A FACILE ONE POT SYNTHESIS OF SEVERAL NEW FUSED PYRAZOLES OF EXPECTED BIOLOGICAL ACTIVITIES VIA DIPOLAR CYCLOADDITION REACTIONS WITH ARYL SEMICARBAZONES

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Author: PROF. Sami S. Ghobrial

A FACILE ONE POT SYNTHESIS OF SEVERAL NEW FUSED PYRAZOLES OF EXPECTED BIOLOGICAL ACTIVITIES VIA DIPOLAR CYCLOADDITION REACTIONS WITH ARYL SEMICARBAZONES

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Sami S. Ghabrial, Diaa A. Ibrahim , Kadria A. Genady (National Organisation for Drug Control and Research NODCAR)

This project deals with the synthesis of new fused pyrazole derivatives with the objective of studying their biological activities. From our gained experience in this field, the one pot dipolar cycloaddition reaction of aryl semicarbazones with different dipolarophiles constitutes an easy and unique route for the desired compounds.

This study involves:

Synthesis of several aryl semicarbazones

(1) via the reactions of aromatic aldehydes with semicarbazide hydrochloride.

Reaction of the resulting semicarbazones

(1) with N-chlorosuccinimide to obtain the corresponding chloro derivatives (2). Synthesis of the corresponding di-ionic species (3) by simple in situ treatment of (2) with triethylamine.

Synthesis of the corresponding pyrazolines

(4) by treatment of (3) with a variety of thiocarboxamidocinnamonitrile derivatives (5) which could be dehydrocyanated to give the corresponding pyrazole derivatives (6) via the reaction with ethanolic sodium ethoxide. Synthesis of the corresponding pyrazolines (7) by treatment of (3) with a variety of cyanocinnamonitrile derivatives (8) which could be dehydrocyanated to give the corresponding pyrazole derivatives (9) via the reaction with ethanolic sodium ethoxide.

Synthesis of the corresponding pyrazolines

(10) by treatment of (3) with a variety of the ethoxycarbonylcinnamonitrile derivatives (11) which could be dehydrocyanated to give the corresponding pyrazole derivatives (12) via the reaction with ethannolic sodium ethoxide.

Synthesis of the corresponding nitropyrazolines

(13) by treatment of (3) with a variety of w-nitrostyrene derivatives (14) which could be dehydrogenated to give the corresponding niotropyrazole derivatives (15) via boiling their solutions in nitrobenzene.

The structures of the newly synthesized heterocyclic derivatives were established using elemental analysis, IR, NMR, and MS spectral data.

The pyrazolidine derivatives showed high broad spectrum activity against some gram (+) and gram (-) bacteria while the cyanopyrazole derivative showed moderate activity. The rest of the new compounds showed low or no activity.

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