title: 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.
authors.affiliation: State Key Laboratory of Elemento-Organic Chemistry, Nankai University, No. 94 Weijin Road, Nankai District, Tianjin 300071, People's Republic of China.
authors.forename: Zhijin
authors.initials: Z
authors.lastname: Fan
authors.forename: Zhikun
authors.initials: Z
authors.lastname: Yang
authors.forename: Haike
authors.initials: H
authors.lastname: Zhang
authors.forename: Na
authors.initials: N
authors.lastname: Mi
authors.forename: Huan
authors.initials: H
authors.lastname: Wang
authors.forename: Fei
authors.initials: F
authors.lastname: Cai
authors.forename: Xiang
authors.initials: X
authors.lastname: Zuo
authors.forename: Qingxiang
authors.initials: Q
authors.lastname: Zheng
authors.forename: Haibin
authors.initials: H
authors.lastname: Song
mesh_terms: D002851:Chromatography, High Pressure Liquid; D018360:Crystallography, X-Ray; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure; D017550:Spectroscopy, Fourier Transform Infrared; D013329:Structure-Activity Relationship; D013830:Thiadiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D013830:Thiadiazoles