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Pyrimidine (; ) is an aromatic, heterocyclic, organic compound similar to pyridine (). One of the three (six-membered heterocyclics with two nitrogen atoms in the ring), it has nitrogen atoms at positions 1 and 3 in the ring. (2025). 9781405133005, Wiley. ISBN 9781405133005 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 derivatives: cytosine (C), thymine (T), and uracil (U).
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 and its reverse.
Electron lone pair availability (basicity) is decreased compared to pyridine. Compared to pyridine, N-alkylation and N-oxidation are more difficult. The pKa 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. 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.
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 , but scientists still do not know its origin. Pyrimidine also photolysis decomposes into uracil under ultraviolet light.
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.
As a class, pyrimidines are typically synthesized by the principal synthesis involving cyclization of β-dicarbonyl compounds with N–C–N compounds. Reaction of the former with to give 2-substituted pyrimidines, with urea to give 2-, and to give 2- are typical.
Pyrimidines can be prepared via the Biginelli reaction and other multicomponent reactions. Many other methods rely on condensation of with diamines for instance the synthesis of 2-thio-6-methyluracil from thiourea and ethyl acetoacetate or the synthesis of 4-methylpyrimidine with 4,4-dimethoxy-2-butanone and formamide.
A novel method is by reaction of N-vinyl and N-aryl with under electrophilic activation of the amide with 2-chloro-pyridine and trifluoromethanesulfonic anhydride:
Electrophilic C-substitution of pyrimidine occurs at the 5-position, the least electron-deficient. Nitration, nitrosation, azo coupling, , sulfonation, , hydroxymethylation, and aminomethylation have been observed with substituted pyrimidines.
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.
Free radical attack has been observed for pyrimidine and photochemical reactions have been observed for substituted pyrimidines. Pyrimidine can be hydrogenated to give tetrahydropyrimidine.
| + Pyrimidine derivatives ! Formula !! Name !! Structure !! N1 !! N3 !! C2 !! C4 !! C5 !! C6 |
| –H |
| –H |
| –H |
| –H |
| –H |
| –H |
| =O |
| -COOH |
In DNA and RNA, these bases form with their complementary . 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 versions of major ones and are postulated to have regulatory functions. (2025). 9781429208925, W. H. Freeman. ISBN 9781429208925
These hydrogen bonding modes are for classical Watson–Crick . 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.
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