Pyridines annelated/substituted

The applied Gould-Jacobs reaction is very often used to prepare angularly annelated pyridine-ring-substituted imidazoquinolines in inert media under conditions of thermal cyclocondensation, for example at temperatures above 250°C. 

Pyridine annelation.1 1,2,4-Triazine can function as a reactive azadiene in Diels-Alder reactions with enamines, particularly pyrrolidine enamines, to form substituted pyridines. 

These results show that inverse Diels-Alder reactions of pyrimidines open an easy access to a number of differently substituted pyridines and especially to compounds, in which the carbocyclic ring and the heterocyclic rings are annelated on the b position of pyridine. An interesting illustrating example... 

Fluoropyridines form valuable starting materials for a range of disubstituted pyridines because, after lithiation, nucleophilic substitution of fluoride (sometimes via the N-oxide) can be used to introduce, say, N or O substituents as in 191 and 192 (Scheme 96). Subsequent annelations can allow complex polycyclic heteroaromatics to be constructed. ... 

The electrochemical generation of a nitrilimine provides an entrance to a wide range of heterocyclic systems via anodic oxidation of aldehyde hydra-zones. The same reaction was used for annelation of various heterocyclic systems,86 e.g., substituted pyridines, quinolines, isoquinolines, indoles, imidazoles, benzimidazoles, and benzotriazoles. 

In the annelation of pyrazole-3 (or 5)-acetonitriles or -acetic acids, a cyano or carboxamido substituent in the 4-position is necessary to supply the nitrogen atom of the pyridine ring. The majority of reports concern the formation of 2-substituted products. Thus cyclization of the nitriles 142a... 

Annelation has also been achieved by N-amination of appropriate pyridines. For example, mesitylaminosulfonic acid converted 206 (R = Me, Ph, OEt) to the 2-substituted pyrazolo[l,5-a]pyridines 207 (R = H, Me, OH).165 166 Ylides were not detected. 

The imidazolyl-annelated dihydroisoquinoline 78 was accessible from the cyclization of imidazole 79. The outcome of intramolecular substitutions on pyridines turned out to be strongly dependent on the linker between the aromatic cores (Scheme 30). With a c/.v-configured alkene in place, as in 80, the expected benzoisoquinoline 81 was isolated in excellent yield. The frans-configured alkene and the saturated C2-alkane were shown to be less suitable tethers due to the formation of side products. 

Since there are no extensive studies on the relative aromaticity of the heterocycles covered in this chapter, the relative order of aromaticity of these systems has been gleaned from disparate studies. A priori, the combined effects of the 7i-electron-deficient five-membered heterocycles annelated to a pyridine nucleus provides a series of bicyclic heterocycles with low reactivity towards electrophiles. In the presence of suitable leaving groups, they are prone to undergo nucleophilic substitution. Since these heterocycles are readily obtained from either appropriately substituted pyridines or five-membered heterocycles, methods for direct functionalization of the parent heterocycles are not frequently studied. Based on the diversity of reactions these heterocycles undergo, it can be inferred that the pyridofuroxans are the least aromatic. 

Annelated and Substituted Pyridines by a Consecutive 4CR of (Hetero)aryI Halides, Propargyl Alcohols, Enamines, and Ammonium Chloride... 

Scheme 55 Mechanistic rationalization of the Cl-cycloaddition-cyclocondensation sequence to annelated and substituted pyridines 99-102...

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-... 

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