Orientation electrophilic aromatic substitution

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. 

Reactivity and orientation in electrophilic aromatic substitution can also be related to the concept of hardness (see Section 1.2.3). Ionization potential is a major factor in determining hardness and is also intimately related to the process of (x-complex formation when an electrophile interacts with the n HOMO to form a new a bond. In MO terms, hardness is related to the gap between the LUMO and HOMO, t] = (sujmo %omo)/2- Thus, the harder a reactant ring system is, the more difficult it is for an electrophile to complete rr-bond formation. 

At this point, attention can be given to specific electrophilic substitution reactions. The kinds of data that have been especially useful for determining mechanistic details include linear ffee-energy relationships, kinetic studies, isotope effects, and selectivity patterns. In general, the basic questions that need to be asked about each mechanism are (1) What is the active electrophile (2) Which step in the general mechanism for electrophilic aromatic substitution is rate-determining (3) What are the orientation and selectivity patterns ... 

Trialkyltin substituents are also powerful ipso-directing groups. The overall electronic effects are similar to those in silanes, but the tin substituent is a better electron donor. The electron density at carbon is increased, as is the stabilization of /S-carbocation character. Acidic cleavage of arylstannanes is formulated as an electrophilic aromatic substitution proceeding through an ipso-oriented c-complex. ... 

Table 12.2 summarizes orientation and rate effects in electrophilic aromatic substitution reactions for a variety of frequently encountered substituents. It is arianged in order of decreasing activating power the most strongly activating substituents are at the top, the most strongly deactivating substituents are at the bottom. The main features of the table can be summarized as follows ... 

In the discussion of electrophilic aromatic substitution (Chapter 11) equal attention was paid to the effect of substrate structure on reactivity (activation or deactivation) and on orientation. The question of orientation was important because in a typical substitution there are four or five hydrogens that could serve as leaving groups. This type of question is much less important for aromatic nucleophilic substitution, since in most cases there is only one potential leaving group in a molecule. Therefore attention is largely focused on the reactivity of one molecule compared with another and not on the comparison of the reactivity of different positions within the same molecule. 

The frontier orbital theory was developed for electrophilic aromatic substitution (Chapter Elements of a Chemical Orbital Theory by Inagaki in this volume). Application is successful to the ortho-para orientation (Scheme 23a) for the benzenes substituted with electron donating groups. The ortho and para positions have larger HOMO amplitudes. The meta orientation (Scheme 23b) for the electron accepting groups is under control of both HOMO and the next HOMO [25]. 

The structural theory of organic chemistry was developed in the last half of the nineteenth century. It led to the concept that chemical, physical and biological properties of all kinds must be a function of structural change. The earliest structure-property relationships (SPR) were qualitative. Examples are the directional effect of substituents on the benzene ring with respect to electrophilic aromatic substitution and orientation in... 

The observed effects of structure on rate and on orientation, confirmed by the Brown selectivity relationship, show that there is no basic difference between heterogeneous catalytic alkylation of aromatic compounds and homogeneous electrophilic aromatic substitution, cf. nitration, sul-phonation etc. This agreement allows the formulation of the alkylation mechanism as an electrophilic attack by carbonium ion-like species formed on the surface from the alkene on Br0nsted acidic sites. The state of the aromatic compound attacked is not clear it may react directly from the gas phase (Rideal mechanism ) [348] or be adsorbed weakly on the surface [359]. 

SAMPLE SOLUTION (a) The ring that bears the hydroxyl group is much more reactive than the other ring. In electrophilic aromatic substitution reactions of rings that bear several substituents, it is the most activating substituent that controls the orientation. Bromination occurs para to the hydroxyl group. 

EFFECT OF SUBSTITUENTS ON REACTIVITY AND ORIENTATION IN ELECTROPHILIC AROMATIC SUBSTITUTION... 

Effect of Substitutents on Reactivity and Orientation in Electrophilic Aromatic Substitution... 

Exercise 22-24 Draw the structures of the intermediate cations for nitration of nitrobenzene in the 2, 3, and 4 positions. Use the structures to explain why the nitro group is meta-orienting with deactivation. Use the same kind of arguments to explain the orientation observed with —CF3, —CHO, —CH2Ci, and —NH2 groups in electrophilic aromatic substitution (Table 22-6),... 

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 ... 

Electrophilic aromatic substitution is a typical reaction for BHs. In the MO treatment, some indices such as free valence [40], localization energy [41], and other quantities [42,43] have been introduced to predict the orientation of electrophilic aromatic substitution. Within the VB framework, several indices have also been formulated [44]. Here we introduce an alternative index, which is available from accurate VB wave functions, and demonstrate its applicability in accounting for the electrophilic aromatic substitution. 

Iodination of arenes2 Iodination of arenes can be effected by reaction with HgO HBF4 in the presence of iodine. The orientation conforms to that observed in electrophilic aromatic substitution except that ortho-attack is favored over para-attack in activated arenes. The method is particularly useful for meta-iodination of deactivated arenes (99% selectivity). 

The coupling reaction is probably that electrophilic aromatic substitution which is characterized to the highest degree by its sensitivity to orientation. In practically all cases the aromatic substrate reacts only if a strong electron donor (O, NH etc.) is present. The reaction takes plare exclusively at the o- and p-positions m-sub-stitution has never been observed nor a reaction at the 3-position of 2-naphthol and 2-naphthylamine (in contrast to, for example, sulfonation). 

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