Oxidative cyclization leading to charged sulfur-containing tricyclic heteroarenes

Abstract

Fused heterocycles are of crucial importance to the pharmaceutical and agrochemical industry. While their neutral analogues including the fungicide tricyclazole have been investigated for various applications and can be prepared via several synthetic pathways, charged N-substituted benzo[4,5]thiazolo[2,3-c][1,2,4]triazol-1-ium salts are not as easily accessible. In this review we summarize a new method for the synthesis of novel N-arylated and N-alkylated benzo[4,5]thiazolo[2,3-c][1,2,4]triazol-1-ium salts from air stable precursors and present an expanded substrate scope for this reaction. The N-aryl substituted precursors are available through a catalytic N-arylation previously developed in our group, while N-alkyl substituted precursors were prepared by a nucleophilic substitution reaction. Selective deprotection of the para-methoxybenzyl protected precursor leads to the free thiol which under oxidative conditions undergoes C–H functionalization of the linked 1,2,4-triazolium salt, thereby forming the fused aromatic heterocycle. A wide range of functional groups such as alcohols, amides, and alkynes are tolerated. Mechanistic investigations indicate the involvement of a disulfide intermediate in the oxidative cyclization step.

GRAPHICAL ABSTRACT

Keywords:

• Sulfur heterocycles
• oxidative cyclization
• C–H functionalization
• heteroarenes

Additional information

Funding

This work was supported by American Chemical Society Petroleum Research Fund for partial support of this research (ACS PRF DOCTORAL NEW INVESTIGATOR (DNI) RESEARCH GRANT; proposal number: 58507 DNI-1).