Computational Study of the Aminolysis of Anhydrides: Effect of the Catalysis to the Reaction of Succinic Anhydride with Methylamine in Gas Phase and Nonpolar Solution

Abstract

Different possible pathways of the aminolysis reaction of succinic anhydride were investigated by applying high level electronic structure theory, examining the general base catalysis by amine and the general acid catalysis by acetic acid, and studying the effect of solvent. The density functional theory at the B3LYP/6-31G(d) and B3LYP/6-311++G(d,p) levels was employed to investigate the reaction pathways for the aminolysis reaction between succinic anhydride and methylamine. The single point ab initio calculations were based on the second-order Møller-Plesset perturbation theory (MP2) with 6-31G(d) and 6-311++G(d,p) basis sets and CCSD(T)/6-31G(d) level calculations for geometries optimized at the B3LYP/6-311++G(d,p) level of theory. A detailed analysis of the atomic movements during the process of concerted aminolysis was further obtained by intrinsic reaction coordinate calculations. Solvent effects were assessed by the polarized continuum model method. The results show that the concerted mechanism of noncatalyzed aminolysis has distinctly lower activation energy compared with the addition/elimination stepwise mechanism. In the case of the process catalyzed by a second methylamine molecule, asynchronous proton transfer takes place, while the transition vectors of the acid-catalyzed transition states correspond to the simultaneous motion of protons. The most favorable pathway of the reaction was found through the bifunctional acid catalyzed stepwise mechanism that involves formation of eight-membered rings in the transition state structures. The difference between the activation barriers for the two mechanisms averages 2 kcal/mol at various levels of theory.

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.…”

Computational Study and Kinetic Analysis of the Aminolysis of Thiolactones

“…It should be noted that most computational studies reported so far only support the concerted and the neutral stepwise mechanism. In one study, 51 computational evidence for the existence of a zwitterionic intermediate in the aminolysis of anhydrides has been mentioned, but the zwitterionic intermediate could only be located as a stable minimum on the potential energy surface if a polarizable continuum model for water is considered during the geometry optimization. However, for benzoxazolinones a similar approach did not result in stable zwitterionic geometries 50 and neither for esters nor thioesters have such zwitterionic intermediates been reported.…”

Pivotal role of intramolecular catalysis in the selective acetylation of alkyl amines

“…Free energies of transition states and intermediates were calculated taking 3Ac and hexylamine, optimized separately, as the reference. For conversion from 1 atm standard state to 1 mol L −1 standard state, ΔG values were corrected by subtracting 1.90 kcal mol ‐1 to the calculated value according to an A + B → C reaction as recommended …”