View source for Hydantoin

{{chembox
|Watchedfields = changed
|verifiedrevid = 443859459
|ImageFileL1 = Hydantoin.svg
|ImageAltL1 = Skeletal formula of hydantoin
|ImageFileR1 = Hydantoin-3D-balls.png
|ImageAltR1 = Ball-and-stick model of hydantoin
|PIN =Imidazolidine-2,4-dione
|Section1={{Chembox Identifiers
|ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
|ChemSpiderID = 9612
|KEGG_Ref = {{keggcite|correct|kegg}}
|KEGG = C05146
|InChI = 1/C3H4N2O2/c6-2-1-4-3(7)5-2/h1H2,(H2,4,5,6,7)
|InChIKey = WJRBRSLFGCUECM-UHFFFAOYAD
|ChEMBL_Ref = {{ebicite|correct|EBI}}
|ChEMBL = 122334
|StdInChI_Ref = {{stdinchicite|correct|chemspider}}
|StdInChI = 1S/C3H4N2O2/c6-2-1-4-3(7)5-2/h1H2,(H2,4,5,6,7)
|StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
|StdInChIKey = WJRBRSLFGCUECM-UHFFFAOYSA-N
|CASNo_Ref = {{cascite|correct|CAS}}
|CASNo =461-72-3
|PubChem =10006
|ChEBI_Ref = {{ebicite|correct|EBI}}
|ChEBI = 27612
|SMILES = O=C1NC(=O)NC1
|UNII = I6208298TA
}}
|Section2={{Chembox Properties
|C=3|H=4|N=2|O=2
|MeltingPtC = 220
|Solubility = 39.7 g/l (100 °C)
}}
}}

'''Hydantoin''', or '''glycolylurea''', is a [[heterocyclic]] [[organic compound]] with the formula CH<sub>2</sub>C(O)NHC(O)NH.  It is a colorless solid that arises from the reaction of [[glycolic acid]] and [[urea]]. It is an oxidized derivative of [[imidazolidine]]. In a more general sense, hydantoins can refer to [[Functional group|groups]] or a class of compounds with the same ring structure as the parent compound. For example, [[phenytoin]] (mentioned below) has two [[phenyl]] groups substituted onto the number 5 carbon in a hydantoin molecule.<ref name= Konnert>{{cite journal |doi=10.1021/acs.chemrev.7b00067|title=Recent Advances in the Synthesis of Hydantoins: The State of the Art of a Valuable Scaffold |year=2017 |last1=Konnert |first1=Laure |last2=Lamaty |first2=Frédéric |last3=Martinez |first3=Jean |last4=Colacino |first4=Evelina |journal=Chemical Reviews |volume=117 |issue=23 |pages=13757–13809 |pmid=28644621 |s2cid=23653941 |url=https://hal.archives-ouvertes.fr/hal-02385289/file/Hal-126.pdf }}</ref>

==Synthesis==
Hydantoin was first isolated in 1861 by [[Adolf von Baeyer]] in the course of his study of [[uric acid]]. He obtained it by [[hydrogenation]] of [[allantoin]], hence the name.

