Ortho‐Substituent effects in N‐arylacetamides. NMR and molecular mechanics investigation

Abstract

Abstract1H, 13C, 15N and 17O NMR spectra of N‐phenylacetamide (acetanilide) and 21 ortho‐substituted acetanilides were measured and assigned. The observed NMR parameters are related to the Hammett substituent parameters and conformational characteristics of the acetamido moiety estimated by molecular mechanics calculations. Significant relationships were found for the 13C NMR chemical shifts of C‐5 (para to substituent) and the direct spin–spin coupling constant, 1J(C, H), of C‐3 (ortho to substituent) with Hammett substituent parameters. For 15N NMR chemical shifts of the amido nitrogen, no general correlation with the Hammett substituent parameters was found. The interactions between functionalities contiguous to the carbonyl group and the amino nitrogen in acetanilides are effectively hampered owing to the increased twist angle between the planes containing the phenyl ring and the H–N–C fragment in derivatives bearing bulky ortho substituents. Especially in ortho‐halogen‐substituted derivatives the 15N NMR chemical shift of the amino nitrogen is very clearly related to the twist angle between the phenyl ring and H–N–C fragment. For 17O NMR chemical shifts of the acetamido carbonyl, the observed variations can be related to the steric inhibition of resonance between the benzene ring and the acetamido group.