Convenient and efficient N-methylation of secondary amines under solvent-free ball milling conditions

Abstract

Abstract In the present work, we report the development of a rapid, efficient, and solvent-free procedure for the N-methylation of secondary amines under mechanochemical conditions. After optimization of the milling parameters, a vibrational ball mill was used to synthesize 26 tertiary N-methylated amine derivatives. During our research, we investigated alternate reaction selectivity occurring in compounds able to form ring closure products that are 3,4-dihydro-2H-1,3-benzoxazine derivatives instead of N-methylated products. The liquid-assisted grinding (LAG) technique has been applied using formalin as a methylating agent and sodium triacetoxyborohydride as a reducing agent in a reductive amination reaction.