Ring-deactivating groups

Deactivating group (Section 16.4) An electron-withdrawing substituent that decreases the reactivity of an aromatic ring toward electrophilic aromatic substitution. 

Most electrophilic substitutions in benzimidazole (31 R = H) occur primarily in the 5-position. In multiple bromination the order followed, 5 > 7 > 6,4 > 2, parallels molecular orbital calculations. In benzimidazole itself the 4(7)- and 5(6)-positions are tautomerically equivalent. Fusion of a benzene ring deactivates C-2 to electrophilic attack to such an extent that it is around 5000 times less reactive than the 2-position of imidazole. Strong electron donors at C-5 direct halogenation to the 4-position, whereas electron-withdrawing groups favor C-4 or C-6 substitution (84MI21). 

For substituted benzenes, ring activators (electron-releasing groups) increase sensitivity and ring deactivators (electron-withdrawing groups) decrease sensitivity (exception halogenated benzenes)... 

Usual problems for the application of the PFR to organic synthesis are the occurrence of competing photochemical reactions (like trans-cis isomerization) or the presence of deactivating groups in the phenolic ring. In this subsection, it will be shown how these problems can be circumvented. 

For the aromatic carboxylic acids, substituents on the aromatic ring may also influence the acidity of the acid. Benzoic acid, for example, has = 4.3 x 10 . The placements of various activating groups on the ring decrease the value of the equilibrium constant, and deactivating groups increase the value of the equilibrium constant. Table 12-2 illustrates the influence of a number of para-substituents upon the acidity of benzoic acid. 

The most advantageous 2-pyridinecarbaldehyde derivative proved to be the acetal (example 3, Table 9) although, unlike the oxime, it was not commercially available. The acetal also usually afforded crystalline intermediate salts (181 Z = 0(CH2)20), but in addition made possible for the first time high temperature cyclization in PPA, permitting cyclization to rings deactivated by a nitro (example 25) or sulfo group (example 24). 

A deactivating group (electron-withdrawing) directs electrophiles into the other ring, usually at a positions. 

Side chain is oxidized when a deactivating group (NO,) rather than an activating group (NH,) is attached to ring. 

Know which groups are ring-activating, ring-deactivating, and explain why each group affects the rate of electrophilic aromatic substitution as it does. 

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