Editing Urea (section)

==History==
Urea was first discovered in urine in 1727 by the Dutch scientist [[Herman Boerhaave]],<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), [https://archive.org/stream/newmethodofchemi00boer#page/192/mode/2up page 193: Process LXXXVII].
* Boerhaave, Herman ''Elementa Chemicae'' …, volume 2, (Leipzig ("Lipsiae"), (Germany): Caspar Fritsch, 1732), [https://books.google.com/books?id=OH45AAAAcAAJ&pg=PA276 page 276].
* For an English translation of the relevant passage, see: Peter Shaw, ''A New Method of Chemistry'' …, 2nd ed., (London, England: T. Longman, 1741), [https://archive.org/stream/newmetchemi02boer#page/198/mode/2up/ page 198: Process CXVIII: The native salt of urine]
* Lindeboom, Gerrit A. ''Boerhaave and Great Britain'' …, (Leiden, Netherlands: E.J. Brill, 1974), [https://books.google.com/books?id=yOIUAAAAIAAJ&pg=PA51 page 51].
* 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 [[France|French]] chemist [[Hilaire Rouelle]] as well as [[William Cruickshank (chemist)|William Cruickshank]].<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>
# Boiled off water, resulting in a substance similar to fresh cream
# Used filter paper to squeeze out remaining liquid
# Waited a year for solid to form under an oily liquid
# Removed the oily liquid
# Dissolved the solid in water
# Used [[Recrystallization (chemistry)|recrystallization]] to tease out the urea

In 1828, the [[Germany|German]] chemist [[Friedrich Wöhler]] obtained urea artificially by treating [[silver cyanate]] with [[ammonium chloride]].<ref>Wöhler, Friedrich (1828) [http://gallica.bnf.fr/ark:/12148/bpt6k15097k/f261.image "Ueber künstliche Bildung des Harnstoffs"] (On the artificial formation of urea), ''Annalen der Physik und Chemie'', '''88''' (2) : 253–256. Available in English at [http://www.chemteam.info/Chem-History/Wohler-article.html Chem Team].
</ref><ref>
{{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>
{{block indent |left=1.5 |text={{chem2|AgNCO + [NH4]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 [[vitalism]], the theory that the chemicals of living organisms are fundamentally different from those of inanimate matter. This insight was important for the development of [[organic chemistry]]. His discovery prompted Wöhler to write triumphantly to [[Jöns Jakob Berzelius]]:
{{bq|text=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. [[Ammonium cyanate]] {{chem2|[NH4]+[OCN]-}} and urea {{chem2|CO(NH2)2}} are two different chemicals with the same [[empirical formula]] {{chem2|CON2H4}}, which are in chemical equilibrium heavily favoring urea under [[standard conditions]].<ref>{{Cite journal | author = Shorter, J. | year = 1978 | title = The conversion of ammonium cyanate into urea—a saga in reaction mechanisms | journal = [[Chemical Society Reviews]] | 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.

[[Uremic frost]] was first described in 1865 by [[Harald Hirschsprung]], 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 [[Kidney dialysis|dialysis]]. 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 preparation===
Urea was first noticed by [[Herman Boerhaave]] in the early 18th century from evaporates of urine. In 1773, [[Hilaire Rouelle]] obtained crystals containing urea from human urine by evaporating it and treating it with alcohol in successive filtrations.<ref>Rouelle (1773) [https://books.google.com/books?id=q1ATAAAAQAAJ&pg=PA451 "Observations sur l'urine humaine, & sur celle de vache & de cheval, comparées ensemble"] (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 [[Carl Wilhelm Scheele]]'s discovery that urine treated by concentrated [[nitric acid]] precipitated crystals. [[Antoine François, comte de Fourcroy]] and [[Louis Nicolas Vauquelin]] discovered in 1799 that the nitrated crystals were identical to Rouelle's substance and invented the term "urea."<ref>Fourcroy and Vauquelin (1799) [https://books.google.com/books?id=LsrBxKHCiAwC&pg=PA48 "Extrait d’un premier mémoire des cit. Fourcroy et Vaulquelin, pour servir à l’histoire naturelle, chimique et médicale de l’urine humaine, contenant quelques faits nouveaux sur son analyse et son altération spontanée"] (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) [https://books.google.com/books?id=0zhOAAAAcAAJ&pg=PA80 "Deuxième mémoire: Pour servir à l’histoire naturelle, chimique et médicale de l’urine humaine, dans lequel on s’occupe spécialement des propriétés de la matière particulière qui le caractérise,"] (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> [[Berzelius]] 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 [[William Prout]], 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 [[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 [[barium carbonate]] added. The water is then evaporated and anhydrous alcohol added to extract the urea. This solution is drained off and evaporated, leaving pure urea.