Supramolecular assembly in designing co-crystals of fumaric acid and pyrimidine/picolinate derivatives

Abstract

Two co-crystals possessing fumaric acid and 2-amino-4,6-dimethoxypyrimidine (1) and fumaric acid and ethyl 2-picolinate (2) were prepared. The structure of both compounds was determined using single-crystal X-ray crystallography. The asymmetric unit of cocrystal 1 formed in a triclinic system with space group P-1 consists of one 2-amino-4,6-dimethoxypyrimidine and one half of fumarate, whereas cocrystal of 2 formed in a monoclinic system with space group P2₁/c consists of an ethyl-2-picolinate and a half of fumarate. Co-crystal 1 exhibits intramolecular O–H···N and N–H···O hydrogen bonds as well as intermolecular N–H···O hydrogen bonds, whereas co-crystal 2 exhibits intermolecular C–H···O and O–H···N hydrogen bonds as well as weak π‒π stacking interactions. Intermolecular interactions were investigated using Hirshfeld surface analyses. H···H (40.9%), O···H (32.9%), and C···H (8.2%) are the major interactions in 1 and H···H (41.6%), O···H (34.8%), and C···H (8.5%) are the most common in 2. Furthermore, density functional theory (DFT) was used to investigate the structural features of the molecules using the B3LYP-D3/6-311G(d,p) basis set. Molecular electrostatic potential (MEP) surface and global reactivity descriptors for molecules were determined to explain the reactivity of molecular behavior, structural activity, and hydrogen bonds.