View source for Pyrimidine

{{short description|Aromatic compound (C4H4N2)}}
{{Distinguish|Pyridine}}
{{Chembox
| Verifiedimages = changed
| Watchedfields = changed
| verifiedrevid = 464377262
| ImageFileL1 = Pyrimidine 2D aromatic full.svg
| ImageClassL1 = skin-invert-image
| ImageFileR1 = Pyrimidine 2D numbers.svg
| ImageClassR1 = skin-invert-image
| ImageFileL2 = Pyrimidine-3D-balls-2.png
| ImageAltL2 = Pyrimidine molecule
| ImageFileR2 = Pyrimidine-3D-spacefill.png
| ImageAltR2 = Pyrimidine molecule
| PIN = Pyrimidine<ref name=iupac2013>{{cite book | title =  Nomenclature of Organic Chemistry : IUPAC Recommendations and Preferred Names 2013 (Blue Book) | publisher = [[Royal Society of Chemistry|The Royal Society of Chemistry]] | date = 2014 | location = Cambridge | page = 141 | doi = 10.1039/9781849733069-FP001 | isbn = 978-0-85404-182-4| chapter = Front Matter }}</ref>
| SystematicName = 1,3-Diazabenzene
| OtherNames = 1,3-Diazine<br />''m''-Diazine
|Section1={{Chembox Identifiers
| CASNo_Ref = {{cascite|correct|CAS}}
| CASNo=289-95-2
| Beilstein = 103894
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 16898
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 15562
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 8903
| EC_number = 206-026-0
| Gmelin = 49324
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = C00396
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = K8CXK5Q32L
| PubChem=9260
| InChI = 1/C4H4N2/c1-2-5-4-6-3-1/h1-4H
| InChIKey = CZPWVGJYEJSRLH-UHFFFAOYAT
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C4H4N2/c1-2-5-4-6-3-1/h1-4H
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = CZPWVGJYEJSRLH-UHFFFAOYSA-N
| SMILES = n1cnccc1
| MeSHName=pyrimidine
 }}
|Section2={{Chembox Properties
| Formula = {{chem2|C4H4N2}}
| MolarMass = 80.088 g mol<sup>−1</sup>
| Appearance =
| Density = 1.016 g cm<sup>−3</sup>
| MeltingPtC = 20 to 22
| BoilingPtC = 123 to 124
| Solubility=Miscible (25°C)
| pKa=1.10<ref>{{cite book|last1=Brown |first1=H. C. |editor1-last=Baude |editor1-first=E. A. |editor2-first=Nachod |editor2-last=F. C. |title=Determination of Organic Structures by Physical Methods |publisher=Academic Press |location=New York, NY |date=1955}}</ref> (protonated pyrimidine)
 }}
|Section3={{Chembox Hazards
| GHS_ref=[https://pubchem.ncbi.nlm.nih.gov/compound/9260#section=Safety-and-Hazards]
| GHSPictograms = {{GHS02}}{{GHS05}}
| GHSSignalWord = Danger
| HPhrases = {{H-phrases|226|318}}
| PPhrases = {{P-phrases|210|233|240|241|242|243|264+265|280|303+361+353|305+354+338|317|370+378|403+235|501}}
| MainHazards=
| FlashPt=
| AutoignitionPt =
 }}
}}

'''Pyrimidine''' ({{chem2|C4H4N2}}; {{IPAc-en|p|ɪ|ˈ|ɹ|ɪ|.|m|ɪ|ˌ|d|iː|n|,_|p|aɪ|ˈ|ɹ|ɪ|.|m|ɪ|ˌ|d|iː|n}}) is an [[aromatic]], [[heterocyclic compound|heterocyclic]], [[organic compound]] similar to [[pyridine]] ({{chem2|C5H5N}}).<ref name="isbn0-582-27843-0">{{cite book |last=Gilchrist |first=Thomas Lonsdale |title=Heterocyclic chemistry |publisher=Longman |location=New York |year=1997 |isbn=978-0-582-27843-1 }}</ref> One of the three [[diazine]]s (six-membered heterocyclics with two [[nitrogen]] atoms in the ring), it has nitrogen atoms at positions 1 and 3 in the ring.<ref name="JouleMills5th">{{cite book | title=Heterocyclic Chemistry |edition=5th |editor1-last=Joule |editor1-first=John A. |editor2-last=Mills |editor2-first=Keith |publisher=Wiley |location=Oxford |year=2010 |isbn=978-1-405-13300-5 }}</ref>{{rp|250}} The other diazines are [[pyrazine]] (nitrogen atoms at the 1 and 4 positions) and [[pyridazine]] (nitrogen atoms at the 1 and 2 positions). 

