Electrochemical Synthesis of 1,2,3-Thiadiazoles from α-Phenylhydrazones

Abstract

We have developed an electrochemical approach for the synthesis of fully substituted 1,2,3-thiadiazoles from α-phenylhydrazones at room temperature, which is very challenging and complementary to the conventional thermal reactions. The key step involves anodic oxidation of phenylhydrazone derivatives at a constant current followed by N,S-heterocyclization. The protocol is remarkable in that it is free of a base and free of an external oxidant and can be converted to a gram scale for postsynthetic drug development with functional thiadiazoles. Most importantly, the electrochemical transformation reflected efficient electro-oxidation with an operationally friendly easy procedure with ample functional molecules. Cyclic voltammograms support the mechanism of this electro-oxidative cyclization process.

Access to Nitrones from Amines via Electrocatalysis at Room Temperature

“…The 1 H and 13 C NMR spectra were recorded on a JEOL 500 FT-NMR spectrometer operating at 500 and 125 MHz, respectively. Chemical shifts (δ) for 1 H and 13 C { 1 H} NMR are given in parts per million (ppm) using the residual solvent peaks as reference relative to tetramethylsilane (TMS). Coupling constant (J) values are reported in Hz.…”

“…[12] Although, the reported method defined the clean synthesis of aryl nitrones in good yields, but pH based typical reaction procedure and limited to only aryl nitrones make this protocol practically tough. In alignment with our continuing efforts in organic electrochemistry, [13] herein, we devised a metal and external oxidant-free electrochemical cross coupling approach between benzyl amines and aryl/alkyl nitro compounds leading aryl/alkyl nitrones in good yields for the very first time (Scheme 1c).…”

Advances in S–N bond formation via electrochemistry: a green route utilizing diverse sulfur and nitrogen sources

“…In 2021, Singh and co-workers developed an electrosynthesis of fully substituted 1,2,3-thiadiazoles 54 from easily accessed α-phenylhydrazones 53 at room temperature via galvanostatic electrolysis (Scheme 29). 106 The α-phenylhydrazones 53 were obtained from β-ketothioamides with diazonium salts (aryl diazonium tetrafluoroborate) in dry acetonitrile at room temperature. Electrolyzing a solution of DMF containing n Bu 4 NBF 4 and α-phenylhydrazones in an undivided cell with a carbon rod anode and platinum plate cathode at a constant current of 3 mA for 3 h afforded the 1,2,3-thiadiazoles in good to excellent yields.…”

Access to Functionalized Thiazolothiadiazoles via the Chemoselective Cascade Heteroannulation of Thioamides with Hypervalent Iodine Reagents

“…Our research group is focused on developing a novel platform in organic synthesis using tailored hypervalent iodine reagents as an electrophilic diazo source. , To date, the reaction between β-ketothioamides and α-aryliodonio diazo compounds has not yet been accomplished and remains unexplored. As part of our continuing efforts on β-ketothioamides and α-aryliodonio diazo compounds, a new transition-metal- and base-free approach for the construction of thiazolothiadiazoles has been devised. This approach revealed the diverse reactivity of iodanes.…”