Research On The Synthesis And Biological Evaluation Of Neonicotinoid Analogues

The discovery of imidacloprid in the 1990s was regarded as a milestone in insecticide research, which lead to the fast growth and systematic research in neonicotinoid insecticides. The neonicotinoid insecticides act on insect nicotinic acetylcholine receptor (nAChR), and they presented high insecticidal activity in piercing-sucking insects. The growing resistance and high bee-toxicity of neonicotinoids resulted in great economic losses. In this paper, four new series of neonicotinoid analogues were designed and synthesized, which aimed at obtaining high activity compounds and getting pests under control.1. Five member heterocycle-fused neonicotinoid analogues were constructed to fix the nitro group into cis-configuration by reacting nitroenamine with methylglyoxal. Twenty-one new structures of pyrrole and dihydropyrrole fused cyclic and noncyclic neonicotinoids were acquired with high selectivity and yields under the optimized condition. Cyclic neonicotinoid derivatives presented pleasing insecticidal activity against cowpea aphid (Aphis craccivora), armyworm (Pseudaletia separate Walker), and brown rice planthopper (Laodelphasx striatellus). Compound Al-c showed higher activity than imidacloprid and nitenpyran.2. A bigger conjugating system was constructed by reacting nitroenamine with diazonium salt to enhance theπ-πinteraction. Those compounds with electron donating groups on both position 2 and 6 of the phenyl ring displayed excellent activity against cowpea aphid (Aphis craccivora) and brown rice planthopper (Laodelphasx striatellus). Extraordinarily, as showed in the crystal structure spectra of compound B1-q, a large angle-104.5°was exist between the nitromethyl plane and the imidazoline plane, which showed some divergence with the classic theory. However, the molecular docking result proved the existence ofπ-πinteraction with the collaborative effect of nitro group-introduced hydrogen bonding.3.1,4-dihydropyridine fused neonicotinoid analogues were constructed to fix the nitro group into trans-configuration by reacting nitroenamine with chalcone. Seven new molecules were obtained through [3+3] ring cyclization and elimination reaction. No impressive insecticidal results were observed from the target compounds. It was presumed that the rigidity of the target structures were thus enhanced by introducing the 1,4-dihydropyridine ring.4.1,4-dihydropyran fused neonicotinoid analogues were constructed by one pot reaction of aldehydes, malononitrile, and fluorochloro pyridine reactant. After optimization of the reaction, thirteen compounds were obtained in high yields via catalyzed by 10 mol% piperidine, and their insecticidal activities were low against cowpea aphid (Aphis craccivora) and armyworm (Pseudaletia separate Walker) under 500 mg L-1.