title: Regioselective synthesis of 2-amino-substituted 1,3,4-oxadiazole and 1,3,4-thiadiazole derivatives via reagent-based cyclization of thiosemicarbazide intermediate.
abstract: A regioselective, reagent-based method for the cyclization reaction of 2-amino-1,3,4-oxadiazole and 2-amino-1,3,4-thiadiazole core skeletons is described. The thiosemicarbazide intermediate 3 was reacted with EDC·HCl in DMSO or p-TsCl, triethylamine in N-methyl-2-pyrrolidone to give the corresponding 2-amino-1,3,4-oxadiazoles 4 and 2-amino-1,3,4-thiadiazoles 5 through regioselcective cyclization processes. The regioselectivity was affected by both R(1) and R(2) in p-TsCl mediated cyclization. It is shown in select sets of thiosemicarbazide 3 with R(1)(benzyl) and R(2)(phenyl). 2-Amino-1,3,4-oxadiazole 4 was also shown in the reaction of p-TsCl mediated cyclization. The resulting 2-amino-1,3,4-oxadiazole and 2-amino-1,3,4-thiadiazole core skeleton are functionalized with various electrophiles such as alkyl halide, acid halides, and sulfornyl chloride in high yields.
authors.affiliation: Center for Innovative Drug Library Research, Department of Chemistry, College of Science, Dongguk University, 26, 3-ga, Pil-dong Jung-gu, Seoul 100-715, Korea.
authors.forename: Seung-Ju
authors.initials: SJ
authors.lastname: Yang
authors.forename: Seok-Hyeong
authors.initials: SH
authors.lastname: Lee
authors.forename: Hyun-Jung
authors.initials: HJ
authors.lastname: Kwak
authors.forename: Young-Dae
authors.initials: YD
authors.lastname: Gong
mesh_terms: D003500:Cyclization; D007202:Indicators and Reagents / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010069:Oxadiazoles / Q000138:chemical synthesis* / Q000737:chemistry; D010080:Oxazoles / Q000138:chemical synthesis* / Q000737:chemistry; D012663:Semicarbazides / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D013830:Thiadiazoles / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: C583345:2-amino-1,3,4-oxadiazole; D007202:Indicators and Reagents; D010069:Oxadiazoles; D010080:Oxazoles; D012663:Semicarbazides; D013830:Thiadiazoles; C058949:1,3,4-thiadiazole; C005151:thiosemicarbazide; C010852:2-amino-1,3,4-thiadiazole