Herein, modern green synthesis approaches are studied to assemble N-heterylarenes scaffolds via a non-catalyzed intramolecular 5/6-exo-dig cyclocondensation reaction based on the in-situ generation of arenehydrazonopentan-/hexan-2-one. Accordingly, the formation of two N-heteryl moieties, pyrazol-1-yl and pyridazin-1(4H)-yl, was initially studied. Therefore, appropriate fluorophenyl was first converted into their respective phenylhydrazine by SNAr reaction and then reacted with different trigonal carbonyl bielectrophiles (-CO-, -CO₂R, and -CO₂H) in ethanol in the presence of US, MW, IR, and an IR· US irradiation mixture. Cyclic nitrogenous cores were best obtained when subjected to microwave irradiation with ketone and arylhydrazine as starting reagents, allowing them to get excellent yields quickly. Arylhydrazine reactants featuring Π-donor groups underwent the best 5/6-exo-dig type annulment reaction. Presumably, the observed improvements in EDG-dependent reaction efficiency reflect changes in the nucleophilicity of arylhydrazines intermediates as α-nucleophilic reactants.

A series of new 4-(1,3,4-thiadiazol-2-yl)-containing polysubstituted pyrroles 3 a-k has been synthesized by a preparative convenient method from ethyl 5-chloro-4-formyl-1H-pyrrole-3-carboxylates 1 a-e, which were selectively transformed into the corresponding polysubstituted pyrrole-4-carboxylic acids 2 а-е using sodium hypochlorite as an oxidizer. Further, they were transformed into the target compounds with a high yield using the cyclocondensation with N-mono- or N,N-disubstituted thiosemicarbazides in the boiling phosphorus trichloroxide. As seen from the screening of antimicrobial activity, the synthesized compounds exhibit the inhibiting and bactericide activity against some bacteria and fungi. The highest activity has been established for the compounds 3 a, c, e-h, j against the strain Klebsiella pneumoniae (МІС=31.25 µg/mL). The calculated HOMO energy level proves that the compound 3 с is the most reactive ligand for the interaction with a protein receptor. The molecular docking data show that the compound 3 h has the highest affinity to the ThiM Klebsiella pneumoniae kinase.