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Revision as of 07:14, 6 August 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Script assisted update of identifiers for the Chem/Drugbox validation project (updated: 'ChEBI').← Previous edit		Latest revision as of 03:47, 3 January 2025 edit undo38.49.72.163 (talk) →Medical use: link euvolemicTags: Mobile edit Mobile web edit
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			{{Short description|Organic compound}}
	{{refimprove|date=January 2011}}
			{{Distinguish|uric acid|urine}}
			{{Redirect|Carbonic diamide|the azide|carbonyl diazide}}
			{{Use dmy dates|date=October 2020}}
	{{chembox		{{chembox
			| Verifiedfields = correct
	| verifiedrevid = 410162866
			| Watchedfields = correct
	| Name =
			| verifiedrevid = 443307328
	| ImageFile_Ref = {{chemboximage|correct|??}}
			| ImageFileL1 = Urea Structural Formula V2.svg
	| ImageFile = Harnstoff.svg
			| ImageFileR1 = Urea 3D ball.png
	| ImageSize = 150px
	| ImageFileL1 = Urea-3D-balls.png		| ImageFileL2 = Urea 3D spacefill.png
			| ImageFileR2 = Sample of Urea.jpg
	| ImageSizeL1 = 120px
			| PIN = Urea<ref name=iupac2013>{{cite book | title = Nomenclature of Organic Chemistry : IUPAC Recommendations and Preferred Names 2013 (Blue Book) | publisher = ] | date = 2014 | location = Cambridge | pages = 416, 860–861 | doi = 10.1039/9781849733069-FP001 | isbn = 978-0-85404-182-4 | quote = The compound H<sub>2</sub>N-CO-NH<sub>2</sub> has the retained name ‘urea’, which is the preferred IUPAC name, with locants N and N′, as shown above the structure below. The systematic name is ‘carbonic diamide’, (…).}}</ref>
	| ImageFileR1 = Urea-3D-vdW.png
			| SystematicName = Carbonic diamide<ref name=iupac2013 />
	| ImageSizeR1 = 100px
			| pronounce = urea {{IPAc-en|j|ʊəˈr|iː|ə}}, carbamide {{IPAc-en|ˈ|k|ɑːr|b|ə|m|aɪ|d}}
	| IUPACName = Urea
			| OtherNames = {{ubl|Carbamide|Carbonyldiamide|Carbonyldiamine|Diaminomethanal|Diaminomethanone}}
	| OtherNames = Carbamide, carbonyl diamide, carbonyldiamine, diaminomethanal, diaminomethanone <!-- See discussion on talk page -->
	| Section1 = {{Chembox Identifiers		| IUPACName =
			|Section1 = {{Chembox Identifiers
	| ChEBI = 16199		| IUPHAR_ligand = 4539
			| ChEBI_Ref = {{ebicite|correct|EBI}}
			| ChEBI = 16199
			| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
			| DrugBank = DB03904
	| SMILES = C(=O)(N)N		| SMILES = C(=O)(N)N
	| UNII_Ref = {{fdacite|correct|FDA}}		| UNII_Ref = {{fdacite|correct|FDA}}
	| UNII = 8W8T17847W		| UNII = 8W8T17847W
	| KEGG_Ref = {{keggcite|correct|kegg}}		| KEGG_Ref = {{keggcite|correct|kegg}}
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	| StdInChIKey = XSQUKJJJFZCRTK-UHFFFAOYSA-N		| StdInChIKey = XSQUKJJJFZCRTK-UHFFFAOYSA-N
	| CASNo = 57-13-6		| CASNo = 57-13-6
	| CASNo_Ref = {{cascite|correct|CAS}}		| CASNo_Ref = {{cascite|correct|CAS}}
	| PubChem = 1176		| PubChem = 1176
	| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}		| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
	| ChemSpiderID = 1143		| ChemSpiderID = 1143
	| RTECS = YR6250000		| RTECS = YR6250000
			| Beilstein = 635724
	}}
	| Section2 = {{Chembox Properties		| Gmelin = 1378
			}}
			|Section2 = {{Chembox Properties
			| Formula = {{chem2|CO(NH2)2}}
	| C=1|H=4|N=2|O=1
	| Appearance = White solid		| MolarMass = 60.06 g/mol
			| Appearance = White solid
	| Density = 1.32 g/cm<sup>3</sup>
			| Density = 1.32 g/cm<sup>3</sup>
	| Solubility = 107,9 g/100 ml (20 °C)<br/>167 g/100ml (40 °C)<br/>251 g/100 ml (60 °C)<br/>400 g/100 ml (80 °C)
			| Solubility = 545 g/L (at 25 °C)<ref name="Solubility">{{cite book|url=https://books.google.com/books?id=cfFzJFthLCIC&pg=PP1|title = Handbook of Aqueous Solubility Data|isbn = 9781439802465|last1 = Yalkowsky|first1 = Samuel H.|last2 = He|first2 = Yan|last3 = Jain|first3 = Parijat|date = 19 April 2016| publisher=CRC Press }}</ref>
	| MeltingPt = 133–135 °C
			| SolubleOther = 500 g/L glycerol<ref>{{cite web|url=http://msdssearch.dow.com/PublishedLiteratureDOWCOM/dh_0032/0901b8038003228b.pdf?filepath=glycerine/pdfs/noreg/115-00668.pdf|title=Solubility of Various Compounds in Glycerine|work=msdssearch.dow.com|access-date=2014-04-12|archive-url=https://web.archive.org/web/20140413155224/http://msdssearch.dow.com/PublishedLiteratureDOWCOM/dh_0032/0901b8038003228b.pdf?filepath=glycerine%2Fpdfs%2Fnoreg%2F115-00668.pdf|archive-date=2014-04-13|url-status=dead}}</ref>
	| pKa =
			&nbsp;&nbsp;50&nbsp;g/L ethanol<br>
	| pKb = p''K''<sub>BH<sup>+</sup></sub> = 0.18<ref>{{cite web|url=http://research.chem.psu.edu/brpgroup/pKa_compilation.pdf|title=pKa Data|last1=Williams|first1=R.|date=2001-10-24|accessdate=2009-11-27}}</ref>
			&nbsp;&nbsp;~4&nbsp;g/L ]<ref>{{cite journal|last1=Loeser|first1=Eric|last2=DelaCruz|first2=Marilyn|last3=Madappalli|first3=Vinay | name-list-style = vanc |title=Solubility of Urea in Acetonitrile–Water Mixtures and Liquid–Liquid Phase Separation of Urea-Saturated Acetonitrile–Water Mixtures|journal=Journal of Chemical & Engineering Data|date=9 June 2011|volume=56|issue=6|pages=2909–2913|doi=10.1021/je200122b}}</ref>
	}}
			| MeltingPtC = 133 to 135
	| Section3 = {{Chembox Structure
			| BoilingPt = decomposes
	| Dipole = 4.56 ]
			| MeltingPt_notes =
	}}
			| pKa =
	| Section7 = {{Chembox Hazards
			| pKb = 13.9<ref name=pK>Calculated from 14−pK<sub>a</sub>. The value of pK<sub>a</sub> is given as 0.10 by the ''CRC Handbook of Chemistry and Physics'', 49th edition (1968–1969). A value of 0.18 is given by {{cite web|url=http://research.chem.psu.edu/brpgroup/pKa_compilation.pdf|title=pKa Data|last1=Williams|first1=R.|date=2001-10-24|archive-url=https://web.archive.org/web/20030824213333/http://research.chem.psu.edu/brpgroup/pKa_compilation.pdf|archive-date=August 24, 2003}}</ref>
	| ExternalMSDS =
			| ConjugateAcid = Uronium
	| EUIndex = Not listed
			| MagSus = −33.4·10<sup>−6</sup> cm<sup>3</sup>/mol
	| FlashPt = Non-flammable
			}}
	| NFPA-H =
			|Section3 = {{Chembox Structure
	| NFPA-F =
			| Dipole = 4.56 ]
	| NFPA-R =
	}}		}}
	| Section8 = {{Chembox Related		|Section4 = {{Chembox Thermochemistry
			| Thermochemistry_ref = CRC Handbook
	| OtherFunctn = ]<br/>]
			| HeatCapacity =
	| Function = ureas
			| Entropy =
	| OtherCpds = ]<br/>]
			| DeltaHf = −333.19 kJ/mol
	}}
			| DeltaGf = −197.15 kJ/mol
			| DeltaHc =
			}}
			|Section5 =
			|Section6 = {{Chembox Pharmacology
			| ATCCode_prefix = B05
			| ATCCode_suffix = BC02
			| ATC_Supplemental = {{ATC|D02|AE01}}
			}}
			|Section7 = {{Chembox Hazards
			| ExternalSDS =
			| FlashPt = Non-flammable
			| LD50 = 8500 mg/kg (oral, rat)
			| NFPA-H = 1
			| NFPA-F = 1
			| NFPA-R = 0
			}}
			|Section8 = {{Chembox Related
			| OtherFunction = ]<br />]
			| OtherFunction_label = ureas
			| OtherCompounds = {{ubl|]|]|]|]|]}}
			}}
	}}		}}
	'''Urea''' or '''carbamide''' is an ] with the ] (]]<sub>2</sub>)<sub>2</sub>]]. The molecule has two ] (-NH<sub>2</sub>) groups joined by a ] (C=O) ].		'''Urea''', also called '''carbamide''' (because it is a ] of ]), is an ] with ] {{chem2|CO(NH2)2}}. This ] has two ] (–{{chem2|NH2}}) joined by a ] ] (–C(=O)–). It is thus the simplest amide of ].<ref>{{cite web | url=https://pubchem.ncbi.nlm.nih.gov/compound/Carbamic-acid | title=Carbamic acid }}</ref>
			Urea serves an important role in the cellular ] of ]-containing compounds by animals and is the main nitrogen-containing substance in the ] of ]s. ''Urea'' is ], {{etymology|fr|{{Wikt-lang|fr|urée}}|}}, {{etymology|grc|''{{Wikt-lang|grc|οὖρον}}'' ({{grc-transl|οὖρον}})|urine}}, itself from ] ''*h₂worsom''.
