Electrophilic aromatic substitution meta-directing groups

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... 

Such a representation is referred to as a local ionization potential map. Local ionization potential maps provide an alternative to electrostatic potential maps for revealing sites which may be particularly susceptible to electrophilic attack. For example, local ionization potential maps show both the positional selectivity in electrophilic aromatic substitution (NH2 directs ortho para, and NO2 directs meta), and the fact that TC-donor groups (NH2) activate benzene while electron-withdrawing groups (NO2) deactivate benzene. 

Molten 2-ethoxybenzoic acid (7) was added to a mixture of chlorosulfonic acid and thionyl chloride while keeping the reaction temperature below 25 °C. In this straightforward electrophilic aromatic substitution the ethoxy group directs the electrophile towards the ortho and para position whereas the carboxylic acid directs meta giving an overall selectivity for the attack at C-5. It was necessary to add thionyl chloride to transform the intermediate sulfonic acid into... 

It has also been known for many years that sulfonyl groups, like carbonyl groups, promote the addition of nucleophilic reagents to carbon- carbon double bonds . The meta-directing properties of the S02Me group in electrophilic aromatic substitution were discovered in the mid-1920s . ... 

Two of three nitrofluorobenzene isomers react with methoxide, but the third is unreactive. Obtain energies of methoxide anion (at left), ortho, meta and para-nitrofluorobenzene, and the corresponding ortho, meta and para-methoxide anion adducts (so-called Meisenheimer complexes). Calculate the energy of methoxide addition to each of the three substrates. Which substrate is probably unreactive What is the apparent directing effect of a nitro group Does a nitro group have the same effect on nucleophilic aromatic substitution that it has on electrophilic aromatic substitution (see Chapter 13, Problem 4) Examine the structures and electrostatic potential maps of the Meisenheimer complexes. Use resonance arguments to rationalize what you observe. 

The isopropyl group is ortho, para-directing, and the nitro group is meta-directing. In this case their orientation effects reinforce each other. Electrophilic aromatic substitution takes place ... 

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 ... 

To determine why a CH3 group directs electrophilic aromatic substitution to the ortho and para positions, first draw all resonance structures that result from electrophilic attack at the ortho, meta, and para positions to the CH3 group. 

To determine why a nitro group (NO2) directs electrophilic aromatic substitution to the meta position, follow the same procedure. 

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

Ortho effect In electrophilic substitution of aromatic rings that already have two substituents, one of which is a meta directing group and that positioned meta to an ortho/para directing group, then the new substituent tends to go to the ortho position. In mass spectrometry, the ortho effect is the loss of a neutral species, usually a stable molecule such as water, derived from the ortho-... 

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