Design, Synthesis And Biological Activities Of Novel Neonicotinoid Compounds Containing The Thioether Structure

Imidacloprid was an important pesticides. It entered into the market in 1991 and then established a new insecticide field. Such pesticides used to be called neonicotinoid or chloronicotinyl insecticide. It binded to the nicotinic acetylcholine receptor (nAChR), and was characterized by their high insecticidal activities against insects and relative safety toward mammals and aquatic life. Therefore, the development of neonicotinoids insecticides was the hot field of green pesticides.Compared with Imidacloprid, nitromethylene compounds exhibits much higher binding activity with nAChRs, but they were limited in crop-protection because of their photoinstability and weak hydrophobicity. To overcome these shortcomings, based on the extensive review of the literature, the structure characteristics of neonicotinoid insecticides were analyzed and compared carefully, and their mode of action was summarized, 20 compounds were designed and synthesized through modifying the lead structure——nitromethylene compound. All these compounds were structurally characterized by 1H NMR, Elemental Analysis and IR. Their insecticides bioactivities were evaluated and some of them exhibited moderate insecticidal activities against Aphis laburni Kaltenbach.Based on N-(2-((5-((dimethylamino)methyl)furan-2-yl)methylthio)ethyl)-N-methyl- 2-nitroethene-1, 1-diamine(ranitidine) as the lead compound. Our interest was focused on introducing the thioether structure and hexatomic ring into the lead structure in order to increase the liposolubility of neonicotinoid insecticides and improve the photoinstability of nitromethylene compounds. We designed and synthesized two types novel neonicotinioid compounds containing the thioether structure, which have not been reported in the literature.The target compounds of tetrahydropyrimidines were obtained from the reaction of N-(2-((5-((dimethylamino)methyl)furan-2-yl)methylthio)ethyl)-N-methyl-2-nitroethene- 1, 1-diamine(ranitidine) as a lead compound, with formaldehyde solution and a variety of primary amines at room temperature.The target compounds of tetrahydropyridines were obtained from the reaction of N-(2-((5-((dimethylamino)methyl)furan-2-yl)methylthio)ethyl)-N-methyl-2-nitroethene- 1, 1-diamine(ranitidine) as a lead compound, with acrolein and a variety of alcohols, via Michael addition, nucleophilic addition and etherification.Through studying the reaction conditions to find a one-pot approach that makes Michael addition, nucleophilic addition and etherification occur simultaneously, changing the past methods of step-by-step synthesis and column chromatographical separation to improve the reaction yield.In this work, the structure of neonicotinoids compound was modified by introducing the thioether structure, the tetrahydropyrimidine ring and the tetrhydropyridine ring. It was also attempted to optimize the nitromethylene structure by increasing the liposolubility and improving the photoinstability so that compounds of higher bioactivity were obtained. It will explore a new way for developing neonicotinoid insecticides.