Synthesis Of Heterocyclic Sulfonylurea Compounds

Sulfonylurea herbicides are the most widely used herbicides in the world,they have the features of high-activity,low dosage,good selectivity and low-poisonous to human beings and animals.In recent years,studies have found that some sulfonylurea herbicides have problems such as difficulty in degradation and reduced sensitivity to weeds.Therefore,the development of novel sulfonylurea herbicides is particularly critical.In the previous work,the researchers used molecular dynamics computer simulation and virtual screening techniques to design four new potential inhibitors of ALS:?1?N-??4-chloro-6-methoxypyrimidin-2-yl?carbamoyl?-4-nitro-1H-imidazole-1-su lfonamide?Compound 1?;?2?N-??4-chloro-6-methoxypyrimidin-2-yl?carbamoyl?-4-methylbenzenesulfonamide?C ompound 2?;?3?N-??4-chloro-6-methoxypyrimidin-2-yl?carbamoyl?-3,4-dimethylbenzenesulfonami-de?Compound 3?;?4?N,N'-carbonylbis?4-methylbenzenesulfonamide??Compound 4?,simulated data indicated that they showed high affinity with drug-resistant mutant ALS.This dissertation described the synthesis and characterization of these four sulfonylurea ALS potential inhibitors:?1?Compound 1 was synthesized by nucleophilic addition and nucleophilic substitution reaction using 2-amino-4-chloro-6-methoxypyrimidine,chlorosulfonyl isocyanate and 4-nitroimidazole as raw materials.?2?With benzene sulfonyl chloride and 2-amino-4-chloro-6-methoxypyrimidine as raw materials,the synthesis paths were based on the amination reaction and isocyanate method to produce Compound 2 and Compound 3.?3?A new synthesis method was designed,which was to synthesize Compound 4 by carbamate method.The new synthesis method has the advantages of simple operation,high safety,low reaction cost and environmental friendliness.?4?The synthesis process of the target products and intermediates were preliminarily optimized.?5?The structures of four target products were characterized by one or several methods including ¹H NMR,¹³C NMR,IR and LC-MS.