Supramolecular interplay: how non-covalent bonds affect the crystal packing of 2-arylmethylidenethiazolo[3,2-a]pyrimidines

Abstract

A series of new halogen-substituted thiazolo[3,2-a]pyrimidine derivatives were obtained with high yields and characterized by ¹H and ¹³C NMR, IR-spectroscopy, ESI, MALDI-TOF-mass-spectrometry and SCXRD. The study demonstrated that structural diversity in 2-arylmethylidene thiazolo[3,2-a]pyrimidine derivatives – introduced through halogen atoms, aryl groups, and the heterocyclic core – enables a wide range of non-covalent interactions (CH⋯Hal hydrogen bonds, Hal⋯O/N halogen bonds, and π⋯π-stacking). Crystal packing was found to be tunable by varying halogen positions in the aryl fragments: di-meta-substitution favored van der Waals-dominated assembly without halogen bonding, while di-para-substitution led to a unique supramolecular motif of heterochiral halogen-bonded (Hal⋯O) dimers. Notably, para–meta-substitution produced homochiral halogen-bonded chains, suggesting potential for chiral discrimination and enantiopure crystallization. Polymorphism observed in these systems further supports their versatility in solid-state organization.