Starting with a concise and practical synthesis of acyl thiosemicarbazides (3a-h), a series of new 1,2,4-triazole derivatives (4a-h), have been synthesized by intramolecular cyclization in alkaline medium. The acyl thiosemicarbazides required for this purpose were obtained by reaction of carbohydrazides (1a-b) with appropriate aromatic isothiocyanates (2a-h). Subsequently, 4a-h which upon treatment with phenacyl bromide underwent S-phenacylation in presence of triethylamine afforded 5a-h. The structural identities of 3a, 4a and 5a compound were established on the basis of elemental analysis and spectral studies such as 1H NMR, IR, 13C NMR and mass while rest of the compounds were characterized by elemental analysis and IR spectroscopy. The synthesized compound acyl thiosemicarbazide (3a) and 1,2,4-triazole (5a) were evaluated for their in vitro antibacterial activity against pathogenic bacteria and the results were comparable with Chloramphenicol antibiotic. The rapid development of bacterial resistance to conventional drugs is one of the major difficulties in the treatment of bacterial infection, thus it is still necessary to search for new antibacterial agent. Triazole derivatives have occupied a unique position in heterocyclic chemistry due to their antimicrobial activities. 1,2,4-triazoles as antibacterial agents can be grouped according to the mode of action, i.e., the ability to inhibit the synthesis of the cell wall, cell membrane, proteins and nucleic acids of bacteria. 1,2,4-triazoles exhibit a wide range of therapeutical properties like antibacterial, antifungal, anti-inflammatory, antituberculosis, anticancer, antioxidant, InhA inhibitory activity, antidepressant, etc. Some of the modern day drugs with triazole nucleus are as fluconazole, itraconazole, terconazole, posaconazole, voriconazole. Moreover, now a day researchers prefer to synthesize hybrids of heterocycles to enhance the therapeutically activities. 1,2,4-triazoles with other heterocyclic derivatives possess a wide spectrum of biological activities. The huge number of 1,2,4-triazoles containing hybrid systems exhibits anticonvulsant and CNS depressant, anticancer, antioxidant activity, etc.

The melting points were recorded in open capillary in paraffin bath and are uncorrected. IR spectra were recorded on a Shimadzu IR Spectrophotometer (KBr, v max in cm^-1). ¹H NMR spectra are recorded on a Bruker AM 400 instrument (400 MHz) using tetramethylsilane (TMS) as an internal reference and DMSO-d₆ as solvent and 13C NMR spectra are recorded on a Bruker AM 400 instrument (100 MHz) and DMSO-d₆ as solvent. Chemical shifts are given in parts per million (ppm). Positive-ion Electro Spray Ionization (ESI) mass spectra were obtained with a Waters Micromass Q-TOF Micro, Mass Spectrophotometer. Elemental (CHN) analysis was done using Thermo Scientific (Flash-2000). The compounds were analyzed for carbon, hydrogen, nitrogen and sulphur and the results obtained are in good agreement with the calculated values. Chemicals used for the synthesis were of AR grade of Merck, S.D. Fine and Aldrich. The reactions were monitored by E. Merck TLC aluminum sheet silica gel60F254 and visualizing the spot in UV Cabinet and iodine chamber. The schemes of the targeted synthesized compounds 3a-h, 4a-h and 5a-h are described in Schemes 1-3 respectively. The purity of synthesized compound at every synthetic stage was monitored by TLC technique. The structures of the newly synthesized products were substantiated based on elemental and spectral analysis such as IR, ¹H NMR and mass. The synthesis of the starting compound, 5-(5-H/Br benzofuran-2-yl)-1-phenyl-1H-pyrazole-3-carbohydrazides (1a-b) were achieved in quantitative yields by adopting published literature method. The reaction of 1a-b with aryl isothiocyanates 2a-h in chloroform as a solvent led to the formation of 3a-h. The IR spectrum of 3a showed -NH stretch of amine at 3312 cm^-1 and C=O stretching in amide group at 1650 cm^-1. The 1H NMR spectrum showed singlet at δ 2.3 ppm for -CH₃ protons, hence it confirms that aryl isothiocyanates has condensed with 5-(benzofuran-2-yl)-1-phenyl-1H-pyrazole-3-carbohydrazide to afford 1-(5-(H/Br benzofuran- 2-yl)-1-phenyl-1H-pyrazole-3-carbonyl)-4-substituted/unsubstituted phenyl thiosemicarbazide derivatives 3a-h. The elemental analysis of this product gave C, 66.12; H, 4.24; N, 14.33 and S, 6.23. The mass spectra of the products revealed a molecular ion peak at m/z 468 [M+H]⁺ which is in agreement with the molecular formula C₂₆H₂₁O₂N₅S.

With Regards,
Joseph Kent
Journal Manager
Journal of Der Chemica Sinica