15.4: Nucleophilic Aromatic Substitution

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We’ve said that the aromatic stabilization energy lowers the HOMO, but it also lowers the LUMO. When deactivating groups are added so that the aromatic ring is really electron-deficient, it no longer reacts with electrophiles, but instead with nucleophiles. This is called nucleophilic aromatic substitution (S_NAr).

The general mechanism for this reaction is called an addition-elimination mechanism.

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This reaction will only work if there is a pathway whereby the negative charge in the arenium ion is stabilized by an electron-withdrawing group in an ortho-/para-position.

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Note that the following reaction will not work because the nitro group is never used to stabilize the negative charge. Can you draw the resonance forms that illustrate this?

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The rates of S_NAr reactions increase as the number of electron-withdrawing groups increase, due to the lowering of the LUMO even more.

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Groups that sufficiently stabilize the negative charge are R₃N⁺, NO₂, CF₃. Groups that are good leaving groups react on the order F > Cl > Br > I. This is peculiar since fluoride is not a good leaving group. However, the rate-determining step of this reaction is the addition of the nucleophile to the arene. The fluoride is more electronegative, so it uses the inductive effect to lower the LUMO more effectively for a reaction to occur. The loss of the leaving group is fast and does not contribute to the rate law.

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Another system that has S_NAr reactivity is the heteroaromatics:

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