1. William Brown Thomas Poon www.wiley.com/college/brown Chapter Seven Haloalkanes

2. 7-2 Structure Haloalkane (alkyl halide):Haloalkane (alkyl halide): A compound containing a halogen atom covalently bonded to an sp 3 hybridized carbon. given the symbol RX

3. 7-3 Nomenclature - IUPAC Locate the parent alkane. Number the parent chain to give the substituent encountered first the lower number. Show halogen substituents by the prefixes fluoro-, chloro-, bromo-, and iodo- and list them in alphabetical order with other substituents. Locate each halogen on the parent chain.

4. 7-4 Nomenclature Several polyhaloalkanes are common solvents and are generally referred to by their common or trivial names.

5. 7-5 Freons & Their Alternatives The Freons are chlorofluorocarbons (CFCs) Among the most widely used are/were Much lower ozone-depleting alternatives are the hydrofluorocarbons (HFCs) and the hydrochlorofluorocarbons (HCFCs), including

6. 7-6 Substitution & Elimination In this chapter we, concentrate on two types of reactions: nucleophilic substitution  -elimination

7. 7-7 Nucleophilic Substitution In the following general reaction, substitution takes place on an sp 3 hybridized (tetrahedral) carbon.

8. 7-8 Nucleophilic Substitution Table 7.1 Some Nucleophilic Substitution Reactions

9. 7-9 Mechanism Chemists propose two limiting mechanisms for nucleophilic substitutions. A fundamental difference between them is the timing of bond breaking and bond forming steps. S N 2At one extreme, the two processes take place simultaneously; designated S N 2. S = substitution N = nucleophilic 2 = bimolecular (two species are involved in the rate- determining step) rate = k[haloalkane][nucleophile]

10. 7-10 SN2SN2 Both reactants are involved in the transition state of the rate-determining step. The nucleophile attacks the reactive center from the side opposite the leaving group.

11. 7-11 SN2SN2 Table 7.1 An energy diagram for an S N 2 reaction. There is one transition state and no reactive intermediate.

12. 7-12 SN1SN1 In the other limiting mechanism, bond breaking between carbon and the leaving group is entirely completed before bond forming with the nucleophile begins. S N 1This mechanism is designated S N 1 where S = substitution N = nucleophilic 1 = unimolecular (only one species is involved in the rate- determining step) rate = k[haloalkane]

13. 7-13 SN1SN1 S N 1 is illustrated by the solvolysis of tert-butyl bromide. Step 1: Ionization of the C-X bond gives a carbocation intermediate.

14. 7-14 SN1SN1 Step 2: Reaction of the carbocation (an electrophile) with methanol (a nucleophile) gives an oxonium ion. Step 3: Proton transfer to methanol completes the reaction.

15. 7-15 SN1SN1 Figure 7.2 An energy diagram for an S N 1 reaction.

16. 7-16 SN1SN1 For an S N 1 reaction at a stereocenter, the product is a racemic mixture.

17. 7-17 SN1SN1 The nucleophile attacks with equal probability from either face of the planar carbocation intermediate.

18. 7-18 Evidence for S N Reactions Let us examine some of the experimental evidence on which these two mechanisms are based and, as we do, consider the following questions. What affect does the structure of the nucleophile have on the rate of reaction? What effect does the structure of the haloalkane have on the rate of reaction? What effect does the structure of the leaving group have on the rate of reaction? What is the role of the solvent?

19. 7-19 Nucleophilicity NucleophilicityNucleophilicity: a kinetic property measured by the rate at which a Nu: attacks a reference compound under a standard set of experimental conditions. For example, the rate at which a set of nucleophiles displaces bromide ion from bromoethane in ethanol at 25°C. Table 7.2 shows common nucleophiles and their relative nucleophilicities

20. 7-20 Relative Nucleophilicity Table 7.2 Some Common Nucleophiles and their Relative Effectiveness

21. 7-21 Structure of the Haloalkane S N 1 reactions electronic factorsGoverned by electronic factors, namely the relative stabilities of carbocation intermediates. Relative rates: 3° > 2° > 1° > methyl S N 2 reactions steric factorsGoverned by steric factors, namely the relative ease of approach of the nucleophile to the site of reaction. Relative rates: methyl > 1° > 2° > 3°

22. 7-22 Structure of the Haloalkane Steric factors Compare access to the reaction center in bromoethane and 2-bromo-2-methylpropane (tert-butyl chloride).

23. 7-23 Structure of the Haloalkane Figure 7.3 Effect of electronic and steric factors in competition between S N 1 and S N 2 reactions of haloalkanes.

24. 7-24 The Leaving Group The best leaving groups in this series are the halogens I -, Br -, and Cl -. OH -, RO -, and NH 2 - are such poor leaving groups that they are rarely if ever displaced in nucleophilic substitution reactions.

25. 7-25 The Solvent Protic solventProtic solvent: a solvent that contains an -OH group. Table 7.3 Common Protic Solvents

26. 7-26 The Solvent Aprotic solventAprotic solvent: does not contain an -OH group. Aprotic solvents favor S N 2 reactions. Although the solvents at the top of the table are polar, formation of carbocations in them is more difficult than in protic solvents.

27. 7-27 Table 7.5 Summary of S N 1 and S N 2

28. 7-28 Nucleophilic Substitution Examples: predict the product of each reaction, the mechanism, and the stereochemistry of the product

29. 7-29  -Elimination  -Elimination  -Elimination: Removal of atoms or groups of atoms from adjacent carbons to form a carbon-carbon double bond. dehydrohalogenationWe study a type of  -elimination called dehydrohalogenation (the elimination of HX).

30. 7-30  -Elimination Zaitsev rule:Zaitsev rule: The major product of a  -elimination is the more stable (the more highly substituted) alkene.

31. 7-31  -Elimination There are two limiting mechanisms for  -elimination reactions. E1 mechanism:E1 mechanism: at one extreme, breaking of the C-X bond is complete before reaction with base breaks the C-H bond. Only R-X is involved in the rate-determining step. E2 mechanism:E2 mechanism: at the other extreme, breaking of the C-X and C- H bonds is concerted. Both R-X and base are involved in the rate-determining step.

32. 7-32 E1 Mechanism Step 1: Rate-determining ionization of C-X gives a carbocation intermediate. Step 2: Proton transfer from the carbocation intermediate to a base (in this case, the solvent) gives the alkene.

33. 7-33 E2 Mechanism A one-step mechanism; all bond-breaking and bond- forming steps are concerted.

34. 7-34 Elimination Reactions Table 7.6 Summary of E1 versus E2 Reactions for Haloalkanes

35. 7-35 Substitution versus Elimination Because many nucleophiles are also strong bases (OH - and RO - ), S N and E reactions often compete. The ratio of S N /E products depends on the relative rates of the two reactions.

36. 7-36 S N 1 versus E1 Reactions of 2° and 3° haloalkanes in polar protic solvents give mixtures of substitution and elimination products. Product ratios are difficult to predict.

37. 7-37 S N 2 versus E2 It is considerably easier to predict the ratio of S N 2 to E2 products.

38. 7-38 Summary of S versus E for Haloalkanes For methyl and 1° haloalkanes

39. 7-39 Summary of S versus E for Haloalkanes For 2° and 3° haloalkanes

40. 7-40 Summary of S versus E for Haloalkanes Examples: Predict the major product and the mechanism for each reaction.

41. 7-41 Haloalkanes End Chapter 7