PNASM, New synthesis approaches

The classical and mechanochemical synthesis routes are compared. The hydrazones synthesis from low reactive hydrazines in solution and heteroaromatic aldehydes are carried out with total conversions by mechanochemistry aprroach. The first results are very encouraging showing a good reactivity and formation of hydrazones in the presence of Lewis acids. The exploration of this reaction also extends through collaborations to study the theoretical aspect and to understand the differences of reactivity observed in solution and by mechanochemistry (electronic aspects, crystalline aspects density and reactivity).
At the same time, all hydrazones are screened for their biological activities:
a) against herpes virus; several compounds are active at μM concentration
b) the compounds resulting from the coupling with isoniazid are very active on M. tuberculosis strains with a MIC of  nM range (collaboration MR Pasca, University of Pavia, Italy and J. Kordulakova, Comenius University, Slovak Republic ).
   The synthesis of conventionally constrained 1,2,4-triazole molecules usually involves long reactions at high temperatures and in the presence of solvents. Recent work in the literature has described an original route for obtaining 1,2,4-triazoles fused by oxidative cyclization of heterocyclic hydrazones under mild conditions. Our current project is to compare the conventional and mechanochemical approaches for variously substituted condensed triazoles from hydrazones prepared in the laboratory. The synthesized compounds are studied for their different biological properties.