Design And Discovery Of A Highly Active Herbicide Based On Pyrimidine

Design and discovery of a herbicide with good ecological profiles, high efficiency, novel mechanism and structure are still important research tasks.In this paper, molecular design of a highly active herbicide is studied based on pyrimidine with ecological profiles. The pyrimidine lead compound is obtained via herbicidal activity screen. The optimization of lead compound leads to find the good pyrimidine benzylamine candidates with highly effective herbicidal activity. The novel herbicidal mechanism of pyrimidine benzylamine is put forward. N-(2-bromophenyl)-2-(4, 6-dimethoxypyrimidin-2-yloxy)benzylamine (103-1) has potential as a new selective post-emergent herbicide in oilseed rape. This discovery will lead to open a new way for oilseed rape herbicide design. The dissertation is divided into six chapters.In the first chapter, the development, target, selectivity, environmental behavior and molecular design of herbicides are reviewed. The comments on research and molecular design of highly active pyrimidine herbicides are involved. The research target of the dissertation is put forward in this chapter.In the second chapter, the lead compound is found via molecular design and biological screen test. The library containing 72 compounds with six different pyrimidine cores is designed and synthesized based on the random screen combined with analogues design. The results of bioassay suggest that 2-methylthio-6-methyl-4-substituted pyrimidine and 4, 6-dimethoxy-2-substituted pyrimidine derivatives show herbicidal activity. In these target compounds, 4, 6-dimethoxy-2-substituted pyrimidine benzylamine and 4, 6-dimethoxy-2-Substituted pyrimidine benzylidene amine exhibit good herbicidal activity, and the herbicidal will be affected by the substituents in the benzene ring. In summary, 4, 6-dimethoxy-2-substituted pyrimidine benzylamine is chosen as a lead compound based on the possibility of synthesis, optimization, and the herbicidal activity.In the third chapter, the good candidate will be obtained via optimization of the lead compound. The design and structure-relationships of five different 4, 6-dimethoxy-2-substituted pyrimidine benzylamine derivatives are summarized: (1) Some N-(monohalo-substituted phenyl)-2-(4, 6-dimethoxy-2-yloxy)benzyl-amine derivatives are high post-emergent and pre-emergent herbicidal activity at low dosage of 75 gai/hm².(2) The good herbicidal activity can not be observed at low dosage of 75 g ai/hm² for N-(mono-ester substituted phenyl)-2-(4, 6-dimethoxy-pyrimidin-2-yloxy)benzylamine derivatives in post-emergent and pre-emergent application.(3) The high post-emergent and pre-emergent herbicidal activity at low dosage of 75 g ai/hm² can be found for some N-(mono-substituted phenyl)-2-(4, 6-dimethoxypyrimidin-2-yloxy)benzylamine derivatives.(4) The good post-emergent herbicidal activity is observed in N-(bis-substituted phenyl)-2-(4, 6-dimethoxypyrimidin-2-yloxy)benzylamine derivatives.:(5) N-(mono-substituted phenyl)2-(4, 6-dimethoxypyrimidin-2-ylthio)benzyl-amine derivatives are inactive at 75 g ai/hm².In summary, 15 new N-(substituted phenyl)-2-(4, 6-dimethoxypyrimidin-2-yl-oxy)benzylamine derivatives with high herbicidal activity are obtained. The compounds 103-1 and 105-3 are showed to have good selectivity and be chosen as good candidate for the further evaluation in field trials.In the forth chapter, the mechanism of pyrimidine benzylamine compounds is studied by the conventional bioassay and biochemical methods based on probe compound 104-4. The results presented here indicated that the addition of 5 mg/L of 3 branched-amino acids to sorghum seedling cultures incubated in the presence of 104-4 completely alleviated herbicide-induced stem growth inhibition, but each of Val, Ile and Leu single is only partly effective in reversing 104-4-induced growth inhibition at the same concentrations. The IC₅₀ values of 104-4 and bispyribac-sodium are about 100 mg/L and in the ranges of 10^-5～10^-4 mg/L respectively in vitro, so 104-4 shows little inhibition effect on acetolactate synthase (ALS). ALS is greatly inhibited by 104-4 in vivo, and the activity of ALS is lowered with the increase of treat time. It is Concluded that the mode of action of pyrimidine benzylamine differs from the other typically commercial ALS inhibitors, such as sulfonylurea and pyrimidine salicylic acid herbicides. Its herbicidal activity is activated by the metabolic processes in the plants.In the five chapter, the research is related to the further evaluation of good candidate as a potential herbicides for the application in field. The compound 103-1 is investigated in synthesis method, structure analysis, herbicidal activity, crop safety and toxicological test. The results show: (1) It is easily synthesized based on the simple industry processes with obtainable substances, low cost and low pollution; (2) it is effective against major grass weed species, as well as broadleaf weeds in oilseed rape, its inhibition is 80-100% at rates of 25 to 45 g ai/hm² and its dosage is the same level of highly active herbicides. Oilseed rape exhibits excellent tolerance to compound 103-1; (3) compound 103-1 has favourable toxicological and environmental profiles.These results suggest that compound 103-1 has potential as a new selective post-emergent herbicide in oilseed rape.In the six chapter, the major results and the prospects for the further research are reviewed.