Studies On The Synthesis Technology Of Spirodiclofen And The Synthesis, Bioactivity Evaluation Of The Derivatives

The acaricide Spirodiclofen and insecticide Spiromesifen developed by Bayer CropScience belong to the special spiralcyclic tetronic acid compound. Because of their novel mode of action and excellent biological activities, the studies on Spirodiclofen have excellent potential to develop new insecticides and miticides. Therefore, spiralcyclic tetronic acid compounds have been playing an important role in the new pharmaceutical and pesticides development.In this thesis, an economic, simple operational and environmental friendly synthetic process was developped by optimizing the literature synthetic methods of the Spirodiclofen and its key intermediates. Starting from cyclohexanone, Spirodiclofen was obtained following cyanic reaction, ester reaction, phenyl-acetyl reaction, condensation, and acyl reaction. Firstly, when preparing 1-hydroxy cyclohexanecarbonitrile (1), different proton acids, starting material rate and the amount of phase-trasfer catalyst TBAB were all discussed. The yield reached 93.5% by using TBAB, which exceeded 17% than the date of literature. And the purity of 1 can reach 98% after simple distillation. Secondly, during the preparation of ethyl 1-hydroxy cyclohexanecarboxylate (2a-2), hydrochlo ric acid in ethanol was used as esterification reagent and got a 48% more yield than literature's method. On the third, when preparing ethyl 1-[2-(2, 4-dichlorophenyl)-acetoxy]-cyclohexanecarboxylate, HPLC and RSM method was used to track the optimized situation of solvents, starting material ratio, catalyst and so on. After verification, the prediction and experimental validation error in RSM method was only 0.7%. Finally, 3-(2, 4-dichlorophenyl)-2-oxo-1-oxa-spiro[4,5]-decyl-3-en-4-ol was also obtained by optimizing the reaction situation of solvents, temperature, catalysts and purification method, which dramatically improved the manufacturing condition. During the preparation of Spirodiclofen, DMAP was used as catalyst with a yield of 98%.Due to Spirodiclofen and Spiromesifen's excellent bioacitvities and new structure, they can act as an excellent lead compounds to develop new pesticides. Here, 61 new derivatives of them were synthesized. Their structures were confirmed by 1H NMR and MS even by X-ray diffraction. And their bioactivities against spider mites, armyworm and aphid were also evaluated. Interestingly, compound 5a-12,5a-17,5a-26 and 5a-33 show better activity than Spirodiclofen against spider mites at the concentration of 600 mg/L. The LC50 of the compound 5a-17 and 5a-33 against spider mites are 231.77mg/L and 293.03mg/L, respectively. The compound 5a-8,5a-15,5a-19,5a-20,5a-22,5a-26,5a-33 and 5a-34 show an excellent inhibition activity against aphid, from which the LC50 of 5a-20 even get to 21.90 mg/L. Furthermore, compound 5a-8,5a-12,5a-15,5a-19,5a-26,5a-27 and 5a-32 show an excellent inhibition activity against armyworm, and the LC50 of 5a-8 reaches 18.01mg/L. At the same time, we studied the relationship of the structure and biological activities by single-crystal X-ray diffraction of representative compound.