In the first nucleophilic aromatic substitution that we showed you, we used fluoride ion as a leaving group. Fluoride works very well in these reactions and even such a simple com pound as 2-halo-l-nitrophenyl fluoride reacts efficiently with a variety of nucleophiles, as in these examples.

The same reactions happen with the other 2-halo-l-nirtobenzenes but less efficiently. The fluoro-compound reacts about 102–103 times faster than the chloro or bromo compounds and the iodo compound is even slower. This ought to surprise you. When we were looking at other nucleophilic substitutions such as those at the carbonyl group or saturated carbon, we never used fluoride as a leaving group! The C–F bond is very strong—the strongest of all the single bonds to carbon—and it is difficult to break. As a consequence, these reactions are not a good prospect:

So why is fluoride so good in nucleophilic aromatic substitution when the reverse is true with other reactions? You will notice that we have not said that fluoride is a better leaving group in nucleophilic aromatic substitution. It isn’t! The explanation depends on a better understanding of the mechanism of the reaction. We shall use azide ion as our nucleophile because this has been well studied and because it is one of the best. The mechanism is exactly the same as that we have been discussing all along—a two-stage addition–elimination sequence. In a two-step mechanism, one step is slower and rate deter mining; the other is unimportant to the rate. You may guess that, in the mechanism for nucleophilic aromatic substitution, it is the fi rst step that is slower because it disturbs the aromaticity. The second step restores the aromaticity and is faster. The effect of fluoride, or any other leaving group, can only come from its effect on the fi rst step. How good a leaving group it might be does not matter: the rate of the second step—the step where fluoride leaves— has no effect on the overall rate of the reaction.

Fluoride accelerates the first step through its inductive effect. It is the most electronegative element of all and it stabilizes the anionic intermediate, assisting the acceptance of electrons by the benzene ring.

مواضيع ذات صلة

How to reduce carboxylic acids to alcohols

How to reduce amides to amines

The benzyne mechanism

Other nucleophiles

The SN1 mechanism for nucleophilic aromatic substitution: diazonium compounds

The activating anion-stabilizing substituent

The intermediate in the addition–elimination mechanism

The addition–elimination mechanism

Nucleophilic aromatic substitution

Nucleophilic epoxidation

Conjugate substitution reactions

Unsaturated nitriles and nitro compounds