Cyano-3-phenylurea

Submitted by Frederick Kurzer and J. Roy Powell. Checked by John C. Sheehan and Ernest R. Gilmont. 

To a solution of 16.8 g. (0.40 mole) of cyanamide in 50 ml. of water (Note 1) contained in a 400-ml. flask or beaker is added SO ml. of aqueous 3 N sodium hydroxide (0.15 mole). To the resulting solution, cooled to 15-18°, is added, in 2-ml. portions with shaking over a 15-18 minute period, 23.8 g. (22.0 ml.. 

The checkers used 16.8 g. of Eastman Kodak Company cyanamide (P1995) without further purification. A convenient method of preparing cyanamide from commercial calcium cyan-amide has been described. According to the submitters, an aqueous solution of crude cyanamide is satisfactory in the present synthesis and is obtained by adapting this published procedure as follows. 

The residual crude cyanamide remaining after evaporation of the ethereal extracts (which need not be dried previously) is dissolved readily in the appropriate volume of cold water. A small quantity of water-insoluble oily or semisolid by-products is removed by shaking the solution with carbon and filtering the liquid through a small ordinary filter, followed by rinsing with a few milliliters of water. The clear filtrate is suitable for the subsequent operation. 

In order to allow for small losses in the filtration and for the presence of impurities (such as solvent and oily by-products) an excess of approximately 10-15% by weight of crude cyanamide is allowed. 

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N-Cyanoguanidine, 35, 69 Cyanohydrin formation, 33, 7 3-Cyano-6-isobutyl-2(l)-pyridone, 32, 34 3-Cyano-6-methyl-2(1)-pyridone, 32, 32 l-Cyano-3-a-naphthylurea, 36, 11 1-Cyano-3-phenylurea, 36, 8 Cyclic acyloins, 36, 82 Cyclization, (3-aminoethylsulfuric acid to ethylenimine, 30, 38 1,2-benzo-3,4-dihydrocarbazole from phenylhydrazine and a-tetralone,... 

I-Cyano-3-phenylurea, first obtained by the alkaline hydrolysis of 5-anilino-3- -toluyl-l,2,4-oxadiazole, has been prepared by tlic condensation of phenyl isocyanate and the sodium salt of cyanamide. However, in these publications an incorrect structural assignment for the product was made. 1-Cyano-3-phenyl-urea is obtained also, together with other products, by warming gently l-cyano-3-phenylthiourea with caustic soda in the presence of ethylene chlorohydrin, or by gradually adding caustic )otash to a boiling solution of 1-phenyldithiobiuret and ethylene clilorohydrin in ethanol. ... 

Condensation of phenyl isocyanate with an aqueous solution of the sodium salt of cyanamide and acidification affords l-cyano-3-phenylurea (4). ... 

Preparation of Af-Cyano-4-Methyl-A -Phenyl-Benzene-sulfonamide (1). Dehydrative tosylation of iV-phenylurea 2 with p-toluenesulfonyl chloride in pyridine at room temperature gave iV-cyano-4-methyl-iY-phenyl-benzenesulfonamide in 76% yield (eq 1). Notably, title compound 1 is synthesized in a user-friendly and environmentally benign fashion, eliminating the use of toxic cyanation reagents such as BrCN and HCN. Alternative methods of preparation involve the direct tosylation of phenyl cyanamide in pyridine. Structural analogs, such as ben-zenesulfonyl IV-phenyl cyanamide 3 and p-nitrobenzenesulfonyl //-phenyl cyanamide 4, are accessible in a similar manner. ... 

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