Synthesis Of Unsymmetrical Ureas And Semicarbazides Under Microwave Irradiation

Unsymmetrical ureas and semicarbazides are very useful fine chemicals. They are widely used as herbicides, pesticides, plant growth regulators and medicinal intermediates. Ureas and semicarbazides bearing heterocyclic substituents, for example benzofuran and 1, 3, 4-thiadiazole, may be good candidates for biologically active compounds.However, the synthetic protocols of ureas and semicarbazides generally utilize phosgene or phosgene-based isocyanates as starting materials, both of which are toxic or unstable. Therefore, it is necessary to develop some phosgene-free routes for unsymmetrical ureas and semicarbazides.A series of unsymmetrical ureas and semicarbazides, in anhydrous aprotic solvents, were synthesized by reactions of benzofuran isocyanate, which were prepared by treating benzofuran-2-carboxylic acid with sodium azide and ethyl chlorocarbamate in the presence of triethylamine followed by Curtius rearrangement, with various aromatic amines, aryl carboxylic acid hydrazides, aryloxyacetic acid hydrazides, or 2-amino-5-aryloxymethylene-l, 3, 4-thiadiazoles respectively under microwave irradiation using one pot procedures. Eleven N-aryl-N'-(benzofiiran-2-yl) ureas, ten N-benzofuran-2-yl-N'-(l, 3, 4-thiadiazol-2-yl) ureas, ten l-arylformyl-4-(benzofuran-2-yl) semicarbazides and eleven l-aryloxyacetyl-4-(benzofuran-2-yl) semicarbazides were obtained. In addition, ethyl N-(5-aryloxymethylene-l, 3, 4-thiadiazol-2-yl) carbamates were also efficiently synthesized by the reactions of 2-amino-5-aryloxymethylene-l, 3, 4-thiadiazoles with ethyl chlorocarbamate under liquid-liquid phase transfer catalysis using PEG-400 as catalyst. The structures of compounds were characterized by elemental analyses, IR and 1H NMR.The experimental results showed that these reactions proceeded efficiently under reaction conditions studied. The all microwave irradiation reactions can be completed within a few minutes in a satisfactory yield. In contrast, the same reactions required several hours in lower yield by traditional heating method. The main advantages of microwave method are rapid reaction rate, high yield, less by-products, and convenient manipulation.