Copper(I)-catalysed regioselective synthesis of pyrazolo[5,1-c]-1,2,4-triazoles: A DFT mechanistic study.

Formation of pyrazolo[5,1- c ]-1,2,4-triazoles by means of Cu(I)-catalysed [3+2] cycloaddition (32CA) reactions of C,N -cyclic azomethine imines with phenylacetylene, experimentally reported by Katritzky et al. (JOC 2012, 77, 5813), was studied using the density functional theory (DFT) method. Comparison with the uncatalysed 32CA reaction indicates that the Cu(I) catalyst provides new reaction pathways with lower electronic energy barriers in dichloromethane as solvent. The mechanism proposed by Katritzky for the Cu(I) catalysed reaction is compared with that proposed by Sharpless et al. (JACS 127, 2005, 210). The major difference between these two mechanisms lies in the coordination of the Cu(I) acetylide to the C,N -cyclic azomethine imine moiety. DFT calculations suggest that the mechanism proposed by Katritzky is kinetically favoured over that of CuAAC-type. ELF topological analysis of the electron density of the stationary points involved in the most favourable reaction pathway associated with the Cu(I)-catalysed 32CA reactions explains the bond formation. This study also reveals the requirement of C,N -cyclic azomethine imines rather than acyclic azomethine imines to favour the mechanism proposed by Katritzky. [ABSTRACT FROM AUTHOR]