Electrophilic aromatic substitution ortho-para-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... 

The electrophile in the Friedel-Crafts acylation appears to be a large, bulky complex, such as R—C=0 A1C14. Para substitution usually prevails when the aromatic substrate has an ortho, para-directing group, possibly because the electrophile is too bulky for effective attack at the ortho position. For example, when ethylbenzene reacts with acetyl chloride, the major product is p-ethylacetophenone. 

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-... 

Resonance effects are the primary influence on orientation and reactivity in electrophilic substitution. The common activating groups in electrophilic aromatic substitution, in approximate order of decreasing effectiveness, are —NR2, —NHR, —NH2, —OH, —OR, —NO, —NHCOR, —OCOR, alkyls, —F, —Cl, —Br, —1, aryls, —CH2COOH, and —CH=CH—COOH. Activating groups are ortho- and para-directing. Mixtures of ortho- and para-isomers are frequently produced the exact proportions are usually a function of steric effects and reaction conditions. 

Anticipating the products of electrophilic aromatic substitution can be more difficult when two or more substituents compete for control. For example, both methyl and methoxy groups are ortho para directors, and compete for control in electrophilic substitution of 2-methylanisole. The reaction product depends on which substituent has the stronger directing influence. 

The hydroxyl group is a strongly activating, ortho- and para-directing substituent in electrophilic aromatic substitution reactions (Section 16.4). As a result, phenols are highly reactive substrates for electrophilic halogenation, nitration, sulfonation, and lTiedel-Crafts reactions. 

Example lO.Q Altliougli clilorine is an electron withdrawing group, yet it is ortho-, para- directing in electrophilic aromatic substitution reactions. Why ... 

The alkojq/ group (-OR) is ortho, para directing and activates the aromatic ring towards electrophilic substitution in the same way as in phenol. 

Table 8.1 Directing effects of substituents in electrophilic aromatic substitution Electron-releasing groups ortho and para directors...

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. 

Protecting the amino group of an arylamine in this way moderates its reactivity and permits nitration of the ring to be achieved. The acetamido group is activating toward electrophilic aromatic substitution and is ortho, para-directing. 

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 phenolic group is activating and ortho-para directing. The electrophilic substitution reactions in the nucleus in (a) nitrosation and nitration (b) halogenation and (c) acylation and alkylation, are therefore particularly facile, and various experimental procedures need to be adopted to control the extent of substitution (cf. substitution reactions of aromatic amines and their acylated derivatives, Sections 6.6.1 and 6.6.2, pp. 906 and 916 respectively). 

Electrophilic aromatic substitution in biphenyl is best understood by considering one ring as the functional group and the other as a substituent. An aryl substituent is ortho, para-directing. Nitration of biphenyl gives a mixture of o-nitrobiphenyl and p-nitrobiphenyl. 

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 ... 

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