Effect, directive substituents

There were two schools of thought concerning attempts to extend Hammett s treatment of substituent effects to electrophilic substitutions. It was felt by some that the effects of substituents in electrophilic aromatic substitutions were particularly susceptible to the specific demands of the reagent, and that the variability of the polarizibility effects, or direct resonance interactions, would render impossible any attempted correlation using a two-parameter equation. - o This view was not universally accepted, for Pearson, Baxter and Martin suggested that, by choosing a different model reaction, in which the direct resonance effects of substituents participated, an equation, formally similar to Hammett s equation, might be devised to correlate the rates of electrophilic aromatic and electrophilic side chain reactions. We shall now consider attempts which have been made to do this. 

The mix of inductive and resonance effects varies from one halogen to another but the net result is that fluorine chlorine bromine and iodine are weakly deactivating ortho para directing substituents... 

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 effect of substituents on the reactivity of heterocyclic nuclei is broadly similar to that on benzene. Thus mem-directing groups such as methoxycarbonyl and nitro are deactivating. The effects of strongly activating groups such as amino and hydroxy are difficult to assess since simple amino compounds are unstable and hydroxy compounds exist in an alternative tautomeric form. Comparison of the rates of formylation and trifiuoroacetylation of the parent heterocycle and its 2-methyl derivative indicate the following order of sensitivity to substituent effects furan > tellurophene > selenophene = thiophene... 

Because nitration has been studied for a wide variety of aromatic compounds, it is a useful reaction with which to illustrate the directing effect of substituent groups. Table 10.3 presents some of the data. A variety of reaction conditions are represented, so direct comparison is not always valid, but the trends are nevertheless clear. It is important to remember that other electrophiles, while following the same qualitative trends, show large quantitative differences in position selectivity. 

Table 11.1 Directive Effect of Substituents on Inward/Outward Conrotation in Cyclobutene Ring Opening"...

Previously mentioned was the importance of directing substituents of the anil in expediting cyclization and that when powerful EWGs are present, cyclization might be inhibited entirely. A study was conducted to consider the steric influence of methyl substituents on the anil and their effect on the cyclization. It was proposed that a methyl group on the anil had a profound effect on the site of cyclization. For example, while 42 was isolated in only 22% yield, the other isomer 43 was not observed. This... 

This difference in selectivity makes it necessary to consider both the substituent and the reagent when discussing the directing effects of substituents to a much larger extent than is necessary in the benzene series. 

In aromatic nucleophilic substitution, two general effects of substituents are (2) to alter the ground state in a direction toward or away from the transition state and (2) to withdraw electrons from or donate them to the pentadienoid anion in the transition state and... 

Inductive and resonance effects account for the directing effects of substituents as well as for their activating or deactivating effects. Take alkyl groups, for instance, which have an electron-donating inductive effect and are ortho and para directors. The results of toluene nitration are shown in Figure 16.13. 

A Summary of Substituent Effects in Aromatic Substitution A summary of the activating and directing effects of substituents in electrophilic aromatic substitution is shown in Table 16.2. 

However, the hydride reduction of FeCp(arene)+ salts [124, 125] gives [FeCp(r 5-cyclohexadienyl)] complexes [125, 126] (via an ET mechanism [127] for the directing effect of substituents see Refs. [126, 128-130]. The electrochemical reduction of the carboxylic substituents at an Hg cathode in water leads to the primary alcohol [131-133] Eq. (39) ... 

Sulfinyl and sulfonyl groups were involved in early studies of the directive effects of substituents in nitration and other reactions with electrophilic reagents. Thus Twist and Smiles (in 1925) showed that nitration of phenyl methyl sulfone gave exclusively 3-nitrophenyl methyl sulfone. The results of bromination and sulfonation were analogous, so S02Me was established, like NO2, as a mefa-directing group. 

This is a strong directing effect that can exert stereochemical control even when steric effects are opposed. Entries 4 and 5 in Scheme 12.11 illustrate the hydroxy-directing effect. Other substituents capable of hydrogen bonding, in particular amides, also can exert a. vyn-directing effect.79... 

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