	Urea serves an important role in the ] of nitrogen-containing compounds by animals and is the main nitrogen-containing substance in the ] of ]s. It is solid, colourless, and odorless (although the ] which it gives off in the presence of water, including water vapor in the air, has a strong odor). It is highly soluble in water and non-toxic. Dissolved in water it is neither ] nor ]. The body uses it in many processes, most notably nitrogen excretion. Urea is widely used in ]s as a convenient source of nitrogen. Urea is also an important ] for the ]. The synthesis of this organic compound by ] in 1828 from an inorganic precursor was an important milestone in the development of organic chemistry, as it showed for the first time that a molecule found in living organisms could be synthesized in the lab without biological starting materials.
			It is a colorless, odorless solid, highly soluble in water, and practically non-toxic ({{LD50}} is 15 g/kg for rats).<ref>{{cite web |title=Urea - Registration Dossier - ECHA |url=https://echa.europa.eu/registration-dossier/-/registered-dossier/16152/7/1 |website=echa.europa.eu}}</ref> Dissolved in water, it is neither ]ic nor ]. The body uses it in many processes, most notably ]. The ] forms it by combining two ] molecules ({{chem2|NH3}}) with a ] ({{chem2|CO2}}) molecule in the ]. Urea is widely used in ]s as a source of nitrogen (N) and is an important ] for the ].
	The terms '''urea''' and '''carbamide''' are also used for a class of ]s sharing the same ] RR'N-CO-NRR', namely a carbonyl group attached to two organic amine residues. Examples include ], ], and ]. Ureas are closely related to ]s and related in structure to ]s, ]s, ]s, and ]s.
			In 1828, ] ] that urea can be produced from inorganic starting materials, which was an important conceptual milestone in chemistry. This showed for the first time that a substance previously known only as a byproduct of life could be synthesized in the laboratory without biological starting materials, thereby contradicting the widely held doctrine of ], which stated that only living organisms could produce the chemicals of life.
	==History==
			{{TOC limit|3}}
	Urea was first discovered in urine in 1773 by the ] chemist ]. In 1828, the ] chemist ] obtained urea by treating silver ] with ].<ref>{{cite book
	|title=Molecules That Changed The World
	|last=Nicolaou
	|first=Kyriacos Costa
	|authorlink=K. C. Nicolaou
	|coauthors=Tamsyn Montagnon
	|year=2008
	|publisher=Wiley-VCH
	|isbn=978-3-527-30983-2
	|page=11}}</ref><ref>{{Cite journal
	|last1=Gibb
	|first1=Bruce C.
	|year=2009
	|title=Teetering towards chaos and complexity
	|journal=Nature Chemistry
	|volume=1
	|pages=17-18
	|publisher=Nature Publishing Group
	|doi=10.1038/nchem.148
	|accessdate=2011-06-29
	|url=http://www.nature.com/nchem/journal/v1/n1/full/nchem.148.html}}</ref>
	: AgNCO + NH<sub>4</sub>Cl → (NH<sub>2</sub>)<sub>2</sub>CO + AgCl
	This was the first time an organic compound was artificially synthesized from inorganic starting materials, without the involvement of living organisms. The results of this experiment implicitly discredited ]: the theory that the chemicals of living organisms are fundamentally different from inanimate matter. This insight was important for the development of ]. His discovery prompted Wöhler to write triumphantly to ]: "I must tell you that I can make urea without the use of kidneys, either man or dog. Ammonium cyanate is urea." For this discovery, Wöhler is considered by many{{Who|date=March 2011}} the father of organic chemistry.
	==Physiology==		==Properties==
	Urea is synthesized in the body of many organisms as part of the ], either from the oxidation of ] or from ]. In this cycle, ] groups donated by ammonia and L-] are converted to urea, while L-], ], L-], and L-] act as intermediates. Urea production occurs in the ] and is regulated by ]. Urea is found dissolved in blood (in the ] of 2.5 to 6.7&nbsp;mmol/liter) and is excreted by the kidney as a component of ]. In addition, a small amount of urea is excreted (along with ] and water) in ].
			===Molecular and crystal structure===
	Amino acids from ingested food which are not used for the synthesis of proteins and other biological substances are oxidized by the body, yielding urea and carbon dioxide, as an alternative source of energy.<ref>{{cite journal |author=Sakami W, Harrington H |title=Amino acid metabolism |journal= Annual Review of Biochemistry |volume=32 |issue= 1|pages=355–98 |year= 1963|pmid=14144484 |doi=10.1146/annurev.bi.32.070163.002035}}</ref> The oxidation pathway starts with the removal of the amino group by a ], the amino group is then fed into the urea cycle.
			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 ] 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 ] angle of 120° and the ] angle of 109.5°. In solid urea, the oxygen center is engaged in two N–H–O ]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 ]s, the organic "guest" molecules are held in channels formed by interpenetrating helices composed of ] 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>
	Ammonia (NH<sub>3</sub>) is another common byproduct of the metabolism of nitrogenous compounds. Ammonia is smaller, more volatile and more mobile than urea. If allowed to accumulate, ammonia would raise the pH in cells to toxic levels. Therefore many organisms convert ammonia to urea, even though this synthesis has a net energy cost. Being practically neutral and highly soluble in water, urea is a safe vehicle for the body to transport and excrete excess nitrogen.
			===Reactions===
	In water, the amine groups undergo slow displacement by water molecules, producing ammonia and carbonate anion. For this reason, old, stale urine has a stronger odor than fresh urine.
			(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 = http://web.archive.org/web/20240602043109/https://ris.utwente.nl/ws/portalfiles/portal/6487049/Harkema69crystal.pdf | archive-date = 2 June 2024}}</ref> It is also a ], forming metal complexes of the type {{chem2|^{''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 ] esters to make ]s.
	===In humans===
	The ] is a vital part of human metabolism. Besides its role as carrier of waste nitrogen, urea also plays a role in the ] of the ], that allows for re-absorption of water and critical ions from the excreted ]. Urea is reabsorbed in the ]s of the nephrons,<ref name=boron837>{{cite book |author=Walter F. Boron |title=Medical Physiology: A Cellular And Molecular Approach |publisher=Elsevier/Saunders |location= |year= |pages= |isbn=1-4160-2328-3 |oclc= |doi=}} Page 837</ref> thus raising the ] in the medullary ] surrounding the ], which in turn causes water to be reabsorbed. By action of the ], some of this reabsorbed urea will eventually flow back into the thin ascending limb of the tubule, through the collecting ducts, and into the excreted urine.
			====Thermolysis====
	This mechanism, which is controlled by the ], allows the body to create ] urine, that has a higher concentration of dissolved substances than the ]. This mechanism is important to prevent the loss of water, to maintain ], and to maintain a suitable concentration of ] ions in the blood plasmas.
			Molten urea decomposes into ] at about 152&nbsp;°C, and into ] and ] 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>
			:{{chem2|CO(NH2)2 → +- → NH3 + HNCO}}
			Heating above 160&nbsp;°C yields ] {{chem2|NH2CONHCONH2}} and ] {{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"/>
	The equivalent nitrogen content (in ]) of urea (in ]) can be estimated by the conversion factor 0.028 g/mmol.<ref>Section 1.9.2 (page 76) in: {{cite book |author=Jacki Bishop; Thomas, Briony |title=Manual of Dietetic Practice |publisher=Wiley-Blackwell |location= |year=2007 |pages= |isbn=1-4051-3525-5 |oclc= |doi= |accessdate=}}</ref> Furthermore, 1&nbsp;gram of nitrogen is roughly equivalent to 6&nbsp;gram of protein, and 1&nbsp;gram of protein is roughly equivalent to 4&nbsp;gram of muscle tissue. Subsequently, in situations such as ], 1&nbsp;mmol of excessive urea in the urine (as measured by urine volume in litres multiplied by urea concentration in mmol/l) roughly corresponds to a muscle loss of 0.67&nbsp;gram.
