Features of switchable multicomponent heterocyclizations of salicylic aldehydes and 5-aminopyrazoles with pyruvic acids and antimicrobial activity of the reaction products

Three-component reactions of 5-aminopyrazoles and salicylic aldehydes with pyruvic acids were studied. The method of tuning of the selectivity of the heterocyclizations allowing to change its direction by variation of the reaction parameters was worked out. The treatment involving pyruvic acid can be selectively directed to the formation to either 3-aryl-10,11-dihydro-4,10-methano-pyrazolo[4,3-c][1,5]benzoxazocine-4-carboxylic acids or 3,6-diarylpyrazolo[3,4-b]pyridine-4-carboxylic acids, while the reaction involving arylpyruvic acid leads only to 7-hydroxy-2,5,6-triaryl-4,5,6,7-tetrahydro-pyrazolo[1,5-a]pyrimidine-7-carboxylic acids. Antimicrobial activity of the compounds obtained was also studied: Gram-positive bacteria (Bacillus subtilis and Staphylococcus aureus) were found sensitive to the substances tested, however, only in the highest concentration.     

Switchable selectivity in multicomponent heterocyclizations of acetoacetamides, aldehydes, and 3-amino-1,2,4-triazoles/5-aminopyrazoles

Multicomponent heterocyclizations of 3-amino-1,2,4-triazoles/5-aminopyrazoles with acetoacetamides and aromatic aldehydes were studied in detail using conventional thermal heating, ultrasonication, and microwave irradiation. Several different synthetic pathways for these cyclocondensations occurring under either kinetic or thermodynamic control were established depending on the temperature regime and building block selection. The experimental data obtained and the procedures developed allow tuning selectivity of the multicomponent reactions studied.     

Features of two- and multicomponent heterocyclization reactions involving 3,4-disubstituted 5-aminopyrazoles and alkyl pyruvates

Three-component heterocyclizations of pyruvic acids and their esters with 5-aminopyrazoles and aromatic aldehydes, in addition to the sequential versions of these reactions, under different activating conditions were studied. Under conventional heating, pyrazolopyrimidine derivatives containing a hydroxyl group in the 6-position were formed in both two- and three-component treatments. Whereas the application of an inert atmosphere did not influence the outcome of these reactions, the use of ultrasonic irradiation led to the formation of 7-hydroxy-tetrahydropyrazolopyrimidines in multi-component reactions and 6-hydroxy-dihydropyrazolopyrimidines in the case of a step-by-step approach. The products of the latter treatment were further transformed into heteroaromatized 6-hydroxy-pyrazolopyrimidines by conventional heating.