Editing Urea (section)

==Properties==

===Molecular and crystal structure===
The structure of the molecule of urea is {{chem2|O\dC(\sNH2)2}}. The urea molecule is planar when in a solid crystal because of [[Orbital hybridisation#sp2|sp<sup>2</sup> hybridization]] of the N orbitals.<ref name="Godfrey 1997">{{cite journal | last1=Godfrey | first1=Peter D. | last2=Brown | first2=Ronald D. | last3=Hunter | first3=Andrew N. | title=The shape of urea | journal=Journal of Molecular Structure | volume=413–414 | date=1997 | doi=10.1016/S0022-2860(97)00176-2 | pages=405–414| bibcode=1997JMoSt.413..405G }}</ref><ref name="Ishida 2004">{{cite journal | last1=Ishida | first1=Tateki | last2=Rossky | first2=Peter J. | last3=Castner | first3=Edward W. | title=A Theoretical Investigation of the Shape and Hydration Properties of Aqueous Urea: Evidence for Nonplanar Urea Geometry | journal=The Journal of Physical Chemistry B | volume=108 | issue=45 | date=2004 | issn=1520-6106 | doi=10.1021/jp0473218 | pages=17583–17590}}</ref> It is non-planar with C<sub>2</sub> symmetry when in the gas phase<ref name="West 2015">{{cite journal | last1=West | first1=Aaron C. | last2=Schmidt | first2=Michael W. | last3=Gordon | first3=Mark S. | last4=Ruedenberg | first4=Klaus | title=A Comprehensive Analysis in Terms of Molecule-Intrinsic, Quasi-Atomic Orbitals. III. The Covalent Bonding Structure of Urea | journal=The Journal of Physical Chemistry A | volume=119 | issue=41 | date=2015-10-15 | issn=1089-5639 | doi=10.1021/acs.jpca.5b03400 | pages=10368–10375| pmid=26371867 | bibcode=2015JPCA..11910368W | url=https://lib.dr.iastate.edu/cgi/viewcontent.cgi?article=1624&context=chem_pubs }}</ref> or in aqueous solution,<ref name="Ishida 2004" /> with C–N–H and H–N–H bond angles that are intermediate between the [[Trigonal planar molecular geometry|trigonal planar]] angle of 120° and the [[Tetrahedral molecular geometry|tetrahedral]] angle of 109.5°. In solid urea, the oxygen center is engaged in two N–H–O [[hydrogen bond]]s. The resulting hydrogen-bond network is probably established at the cost of efficient molecular packing: The structure is quite open, the ribbons forming tunnels with square cross-section. The carbon in urea is described as sp<sup>2</sup> hybridized, the C-N bonds have significant double bond character, and the carbonyl oxygen is relatively basic. Urea's high aqueous solubility reflects its ability to engage in extensive hydrogen bonding with water.

By virtue of its tendency to form porous frameworks, urea has the ability to trap many organic compounds. In these so-called [[clathrate]]s, the organic "guest" molecules are held in channels formed by interpenetrating helices composed of [[hydrogen bond|hydrogen-bonded]] urea molecules.  In this way, urea-clathrates have been well investigated for separations.<ref name="Worsch 2002">{{cite book | date=2002 | last1=Worsch | first1=Detlev | last2=Vögtle | first2=Fritz | title=Topics in Current Chemistry | chapter=Separation of enantiomers by clathrate formation | publisher=Springer-Verlag | isbn=3-540-17307-2 | doi=10.1007/bfb0003835 | pages=21–41}}</ref>

