Chemistry 350 Organic Chemistry I

Study Guide :: Unit 16

Chemistry of Benzene: Electrophilic Aromatic Substitution

Unit Preview

In the preceding unit, you studied the concept of aromaticity and spent considerable time on the theoretical aspects of the chemistry of aromatic compounds. In this unit, you will begin to study the chemical reactions of aromatic compounds, focusing on electrophilic aromatic substitution, and to a lesser extent on nucleophilic aromatic substitution. We will discuss, in detail, the mechanism of electrophilic substitution, paying particular attention to the factors that determine both the rate and position of substitution in those aromatic compounds which already have one or more substituents present in the aromatic ring. You will see that nucleophilic aromatic substitution can be achieved by two different mechanisms, one of which involves the formation of an unusual looking intermediate, benzyne.

You will also see how alkyl and acyl groups can be introduced on to an aromatic ring; how, once introduced, alkyl groups can be converted to carboxyl groups; and how bromine can be introduced to the alkyl side chain of alkylbenzene. The latter reaction is particularly useful because the benzylic bromide so produced undergoes the reactions of a typical alkyl bromide, thus providing a synthetic route to a large variety of compounds.

Unit Objectives

When you have completed Unit 16, you should be able to

  1. fulfil all of the detailed objectives listed under each individual section.
  2. solve road-map problems that require an understanding of the chemistry discussed in this unit and those preceding it.
  3. design multistep syntheses using the reactions discussed in this and preceding units. In particular you should be prepared to show how an aromatic compound containing two or more substituents could be synthesized, taking care to introduce the substituents into the ring in the correct order.
  4. define, and use in context, the key terms introduced.

16.0  Introduction

Objectives

After completing this section, you should be able to

  1. identify electrophilic substitution as the single most important reaction of aromatic compounds.
  2. explain why aromatic compounds, such as benzene, are susceptible to attack by electrophiles.

Learning Activities

Read 16.0 Introduction and do any associated exercises.

16.1  Electrophilic Aromatic Substitution Reactions: Bromination

Objectives

After completing this section, you should be able to

  1. write the detailed mechanism for the reaction of bromine with benzene in the presence of a suitable catalyst.
  2. draw the resonance contributors for the carbocation which is formed during the reaction of bromine with benzene.
  3. compare the reaction which takes place between bromine and benzene and the reaction which takes place between bromine and an alkene.
  4. draw an energy diagram for the reaction of bromine with benzene.
  5. identify the reagents required to bring about aromatic bromination.
  6. write an equation to represent aromatic bromination.

Learning Activities

Read 16.1 Electrophilic Aromatic Substitution Reactions: Bromination and do any associated exercises.

16.2  Other Aromatic Substitutions

Objectives

After completing this section, you should be able to

  1. write a balanced equation for the halogenation (F, Cl, Br, I) of benzene in the presence of a suitable catalyst or promoter.
  2. draw the resonance contributors for the carbocation which is formed during the reaction of chlorine or bromine with benzene.
  3. write the equation for the nitration and sulfonation of benzene.
  4. write the detailed mechanism for the nitration and sulfonation of benzene.
  5. write the equation for the reduction of an aromatic nitro compound to an amine.
  6. identify aromatic sulfonation as being a reversible process, and describe the conditions under which the forward and reverse reactions are favoured.
  7. write the equation for the desulfonation of an aromatic sulfonic acid.
  8. identify aromatic sulfonic acids as being key intermediates in the manufacture of sulfa drugs.

Learning Activities

Read 16.2 Other Aromatic Substitutions and do any associated exercises.

16.3  Alkylation and Acylation of Aromatic Rings: The Friedel-Crafts Reaction

Objectives

After completing this section, you should be able to

  1. write the equation for the preparation of an alkylbenzene by a Friedel-Crafts alkylation reaction.
  2. identify the product formed from the Friedel-Crafts alkylation of a given aromatic compound.
  3. identify the aromatic compound needed to prepare a given arene by a Friedel-Crafts alkylation.
  4. identify the alkyl halide and catalyst needed to form a specified arene from a given aromatic compound.
  5. write the detailed mechanism for the Friedel-Crafts alkylation reaction, and identify the similarities between this reaction and those electrophilic aromatic substitution reactions you studied in Sections 16.1 and 16.2.
  6. show how alkyl halides and acylhalides can be used as alkylating agents in Friedel-Crafts alkylation reactions.
  7. discuss the limitations of the Friedel-Crafts alkylation reaction, paying particular attention to the structure of the alkyl halide, the structure of the aromatic substrate and the problem of polyalkylation.
  8. write an equation for a typical Friedel-Crafts acylation.
  9. write the detailed mechanism of the Friedel-Crafts acylation reaction.
  10. identify the product formed by the Friedel-Crafts acylation of a given aromatic compound.
  11. identify the aromatic compound, and the reagent and catalyst needed to prepare a given ketone through a Friedel-Crafts acylation reaction.

