Orientation of substitution

Further evidence that the nitronium ion was not the electrophile in the uncatalysed reaction, and yet became effective in the catalysed reaction, came from differences in the orientation of substitution. The nitration of chlorobenzene in the uncatalysed reaction yielded only 43 % of the para compound, whereas, when the catalysed reaction was made important by adding some nitric acid, the ratio of substitution was that usually observed in nitration involving the nitronium ion ( 5.3.4). In the case of the uncatalysed reaction however, the reaction was complicated by the formation of nitrophenols. 

Nitration using this reagent was first investigated, by Francis. He showed that benzene and some of its homologues bromobenzene, benzonitrile, benzoyl chloride, benzaldehyde and some related compounds, and phenol were mono-nitrated in solutions of benzoyl nitrate in carbon tetrachloride anilines would not react cleanly and a series of naphthols yielded dinitro compounds. Further work on the orientation of substitution associated this reagent with higher proportions of o-substitution than that brought about by nitric acid this point is discussed below ( 5.3.4). 

The orientation of substitution into phenol was strongly dependent on the conditions of reaction (see below). 

This h)rpothesis has, however, been supported. The o p-ratio in chlorobenzene was found to be lower when acetic anhydride was the solvent, than when nitric acid or mixed acids were used. The ratio was still further reduced by the introduction into the solution of an even less polar solvent such as carbon tetrachloride, and was increased by the addition of a polar solvent such as acetonitrile. The orientation of substitution in toluene in which the substituent does not posses a strong dipole was found to be independent of the conditions used. The author... 

Phenol. The change in the orientation of substitution into phenol as a result of the superimposition of nitrosation on nitration is a well-established phenomenon. In aqueous sulphuric acid it leads to a change from the production of 73 % of o-nitrophenol under nitrating... 

The use of q and tt separately as reactivity indices can lead to misleading results. Thus, whilst within the approximations used, the use of either separately leads to the same conclusions regarding electrophilic substitution into halogenobenzenes ( 9.1.4), the orientation of substitution in quinoline ( 9.4.2) cannot be explained even qualitatively using either alone. By taking the two in combination, it can be shown that as the values of Sa are progressively increased to simulate reaction, the differences in SE explain satisfactorily the observed orientation. ... 

Consideration of the orientation of substitution Orientation is an important factor to be considered in recognising both changes in the effective electrophile and in the nature of the aromatic substrate. Cases of the former type, which will be met at several places... 

The significance of frontier electron densities is limited to the orientation of substitution for a given aromatic system, but this approach has been developed to give two more complex reactivity indices termed superdelocalizabilities and Z values, which indicate the relative reactivities of different aromatic systems. 

In compounds with a fused benzene ring, electrophilic substitution on carbon usually occurs in the benzenoid ring in preference to the heterocyclic ring. Frequently the orientation of substitution in these compounds parallels that in naphthalene. Conditions are often similar to those used for benzene itself. The actual position attacked varies compare formulae (341)-(346) where the orientation is shown for nitration sulfonation is usually similar for reasons which are not well understood. 

Quinoxalin-2-one is a very weak base (pK — 1.37) and so the different orientation of substitution in acetic and sulfuric acids may mean that in acetic acid the principal species undergoing nitration is the neutral molecule, and in sulfuric acid, the mono-cation. Treatment of quinoxaline-2,3-dione, or its iViV -dimethyl derivative in sulfuric acid, with 1 equivalent of potassium nitrate, results in nitration at position 6 with 2 equivalents of potassium nitrate, 6,7-dinitro compounds are formed. When quinoxaline is boiled with aqueous nitric acid, 6-... 

A benzene ring fused to a 7r-excessive heterocycle is less reactive toward electrophiles than the heteroring, and it frequently reduces the reactivity of the latter, and may modify the orientation of substitution. Where the... 

Electronegative groups do not invariably prevent nuclear bromination, but reaction conditions must be much more severe, and the orientation of substitution may be affected by the substituent. Thus 6-nitroquinoline was brominated in sulfuric acid at 100°C to give the 8-bromo product (71) in 51% yield 8-methyl-5-nitroquinoline gave a 69% yield of the 7-bromo derivative (72) under similar conditions, whereas 7-chloroquinoline was transformed into the 5-bromo product (93%) (88CHE892) (Scheme 35). In a sealed tube reaction with bromine, 8-nitroquinoline gave a mixture... 

Compounds with axial and equatorial orientation of substitutents not only differ in physical properties but in reactivity as well, because the rates of formation of equatorial and axial isomers and rates of substituion and elimination reactions are different. 

A specialized system of nomenclature has been developed, principally by Smith,16 for naming skeletons consisting of aromatic residues linked in various ways by saturated bridges. Those skeletons containing benzene residues only are termed cyclophanes, and names for heteroaromatic analogues are based on the name of the heterocycle with the termination -ophane. The numbers of atoms in the bridges are indicated in square brackets, and the orientation of substitution on the aromatic residue(s) is shown in parentheses. A few simple examples are given (149-151), with alternative names. 

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