The amide bond represents one of the most fundamental functional groups in chemistry. The properties of amides are defined by amidic resonance (nN→π*C=O conjugation), which enforces planarity of the six atoms comprising the amide bond. Despite the importance of 4-halo-substituted benzamides in organic synthesis, molecular interactions and medicinal chemistry, the effect of 4-halo-substitution on the properties of the amide bond in N,N-disubstituted benzamides has not been studied. Herein, we report the crystal structures and energetic properties of a full series of 4-halobenzamides. The structures of four 4-halobenzamides (halo = iodo, bromo, chloro and fluoro) in the N-morpholinyl series have been determined, namely 4-[(4-halophenyl)carbonyl]morpholine, C11H12XNO2, for halo = iodo (X = I), bromo (X = Br), chloro (X = Cl) and fluoro (X = F). Computations have been used to determine the effect of halogen substitution on the structures and resonance energies. 4-Iodo-N-morpholinylbenzamide crystallized with a significant distortion of the amide bond (τ + χN = 33°). The present study supports the correlation between the Ar-C(O) axis twist angle and the twist angle of the amide N-C(O) bond. Comparison of resonance energies in synthetically valuable N-morpholinyl and N-piperidinyl amides demonstrates that the O atom of the morpholinyl ring has a negligible effect on amidic resonance in the series.
Keywords: amide bonds; crystal structure; morpholinyl amides; resonance energies; twisted amides.