Ch12 : Electrophilic Aromatic Substitution

Chapter 12 : Reactions of Arenes. Electrophilic Aromatic Substitution

Making Polysubstituted Benzenes

Since the position of electrophilic attack on a substituted benzene ring is controlled by the substitutent already present rather than the approaching electrophile, the order of events in the synthesis of polysubstituted benzenes need careful planning to ensure success.

The two factors that need to be monitored are:

regiochemistry (e.g. what are the substituent directing effects)
reactivity (e.g. Friedel-Crafts reactions are limited to halobenzenes and activated benzenes)

Study Tip:
Some students get confused over which group does the directing, the incoming electrophile, E⁺, or the initial substituent, -X.
Try thinking about it in terms of an aircraft (the E⁺) coming into land at an airport (the Ar-X )... it is the control tower at the airport on the ground (-X) that does the "directing" of which runway and which ramp the aircraft should go to)

Draw the target product and label the substituents with their directing effects
Look at these directing effects to see which (if any !) align to allow the introduction of the appropriate group
If there is a choice, introduce the more activating group first... it will make the subsequent reactions easier
Remember that some functional groups can undergo reactions that change their directing effects
Check the order of reactions for compatibility

Here are a couple of examples:

	Here the nitro group could direct to bromine to the correct position. Therefore in planning the synthesis we should use the nitro group to introduce the bromine
PLANNED SYNTHESIS
COMPLETE SYNTHESIS

QUESTION : What would the product be if the order of the steps in the synthesis shown above were reversed ? ANSWER

	Here neither group directs to the correct location of the other. But since the carboxylate could be introduced by the oxidation of a methyl group, which directs o,p- we can use the methyl to direct the nitro group to the correct position.
PLANNED SYNTHESIS
COMPLETE SYNTHESIS
	Note that the oxidation has to be after the nitration to get the correct orientation and that the Friedel-Crafts alkylation has to before the nitration since nitrobenzene is too deactivated to undergo alkylation.