In [[nucleic acids]], three types of [[nucleobases]] are pyrimidine [[Derivative (chemistry)|derivative]]s: [[cytosine]] (C), [[thymine]] (T), and [[uracil]] (U).

==Occurrence and history==
[[File:PinnerPyrimidin.png|thumb|left|77px|Pinner's 1885 structure for pyrimidine]]
The pyrimidine ring system has wide occurrence in nature<ref name=Lagoja1>{{Cite journal
 | last = Lagoja |first= Irene M.
 | year = 2005
 | title = Pyrimidine as Constituent of Natural Biologically Active Compounds
 | journal = Chemistry and Biodiversity
 | volume = 2
 | issue = 1
 | pages = 1–50
 | url = http://homepage.univie.ac.at/mario.barbatti/papers/pyrazine_pyrimidine/pyrimidine.pdf
 | doi = 10.1002/cbdv.200490173
 | pmid = 17191918
 |s2cid= 9942715
 }}</ref>
as substituted and ring fused compounds and derivatives, including the [[#Nucleotides|nucleotides]] [[cytosine]], [[thymine]] and [[uracil]], [[thiamine]] (vitamin B1) and [[alloxan]]. It is also found in many synthetic compounds such as [[barbiturate]]s and the HIV drug [[zidovudine]]. Although pyrimidine derivatives such as alloxan were known in the early 19th century, a laboratory synthesis of a pyrimidine was not carried out until 1879,<ref name=Lagoja1/> when Grimaux reported the preparation of [[barbituric acid]] from [[urea]] and [[malonic acid]] in the presence of [[phosphorus oxychloride]].<ref name=Grimaux1879>{{Cite journal
 | last = Grimaux | first = E.
 | year = 1879
 | title = Synthèse des dérivés uriques de la série de l'alloxane
 | trans-title = Synthesis of urea derivatives of the alloxan series
 | journal = Comptes Rendus Hebdomadaires des Séances de l'Académie des Sciences
 | volume = 88
 | pages = 85–87
 | url = http://visualiseur.bnf.fr/ark:/12148/bpt6k30457/f85.image 
 }} {{free access}}</ref>
The systematic study of pyrimidines began<ref name="ElderfieldVol6">{{cite book |last1=Kenner |first1=G. W. |last2=Todd |first2=Alexander |editor = Elderfield |editor-first=R.C. |title=Heterocyclic Compounds |volume=6 |publisher=Wiley |location=New York |year=1957 |pages=235 }}</ref> in 1884 with [[Adolf Pinner|Pinner]],<ref name=Pinner1884>{{Cite journal
 | author-link = Adolf Pinner
 | last = Pinner | first = A.
 | year = 1884
 | title = Ueber die Einwirkung von Acetessigäther auf die Amidine
 | trans-title = On the effect of acetylacetonate ester on amidines
 | journal = [[Chemische Berichte|Berichte der Deutschen Chemischen Gesellschaft]]
 | volume = A17
 | issue = 2
 | pages = 2519–2520
 | url = http://gallica.bnf.fr/ark:/12148/bpt6k90700r/f942.image|doi=10.1002/cber.188401702173 
 }} {{free access}}</ref>
who synthesized derivatives by condensing [[ethyl acetoacetate]] with [[amidine]]s. Pinner first proposed the name “pyrimidin” in 1885.<ref name=Pinner1885>{{Cite journal
 | author-link = Adolf Pinner
 | last = Pinner | first = A.
 | year = 1885
 | title = Ueber die Einwirkung von Acetessigäther auf die Amidine. Pyrimidin
 | trans-title = On the effect of acetylacetonate ester on amidines. Pyrimidine
 | journal = [[Chemische Berichte|Berichte der Deutschen Chemischen Gesellschaft]]
 | volume = A18
 | pages = 759–760
 | url = http://visualiseur.bnf.fr/ark:/12148/bpt6k90702f/f761.image |doi=10.1002/cber.188501801161 
| url-access = subscription
 }} {{free access}}</ref> The parent compound was first prepared by [[Siegmund Gabriel|Gabriel]] and Colman in 1900,<ref name=Gabriel1900>{{Cite journal
 | author-link = Siegmund Gabriel
 | last = Gabriel | first = S.
 | year = 1900
 | title = Pyrimidin aus Barbitursäure
 | trans-title = Pyrimidine from barbituric acid
 | journal = [[Chemische Berichte|Berichte der Deutschen Chemischen Gesellschaft]]
 | volume = A33
 | issue = 3
 | pages = 3666–3668
 | url = http://visualiseur.bnf.fr/ark:/12148/bpt6k90757q/f879.image |doi=10.1002/cber.190003303173 
 | url-access = subscription
 }} {{free access}}</ref>
<ref name=Lythgoe1951>{{Cite journal
 | last1 = Lythgoe | first1 = B.
 | last2 = Rayner | first2 = L. S.
 | year = 1951
 | title = Substitution Reactions of Pyrimidine and its 2- and 4-Phenyl Derivatives
 | journal = [[Journal of the Chemical Society]]
 | volume = 1951
 | pages = 2323–2329
 | doi= 10.1039/JR9510002323
 }}</ref>
by conversion of [[barbituric acid]] to 2,4,6-trichloropyrimidine followed by reduction using [[zinc]] dust in hot water.

