Understanding the mechanism of base-assisted decomposition of (N-halo),N-alkylalcoholamines

Abstract

The base-assisted decomposition of (N-X),N-methylethanolamine (X = Cl, Br) takes place mainly through two concurrent processes: a fragmentation and an intramolecular elimination. The global process follows second order kinetics, first order relative to both (N-X),N-methylethanolamine and base. Interaction of the base with the ionizable hydroxylic hydrogen triggers the reaction. The intramolecular elimination pathway leads to formaldehyde and 2-aminoethanol as reaction products via base-assisted proton transfer from the methyl to the partially unprotonated hydroxylic oxygen, with loss of halide. Meanwhile, the fragmentation pathway leads to methylamine and two equivalents of formaldehyde via bimolecular base-promoted concerted breakage of the molecule into formaldehyde, halide ion and N-methylmethanimine. Kinetic evidences allow a crude estimation of the concertedness and characterization of the transition structure for both processes, which are slightly asynchronous, the proton transfer to the base taking place ahead of the rest of the molecular events. The degree of asynchroneity increases as the bases become weaker. Electronic structure calculations, at the B3LYP/6-31++G** level, on the fragmentation pathway support the proposed mechanism.

A theoretical study on the mechanism of the base-promoted decomposition of N-chloro,N-methylethanolamine

“…It has been observed experimentally that the decomposition reaction of N-chloro,N-methylethanolamine in basic medium fulfils a second-order rate law, being first-order relative to both chloramine and base, 14 i.e., in the present case:…”

“…1(right). In this case the kinetically favoured process is the bimolecular fragmentation, as experimentally found, 14 followed by the sequence: intramolecular, Hofmann and Zaitsev eliminations.…”

“…2, 14 Six bonds are involved along the breaking/forming processes of the intramolecular elimination and bimolecular fragmentation, while only four bonds are directly involved in the Hofmann and Zaitsev eliminations (Scheme 2 and ESI).…”

Base-catalyzed reactions of environmentally relevant N-chloro-piperidines. A quantum-chemical study

“…This is in agreement with earlier experimental findings, where a dramatic acceleration of the decomposition process in N-chlorinated carbinolamines, in comparison to N-chlorinated amines lacking the hydroxyl moiety, has been observed. 50 Due to the introduction of the hydroxymethyl group in the piperidine ring system the elimination reaction mechanism becomes more complex. Several different reaction pathways can, in principle, be operative as illustrated in Scheme 6.…”

“…13, 49 The two main reaction paths were found to be intramolecular dehydrohalogenation and Grob fragmentation. [50][51][52] As the N-chloramine 4 cannot undergo Groblike fragmentation, the intramolecular dehydrochlorination is the most feasible rearrangement mechanism in an alkaline aqueous environment (see Scheme 5). It has been shown earlier that bimolecular eliminations, in which OHassists in base-promoted eliminations, are much slower processes in comparison to intramolecular dehydrohalogenations, in which a free hydroxyl group catalyzes the reaction.…”