Solvent effects in the conformational stability of α-substituted acetamides through theoretical and experimental data

The conformational stability of fluoroacetamide (1), chloroacetamide (2), cyanoacetamide (3) and bromoacetamide (4) was studied using theoretical calculations in vapor phase and taking into account solvent effects. The conformational preference was determined by theoretical and experimental coupling constant values (2JCH and 3JCH). Theoretical results, including the solvent effects by PCM, allowed the characterization of the most stable conformers present in the studied solutions: trans rotamer for compounds 1 and 2, cis rotamer for compound 3 and gauche and trans rotamers for compound 4. The conformational preferences were explained by electrostatic and dipole–dipole interactions, steric effects and by the hyperconjugative interactions, which were revealed by NBO data.