Ammonium Acetate Catalyzed Formation of 1,5-Benzodiazepines through [4+2+1] Cycloaddition Involving 5-Hydroxymethylfurfural

The use of the renewable platform molecule 5-hydroxymethylfurfural (5-HMF) in multi-component reaction with a diamine and an alkynone to generate seven-membered 1,5-benzodiazepines is described. Due to the sensitivity of 5-HMF to strong acidic and basic conditions, the investigation required an in-depth revisit of reaction parameters as compared to benchmark aldehydes. Among catalysts/solvents couples, ammonium acetate in ethanol proved to be a clean and efficient system. These optimized conditions were subsequently used to investigate the scope of the reaction providing a library of 1,5-benzodiazepines in moderate to good yields from a wide range of diversely substituted diamines and alkynones or alkyl alkynoates.

Automated summary

The use of the renewable platform molecule 5-HMF in multi-component reaction with a diamine and an alkynone to generate seven-membered 1,5-benzodiazepines is described. Ammonium acetate in ethanol proved to be a clean and efficient system among catalysts/solvents couples. The optimized conditions were used to investigate the scope of the reaction providing a library of 1,5-benzodiazepines in moderate to good yields from a wide range of diversely substituted diamines and alkynones or alkyl alkynoates.