Potential Safety Hazards of DMF in the Presence of...
Org. Process Res. Dev. 2019, 23, 2133. DOI:10.1021/acs.oprd.9b00128
◆An uncontrollable exotherm in a small-scale oxidation using sodium persulfate (Na2S2O8) in DMF was observed by Yang et al. at Corteva Agriscience during the development of an insecticidal candidate, tyclopyrazoflor (1).
◆Although the desired product 2 was observed when dihydropyrazole 33 was treated with Na2S2O8 in DMF at 80oC, it was isolated in low yields of < 30% with many impurities.
◆The reaction was incomplete even with an excess amount of Na2S2O8, presumably caused by the decomposition of Na2S2O8 in DMF.
◆After optimization, the researchers were able to identify safer and greener alternative conditions to effect this oxidation reaction, namely, the use of potassium ferricyanide (K3FeCN6) in the presence of aqueous KOH at 70−90 °C, which afforded a cleaner reaction profile and a higher isolated yield.