Substitution, electrophilic ortho effect

A review of experimental work prompted the suggestion of the importance of dipolar interactions (Hammond and Hawthorne, 1956). de la Mare and Kidd (1959), observing a parallelism in the parajmeta and ortho/meta ratios, predicted the ortho effect to be primarily electronic in origin. Norman and Radda (1961) explored the general significance of this idea. They studied the orthojpara ratios for the substitution of a series of monosubstituted benzenes by two reagents with the same electrophilic properties but different steric requirements. The reactions, nitration by N02+ and chlorination by CI+, fulfill the requirements. The results are summarized in Table 3. 

The 0 substituent is ortho, para-directing but the electrophilic substitution step with CO2 gives mostly the orlho product so there must be some coordination between the sodium ion and two oxygen atoms, one from the phenoxide and one from C02. The electrophile is effectively delivered to the ortho position. 

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-... 

We cannot, then, expect this approach to understanding chemical reactivity to explain everything. We should bear in mind its limitations, particularly when dealing with subjects like ortho/para ratios in aromatic electrophilic substitution, where steric effects are well known to be important. Likewise solvent effects (which usually make themselves felt in the entropy of activation term) are also well known to be part of the explanation of the principal of hard and soft acids and bases. Some mention of all these factors will be made again in the course of this book. Arguments based on the interaction of frontier orbitals are powerful, as we shall see, but they must not be taken so far that we forget these very important limitations. 

Electrophilic Substitution Reactions of Monocyclic Thiophens. - A careful kinetic investigation of the protodesilylation of substituted trimethylsilyl-thiophens, either with aqueous HCIO4 in methanol or aqueous H2SO4 in acetic acid, gave values of log k which, except for the nitro-compounds, showed excellent linear correlations with the corresponding ortho-, meta-, or para-substituted trimethylsilylbenzenes. The effect of substituents was larger in the thiophen than in the benzene series. Mixtures of 2- and 3-... 

In electrophilic substitution reactions of anisole, both the ortho and the para products are preferred. It is common to see that a higher percentage of the ortho product is formed. Using bromination as an example, offer an explanation for this ortho effect. ... 

Electrophilic aromatic substitution can be effected on aryl halides. In contrast to nucleophilic substitution vide supra), electrophihc substitution does not generally result in substitution of the electrophihc reagent for the halogen. Instead, the incoming electrophile is substituted for a proton on the aromatic ring and, as shown in Table 7.6 for the nitration of halobenzenes, the substitution occurs largely ortho and para to the halogen. 

The term ferf-amino effect is used to describe ring-closure of N, A -dialkyl-substituted anilines with an unsaturated electrophilic ortho substituent to afford fused tetrahydroquinolines [22] or other iV-heterocycles [15, 19, 20,46, 85-87]. The terf-amino effect has been widely utilized in the synthesis of pyridine, pyrimidine, and pyridazine derivatives, which has been well reviewed by Matyus et al. [15]. 

The rates of electrophilic substitution on other even aromatic systems, and the effects of substituents, can be deduced in the usual way. Thus since -1- / substituents destabilize odd AH cations while — / substituents stabilize them, substitution should tend to take place in such a way as to ensure that + / substituents are at inactive positions in the arenonium intermediate and - / substituents at active positions. For example, in benzene, where the positions ortho and para to the point of substitution are active in the intermediate benzonium ion (89), +/ substituents (e.g., CF3) are best placed in the meta position, while — / substituents (e.g., CH3) should be ortho or para. Benzotrifluoride (PhCF3) consequently substitutes mainly meta, nitration, for example, giving (90), while toluene (PhCH3) substitutes mainly ortho and para, giving, e.g., (91) and (92) on nitration. 

Sections How substituents control rate and regioselectivity m electrophilic aro 12 10-12 14 matic substitution results from their effect on carbocation stability An electron releasing substituent stabilizes the cyclohexadienyl cation inter mediates corresponding to ortho and para attack more than meta... 

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. 

The effect of substituents on electrophilic substitution can be placed on a quantitative basis by use ofpartial rate factors. The reactivity of each position in a substituted aromatic compound can be compared with that of benzene by measuring the overall rate, relative to benzene, and dissecting the total rate by dividing it among the ortho, meta, and para... 

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