Stereochemistry and active conformation of a novel insecticide, acetamiprid

Acetamiprid, (NI-25; (E)-N1-[(6-chloro-3-pyridyl)methyl]-N2-cyano-N1-methylacetamidine), is a novel neonicotinoid insecticide having an N-cyanoacetamidine structure as its characteristic feature. The [1H] and [13C]-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 [13C] chemical shifts of N-CH3 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.