Study On Synthetic Process Of Bupropion Hydrochloride

In this paper, bupropion hydrochloride, a new antidepressant and stop-smoking drugs, was synthesized by using m-chloropropiophenone as the primal material.The synthetic process undergo two steps, including m-chloropropiophenone's bromination and m-chloro-a-bromopropiophenone's amination and acidification. On the step of bromination, three different brominating agents were investigated, including bromine, Py-HBr-Br2 and [Bmim]Br3.The optimal reaction conditions were obtained through optimizing test separately.The m-chloro-a-bromopropiophenone was synthesized with bromine as brominating agent. The yield of the product was 97.4%, and its purity was 98.2%. The optimal reaction conditions were as follows:CH2Cl2 as solvent, molar ratio of m-chloropropiophenone to bromine was 1:1.02,TsOH as catalyst, the amount of the catalyst was 2%(mass fraction), reaction was carried out for 1.5 h at 30℃,and the bromine was added in 0.5 h.The m-chloro-a-bromopropiophenone was synthesized with Py-HBr-Br2 as brominating agent. The yield of the product was 95.6%, and its purity was 98.1%.The optimal reaction conditions were as follows:ethanol as solvent, molar ratio of m-chloropropiophenone to Py-HBr-Br2 was 1:1.2,reaction was carried out for 3 h at 60℃,and the brominating agent was added in four.The m-chloro-a-bromopropiophenone was synthesized with [Bmim]Br3 as brominating agent. The yield of the product was 94.7%, and its purity was 97.5%.The optimal reaction conditions were as follows:molar ratio of m- chloropropiophenone to [Bmim]Br3 was 1:1.05, reaction was carried out for 0.5 h at 30℃.The bupropion hydrochloride was synthesized through the amination of t-butyl amine and m-chloro-a-bromopropiophenone. The yield of the product was upon 89%, and its purity was about 99.7%. The optimal reaction conditions were as follows:NMP as solvent, molar ratio of m-chloro-a-bromopropiophenone, t-butyl amine and hydrogen chloride was 1:5:1.5, TBAI as catalyst, the amount of the catalyst was 2%(mass fraction), reaction was carried out for 1.5 h at 50℃.