Conformational preferences for some 2-substituted N-methoxy- N-methylacetamides through spectroscopic and theoretical studies

Abstract

The analysis of the IR carbonyl band of the 2-substituted N-methoxy- N-methylacetamides Y–CH 2C(O)N(OMe)Me (Y = F 1, OMe 2, OPh 3, Cl 4), supported by B3LYP/6-311++G(3df, 3pd) calculations along with the NBO analysis for 1– 4, indicated the existence of cis– gauche conformers i.e. ( c) and ( g) for 1 and 3, ( c 1 , c 2) and ( g 1 , g 2) for 2, and ( c) and ( g 1 , g 2) for 4. In the gas phase, the g conformer population prevails over the c one, for 1 and 3, the ( c 1 + c 2) population prevails over the ( g 1 + g 2) one for 2, and the ( g 1 + g 2) conformer population is more abundant than ( c) one for 4. In n-hexane solution, the cis conformer is more abundant for 1– 3. The occurrence of Fermi resonance in the ν CO region, in n-hexane, precludes the estimative of relative populations of the ( c, g 1, g 2) conformers for 4. The SCI-PCM calculations agree with the solvent effect on the ν CO band component relative intensities for 1– 3. NBO analysis showed that the n N → π co ∗ orbital interaction is the main factor which stabilizes the gauche ( g, g 1, g 2) conformers for 1– 4 into a larger extent relative to the cis ( c, c 1, c 2) ones. The n Y → π co ∗ , σ C Y → π co ∗ , π co → σ C Y ∗ and π co ∗ → σ C Y ∗ orbital interactions still contribute, but into a minor extent for the stabilization of the gauche conformers relative to the cis ones. The existence of some pyramidalization at the nitrogen atom of the Weinreb amides 1– 4 is responsible for the occurrence of Y δ −(4)···O δ −(9) and Y δ −(4)···N δ −(7) short contacts in the gauche ( g, g 1, g 2) conformers, which originates strong repulsive Coulombic interactions, acting in opposition to the large orbital stabilization of the gauche conformer with respect to the cis one. Therefore, a delicate balance of the Coulombic and orbital interactions seems to be responsible for the observed stabilization of the gauche ( g, g 1, g 2) and cis ( c, c 1, c 2) conformers, both in the gas phase and in the solution for 1– 4. However, the cis conformer predominance, in non polar solvents, for the 2-substituted N-methoxy- N-methyl acetamides 1– 3, bearing in α first raw (fluorine and oxygen) atoms, is in the opposite direction to the gauche conformer preference for the corresponding 2-substituted N, N-dialkyl-acetamides.