Synthesis, Crystal Structure, and Biological Activity of 4-Methyl-1,2,3-thiadiazole-Containing 1,2,4-Triazolo[3,4-b][1,3,4]thiadiazoles

Abstract

Heterocyclic compounds play an important role as the main sources of lead molecules of agrochemicals. Synthesis and biological activity of thiadiazole-containing 1,2,4-triazolo[3,4-b][1,3,4]-thiadiazoles were seldom reported. To find novel lead compounds with various biological activities, a series of 6-substituted-3-(4-methyl-1,2,3-thiadiazolyl)[1,2,4]triazolo[3,4-b][1,3,4]thiadizoles were rationally designed and synthesized according to the principle of combinations of bioactive substructures by the condensation of 3-(4-methyl-1,2,3-thiadiazolyl)-4-amino-1,2,4-triazole-5-thione with various carboxylic acids and phosphorus oxychloride. All newly synthesized compounds were identified by proton nuclear magnetic resonance ((1)H NMR), infrared spectroscopy (IR), electroionization mass spectrometry (EI/MS), and elementary analysis. The crystal structure of 3-(4-methyl-1,2,3-thiadiazolyl)-6-(4-methylphenyl)[1,2,4]triazolo[3,4-b][1,3,4]thiadizole was determined by X-ray diffraction crystallography. In this crystal, two intermolecular hydrogen bonds (N2...H-C12 and N3...H-C13), a weak intermolecular interaction (S...S), and the weak ppi-ppi intermolecular interaction were observed. Fungicide screening indicated that all of the target compounds showed certain extent of growth inhibition against fungi tested. 3-(4-Methyl-1,2,3-thiadiazolyl)-6-n-propyl[1,2,4]triazolo[3,4-b][1,3,4]thiadizole and 3-(4-methyl-1,2,3-thiadiazolyl)-6-trichloromethyl[1,2,4]triazolo[3,4-b][1,3,4]thiadizole were found to have potential wide spectrum of fungicide activity. The median effective concentrations (EC(50)) detected for 3-(4-methyl-1,2,3-thiadiazolyl)-6-trichloromethyl[1,2,4]triazolo[3,4-b][1,3,4]thiadizole to six fungi were from 7.28 micromol/L against Pellicularia sasakii (Shirai) to 42.49 micromol/L against Alternaria solani . The results indicated that thiadiazole-containing 1,2,4-triazolo[3,4-b][1,3,4]-thiadiazoles were potential fungicide lead compounds.

Synthesis, characterization and properties of 1,2,4-triazolo[3,4-b][1,3,4]thiadiazole derivatives and their europium complexes

“…[14]. Pyridine-2,6-dihydrazide (5 mmol, 0.98 g) was mixed with a solution of potassium hydroxide (20 mmol, 1.12 g) in anhydrous ethanol (30 mL) under stirring.…”

Design and Synthesis of New Bioactive 1,2,4-Triazoles, Potential Antitubercular and Antimicrobial Agents

“…Various isonicotinic acid derivatives like isonicotinyl hydrazides [32] , isonicotinamide derivatives [33] , 1,2,4-triazoles from isonicotinic acid hydrazide [34] , novel nalidixic acid derived 1,2,4-triazole [35] , 5-mercapto-1,2,4-triazole, novel 4H-1,2,4-triazol-3-yl-cycloalkanols [36] , new imidazole and 1,2,4-triazole substituted fluorobenzimidazoles [37] , and diphenylamine containing 1,2,4-triazoles [38] , have been reported to possess diverse activity including antimicrobial and antitubercular. The therapeutic potential of 1,2,4-triazole prompted us to synthesize new compounds in which substituent could be arranged in a pharmacophoric pattern to display high order of antimycobacterial activity.…”

Crystal Structure and Fungicidal Activity Evaluation of 2-(2-Bromophenyl)-5-Ethyl-1,3-Dioxan-5-yl-Methanol Synthesized with Nanosolid Superacid

“…16 A stock solution of the title compound was prepared at 500 g/mL using sterilized water containing 2 drops of N ,N -dimethylformamide (DMF) as the solvent. Subsequently, 1 mL of the stock solution was transferred into a Petri dish with 10 cm in diameter, and 9 mL of PDA was added to prepare the plate containing 50 g/mL of the test compound.…”