			:{{chem2|CO(NH2)2 + HNCO → NH2CONHCONH2}}
			:{{chem2|NH2CONHCONH2 + HNCO → NH2CONHCONHCONH2}}
			At higher temperatures it converts to a range of ]s, including ] {{chem2|(CNOH)3}}, ] {{chem2|HNC(NH2)2}}, and ].<ref name="Meessen 2012" /><ref name="Schaber 2004"/>
	===In other species===
	In ] organisms the most common form of nitrogen waste is ammonia, while land-dwelling organisms convert the toxic ammonia to either urea or ]. Urea is found in the urine of ]s and ]s, as well as some ]. ]s and ] ]s have a different form of nitrogen metabolism, that requires less ] and leads to nitrogen being excreted in the form of ]. It is noteworthy that ]s excrete ammonia but shift to urea production during ]. Despite the generalization above, the urea pathway has been documented not only in mammals and amphibians but in many other organisms as well, including birds, ]s, ]s, ]s, ], ], and even ]s.{{Citation needed|date=January 2010}}
			====Aqueous stability====
			In aqueous solution, urea slowly equilibrates with ammonium cyanate. This ]<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 ], which can ] proteins, in particular the N-terminal amino group, the side chain amino of ], and to a lesser extent the side chains of ] and ].<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 ] to the mass of the protein, which can be observed in ].<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 ] 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 ] to a concentrated urea solution decreases formation of cyanate because of the ].<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 ] (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>
			==Related compounds==
			{{main|ureas}}
			] describes a ''class'' of ]s that share the same functional group, a carbonyl group attached to two organic amine residues: {{chem2|R^{1}R^{2}N\sC(\dO)\sNR^{3}R^{4}|}}, where {{chem2|R^{1}, R^{2}, R^{3} and R^{4}|}} groups are ] (–H), ] or other groups. Examples include ], ], and ]. Ureas are closely related to ]s and related in structure to ]s, ]s, ]s, and ]s.
	==Uses==		==Uses==
	===Agriculture===		===Agriculture===
			] that produces urea fertilizer.]]
	More than 90% of world production of urea is destined for use as a nitrogen-release fertilizer. Urea has the highest nitrogen content of all solid nitrogenous fertilizers in common use. Therefore, it has the lowest transportation costs per unit of nitrogen ]. The standard crop nutrient rating of urea is '''46-0-0'''.{ICIS, http://www.icis.com/v2/chemicals/9076559/urea/uses.html}
			More than 90% of world industrial production of urea is destined for use as a nitrogen-release ].<ref name="Meessen 2012" /> Urea has the highest nitrogen content of all solid nitrogenous fertilizers in common use. Therefore, it has a low transportation cost per unit of ]. The most common impurity of synthetic urea is ], which impairs plant growth. Urea breaks down in the soil to give ] ({{chem2|NH4+}}). The ammonium is taken up by the plant through its roots. In some soils, the ammonium is oxidized by bacteria to give ] ({{chem2|NO3-}}), which is also a nitrogen-rich plant nutrient. The loss of nitrogenous compounds to the atmosphere and runoff is wasteful and environmentally damaging so urea is sometimes modified to enhance the efficiency of its agricultural use. Techniques to make ]s that slow the release of nitrogen include the encapsulation of urea in an inert sealant, and conversion of urea into derivatives such as ] compounds, which degrade into ammonia at a pace matching plants' nutritional requirements.
			===Resins===
	Many soil bacteria possess the enzyme, ], which catalyzes the conversion of the urea molecule to two ] molecules and one ] molecule, thus urea fertilizers are very rapidly transformed to the ammonium form in soils. Among soil bacteria known to carry urease, some ammonia-oxidizing bacteria (AOB), such as species of ] are also able to assimilate the carbon dioxide released by the reaction to make biomass via the ], and harvest energy by oxidizing ammonia (the other product of urease) to nitrite, a process termed ].<ref>Marsh, K. L., G. K. Sims, and R. L. Mulvaney. 2005. Availability of urea to autotrophic ammonia-oxidizing bacteria as related to the fate of 14C- and 15N-labeled urea added to soil. Biol. Fert. Soil. 42:137-145.</ref> Nitrite-oxidizing bacteria, especially, ], oxidize nitrite to nitrate, which is extremely mobile in soils and is a major cause of water pollution from agriculture. Ammonia and nitrate are readily absorbed by plants, and are the dominant sources of nitrogen for plant growth. Urea is also used in many multi-component solid fertilizer formulations. Urea is highly soluble in water and is, therefore, also very suitable for use in fertilizer solutions (in combination with ]: ]), e.g., in 'foliar feed' fertilizers. For fertilizer use, granules are preferred over prills because of their narrower particle size distribution which is an advantage for mechanical application.
			Urea is a raw material for the manufacture of ]s, such as UF, MUF, and MUPF, used mainly in wood-based panels, for instance, ], ], OSB, and ].
			=== Explosives ===
	The most common impurity of synthetic urea is ], which impairs plant growth.
			Urea can be used in a reaction with ] to make ], a ] that is used industrially and as part of some ]s.
			===Automobile systems===
	Urea is usually spread at rates of between 40 and 300&nbsp;kg/ha but rates vary. Smaller applications incur lower losses due to leaching. During summer, urea is often spread just before, or during rain to minimize losses from ] (process wherein nitrogen is lost to the atmosphere as ammonia gas). Urea is not compatible with other fertilizers.
			Urea is used in ] and ] reactions to reduce the ] ]s in ]es from ] from ], dual fuel, and lean-burn ] engines. The ] system, for example, injects a water-based urea solution into the exhaust system. Ammonia ({{chem2|NH3}}) produced by the ] of urea reacts with nitrogen oxides ({{chem2|NO_{''x''}|}}) and is converted into nitrogen gas ({{chem2|N2}}) and water within the catalytic converter. The conversion of noxious {{chem2|NO_{''x''}|}} to innocuous {{chem2|N2}} is described by the following simplified global equation:<ref>Duo et al., (1992). Can. J. Chem. Eng, '''70''', 1014–1020.</ref>
			:{{chem2|4 NO + 4 NH3 + O2 → 4 N2 + 6 H2O}}
			When urea is used, a pre-reaction (hydrolysis) occurs to first convert it to ammonia:
			:{{chem2|CO(NH2)2 + H2O → 2 NH3 + CO2}}
			Being a solid highly ] in water (545 g/L at 25&nbsp;°C),<ref name="Solubility" /> urea is much easier and safer to handle and store than the more ], ] and hazardous ] ({{chem2|NH3}}), so it is the reactant of choice. Trucks and cars using these catalytic converters need to carry a supply of ], also sold as ], a solution of urea in water.
			===Laboratory uses===
	Because of the high nitrogen concentration in urea, it is very important to achieve an even spread. The application equipment must be correctly calibrated and properly used. Drilling must not occur on contact with or close to seed, due to the risk of germination damage. Urea dissolves in water for application as a spray or through irrigation systems.
			Urea in concentrations up to 10&nbsp;] is a powerful ] ] as it disrupts the noncovalent bonds in the proteins. This property can be exploited to increase the solubility of some proteins. A mixture of urea and ] is used as a ] (DES), a substance similar to ]. When used in a deep eutectic solvent, urea gradually denatures the proteins that are solubilized.<ref>{{cite journal | first1 = Erwann | last1 = Durand | first2 = Jérôme | last2 = Lecomte | first3 = Bruno | last3 =Baréa | first4 = Georges | last4 = Piombo | first5 = Éric | last5 = Dubreucq | first6 = Pierre | last6 = Villeneuve | title = Evaluation of deep eutectic solvents as new media for ''Candida antarctica'' B lipase catalyzed reactions | journal = Process Biochemistry | publisher = ] | volume = 47 | issue = 12 | date = 2012-12-01 | pages = 2081–2089 | doi = 10.1016/j.procbio.2012.07.027 | issn = 1359-5113 | df = dmy-all}}.</ref>
			Urea in concentrations up to 8&nbsp;M can be used to make fixed brain tissue transparent to visible light while still preserving fluorescent signals from labeled cells. This allows for much deeper imaging of neuronal processes than previously obtainable using conventional one photon or two photon confocal microscopes.<ref>{{cite journal | vauthors = Hama H, Kurokawa H, Kawano H, Ando R, Shimogori T, Noda H, Fukami K, Sakaue-Sawano A, Miyawaki A | title = Scale: a chemical approach for fluorescence imaging and reconstruction of transparent mouse brain | journal = Nature Neuroscience | volume = 14 | issue = 11 | pages = 1481–8 | date = August 2011 | pmid = 21878933 | doi = 10.1038/nn.2928 | s2cid = 28281721 }}</ref>
	In grain and cotton crops, urea is often applied at the time of the last cultivation before planting. In high rainfall areas and on sandy soils (where nitrogen can be lost through leaching) and where good in-season rainfall is expected, urea can be side- or top-dressed during the growing season. Top-dressing is also popular on pasture and forage crops. In cultivating sugarcane, urea is side-dressed after planting, and applied to each ] crop.
			===Medical use===
	In irrigated crops, urea can be applied dry to the soil, or dissolved and applied through the irrigation water. Urea will dissolve in its own weight in water, but it becomes increasingly difficult to dissolve as the concentration increases. Dissolving urea in water is endothermic, causing the temperature of the solution to fall when urea dissolves.