:[[File:Harnsäureabbau.svg|left|700px]]
{{clear left}}

Friedrich Urech synthesized 5-methylhydantoin in 1873 from [[alanine]] [[sulfate]] and [[potassium cyanate]] in what is now known as the [[Urech hydantoin synthesis]].<ref>{{cite journal|first = Friedrich|last = Urech|journal = [[Liebigs Ann.]]|title = Ueber Lacturaminsäure und Lactylharnstoff|language = de|volume = 165|issue = 1|pages = 99–103|year = 1873|doi = 10.1002/jlac.18731650110|url = https://zenodo.org/record/1427313}}</ref>  The method is very similar to the modern route using alkyl and arylcyanates. The 5,5-dimethyl compound can also be obtained from [[cyanohydrin|acetone cyanohydrin]] (also discovered by Urech: see [[cyanohydrin reaction]]) and [[ammonium carbonate]].<ref>{{OrgSynth|collvol = 3|collvolpages = 323|volume = 20|pages = 42|year = 1940|prep = CV3P0323|doi = 10.15227/orgsyn.020.0042|title = 5,5-Dimethylhydantoin|first1 = E. C.|last1 = Wagner|first2 = Manuel|last2 = Baizer}}</ref> This reaction type is called the [[Bucherer–Bergs reaction]].<ref>{{cite journal|last1 = Bucherer|first1 = H. T.|author-link1 = Hans Theodor Bucherer|last2 = Steiner|first2 = W.|language = de|title = [[J. Prakt. Chem.]]|volume = 140|page = 291|year = 1934}}</ref><ref>Bergs, Ger. pat. 566,094 ('''1929''') [C. A., 27, 1001 ('''1933''')].</ref>

Hydantoin can also be synthesized either by heating [[allantoin]] with [[hydroiodic acid]] or by "heating bromacetyl urea with alcoholic ammonia".<ref>{{cite EB1911 |wstitle=Hydantoin |volume=14 |pages=29–30}}</ref> The cyclic structure of hydantoins was confirmed by [[Dorothy Hahn]] 1913.<ref>{{cite encyclopedia| title = Encyclopedia of World Scientists|last = Oakes|first = Elizabeth H.|publisher = [[Facts on File]]|year = 2007|isbn = 9780816061587|pages = 298}}</ref>

Of practical importance, hydantoins are obtained by condensation of a [[cyanohydrin]] with [[ammonium carbonate]].  Another useful route, which follows the work of Urech, involves the condensation of ⍺-amino acids or ⍺-amino esters with cyanates and isocyanates:<ref>{{cite journal|last1 = Blanco-Ania|first1 = Daniel|last2 = Hermkens|first2 = Pedro H. H.|last3 = Sliedregt|first3 = Leo A. J. M.|last4 = Scheeren|first4 = Hans W.|last5 = Rutjes|first5 = Floris P. J. T.|title = Synthesis of Hydantoins and Thiohydantoins Spiro-Fused to Pyrrolidines: Druglike Molecules Based on the 2-Arylethyl Amine Scaffold|journal = [[Journal of Combinatorial Chemistry]]|year = 2009|volume = 11| issue=4 |pages = 527–538|doi = 10.1021/cc800190z| pmid=19472985 | url=https://repository.ubn.ru.nl//bitstream/handle/2066/75771/75771.pdf }}</ref>
:[[File:AA+RNCO.png|420px]]

==Uses and occurrence==
===Pharmaceuticals===
The hydantoin group can be found in several medicinally important compounds.<ref name= Konnert/>   In pharmaceuticals, hydantoin [[derivative (chemistry)|derivatives]] form a class of [[anticonvulsants]];<ref>{{cite web | url = https://www.drugs.com/drug-class/hydantoin-anticonvulsants.html | title = Hydantoin anticonvulsants | publisher = [[drugs.com]]}}</ref> [[phenytoin]] and [[fosphenytoin]] both contain hydantoin moieties and are both used as anticonvulsants in the treatment of seizure disorders.   The hydantoin derivative [[dantrolene]] is used as a muscle relaxant to treat [[malignant hyperthermia]], [[neuroleptic malignant syndrome]], [[spasticity]], and [[ecstasy (drug)|ecstasy]] intoxication. [[Ropitoin]] is an example of an [[antiarrhythmic]] hydantoin.

