Q4(b). 3-Bromoanisole and amide ion: benzyne regiochemistry

Introduction. Aryl halides without activating groups react with NH₂⁻ in liquid ammonia by elimination–addition: benzyne is formed first, and NH₂⁻ then adds to it. The positions of H removal and of NH₂⁻ addition are both controlled by the inductive effect of OMe.

Scheme: H-2 (between OMe and Br) is removed; NH₂⁻ adds meta to OMe.

1. Which benzyne. Two hydrogens are ortho to Br: H-2 (between OMe and Br) and H-4. H-2 is more acidic: both the -I effect of OMe and of Br act on it. Removal of H-2 and loss of Br⁻ give 3-methoxybenzyne (the triple bond between C-1 and C-2, OMe on C-3).
2. Where NH₂⁻ adds. Addition at C-1 places the new carbanion on C-2, ortho to OMe, where the -I effect of oxygen stabilises it (the sp² lone pair is in the ring plane, so resonance does not matter). Addition at C-2 would put the anion meta to OMe, far less stabilised.
3. Protonation by NH₃ gives the amine and regenerates NH₂⁻.
4. Both steps point the same way, so only one product forms: 3-methoxyaniline. The amino group enters at the carbon that carried Br (cine substitution does not happen here).

Conclusion. m-Anisidine (3-methoxyaniline) is the only product, via 3-methoxybenzyne: H-2 is removed because it is flanked by two -I groups, and NH₂⁻ adds to C-1 so that the aryl anion sits ortho to OMe.

Application. The same inductive control gives m-anisidine from o-bromoanisole as well; benzyne chemistry is used to make meta-substituted anilines that electrophilic substitution cannot give.