==Nomenclature==
The nomenclature of pyrimidines is straightforward. However, like other heterocyclics, [[tautomer]]ic [[hydroxyl]] groups yield complications since they exist primarily in the cyclic [[amide]] form. For example, 2-hydroxypyrimidine is more properly named 2-pyrimidone. A partial list of trivial names of various pyrimidines exists.<ref name="BrownPyrimidines1994">{{cite book |last1=Brown |first1=D. J. |last2=Evans |first2=R. F. |last3=Cowden |first3=W. B. |last4=Fenn |first4=M. D. |title=The Pyrimidines |publisher=John Wiley & Sons |location=New York, NY |year=1994 |isbn=978-0-471-50656-0}}</ref>{{rp|5–6}}

==Physical properties==
Physical properties are shown in the data box. A more extensive discussion, including spectra, can be found in Brown ''et al.''<ref name="BrownPyrimidines1994"/>{{rp|242–244}}

== Chemical properties ==
Per the classification by [[Adrien Albert|Albert]],<ref name="Albert1968">{{cite book |last=Albert |first=Adrien |title=Heterocyclic Chemistry, an Introduction |publisher=Athlone Press |location=London |year=1968 }}</ref>{{rp|56–62}} six-membered heterocycles can be described as π-deficient. Substitution by electronegative groups or additional nitrogen atoms in the ring significantly increase the π-deficiency. These effects also decrease the basicity.<ref name="Albert1968"/>{{rp|437–439}}

Like pyridines, in pyrimidines the π-electron density is decreased to an even greater extent. Therefore, [[electrophilic aromatic substitution]] is more difficult while [[nucleophilic aromatic substitution]] is facilitated. An example of the last reaction type is the displacement of the [[amino]] group in 2-aminopyrimidine by [[chlorine]]<ref>{{OrgSynth|last1=Kogon |first1=Irving C. |last2=Minin |first2=Ronald |last3=Overberger |first3=C. G. |title=2-Chloropyrimidine |collvol=4 |collvolpages=182 |volume=35 |page=34 |date=1955 |prep=CV4P0182 |doi=10.15227/orgsyn.035.0034 |doi-access=free}}</ref> and its reverse.<ref>{{OrgSynth|last1=Overberger |first1=C. G. |last2=Kogon |first2=Irving C. |last3=Minin |first3=Ronald |title=2-(Dimethylamino)pyrimidine |collvol=4 |collvolpages=336 |volume=35 |page=58 |date=1955 |prep=CV4P0336 |doi=10.15227/orgsyn.035.0058|doi-access=free}}</ref>