===Pesticides===
The hydantoin derivative [[Imiprothrin]] is a pyrethroid [[insecticide]]. [[Iprodione]] is a popular fungicide containing the hydantoin group.<ref name = Ullmann>{{cite encyclopedia|encyclopedia = [[Ullmann's Encyclopedia of Industrial Chemistry]]|doi = 10.1002/14356007.a02_057.pub2|first1 = Karlheinz|last1 = Drauz|first2 = Ian|last2 = Grayson|first3 = Axel|last3 = Kleemann|first4 = Hans-Peter|last4 = Krimmer|first5 = Wolfgang|last5 = Leuchtenberger|first6 = Christoph|last6 = Weckbecker|year = 2007|isbn = 978-3527306732|chapter = Amino Acids}}</ref>

===Synthesis of amino acids===
Hydrolysis of hydantoins affords amino acids:
:{{chem2 | RCHC(O)NHC(O)NH  +  H2O  ->   RCHC(NH2)COOH  +  NH3 }}
Hydantoin itself reacts with hot, dilute [[hydrochloric acid]] to give [[glycine]].  Methionine is produced industrially via the hydantoin obtained from [[methional]].<ref name = Ullmann/>

===Methylation===
[[Methylation]] of hydantoin yields a variety of derivatives. '''Dimethylhydantoin''' (DMH) <ref>{{Cite web | url=https://www.tappi.org/21969/ | title=5,5-Dimethylhydantoin (DMH) a Highly Effective, Halogen Stabilizer for Wet End Applications, PaperCo}}</ref> may refer to any dimethyl derivative of hydantoin, but especially '''5,5-dimethylhydantoin'''.<ref>{{Cite web | url=https://pubchem.ncbi.nlm.nih.gov/compound/5_5-dimethylhydantoin | title=5,5-Dimethylhydantoin}}</ref>

===Halogenation===
Some ''N''-halogenated derivatives of hydantoin are used as chlorinating or brominating agents in [[disinfectant]]/sanitizer or [[biocide]] products. The three major ''N''-halogenated derivatives are '''dichlorodimethylhydantoin''' (DCDMH), [[BCDMH|bromochlorodimethylhydantoin]] (BCDMH), and [[dibromodimethylhydantoin]] (DBDMH). A mixed ethyl-methyl analogue, 1,3-dichloro-5-ethyl-5-methylimidazolidine-2,4-dione ('''bromochloroethylmethylhydantoin'''), is also used in mixtures with the above.

[[Image:Iprodione.png|thumb|right|[[Iprodione]] is a popular fungicide containing the hydantoin group.]]

===DNA oxidation to hydantoins after cell death===
A high proportion of [[cytosine]] and [[thymine]] bases in [[DNA]] are oxidized to hydantoins over time after the death of an organism. Such modifications block DNA polymerases and thus prevents [[Polymerase chain reaction|PCR]] from working. Such damage is a problem when dealing with ancient DNA samples.<ref>{{cite journal|last1 = Hofreiter|first1 = Michael|last2 = Serre|first2 = David|last3 = Poinar|first3 = Hendrik N.|last4 = Kuch|first4 = Melanie|last5 = Pääbo|first5 = Svante|title = Ancient DNA|journal = [[Nature Reviews Genetics]]|year = 2001|volume = 2|issue = 5|pages = 353–359|doi = 10.1038/35072071|pmid = 11331901|s2cid = 205016024}}</ref>

==External links and further reading==
{{wiktionary|dimethylhydantoin}}
* {{cite journal|title = The Chemistry of the Hydantoins|first = Elinor|last = Ware|journal = [[Chem. Rev.]]|year = 1950|volume = 46|issue = 3|pages = 403–470|doi = 10.1021/cr60145a001|pmid = 24537833}}
* [http://www.mjlphd.net/translations.html] {{Webarchive|url=https://web.archive.org/web/20201018004942/https://www.mjlphd.net/translations.html |date=2020-10-18 }} English Translation of 1926 German review article on the Preparation of hydantoins by Heinrich Biltz and Karl Slotta

==References==
{{reflist}}
{{Anticonvulsants}}

[[Category:Hydantoins| ]]
[[Category:Substances discovered in the 19th century]]