Comparative Study of the Regioselectivity and Reaction Media for the Synthesis of 1‐tert‐Butyl‐3(5)‐trifluoromethyl‐1H‐pyrazoles

A study is presented for the synthesis of a series of 1‐tert‐butyl‐3(5)‐(trifluoromethyl)‐1H‐pyrazoles from the reaction of 4‐alkoxy‐1,1,1‐trifluoro‐3‐alken‐2‐ones [CF3C(O)CH=C(R1)(OR), where R = Et and R1 = H or R = Me and R1 = Me, Ph, 4‐Me‐C6H4, 4‐MeO‐C6H4, 4‐F‐C6H4, 4‐Cl‐C6H4, 4‐Br‐C6H4, 4‐I‐C6H4, fur‐2‐yl, thien‐2‐yl, or naphth‐2‐yl] with tert‐butylhydrazine hydrochloride. When [BMIM][BF4] (1‐butyl‐3‐methylimidazolium tetrafluoroborate) and pyridine were used as the reaction media, we obtained a mixture of 1‐tert‐butyl‐3(5)‐trifluoromethylpyrazoles. The formation of 5‐trifluoromethyl‐1‐tert‐butyl‐1H‐pyrazoles with high regioselectivity occurred when the reaction was carried out with NaOH in EtOH. The formation of 1‐tert‐butyl‐3‐trifluoromethyl‐1H‐pyrazoles occurred, after hydrolysis of the 4‐alkoxy‐1,1,1‐trifluoro‐3‐alken‐2‐ones in H2O and H2SO4, followed by cyclization in [BMIM][BF4] and pyridine.