A Greener Synthesis of the Antidepressant Bupropion Hydrochloride

Abstract

A laboratory experiment was developed to introduce systems thinking and green chemistry concepts through the synthesis of the antidepressant and smoking cessation aid, bupropion hydrochloride. The traditional synthesis has several issues from a green chemistry perspective: it uses the toxic solvents N-methylpyrrolidinone (NMP) and dichloromethane (DCM) and other hazardous chemicals including bromine and 12 M hydrochloric acid resulting in 138 kg of waste per kg of product. A greener synthesis has been developed with suitable improvements to the traditional procedure. The reprotoxic NMP and potentially carcinogenic DCM solvents have been substituted with the green biobased solvent Cyrene and ethyl acetate, respectively, and bromine has been substituted with N-bromosuccinimide. An alternate extraction method has also been developed using 1 M hydrochloric acid and ethyl acetate rather than 12 M hydrochloric acid and diethyl ether. These changes have also reduced waste by 92 kg kg–1, and the resultant experiment is much safer to perform. As part of this laboratory experiment, students synthesize bupropion hydrochloride, and the adaptations to the traditional process are discussed and evaluated. Students are also introduced to the green metrics of atom economy, process mass intensity, and E-factor, which they use to quantify the greenness of the original and adapted procedures.