Green Synthesis Of O- And Its Application Methylisourea Amine Salt In Pyrimidine Synthesis

Pyrimidinamine compounds are a kind of nitrogen heterocyclic compounds with good biological activities, such as sterilization, insecticide, herbicide, antidote, anticancer effect, etc. They have been widely used in the fields of biology, medicine and agriculture, etc. In this paper, a feasible, environmental friendly, simple and high-efficient synthetic route was designed. First, O-methylisourea was synthesized with starting materials of dimethyl carbonate (DMC) and urea. Then, N-substituted guanidiniums were synthesized. Finally, the target product N-substituted-4-(3-pyridinyl)-2-pyrimidinamines were synthesized. In each step, reaction conditions were screened and optimized, the possible reaction mechanisms were analyzed and discussed, and the structures of all products were confirmed by IR,1HNMR and elemental analysis.O-methylisourea sulfate was synthesized with the method of grinding reaction-low thermal solid phase without solvent at room temperature. In this reaction, firstly urea was methylated by dimethyl carbonate to give free O^-methylisourea. Then free O-methylisourea was extracted by methyl alcohol and was neutralized by O-methylisourea bisulfate to give0-methylisourea sulfate. The grinding time was15min and the yield of O-methylisourea sulfate was above83%.O-methylisourea sulfate was reacted with different structures of6kinds of aliphatic amines and aromatic amine in ethanol-water mixed solvent under70℃for4～12hours.6kinds of corresponding N-substituted guanidinium were synthesized. After screening of reaction conditions, the yields of6kinds of N-substituted guanidinium were between60%-82%.Six kinds of N-substituted guanidinium synthesized in the previous step were reacted with3-(dimethylamino)-1-(3-pyridinyl)-2-propen-l-one in ethylene glycol under150℃for12hours. In the end, six kinds of N-substituted-4-(3-pyridinyl)-2-pyrimidinamine compounds were synthesized. After screening and optimization of reaction conditions, due to different biological activities and space steric effect of6N-substituted guanidinium, the yields of six kinds of N-substituted-4-(3-pyridinyl)-2-pyrimidinamine compounds were between73%～90%. In total,14compounds were synthesized in our work, including intermediates and target products. Both intermediates synthesized in each step and final target products are important organic compounds, used in organic synthesis, medicine and agriculture, etc.