Learning Activities

Read 16.3 Alkylation and Acylation of Aromatic Rings: The Friedel-Crafts Reaction and do any associated exercises.

16.4  Substituent Effects in Substituted Aromatic Rings

Objectives

After completing this section, you should be able to

  1. describe the two ways in which a substituent influences the electrophilic substitution of a monosubstituted aromatic compound.
  2. classify each of the following substituents as being either activating or deactivating with respect to electrophilic aromatic substitution: $\ce{\sf{-NH2}}$, $\ce{\sf{-OH}}$, $\ce{\sf{-NHR}}$, $\ce{\sf{-NR2}}$, $\ce{\sf{-OR}}$, $\ce{\sf{-NHCOR}}$, alkyl (R), phenyl, R3N+, $\ce{\sf{-NO2}}$, $\ce{\sf{-CN}}$, $\ce{\sf{-COR}}$, $\ce{\sf{-CO2H}}$, $\ce{\sf{-CO2R}}$, $\ce{\sf{-CHO}}$, halogens.
  3. list a given series of substituents (selected from those given in Objective 2) in order of increasing or decreasing ability to activate or deactivate an aromatic ring with respect to electrophilic substitution.
  4. explain, in general terms, the factors that determine whether a given substituent will activate or deactivate an aromatic ring with respect to electrophilic substitution.
  5. list a given series of aromatic compounds in order of increasing or decreasing reactivity with respect to electrophilic substitution.
  6. explain the inductive effects displayed by substituents such as nitro, carboxyl, alkyl and the halogens during electrophilic aromatic substitution reactions.
  7. explain the resonance effects displayed by substituents such as nitro, carbonyl-containing, hydroxy, alkoxy and amino groups during electrophilic aromatic substitution reactions.

Learning Activities

Read 16.4 Substituent Effects in Substituted Aromatic Rings and do any associated exercises.

16.5  An Explanation of Substituent Effects

Objectives

After completing this section, you should be able to

  1. draw the resonance contributors for the carbocation intermediate formed during the reaction of a given monosubstituted benzene derivative with any of the electrophiles discussed in this unit.
  2. classify each of the substituents listed in Objective 2 of Section 16.4 as being either meta or ortho/para directing.
  3. classify each of the substituents listed in Objective 2 of Section 16.4 as being ortho/para directing activators, ortho/para directing deactivators or meta directing deactivators.
  4. predict the product or products formed from the reaction of a given monosubstituted benzene derivative with each of the electrophiles discussed in this unit.
  5. explain, by drawing the resonance contributors for the intermediate carbocation, why the electrophilic substitution of an alkyl benzene results in a mixture of mainly ortho- and para- substituted products.
  6. explain why the electrophilic substitution of phenols, amines and their derivatives proceeds more rapidly than the electrophilic substitution of benzene itself.
  7. explain, by drawing the resonance contributors for the intermediate carbocation, why meta substitution predominates in electrophilic aromatic substitution reactions carried out on benzene derivatives containing one of the substituents R3N+, NO2, CO2H, CN, CO2R, COR or CHO.
  8. explain why electrophilic aromatic substitution of benzene derivatives containing one of the substituents listed in Objective 7, above, proceeds more slowly than the electrophilic substitution of benzene itself.
  9. explain, by drawing the resonance contributors for the intermediate carbocation, why the electrophilic aromatic substitution of halobenzenes produces a mixture of mainly ortho- and para-substituted products.
  10. explain why the electrophilic aromatic substitution of halobenzenes proceeds more slowly than does the electrophilic substitution of benzene itself.
  11. use the principles developed in this unit to predict in which of the three categories listed in Objective 3, above, a previously unencountered substituent should be placed.

Learning Activities

Read 16.5 An Explanation of Substituent Effects and do any associated exercises.

16.6  Trisubstituted Benzenes: Additivity of Effects

Objectives

After completing this section, you should be able to

  1. predict the position or positions at which electrophilic substitution will occur when a third substituent is introduced into a disubstituted benzene ring.
  2. explain the observed substitution pattern when a third substituent is introduced into a disubstituted benzene ring.

Learning Activities

Read 16.6 Trisubstituted Benzenes: Additivity of Effects and do any associated exercises.

16.7  Nucleophilic Aromatic Substitution

Objectives

After completing this section, you should be able to

  1. identify the conditions necessary for an aryl halide to undergo nucleophilic aromatic substitution, and give an example of such a reaction.
  2. write the detailed mechanism for a nucleophilic aromatic substitution reaction.
  3. compare the mechanism of a nucleophilic aromatic substitution reaction and the SN1 and SN2 mechanisms discussed earlier.
  4. identify the product formed when a given nucleophile reacts with a given aryl halide in a nucleophilic aromatic substitution reaction.