			]s are used as topical ] products to promote ] of the ]. Urea 40% is indicated for ], ], ], ], ], ], ], corns, and ]. If covered by an ], 40% urea preparations may also be used for nonsurgical ] of ]. Urea 40% "dissolves the intercellular matrix"<ref>{{cite web|url=http://www.odanlab.com/urisec/winter/|title=UriSec 40 How it Works|date=January 2009|publisher=Odan Laboratories|access-date=February 15, 2011|archive-date=2 February 2011|archive-url=https://web.archive.org/web/20110202150107/http://www.odanlab.com/urisec/winter/|url-status=dead}}</ref><ref name="Urea40">{{cite web |url=https://odanlab.com/product/urisec-40/ |title=UriSec 40% Cream |publisher=Odan Laboratories |access-date=August 20, 2021}}</ref> of the nail plate. Only diseased or dystrophic nails are removed, as there is no effect on healthy portions of the nail.<ref>{{Cite book |last=Habif |first=Thomas P. |url=https://books.google.com/books?id=kDWlWR5UbqQC&dq=Urea+removed+dystrophic+nails&pg=PA961 |title=Clinical Dermatology E-Book |date=2009-11-25 |publisher=Elsevier Health Sciences |isbn=978-0-323-08037-8 |language=en}}</ref> This drug (as ]) is also used as an earwax removal aid.<ref name="WebMD-eardrops">{{cite web |title=Carbamide Peroxide Drops GENERIC NAME(S): CARBAMIDE PEROXIDE |url=https://www.webmd.com/drugs/2/drug-3616/carbamide-peroxide-otic-ear/details |publisher=WebMD |access-date=August 19, 2021}}</ref>
			Urea has also been studied as a ]. It was first used by Dr. W. Friedrich in 1892.<ref>{{cite journal | vauthors = Crawford JH, McIntosh JF | title = The use of urea as a diuretic in advanced heart failure | journal = ] | volume = 36 | issue = 4 | pages = 530–541 | location = New York | date = 1925 | doi = 10.1001/archinte.1925.00120160088004 }}
	As a practical guide, when preparing urea solutions for ] (injection into irrigation lines), dissolve no more than 30&nbsp;kg urea per 100 L water.
			</ref> In a 2010 study of ICU patients, urea was used to treat ] ] and was found safe, inexpensive, and simple.<ref>{{cite journal | vauthors = Decaux G, Andres C, Gankam Kengne F, Soupart A | title = Treatment of euvolemic hyponatremia in the intensive care unit by urea | journal = Critical Care | volume = 14 | issue = 5 | pages = R184 | date = 14 October 2010 | pmid = 20946646 | pmc = 3219290 | doi = 10.1186/cc9292 | doi-access = free }}</ref>
			Like ], urea has been injected into the ] to induce ], although ] is no longer in widespread use.<ref>{{cite journal | vauthors = Diggory PL | title = Induction of therapeutic abortion by intra-amniotic injection of urea | journal = British Medical Journal | volume = 1 | issue = 5739 | pages = 28–9 | date = January 1971 | pmid = 5539139 | pmc = 1794772 | doi = 10.1136/bmj.1.5739.28 }}</ref>
	In foliar sprays, urea concentrations of 0.5% – 2.0% are often used in horticultural crops. Low-] grades of urea are often indicated.
			The ] (BUN) test is a measure of the amount of nitrogen in the blood that comes from urea. It is used as a marker of ], though it is inferior to other markers such as ] because blood urea levels are influenced by other factors such as diet, dehydration,<ref>{{cite journal | vauthors = Traynor J, Mactier R, Geddes CC, Fox JG | title = How to measure renal function in clinical practice | journal = BMJ | volume = 333 | issue = 7571 | pages = 733–7 | date = October 2006 | pmid = 17023465 | pmc = 1592388 | doi = 10.1136/bmj.38975.390370.7c }}</ref> and liver function.
	Urea absorbs moisture from the atmosphere and therefore is typically stored either in closed/sealed bags on pallets, or, if stored in bulk, under cover with a tarpaulin. As with most solid fertilizers, storage in a cool, dry, well-ventilated area is recommended.
			Urea has also been studied as an excipient in Drug-coated Balloon (DCB) coating formulation to enhance local drug delivery to stenotic blood vessels.<ref>{{Cite journal|last1=Werk Michael|last2=Albrecht Thomas|last3=Meyer Dirk-Roelfs|last4=Ahmed Mohammed Nabil|last5=Behne Andrea|last6=Dietz Ulrich|last7=Eschenbach Götz|last8=Hartmann Holger|last9=Lange Christian|date=2012-12-01|title=Paclitaxel-Coated Balloons Reduce Restenosis After Femoro-Popliteal Angioplasty|journal=Circulation: Cardiovascular Interventions|volume=5|issue=6|pages=831–840|doi=10.1161/CIRCINTERVENTIONS.112.971630|pmid=23192918|doi-access=free}}</ref><ref>{{Cite journal|last=Wöhrle|first=Jochen|date=2012-10-01|title=Drug-Coated Balloons for Coronary and Peripheral Interventional Procedures|journal=Current Cardiology Reports|volume=14|issue=5|pages=635–641|doi=10.1007/s11886-012-0290-x|pmid=22825918|s2cid=8879713}}</ref> Urea, when used as an ] in small doses (~3&nbsp;μg/mm<sup>2</sup>) to coat DCB surface was found to form crystals that increase drug transfer without adverse toxic effects on vascular ].<ref>{{Cite journal|last1=Kolachalama|first1=Vijaya B.|last2=Shazly|first2=Tarek|last3=Vipul C. Chitalia|last4=Lyle|first4=Chimera|last5=Azar|first5=Dara A.|last6=Chang|first6=Gary H.|date=2019-05-02|title=Intrinsic coating morphology modulates acute drug transfer in drug-coated balloon therapy|journal=Scientific Reports|volume=9|issue=1|pages=6839|doi=10.1038/s41598-019-43095-9|pmid=31048704|pmc=6497887|bibcode=2019NatSR...9.6839C}}</ref>
	===Chemical industry===
	Urea is a raw material for the manufacture of many important chemical compounds, such as
	*Various ]s, especially the ]s.
	*Various ]s, such as urea-formaldehyde or the ] used in marine ].
	*], another industrial feedstock.
			Urea labeled with ] or ] is used in the ], which is used to detect the presence of the bacterium '']'' (''H. pylori'') in the ] and ] of humans, associated with ]s. The test detects the characteristic enzyme ], produced by ''H. pylori'', by a reaction that produces ammonia from urea. This increases the pH (reduces the acidity) of the stomach environment around the bacteria. Similar bacteria species to ''H. pylori'' can be identified by the same test in animals such as ]s, ]s, and ]s (including ]s).
	===Explosive===
	Urea can be used to make ], a ] which is used industrially and as part of some ]s.
	===Automobile systems===		===Miscellaneous uses===
			* An ingredient in ] (DEF), which is 32.5% urea and 67.5% de-ionized water. DEF is sprayed into the exhaust stream of diesel vehicles to break down dangerous {{chem2|NO_{''x''}|}} ] into harmless ] and ].
	Urea is used in ] and ] reactions to reduce the ] ]s in ]es from ] from ], dual fuel, and lean-burn ] engines. The ] system, for example, injects water-based urea solution into the exhaust system. The ammonia produced by the ] of the urea reacts with the nitrogen oxide emissions and is converted into nitrogen and water within the catalytic converter.
