Polymorphism of Crystalline 4-Amino-2-Nitroacetanilide

Abstract

This paper reports the preparation and structural characterization of 4-amino-2-nitroacetanilide (ANA). Comprehensive analysis of the conformational, hydrogen bonding, and crystal packing preferences of ANA has been performed using X-ray crystallography, verified using high-resolution solid-state 13C, 15N, and 1H MAS NMR, and rationalized using ab initio calculations. The compound crystallizes in two different polymorphic forms, red (P21/n space group) and orange (P21/c space group), and as a monohydrate (C2/c space group). The latter pseudopolymorph has a deep, red wine color. All three forms crystallize in the monoclinic space group with comparable molecular volumes (V/Z) for the polymorphs and a significantly larger molecular volume for the monohydrate. Significant structural relationships have been identified for the crystal forms of ANA. The crystal color is dependent on the conformation of the molecule and its ability to form an intramolecular hydrogen bond (HB) involving the nitro group. In the orange polymorph, both nitro and acetanilide groups are twisted relative to the plane of the phenyl ring. This arrangement precludes formation of the intramolecular HB between these groups. In contrast, the groups in the red polymorph and in the monohydrate are favorably disposed, and thereby, such HBs are formed. Our work demonstrates the utility of integrating crystallography, spectroscopy, and ab initio calculations in detailed structural studies of polymorphism and hydrate formation. The most significant result is that the experimental molecular geometries of ANA in the studied crystal forms correspond well to the minimum values of the theoretical DFT energy curve for the amide group rotation.