Synthesis and reactivity of 4-(2-chloro-5-nitrophenyl)-1,2,3-thiadiazole. A novel one-pot synthesis of N-substituted indole-2-thiols.
4-(2-Chloro-5-nitrophenyl)-1,2,3-thiadiazole undergoes ring opening to produce a thioketene intermediate that reacts with an O- or N-nucleophile, forming an ester or an amide of the aryl-substituted thioacetic acid. Intermolecular cyclization of the thioacetic acid derivative via nucleophilic substitution of halogen in the aromatic ring gives an N-substituted indole-2-thiol (in case of an N-nucleophile) or a 2-alkoxy-substituted benzo[b]thiophene (in case of an O-nucleophile). The reaction is also applicable to the synthesis of heterocyclic analogues of N-substituted indole-2-thiols: 1-butyl-1,3-dihydropyrrolo[2,3-b]pyridine-2-thione was synthesized as an example. In the presence of potassium thioacetate (an S-nucleophile) 4-nitro-2-(1,2,3-thiadiazol-4-yl)benzenethiol is formed more quickly than thiadiazole ring opening occurs, making the heterocyclic ring tolerant toward the base.
Androsov
Dmitry A
DA
Center for Photochemical Sciences, Bowling Green State University, Bowling Green, Ohio 43403, USA.
Neckers
Douglas C
DC
D007211:Indoles / Q000737:chemistry*; D015394:Molecular Structure; D009574:Nitro Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry
C521836:4-(2-chloro-5-nitrophenyl)-1,2,3-thiadiazole; D007211:Indoles; D009574:Nitro Compounds; D013438:Sulfhydryl Compounds; D013844:Thiazoles; C030374:indole