	===Other commercial uses===
	{{Unreferenced section|date=May 2010}}
	* A stabilizer in ] ]s
	* A component of ], providing a relatively cheap source of ] to promote growth		* A component of ], providing a relatively cheap source of ] to promote growth
			* A non-corroding alternative to ] for road ].<ref>{{cite book|title=Heavy Duty Truck Systems|date=2015|publisher=Cengage Learning|isbn=9781305073623|page=1117|url=https://books.google.com/books?id=bxrDCgAAQBAJ&pg=PA1117}}</ref> It is often the main ingredient of pet friendly salt substitutes although it is less effective than traditional rock salt or calcium chloride.<ref>{{cite book|title=Chlorides—Advances in Research and Application: 2013 Edition|date=2013|publisher=ScholarlyEditions|isbn=9781481674331|page=77|url=https://books.google.com/books?id=hydgJr0zayAC&pg=PA77}}</ref>
	* A non-corroding alternative to ] for road ], and the resurfacing of ] halfpipes and terrain parks
	* A ]-enhancing additive for ]s
	* A main ingredient in hair removers such as ] and ]		* A main ingredient in hair removers such as ] and ]
	* A browning agent in factory-produced ]		* A browning agent in factory-produced ]s
	* An ingredient in some ],<ref>{{cite web|author=www.dooyoo.co.uk |url=http://www.dooyoo.co.uk/skin-care/lacura-multi-intensive-serum/1264192/ |title=Lacura Multi Intensive Serum - Review - Excellent value for money - Lacura Multi Intensive Serum "Aqua complete" |publisher=Dooyoo.co.uk |date=2009-06-19 |accessdate=2010-12-28}}</ref> ]s, ]s		* An ingredient in some ],<ref>{{cite web|url=http://www.dooyoo.co.uk/skin-care/lacura-multi-intensive-serum/1264192/ |title=Lacura Multi Intensive Serum – Review – Excellent value for money – Lacura Multi Intensive Serum "Aqua complete" |publisher=Dooyoo.co.uk |date=2009-06-19 |access-date=2010-12-28}}</ref> ]s, ]s, and ]s
			* A ] agent, along with other salts<ref>{{cite journal |last1=Knollenberg |first1=Robert G. |title=Urea as an Ice Nucleant for Supercooled Clouds |journal=American Meteorological Society |date=March 1966 |volume=23 |issue=2 |page=197 |doi=10.1175/1520-0469(1966)023<0197:UAAINF>2.0.CO;2 |bibcode=1966JAtS...23..197K |doi-access=free }}</ref>
	* A ] in some ready-to-use ]es for first-aid use, due to the ] reaction it creates when mixed with ]
	* A ] agent, along with other salts
	* A ], commonly used in dry chemical ] charges such as the urea-] mixture		* A ], commonly used in dry chemical ] charges such as the urea-] mixture
	* An ingredient in many ] products		* An ingredient in many ] products
	* An ingredient in ]		* An ingredient in ]
	* Along with ], as a ], for fermentation of ]s into ]		* Along with ], as a ], for fermentation of ]s into ]
	* A nutrient used by ] in ] experiments for ] purposes		* A nutrient used by ] in ] experiments for ] purposes
	* As an additive to extend the working temperature and open time of ]		* As an additive to extend the working temperature and open time of ]
	* As a solubility-enhancing and moisture-retaining additive to ] baths for textile dyeing or printing		* As a solubility-enhancing and moisture-retaining additive to ] baths for textile dyeing or printing<ref>{{cite web |last1=Burch |first1=Paula E. |title=Dyeing FAQ: What is urea for, in dyeing? Is it necessary? |url=http://www.pburch.net/dyeing/FAQ/urea.shtml |website=All About Hand Dyeing |date= 13 November 1999|access-date=24 August 2020}}</ref>
			* As an optical parametric oscillator in nonlinear optics<ref>{{cite web|url=https://patents.google.com/patent/US4639923A/en |title=Optical parametric oscillator using urea crystal
			|publisher=Google Patents}}</ref><ref>{{cite journal|title=Urea optical parametric oscillator |journal=Applied Physics Letters |volume=44 |issue=1 |pages=25–27 |publisher=AIP Publishing|doi=10.1063/1.94590 |year=1984 |last1=Donaldson |first1=William R. |last2=Tang |first2=C. L. |bibcode=1984ApPhL..44...25D }}</ref>
			==Physiology==
	===Laboratory uses===
			Amino acids from ingested food (or produced from catabolism of muscle protein) that are used for the synthesis of proteins and other biological substances can be oxidized by the body as an alternative source of energy, yielding urea and ].<ref>{{cite journal | vauthors = Sakami W, Harrington H | title = Amino acid metabolism | journal = Annual Review of Biochemistry | volume = 32 | issue = 1 | pages = 355–98 | year = 1963 | pmid = 14144484 | doi = 10.1146/annurev.bi.32.070163.002035 }}</ref> The oxidation pathway starts with the removal of the amino group by a ]; the amino group is then fed into the ]. The first step in the conversion of amino acids into ] in the liver is removal of the alpha-amino nitrogen, which produces ]. Because ammonia is toxic, it is excreted immediately by fish, converted into ] by birds, and converted into urea by mammals.<ref>{{cite web | title = Urea | publisher = ] | url = http://www.ch.ic.ac.uk/rzepa/mim/environmental/html/urea_text.htm | access-date = 2015-03-23 }}</ref>
	Urea in concentrations up to 10 ] is a powerful ] ] as it disrupts the noncovalent bonds in the proteins. This property can be exploited to increase the solubility of some proteins.
	A mixture of urea and ] is used as a ], a type of ].
			Ammonia ({{chem2|NH3}}) is a common byproduct of the metabolism of nitrogenous compounds. Ammonia is smaller, more volatile, and more mobile than urea. If allowed to accumulate, ammonia would raise the ] in cells to toxic levels. Therefore, many organisms convert ammonia to urea, even though this synthesis has a net energy cost. Being practically neutral and highly soluble in water, urea is a safe vehicle for the body to transport and excrete excess nitrogen.
	Urea can in principle serve as a hydrogen source for subsequent power generation in ]s. Urea present in urine/wastewater can be used directly (though bacteria normally quickly degrade urea.) Producing hydrogen by electrolysis of urea solution occurs at a lower voltage (0.37V) and thus consumes less energy than the electrolysis of water (1.2V).<ref></ref>
			Urea is synthesized in the body of many organisms as part of the ], either from the oxidation of ]s or from ]. In this cycle, ] groups donated by ammonia and {{sc|L}}-] are converted to urea, while {{sc|L}}-], ], {{sc|L}}-], and {{sc|L}}-] act as intermediates. Urea production occurs in the ] and is regulated by ]. Urea is then dissolved into the blood (in the ] of 2.5 to 6.7&nbsp;mmol/L) and further transported and excreted by the kidney as a component of ]. In addition, a small amount of urea is excreted (along with ] and water) in ].
	===Medical use===
	]s are used as topical ] products to promote ] of the ]. Urea 40% is indicated for ], ], ], ], ], ], ], corns and ]. If covered by an ], 40% urea preparations may also be used for nonsurgical ] of ]. Urea 40% "dissolves the intercellular matrix"<ref>{{cite web|url=http://www.odanlab.com/urisec/winter/|title=UriSec 40 How it Works|date=January 2009|publisher=Odan Laboratories|accessdate=February 15, 2011}}</ref> of the nail plate. Only diseased or dystrophic nails are removed as there is no effect on healthy portions of the nail. This drug is also used as an earwax removal aid.
			In water, the amine groups undergo slow displacement by water molecules, producing ammonia, ]s, and ]s. For this reason, old, stale urine has a stronger odor than fresh urine.
	Certain types of ]s (or ice packs) contain water and separated urea crystals. Rupturing the internal water bag starts an endothermic reaction and allows the pack to be used to reduce ].
			===Humans===
	Like ], urea injection is used to perform ]s.
			The ] is a vital part of mammalian metabolism. Besides its role as carrier of waste nitrogen, urea also plays a role in the ] of the ]s, that allows for reabsorption of water and critical ions from the excreted ]. Urea is reabsorbed in the ]s of the nephrons,<ref name=boron837>{{cite book |author=Walter F. Boron |title=Medical Physiology: A Cellular And Molecular Approach |publisher=Elsevier/Saunders |isbn=1-4160-2328-3 |year=2005 }} Page 837</ref> thus raising the ] in the ] surrounding the ], which makes the water reabsorb.
			By action of the ], some of this reabsorbed urea eventually flows back into the thin descending limb of the tubule,<ref>{{cite book | pmid = 23737200| year = 2011| vauthors = Klein J, Blount MA, Sands JM | title = Comprehensive Physiology| volume = 1| issue = 2| pages = 699–729 | doi = 10.1002/cphy.c100030| chapter = Urea Transport in the Kidney| isbn = 9780470650714}}</ref> through the collecting ducts, and into the excreted urine. The body uses this mechanism, which is controlled by the ], to create ] urine — i.e., urine with a higher concentration of dissolved substances than the ]. This mechanism is important to prevent the loss of water, maintain ], and maintain a suitable concentration of ] ions in the blood plasma.
	Urea is the main component of an ] treatment referred to as ].
			The equivalent nitrogen content (in ]s) of urea (in ]) can be estimated by the conversion factor 0.028&nbsp;g/mmol.<ref>Section 1.9.2 (page 76) in: {{cite book |author=Jacki Bishop |author2=Thomas, Briony |title=Manual of Dietetic Practice |publisher=Wiley-Blackwell |year=2007 |isbn=978-1-4051-3525-2}}</ref> Furthermore, 1&nbsp;gram of nitrogen is roughly equivalent to 6.25&nbsp;grams of ], and 1&nbsp;gram of protein is roughly equivalent to 5&nbsp;grams of ] tissue. In situations such as ], 1&nbsp;mmol of excessive urea in the urine (as measured by urine volume in litres multiplied by urea concentration in mmol/L) roughly corresponds to a muscle loss of 0.67&nbsp;gram.
	The ] (BUN) test is a measure of the amount of nitrogen in the blood that comes from urea. It is used as a marker of ].
			===Other species===
	Urea labeled with ] or ] is used in the ], which is used to detect the presence of the bacteria '']'' (''H. pylori'') in the ] and ] of humans, associated with ]s. The test detects the characteristic enzyme ], produced by ''H. pylori'', by a reaction that produces ammonia from urea. This increases the pH (reduces acidity) of the stomach environment around the bacteria. Similar bacteria species to ''H. pylori'' can be identified by the same test in animals such as ]s, ]s, and ]s (including ]s).
