A series of new 2-hydroxy-3-methoxybenzylidenethiazolo[3,2-a]pyrimidines with different aryl substituents at the 5 position are synthesized and characterized by ¹H/ ¹³C NMR and IR-spectroscopy and mass-spectrometry, as well as single crystal X-ray diffraction (SCXRD). It was demonstrated that the type of hydrogen bonding can play a key role in the chiral discrimination of these compounds in the crystalline phase. The hydrogen bond of the O–H...N type leads to 1D supramolecular heterochiral chains or conglomerate crystallization in the case of the formation of homochiral chains. The hydrogen bond of O–H...O type gave racemic dimers, which are packed into 2D supramolecular layers with a parallel or angular dimers arrangement. Halogen bonding of the N...Br or O...Br type brings a new motif into supramolecular self-assembly in the crystalline phase: the formation of 1D supramolecular homochiral chains instead 2D supramolecular layers. The study of cytotoxicity against various tumor cells in vitro was carried out. It was found that 2-hydroxy−3-methoxybenzylidenethiazolo[3,2-a]pyrimidines with 3-nitrophenyl substituent at C5 carbon atom demonstrated a high efficiency against M-HeLa (cervical adenocarcinoma) and low cytotoxicity against normal liver cells.

A series of new thiazolo[3,2-a]pyrimidines different by aryl substituents in 2 and 5 positions are synthesized and characterized in solution as well as in the crystalline phase using ¹H and ¹³C NMR-, IR-spectroscopies, mass-spectrometry methods, and single crystal X-ray diffraction (SCXRD). The SCXRD study revealed the role of intermolecular H-bonding in the formation of supramolecular architectures (racemic monomers, centrosymmetric racematic dimers, or homochiral 1D chains) of obtained thiazolo[3,2-a]pyrimidines derivatives depending on solvents (aprotic DMSO or protic EtOH) used upon the crystallization process. Moreover, the in vitro study of cytotoxicity toward different tumor cells showed their high or moderate efficiency with moderate cytotoxicity against normal liver cells which allows to consider the obtained thiazolo[3,2-a]pyrimidine derivatives as promising candidates for application as antitumor agents.

Triazolo[4,3-a]pyrimidine is one of the promising structural fragments for the development of drugs, including anticancer drugs. This work is devoted to the synthesis of a number of new 2-arylhydrazone derivatives of thiazolo[3,2-a]pyrimidine, which are synthetic precursors for triazolo[4,3-a]pyrimidines. The crystal structure of 6-acetyl-7-methyl-5-phenyl-2-(2-phenylhydrazineylidene)-5H-thiazolo[3,2-a]pyrimidin-3(2H)-one was established by SCXRD. In the reduction reaction of the compound, the following system was used: vanadium(V) oxide, and sodium borohydride in ethanol at room temperature, which led to the formation of only one pair of diastereomers (1R*)-1-((5S*,6R*,7R*)-(1-(hydroxymethyl)-7-methyl-1,5-diphenyl-1,5,6,7-tetrahydro[1,2,4]triazolo[4,3-a]pyrimidin-6-yl)ethan-1-ol.

The [3+2]-cycloaddition of azomethinylides formed in situ to dipolarophiles is a promising approach for the synthesis of dispyroderivatives of oxindole and acenaphthenedione. In the course of our studies, it was shown that the cycloaddition of azomethinylides occurs specifically through the exocyclic double C=C bond resulting in the formation of a new pyrrolidine cycle as part of the molecule and, consequently, a dispyroheterocycle. This work is devoted to the synthesis and structural analysis of dispyrothiazolo[3,2-a]pyrimidine in the crystalline phase.

Thiazolopyrimidines are attractive to medical chemists as new antitumor agents due to their high inhibitory activity against the replication process of tumor cells and the easy modification of their structure by changing the number and nature of substituents. The presence of asymmetric C5 carbon atoms requires the development of racemic mixture separation procedures for these heterocycles. One of the most effective methods is the crystallization of a racemic compound in the form of a conglomerate. The prerequisite for such separation is the construction of chiral, supramolecular ensembles in the crystalline state. Halogen-π interactions were chosen as supramolecular synthons. In this context, ethyl 7-methyl-3-oxo-2,3-dihidro-5H-thiazolo[3,2-a]pyrimidine-6-carboxylate containing a 4-bromophenyl fragment at C5 was synthesized. The crystal structure of the resulting compound was established using SCXRD. The role of the halogen-π interaction on the formation of one-dimensional homochiral chains is revealed.

Synthesis of para-carboxyhydrazinylidene, the derivative of 3-nitrophenylthiazolo[3,2-a]pyrimidine, was successfully performed with good yields. It was established that different types of non-covalent intermolecular interaction may influence the supramolecular motif-synthesized compound. Hydrogen- and chalcogen-bonding supramolecular driving forces collectively impacted the results of two types of the centrosymmetric racemic dimeric self-assembly in crystalline phase.