The Research On The Methods Of Synthesizing Asymmetrical New Aromatic Urea Compounds

The paper describes the work on synthesizing and detecting 16 aromatic urea compounds with new asymmetric structures, aiming at constructing a diverse compounds library of asymmetric ureas, which are useful for researchers to screen bioactivities on them.In this paper, N, N’-carbonyl diimidazole, triphosgene, and p-nitrophenyl chloroformate were chosen as the carbonyl source. With following three methods, a plethora of designed asymmetric aromatic urea compounds were synthesized under mild conditions in the laboratory.(1) An aromatic amine as the substrate dissolved in DMSO or DMF with triethylamine working as catalyst in room temperature, then N, N’-carbonyl diimidazole was added in order to form activated intermediate, followed the other aromatic amine was dropped to react with the intermediate. Finally, the desired aromatic urea was obtained. The method is simple, mild, and the conversion rate is ideal, aromatic urea compounds can be synthesized in two steps.(2) A aromatic amine reacted with triphosgene in anhydrous solvents including THF, DCM, DMF, in the presence of DIEA at room temperature. Then another aromatic amine was added to react with the forming isocyanate, producing the targeted compound. The method was not easy to operate and was very strict with anhydrous condition. The remaining triphosgene in first step could worsen the second step; some amines could form symmetric urea in first step.(3) An aromatic amine reacted with p-nitrophenyl chloroformate in THF under basic conditions at room temperature to form the corresponding isocyanate. Then the active intermediate reacted with another amine to generate the corresponding aromatic urea. Nitrophenyl chloroformate method was mainly used in the reaction of primary amines with mild conditions and good feasibility. But the first step would be to form a yellow precipitate nitrophenol byproduct, and the second step reflux longer.The designed new asymmetric aromatic ureas contained not only benzene rings, but also the aromatic heterocyclic rings. Besides, the rings were conjugated with a diversity of groups including halogen groups, electron-withdrawing groups and electron-donating groups. The paper found the optimized method for every one of the compounds, giving a conclusion for the operating skills, the applying scopes and the reacting characteristics of above three methods.