Heterocycles Containing More Than Two Hetero Atoms

In systems which contain more than two hetero atoms in the same ring we find the trends in properties, which this book has described, taken to further extremes. In particular, the additional hetero atoms, in both six- and five-membered systems, lead to a suppression of electrophilic substitution and a slowing of electrophilic addition to nitrogen. On the other hand, further increases in tendencies for nucleophilic substitution and addition, and in the five-membered compounds, further increases in acidities of A -hydrogen are found. 

Multihetero atom heterocycles are comparatively rare in nature, dendrodoine, a cytotoxic substance from a marine tunicate, is an example, however in medicinal chemistry they are of considerable significance Alprazolam is a major drug for the treatment of anxiety, Acetazolamide is an inhibitor of the enzyme carbonic anhydrase and is used principally for the treatment of glaucoma, and Fluconazole, is an antifungal agent. 

Analogues of the pyrimidine nucleosides have been extensively studied 5-Azacytidine is antileukemic and Ribavirin, an antiviral agent, is used in the treatment of lung infections in infants. Lamotrigine is used for the treatment of epilepsy. Melamine, which on condensation with formaldehyde produces the melamine resins well known in kitchen utensils, is an important industrial intermediate. 

The triazoles are numbered to indicate the relative positions of the nitrogen atoms, tetrazole and pentazole are unambiguous names. 1,2,3-Triazoles are surprisingly stable, when one considers that they contain three directly-linked nitrogen atoms, but on flash vacuum pyrolysis at 500 °C they do lose nitrogen to give 2. f-azirines, 

The additional hetero atoms make these systems less basic but more acidic than comparable 1,2- and 1,3-azoles. Each is subject to the same kind of tautomerism as discussed for the 1,2- and 1,3-azoles (section 21.1.1.1), in which the tautomers are equivalent (not shown) but also, in these systems, to tautomerism which generates different arrangements. 

HETEROCYCLES CONTAINING MORE THAN TWO HETERO ATOMS 

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Heterocycles containing more than two hetero atoms... 

Compounds that have one or more atoms other than carbon in the ring are heterocyclic. Hetero-cycUc compounds containing two or more nitrogen atoms are required for the transmission of genetic information. DNA (deoxyribonucleic acid) and RNA (ribonucleic acid) contain substituted pyrimidine and purine rings. 

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