Efeito dos substituintes no equilíbrio conformacional do cis-3-aminocicloexanol e de seus derivados utilizando análise topológica, termodinâmica estatística e NBO

Abstract

The computational chemistry has long since reached a position of competitiveness withexperimental methods, generating many data as geometrical arrangement and relative energies, enabling studies of conformational analysis and hydrogen bonding (HB). For these studies, the rings of six members mono, 1,2-, 1,3- and 1,4-disubstituted models are widely used. Knowledge of the stability of hydrogen bonds becomes important to determine three-dimensional structures such as proteins, DNA and RNA. In this work five cis-1.3-disubstituted aminocyclohexanols were theoretically studied by calculation using the density functional theory with the level M06- 2X / 6-311 ++ G (3df, 3pd). The theoretical results were in agreement with the experimental to the MACOL, EACOL and DEACOL, showing that the diaxial conformer for these conformers were 92% (ΔG = 1.73 kcal.mol-1), 96% (ΔG = 1.80 kcal.mol-1) and 41% (ΔG = -0.21 kcal.mol 1), respectively. For ACOL and DMACOL the diaxial predominant conformation was also 83% (ΔG = 0.93 kcal mol-1) and 91% (ΔG = 1.34 kcal.mol-1), respectively, but slightly diverging from the experimental results. The topological analysis using the AIMALL and NCIPLOT programs confirmed and characterized the presence of intramolecular hydrogen bond O-H∙∙∙N in all diaxial conformers. The results obtained by NBO 6.0 showed increased electron density on the nitrogen to ACOL, MACOL, EACOL and DEACOL respectively. The interaction LP(1)N→σ*O-H increases with increasing nitrogen in the substituent group, demonstrating increased donor inductive effect of the electron density with the increase in the volume of these groups. The results showed that the NLMO of DMACOL (43.82 kcal.mol-1) and DEACOL (43.32 kcal.mol-1) had higher energy than the steric effect for MACOL (41.07 kcal.mol-1) and EACOL (40.94 kcal.mol-1), respectively. The ACOL was presented the lower energy value (39.49 kcal.mol-1). The results obtained by NBO and NLMO showed that the inductive effect of donor electron density and the steric effect increases in the same order, but with the predominance of steric effects.