Reaction Diversity Of Heterocyclic Ketene Aminals And Their Application In Neonicotinoids Development

Heterocyclic ketene aminals (HKAs) are versatile building blocks and active skeleton in organic chemistry. In this thesis, we comprehensively studied the reaction diversity of HKAs including Spiro-and bridged-heterocyclic cyclization, isomerization of HKA-ninhydrin adducts and their selective etherification. Futher applications of these synthetic methodologies on neonicotinoids development were explored base on rational molecular design and three new types of insecticidal skeleton were found.1. Spiro heterocycle containing neonicotinoid analogues:Spiro heterocycles were introduced to neonicotinoid scanfold due to their unique action mechanisms and anti-resistance. Fifteen novel spiro neonicotinoid analogues were synthesized, and insecticidal activity showed that IPP181102, IPP181109and IPP181117had more than50%inhibition rate against Meloidogyne incongnita.2. Bridged-heterocyclic neonicotinoid analogues. A total of5compounds were designed and synthesized. Compound IPP181010has moderate insecticidal activity against aphids and brown planthopper. Some of the compounds such as IPP181002have good inhibition against Meloidogyne incongnita.3. Exploration on the reactions of HKAs with ninhydrin. In the process of researching on the reactions of HKAs with ninhydrin, a novel isomerization had been discovered. That is the isomerization reaction of indeno[1,2-b]pyrrol-4(1H)-one to indeno[2,1-b]pyrrol-8(1H)-one. The reaction conditions, scopes and isomerization mechanism were studied. The isomerization showed a strong solvent dependency and occurred via decomposition-reconstruction pathway.4. Indeno[2,1-b]pyrrol-8(1H)-ones as novel neonicotinoid analogues. A series of novel four-ring neonicotinoid analogues were synthesized. Twenty-three new molecules were obtained. The etherification products had moderate mortality against aphids and brown planthopper. The chlorine-substituted products had good activities against aphids, brown planthopper and armyworm. Against aphid and brown planthopper, esterification products had high activity and some of them were comparable to Cycloxaprid. Furthermore, the majority of esterification products such as IPP181031, IPP181032and IPP181036were far better than Cycloxaprid against armyworm.