ABSTRACT
The mechanism for nucleophilic substitution is similar to that for electrophilic aromatic substitutions, except that an anionic rather than a cationic intermediate is involved. Since hydroxide is a nucleophilic reagent, the order of decreasing reactivity reflects increasing electron density and chlorodinitrobenzene is the most reactive. Nucleophilic substitution at the 1-position is favoured in isoquinoline for two reasons. First, attack at this site produces an intermediate in which the negative charge resides mainly on nitrogen, which is more electronegative than carbon. Second, two canonical structures have retained benzenoid character; this provides a more stable intermediate and lower energy transition to substitution than is seen at the 3-position, where only one canonical structure has benzenoid character. The aromatic ring is activated to nucleophilic attack by the appropriately placed electron-withdrawing nitro groups, and substitution with hydrazine completes the synthesis. The nucleophilic substitution is carried out in an excess of hydrazine to avoid the product undergoing further reaction with substrate.
