Synthesis of sulfur heterocycles by C-H bond functionalization of disulfide intermediates

• Published in: Phosphorus, sulfur, and silicon and the related elements sulfur, and silicon and the related elements, 2023-06, Vol.198 (6), p.507-512
• Main Authors: Ardón-Muñoz, Luis G., Bolliger, Jeanne L.
• Format: Article
• Language: English
• Subjects: Agrochemicals; C-H functionalization; disulfides; Fungicides; heteroarenes; Hydrogen bonds; Natural products; oxidative cyclization; Sulfur; Sulfur heterocycles; Thiols; Triazoles
• ISSN: 1042-6507; 1563-5325
• DOI: 10.1080/10426507.2023.2171040

Sulfur- and nitrogen-containing heterocycles are found in many natural products but also in most biologically active molecules used in the pharmaceutical and agrochemical industry. Among these molecules are substituted benzo[4,5]thiazolo[2,3-c][1,2,4]triazoles which exhibit a broad range of biological activities. Tricyclazole, a fungicide used to treat rice blast, belongs to this class of compounds. In this review we summarize the development of a new synthetic strategy to prepare benzo[4,5]thiazolo[2,3-c][1,2,4]triazole derivatives. The target compounds are conveniently obtained in a one pot-two step procedure from air stable para-methoxybenzyl protected 4-(2-mercaptophenyl)triazole derivatives which upon deprotection of the thiols undergo an oxidative cyclization to the corresponding tricyclic heteroarenes. Using this procedure, it is possible to obtain a variety of tricyclic heteroarenes which contain both electron-withdrawing and electron donating substituents as well as a wide range of synthetically useful groups, thus allowing biologically relevant groups to be introduced either before or after the heterocycle formation. Mechanistic investigations suggest that the oxidative cyclization proceeds via a disulfide intermediate.