Electron [[lone pair]] availability ([[basicity]]) is decreased compared to pyridine. Compared to pyridine, [[N-alkylation|''N''-alkylation]] and [[N-oxidation|''N''-oxidation]] are more difficult. The [[pKa|p''K''<sub>a</sub>]] value for protonated pyrimidine is 1.23 compared to 5.30 for pyridine. Protonation and other electrophilic additions will occur at only one nitrogen due to further deactivation by the second nitrogen.<ref name="JouleMills5th"/>{{rp|250}} The 2-, 4-, and 6- positions on the pyrimidine ring are electron deficient analogous to those in pyridine and nitro- and dinitrobenzene. The 5-position is less electron deficient and substituents there are quite stable. However, electrophilic substitution is relatively facile at the 5-position, including [[nitration]] and halogenation.<ref name="BrownPyrimidines1994"/>{{rp|4–8}}

Reduction in [[resonance stabilization]] of pyrimidines may lead to addition and ring cleavage reactions rather than substitutions. One such manifestation is observed in the [[Dimroth rearrangement]].

Pyrimidine is also found in [[meteorite]]s, but scientists still do not know its origin. Pyrimidine also [[photolysis|photolytically]] decomposes into [[uracil]] under [[ultraviolet]] light.<ref name="pmid19778279">{{cite journal |last1=Nuevo |first1=M. |last2=Milam |first2=S. N. |last3=Sandford |first3=S. A. |last4=Elsila |first4=J. E. |last5=Dworkin |first5=J. P. |title=Formation of uracil from the ultraviolet photo-irradiation of pyrimidine in pure H<sub>2</sub>O ices |journal=Astrobiology |volume=9 |issue=7 |pages=683–695 |year=2009 |pmid=19778279 |doi=10.1089/ast.2008.0324|bibcode = 2009AsBio...9..683N }}</ref>

== 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 | bibcode = 2006JAChS.12814254M }}</ref>

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

==Reactions==
Because of the decreased basicity compared to pyridine, electrophilic substitution of pyrimidine is less facile. [[Protonation]] or [[alkylation]] typically takes place at only one of the ring nitrogen atoms. Mono-''N''-oxidation occurs by reaction with peracids.<ref name="JouleMills5th"/>{{rp|253–254}}

[[Electrophilic]] ''C''-substitution of pyrimidine occurs at the 5-position, the least electron-deficient. [[Nitration]], [[nitrosation]], [[azo coupling]], [[halogen]]ation, [[sulfonation]], [[formyl]]ation, hydroxymethylation, and aminomethylation have been observed with substituted pyrimidines.<ref name="BrownPyrimidines1994"/>{{rp|9–13}}

[[Nucleophilic]] ''C''-substitution should be facilitated at the 2-, 4-, and 6-positions but there are only a few examples. Amination and hydroxylation have been observed for substituted pyrimidines. Reactions with Grignard or alkyllithium reagents yield 4-alkyl- or 4-aryl pyrimidine after aromatization.<ref name="BrownPyrimidines1994"/>{{rp|14–15}}

Free radical attack has been observed for pyrimidine and photochemical reactions have been observed for substituted pyrimidines.<ref name="BrownPyrimidines1994"/>{{rp|15–16}} Pyrimidine can be hydrogenated to give tetrahydropyrimidine.<ref name="BrownPyrimidines1994"/>{{rp|pages=17}}

== Derivatives ==
{| class="wikitable centered" style="text-align:center" border="1" cellpadding="3"
|+ Pyrimidine derivatives
! Formula !! Name !! Structure !! N1 !! N3 !! C2 !! C4 !! C5 !! C6
|-
| C<sub>4</sub>H<sub>4</sub>N<sub>2</sub>O || [[Pyrimidone|2-Pyrimidone]] ||rowspan=8| [[File:Pyrimidin num.svg|75px|class=skin-invert-image]] || -H ||  || =O || -H || –H || –H
|-
| C<sub>4</sub>H<sub>4</sub>N<sub>2</sub>O || [[Pyrimidone|4-Pyrimidone]] ||  || –H || -H || =O || –H || –H
|-
| C<sub>4</sub>H<sub>5</sub>N<sub>3</sub>O || [[cytosine]] || -H ||  || =O || –NH<sub>2</sub> || –H || –H
|-
| C<sub>4</sub>H<sub>4</sub>N<sub>2</sub>O<sub>2</sub> || [[uracil]] || -H || –H || =O || =O || –H || –H
|-
| C<sub>4</sub>H<sub>3</sub>FN<sub>2</sub>O<sub>2</sub>|| [[fluorouracil]] || -H || –H || =O || =O || –F || –H
|-
| C<sub>5</sub>H<sub>6</sub>N<sub>2</sub>O<sub>2</sub> || [[thymine]] || -H || –H || =O || =O || –CH<sub>3</sub> || –H
|-
|C<sub>4</sub>H<sub>4</sub>N<sub>2</sub>O<sub>3</sub>  || [[barbituric acid]] || -H || –H || =O || =O || –H || =O
|-
| C<sub>5</sub>H<sub>4</sub>N<sub>2</sub>O<sub>4</sub> || [[orotic acid]] || -H || –H || =O || =O || –H || -COOH
|}