			In ] organisms the most common form of nitrogen waste is ammonia, whereas land-dwelling organisms convert the toxic ammonia to either urea or ]. Urea is found in the urine of ]s and ]s, as well as some fish. Birds and ] reptiles have a different form of nitrogen metabolism that requires less water, and leads to nitrogen excretion in the form of uric acid. ]s excrete ammonia, but shift to urea production during ]. Despite the generalization above, the urea pathway has been documented not only in mammals and amphibians, but in many other organisms as well, including birds, ]s, insects, plants, ], ], and even ]s.<ref>{{Cite web|last=PubChem|title=urea cycle|url=https://pubchem.ncbi.nlm.nih.gov/pathway/PlantCyc:TEA_PWY-4984|access-date=2021-06-28|website=pubchem.ncbi.nlm.nih.gov|language=en}}</ref>
	===Analysis===		==Adverse effects==
			Urea can be irritating to skin, eyes, and the respiratory tract. Repeated or prolonged contact with urea in fertilizer form on the skin may cause ].<ref>{{Cite book |last1=Schliemann |first1=S. |url=https://books.google.com/books?id=0yyx-DzCymIC&dq=Urea+can+be+irritating+to+skin&pg=PA52 |title=Skin Protection: Practical Applications in the Occupational Setting |last2=Elsner |first2=Peter |date=2007-01-01 |publisher=Karger Medical and Scientific Publishers |isbn=978-3-8055-8218-6 |language=en}}</ref>
	Urea is readily quantified by a number of different methods, such as the diacetyl monoxime colorimetric method, and the 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>Baumgartner, M., M. Flöck, P. Winter, W. Lu, and W. Baumgartner. 2005. Evaluation of flow injection analysis for determination of urea in sheep's and cow's milk. Acta Veterinaria Hungarica. 50 (3): 263-271.</ref> and 96-well micro-plate spectrophotometers.<ref>Greenan, N. S., R.L. Mulvaney, and G.K. Sims. 1995. A microscale method for colorimetric determination of urea in soil extracts. Communications in Soil Science and Plant Analysis. 26:2519-2529.</ref>
			High concentrations in the blood can be damaging. Ingestion of low concentrations of urea, such as are found in typical human ], are not dangerous with additional water ingestion within a reasonable time-frame. Many animals (e.g. ]s, rodents or dogs) have a much more concentrated urine which may contain a higher urea amount than normal human urine.
	==Production==
	Urea is produced on a scale of some 100,000,000 tons per year worldwide.<ref name=Ullmann>Jozef H. Meessen and Harro Petersen “Urea” in Ullmann's Encyclopedia of Industrial Chemistry 2002, Wiley-VCH, Weinheim. {{DOI|10.1002/14356007.a27_333}}</ref>
			Urea can cause ]s to produce toxins, and its presence in the runoff from fertilized land may play a role in the increase of toxic blooms.<ref>{{cite journal|url=https://www.nature.com/news/2008/081027/full/news.2008.1190.html|title=Urea pollution turns tides toxic|first=Amy|last=Coombs | name-list-style = vanc |date=27 October 2008|journal=Nature|access-date=5 August 2018|doi=10.1038/news.2008.1190}}</ref>
	===Industrial methods===
	For use in industry, urea is produced from synthetic ] and ]. Large quantities of carbon dioxide are produced during the manufacture of ammonia from coal or from ] such as natural gas and petroleum-derived raw materials. Such point sources of CO<sub>2</sub> facilitate direct synthesis of urea.
			The substance decomposes on heating above melting point, producing toxic gases, and reacts violently with strong oxidants, nitrites, inorganic chlorides, chlorites and perchlorates, causing fire and explosion.<ref>. cdc.gov</ref>
	The basic process, developed in 1922, is also called the ] after its discoverers. The various urea processes are characterized by the conditions under which urea formation takes place and the way in which unconverted reactants are further processed. The process consists of two main ]s, with incomplete conversion of the reactants. The first is an ] reaction of liquid ammonia with ] to form ] (H<sub>2</sub>N-COONH<sub>4</sub>):<ref>{{cite web|url=http://www.hillakomem.com/tag/ammonium-carbamate |title=Inorganic Chemicals » AMMONIUM CARBAMATE |publisher=Hillakomem.com |date=2008-10-02 |accessdate=2010-12-28}}</ref>
	:2 NH<sub>3</sub> + CO<sub>2</sub> ↔ H<sub>2</sub>N-COONH<sub>4</sub> ()
	The second is an ] decomposition of ammonium carbamate into urea and water:
	:H<sub>2</sub>N-COONH<sub>4</sub> ↔ (NH<sub>2</sub>)<sub>2</sub>CO + H<sub>2</sub>O
	Both reactions combined are exothermic.<ref name=Ullmann/>
			==History==
	Unconverted reactants can be used for the manufacture of other products, for example ] or ], or they can be recycled for complete conversion to urea in a total-recycle process.
			Urea was first discovered in urine in 1727 by the Dutch scientist ],<ref>
			Boerhaave called urea "sal nativus urinæ" (the native, ''i.e.'', natural, salt of urine). See:
			* The first mention of urea is as "the essential salt of the human body" in: Peter Shaw and Ephraim Chambers, ''A New Method of Chemistry'' …, vol 2, (London, England: J. Osborn and T. Longman, 1727), .
			* Boerhaave, Herman ''Elementa Chemicae'' …, volume 2, (Leipzig ("Lipsiae"), (Germany): Caspar Fritsch, 1732), .
			* For an English translation of the relevant passage, see: Peter Shaw, ''A New Method of Chemistry'' …, 2nd ed., (London, England: T. Longman, 1741),
			* Lindeboom, Gerrit A. ''Boerhaave and Great Britain'' …, (Leiden, Netherlands: E.J. Brill, 1974), .
			* Backer, H. J. (1943) "Boerhaave's Ontdekking van het Ureum" (Boerhaave's discovery of urea), ''Nederlands Tijdschrift voor Geneeskunde'' (Dutch Journal of Medicine), '''87''' : 1274–1278 (in Dutch).
			</ref> although this discovery is often attributed to the ] chemist ] as well as ].<ref>{{Cite journal | last1 = Kurzer | first1 = Frederick | last2 = Sanderson | first2 = Phyllis M. | name-list-style = vanc | year = 1956 | title = Urea in the History of Organic Chemistry | journal = Journal of Chemical Education | volume = 33 | pages = 452–459 | doi = 10.1021/ed033p452 | issue = 9 | bibcode = 1956JChEd..33..452K }}
			</ref>
			Boerhaave used the following steps to isolate urea:<ref>{{cite web |title=Why Pee is Cool – entry #5 – "How Pee Unites You With Rocks" |date=October 11, 2011 |url=http://www.scienceminusdetails.com/2011/10/why-pee-is-cool-entry-5-how-pee-united.html |publisher=Science minus details |access-date=August 9, 2016}}</ref><ref>{{Cite journal|last1=Kurzer|first1=Frederick|last2=Sanderson|first2=Phyllis M.|year=1956|title=Urea in the History of Organic Chemistry|journal=Journal of Chemical Education|volume=33|issue=9|at=p. 454|bibcode=1956JChEd..33..452K|doi=10.1021/ed033p452|name-list-style=vanc}}</ref>
	Urea can be produced as ]s, ], pellets, crystals, and solutions. Solid urea is marketed as ]s or granules. The advantage of prills is that, in general, they can be produced more cheaply than granules. Properties such as impact strength, crushing strength, and free-flowing behaviour are, in particular, important in product handling, storage, and bulk transportation. Typical impurities in the production are biuret and isocyanic acid:
			# Boiled off water, resulting in a substance similar to fresh cream
	:2 NH<sub>2</sub>CONH<sub>2</sub> → H<sub>2</sub>NCONHCONH<sub>2</sub> + NH<sub>3</sub>
			# Used filter paper to squeeze out remaining liquid
	:NH<sub>2</sub>CONH<sub>2</sub> → HNCO + NH<sub>3</sub>
			# Waited a year for solid to form under an oily liquid
	The biuret content is a serious concern because it is often toxic to the very plants that are to be fertilized. Urea is classified on the basis of its biuret content.
			# Removed the oily liquid
			# Dissolved the solid in water
			# Used ] to tease out the urea
			In 1828, the ] chemist ] obtained urea artificially by treating ] with ].<ref>Wöhler, Friedrich (1828) (On the artificial formation of urea), ''Annalen der Physik und Chemie'', '''88''' (2) : 253–256. Available in English at .
	===Laboratory preparation===
			</ref><ref>
	Ureas in the more general sense can be accessed in the laboratory by reaction of ] with primary or secondary ]s, proceeding through an ] intermediate. Non-symmetric ureas can be accessed by reaction of primary or secondary amines with an isocyanate.
			{{cite book | title = Molecules That Changed The World | last1 = Nicolaou | first1 = Kyriacos Costa | name-list-style = vanc | author-link = K. C. Nicolaou | first2 = Tamsyn | last2 = Montagnon | year = 2008 | publisher = Wiley-VCH | isbn = 978-3-527-30983-2 | page = 11 }}
			</ref><ref>
			{{cite journal | vauthors = Gibb BC | title = Teetering towards chaos and complexity | journal = Nature Chemistry | volume = 1 | issue = 1 | pages = 17–8 | date = April 2009 | pmid = 21378787 | doi = 10.1038/nchem.148 | bibcode = 2009NatCh...1...17G }}
			</ref>
			:{{chem2|AgNCO + Cl → CO(NH2)2 + AgCl}}
			This was the first time an organic compound was artificially synthesized from inorganic starting materials, without the involvement of living organisms. The results of this experiment implicitly discredited ], the theory that the chemicals of living organisms are fundamentally different from those of inanimate matter. This insight was important for the development of ]. His discovery prompted Wöhler to write triumphantly to ]:
			:"''I must tell you that I can make urea without the use of kidneys, either man or dog. Ammonium cyanate is urea.''"
