Synthesis And Biological Activities Of Fluorine-contained Neonicotinoids Based On Active Structures

Neonicotinoids act selectively on the insect nicotinic acetylcholine receptors(nAChRs), and it has attracted extensive attention of worldwide and higher market share because of their novel mode of action, high efficiency, broad insecticidal spectrum, and friendly environment. But frequent use has led to serious resistance, and bee toxicity has also been reported in many countries and regions. Commercialized neonicotinoids have strong similar molecular structures(nitro, nitrile as pharmacophore) and mode of action which led to cross-resistance between each other. As a result, it is very important to develop neonicotinoids with novel structures.Comparing with Imidacloprid, neonicotinoid compounds with trifluoroacetyl pharmacophores, which have become a new research field, have similar biological activity, different binding site and low cross-resistance. In this paper, Ⅰand Ⅱ series of new compounds with trifluoroacetyl group were synthesized after multi-step reactions starting from hexafluoroacetylacetonate and trifluoroacetic anhydride to solve the current problem of cross-resistance and bee toxicity. The structures of synthesized compounds were confirmed by 1H NMR, 13 C NMR, IR and EA. Bioactivities were tested and structure-activity relationships were analyzed.1) Thirteen open-ring neonicotinoid compounds with trifluoroacetyl pharmacophores were synthesized through halogenated, nucleophilic substituted reaction from hexafluoroacetyl acetonate. Biological results showed that most of the synthesized compounds exhibited high insecticidal activity against aphids. Especially, the corrected mortality of compounds A01 and A02 were over 80% at 10 mg/L and 50% at 1 mg/L. Structure-activity relationship study indicated that the activities of compounds containing pyridine ring had higher activities than those containing thiazole ring, while compounds with a large steric hindrance group exhibited lower activities than those with smaller group compounds.2) Fourteen cis open-ring neonicotinoids containing trifluoroacetyl pharmacophore were synthesized by nucleophilic and nucleophilic substitution two-step reaction from trifluoroacetic anhydride. Trifluoroacetyl pharmacophore and heterocyclic were in the same side of the double bond to reduce the steric hindrance. Biological test showed that the corrected mortality of compound C01 was over 80% at 500 mg/L and C02,D01 exceed 50%. Insecticidal activities But some of the series did not exhibit insecticidal activities. Through the structural analysis of the target compounds, we deduce that the size of ring and substituents may be the main factors. The large size of ring and substituents could decrease affinity with nAChRs. This synthesis method has the advantages of mild condition, simple operation, facile purification, and high yield. The optimum reaction conditions were obtained by analyzing the effects of reaction temperature, catalyst, solvents and purification method on the reaction rate and yield.