Synthesis Of Pyrimidin Derivatives And The Application Of Mannich Reaction In Pesticide Synthesis

In this artical, new compounds nitramide pyrimidin derivatives were designed and synthesized and the fungicidal activity was evaluated. The application of Mannich Reaction on the synthesis of pesticide Thiamethoxam and Clothianidin was explored. It mainly contains two parts as below:Part I: Design & synthesis and fungicidal activity of substitute nitramide pyrimidin derivativesAcetylacetone, methyl acetoacetate, ethyl acetoacetate, dimethyl malonate, diethyl malonate and nitroguanidine were designed as starting materials to synthesize the nitramide pyrimidin derivatives. The OMe and OEt group of the starting materials were hydrolyzed to hydroxyl in the process of synthesis. Therefore, two series and 17 compounds were synthesized in good yields and high efficiency in this paper. No title compound was found from acetylacetone because of its strongly keto-enol tautomerism. The structures were identified by the 1^H NMR, (13)^C NMR, HRMS, IR et al. The fungicidal activity of the synthesized compounds against nine fungus species: Rhizoctonia solani Kühn, Phytophthora parasitica Dast, Phomopsis asparagi (Sacc.) Bubak, Botrytis cinerea Pers., Fusarium oxysporum Schl., Sclerotinia sclerotiorum (Lib.) de Bary, Pythium cucurbitacearum Takim, Pythium aphanidermatum and Blumeria graminis(D C.) Speer was evaluated using the mycelium growth rate test. The results showed that some of these compounds showed obvious inhibitory of the mycelium growth. The compounds 1d and 1″g against Blumeria graminis (D C.) Speer, 2a against Phomopsis asparagi (Sacc.) Bubak and 2d against Botrytis cinerea Pers showed the best fungicidal activity among the synthesized compounds. The structure-activity relationship was also discussed. The nitramide is a strong polar hydrophility group. All the compounds have good water solubility affected by the nitramide and hydroxyl group. The structures of these synthesized compounds are similar to the commercial fungicides dimethirimol and ethirimol. The hydrophobicity of N, N-dimethyl group and N-ethyl group in the dimethirimol and ethirimol was stronger than nitramide group in the synthesized compounds. The bioactivity of the compounds was affected by the property of the group, in these compounds, stronger hydrophobicity cause higher activity. Therefore, the nitramide group of the synthesized compounds caused the low activity.Part II: Application of Mannich Reaction on the sythesis of pesticideIn this section, the application of Mannich Reaction on the synthesis of new neonicotinoids pesticide Thiamethoxam and Clothianidin was described. The compound 3-methyl-4-nitroimino- tetrahydro-1,3,5-oxadiazine is an important intermediate of the pesticide Thiamethoxam and Clothianidin. The reaction of N-methyl-N′-nitroguanidine to 3-methyl-4-nitroimino-tetrahydro-1,3,5- oxadiazine was a Mannich-type reaction and was catalyzed by the acid catalyst described in some literature. Some research work was carried out on the basis of the previous work. In this paper, the reaction was catalyzed by several organic and inorganic bases and got good yields. Three inorganic base catalysts: potassium carbonate (K₂CO₃), sodium hydrogen carbonate (NaHCO₃), sodium hydroxide (NaOH) and several organic bases: methylamine, ethamine, isopropylamine and n-butylamine have been used and studied. The results showed that both the inorganic and organic base catalysts can be used as catalysts with the organic bases performing better. The effects on the products from the intensity of inorganic base catalysts, reaction temperature and reaction time were also explored. The stronger base intensity, higher reaction temperature and longer reaction time can promote the decomposed of the N-methyl-N'-nitroguanidine and cause significant effects on the title compounds.