Applications of 2-arylhydrazononitriles in synthesis: Preparation of new indole containing 1,2,3-triazole, pyrazole and pyrazolo[1,5-a]pyrimidine derivatives and evaluation of their antimicrobial activities

In this effort, 2-arylhdrazononitriles were used as key synthons for the preparation of wide variety of new, uniquely substituted heterocyclic substances. In addition, the results of biological evaluations demonstrate that members of the group prepared have promising antimicrobial activities against Gram negative bacteria, Gram positive bacteria and Yeast. In the synthetic sequences, 3-(1-methyl-1H-indol-3-yl)-3-oxo-2-(phenylhydrazono)propanenitrile 2a and its 2-methyl derivative 2b were found to react with hydroxylamine hydrochloride to yield the corresponding indolyl-5-amino-2-phenyl-1,2,3-triazoles 4a,b. These amines react with cyanoacetic acid in presence of acetic anhydride either thermally or under microwave irradiation conditions to yield the corresponding cyanoacetamides 5a,b, which condensed readily with dimethylformamide dimethylacetal to yield the enaminonitriles 6a,b. Whereas heating of 6a,b with hydrazine hydrate affords compound 8, compound 12 is produced when these reactants are subjected to microwave irradiation. We observed that the aminopyrazole 9 reacts with enaminal 13 to yield 14 and that its reactions with enaminones 15 afford 17. Finally, compound 5 reacts with cinnamaldehyde to yield the corresponding Schiff’s base 18 that does not undergo cyclization to form the pyridine derivative 19. The activities of all new substances synthesized in this investigation were evaluated against a panel of microbial organisms. The results show that 4a, 4b, 5b and 9b display strong antimicrobial activities against all of the tested organisms.

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► 2-arylhdrazononitriles were used as a precursors for the preparation of a variety of new heterocyclic compounds.
► A new classes of 1,2,3-triazole, pyrazole and pyrazolo[1,5-a]pyrimidine incorporating an indole moiety were prepared.
► A green methodology using the microwave irradiation as energy source was used.
► The biological evaluations of these compounds demonstrate that they having promising antimicrobial activities.