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

• Published in: Journal of agricultural and food chemistry Vol. 58; no. 5; pp. 2630 - 2636
• Main Authors: Fan, Zhijin, Yang, Zhikun, Zhang, Haike, Mi, Na, Wang, Huan, Cai, Fei, Zuo, Xiang, Zheng, Qingxiang, Song, Haibin
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 10.03.2010; Amer Chemical Soc
• Subjects: Agriculture; Agriculture, Multidisciplinary; agrochemicals; antifungal properties; bioactive properties; Biological and medical sciences; chemical analysis; chemical composition; Chemistry; Chemistry, Applied; Chromatography, High Pressure Liquid; crystal structure; Crystallography, X-Ray; Food industries; Food Science & Technology; Fundamental and applied biological sciences. Psychology; heterocyclic compounds; Life Sciences & Biomedicine; Magnetic Resonance Spectroscopy; Mass Spectrometry; Molecular Structure; Physical Sciences; Science & Technology; Spectroscopy, Fourier Transform Infrared; Structure-Activity Relationship; structure-activity relationships; synthesis; Thiadiazoles - chemical synthesis; Thiadiazoles - chemistry; Thiadiazoles - pharmacology; Tobacco mosaic virus; triazoles; 4-methyl-1,2,3-thiadiazole; systemic acquired resistance; fungicide bioassay; 1,2,4-Triazolo[3,4-b][1,3,4]thiadiazole; ELICITORS; PHARMACOLOGICAL-ACTIVITIES; CHEMISTRY; DERIVATIVES; Resistance; Bioassay; Synthesis; Pesticides; Biological activity; Fungicide; Crystalline structure
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/jf9029628

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 (1H 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 pπ−pπ 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 (EC50) 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 μmol/L against Pellicularia sasakii (Shirai) to 42.49 μmol/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.