Studies on Synthesis of Antibacterial Agent (NM441). I. Kinetics and Mechanism of the Reaction of 4-(Bromomethyl)-5-methyl-1,3-dioxol-2-one with 1-Substituted Piperazine (NM394)

When a tertiary amine (4,NM441) is synthesized from 4-bromomethyl-5-methyl-1,3-dioxol-2-one (DMDO-Br) and a secondary amine (3,NM394) in N,N-dimethylformamide (DMF), the quaternary ammonium salt 5, the ring-opened compound 6, and the 1,2-adduct 7 are formed as by-products. The tertiary amine 4 is formed by nucleophilic attack of 3 on the α-carbon to the bromine atom of DMDO-Br. The ring-opened compound 6 is formed by nucleophilic attack of 3 on carbonyl carbon of DMDO-Br. The quaternary ammonium salt 5 is formed by the reaction of DMDO-Br with 4 (the Menshutkin reaction). Main pathway for the formation of 7 is the Michael addition of 3 to 6. Kinetics of the reactions have been studied and the methods to obtain 4 suppressing the formations of 5, 6, and 7 have been proposed based on the kinetic results.