The discovery of thiamethoxam: a second-generation neonicotinoid

Publisher Website
Google Scholar
Abstract
Neonicotinoids represent a novel and distinct chemical class of insecticides with remarkable chemical and biological properties. In 1985, a research programme was started in this field, in which novel nitroimino heterocycles were designed, prepared and assayed for insecticidal activity. The methodology for the synthesis of 2‐nitroimino‐hexahydro‐1,3,5‐triazines, 4‐nitroimino‐1,3,5‐oxadiazinanes and 4‐nitroimino‐1,3,5‐thiadiazinanes is outlined. Bioassays demonstrated that 3‐(6‐chloropyridin‐3‐ylmethyl)‐4‐nitroimino‐1,3,5‐oxadiazinane exhibited better insecticidal activity than the corresponding 2‐nitroimino‐hexahydro‐1,3,5‐triazine and 4‐nitroimino‐1,3,5‐thiadiazinane. In most tests, this compound was equally or only slightly less active than imidacloprid. A series of structural modifications on this lead structure revealed that replacement of the 6‐chloro‐3‐pyridyl group by a 2‐chloro‐5‐thiazolyl moiety resulted in a strong increase of activity against chewing insects, whereas the introduction of a methyl group as pharmacophore substituent increased activity against sucking pests. The combination of these two favourable modifications led to thiamethoxam (CGA 293 343). Thiamethoxam is the first commercially available second‐generation neonicotinoid and belongs to the thianicotinyl sub‐class. It is marketed under the trademarks Actara® for foliar and soil treatment and Cruiser® for seed treatment. The compound has broad‐spectrum insecticidal activity and offers excellent control of a wide variety of commercially important pests in many crops. Low use rates, flexible application methods, excellent efficacy and the favourable safety profile make this new insecticide well‐suited for modern integrated pest management programmes in many cropping systems. © 2001 Society of Chemical Industry