Comparison of Conventional and Microwave Assisted Synthesis, Structural Study and Antimicrobial Screening of Substituted [1,2,4,5]-Tetrazines

Abstract

A series of 5,6-diaryl-[1,2,3,4]-tetrazines 4 have been obtained by microwave irradiation followed by the basification of their dihydroiodides 3 with dilute ammonium hydroxide solution. These compounds were synthesized also by conventional heating for comparison. The latter were synthesized by the oxidative cyclization of 1,2-diaryl-2-hydrazino-ethylidine amines 2 using ethanolic iodine. The parent compounds 2 were prepared by refluxing the mixtures of substituted benzils 1 and hydrazine hydrate in n-propanol for 60 hr. Compounds 4 on acylation with acetic anhydride in 1:2 ratio afforded 2,3-diacetyl derivatives 5 and on reaction with sodium nitrite in 1:2 ratio in acidic medium afforded 2,5-dinitroso derivatives 6. The structures of synthesized compounds were established on the basis of chemical transformation, elemental analysis, IR,1H-NMR and Mass spectral studies. The title compounds have been assayed for their antimicrobial activity against gram-positive as well as gram-negative microorganisms.

Introduction

The text describes the use of microwave-assisted synthesis, a green chemistry technique, for the preparation of tetrazine compounds. This method is eco-friendly, reduces reaction time, and provides higher yields compared to conventional synthesis. The study focuses on synthesizing 5,6-diaryl-[1,2,3,4]-tetrazines using substituted benzils and iodine, offering an alternative to previously reported methods.

In the results and discussion, intermediate compounds (2a–c) are synthesized by reacting substituted benzils with hydrazine hydrate. These are further treated with iodine to form tetrazine dihydroiodides (3a–c), which are converted into free bases (4a–c). These compounds are then modified to produce diacetyl derivatives (5a–c) and dinitroso derivatives (6a–c).

The antimicrobial activity study shows that some synthesized compounds (especially 4b and 4c) exhibit strong antibacterial activity against certain bacteria like Bacillus subtilis and Salmonella typhi, moderate activity against E. coli, and little to no effect on others.

A comparison of microwave vs conventional methods demonstrates that microwave synthesis significantly reduces reaction time (minutes instead of hours) while slightly improving yields.

The experimental section details synthesis procedures and characterization techniques, including melting point determination, IR spectroscopy, NMR, mass spectrometry, and TLC for purity analysis.

References

[1] Ponzio G & Gastaldi C, Gazz Chim Ital, 1913, 53(2), 129; Ponzio G & Gastaldi C, Ibid, 1914, 44(1), 277; 1915, 45(1), 181. [2] Curtius T & Lang C, J Parkt Chem, 1888, 38, 532. [3] Wiley P F & Weiss-berger A, Interscience, New York, 1956. [4] Wystach V P, “Heterocyclic Compounds,Volume-8”, Wiley, New York, 1967. [5] Pilgram K & Skiles R K, J Org Chem, 1976, 41, 3392. [6] Lang S A, Jr Johnson B D & Cohen E, J Hetero Chem, 1976, 12, 1143. [7] Rita Sharma, Rajinder Dahiya & Pujari H K, Indian J Chem, 1991, 30B, 508-510. [8] Jag Mohan, Virender Singh & Sangeeta Kataria, Indian J Hetero Chem, 2(3), 189-190; Chem Abstr, 1993, 119, 160243K. [9] Jag Mohan, Indian J Chem, 40B(7), 584-586; Chem, Abstr, 2001, 135, 318483f. [10] Bansal R K & Cope Bhagchandani, Indian J Chem, 1979, 18B, 362-363. [11] Barry A L, The Antimicrobial Suspectibility test; Principle and practices, edited by Illus Lea and Fibiger (Philadephia, Pa, U S A), 180. [12] Cavanagh F, Analytical Microbiology, (Academic Press, New York), 1963, 126. [13] Colthup N B, Daly L H & Wiberly S E, Introduction to Infrared and Raman Spectroscopy, (Academic Press, New York), 1964. [14] Silverstein R M, Bassler G C & Morril T C, Spectrometric Identification of Organic Compounds, 4th Edn, (John Wiley & Sons, New York), 1981.

Copyright

Copyright © 2026 Rajesh M. Kharate. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.