Ortho-Bromoanisole

Bromoanisole. The competition between ortho and ipso attack (83) is also pertinent to the simultaneous nitration and transbromination of 4-bromoani-sole (Perrin and Skimer, 1971). Charge-transfer nitration leads to mixture of 2-nitro-4-bromoanisole and 2,4-dibromoanisole (and 4-nitroanisole), the relative amounts of which are equivalent to those obtained in the electrophilic nitration of 4-bromoanisole. 

Problem 11.28 How do the following observations support the benzyne mechanism (a) Compounds lacking ortho H s, such as 2,6-dimethylchlorobenzene, do not react, (t) 2,6-Dideuterobromobenzene reacts more slowly than bromobenzene. (c) o-Bromoanisole, o-CHjOC H Br, reacts with NaNH /NH, to form m-CHjOC H.NHj. 

When 2-bromoanisole (160) reacts with sodium amide (NaNHg) in liquid ammonia (at -33°C), a reaction occurs to give 2-aminoanisole (165) along with 3-aminoanisole (166). This appears to be a substitution reaction where a hydrogen is replaced by -NHg. However, substitution occurs at two different carbon atoms, so direct substitution is ruled out as a mechanism. To rationalize these experimental observations, first recognize that sodium amide is a powerful base, and an acid-base reaction removes the hydrogen atom ortho to the bromine to give 161. 

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