One-pot synthesis of substituted 2-esteryl-3-acyl-1,5-benzodiazepines via three-component or domino reactions

【作者】 Laiyun Zhou； Jingtian Chen； 王兰芝；

【Author】 Laiyun Zhou;Jingtian Chen;Lanzhi Wang;The College of Chemistry and Material Science Hebei Normal University;

【机构】 The College of Chemistry and Material Science Hebei Normal University； 河北师范大学；

【摘要】 1,5-Benzodiazepine is a kind of extremely significant compounds,which have high biologicaland pharmacological activity in the last decades.¹ Previous studies on 1,5-benzodiazepines have indicated that free ester and acyl groups at different positions in the nuclei of the molecules can enhance the pharmacological properties of the compounds.2 Consequently,in view of our continuous interest in the synthesis of 1,5-benzodiazepine derivatives,we wished to synthesize 1,5-benzodiazepines with C2-position ester group and C3-position acyl group on the seven-membered ring structure.A multicomponent or domino reaction is one of the most desirable methods due to its efficient atom economy and green characteristics.3 Thus we have designed and one-pot synthesized a series of novel substituted 2-esteryi-3-acyl-1,5-benzodiazepines compounds via domino reactions（Scheme 1）.The compound（1） was obtained by two nucleophilic substitution reactions of acetophenone and N.N-dimethylformamide dimethyl acetal with the removal of the methanol molecules.And then,the compounds（2） were synthesized via nucleophilic substitution reaction.Finally,the compounds（3） were obtained via nucleophilic addition,dehydration,cyclization and hydrogen transfer of compound（2） with ethyl pyruvate.Six target compounds（3） were finally obtained via above domino reactions with excellent yields（80%-92 %）.These compounds are determined by ¹ H NMR,¹³C NMR,MS,and IR.Simple operation,short reaction time,high yields are the advantages of this synthesis method.更多还原

【Abstract】 1,5-Benzodiazepine is a kind of extremely significant compounds,which have high biologicaland pharmacological activity in the last decades.¹ Previous studies on 1,5-benzodiazepines have indicated that free ester and acyl groups at different positions in the nuclei of the molecules can enhance the pharmacological properties of the compounds.2 Consequently,in view of our continuous interest in the synthesis of 1,5-benzodiazepine derivatives,we wished to synthesize 1,5-benzodiazepines with C2-position ester group and C3-position acyl group on the seven-membered ring structure.A multicomponent or domino reaction is one of the most desirable methods due to its efficient atom economy and green characteristics.3 Thus we have designed and one-pot synthesized a series of novel substituted 2-esteryi-3-acyl-1,5-benzodiazepines compounds via domino reactions（Scheme 1）.The compound（1） was obtained by two nucleophilic substitution reactions of acetophenone and N.N-dimethylformamide dimethyl acetal with the removal of the methanol molecules.And then,the compounds（2） were synthesized via nucleophilic substitution reaction.Finally,the compounds（3） were obtained via nucleophilic addition,dehydration,cyclization and hydrogen transfer of compound（2） with ethyl pyruvate.Six target compounds（3） were finally obtained via above domino reactions with excellent yields（80%-92 %）.These compounds are determined by ¹ H NMR,¹³C NMR,MS,and IR.Simple operation,short reaction time,high yields are the advantages of this synthesis method.更多还原