O-H...O AND O-H...N HYDROGEN BONDS AS SUPRAMOLECULAR SYNTONS IN THE FORMATION OF CHIRAL ARCHITECTURES ON THIAZOLO[3,2-a]PYRIMIDINE 2-ARILMETHYLIDENE DERIVATIVE FRAMEWORKS IN THE CRYSTALLINE PHASE

The synthesis of new antitumor drugs is a promising direction in modern science. Nowadays, some thiazolopyrimidine derivatives are already known to exhibit different antitumor activities. Since the biological activities of racemate and pure enantiomers of many biologically active compounds may greatly differ from each other, the question of their separation, i.e., obtaining them in enantiopure form, is a pressing one.

Non-covalent interactions may be important for understanding the mechanism of drug action and can also be used in crystallization to separate racemic mixtures into pure enantiomers. Since a racemic mixture is formed during the synthesis of thiazolo[3,2-a]pyrimidine derivatives, the study of these derivatives in the crystalline phase is an essential problem.

This work is devoted to the synthesis and study of the supramolecular organization of new thiazolo[3,2-a]pyrimidine derivatives in the crystalline phase. The structure of all obtained compounds was characterized by IR, NMR ¹H and ¹³C spectroscopy, ESI-MS spectrometry, and SCXRD analysis.

The influence of the synthesized derivatives’ structure and the used solvent’s nature on the supramolecular motif of their organization in the crystal phase due to the presence of O-H...N and O-H...O type hydrogen bonds was established.

The majority of derivatives containing the o-vanillin fragment form racemic dimers. Derivatives containing a 4-hydroxybenzylidene fragment form zigzag homochiral chains. When derivatives containing a 2-hydroxybenzylidene fragment crystallize, bridging hydrogen O-H...N and O-H...O bonds are produced with a solvate molecule. It causes the formation of zigzag homochiral chains in the crystalline phase.

The crystallization of derivatives containing 2-methoxyphenyl with 2-hydroxybenzylidene and phenyl with 2-hydroxy-3-methoxybenzylidene moieties, respectively, from ethanol resulted in the formation of conglomerates.