Study On Synthesis And Biological Activity Of Pyrazolylpyrimidine Derivatives

Photosynthetic pigments inhibitors with chlorophylls and carotenoids as the site of action ensure the selectivity between plants and animals and become a hot focus in developing new herbicides due to their ultra-high efficiency and low toxicity. According to the chemical structure of protoporphyrinogen oxidase inhibitors with effective inhibition to the chlorophyll biosynthesis and lead compound 4-(5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)-6-(prop-2-yn-1-yloxy)pyrimidine with excellent bleaching activity,20 different types of new pyrazolyl pyrimidine compounds were designed and synthesized. Then it was performed for assaying biological activity of 31 pyrazolyl pyrimidine derivatives against Brassica campestris L. and Pennisetum alopecuroides L. And the structure-activity relationship was preliminarily discussed in this paper.Intermediates 4-alkoxy (alkyl amino)-6-chloropyrimidine or 2-methyl-4-alkoxy (alkyl amino) 6-chloropyrimidine derivatives were gained by the reaction of 4, 6-dichloropyrimidine or 2-methyl-4,6-dichloropyrimidine and different alcohols or amine compounds. Then the intermediates above and 2-amino-4-chloro-6-methy pyrimidine were reacted with pyrazole intermediates in alkaline DMF solvent to obtain target products of 4-alkoxy-6-1H-pyrazolyl pyrimidine derivatives,N-alkyl-6-1H-pyrazolyl pyrimidinyl-4-amine derivatives and 4-1H-pyrazolyl-6-methylthio pyrimidine derivatives. In addition,4-1H-pyrazolyl-6-methylthio pyrimidine derivatives were oxidized by m-CPBA to obtain 4-1H-pyrazolyl-6-methylsulfonyl pyrimidine derivatives.1H-Pyrazole derivative was reacted with the product of ammoniation and acetylation of 4,6-dichloropyrimidine to synthesize the compound N-6-1H pyrazolylpyrimidinyl acetamide derivative. The struetures of all novel target compounds were confirmed by elementary analysis,1H NMR, IR,13CNMR and LC-MS.Preliminary experimental indicated that all compounds in the concentration of 100 mg/L have different effect for root length and pigment synthesis of Brassica campestris L. and Pennisetum alopecuroides L. The sensitivity of Pennisetum alopecuroides L. is higher than Brassica campestris L. to target compounds. In general, the compounds 3a, 3e,3f,5a,5b,8a,8b,8c and 8h showed good herbicidal activity for Pennisetum alopecuroides L. Among them,8c showed the strongest inhibitory activity for the root length of Pennisetum alopecuroides L. with the IC50 of 1.90 mg/L.3e showed obvious whitening effect for Pennisetum alopecuroides L. with the IC50 of 3.14 mg/L. The structure-activity relationship showed that the activity of small molecules groups with linear or branched chain located 6-position in pyrimidine were better than aromatic group, especially propargyl and alkoxy with two or three carbon chain length. The electron-withdrawing groups substituted at 3-position and hydrogen atom substituted at 4-position of pyrazole ring were more favourable for improving the activity of 4-1H-pyrazolyl pyrimidine derivatives. The activity of 4-pyrazolyl pyrimidine derivatives was better than that of 2-pyrazolyl pyrimidine derivatives.