Pyrimidine

Pyrimidine is a heterocyclic aromatic organic compound similar to benzene and pyridine, containing two nitrogen atoms at positions 1 and 3 of the six-member ring. It is isomeric with two other forms of diazine.

Nucleotides
Three nucleobases found in nucleic acids, cytosine (C), thymine (T), and uracil (U), are pyrimidine derivatives:


 * [[Image:Cytosine chemical structure.png|101px|Chemical structure of cytosine]] [[Image:Thymine chemical structure.png|127px|Chemical structure of thymine]][[Image:Uracil chemical structure.png|102px|Chemical structure of uracil]]

In DNA and RNA, these bases form hydrogen bonds with their complementary purines. 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. Other than the three major pyrimidine bases presented, some minor pyrimidine bases can also occur in nucleic acids. These minor pyrimidines are usually methylated versions of major ones and are postulated to have regulatory functions.

These hydrogen bonding modes are for classical Watson-Crick base pairing. 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.

Chemical properties
A pyrimidine has many properties in common with pyridine, as the number of nitrogen atoms in the ring increases the ring pi electrons become less energetic and electrophilic aromatic substitution gets more difficult while nucleophilic aromatic substitution gets easier. An example of the last reaction type is the displacement of the amino group in 2-aminopyrimidine by chlorine and its reverse. 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.

Compared to pyridine, N-alkylation and N-oxidation is more difficult, and pyrimidines are also less basic: The pKa value for protonated pyrimidine is 1.23 compared to 5.30 for pyridine.

Pyrimidine also is found in meteorites, although scientists still do not know its origin. Pyrimidine also photolytically decomposes into Uracil under UV light.

Organic synthesis
Pyrimidines can also be prepared within the laboratory by organic synthesis. One method is the classic Biginelli reaction. Many other methods rely on condensation of carbonyls with amines 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 certain amides with carbonitriles under electrophilic activation of the amide with 2-chloro-pyridine and trifluoromethanesulfonic anhydride :


 * [[Image:PyrimidineSynthAmideCarbonitrile.png|400px|Pyrimidine Synthesis Movassaghi 2006]]