Brønsted ionic liquids as catalysts for synthesis of 2-pyrazoline derivatives from ketazines: A combined experimental and theoretical approach

Brønsted ionic liquids (BILs) were designed and applied to catalyze intramolecular cyclization of ketazines to 2-pyrazoline derivatives. Under the optimal conditions as 90 °C, 15 mol% [PsBim][CF 3 SO 3 ] dosage and 4 h, the conversion rate and selectivity of the reaction are up to 98 % and 99 % respectively. Through the substrate screening, it shows that the steric hindrance of the R group in ketazines is a big factor of cyclization activities, following the order of methyl (98 %) > ethyl (93 %) > n - propyl (87 %) > n‑butyl (81 %) > isopropyl (52 %) > isobutyl (46 %)> neobutyl (13 %). Moreover, the results of the density functional theory (DFT) calculations indicate that the cations and anions of BIL can synergistically participate in the ketazines configuration transformation step so as to significantly reduce the Gibbs free barrier energy from 30.65 to 20.12 kcal/mol, thereby promoting the cyclization reaction to synthesize 2-pyrazoline derivatives.