DFT Study and Monte Carlo Simulation on the Aminolysis of XC(O)OCH₃ (X = NH₂, H, and CF₃) with Monomeric and Dimeric Ammonias

Abstract

The aminolysis of substituted methylformates (XC(O)OCH3, X = NH2, H, and CF3) in the gas phase and acetonitrile are investigated by the density functional theory B3LYP/6-311+G(d,p) method and Monte Carlo (MC) simulation with free energy perturbation (FEP) techniques. The direct and the ammonia-assisted aminolysis processes are considered, involving the monomeric and dimeric ammonia molecules, respectively. In each case, two different pathways, the concerted and stepwise, are explored. The calculated results show that, for the direct aminolysis, the activation barrier of the concerted path is lower than that of the rate-controlling step of the stepwise process for all three reaction systems. In contrast, for the ammonia-assisted mechanism, the stepwise process is more favorable than the concerted pathway. The substituent effects at the carboxyl C atom of methylformate are discussed. This aminolysis of substituted methylformates is more favored for X = CF3 than for X = H and NH2 in the gas phase for both the direct and the ammonia-assisted processes. Solvent effects of CH3CN on the reaction of HC(O)OCH3 + nNH3 (n = 1, 2) are determined by Monte Carlo simulation. The potential energy profiles along the minimum energy paths in the gas phase and in acetonitrile are obtained. It is shown that CH3CN lowers the energy barriers of all reactions.

Concerted Amidation of Activated Esters: Reaction Path and Origins of Selectivity in the Kinetic Resolution of Cyclic Amines via N-Heterocyclic Carbenes and Hydroxamic Acid Cocatalyzed Acyl Transfer

“… 22 , 23 A second amine molecule can also facilitate the proton transfer via the general base pathway. 24 − 27 Theoretical 19 and experimental 28 studies have shown that 2-pyridinone, acetic acid, 29 and triazabicyclodecene (TBD) 30 can also act as proton conduits. In many systems, the two-step and concerted pathways are nearly isoelectronic; greater differentiation comes from steric and electronic interactions between the reacting partners.…”

Microsolvated transition state models for improved insight into chemical properties and reaction mechanisms

“…45 In a more recent study by Xue and coworkers on the aminolysis of a large family of methylformates using the B3LYP/6-311+G** level of theory it was suggested that the reaction follows a general-base-catalyzed neutral stepwise mechanism. 46 Particularly noteworthy is their observation that the most favored ammonia-assisted mechanism proceeds through a stepwise pathway, wherein the proton transfer is facilitated by the explicit ammonia molecule in the transition state. The solvation effects exerted by acetonitrile, as obtained through Monte Carlo simulations, suggested that the role of polar solvent is relatively more pronounced in the ammoniaassisted stepwise pathway as compared to the unassisted direct pathway for aminolysis.…”

Mechanism of the Aminolysis of Fischer Alkoxy and Thiocarbene Complexes: A DFT Study

“…Although several kinetic studies regarding the aminolysis Fischer carbene complexes have been carried out, no computational studies have been reported until now to the best of our knowledge. On the other hand, the analogue organic reaction of the ester aminolysis has been the subject of both experimental kinetic − and theoretical studies. − Since the aminolysis mechanism was found to strongly depend on the nature of ester, amine, and solvent, several studies have been made focusing on different aspects of this reaction. Experimentally, in many of the aminolysis reactions of esters, zwitterionic tetrahedral intermediates are predicted to be involved, and either the formation or breakdown of intermediate can be rate-limiting. ,,, Computational studies have been performed focusing on the understanding of the aminolysis mechanism and the catalytic influence of solvents such as water and alcohol, although general base catalysis by amine/ammonia as well as general acid catalysis has also attracted much attention. ,− , Theoretical calculations are in disagreement with the mechanism of ester aminolysis in the possible formation of zwitterionic intermediates.…”