ABSTRACT
The presence of halogen substituents, which have a base-weakening effect and are only weakly deactivating, can allow substitution to take place in a different way by allowing an appreciably larger concentration of the un-protonated pyridine to be present. Since the resonance stabilisation of the bicyclic aromatic is considerably less than twice that of either benzene or pyridine, the loss in resonance stabilisation in proceeding from the bicyclic system to the intermediate is considerably less than in going from pyridine to an intermediate adduct. Repulsion between the electrons in the orbital of the ‘anion’ and an adjacent heteroatom lone pair has a destabilising influence. Lithiations are normally carried out with alkyllithiums or lithium amides. n-Butyllithium is the most widely used alkyllithium but t-butyllithium and occasionally s-butyllithium are used when more powerful reagents are required. The preparation of lithiated derivatives of six-membered heterocycles like pyridines, quinolines and diazines overcome the problem that they are susceptible to nucleophilic addition/substitution by the lithium reagents.
