Formation of a New Cocrystal Methyl‐4‐hydroxybenzoate:Urea and Its Structural and Thermal Properties

Abstract

A new cocrystal comprising two pharmaceutically important molecules methyl‐4‐hydroxybenzoate (p‐MHB) (C8H8O3) and carbonyl diamide (urea) [CO(NH2)2] is crystallized together for the first time through restricted solvent evaporation method at ambient conditions. The single crystal X‐ray diffraction analysis shows that the engineered cocrystal p‐MHB:urea (1:1) (C9H12N2O4) crystallizes in monoclinic system with centrosymmetric space group C12/c1. The internal structure analysis shows that the urea molecule with its unique ability forms hydrogen bonding network throughout the cocrystal system. Different orientations of the identified synthons form the networks via supramolecular connections such as C═O⋯H─O and C═O⋯N─H. Correlation between the internal molecular configurations in the unit cell, protruding molecular groups on different growth faces, and attachment energies of different crystal planes is studied. The Hirshfeld surface analysis shows that the higher percentage of overall interactions between the carbon and oxygen atoms at the outer surfaces of the cocrystal induces further incorporation of molecular aggregation and crystal growth. The 2D finger print plots infer that about 90.9% of the overall interactions are mainly due to the H bonds. Differential scanning calorimetry analysis reveals that the grown cocrystal undergoes an observable phase transition at 105.65 °C prior to its melting endotherm that peaks at 110.29 °C.