Chapter 9 The Chemistry of Alkyl Halides

Transcription

1 Organic Chemistry, 5th ed. Marc Loudon Chapter 9 The Chemistry of Alkyl Halides Eric J. Kantorowski California Polytechnic State University San Luis Obispo, CA

2 Chapter 9 Overview 9.1 An Overview of Nucleophilic Subs8tu8on and β Elimina8on Reac8ons 9.2 Equilibria in Nucleophilic Subs8tu8on Reac8ons 9.3 Reac8on Rates 9.4 The S N 2 Reac8on 9.5 The E2 Reac8on 9.6 The S N 1 and E1 Reac8on 9.7 Summary of Subs8tu8on and Elimina8on Reac8ons of Alkyl Halides 9.8 Carbenes and Carbenoids 2

3 Subs2tu2on and Elimina2on Reac2ons Alkyl halides provide simple models for these reac8ons Nucleophilic subs8tu8on reac8ons: 9.1 An Overview of Nucleophilic SubsAtuAon and β EliminaAon ReacAons 3

4 Subs2tu2on and Elimina2on Reac2ons 9.1 An Overview of Nucleophilic SubsAtuAon and β EliminaAon ReacAons 4

5 Subs2tu2on and Elimina2on Reac2ons Intramolecular reac8ons are also possible: 9.1 An Overview of Nucleophilic SubsAtuAon and β EliminaAon ReacAons 5

6 Subs2tu2on and Elimina2on Reac2ons β Elimina8on reac8ons: 9.1 An Overview of Nucleophilic SubsAtuAon and b EliminaAon ReacAons 6

7 Subs2tu2on and Elimina2on Reac2ons The carbon bearing the halogen is ooen labeled as the α carbon Any adjacent carbons are labeled as β carbons Loss of two groups from adjacent carbons is a β elimina8on 9.1 An Overview of Nucleophilic SubsAtuAon and b EliminaAon ReacAons 7

8 Subs2tu2on vs Elimina2on Nucleophilic subs8tu8on and β elimina8on reac8ons ooen compete with one another 9.1 An Overview of Nucleophilic SubsAtuAon and b EliminaAon ReacAons 8

9 Equilibria in Subs2tu2on Reac2ons Some subs8tu8on reac8ons proceed to comple8on, others may be unfavorable 9.2 Equilibria in Nucleophilic SubsAtuAon ReacAons 9

10 Equilibria in Subs2tu2on Reac2ons Recognize that each nucleophilic subs8tu8on reac8on is similar to a BrØnsted Lowry acidbase reac8on The equilibrium in a nucleophilic subs8tu8on reac8on favors the release of the weaker base 9.2 Equilibria in Nucleophilic SubsAtuAon ReacAons 10

11 Defini2on of Reac2on Rates Knowledge of the equilibrium constant for a reac8on says nothing about how fast it will take place The quan88es that changes with 8me in a chemical reac8on are [reactants] & [products] 9.3 ReacAon Rates 11

12 The Rate Law The rate law expresses how the reac8on rate depends on the concentra8ons of reactants For example, Overall kine8c order is second order First order in [A], first order in [B] 9.3 ReacAon Rates 12

13 Rate Constant and ΔG The rate constant is related to the standard free energy of ac8va8on, ΔG 9.3 ReacAon Rates 13

14 Rate Constant and ΔG 9.3 ReacAon Rates 14

15 Rate Constant and ΔG Most ooen we are interested in the relaave rates of two reac8ons 9.3 ReacAon Rates 15

16 The S N 2 Reac2on The rate law for this reac8on was experimentally determined to be: Specifically, the concentra8on terms indicate which atoms are present in the transiaon state of the rate limiang step 9.4 The S N 2 ReacAon 16

17 The S N 2 Reac2on The simplest possible mechanism is then: This one step, concerted mechanism is classified as an S N 2 reac8on: 9.4 The S N 2 ReacAon 17

