical Journal of Chinese Universities, 2001 , 22, 1141), found that 1,3-dibenzylimidazolin-2-ketone-cis-4,5-dicarboxylic acid and acetic anhydride must be reacted at 1:3 in mol ratio, yield 90%, However, there are still 5 to 10% of 1,3-dibenzyl imidazolin-2-one-cis-4,5-dicarboxylic acid raw materials not completely reacted, even if the reaction time is prolonged to 40h, the content of cyclic anhydride I is only 90-100%. 93%, it is difficult to obtain a high-purity product, and a large amount of acetic anhydride and acetic acid mixture are formed after the reaction, and the two are not easy to separate and apply mechanically

Chen Fen'er et al. (Chemical Journal of Chinese Universities, 2001, 22, 1141) added a catalytic amount of phosphoric acid to the above system and almost quantitatively completed the reaction within 3 hours, with a yield > 98%, but 1,3-dibenzylimidazoline -2-keto-cis-4,5-dicarboxylic acid and acetic anhydride molar ratio still needs 1:3 reaction to complete, otherwise the reaction is difficult to complete, and these disadvantages have not been properly solved fundamentally

Images