SolutionsFused heterocycles: indole and quinoline
Exercise 1
Why does pyrrole react with electrophiles at C2 but indole at C3? Draw the σ-complex for attack at C3 of indole and explain what would happen to the benzene ring on attack at C2.
In indole, attack at C3 gives a cation at C2 that the nitrogen lone pair stabilizes directly (an iminium ion), and the benzene keeps its sextet intact. On attack at C2, the charge is left at C3; to delocalize it onto nitrogen the π electrons of the benzene must be used, losing its aromaticity. In pyrrole there is no benzene to protect, and attack at C2, with more resonance forms, wins.
Exercise 2
Give the product of quinoline with: a) HNO3/H2SO4 at 0 °C; b) NaNH2 in refluxing toluene; c) basic KMnO4. Justify in each case which ring reacts.
a) A mixture of 5- and 8-nitroquinoline: in acid, the nitrogen is protonated and the pyridine ring is strongly deactivated, so the benzene ring reacts, at the positions that keep an intact sextet in the σ-complex. b) 2-Aminoquinoline (Chichibabin): amide attacks the π-deficient ring at the position next to nitrogen. c) Pyridine-2,3-dicarboxylic acid: the oxidant destroys the more electron-rich ring, the benzene ring.