Synthesis of Diphenhydramine Using Microwave Irradiation and Phase-Transfer Catalysis

In continuation of the search for effective, economical, and environmental methods of synthesizing the antihistamine agent diphenhydramine, alkylation of dimethylethanolamine by bromo- (or chloro-)diphenylmethane under phase-transfer catalysis (PTC) conditions and in a microwave oven was studied. The efficiencies of a two-phase liquid(liquid system and a solid-phase(liquid system were compared. The quaternary ammonium salt tetrabutylammonium bromide (TBAB) was used as a catalyst. The proposed microwave irradiation was found to be effective and allowed diphenhydramine to be synthesized in a short time in high yield and purity, suggesting that the proposed method could be used in practice.