Synthesis And Biological Activity Of Novel N-Cyano Enamines

In recent years, novel species of pesticides, which are super-efficient, low toxicity, low-residue, have been developed. Some chemical structure of them are monoheterocycles or fused heterocycles, which are different from the conventional organophosphorus, carbamate and pyrethroid pesticides.Enamine compounds serve as potential intermediates in organic synthesis due to their high reactivity. Importantly, the synthesis of heterocyclic compounds, such as pyrrole, pyrazole, piperidine, pyridine, pyrimidine, isoxazole, indole and quinoline derivatives, can be synthesized from the enamines. Furthermore, enamine compounds are versatile core structures widely present in numerous pharmacological active molecules, such as pethoxamid (herbicides), nitenpyram (insecticide) and JS399-19(fungicide). Therefore, it is very important to study the new synthetic methods of enamine compounds, especially the synthesis of novel biologically active ones.This dissertation mainly developed a new method to synthesize the enamine compounds with starting material of tetrazoles and alkyl propiolates; some of their biological activities were also screened, expecting to find new biological activity pesticides.The main achievements are described in the following five aspects:1. A stereocontrolled1,2-additon reaction of tetrazoles with alkyl propiolates for the synthesis of highly functionalized enamines was developed. In the presence of silver oxide (Ag2O), the1,2-additon reaction generated (Z)-N-cyano enamines in high yields with exclusive Z-isomers. Meanwhile, the1,2-additon reaction generated (E)-N-cyano enamines in the presence of Ag2O and potassium carbonate (K2CO3) in good yields with high stereo selectivity. The resulting compounds have all been verified by high resolution mass spectrometry,1H and13C NMR;2. The reaction conditions have been optimized and the yields were improved under the optimal reaction condition;3. The scope of the substrates was extended to explore the broad spectrum of the reactions;4. The plausible mechanism of the reaction of synthetic (Z)-N-cyano-enamine and (E)-N-cyano-enamine was proposed and verified through some other experiments respectively; 5. Some of the synthesized enamine compounds were selected to make a vitro activity test with Fusarium graminearum.In conclusion, a novel, simple, efficient synthesis method has been developed, and48new enamines which have not been reported in the literature before were synthesized. There are no byproducts generated throughout the experiment, indicating that this method is in line with the principles of "atom economy" in green chemistry; the enamine compounds with a cyano group can be obtained by using the tetrazole as a starting material in the absence of highly toxic brominated carbonitrile, suggesting that this method is also in line with the requirements of "green materials" in green chemistry. At last, the preliminary bioassay of the synthesized products found several compounds to show vitro activity to Fusarium graminearum.