Precise synthesis of cyclopropyl methyl ketone via proton transfer of 5-chloro-2-pentanone driven by hydrogen bonds

Abstract

The traditional synthesis methods of cyclopropyl methyl ketone (CPMK) have some disadvantages such as low yield, slow reaction rate and unclear catalytic mechanism. To solve these problems, a new strategy is developed to synthesize CPMK from 5-chloro-2-pentanone (CPE) using 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). Experiment results show that the yield of CPMK reached a maximum of 96.5% in DBU at 40°C for 30min. The mechanism study shows that the hydrogen bond between DBU and CPE is the key to drive the deprotonation and cyclization of CPE. The hydrogen bond is formed between the N atom on C=N of DBU and the α-H on the methylene group associated with the carbonyl group on CPE. The catalyst DBU is converted into [DBUH]+Cl−, which can be reclaimed and recycled completely. The density functional theory (DFT) calculation confirmed the existence of molecular hydrogen bonds and proved that the hydrogen bond driving force is the key to the reaction. The hydrogen bond driven mechanism provides a new idea for the basic research of cyclization reaction.