Substituent groups meta-directing

As Table 12.2 indicates, a number of substituents are meta-directing and strongly deactivating. We have already discussed one of these, the trifluoromethyl group. Several others have a carbonyl group attached directly to the aromatic ring. 

Several alkyl groups bearing electron-attracting substituents are meta -directing and deactivating, as indicated in Table 9.3, with nitration as the electrophilic substitution reaction. In these molecules, resonance stabilization of the ortho or para... 

Alkyl groups, phenyl groups, and substituents in which the atom bonded to the ring has an unshared pair of electrons are ortho-para directing. AU other substituents are meta directing. 

Next, the ester carbonyl substituent is meta directing and might also be useful, because it could be employed to introduce the meta amino nitrogen in the form of a nitro group. 

Our analysis of substituent effects has so far centered on two groups methyl and triflu oromethyl We have seen that a methyl substituent is activating and ortho para directing A trifluoromethyl group is strongly deactivating and meta directing What about other substituents ... 

The next group of substituents in Table 12 2 that we 11 discuss are the ones near the bottom of the table those that are meta directing and strongly deactivating... 

Often the directing effects of substituents reinforce each other Brommation of p mtrotoluene for example takes place at the position that is ortho to the ortho para directing methyl group and meta to the meta directing nitro group... 

Because the position of electrophilic attack on an aromatic nng is controlled by the direct ing effects of substituents already present the preparation of disubstituted aromatic com pounds requires that careful thought be given to the order of introduction of the two groups Compare the independent preparations of m bromoacetophenone and p bromoace tophenone from benzene Both syntheses require a Friedel-Crafts acylation step and a bromination step but the major product is determined by the order m which the two steps are carried out When the meta directing acetyl group is introduced first the final product IS m bromoacetophenone... 

The entrance of a third or fourth substituent can be predicted by Beilstein s rule. If a substituent Z- enters into a compound C H XY, both X and Y exert an influence, but the group with the predominant influence directs Z- to the position it will occupy. Since all meta-directing groups are deactivating, it follows that ortho—para activating groups predominate when one of them is present on the benzene ring. 

Existing substituent groups such as CH3, OCH3, and +N(CH3)3 exert a directive effect, often resulting in a major amount of the meta substitution product.323 The intermediate adducts can be converted to cyclohexadiene derivatives if the adduct is protonolyzed.324... 

In a study aimed at the identification of products of free radical reactions with polystyrene- and aromatic-based PEMs using model compounds, Hiibner and Roduner observed the addition of free radicals to the aromatic rings, preferentially in the ortho position to alkyl- and RO-substituents (in polystyrene- and aromatic-based PEMs, the para position is blocked by the presence of the sulfonic acid group). This study demonstrated the combined ortho-activation by these substituents and the meta-directing effect... 

The hydrolysis of substituted phenyl acetates has been studied in the presence of cyclodextrins (Van Etten et al, 1967a, b). No correlation was found between the rate constants for hydrolysis and a for the substituent group. Specificity was directed towards meta-substituents. m-t-Butylphenyl acetate hydrolyses 240 times faster in the presence of 0-01 M cyclohepta-amylose. Comparison of spectral shifts upon inclusion of p-t-butyl and m-t-butylphenol indicated that benzene rings of p-substituted phenols are included within the cavity of cyclodextrins [45], but that the benzene ring of the meta-isomer... 

A survey of many such reactions suggests that there is no single, simple pattern that can be used to predict the outcome of photochemical nucleophilic substitutions, but rather a situation in which oneof at least three mechanisms may operate, and this has been borne out by more detailed mechanistic studies. One approach to rationalizing the preferred orientation in the excited-state reactions is to calculate electron densities at the various ring carbon atoms for a particular pattern of substituents, and to assume that preferential attack by a nucleophile will take place at the position of lowest electron density. This static reactivity leads to the prediction that a nitro group is meta-directing for direct nucleophilic attack in the excited state,... 

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