Deactivating, Meta-Directing Substituents

When bromine is added to two beakers, one containing phenyl isopropyl ether and the other containing cyclohexene, the bromine color in both beakers disappears. What observation could you make while performing this test that would allow you to distinguish the alkene from the aryl ether  

Nitrobenzene is about 100,000 times less reactive than benzene toward electrophilic aromatic substitution. For example, nitration of nitrobenzene requires concentrated nitric and sulfuric acids at temperatures above 100°C. Nitration proceeds slowly, giving the meta isomer as the major product. 

These results should not be surprising. We have already seen that a substituent on a benzene ring has its greatest effect on the carbon atoms ortho and para to the substituent. An electron-donating substituent activates primarily the ortho and para positions, and an electron-withdrawing substituent (such as a nitro group) deactivates primarily the ortho and para positions. 

The EPM of nitrobenzene shows the aromatic ring to be electron-poor (blue tinge), consistent with the observation that nitrobenzene is deactivated toward reactions with electrophiles. 

This selective deactivation leaves the meta positions the most reactive, and meta substitution is seen in the products. Meta-directors, often called meta-allowing substituents, deactivate the meta position less than the ortho and para positions, allowing meta substitution. 

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Friedel-Crafts reactions are the slowest of the electrophilic aromatic substitution reactions. Therefore, if a benzene ring has been moderately or strongly deactivated— that is, if it has a meta-directing substituent—it will be too unreactive to undergo either Friedel-Crafts acylation or Friedel-Crafts alkylation. In fact, nitrobenzene is so unreactive that it is often used as a solvent for Friedel-Crafts reactions. 

Why IS there such a marked difference between methyl and trifluoromethyl substituents m their influence on electrophilic aromatic substitution s Methyl is activating and ortho para directing trifluoromethyl is deactivating and meta directing The first point to remember is that the regioselectivity of substitution is set once the cyclohexadienyl cation intermediate is formed If we can explain why... 

Our analysis of substituent effects has so far centered on two groups methyl and triflu oromethyl We have seen that a methyl substituent is activating and ortho para directing A trifluoromethyl group is strongly deactivating and meta directing What about other substituents ... 

The next group of substituents in Table 12 2 that we 11 discuss are the ones near the bottom of the table those that are meta directing and strongly deactivating... 

As Table 12 2 indicates a variety of substituent types are meta directing and strongly deactivating We have already discussed one of these the trifluoromethyl group Several of the others have a carbonyl group attached directly to the aromatic ring... 

Deactivating and meta directing These substituents are strongly electron withdrawing and destabilize carbocations They include... 

The entrance of a third or fourth substituent can be predicted by Beilstein s rule. If a substituent Z- enters into a compound C H XY, both X and Y exert an influence, but the group with the predominant influence directs Z- to the position it will occupy. Since all meta-directing groups are deactivating, it follows that ortho—para activating groups predominate when one of them is present on the benzene ring. 

The effect of substituents on the reactivity of heterocyclic nuclei is broadly similar to that on benzene. Thus meta-directing groups such as methoxycarbonyl and nitro are deactivating. The effects of strongly activating groups such as amino and hydroxy are difficult to assess since simple amino compounds are unstable and hydroxy compounds exist in an alternative tautomeric form. Comparison of the rates of formylation and trifiuoroacetylation of the parent heterocycle and its 2-methyl derivative indicate the following order of sensitivity to substituent effects furan > tellurophene > selenophene = thiophene... 

A more detailed exploration of the reactivity of biphenyl resolves the problem. The ra-phenyl substituent reduces the rate of substitution in the benzene nucleus (Table 7). Qualitatively, this effect is in agreement with the predictions based on the rate of solvolysis of ra-phenylphenyl-dimethylcarbinyl chloride (Brown and Okamoto, 1958) and with the expected electron-withdrawing properties of the phenyl group. The data conform to the Selectivity Relationship with reasonable precision (Fig. 31). In view of the activation of the ortho and para positions, direct evaluation of the partial rate factors for the deactivated meta position is not always possible. Hence, indirect kinetic procedures were employed in several cases, halogenation and acylation, to estimate the values. Graphical analysis of the data shows that mfb is independent of the reagent selectivity. Deviations from the relationship are no greater than for the ordinary side-chain reactions. 

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