Fused pyridines, aromaticity

Azonia substitution at a naphthalene bridgehead position gives the quinolizinium ion (16). Oxonia substitution, elsewhere, forms the 1- and 2-benzopyrylium ions (17) and (18). The two most well-known monoaza systems with three aromatic fused rings are acridine (19), derived structurally from anthracene, and phenanthridine (20), an azaphenanthrene. The better-known diaza systems include phenazine (21) and 1,10-phenanthroline (22), while systems with three linearly fused pyridine rings are called anthyridines, e.g. the 1,9,10-isomer (23). 

The dominant influence of secondary orbital interactions is observed in the reaction of the cyclopenta[e][l,2,4]triazine ester (415) witl the two enamines (416) and (417). In the first case the fused pyridine (418) was obtained directly in the latter the dihydropyridine (419) was isolated, and aromatized, by iV-oxidation and Cope elimination, to (420) <82CB2807>. 

The presence in the aminoazole molecule of nonequivalent endocyclic reaction centers can lead to several directions of the interaction as is observed in the case of multicomponent treatment of 5-aminopyrazoles 220-222 with dime-done 200 and aldehydes 201. In [189, 190, 191] it was shown that reactions of amines 220 and 221 with 1,3-diketone 200 and aromatic aldehydes in boiling ethanol or DMF yielded fused pyridines 225 and 226 when R is CH3 irrespective of the electronic nature of the substituent Ar (Scheme 3.61). 

The most well-known monoaza aromatic systems with three six-membered rings are acridine 25 and phenanthridine 26 (Figure 3). Acridine derivatives were among the earliest antibacterial agents. The better known diaza systems include phenazine 27 and 1,10-phenanthroline 28. Systems with three linearly fused pyridine rings are called anthyr-idines, e.g., 29. A derivative of the tetraza ring system 30 is found in vitamin B2. 

Ring-fused pyridines of type 300 and 301 have been prepared by condensation of enamines with immonium salts170, and by reaction of morpholino enamines derived from a-pyridyl ketones with aromatic aldehydes and further treatment with ammonium acetate171,172, respectively. 

The dominant influence of secondary orbital interactions is apparent in the reaction of methyl cyclopenta[e]-l,2,4-triazine-3-carboxylate with enamines from 3,4-dihydronaphthalen-1 (2//)-or -2(l/f)-ones. In the case of the 3,4-dihydronaphthalen-2-amine the fused pyridine 24 is obtained directly using the 3,4-dihydronaphthalen-l-amine the dihydropyridine is isolated, but can be oxidized to give the aromatic pyridine 25 derivative via a Cope elimination.403... 

A general synthesis of c-fused pyridines under neutral conditions involves the thermolysis of vinyl azides, prepared from aromatic aldehydes that bear an ortho methyl group and ethyl azidoacetate. Thus thermolysis of the vinyl azide (151) from mesitaldehyde (150) gives the isoquinoline (152) in 45—50% yield (Scheme... 

Quinoline and isoquinoline, the two possible structures in which a benzene ring is annelated to a pyridine ring, represent an opportunity to examine the effect of fusing one aromatic ring to another. Clearly, both the effect the benzene ring has on the reactivity of the pyridine ring, and vice versa, and comparisons with the chemistry of naphthalene must be made. Thus the regiose-lectivity of electrophilic substitution, which in naphthalene is faster at an a-position, is mirrored in quinoline/isoquinoline chemistry by substitution at 5-... 

Heterocyclic amines are compounds that contain one or more nitrogen atoms as part of a ring. Saturated heterocyclic amines usually have the same chemistry as their open-chain analogs, but unsaturated heterocycles such as pyrrole, imidazole, pyridine, and pyrimidine are aromatic. All four are unusually stable, and all undergo aromatic substitution on reaction with electrophiles. Pyrrole is nonbasic because its nitrogen lone-pair electrons are part of the aromatic it system. Fused-ring heterocycles such as quinoline, isoquinoline, indole, and purine are also commonly found in biological molecules. 

---