Orientation in aromatic substitution

We have shown how the combination of the u-electron system, R and S, may lead to different approximate values for a given hydrocarbon depending upon how R and S are chosen. With naphthalene, for example. 

Dewar uses these differences as a way of approximating localization energies. In other words, instead of calculating the ir—electron energy of naphthalene by the RS procedure, it is used to estimate the energy of the localized intermediates that corresponds to substitution at the 1 and 2 positions. The outcome is as follows (omitting the appropriate multiples of 

This method of calculating localization energies is very quick and easy, especially for complicated polycyclic alternant hydrocarbons. 

Estimate the order of ease of attack of NQz on each of the positions of the following substances by Dewar s procedure  

Use Dewar s method in combination with other more qualitative reasoning to estimate the relative ease of displacement of chlorine by ethoxide ion for the mono-chloroquinolines and the monochloroisoquinolines. 

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Resonance and induction have a marked effect on orientation in aromatic substitution. One would therefore expect some correlation between orientation in substitution and the electronic absorption spectra of benzene derivatives. In Table 5.4 the position of the 200 mp benzene band10 and the spectroscopic moments14 have been compared with the percentage of the meta isomer produced in nitration. A fair parallelism is apparent in the three columns. 

This procedure was used with considerable success by Wheland and Pauling in the first application of molecular orbital theory to predicting orientation in aromatic substitution. 

We can account for the electron-withdrawing and electron-releasing properties of groups on the basis of two factors inductive ects and resonance ects. We shall also see that these two factors determine orientation in aromatic substitution reactions. 

While at Leeds from 1924 to 1930, Ingold s laboratory focused on three main topics of research (1) the nature and mechanism of orienting effects of groups in aromatic substitution (mainly nitration) (2) the study of prototropic rearrangements (shifts of H+) and aniontropic rearrangements (shifts of anions) as the ionic mechanisms of tautomerism and (3) the effect of polar substituents on the velocity and orientation of addition reactions to unsaturated systems. One of Ingold s students at Leeds, John William Baker, wrote a widely read book on tautomerism. 16... 

N. Vass, "The Nature of the Alternating Effect in Carbon Chains. Pt. XXIII. Anomalous Orientation by Halogens, and Its Bearing on the Problem of the Ortho-Para-Ratio in Aromatic Substitution," JCS 131 (1928) 417425. 

The ratios of isomers formed in substitution reactions can be determined by spectroscopic means or by the analytical separation methods discussed in Section 9-2. We mainly are concerned in this chapter with the reactivity and orientation observed in aromatic substitution. 

It undergoes electrophilic substitution, chiefly at position 3, Account (a) for the aromatic properties of indole, and (b) for the orientation in electrophilic substitution. Hint See Sec. 30.9.)... 

The orientation of aromatic substitution reactions and chemical reactivities in general actually do not measure the effect of resonance alone upon a resting system but rather the combined operation of resonance and the polarizability of double bonds or conjugated systems (p. 28). For many reactions it is not necessary to consider each separately since polarizability simply intensifies the contribution of certain resonance structures. (For example, see p. 156.)... 

The principle enunciated above may be extended to obtain other polysubstituted phthalides. The substituents are chosen with due consideration of the trends in orientation in aromatic lithiation reactions. A list of substituted phthalides, synthesised by lithiation reaction, has recently been published... 

A very interesting observation is that incorporation of anihnes into coordination compounds does not affect the reactivity of the former towards bromination nor their orientation in the substitution . Palladium (ii) complexes of the type [Pd (aniline) 2 r2] show that the NH2 group favors ortho and para bromination even in strongly acid solution, where any comphcation due to partial dissociation should be absent. In order to account for these results, it seems that the coordination process may involve the p electrons of the nitrogen atom in some manner fundamentally different from that in aromatic ammonium compounds, i.e. that coordination does not impart a positive charge to the nitrogen of anihnes. 

A brief account of aromatic substitution may be usefully given here as it will assist the student in predicting the orientation of disubstituted benzene derivatives produced in the different substitution reactions. For the nitration of nitrobenzene the substance must be heated with a mixture of fuming nitric acid and concentrated sulphuric acid the product is largely ni-dinitrobenzene (about 90 per cent.), accompanied by a little o-dinitrobenzene (about 5 per cent.) which is eliminated in the recrystallisation process. On the other hand phenol can be easily nitrated with dilute nitric acid to yield a mixture of ortho and para nitrophenols. It may be said, therefore, that orientation is meta with the... 

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... 

Diazo coupling follows the rules of orientation of substituents in aromatic systems in accordance with the mechanism of electrophilic aromatic substitution and the concept of resonance. 

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. 

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