Highly Efficient Conversion of Ketazines to Pyrazoline Derivatives Catalyzed by FeCl3

Pyrazoline derivatives as valuable five-membered heterocyclic compounds could be readily prepared through the intramolecular cyclization of ketazines. In this paper, transition metals (Zn2+, Cu2+, Cr3+, Mn2+, Co2+, Ni2+, and Fe3+) were applied for the catalytic synthesis of 3,5,5-trimethyl-2-pyrazoline, and FeCl3 showed the best catalytic performance with 95% conversion and 99% selectivity. Substrate screening exhibited that the steric hindrance of ketazines is a key factor on the conversions of R-substituted pyrazolines, following the order of R as methyl (95%) > ethyl (83%) > propyl (68%) > butyl (55%). Moreover, the mechanism of the cyclization of ketazines catalyzed by FeCl3 is calculated by density functional theory. The energetic profile shows that the cyclization reaction consists of two steps and FeCl3 can efficiently reduce their barrier energies. This work provides a feasible method for the preparation of pyrazoline derivatives using inexpensive, less toxic, and environmentally friendly FeCl3 as a catalyst.