Key to Success Synthetic Strategies Toward Substituted Benzenes

In Summary Electrophilic aromatic substitution of multiply substituted benzenes is controlled by the strongest activator and, to a certain extent, by steric effects. The greatest product selectivity appears when there is only one dominant activator or when the substitution pattern minimizes the number of isomers that can be formed. 

KEYS TO SUCCESS SYNTHETIC STRATEGIES TOWARD SUBSTITUTED BENZENES 

The easiest way to introduce a nitrogen substituent into an arene is by nitration. Yet many desired substituted benzenes have amino functions. Moreover, the nitro group is a meta director, poorly suited for preparing ortho, para-substituted systems. A solution to these problems is provided by the availability of simple reagents that reversibly convert -NO2, a meta director, into -NH2, an ortho, para director. Thus, the nitro group can be reduced to the amino function by either catalytic hydrogenation or exposure to acid in the presence of active metals such as iron or zinc amalgam. The reverse, oxidation of aniline to nitrobenzene, employs trifluoroperacetic acid. 

Interconversion of Nitro (Meta Director) with Amino (Ortho, Para Director) 

For an example of applying this capability in synthetic strategy, consider the preparation of 3-bromobenzenamine. Direct bromination of benzenamine (aniline) leads to complete ortho and para substitution (Section 16-3) and is therefore useless. However, bromination of nitrobenzene allows preparation of 3-bromonitrobenzene, which can be converted into the required target molecule by reduction. The outcome is a benzene derivative in which two ortho, para directors emerge positioned meta to each other. 

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Keys to Success Synthetic Strategies Toward Substituted Benzenes CHAPTER 16... 

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