Chemistry 350 Organic Chemistry I

Study Guide :: Unit 11

Reactions of Alkyl Halides: Nucleophilic Substitutions and Eliminations

Unit Preview

In this course, you have already seen several examples of nucleophilic substitution reactions; now you will see that these reactions can occur by two different mechanisms. You will study the factors that determine which of these two mechanisms will be in operation in a given situation, and examine possible ways for increasing or decreasing the rates at which such reactions occur. The stereochemical consequences of the two mechanisms will also be discussed.

Elimination reactions often accompany nucleophilic substitution; so these reactions are also examined in this unit. Again you will see that two different mechanisms are possible, and, as in the case of nucleophilic substitution reactions, chemists have learned a great deal about the factors that determine which mechanism will be observed when a give alkyl halide undergoes such a reaction.

Unit Objectives

After you have completed Unit 11, you should be able to

  1. fulfil all of the detailed objectives listed under each individual section.
  2. use the reactions studied in this unit with those from previous units when designing multistep syntheses.
  3. use the reactions and concepts discussed in this unit in solving road map problems.
  4. define, and use in context, the key terms introduced.

11.0  Introduction

Objective

After completing this section, you should be able to identify substitution and elimination as being the two most important reactions of alkyl halides.

Learning Activities

Read 11.0 Introduction and do any associated exercises.

11.1  The Discovery of Nucleophilic Substitution Reactions

Objectives

After completing this section, you should be able to

  1. write an equation to represent the Walden inversion.
  2. write a short paragraph describing the Walden inversion.
  3. describe, using equations, a series of reactions interconverting two enantiomers of 1-phenyl-2-propanol which led to the conclusion that nucleophilic substitution of primary and secondary alkyl halides proceeds with inversion of configuration.

Learning Activities

Read 11.1 The Discovery of Nucleophilic Substitution Reactions and do any associated exercises.

11.2  The SN2 Reaction

Objectives

After completing this section, you should be able to

  1. write an expression relating reaction rate to the concentration of reagents for a second-order reaction.
  2. determine the order of a chemical reaction from experimentally obtained rate data.
  3. describe the essential features of the SN2 mechanism, and draw a generalized transition state for such a reaction.

Learning Activities

Read 11.2 The SN2 Reaction and do any associated exercises.

Examine Appendix B: Review of Chemical Kinetics to recall the basic principles of kinetics learned in first-year general chemistry.

11.3  Characteristics of the SN2 Reaction

Objectives

After completing this section, you should be able to

  1. discuss the role of steric effects in SN2 reactions.
  2. arrange a given series of alkyl halides in order of increasing or decreasing reactivity towards nucleophilic substitution through the SN2 mechanism.
  3. suggest a reason why vinyl halides and aryl halides do not undergo SN2 reactions.
  4. discuss how the nature of the nucleophile affects the rate of an SN2 reaction.
  5. arrange a given series of common nucleophiles (e.g., CN−, I−, Br− Cl−, H2O) in order of increasing or decreasing nucleophilicity.
  6. discuss how the nature of the leaving group affects the rate of an SN2 reaction.
  7. arrange a given series of leaving groups in order of increasing or decreasing ability to leave during an SN2 reaction.
  8. discuss the role played by the solvent in an SN2 reaction.
  9. give examples of the solvents which are commonly used for SN2 reactions, and identify those that promote a high reaction rate.
  10. predict which of two given SN2 reactions will proceed faster, by taking into account the structure of the substrates, the nucleophiles involved, leaving-group ability, solvent effects, or any combination of these factors.

Learning Activities

Read 11.3 Characteristics of the SN2 Reaction and do any associated exercises.

11.4  The SN1 Reaction

Objectives

After completing this section, you should be able to

  1. write an expression relating reaction rate and reactant concentration for a first-order reaction.
  2. compare the kinetics of SN1 and SN2 reactions.
  3. identify the rate-limiting step for a reaction, given the reaction energy diagram.
  4. sketch a reaction energy diagram for a reaction, given the mechanism and sufficient information to identify the rate-limiting step.
  5. write the mechanism of a typical SN1 reaction, and discuss the important features of the mechanism.
  6. discuss the stereochemistry of an SN1 reaction, and explain why a racemic mixture is expected when substitution takes place at the chiral carbon atom of an optically pure substrate.
  7. explain why unimolecular nucleophilic substitution at the chiral carbon atom of an optically pure substrate does not result in complete racemization.
  8. compare the stereochemical consequences of the SN1 mechanism with those of the SN2 mechanism.

Learning Activities

Read 11.4 The SN1 Reaction and do any associated exercises.

