Electrophilic aromatic substitution meta-directing substituents

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... 

Sometimes the orientation of two substituents m an aromatic compound precludes Its straightforward synthesis m Chloroethylbenzene for example has two ortho para directing groups m a meta relationship and so can t be prepared either from chloroben zene or ethylbenzene In cases such as this we couple electrophilic aromatic substitution with functional group manipulation to produce the desired compound... 

These polarizations are seen to be in the opposite direction to those in aniline (3.133), so that higher pi density remains at the Ci (junction) and C3 and C5 (meta) positions. These polarity shifts are again consistent with the well-known m-directing effect of nitro substituents in electrophilic aromatic substitution reactions, and the results are again quite independent of which starting Kekule structure is selected for the localized analysis.63... 

The situation is more complicated if there is more than one substituent on the benzene ring. However, it is usually possible to predict the major products that are formed in an electrophilic aromatic substitution reaction. When the substituents direct to the same position, the prediction is straightforward. For example, consider the case of 2-nitrotoluene. The methyl group directs to the positions ortho and para to itself—that is, to positions 4 and 6. The nitro group directs to positions meta to itself—that is, also to positions 4 and 6. When the reaction is run, the products are found to be almost entirely 2,4-dinitrotoluene and 2,6-dinitrotoluene, as expected ... 

Meta director (Section 18.7) A substituent on a benzene ring that directs a new group to the meta position during electrophilic aromatic substitution. 

Electrophilic aromatic substitution is a situation in which it is useful to discuss TS structure in terms of a reaction intermediate. The ortho, para, and meta directing effects of aromatic substituents were among the first structure-reactivity relationships to be developed in organic chemistry. Certain functional groups activate aromatic rings toward substitution and direct the entering electrophile to the ortho and para positions, whereas others are deactivating and lead to substitution in the meta position. The bromination of methoxybenzene (anisole), benzene, and nitrobenzene can serve as examples for discussion. 

The major advantage of thallation is orientational specificity. While thallation is essentially all para to alkyl groups, halides and alkoxy substituents, orientation is almost all ortho to a carboxyl or an ester substituent. We see that such orientation to ester and carboxyl substituents is unusual in that these groups are typically meta-directing in electrophilic aromatic substitution. This behavior can be attributed to an intramolecular interaction involving the electrophilic thallium and the carbonyl group which allows for facile ortho substitution. 

The synthesis of URB597 was extremely challenging, more so for the positions of its substituents than for their structure. Both groups are located in meta positions relative to the bond between the rings. Problem 39 revealed that phenyl rings as substituents are ortho, para directing. Therefore electrophilic aromatic substitution reactions performed on biphenyl cannot serve as an entry to the preparation of this important compound. 

Nitro groups are meta-directing. Both nitro groups of m-dinitrobenzene direct an incoming substituent to the same position in an electrophilic aromatic substitution reaction. Nitration of m-nitrobenzene yields 1,3,5-trinitrobenzene. 

---