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

Abstract

AbstractThe 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.