11.5  Characteristics of the SN1 Reaction

Objectives

After completing this section, you should be able to

  1. discuss how the structure of the substrate affects the rate of a reaction occurring by the SN1 mechanism.
  2. arrange a given list of carbocations (including benzyl and allyl) in order of increasing or decreasing stability.
  3. explain the high stability of the allyl and benzyl carbocations.
  4. arrange a given series of compounds in order of increasing or decreasing reactivity in SN1 reactions, and discuss this order in terms of the Hammond postulate.
  5. discuss how the nature of the leaving group affects the rate of an SN1 reaction, and in particular, explain why SN1 reactions involving alcohols are carried out under acidic conditions.
  6. explain why the nature of the nucleophile does not affect the rate of an SN1 reaction.
  7. discuss the role played by the solvent in an SN1 reaction, and hence determine whether a given solvent will promote reaction by this mechanism.
  8. compare the roles played by the solvent in SN1 and in SN2 reactions.
  9. determine which of two SN1 reactions will occur faster, by taking into account factors such as the structure of the substrate and the polarity of the solvent.
  10. determine whether a given reaction is most likely to occur by an SN1 or SN2 mechanism, based on factors such as the structure of the substrate, the solvent used, etc.

Learning Activities

Read 11.5 Characteristics of the SN1 Reaction and do any associated exercises.

11.6  Biological Substitution Reactions

Objective

After completing this section, you should have an appreciation that SN1 and SN2 mechanisms exist and are well-known in biological chemistry.

Learning Activities

Read 11.6 Biological Substitution Reactions and note that these pathways are important in natural systems and biosynthesis. (You are not responsible for details of the mechanisms presented.)

11.7  Elimination Reactions: Zaitsev’s Rule

Objective

After completing this section, you should be able to apply Zaitsev’s rule to predict the major product in a base-induced elimination of an unsymmetrical halide.

Learning Activities

Read 11.7 Elimination Reactions: Zaitsev’s Rule and do any associated exercises.

11.8  The E2 Reaction and the Deuterium Isotope Effect

Objectives

After completing this section, you should be able to

  1. write the mechanism of a typical E2 reaction.
  2. sketch the transition state of a typical E2 reaction.
  3. discuss the kinetic evidence that supports the proposed E2 mechanism.
  4. discuss the stereochemistry of an E2 reaction, and explain why the anti periplanar geometry is preferred.
  5. determine the structure of the alkene produced from the E2 reaction of a substrate containing two chiral carbon atoms.
  6. describe the deuterium isotope effect, and discuss how it can be used to provide evidence in support of the E2 mechanism.

Learning Activities

Read 11.8 The E2 Reaction and the Deuterium Isotope Effect and do any associated exercises.

11.9  The E2 Reaction and Cyclohexane Conformation

Objectives

After completing this section, you should be able to

  1. identify anti periplanar arrangements of atoms in substituted cyclohexanes.
  2. determine which cyclohexane conformation will generate a specific anti periplanar arrangement.

Learning Activities

Read 11.9 The E2 Reaction and Cyclohexane Conformation and do any associated exercises.

11.10  The E1 and E1cB Reactions

Objectives

After completing this section, you should be able to

  1. write the mechanism for a typical E1 reaction.
  2. explain why E1 elimination often accompanies SN1 substitution.
  3. write an equation to describe the kinetics of an E1 reaction.
  4. discuss the stereochemistry of E1 reactions.
  5. account for the lack of a deuterium isotope effect in E1 reactions.

Learning Activities

Read 11.10 The E1 and E1cB Reactions and do any associated exercises.

11.11  Biological Elimination Reactions

Objective

After completing this section, you should have an appreciation that E1, E2 and E1cB mechanisms exist and are well-known in biological chemistry.

Learning Activities

Read 11.11 Biological Elimination Reactions and note that these pathways are important in natural systems and biosynthesis. (You are not responsible for details of the mechanisms presented.)

11.12  A Summary of Reactivity: SN1, SN2, E1, E1cB, and E2

Objectives

After completing this section, you should be able to

  1. determine whether a specified substrate is most likely to undergo an E1, E2, SN1, or SN2 reaction under a given set of conditions.
  2. describe the conditions under which a given substrate is most likely to react by a specified mechanism (E1, E2, SN1, or SN2).

Learning Activities

Read 11.12 A Summary of Reactivity: SN1, SN2, E1, E1cB, and E2 and do any associated exercises.

Summary

An important point that has been neglected is the ability of certain carbocations to undergo rearrangement. For example, it is often possible for a carbocation formed in an E1 or SN1 process to rearrange to form a more stable carbocation. This ability can result in the formation of some “unexpected” products, and is often cited as another method of determining whether the mechanism of a given reaction involves a carbocation. We will discuss the rearrangement of carbocations in Section 16.3, but we mention it briefly here to warn you that it may be discussed in the nucleophilic substitution section of other organic chemistry textbooks to which you might refer.

When you are confident in your mastery of the material presented in Units 10 and 11, please complete Self Test 4.