18 The S N 2 Reac2on The rate law tells us nothing about how the atoms are arranged 9.4 The S N 2 ReacAon 18

19 S N 2 vs BrØnsted Lowry Reac2on Rates Most ordinary acid base reac8ons occur instantaneously Most nucleophilic subs8tu8on reac8ons are much slower 9.4 The S N 2 ReacAon 19

20 Stereochemistry of the S N 2 Reac2on How does the S N 2 reac8on occur? Via reten8on of configura8on: or via inversion of configura8on? 9.4 The S N 2 ReacAon 20

21 Stereochemistry of the S N 2 Reac2on Experimental results have shown that S N 2 reac8ons proceed via inversion! 9.4 The S N 2 ReacAon 21

22 Stereochemistry of the S N 2 Reac2on 9.4 The S N 2 ReacAon 22

23 MO Analysis of the S N 2 Reac2on 9.4 The S N 2 ReacAon 23

24 Effect of Alkyl Halide Structure The reac8on rate is strongly influenced by structure (a steric effect) 9.4 The S N 2 ReacAon 24

25 Transi2on States for S N 2 Reac2ons 9.4 The S N 2 ReacAon 25

26 Nucleophilicity in the S N 2 Reac2on A wide variety of nucleophiles may be used for the S N 2 reac8on This adds great versa8lity to the S N 2 reac8on There is a correla8on between nucleophilicity and basicity (both are aspects of Lewis basicity) 9.4 The S N 2 ReacAon 26

27 Basicity of the Nucleophile and S N 2 Rates 9.4 The S N 2 ReacAon 27

28 Basicity of the Nucleophile and S N 2 Rates No8ce the reversal of the basicity vs nucleophilicity trend for these cases 9.4 The S N 2 ReacAon 28

29 Basicity of the Nucleophile and S N 2 Rates The following apply to nucleophilic anions in polar, proac solvents (e.g., water, alcohols): For nucleophiles in the same period, more basic nucleophiles are more nucleophilic For nucleophiles in the same group, less basic nucleophiles are more nucleophilic The solvent has the greatest influence on these rela8onships 9.4 The S N 2 ReacAon 29

30 Solvent Effects In pro8c solvents, H bonding can occur with the nucleophilic (Lewis basic) anions Stronger bases form stronger H bonds 9.4 The S N 2 ReacAon 30

31 Solvent Effects Changing to a polar, aproac solvent greatly enhances nucleophilicity 9.4 The S N 2 ReacAon 31

32 Leaving Group Effects in the S N 2 Reac2on The best leaving groups are the ones that give the weakest bases Leaving groups are not limited to halogens A variety of alcohol deriva8ves will soon be introduced 9.4 The S N 2 ReacAon 32

33 Rate Law and Mechanism of E2 9.5 The E2 ReacAon 33

34 A Concerted Mechanism Removal of the β H and loss of the leaving group occurs simultaneously 9.5 The E2 ReacAon 34

35 Leaving Group Effects The trend observed for the S N 2 reac8on is seen again for the E2 reac8on 9.5 The E2 ReacAon 35

36 Deuterium Isotope Effects The C D bond is somewhat stronger than the C H bond This retards the E2 reac8on rate Typically k H /k D is in the range of Referred to as a primary isotope effect 9.5 The E2 ReacAon 36

37 Deuterium Isotope Effects 9.5 The E2 ReacAon 37

38 Stereochemistry of the E2 Reac2on The E2 reac8on can take place in two stereochemically dis8nct ways: Syn elimina2on: the dihedral angle is 0 An& elimina2on: the dihedral angle is The E2 ReacAon 38

39 Stereochemistry of the E2 Reac2on Most E2 elimina8ons are stereoselec8vely ana elimina8ons 9.5 The E2 ReacAon 39

40 Stereochemistry of the E2 Reac2on Some conforma8onally restricted cases may proceed via syn elimina8on 9.5 The E2 ReacAon 40

