TEMPO-Catalyzed Electrochemical C–H Thiolation: Synthesis of Benzothiazoles and Thiazolopyridines from Thioamides

Abstract

Benzothiazoles and thiazolopyridines are widely prevalent in pharmaceuticals and organic materials. Herein, we report a metal-and reagent-free method for the uniform synthesis of benzothiazoles and thiazolopyridines through 2,2,6,6-tetramethylpiperidine-N-oxyl radical (TEMPO)-catalyzed electrolytic C−H thiolation. This dehydrogenative coupling process provides access to a host of benzothiazoles and thiazolopyridines from N-(hetero)arylthioamides. Mechanistic studies suggested that the thioamide substrate was oxidized with the electrochemically generated TEMPO + through an inner-sphere electron transfer to afford a thioamidyl radical, which undergoes homolytic aromatic substitution to form the key C−S bond.

Electrochemically Enabled Intramolecular Aminooxygenation of Alkynes via Amidyl Radical Cyclization

“…Based on the above studies and previous reports, a possible mechanism for the electrochemical cyclization reaction was proposed using carbamate 30 as a model substrate (Scheme ). At the anode, TEMPO ( E p/2 = 0.67 V vs .…”

Synthetic Organic Electrochemical Methods Since 2000: On the Verge of a Renaissance

“…301 Although the thiophenol can also be oxidized to the corresponding disulfide under the reaction conditions, it was believed that the aryl radical cation could engage the disulfide or the intermediary sulfur-centered radical to afford the thiolation product. An intramolecular thiolation process has been devised by Lei to synthesize benzothiazoles from aryl-isothiocyanate electrochemically (Figure 18E)—this reaction presumably occurs through the intermediacy of a sulfur-centered radical; 302,303 …”

Elektrifizierung der organischen Synthese

“…[52] Xu et al reported an elegant synthesis of benzothiazoles from thioanilides.Inanundivided cell under constant-current conditions,many different functional groups and substitution patterns were tolerated (Scheme 44). [135] Thea uthors again confirmed that this was av aluable alternative to classic synthetic routes,a nd that this method can be used to generate natural products or drugs more efficiently.Asimilar substrate underwent the same cyclization reaction. [136] When amidine functional groups were oxidized at the anode,t he generated amidinyl radicals underwent cyclization with the attached aromatic ring system (Scheme 45).…”

“…TEMPO-mediated synthesis of benzothiazoles. [135] Scheme 45. Electrochemical generation of benzimidazoles and pyridoimidazoles.…”