Ureas

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.{{ Ullmann | author = C. Nitschke | author2 = G. Scherr | title = Urea Derivatives | year = 2012| doi = 10.1002/14356007.o27_o04}}

Phosgenation entails the reaction of amines with phosgene, proceeding via the isocyanate (or carbamoyl chloride) as an intermediate:

:COCl₂ + R₂NH → R₂NC(O)Cl + HCl

:COCl₂ + RNH₂ → RNCO + 2 HCl

Overall reaction:

:COCl₂ + 2 R₂NH → (R₂N)₂CO + 2 HCl

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:

:R₂NC(O)N(H)R' + R"NCO → R₂NC(O)NR'C(O)NHR"

Unsymmetrical ureas are generated by condensation of isocyanates with amines:

:RNCO + R'₂NH → (R'₂N)(R(H)N)CO

Analogously, unsymmetrical primary ureas are generated by condensation of ammonium salts and alkali metal cyanates:{{cite journal

|author=Frederick Kurzer

|title=Arylureas I. Cyanate Method p-Bromophenylurea

|journal=Org. Synth.

|year=1951

|volume=31

|page=8

|doi=10.15227/orgsyn.031.0008}}

:Na⁺NCO⁻ + [R₂NH₂]Cl → (R’₂N)(H₂N)CO + NaCl

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.{{cite journal

|author=Roy G. Neville and John J. McGee

|title=N-Mono- and N,N-Disubstituted Ureas and Thioureas

|journal=Org. Synth.

|year=1965

|volume=45

|page=69

|doi=10.15227/orgsyn.045.0069}}

image:OC(NHCH2OH)2.png and related compounds are additives for permanent press clothing.]]

image:IBDU.png.]]

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.{{cite journal |last1=Bigi |first1=Franca |last2=Maggi |first2=Raimondo |last3=Sartori |first3=Giovanni |title=Selected syntheses of ureas through phosgene substitutes |journal=Green Chemistry |date=2000 |volume=2 |issue=4 |pages=140–148 |doi=10.1039/B002127J}}

Urea undergoes transamidation with alkyl and aryl amines:

:(H₂N)₂CO + R₂NH → (R₂N)(H₂N)CO + NH₃

:(R₂N)(H₂N)CO + R₂NH → (R₂N)₂CO + NH₃

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:{{cite journal

|title=Arylureas II. Urea Method p-Ethoxyphenylurea

|journal=Organic Syntheses

|year=1951

|volume=31

|page=11

|doi=10.15227/orgsyn.031.0011}}

:(H₂N)₂CO + [R₂NH₂]Cl → (R₂N)(H₂N)CO + NH₄Cl

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):

:(H₂N)₂CO + (CHO)₂ → (CH(OH)NH)₂CO

Two equivalents of urea condense with isobutyraldehyde giving the alkylidene derivative:

:2(H₂N)₂CO + OC(H)CHMe₂ → (H₂N)C(O)NH]₂CHCHMe₂ + H₂O

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.svgs.{{cite journal |doi=10.1021/ja952836l |title=Engineering the Solid State with 2-Benzimidazolones |date=1996 |last1=Schwiebert |first1=Kathryn E. |last2=Chin |first2=Donovan N. |last3=MacDonald |first3=John C. |last4=Whitesides |first4=George M. |journal=Journal of the American Chemical Society |volume=118 |issue=17 |pages=4018–4029 }}]]