=== Nucleotides ===
[[File:Blausen 0324 DNA Pyrimidines.png|thumb|250px|The pyrimidine nitrogen bases found in [[DNA]] and [[RNA]].]]
Three [[nucleobase]]s found in [[nucleic acid]]s, [[cytosine]] (C), [[thymine]] (T), and [[uracil]] (U), are pyrimidine derivatives:
:{|
|-
| [[Image:Cytosine chemical structure.png|left|101px|class=skin-invert-image|Chemical structure of cytosine]] || [[Image:Thymine chemical structure.png|left|127px|class=skin-invert-image|Chemical structure of thymine]] || [[Image:Uracil chemical structure.png|left|102px|class=skin-invert-image|Chemical structure of uracil]]
|-
| {{center|Cytosine ('''C''')}} || {{center|Thymine ('''T''')}} || {{center|Uracil ('''U''')}}
|}

In [[DNA]] and [[RNA]], these bases form [[hydrogen bond]]s with their [[complementarity (molecular biology)|complementary]] [[purine]]s. Thus, in DNA, the [[purines]] [[adenine]] (A) and [[guanine]] (G) pair up with the pyrimidines thymine (T) and cytosine (C), respectively.

In [[RNA]], the complement of [[adenine]] (A) is [[uracil]] (U) instead of [[thymine]] (T), so the pairs that form are [[adenine]]:[[uracil]] and [[guanine]]:[[cytosine]].

Very rarely, thymine can appear in RNA, or uracil in DNA, but when the other three major pyrimidine bases are represented, some minor pyrimidine bases can also occur in [[nucleic acids]]. These minor pyrimidines are usually [[Methylation|methylated]] versions of major ones and are postulated to have regulatory functions.<ref>{{cite book|last1=Nelson |first1=David L. |first2=Michael M. |last2=Cox |title=Principles of Biochemistry |edition=5th |publisher=W. H. Freeman |date=2008 |pages=272–274 |isbn=978-1429208925}}</ref>

These hydrogen bonding modes are for classical Watson–Crick [[base pair]]ing. Other hydrogen bonding modes ("wobble pairings") are available in both DNA and RNA, although the additional 2′-hydroxyl group of [[RNA]] expands the configurations, through which RNA can form hydrogen bonds.<ref>{{Cite journal|last1=PATIL|first1=SHARANABASAPPA B.|last2=P.|first2=GOURAMMA|last3=JALDE|first3=SHIVAKUMAR S.|title=Medicinal Significance of Novel Coumarins: A Review|date=2021-07-15|journal=International Journal of Current Pharmaceutical Research|pages=1–5|doi=10.22159/ijcpr.2021v13i4.42733|s2cid=238840705|issn=0975-7066|doi-access=free}}</ref>

