Structural determinants of H-bonded layer and ribbon formation in crystals of α-, β-, and γ-substituted primary amides

Abstract

Previous studies observed one-, two-, and three-dimensional H-bonded supramolecular assemblies in crystal structures of primary amides. However, no systematic study of α/β/γ-alkyl- and α/β/γ-aryl-substituted primary amides has been undertaken thus far. In this paper, we report molecular and supramolecular structures of six pharmaceutically relevant primary amides. These include four α-substituted amides (2-methylpropionamide, 2-propylvaleramide, 2-phenylacetamide, and 2-methyl-2-phenylpropionamide), one β-substituted amide (3-methylbutyramide), and one γ-substituted amide (4-phenylbutyramide). Crystal structures of these compounds are stabilized by the N-H…O hydrogen bonds. One-dimensional H-bonded ribbons are observed in 2-propylvaleramide, and two-dimensional H-bonded layers are observed in the other five compounds. By comparing our results to the structures of primary amides (substituted acetamides) previously published by our group and other groups, we were able to formulate the following new structural insights: (i) in crystals of substituted primary amides, ribbons and layers are equally common; (ii) 4-phenylbutyramide molecules form an unusual type of layer based on the R²₄(8)R⁴₄(16) synthon; (iii) the preference for either layer or ribbon is determined by the bulkiness of substituents as well as their positions.