Editing Pyrimidine (section)

== Synthesis ==
[[Pyrimidine metabolism|Pyrimidine biosynthesis]] creates derivatives —like orotate, thymine, cytosine, and uracil— ''de novo'' from carbamoyl phosphate and aspartate.

As is often the case with parent heterocyclic ring systems, the synthesis of pyrimidine is not that common and is usually performed by removing functional groups from derivatives. Primary syntheses in quantity involving [[formamide]] have been reported.<ref name="BrownPyrimidines1994" />{{rp|241–242}}

As a class, pyrimidines are typically synthesized by the principal synthesis involving cyclization of β-di[[carbonyl]] compounds with N–C–N compounds. Reaction of the former with [[amidine]]s to give 2-substituted pyrimidines, with [[urea]] to give 2-[[pyrimidinone]]s, and [[guanidine]]s to give 2-[[aminopyrimidine]]s are typical.<ref name="BrownPyrimidines1994"/>{{rp|149–239}}

Pyrimidines can be prepared via the [[Biginelli reaction]] and other [[multicomponent reaction]]s.<ref>{{cite journal |last1=Anjirwala |first1=Sharmil N. |last2=Parmar |first2=Parnas S. |last3=Patel |first3=Saurabh K. |title=Synthetic protocols for non-fused pyrimidines |journal=Synthetic Communications |date=28 October 2022 |volume=52 |issue=22 |pages=2079–2121 |doi=10.1080/00397911.2022.2137682|s2cid=253219218 }}</ref> Many other methods rely on [[condensation]] of [[carbonyl]]s with diamines for instance the synthesis of 2-thio-6-methyluracil from [[thiourea]] and [[ethyl acetoacetate]]<ref>{{OrgSynth|last1=Foster |first1=H. M. |last2=Snyder |first2=H. R. |title=4-Methyl-6-hydroxypyrimidine |collvol=4 |collvolpages=638 |volume=35 |page=80 |date=1955 |prep=CV4P0638 |doi=10.15227/orgsyn.035.0080|doi-access=free}}</ref> or the synthesis of 4-methylpyrimidine with 4,4-dimethoxy-2-butanone and [[formamide]].<ref>{{OrgSynth|last1=Bredereck |first1=H. |title=4-methylpyrimidine |collvol=5 |collvolpages=794 |volume=43 |page=77 |date=1963 |prep=CV5P0794 |doi=10.15227/orgsyn.043.0077|doi-access=free}}</ref>

A novel method is by reaction of ''N''-vinyl and ''N''-aryl [[amide]]s with [[carbonitrile]]s under electrophilic activation of the amide with 2-chloro-pyridine and [[trifluoromethanesulfonic anhydride]]:<ref>{{cite journal | last1 = Movassaghi | first1 = Mohammad | last2 = Hill | first2 = Matthew D. | year = 2006 | title = Single-Step Synthesis of Pyrimidine Derivatives | journal = [[J. Am. Chem. Soc.]] | volume = 128 | issue = 44| pages = 14254–14255 | doi = 10.1021/ja066405m | pmid = 17076488 }}</ref>

:[[Image:PyrimidineSynthAmideCarbonitrile.png|400px|Pyrimidine synthesis (Movassaghi 2006)]]