N-1,3-thiazole-2-ylacetamide: An efficient novel cocrystal former with carboxylic acids

• Published in: Journal of molecular structure Vol. 1342; p. 142706
• Main Authors: Vidyarani, Kumar, A.H. Udaya, Mahesha, Lokanath, N.K., Naveen, S., Murthy, P. Krishna, Suchetan, P.A.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 15.10.2025
• Subjects: Cocrystal; Energy frameworks; Intermolecular interaction; Lattice energy; N-1,3-thiazole-2-ylacetamide; Intermolecular interaction; Lattice energy; Energy frameworks; Cocrystal; N-1,3-thiazole-2-ylacetamide
• ISSN: 0022-2860
• DOI: 10.1016/j.molstruc.2025.142706

•N-1,3-thiazole-2-ylacetamide (TA) was evaluated for its cocrystallization ability.•Cocrystals of TA with 10 para substituted benzoic acids (4-XBA) were prepared.•Liquid assisted grinding method was used for preparing 10 cocrystals.•All the cocrystals were characterized by DSC, FT-IR and PXRD studies.•Quantum chemical calculations (NBO, MEP, QTAIM, NCI, RDG) were performed on TA-4FBA. The ability of N-1,3-thiazole-2-ylacetamide (TA) as an efficient co-crystallizing agent has been explored by synthesizing novel 1:1 cocrystals with benzoic acid and nine para-substituted benzoic acids. All of them could be easily obtained by liquid-assisted grinding (LAG) using few drops of ethanol, which were then subject to studies such as DSC, FT-IR and PXRD. The cocrystals feature melting points lower than the starting materials. Single crystal XRD study revealed formation of 1:1 cocrystal (TA-4FBA) between TA and 4-fluorobenzoic acid via a pair of N-H…O and O-H…N hydrogen bonds leading to a R22(8) heterosynthon. Weak C-H…F and π…π dispersive interactions extend the heterosynthon into a one-dimensional ladder. The nature and topology of each interaction, the energy frameworks of individual synthons & supramolecular frameworks, and lattice energies of TA, 4FBA and TA-4FBA crystals were computed using CrystalExplorer. The results suggest that TA-4FBA cocrystal formation may be a kinetically driven process, as its formation cannot be accounted on thermodynamically. The TA-4FBA cocrystal was further subject to quantum chemical calculations at the hybrid B3LYP/6-311++G(d,p) level in the gas phase. The type, nature and strength of the intermolecular hydrogen bonds identified and analyzed using NBO analysis, molecular electrostatic potential mapping, QTAIM, NCI, and RDG methods were in agreement with the experimental and computational results obtained from CrystalExplorer. Our attempts to obtain single crystals of TA with 4-trifluoromethyl benzoic acid resulted in a new polymorph of TA. [Display omitted]