High-Level ab Initio Molecular Orbital Calculations of Imine Formation

Abstract

Ab initio molecular orbital calculations at the G2(MP2,SVP) level are reported for the reaction between methylamine and formaldehyde to form the Schiff-base, N-methylmethanimine, with loss of water. The gas-phase barrier to carbinolamine formation through intramolecular proton transfer is found to be dramatically reduced when explicit water molecules are employed to facilitate the proton transfer. The lowest barrier lies 14.7 kJ mol-1 above the complex between methylamine, formaldehyde, and two water molecules and passes through a zwitterionic intermediate. The structural features of the transition state for this process closely resemble those predicted experimentally. Although intramolecular proton transfer through water molecules to form the imine from the carbinolamine requires significantly less energy than without the water, the barrier remains quite large. With two waters the barrier is calculated to be 111.9 kJ mol-1. A considerably smaller barrier is predicted for the protonated carbinolamine, 67.9 kJ mol-1, and while there is no experimental evidence for internal proton transfer, the calculated structure shows characteristics of the experimentally predicted transition state. Calculated aqueous-phase dissociation energies are too small in comparison with the experimentally observed equilibrium constants.

An Internal Reaction Chamber in Dimethylglycine Oxidase Provides Efficient Protection from Exposure to Toxic Formaldehyde

“…The resulting carbinolamine products are in rapid equilibrium with their corresponding amines and aldehydes (48). The oxidation of dimethylglycine to the corresponding iminium ion will therefore lead to rapid formation of formaldehyde.…”

Theoretical studies on models of lysine-arginine cross-links derived from α-oxoaldehydes: a new mechanism for glucosepane formation

“…The free energy barrier for this transformation is less than 4 kcal without participation of water molecule and can be done easily. Then Int2 evolves to the Schiff base as Hall and Smith reported this stage via reaction of MA and formaldehyde [24]. The reaction follows through a concerted proton transfer in which H 11 is transferred from N 1 to O 15 while H 10 from O 15 to O 7 TS2 in Fig.…”

The Hoffmann-Schiff dichotomy: on the reaction between chloral and amines

“…16 Although more extensive proton networking mechanisms may obtain, the observations are consistent with a concerted cyclic process of prototropy. 17 We therefore depicted the complexes for reactants, products and transition structures to involve two water molecules thus generating an eightmembered array for the eliminations. Transition structures for the collapse of the intermediate carbinolamine alternately to a formamide or an E-imine are given in Figure 1.…”