Solvatomorphism of 2-(4-Fluorophenylamino)-5-(2,4-dihydroxybenzeno)-1,3,4-thiadiazole Chloride

Abstract

2-(4-Fluorophenylamino)-5-(2,4-dihydroxybenzeno)-1,3,4-thiadiazole (FABT) is a biologically active compound. It forms planar molecules and cations. Single crystals of the FABTH+ chloride grown from water solutions of different alcohols, such as methanol, propan-2-ol, and butanol, show structural changes induced mostly by hydrogen bond interactions with chloride anions and solvent molecules. For structures with the alcohol molecules built in the crystal lattice, the FABTH+ moiety takes the conformation with the o-OH (ortho position) group from the resorcin ring on the same side of the molecule as the sulfur atom in the thiadiazole ring, whereas, in the alcohol free crystals growth from a butanol−water mixture, this group is situated on the other side of the thiadiazole ring. The incorporation of the alcohol molecules into the crystal structures formed by FABTH+ cations strongly depends on their size, and it influences the properties of crystal lattices. In the case of the FABTH+Cl− crystallized from butanol, the crystal structure consists of columns of FABTH+ cations forming intermolecular channels containing two water molecules and two chloride anions related by centers of symmetry. The crystal structure of FABTH+Cl− crystallized from methanol is built of two separate layers consisting of FABTH+ cations and methanol and chloride anions repeating periodically. FABTH+Cl− crystallized from propan-2-ol forms a 3D structure with separate water and propan-2-ol molecules glued by chloride anions and layers of the FABTH+ cations. The Hirshfeld surface analysis is a very useful tool in identifying subtle differences between the solvates. The DFT computations allow us to estimate the energy difference between the two conformers to be 3.2 kcal/mol and the rotational barrier to be 12.6 kcal/mol.