SUBSTITUTION ON THE BENZENE NUCLEUS

The positive charge will clearly further destabilise any of the a complexes for electrophilic substitution, as did a substituent such as NR3 on the benzene nucleus (p. 152), but the destabilisation will be much more marked than with NR3 as the charge is now on an atom of the ring itself and not merely on a substituent. 

Phenyloxadiazole has been nitrated on the benzene nucleus without substitution occurring on the heterocycle. The hydrolysis of 3-nitrophenyl-oxadiazole has yielded a mixture of p. and m. nitrobenz-amide. 

A more detailed exploration of the reactivity of biphenyl resolves the problem. The ra-phenyl substituent reduces the rate of substitution in the benzene nucleus (Table 7). Qualitatively, this effect is in agreement with the predictions based on the rate of solvolysis of ra-phenylphenyl-dimethylcarbinyl chloride (Brown and Okamoto, 1958) and with the expected electron-withdrawing properties of the phenyl group. The data conform to the Selectivity Relationship with reasonable precision (Fig. 31). In view of the activation of the ortho and para positions, direct evaluation of the partial rate factors for the deactivated meta position is not always possible. Hence, indirect kinetic procedures were employed in several cases, halogenation and acylation, to estimate the values. Graphical analysis of the data shows that mfb is independent of the reagent selectivity. Deviations from the relationship are no greater than for the ordinary side-chain reactions. 

The experimental data on the dipole moments of aliphatic and aromatic compounds clearly indicate the existence of molecular resonance in the latter. The resonance, which produces either positive or negative charges on the carbon atoms in the ortho and para positions, determines the specificity, which has been observed in the substitution of the benzene nucleus. The substituent groups may be divided into two classes depending... 

Further investigations on the structural requirements of activity have shown that alkyl substitution in the para-position on the benzene nucleus may also yield active derivatives, ethyl being optimal (Pallos et al 1971). This finding led to the development of a number of active derivatives, such as 42, 43, 44 and 45 (Hangartner et al., 1976 Piccardi et al., 1977 McGovern and Redfem, 1979). 

The ease of polychlorination of l-chloro-3-phenyl-lA, 2,4-benzothiadiazine (93)- (94) at the carbocyclic ring rather than at the 3-phenyl substituent is indicative of the activating effect of a fused U, 2,4-thiadiazine ring on the benzene nucleus <89JOU550>, a result in direct contrast to the electrophilic substitution of U, 2,4-thiadiazine 1-oxides under strong acid conditions (see Section... 

Although it has been described that ruthenium is an efficient catalyst for the reduction of the aromatic nucleus at raised temperatures and pressures, its superiority is most useful when a nitrogen group is substituted on the benzene ring (16-18). Rhodium catalysts are, however, more efficient, even at raised pressures and temperatures, for the hydrogenation of compounds like benzene, hydroquinone, and /3-naphthol. At a hydrogen... 

As with most 13C NMR spectra, those of Aspidosperma alkaloids can be divided into two regions above 90 ppm, where there is the region of sp2 carbon atoms (olefinic, aromatic, carbonyl) and below 90 ppm, where there is the complex region of sp3 carbons attached to hydrogen, oxygen, or nitrogen. The indole or indoline nucleus shows quite characteristic carbon resonances when there is no substitution on the benzene ring and the order is typically C-13, C-8, C-10, C-ll, C-9, C-12, and C-7. In the / -anilinoacrylate series this order is C-13, C-8, C-ll, C-9, C-10, and C-12. 

Theories put forward rather early and thus based on part of this material only, have not enabled us, however, to frame all of the data into one picture (c/. for a critical discussion, Toothill, Wain and Wightman i). As to chlorine substitution in the benzene nucleus the most important results may be summarized as follows mono-substitution enhances the activity as compared with that of the parent phenoxyacetic acid (POA), most pronoimcedly in 3- and 4-positions. 

In the aromatic series where the hydroxyl group (-OH) is substituted directly on the benzene nucleus, the compounds are known as phenols. These differ significantly from the alcohols and are considered separately. The alcohols as a group are important flavoring materials and are extensively found throughout nature. All contain a hydroxyl group, which largely determines their characteristics. 

When implementing QSAR on flat, symmetrical, usually aromatic molecules, symmetry considerations often affirm that alternative orientations should be insjjected. For phenethylamines, for example, there are five substitution sites on the benzene nucleus. If substituents with profjerty Pi were introduced to site i (i = 2-6), an equation may be formulated ... 

These reactions are typical also of many derivatives of aromatic hydrocarbons in fact, the presence of certain substituents, like the amine and phenolic groups, may facilitate substitution into the benzene nucleus on the other hand, certain other substituents, like the nitro and sulfonic acid groups, will cause sub-... 

With monosubstituted benzenes, para substitution generally is observed, but when the steric factor associated with the substituent on the benzene nucleus is small, ortho substitution can take place (Dolby and Robinson, 1972). The product yields generally are good. 

An example of the construction of dibenzofurans by palladium-catalyzed C—H arylation was reported by Itatani in 1974 (Scheme 3.4) [17]. Compared with previous methods [18], this reaction could obviate the tedious synthetic route and is suitable for the preparation of substituted dibenzofurans with high efficiency. It should be noted that substituents on the benzene nucleus are believed to reduce the interaction between molecules and favor intramolecular coupling rather than intermolecular dimerization. 

Peroxide decomposition in aromatic and other unsaturated solvents homolytic aroniMic substitution and olefin polymerization Decomposition of peroxides in aromatic solvents leads to attack on the aromatic nucleus by radicals and hence to substitution products (for a recent summary, see Williams, 1970). In the substitution of benzene and related substrates by phenyl radicals, for example, cyclohexadienyl... 

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