			In fact, his second sentence was incorrect. ] {{chem2|+-}} and urea {{chem2|CO(NH2)2}} are two different chemicals with the same ] {{chem2|CON2H4}}, which are in chemical equilibrium heavily favoring urea under ].<ref>{{Cite journal | author = Shorter, J. | year = 1978 | title = The conversion of ammonium cyanate into urea—a saga in reaction mechanisms | journal = ] | volume = 7 | issue = 1 | pages = 1–14 | doi = 10.1039/CS9780700001 }}</ref> Regardless, with his discovery, Wöhler secured a place among the pioneers of organic chemistry.
			] was first described in 1865 by ], the first Danish pediatrician in 1870 who also described the disease that carries his name in 1886. Uremic frost has become rare since the advent of ]. It is the classical pre-dialysis era description of crystallized urea deposits over the skin of patients with prolonged kidney failure and severe uremia.<ref>{{Cite web |date=2024-04-15 |title=The discovery of urea and the end of vitalism - Hektoen International |url=https://hekint.org/2024/04/15/the-discovery-of-urea-and-the-end-of-vitalism/ |access-date=2024-04-17 |website=hekint.org |language=en-US}}</ref>
	===Historical process===
	Historically urea was first noticed by ] in the early 18th century from evaporates of urine. In 1773, ] obtained crystals containing urea from dog's urine by evaporating it and treating it with alcohol in successive filtrations. This method was aided by ]'s discovery that urine treated by concentrated nitric acid precipitated crystals. ] and ] discovered in 1799 that the nitrated crystals were identical to Rouelle's substance and invented the term "urea." ] made further improvements to its purification and finally ], in 1817, succeeded in obtaining and determining the chemical composition of the pure substance. In the evolved procedure, urea was precipitated as urea nitrate by adding strong nitric acid to urine. To purify the resulting crystals, they were dissolved in boiling water with charcoal and filtered. After cooling pure crystals of urea nitrate form. To reconstitute the urea from the nitrate, the crystals are dissolved in warm water, and ] added. The water is then evaporated and anhydrous alcohol added to extract the urea. This solution is drained off and allowed to evaporate resulting in pure urea.
			===Historical preparation===
	==Chemical properties==
			Urea was first noticed by ] in the early 18th century from evaporates of urine. In 1773, ] obtained crystals containing urea from human urine by evaporating it and treating it with alcohol in successive filtrations.<ref>Rouelle (1773) (Observations on human urine and on that of the cow and horse, compared to each other), ''Journal de Médecine, de Chirurgie et de Pharmacie'', '''40''' : 451–468. Rouelle describes the procedure he used to separate urea from urine on pages 454–455.</ref> This method was aided by ]'s discovery that urine treated by concentrated ] precipitated crystals. ] and ] discovered in 1799 that the nitrated crystals were identical to Rouelle's substance and invented the term "urea."<ref>Fourcroy and Vauquelin (1799) (Extract of a first memoir by citizens Fourcroy and Vauquelin, for use in the natural, chemical, and medical history of human urine, containing some new facts of its analysis and its spontaneous alteration), ''Annales de Chimie'', '''31''' : 48–71. On page 69, urea is named "urée".</ref><ref>Fourcroy and Vauqeulin (1800) (Second memoir: For use in the natural, chemical and medical history of human urine, in which one deals specifically with the properties of the particular material that characterizes it), ''Annales de Chimie'', '''32''' : 80–112; 113–162. On page 91, urea is again named "urée".</ref> ] made further improvements to its purification<ref>{{cite book| last = Rosenfeld | first = Louis | name-list-style = vanc |title=Four Centuries of Clinical Chemistry|url=https://books.google.com/books?id=KPX6Yvax9jkC&pg=PA41|date=1999|publisher=CRC Press|isbn=978-90-5699-645-1|pages=41–}}</ref> and finally ], in 1817, succeeded in obtaining and determining the chemical composition of the pure substance.<ref>{{cite journal| last = Prout | first = William | name-list-style = vanc |year=1817|url=https://books.google.com/books?id=3-kaAQAAMAAJ&pg=PA526 |title=Observations on the nature of some of the proximate principles of the urine; with a few remarks upon the means of preventing those diseases, connected with a morbid state of that fluid|journal=Medico-Chirurgical Transactions|volume=8|pages=526–549|pmc=2128986| pmid = 20895332 | doi = 10.1177/095952871700800123 }}</ref> In the evolved procedure, urea was precipitated as ] by adding strong nitric acid to urine. To purify the resulting crystals, they were dissolved in boiling water with charcoal and filtered. After cooling, pure crystals of urea nitrate form. To reconstitute the urea from the nitrate, the crystals are dissolved in warm water, and ] added. The water is then evaporated and anhydrous alcohol added to extract the urea. This solution is drained off and evaporated, leaving pure urea.
	===Molecular and crystal structure===
	The urea molecule is planar in the crystal structure, but the geometry around the nitrogens is pyramidal in the gas-phase minimum-energy structure.<ref>{{cite journal|doi=10.1016/S0022-2860(97)00176-2|last=Godfrey|first=Peter|coauthors=Brown, Ronald and Hunter, Andrew|title=The shape of urea|journal=Journal of Molecular Structure|year=1997|volume=413-414|pages=405–414}}</ref> In solid urea, the oxygen center is engaged in two N-H-O ]s. The resulting dense and energetically favourable 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 basic compared to, say, ]. Urea's high aqueous solubility reflects its ability to engage in extensive hydrogen bonding with water.
			==Laboratory preparation==
	By virtue of its tendency to form a porous frameworks, urea has the ability to trap many organic compounds. In these so-called ]s, the organic "guest" molecules are held in channels formed by interpenetrating helices composed of ] urea molecules. This behaviour can be used to separate mixtures, e.g. in the production of ] and ]s, and in the separation of ]s.
			Ureas in the more general sense can be accessed in the laboratory by reaction of ] with primary or secondary ]s:
			:{{chem2|COCl2 + 4 RNH2 → (RNH)2CO + 2 +Cl-}}
			These reactions proceed through an ] intermediate. Non-symmetric ureas can be accessed by the reaction of primary or secondary amines with an isocyanate.
			Urea can also be produced by heating ] to 60&nbsp;°C.
	As the helices are interconnected, all helices in a crystal must have the same ]. This is determined when the crystal is nucleated and can thus be forced by seeding. The resulting crystals have been used to separate ]s.
			:{{chem2|+- → (NH2)2CO}}
			==Industrial production==
	===Reactions===
			In 2020, worldwide production capacity was approximately 180 million tonnes.<ref>{{cite web |title=Urea production statistics |url=https://www.ifastat.org/supply/Nitrogen%20Products/Urea |website=www.ifastat.org |publisher=International Fertilizer Association |access-date=19 April 2023}}</ref>
	Urea reacts with alcohols to form ]s. Urea reacts with ] esters to make ]s.
			For use in industry, urea is produced from synthetic ] and ]. As large quantities of carbon dioxide are produced during the ammonia manufacturing process as a byproduct of burning ] to generate heat (predominantly natural gas, and less often petroleum derivatives or coal), urea production plants are almost always located adjacent to the site where the ammonia is manufactured.
			===Synthesis===
			]
			The basic process, patented in 1922, is called the '']'' after its discoverers ] and Wilhelm Meiser.<ref>{{cite patent |country=US |number=1429483 |title=Process of Manufacturing Urea |gdate=1922-09-19 |fdate=1920-07-09 |invent1=Carl Bosch |invent2=Wilhelm Meiser |assign1=] |url=https://patentimages.storage.googleapis.com/36/5a/32/ccce45be728586/US1429483.pdf}}</ref> The process consists of two main ]s, with incomplete conversion of the reactants. The first is '''carbamate formation''': the fast ] reaction of liquid ammonia with gaseous carbon dioxide ({{chem2|CO2}}) at high temperature and pressure to form ] ({{chem2|+-}}):<ref name="Meessen 2012"/>
			:{{chem2|2 NH3 + CO2 ⇌ NH4CO2NH2}}{{space|5}}(Δ''H'' = −117&nbsp;kJ/mol at 110&nbsp;atm and 160&nbsp;°C)<ref name="Meessen 2012"/><ref name="Brouwer 2009">{{cite web |last1=Brouwer |first1=Mark |title=Thermodynamics of the Urea Process |url=https://ureaknowhow.com/pdflib/391_2009%2006%20Brouwer%20UreaKnowHow.com%20Thermodynamics%20of%20the%20%20Urea%20Process.pdf |website=ureaknowhow.com |access-date=26 February 2023}}</ref>
			The second is '''urea conversion''': the slower ] decomposition of ammonium carbamate into urea and water:
			:{{chem2|NH4CO2NH2 ⇌ CO(NH2)2 + H2O}}{{space|5}}(Δ''H'' = +15.5&nbsp;kJ/mol at 160–180&nbsp;°C)<ref name="Meessen 2012"/><ref name="Brouwer 2009"/>
			The overall conversion of {{chem2|NH3}} and {{chem2|CO2}} to urea is exothermic, with the reaction heat from the first reaction driving the second. The conditions that favor urea formation (high temperature) have an unfavorable effect on the carbamate formation equilibrium. The process conditions are a compromise: the ill-effect on the first reaction of the high temperature (around 190&nbsp;°C) needed for the second is compensated for by conducting the process under high pressure (140–175&nbsp;bar), which favors the first reaction. Although it is necessary to compress gaseous carbon dioxide to this pressure, the ammonia is available from the ammonia production plant in liquid form, which can be pumped into the system much more economically. To allow the slow urea formation reaction time to reach equilibrium, a large reaction space is needed, so the synthesis reactor in a large urea plant tends to be a massive pressure vessel.
