Pyrimidine

chembox
ImageFile=Pyrimidine chemical structure.pngImageSize=368px
IUPACName=pyrimidine
OtherNames=
Section1= Chembox Identifiers
CASNo=289-95-2
PubChem=9260
SMILES=C1=CN=CN=C1
MeSHName=pyrimidine
Section2= Chembox Properties
Formula=C₄H₄N₂
MolarMass=80.088
Appearance=
Density=
MeltingPt=20–22 °C
BoilingPt=123–124 °C
Solubility=
Section3= Chembox Hazards
MainHazards=
FlashPt=
Autoignition=

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. [Heterocyclic Chemistry (3rd Edition) Thomas. L. Gilchrist ISBN 0-582-27843-0 ] It is isomeric with two other forms of diazine.

Nucleotides

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

In DNA and RNA, these bases form hydrogen bonds with their complementary purines. Thus the purines adenine (A) and guanine (G) pair up with the pyrimidines thymine (T) and cytosine (C), respectively.

In RNA, the complement of A is U instead of T and the pairs that form are adenine:uracil and guanine:cytosine.

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.Fact|date=February 2007

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 [Organic Syntheses, Coll. Vol. 4, p.182 (1963); Vol. 35, p.34 (1955) [http://www.orgsynth.org/orgsyn/pdfs/CV4P0182.pdf Link] ] and its reverse. [Organic Syntheses, Coll. Vol. 4, p.336 (1963); Vol. 35, p.58 (1955) [http://www.orgsynth.org/orgsyn/pdfs/CV4P0336.pdf Link] ] 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.

Organic synthesis

Pyrimidines can also be prepared in 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 [Organic Syntheses, Coll. Vol. 4, p.638 (1963); Vol. 35, p.80 (1955) [http://www.orgsynth.org/orgsyn/pdfs/CV4P0638.pdf Link] ] or the synthesis of 4-methylpyrimidine with 4,4-dimethoxy-2-butanone and formamide [Organic Syntheses, Coll. Vol. 5, p.794 (1973); Vol. 43, p.77 (1963) [http://www.orgsynth.org/orgsyn/pdfs/CV5P0794.pdf Link] ] .

A novel method is by reaction of certain amides with carbonitriles under electrophilic activation of the amide with 2-chloro-pyridine and trifluoromethanesulfonic anhydride ["Single-Step Synthesis of Pyrimidine Derivatives" Mohammad Movassaghi and Matthew D. Hill J. Am. Chem. Soc.; 2006; 128(44) pp 14254 - 14255; (Communication) DOI|10.1021/ja066405m] :

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See also

* Purine
* Pyrimidine biosynthesis
* Pyrazine, an analog with the nitrogen atoms in positions 1 and 4
* Pyridazine, an analog with the nitrogen atoms in positions 1 and 2
* Simple aromatic rings
* ANRORC mechanism
*

References