Quinolines, alkylation sulfonation

Isoquinoline, like quinoline, is protonated and alkylated at the nitrogen atom, but electrophilic substitution in the benzene ring is also easily achieved (Scheme 3.14). Sulfonation with oleum gives mainly the 5-sulfonic acid, but fuming nitric acid and concentrated sulfuric acid at 0 C produce a 1 1 mixture of 5- and 8-nitroisoquinolines. Bromination in the presence of aluminium trichloride at 75 °C gives a 78% yield of 5-bromoisoquinoline. 

The lone-pair electron on the nitrogen is responsible for electrophilic reactions on its side. Thus, heterocyclic nitrogen atom of quinoline and isoquinolines react with electrophiles, as alkyl halides, alkyl sulfates, alkyl-toluene-p-sulfonates, etc., providing quinolinium and isoquinolinium salts. 

Keywords Alkyl hydroperoxides Amination Ammonia Benzimidazole Benzisoxazole Carbanions Heterocycles Hydroxylation Indole Nitro compounds Nucleophiles Nucleophilic substitution Oxidation Phenazine Potassium permanganate Pyridine Quinoline Sulfones Vicarious... 

A large variety of chloride or sulfonate-substituted heteroarenes can be subjected to iron-catalyzed cross-coupling. This holds true for pyridines, pyrimidines, triazines, quinolines, isoquinolines, carbazoles, purines, pyridazines, pyrazines, quinoxalines, quinazolines, uracils, thiophenes, and benzothiazoles. In the pyridine system the presence of leaving groups of different reactivity has been demonstrated to allow for sequential introduction of different alkyl groups (Scheme 4—220). ... 

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