Stereochemistry and active conformation of a novel insecticide, acetamiprid

Abstract

Acetamiprid, (NI-25; (E)-N 1 -[(6-chloro-3-pyridyl)methyl]-N 2 -cyano-N 1 -methylacetamidine), is a novel neonicotinoid insecticide having an N-cyanoacetamidine structure as its characteristic feature. The [ 1 H] and [ 13 C]-NMR spectra indicated the existence of two different structures in acetamiprid at room temperature in solution. The measurement of CH-NOE and C-C coupling constants proved the E-configuration at the cyanoimino group in both existing structures. The [ 13 C] chemical shifts of N-CH 3 and the long range C-H coupling in the formamidine analogue of acetamiprid suggested that there exist two conformers generated by the rotation of C-C single bond in the amidine moiety. Dynamic NMR spectra of acetamiprid and the computer simulation of the two-site exchange demonstrated that the two conformers change slowly to each other at room temperature. The conformational analysis by semi-empirical molecular orbital calculations using MNDO-PM3 method predicted four conformers as energy-minimum structures, among which two E-conformers were more stable than Z-conformers. One of the E-conformers in which two methyl groups are in cis configuration was superimposable onto the structure of imidacloprid, which is a known neonicotinoid insecticide having more rigid structure. This E-conformer was assumed as the active conformation of acetamiprid on the basis of the molecular similarity in terms of steric and electrostatic properties.