Substitution, electrophilic fused ring aromatics

As discussed in the theoretical section (4.04.1.2.1), electrophilic attack on pyrazoles takes place at C-4 in accordance with localization energies and tt-electron densities. Attack in other positions is extremely rare. This fact, added to the deactivating effect of the substituent introduced in the 4-position, explains why further electrophilic substitution is generally never observed. Indazole reacts at C-3, and reactions taking place on the fused ring will be discussed in Section 4.04.2.3.2(i). Reaction on the phenyl ring of C- and A-phenyl-pyrazoles will be discussed in Sections 4.04.2.3.3(ii) and 4.04.2.3.10(i), respectively. The behaviour of pyrazolones is quite different owing to the existence of a non-aromatic tautomer. 

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. 

Electrophilic aromatic substitution of other benzo-fused v-deficient systems generally follows predictable pathways. Thus, benzopyrylium salts are in general resistant to electrophilic substitution even in the benzo-fused ring. Chromones behave somewhat similarly, although substitution can be effected under forcing conditions. Coumarins, on the other hand, undergo nitration readily in the 6-position while bromination results in substitution at the 3-position as a consequence of addition-elimination. 

The effects of substituent groups in the benzo-fused ring on the ease of electrophilic aromatic substitution are essentially identical to those of the same substituent groups in benzene, so electron-donating groups facilitate reaction while electron-withdrawing groups... 

Electrophilic Substitution Reactivity Much of the electrophilic reactivity of aromatics is described in great detail in a comprehensive recent book of Taylor [10]. We shall focus attention on the electrophilic substitution reactivity of annelated benzenes and try to interpret the orientational ability of fused small rings. For this purpose we consider here Wheland transition states of the electrophilic substitution reactions. It is also convenient to take the proton as a model of the electrophilic reagent. In order to delineate rehybridization and 7r-electron localization effects, let us consider a series of angularly deformed benzenes (Fig. 21), where two vicinal CH bonds bent toward each other mimick a fused small ring. Angles c of 110° and 94° simulate five and four membered... 

Polycyclic benzenoid hydrocarbons contain two or more fused benzene rings fused rings share two adjacent carbons. Polycychc benzenoid hydrocarbons undergo electrophilic aromatic substitution reactions. Naphthalene undergoes irreversible substitution predominantly at the 1-position and reversible substitution predominantly at the 2-position. The nature of the substituent determines which ring of a substi-tuted-naphthalene undergoes electrophilic substitution. 

An alternate route to fused ring pyrroles involves an interesting cyclization of (5-N-pyrrolyl-2-hydroxypentyl)cobaloxime (31), which proceeds by intramolecular electrophilic aromatic substitution of a cobaloxime n-cation onto the pyrrole ring to provide 6-exo cyclization product 32 enroute to a formal synthesis of (-)-tashiromine (33) <97TL7007>. 

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-... 

The polycyclic aromatic hydrocarbons such as naphthalene, anthracene, and phenan-threne undergo electrophilic aromatic substitution and are generally more reactive than benzene. One reason is that the activation energy for formation of the c-complex is lower than for benzene because more of the initial resonance stabilization is retained in intermediates that have a fused benzene ring. 

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