Identification of robust synthon in the molecular salts of 2-aminothiazole with substituted benzoic acids: A case study

Abstract

Six new salts of an API intermediate 2-aminothiazole with different carboxylic acid coformers were synthesized and characterized by IR (Infrared spectroscopy), 1 H-NMR, DSC (Differential scanning calorimetry), XRPD (X-ray powder diffraction) and single crystal XRD. The crystal structure of the salts with benzoic acid, 2,3-, 2,4-, 2,5-, 2,6-dihydroxybenzoic acids and 2,4-dinitrobenzoic acid were determined. The thiazole moiety exhibited solvent (polarity) assisted tautomerism in all reported salts and proton transfer was noticed to the ring N of thiazole due to which two point supramolecular synthon N + −H(thiazole)· · · O − (acid), N−H(amine)· · · O − (acid) was observed. The crystal structures were studied with respect to the positional effect of the competing functional groups like hydroxyl (−OH) and nitro (−NO 2 ) as well as their donor and acceptor abilities for hydrogen bonding. The presence of the non-conventional hydrogen bond (C−H· · · O) has been found to play a critical role in the formation of secondary supramolecular architectures.