Learning Activities

Read 16.7 Nucleophilic Aromatic Substitution and do any associated exercises.

16.8  Benzyne

Objectives

After completing this section, you should be able to

  1. identify the reagents and conditions required to produce phenol from chlorobenzene on an industrial scale.
  2. write the mechanism for the conversion of an alkyl halide to a phenol through a benzyne intermediate.
  3. discuss the experimental evidence which supports the existence of benzyne intermediates.
  4. discuss the bonding in benzyne, and hence account for its high reactivity.

Learning Activities

Read 16.8 Benzyne and do any associated exercises.

16.9  Oxidation of Aromatic Compounds

Objectives

After completing this section, you should be able to

  1. write an equation to describe the oxidation of an alkylbenzene to a carboxylic acid.
  2. identify the reagents required to oxidize a given alkylbenzene to a carboxylic acid.
  3. identify the product formed from the side-chain oxidation of a given alkylbenzene.
  4. identify the aromatic compound needed to produce a given carboxylic acid through side-chain oxidation.
  5. write the equation for the bromination of an alkylbenzene side chain.
  6. identify the reagents and conditions necessary to bring about bromination in the side chain of an alkylbenzene.
  7. identify the product formed when a given alkylbenzene undergoes side-chain bromination.
  8. identify the alkylbenzene needed to prepare a given benzylic bromide by radical substitution.
  9. write the mechanism for the radical substitution at the benzylic position of an alkylbenzene.
  10. explain the stability of benzylic radicals in terms of resonance, and draw the resonance contributors of a given benzyl radical.
  11. explain, and illustrate with appropriate examples, the importance of benzylic bromides as intermediates in organic syntheses.
  12. arrange a given series of radicals (including benzylic type radicals) in order of increasing or decreasing stability. (Review Section 10.3 if necessary.)

Learning Activities

Read 16.9 Oxidation of Aromatic Compounds and do any associated exercises.

16.10  Reduction of Aromatic Compounds

Objectives

After completing this section, you should be able to

  1. write an equation to represent the reduction of a substituted benzene to a substituted cyclohexane.
  2. identify the catalyst and reagents used to reduce aromatic rings.
  3. compare the ease of reduction of alkenes with the difficulty in reducing benzene rings, and show how this difference in reactivity can be used in organic synthesis.
  4. write an equation to illustrate the reduction of an aromatic ketone to an arene.
  5. explain why Friedel-Crafts acylation, followed by reduction, provides a better route to primary alkylbenzenes than does direct alkylation.
  6. show how a specified alkylbenzene may be prepared by a Friedel-Crafts acylation, followed by reduction. Specify all reagents, the structure of the intermediate ketone, and the necessary starting material.

Learning Activities

Read 16.10 Reduction of Aromatic Compounds and do any associated exercises.

16.11  Synthesis of Polysubstituted Benzenes

Objectives

After completing this section, you should be able to

  1. design a multistep synthesis which may involve reactions in the alkyl side chain of an alkylbenzene and the electrophilic substitution reactions discussed in this unit. You should pay particular attention to
    1. carrying out the reactions in the correct order.
    2. using the most appropriate reagents and conditions.
    3. the limitations of certain types of reactions.
  2. analyse a proposed multistep synthesis involving aromatic substitution to determine its feasibility, point out any errors in the proposal and identify possible problem areas.

Learning Activities

Read 16.11 Synthesis of Polysubstituted Benzenes and do any associated exercises.

Watch Synthesis of Substituted Benzene Rings I and Synthesis of Substituted Benzene Rings II videos by the Khan Academy.

Summary

This unit has two immediate goals: to illustrate the use of Friedel-Crafts alkylations and acylations as methods of introducing carbon-containing substituents into an aromatic ring; and to describe some of the reactions of these compounds once they have been formed. A broader-range goal was to show some of the considerations that must be borne in mind by a chemist who is planning to carry out a multistep synthesis involving aromatic compounds.

We began this unit by showing how a variety of substituents could be introduced into a benzene ring. Subsequently, you saw how the nature of a substituent already present in an aromatic compound would influence the rate at which that compound would undergo electrophilic substitution. The substituent present in the ring also determines at which position or positions electrophilic substitution will occur. The role played by a substituent depends on both resonance and inductive effects.

When you are confident that you understand the material presented in Units 15-16, please complete Self Test 6.

At this point, complete the second assignment, which you will find in the “Assessment” section on the course homepage, and submit your work for grading. You may also wish to make arrangements to write the final examination—see “Procedures for Applying for and Writing Examinations” in the Student Manual.