19. Reactions of Aromatics: EAS and Beyond

Show how each of the following compounds can be prepared from methyl phenyl ketone:

c.

Indicate how the following compounds can be synthesized from cyclohexanone and any other necessary reagents:

d.

Pyrrole undergoes electrophilic aromatic substitution more readily than benzene, and mild reagents and conditions are sufficient. These reactions normally occur at the 2-position rather than the 3-position, as shown in the following example.

b. Explain why pyrrole reacts more readily than benzene, and also why substitution occurs primarily at the 2-position rather than the 3-position.

a. Draw resonance contributors to show why pyridine-N-oxide is more reactive than pyridine toward electrophilic aromatic substitution.

We have considered nucleophilic aromatic substitution of pyridine at the 2-position and 3-position but not at the 4-position. Complete the three possible cases by showing the mechanism for the reaction of methoxide ion with 4-chloropyridine. Show how the intermediate is stabilized by delocalization of the charge onto the nitrogen atom.

What is the major product of the following reactions?

a.

What is the major product of the following reactions?

b.

Show how the following compounds can be prepared from the given starting material.

a.

When pyrrole is added to a dilute solution of D₂SO₄ in D₂O, 2-deuteriopyrrole is formed. Propose a mechanism to account for the formation of this compound.

Rank imidazole, pyrrole, and benzene from most reactive to least reactive toward electrophilic aromatic substitution.

If Kekulé's original hypothesis had been correct and benzene was really an equilibrium between two structures, how many distinct isomers would exist for 1,2-dichlorobenzene?

Electrophilic aromatic substitution usually occurs at the 1-position of naphthalene, also called the a position. Predict the major products of the reactions of naphthalene with the following reagents.

(a) HNO₃, H₂SO₄

(b) Br₂, FeBr₃

(c) CH₃CH₂COCl, AlCl₃

Biphenyl is two benzene rings joined by a single bond. The site of substitution for a biphenyl is determined by (1) which phenyl ring is more activated (or less deactivated), and (2) which position on that ring is most reactive, using the fact that a phenyl substituent is activating and ortho, para-directing.

a. Use resonance forms of a sigma complex to show why a phenyl substituent should be ortho, para-directing.

(vi)

Unlike most other electrophilic aromatic substitutions, sulfonation is often reversible (see Section 17-4). When one sample of toluene is sulfonated at 0 °C and another sample is sulfonated at 100 °C, the following ratios of substitution products result:

a. Explain the change in the product ratios when the temperature is increased.

b. Predict what will happen when the product mixture from the reaction at 0 °C is heated to 100 °C.

In an aqueous solution containing sodium bicarbonate, aniline reacts quickly with bromine to give 2,4,6-tribromoaniline. Nitration of aniline requires very strong conditions, however, and the yields (mostly m-nitroaniline) are poor.

c. Although nitration of aniline is slow and gives mostly meta substitution, nitration of acetanilide (PhNHCOCH₃) goes quickly and gives mostly para substitution. Use resonance forms to explain this difference in reactivity.