The potential health risks of N,N‐dimethylformamide: An updated review

Abstract

N,N‐dimethylformamide (DMF) is a universally used industrial material with exponential growth in production and consumption worldwide. The frequently reported occupational DMF poisoning cases in some countries and the gradually recognized unavoidable health risks to the general population highlight that DMF should still be a matter of concern. Previous studies have demonstrated that the liver is the primary target organ of DMF exposure and multiple mechanisms have been revealed. However, most of these studies investigate the detrimental effects of acute and subacute DMF exposure, while the effects of chronic DMF exposure are rarely studied. Furthermore, the key mechanism for the acute hepatotoxicity of DMF remains to be elucidated. Future research may focus on the identification of efficient preventive measures against the toxicity of DMF to occupational workers, the investigation of the detrimental effects of DMF at environmentally relevant doses, and the studies on the elimination and recycling of DMF in industrial wastes. Herein, we present an updated review of the metabolism of DMF, the biomarker of DMF exposure, underlying molecular mechanisms of DMF‐induced hepatotoxicity, and the toxicity of DMF to both occupational workers and general populations and discuss the possible directions in future studies.

Enantio- and Diastereoselective Total Synthesis of Belzutifan Enabled by Rh-Catalyzed Hydrogenation

“…With this retrosynthetic strategy in mind, we initiated the synthesis by formylation of 2-bromo-1,4-difluorobenzene ( 1 ), an inexpensive bulk material, which afforded 2-bromo-3,6-difluorobenzaldehyde ( 1′ ) in 70% yield (Scheme ). Nucleophilic aromatic substitution (S N Ar) with 3-fluoro-5-hydroxybenzonitrile in DMF formed aldehyde 2 in 73% yield. The introduction of the geminal difluoro motif was accomplished by a Reformatsky reaction with ethyl bromodifluoroacetate to provide geminal difluoroester 3 in 78% yield.…”