Substitution, electrophilic aromatic, activation

Why IS there such a marked difference between methyl and trifluoromethyl substituents m their influence on electrophilic aromatic substitution s Methyl is activating and ortho para directing trifluoromethyl is deactivating and meta directing The first point to remember is that the regioselectivity of substitution is set once the cyclohexadienyl cation intermediate is formed If we can explain why... 

SUBSTITUENT EFFECTS IN ELECTROPHILIC AROMATIC SUBSTITUTION ACTIVATING SUBSTITUENTS... 

Substituent Effects in Electrophilic Aromatic Substitution Activating Substituents... 

Section 12 15 When two or more substituents are present on a nng the regioselectiv ity of electrophilic aromatic substitution is generally controlled by the directing effect of the more powerful activating substituent... 

Other typical electrophilic aromatic substitution reactions—nitration (second entry) sul fonation (fourth entry) and Friedel-Crafts alkylation and acylation (fifth and sixth entnes)—take place readily and are synthetically useful Phenols also undergo elec trophilic substitution reactions that are limited to only the most active aromatic com pounds these include mtrosation (third entry) and coupling with diazomum salts (sev enth entry)... 

The hydroxyl group of a phenol is a strongly activating substituent and electrophilic aromatic substitution occurs readily m phenol and its deriv atives Typical examples were presented m Table 24 4... 

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. 

Scheme 10.1. Electrophilic Species Active in Aromatic Substitution...

C. Electrophiles capable of substituting only strongly activated aromatic rings ... 

The active electrophile is formed by a subsequent reaction, often involving a Lewis acid. As discussed above with regard to nitration, the formation of the active electrophile may or may not be the rate-determining step. Scheme 10.1 indicates the structure of some of the electrophihc species that are involved in typical electrophilic aromatic substitution processes and the reactions involved in their formation. 

The polycyclic aromatic hydrocarbons such as naphthalene, anthracene, and phenan-threne undergo electrophilic aromatic substitution and are generally more reactive than benzene. One reason is that the activation energy for formation of the c-complex is lower than for benzene because more of the initial resonance stabilization is retained in intermediates that have a fused benzene ring. 

At this point, attention can be given to specific electrophilic substitution reactions. The kinds of data that have been especially useful for determining mechanistic details include linear ffee-energy relationships, kinetic studies, isotope effects, and selectivity patterns. In general, the basic questions that need to be asked about each mechanism are (1) What is the active electrophile (2) Which step in the general mechanism for electrophilic aromatic substitution is rate-determining (3) What are the orientation and selectivity patterns ... 

The table below gives first-order rate constants for reaction of substituted benzenes with w-nitrobenzenesulfonyl peroxide. From these data, calculate the overall relative reactivity and partial rate factors. Does this reaction fit the pattern of an electrophilic aromatic substitution If so, does the active electrophile exhibit low, moderate, or high substrate and position selectivity ... 

Table 12.2 summarizes orientation and rate effects in electrophilic aromatic substitution reactions for a variety of frequently encountered substituents. It is arianged in order of decreasing activating power the most strongly activating substituents are at the top, the most strongly deactivating substituents are at the bottom. The main features of the table can be summarized as follows ... 

A hydroxyl group is a very powerful activating substituent, and electrophilic aromatic substitution in phenols occurs far- faster, and under milder conditions, than in benzene. The first entry in Table 24.4, for exfflnple, shows the monobromination of phenol in high yield at low temperature and in the absence of any catalyst. In this case, the reaction was carried out in the nonpolar- solvent 1,2-dichloroethane. In polar- solvents such as water it is difficult to limit the bromination of phenols to monosubstitution. In the following exfflnple, all three positions that are ortho or para to the hydroxyl undergo rapid substitution ... 

Activating substituent (Sections 12.10 and 12.12) A group that when present in place of a hydrogen causes a particular reaction to occur faster. Term is most often applied to substituents that increase the rate of electrophilic aromatic substitution. 

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