Solvent Effects in the Regioselective N-Functionalization of Tautomerizable Heterocycles Catalyzed by Methyl Trifluoromethanesulfonate: A Density Functional Theory Study with Implicit Solvent Model

Autor(es)

Morgon, Nelson H. ; Biswas, Srijit ; Duari, Surajit ; de Souza, Aguinaldo R.

• Tipo de documento: Artigo Científico
• Fonte: COMPUTATION; v. 10, n. 10, p. 9-pg., 2022-10-01.

Resumo

Methyl trifluoromethanesulfonate was found to catalyze the reaction of the nucleophilic substitution of the hydroxyl group of alcohols by N-heterocycles followed by X- to N- alkyl group migration (X = O, S) to obtain N-functionalized benzoxazolone, benzothiazolethione, indoline, benzoimidazolethione and pyridinone derivatives. A high degree of solvent dependency on the yield of the products was observed during optimization of the reaction parameters. The yield of the product was found to be 0%, 48% and 70% in acetonitrile, 1,2-dichloroethane and chloroform, respectively. The mechanism of the reaction was established through experiments as well as DFT calculations. The functional B3LYP and 6-311++G(d) basis function sets were used to optimize the molecular geometries. D3 Grimme empiric dispersion with Becke-Johnson dumping was employed, and harmonic vibrational frequencies were calculated to characterize the stationary points on the potential energy surface. To ensure that all the stationary points were smoothly connected to each other, intrinsic reaction coordinate (IRC) analyses were performed. The influence of solvents was considered using the solvation model based on density (SMD). The free energy profiles of the mechanisms were obtained with vibrational unscaled zero-point vibrational energy (ZPE), thermal, enthalpy, entropic and solvent corrections. (AU)

• Processo FAPESP: 15/22338-9 - Estudo da interação entre fármacos e a albumina do soro humano (HSA) baseado em simulação computacional, DFT e TDDFT, experimentos de dicroísmo circular eletrônico, ECD, e determinação da constante de ligação
• Beneficiário: Aguinaldo Robinson de Souza
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 19/12294-5 - Cálculos teóricos de espectros eletrônicos (UV-Vis, fluorescência e dicroísmo circular) de moléculas de interesses farmacológico e aplicado
• Beneficiário: Nelson Henrique Morgon
• Modalidade de apoio: Auxílio à Pesquisa - Regular