==Theoretical aspects==
In March 2015, [[NASA Ames]] scientists reported that, for the first time, complex [[DNA]] and [[RNA]] [[organic compound]]s of [[life]], including [[uracil]], [[cytosine]] and [[thymine]], have been formed in the laboratory under [[outer space]] conditions, using starting chemicals, such as pyrimidine, found in [[meteorite]]s. Pyrimidine, like [[polycyclic aromatic hydrocarbons]] (PAHs), the most carbon-rich chemical found in the [[universe]], may have been formed in [[red giant]]s or in [[Cosmic dust|interstellar dust]] and gas clouds.<ref name="NASA-20150303">{{cite press release |last=Marlaire |first=Ruth |title=NASA Ames reproduces the building blocks of life in laboratory |url=http://www.nasa.gov/content/nasa-ames-reproduces-the-building-blocks-of-life-in-laboratory |date=3 March 2015 |publisher=[[NASA]] |access-date=5 March 2015 }}</ref><ref name=Nuevo>{{cite journal |last1=Nuevo |first1=M.|last2=Chen |first2=Y. J.|last3=Hu |first3=W. J.|last4=Qiu |first4=J. M.|last5=Wu |first5=S. R.|last6=Fung |first6=H. S.|last7=Yih |first7=T. S.|last8=Ip |first8=W. H.|last9=Wu |first9=C. Y. R. |title=Photo-irradiation of pyrimidine in pure H<sub>2</sub>O ice with high-energy ultraviolet photons |year=2014 |journal=Astrobiology |volume=14 |issue=2|pages=119–131|url=http://www.astrochemistry.org/docs/Nuevo%202014%20H2O.pdf |doi=10.1089/ast.2013.1093|pmid=24512484|pmc=3929345|bibcode=2014AsBio..14..119N}}</ref><ref name=Sanford>{{cite book|last1=Sandford |first1=S. A. |last2=Bera |first2=P. P. |last3=Lee |first3=T. J. |last4=Materese |first4=C. K. |last5=Nuevo |first5=M. |title=Photosynthesis and photo-stability of nucleic acids in prebiotic extraterrestrial environments |date=6 February 2014 |volume=356 |url=http://www.astrochemistry.org/docs/2014%20Sandford%20et%20al.-ToCC%20Chapter%20on%20Nucleobases-Ch.14.pdf |pages=123–164 |doi=10.1007/128_2013_499 |pmid=24500331 |pmc=5737941 |series=Topics in Current Chemistry |bibcode=2014ppna.book..123S |isbn=978-3-319-13271-6 }}, also published as {{cite book |chapter=14: Photosynthesis and photo-stability of nucleic acids in prebiotic extraterrestrial environments |title=Photoinduced phenomena in nucleic acids |editor1=Barbatti |editor1-first=M. |editor2=Borin |editor2-first=A. C. |editor3=Ullrich |editor3-first=S. |publisher=Springer-Verlag |location=Berlin, Heidelberg |page=499 }}</ref>

===Prebiotic synthesis of pyrimidine nucleotides===
In order to understand how [[life]] arose, knowledge is required of the chemical pathways that permit formation of the key building blocks of life under plausible [[abiogenesis|prebiotic conditions]].  The [[RNA world]] hypothesis holds that in the [[primordial soup]] there existed free-floating [[ribonucleotide]]s, the fundamental molecules that combine in series to form [[RNA]].  Complex molecules such as RNA must have emerged from relatively small molecules whose reactivity was governed by physico-chemical processes.  RNA is composed of pyrimidine and [[purine]]  nucleotides, both of which are necessary for reliable information transfer, and thus natural selection and Darwinian [[evolution]].  Becker et al. showed how pyrimidine [[nucleoside]]s can be synthesized from small molecules and [[ribose]], driven solely by wet-dry cycles.<ref>Becker S, Feldmann J, Wiedemann S, Okamura H, Schneider C, Iwan K, Crisp A, Rossa M, Amatov T, Carell T. Unified prebiotically plausible synthesis of pyrimidine and purine RNA ribonucleotides. Science. 2019 Oct 4;366(6461):76-82. doi: 10.1126/science.aax2747. PMID 31604305</ref> Purine nucleosides can be synthesized by a similar pathway.  5’-mono-and diphosphates also form selectively from phosphate-containing minerals, allowing concurrent formation of [[polynucleotide|polyribonucleotides]] with both the pyrimidine and purine bases.  Thus a reaction network towards the pyrimidine and purine RNA building blocks can be established starting from simple atmospheric or volcanic molecules.

== See also ==
{{Div col|colwidth=20em}}
* [[ANRORC mechanism]]
* [[Purine]]
* [[Pyrimidine metabolism]]
* [[Simple aromatic ring]]s
* [[Transition (genetics)|Transition]]
* [[Transversion]]
{{div col end}}

== References ==
{{Reflist|30em}}

{{Nucleobases, nucleosides, and nucleotides}}
{{Molecules detected in outer space}}
{{Purinergics}}
{{Simple aromatic rings}}

{{Authority control}}

[[Category:Biomolecules]]
[[Category:Pyrimidines| ]]
[[Category:Aromatic bases]]
[[Category:Simple aromatic rings]]
[[Category:Substances discovered in the 19th century]]