6- Bromo-2-chloroquinoline, formation

Under conditions more similar to those of the Reimer-Tiemann reaction 3-bromopyridine was obtained from pyrrole and bromo-form. Treatment of pyrrole with chloroform and aqueous alkali gave pyrrole-2-aldehyde curiously, the formation of 3-chloropyridine under these conditions does not appear to have been reported, in spite of being frequently quoted. However, indole gave both indole-3-aldehyde and 3-chloroquinoline under these conditions [Eq. (10)]. 

Nucleophilic substitution most readily occurs at the 2- and 4-position of the more electron-deficient heterocyclic ring of quinolines. However, SNAr reactions at the carbocyclic ring can occur, mainly at positions 5 and 7. 5,7-Dibromo-8-hydroxyquinoline, 5-bromo-8-hydroxyquinoline, and 7-bromo-8-hydroxy-5-methylquinoline undergo conversion to the corresponding chloroquinolines on treatment with neat pyridine hydrochloride at 220 °C in a process that is postulated to proceed via the formation of stabilized Meisenheimer complexes <1996TL6695> (Equations 20 and 21). 

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