===Reactions===
[[File:CSD CIF WITQEV.jpg|thumb|left|Structure of {{chem2|[Fe(urea)6](2+)}} showing intramolecular hydrogen bonds.<ref>{{cite journal|journal=Zh. Neorg. Khim. (Russ. J. Inorganic Chemistry)|first1=N.E.|last1=Kuz'mina|first2=K.K.|last2=Palkina|first3=E.V.|last3=Savinkina|first4=I.A.|last4=Kozlova|volume= 45|year=2000|page = 395}}</ref> Color code: blue = N, red = O.]]
Urea is a weak base, with a p''K''<sub>b</sub> of 13.9.<ref name=pK/> When combined with strong acids, it undergoes protonation at oxygen to form '''uronium''' salts.<ref name="IUPACUroniumSalts">{{GoldBookRef|title=uronium salts|file=U06580}}</ref><ref name="HarkemaFeil1969">{{cite journal | last1=Harkema | first1=S. | last2=Feil | first2=D. | title=The crystal structure of urea nitrate | journal=Acta Crystallographica Section B Structural Crystallography and Crystal Chemistry | volume=25 | issue=3 | date=1 March 1969 | issn=0567-7408 | doi=10.1107/S0567740869002603 | pages=589–591 | bibcode=1969AcCrB..25..589H | url=https://ris.utwente.nl/ws/portalfiles/portal/6487049/Harkema69crystal.pdf | archive-url=https://web.archive.org/web/20240602043109/https://ris.utwente.nl/ws/portalfiles/portal/6487049/Harkema69crystal.pdf | archive-date=2 June 2024 | access-date=26 August 2024 | url-status=live }}</ref> It is also a [[Lewis base]], forming metal complexes of the type {{chem2|[M(urea)6]^{''n''+}|}}.<ref>{{cite journal |doi=10.1021/acsomega.3c09635 |title=Hexakis(urea-O)iron Complex Salts as a Versatile Material Family: Overview of Their Properties and Applications |date=2024 |last1=Béres |first1=Kende Attila |last2=Homonnay |first2=Zoltán |last3=Kótai |first3=László |journal=ACS Omega |volume=9 |issue=10 |pages=11148–11167 |pmid=38496982 |pmc=10938395 }}</ref>

Urea reacts with [[malonic acid|malonic]] esters to make [[barbituric acid]]s.

====Thermolysis====
Molten urea decomposes into [[ammonium cyanate]] at about 152&nbsp;°C, and into [[ammonia]] and [[isocyanic acid]] above 160&nbsp;°C:<ref name="Schaber 2004">{{cite journal | last1=Schaber | first1=Peter M. | last2=Colson | first2=James | last3=Higgins | first3=Steven | last4=Thielen | first4=Daniel | last5=Anspach | first5=Bill | last6=Brauer | first6=Jonathan | title=Thermal decomposition (pyrolysis) of urea in an open reaction vessel | journal=Thermochimica Acta | volume=424 | year=2004 | issue=1–2 | issn=0040-6031 | doi=10.1016/j.tca.2004.05.018 | pages=131–142| bibcode=2004TcAc..424..131S }}</ref>
{{block indent |left=1.5 |text={{chem2|CO(NH2)2 → [NH4]+[OCN]- → NH3 + HNCO}}}}

Heating above 160&nbsp;°C yields [[biuret]] {{chem2|NH2CONHCONH2}} and [[triuret]] {{chem2|NH2CONHCONHCONH2}} via reaction with isocyanic acid:<ref name="Meessen 2012">{{Ullmann |last=Meessen |first=Jozef H. |title=Urea |year=2012 |doi=10.1002/14356007.a27_333.pub2}}</ref><ref name="Schaber 2004"/>
{{block indent |left=1.5 |text={{chem2|CO(NH2)2 + HNCO → NH2CONHCONH2}}}}
{{block indent |left=1.5 |text={{chem2|NH2CONHCONH2 + HNCO → NH2CONHCONHCONH2}}}}

At higher temperatures it converts to a range of [[condensation reaction|condensation product]]s, including [[cyanuric acid]] {{chem2|(CNOH)3}}, [[guanidine]] {{chem2|HNC(NH2)2}}, and [[melamine]].<ref name="Meessen 2012" /><ref name="Schaber 2004"/>

