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

Abstract

Abstract A study is presented for the synthesis of a series of 1‐ tert ‐butyl‐3(5)‐(trifluoromethyl)‐1 H ‐pyrazoles from the reaction of 4‐alkoxy‐1,1,1‐trifluoro‐3‐alken‐2‐ones [CF 3 C(O)CH=C(R 1 )(OR), where R = Et and R 1 = H or R = Me and R 1 = Me, Ph, 4‐Me‐C 6 H 4 , 4‐MeO‐C 6 H 4 , 4‐F‐C 6 H 4 , 4‐Cl‐C 6 H 4 , 4‐Br‐C 6 H 4 , 4‐I‐C 6 H 4 , fur‐2‐yl, thien‐2‐yl, or naphth‐2‐yl] with tert ‐butylhydrazine hydrochloride. When [BMIM][BF 4 ] (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‐1 H ‐pyrazoles with high regioselectivity occurred when the reaction was carried out with NaOH in EtOH. The formation of 1‐ tert ‐butyl‐3‐trifluoromethyl‐1 H ‐pyrazoles occurred, after hydrolysis of the 4‐alkoxy‐1,1,1‐trifluoro‐3‐alken‐2‐ones in H 2 O and H 2 SO 4 , followed by cyclization in [BMIM][BF 4 ] and pyridine.