Process improvements for the preparation of insecticide clothianidin

This article describes the process improvements for the preparation of the insecticide clothianidin 1. (Z)-1-Methyl-N-nitro-5-propyl-1,3,5-triazinan-2- imine (9) which was obtained by Mannich reaction of (Z)-1-methyl-2- nitroguanidine (5) n-Propylamine and 37 % aqueous formaldehyde solution in 97 % yield. Intermediate 9 was electrophilic substituted with 2-chloro-5- (chloromethyl)thiazole (4) in the presence of acid-binding agent to give (E)-1-[(2-chlorothiazol-5-yl)methyl]-3-methyl-N-nitro-5-propyl-1,3, 5-triazinan-2-imine (10) in 90 % yield. The target compound 1 was given by the hydrolyzation of 10 in 88 % yield. The optimized conditions for the preparation of clothianidin were obtained via screening the reaction temperature, reaction time, acid-binding and solvents in three steps. The overall yield of clothianidin 1 was up to 77 %.