====Aqueous stability====
In aqueous solution, urea slowly equilibrates with ammonium cyanate. This [[elimination reaction]]<ref name="AlexandrovaJorgensen2007">{{cite journal |last1=Alexandrova |first1=Anastassia N. |author-link1=Anastassia Alexandrova |last2=Jorgensen |first2=William L. |author-link2=William L. Jorgensen |title=Why Urea Eliminates Ammonia Rather than Hydrolyzes in Aqueous Solution |journal=The Journal of Physical Chemistry B |date=1 February 2007 |volume=111 |issue=4 |pages=720–730 |doi=10.1021/jp066478s|pmid=17249815 |pmc=2995377 }}</ref> cogenerates [[isocyanic acid]], which can [[Isocyanic acid#Reactions|carbamylate]] proteins, in particular the N-terminal amino group, the side chain amino of [[lysine]], and to a lesser extent the side chains of [[arginine]] and [[cysteine]].<ref name="SA_PDF">{{cite web |last1=Aldrich |first1=Sigma |title=Urea Solution Product Information |url=https://www.sigmaaldrich.com/deepweb/assets/sigmaaldrich/product/documents/392/609/u4883dat.pdf |access-date=7 February 2023}}</ref><ref name="Burgess Deutscher 2009">{{cite book | last1=Burgess | first1=Richard R. | last2=Deutscher | first2=Murray P. | title=Guide to protein purification | publisher=Academic Press/Elsevier | publication-place=San Diego, Calif | date=2009 | isbn=978-0-12-374536-1 | oclc=463300660 | page=819}}</ref> Each carbamylation event adds 43 [[Dalton (unit)|daltons]] to the mass of the protein, which can be observed in [[protein mass spectrometry]].<ref name="Burgess Deutscher 2009"/> For this reason, pure urea solutions should be freshly prepared and used, as aged solutions may develop a significant concentration of cyanate (20&nbsp;mM in 8&nbsp;M urea).<ref name="Burgess Deutscher 2009"/> Dissolving urea in ultrapure water followed by removing ions (i.e. cyanate) with a mixed-bed [[ion-exchange resin]] and storing that solution at 4&nbsp;°C is a recommended preparation procedure.<ref name="Deutscher 1990">{{cite book | last=Deutscher | first=M.P. | title=Guide to Protein Purification | publisher=Academic Press | series=Methods in enzymology | year=1990 | isbn=978-0-12-182083-1 | url=https://books.google.com/books?id=zTiRJHpKIQoC&pg=PR11 | access-date=2023-02-24 | page=267}}</ref> However, cyanate will build back up to significant levels within a few days.<ref name="Burgess Deutscher 2009"/> Alternatively, adding 25–50 mM [[ammonium chloride]] to a concentrated urea solution decreases formation of cyanate because of the [[common ion effect]].<ref name="Burgess Deutscher 2009"/><ref>{{cite journal | vauthors = Sun S, Zhou JY, Yang W, Zhang H | title = Inhibition of protein carbamylation in urea solution using ammonium-containing buffers | journal = Analytical Biochemistry | volume = 446 | pages = 76–81 | date = February 2014 | pmid = 24161613 | pmc = 4072244 | doi = 10.1016/j.ab.2013.10.024 }}</ref>

===Analysis===
Urea is readily quantified by a number of different methods, such as the diacetyl monoxime colorimetric method, and the [[Berthelot's reagent|Berthelot reaction]] (after initial conversion of urea to ammonia via urease). These methods are amenable to high throughput instrumentation, such as automated flow injection analyzers<ref>{{cite journal | vauthors = Baumgartner M, Flöck M, Winter P, Luf W, Baumgartner W | title = Evaluation of flow injection analysis for determination of urea in sheep's and cow's milk | journal = Acta Veterinaria Hungarica | volume = 50 | issue = 3 | pages = 263–71 | year = 2005 | pmid = 12237967 | doi = 10.1556/AVet.50.2002.3.2 | s2cid = 42485569 | url = http://real.mtak.hu/49298/1/avet.50.2002.3.2.pdf }}</ref> and 96-well micro-plate spectrophotometers.<ref>{{cite journal| vauthors = Greenan NS, Mulvaney RL, Sims GK |year=1995|title= A microscale method for colorimetric determination of urea in soil extracts|journal= Communications in Soil Science and Plant Analysis|volume= 26|issue=15–16|pages=2519–2529|doi=10.1080/00103629509369465|bibcode=1995CSSPA..26.2519G |url=https://zenodo.org/record/1234433}}</ref>