			===Reactant recycling===
			Because the urea conversion is incomplete, the urea must be separated from the unconverted reactants, including the ammonium carbamate. Various commercial urea processes are characterized by the conditions under which urea forms and the way that unconverted reactants are further processed.
			====Conventional recycle processes====
			In early "straight-through" urea plants, reactant recovery (the first step in "recycling") was done by letting down the system pressure to atmospheric to let the carbamate decompose back to ammonia and carbon dioxide. Originally, because it was not economic to recompress the ammonia and carbon dioxide for recycle, the ammonia at least would be used for the manufacture of other products such as ] or ], and the carbon dioxide was usually wasted. Later process schemes made recycling unused ammonia and carbon dioxide practical. This was accomplished by the "total recycle process", developed in the 1940s to 1960s and now called the "conventional recycle process". It proceeds by depressurizing the reaction solution in stages (first to 18–25 bar and then to 2–5 bar) and passing it at each stage through a steam-heated ''carbamate decomposer'', then recombining the resulting carbon dioxide and ammonia in a falling-film ''carbamate condenser'' and pumping the carbamate solution back into the urea reaction vessel.<ref name="Meessen 2012" />
			==== Stripping recycle process ====
			The "conventional recycle process" for recovering and reusing the reactants has largely been supplanted by a ] process, developed in the early 1960s by ] in The Netherlands, that operates at or near the full pressure of the reaction vessel. It reduces the complexity of the multi-stage recycle scheme, and it reduces the amount of water recycled in the carbamate solution, which has an adverse effect on the equilibrium in the urea conversion reaction and thus on overall plant efficiency. Effectively all new urea plants use the stripper, and many total recycle urea plants have converted to a stripping process.<ref name="Meessen 2012"/><ref name="Meessen 2014">{{cite journal |last=Meessen |first=Jozef |title=Urea synthesis |journal=Chemie Ingenieur Technik |publisher=Wiley |volume=86 | issue=12| date=2014 |issn=0009-286X |doi=10.1002/cite.201400064 |pages=2180–2189|doi-access=free }}</ref>
			In the conventional recycle processes, carbamate decomposition is promoted by reducing the overall pressure, which reduces the partial pressure of both ammonia and carbon dioxide, allowing these gasses to be separated from the urea product solution. The stripping process achieves a similar effect without lowering the overall pressure, by suppressing the partial pressure of just one of the reactants in order to promote carbamate decomposition. Instead of feeding carbon dioxide gas directly to the urea synthesis reactor with the ammonia, as in the conventional process, the stripping process first routes the carbon dioxide through the stripper. The stripper is a carbamate decomposer that provides a large amount of gas-liquid contact. This flushes out free ammonia, reducing its partial pressure over the liquid surface and carrying it directly to a carbamate condenser (also under full system pressure). From there, reconstituted ammonium carbamate liquor is passed to the urea production reactor. That eliminates the medium-pressure stage of the conventional recycle process.<ref name="Meessen 2012"/><ref name="Meessen 2014"/>
			=== Side reactions ===
			The three main side reactions that produce impurities have in common that they decompose urea.
			Urea hydrolyzes back to ammonium carbamate in the hottest stages of the synthesis plant, especially in the stripper, so residence times in these stages are designed to be short.<ref name="Meessen 2012"/>
			] is formed when two molecules of urea combine with the loss of a molecule of ammonia.
			:{{chem2|2 NH2CONH2 → NH2CONHCONH2 + NH3}}
			Normally this reaction is suppressed in the synthesis reactor by maintaining an excess of ammonia, but after the stripper, it occurs until the temperature is reduced.<ref name="Meessen 2012"/> Biuret is undesirable in urea fertilizer because it is toxic to crop plants to varying degrees,<ref name="Mikkelsen 1990">{{cite journal | last=Mikkelsen | first=R. L | title=Biuret in urea fertilizer | journal=Fertilizer Research | volume=26 | issue=1–3 | year=1990 | issn=0167-1731 | doi=10.1007/bf01048769 | pages=311–318| s2cid=5970745 }}</ref> but it is sometimes desirable as a nitrogen source when used in animal feed.<ref>{{cite journal | last1=Fonnesbeck | first1=Paul V. | last2=Kearl | first2=Leonard C. | last3=Harris | first3=Lorin E. | title=Feed Grade Biuret as a Protein Replacement for Ruminants. A Review | journal=Journal of Animal Science | publisher=Oxford University Press (OUP) | volume=40 | issue=6 | date=1975 | issn=0021-8812 | doi=10.2527/jas1975.4061150x | pages=1150–1184 | url=https://academic.oup.com/jas/article-abstract/40/6/1150/4699012}}</ref>
			] HNCO and ] {{chem2|NH3}} results from the thermal decomposition of ] {{chem2|+-}}, which is in ] with urea:
			:{{chem2|CO(NH2)2 → +- → HNCO + NH3}}
			This decomposition is at its worst when the urea solution is heated at low pressure, which happens when the solution is concentrated for prilling or granulation (see below). The reaction products mostly volatilize into the overhead vapours, and recombine when these condense to form urea again, which contaminates the process condensate.<ref name="Meessen 2012"/>
			=== Corrosion ===
			] solutions are highly corrosive to metallic construction materials – even to resistant forms of ] – especially in the hottest parts of the synthesis plant such as the stripper. Historically ] has been minimized (although not eliminated) by continuous injection of a small amount of ] (as air) into the plant to establish and maintain a ] oxide layer on exposed stainless steel surfaces. Highly corrosion resistant materials have been introduced to reduce the need for passivation oxygen, such as specialized ]s in the 1990s, and ] or zirconium-clad titanium tubing in the 2000s.<ref name="Meessen 2012"/>
			=== Finishing ===
			Urea can be produced in solid forms (]s, ], pellets or crystals) or as solutions.
			==== Solid forms ====
			For its main use as a fertilizer urea is mostly marketed in solid form, either as prills or granules. Prills are solidified droplets, whose production predates satisfactory urea granulation processes. Prills can be produced more cheaply than granules, but the limited size of prills (up to about 2.1&nbsp;mm in diameter), their low crushing strength, and the caking or crushing of prills during bulk storage and handling make them inferior to granules. Granules are produced by acretion onto urea seed particles by spraying liquid urea in a succession of layers. ] is added during the production of both prills and granules in order to increase crushing strength and suppress caking. Other shaping techniques such as pastillization (depositing uniform-sized liquid droplets onto a cooling conveyor belt) are also used.<ref name="Meessen 2012"/>
	==Safety==
	Urea can be irritating to skin, eyes, and the respiratory tract. Repeated or prolonged contact with urea in fertilizer form on the skin may cause ].
			==== Liquid forms ====
	High concentrations in the blood can be damaging. Ingestion of low concentrations of urea, such as are found in typical human ], are not dangerous with additional water ingestion within a reasonable time-frame. Many animals (e.g., dogs) have a much more concentrated urine and it contains a higher urea amount than normal human urine; this can prove dangerous as a source of liquids for consumption in a life-threatening situation (such as in a desert).
			Solutions of ] in water (UAN) are commonly used as a liquid fertilizer. In admixture, the combined solubility of ammonium nitrate and urea is so much higher than that of either component alone that it gives a stable solution with a total nitrogen content (32%) approaching that of solid ammonium nitrate (33.5%), though not, of course, that of urea itself (46%). UAN allows use of ammonium nitrate without the explosion hazard.<ref name="Meessen 2012"/> UAN accounts for 80% of the liquid fertilizers in the US.<ref name="Ren 2021">{{cite journal | last1=Ren | first1=Baizhao | last2=Guo | first2=Yanqing | last3=Liu | first3=Peng | last4=Zhao | first4=Bin | last5=Zhang | first5=Jiwang | title=Effects of Urea-Ammonium Nitrate Solution on Yield, N2O Emission, and Nitrogen Efficiency of Summer Maize Under Integration of Water and Fertilizer | journal=Frontiers in Plant Science | volume=12 | date=2021-08-03 | page=700331 | issn=1664-462X | doi=10.3389/fpls.2021.700331 | pmid=34413867 | pmc=8369924 | doi-access=free }}</ref>
	Urea can cause ]s to produce toxins, and its presence in the runoff from fertilized land may play a role in the increase of toxic blooms.<ref> – US set to track toxic algal blooms</ref>
			== See also ==
	The substance decomposes on heating above melting point, producing toxic gases, and reacts violently with strong oxidants, nitrites, inorganic chlorides, chlorites and perchlorates, causing fire and explosion.{{Citation needed|date=January 2010}}
			* ]
			* ]
	==References==		== References ==
	{{Reflist}}		{{Reflist|30em}}
	==External links==		==External links==
			{{Commons category}}
	*
			* {{PPDB|1728}}
	*
			{{Blood substitutes and perfusion solutions}}
			{{Functional Groups}}
	{{E number infobox 920-929}}		{{E number infobox 920-929}}
			{{Authority control}}
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	]
	]
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