Synthesis and conformational study of some N-nitroso-t(3)-benzyl-r(2),c(6)-bis(aryl)piperidin-4-one oximes using NMR spectra

Abstract

A series of heavily substituted N-nitroso-t(3)-benzyl-bis(aryl)piperidin-4-one oximes 9–13 have been synthesized by mixing N-nitroso-t(3)-benzyl-bis(aryl)piperidin-4-ones 5–8 with hydroxylamine hydrochloride and sodium acetate trihydrate in ethanol medium. The synthesized compounds 9–13 were characterized by elemental analysis, IR and NMR spectral studies (1H, 13C, HOMOCOSY and HSQC). At room temperature the N-nitroso-t(3)-benzyl-r(2),c(6)-bis(aryl)piperidin-4-one oximes 9–13 exist in two isomeric forms and the isomers are labeled as syn (nitroso oxygen is same side to N–OH group) and anti (nitroso oxygen is opposite side to N–OH group) isomers. Analysis of the spectral data shows that in 10–13 the NOH group is anti to the benzylic group at C(3). The favoured conformations of both the isomeric forms of N-nitroso oximes were determined by comparison of spectral data with those of the corresponding parent N-nitroso amines 5–8 and with the aid of substituent parameters. The observed coupling constants in 9 predict alternate chair form CA for the syn isomer and a highly distorted boat form B1 (aryl group at C(2) occupies flagpole position) for the anti isomer. Conformational analysis performed through DFT using Gaussian 09 program calculations also supports the conformations for the syn isomer of 9 whereas for the anti isomer of 9 there is a discrepancy between the results derived from theoretical and coupling constant studies. For N-nitroso-t(3)-benzyl oxime derivatives 10–13 the observed coupling constants predict an equilibrium mixture of boat form B1 and alternate chair form CA for the anti isomers and an equilibrium mixture of boat forms B1 and B5 (both the aryl groups occupy axial like orientations) for the syn isomers. The both syn and anti isomers of 9–13 the preferred conformation of benzylic group at C(3) is predicted to be A in which the phenyl group is gauche to C(4) and anti to C(2).