Isoquinolines halo-, nucleophilic displacement

A significant difference in this typical behaviour applies to the isoquinoline 3-position - the special reactivity that the discussion above has developed for positions a to pyridine nitrogen, and that also applies to the isoquinofine 1-position, does not apply at C-3. In the context of nucleophilic displacements, for example, an intermediate for reaction of a 3-halo-isoquinoline cannot achieve delocalisation of negative charge onto the nitrogen unless the aromaticity of the benzene ring is disrupted. Therefore, such intermediates are considerably less stabilised and reactivity considerably tempered. 

An apparent exception to the relative unreactivity of 3-halo-isoquinolines is provided by the reaction of 3-bromoisoquinoline with sodium amide. Here, a different mechanism, known by the acronym ANRORC (Addition of Nucleophile, Ring Opening and Ring Closure), leads to the product, apparently of direct displacement, but in which a switching of the ring nitrogen to become the substituent nitrogen, has occurred. 

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