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Synthesis

Ureas can be prepared many methods, but rarely by direct carbonation, which is the route to urea itself. Instead, methods can be classified according those that assemble the urea functionality and those that start with preformed urea.

Assembly of N-substituted urea functionality

Phosgenation entails the reaction of amines with phosgene, proceeding via the isocyanate (or carbamoyl chloride) as an intermediate: Overall reaction: Tetramethylurea is prepared in this way and in general secondary amines give reliable results. Reactions using primary amines must be carefully controlled as the isocyanate intermediate can react with the urea to form a biuret: Unsymmetrical ureas are generated by condensation of isocyanates with amines: Analogously, unsymmetrical primary ureas are generated by condensation of ammonium salts and alkali metal cyanates:JOURNAL, Frederick Kurzer, Arylureas I. Cyanate Method p-Bromophenylurea, Org. Synth., 1951, 31, 8, 10.15227/orgsyn.031.0008, The artificial sweetener dulcin is produced by the condensation of ethoxyaniline with potassium cyanate. Si(NCO)4 is also used as a precursor to such unsymmetrical ureas.JOURNAL, Roy G. Neville and John J. McGee, N-Mono- and N,N-Disubstituted Ureas and Thioureas, Org. Synth., 1965, 45, 69, 10.15227/orgsyn.045.0069, The very high toxicities of compounds such as phosgene and isocyanates makes them unappealing to work with and there has been a drive towards safer reagents. These have traditionally been more expensive and hence mostly been limited to laboratory-scale work.JOURNAL, Bigi, Franca, Maggi, Raimondo, Sartori, Giovanni, Selected syntheses of ureas through phosgene substitutes, Green Chemistry, 2000, 2, 4, 140–148, 10.1039/B002127J,

From urea

Urea undergoes transamidation with alkyl and aryl amines: These reactions are used to prepare cyclic ureas. Monomethylurea, precursor to theobromine, is produced from methylamine and urea. Phenylurea is produced similarly but from anilinium chloride:JOURNAL, Arylureas II. Urea Method p-Ethoxyphenylurea, Organic Syntheses, 1951, 31, 11, 10.15227/orgsyn.031.0011, Ureas containing N-H bonds, including urea itself, are readily alkylated by aldehydes. The products are α-hydroxyalkylureas. Formaldehyde gives the bis(hydroxymethyl)urea, an intermediate in the formation of urea-formaldehyde resins. Cyclic ureas result from glyoxal ((CHO)2): Two equivalents of urea condense with isobutyraldehyde giving the alkylidene derivative: This derivative, isobutylidenediurea, is used as a slow-release fertilizer because in the soil it slowly hydrolyzes, reverting to urea, an excellent source of fixed nitrogen.File:BenzimidazolinoneTape.svg|thumb|right|Benzimidazolinone "tape" derived from benzimidazolinonebenzimidazolinone

References