Efficient Synthesis of α‐Ketothioamides From α‐Nitroketones, Amines or DMF and Elemental Sulfur Under Oxidant‐Free Conditions

Abstract

We have developed a practical, general protocol for denitration of readily available α‐nitroketones with sulfur and amines to access a broad range of α‐ketothioamides under mild conditions. Such a reaction proceeds under metal‐, oxidant‐, and catalyst‐free conditions to provide synthetically useful α‐ketothioamides. Furthermore, the mild reaction conditions tolerate a wide range of substrates especially for the synthesis of aliphatic α‐ketothioamides which are rarely reported.

Towards More Practical Methods for the Chemical Synthesis of Thioamides Using Sulfuration Agents: A Decade Update

“…α-Nitroketones are also useful substrates for the preparation of α-keto thioamides. In 2021, Sheng and his colleagues [38] described an efficient protocol for the synthesis of diverse α-keto thioamides 43 from α-nitroketones and amines in the presence of sulfur (Scheme 16). This transformation, which proceeds under mild condition, tolerates a broad range of substitutions, especially for the alkyl α-keto thioamides, which are rarely reported in the literature.…”

A Journey from June 2018 to October 2021 with N,N-Dimethylformamide and N,N-Dimethylacetamide as Reactants

“…The reaction occurs via Pd-catalyzed esterification of the carboxylate with the halopyridine followed by amidation of the resulting ester with I3 (Scheme 10(a2)), the latter being issued from the addition of the in situ formed 2-bromopyridin-3-olate to DMAc. Denitration of nitroketones mediated with sulfur and aqueous trimethylamine in DMF provided α-ketothioamides (Scheme 9(b 1 )) [41]. Zhang and co-workers proposed that the ketothiolation of the substrate is followed by nucleophilic attack of dimethylamine produced from decarbonylation of DMF (Scheme 9(b 2 )).…”

Synthesis of α-ketothioamides with elemental sulfur under solvent-free conditions in a mixer mill

“…2 Among them, thioamides and α-ketothioamides have attracted particular attention as interesting building blocks for a large variety of sulfur-containing compounds and natural products. 3 A representative direct application was reported by Frédérick and co-workers, who found inhibitory activities of α-ketothioamide derivatives on phosphoglycerate dehydrogenase (PHGDH) with implications for cancer cell proliferation. 4…”