41 Stereochemistry of the E2 Reac2on Reasons why ana elimina8on is preferred: 9.5 The E2 ReacAon 41

42 Regioselec2vity of the E2 Reac2on When more than one type of β H is available, more than one alkene product can be formed With simple alkoxide bases, the most stable alkene isomer usually dominates 9.5 The E2 ReacAon 42

43 Regioselec2vity of the E2 Reac2on The predominance of the more stable alkene isomer does not result from equilibraaon The alkenes products are stable under the reac8on condi8ons Hence, the product distribu8on reflects the rela8ve rates of their forma8on 9.5 The E2 ReacAon 43

44 Regioselec2vity and Transi2on States 9.5 The E2 ReacAon 44

45 S N 2 vs E2 S N 2 vs E2 is dependent on the structure of the alkyl halide and structure of the base 9.5 The E2 ReacAon 45

46 S N 2 vs E2 Secondary alkyl halides: 9.5 The E2 ReacAon 46

47 Primary alkyl halides: S N 2 vs E2 9.5 The E2 ReacAon 47

48 S N 2 vs E2 Base structure: 9.5 The E2 ReacAon 48

49 Rate Law and Mechanism of S N 1 and E1 The reac8on of an alkyl halide with a solvent (and no other base or nucleophile) is called a solvolysis reac8on 9.6 The S N 1 and E1 ReacAon 49

50 Rate Law and Mechanism of S N 1 and E1 The rate determining first step is common to both reac8ons: For elimina8on: 9.6 The S N 1 and E1 ReacAon 50

51 Rate Law and Mechanism of S N 1 and E1 For subs8tu8on: 9.6 The S N 1 and E1 ReacAon 51

52 Rate Limi2ng and Product Determining Steps The rates of the product forming steps have nothing to do with the rate at which the alkyl halide reacts 9.6 The S N 1 and E1 ReacAon 52

53 Rate Limi2ng and Product Determining Steps 9.6 The S N 1 and E1 ReacAon 53

54 Reac2vity and Product Distribu2on 9.6 The S N 1 and E1 ReacAon 54

55 Reac2vity and Product Distribu2on 9.6 The S N 1 and E1 ReacAon 55

56 Rearrangements Rearrangements are a telltale sign of carbocaaon intermediates 9.6 The S N 1 and E1 ReacAon 56

57 Stereochemistry of the S N 1 Reac2on Racemiza8on is expected 9.6 The S N 1 and E1 ReacAon 57

58 Stereochemistry of the S N 1 Reac2on but, experimentally: ParAal racemizaaon is observed; net inversion is also observed 9.6 The S N 1 and E1 ReacAon 58

59 Stereochemistry of the S N 1 Reac2on 9.6 The S N 1 and E1 ReacAon 59

60 Summary of Subs2tu2on and Elimina2on Key ques8ons for evalua8on: 1. Is the alkyl halide primary, secondary, ter8ary? If primary or secondary, is there significant βsubs8tu8on? 2. Is a Lewis base present? Is it a good nucleophile, strong BrØnsted base, or both? 3. What is the solvent? Polar pro8c or polar apro8c? 9.7 Summary of SubsAtuAon and EliminaAon ReacAons of Alkyl Halides 60

61 Summary of Subs2tu2on and Elimina2on 9.7 Summary of SubsAtuAon and EliminaAon ReacAons of Alkyl Halides 61

62 Summary of Subs2tu2on and Elimina2on 9.7 Summary of SubsAtuAon and EliminaAon ReacAons of Alkyl Halides 62

63 α Elimina2on Reac2ons Alkyl halides with no β H s, but an α H undergo a different elimina8on process This is an example of a carbene, a species with a divalent carbon atom 9.8 Carbenes and Carbenoids 63

64 Carbenes Carbon lacks an octet = electron deficient The lone pair can act as a nucleophile Hence, carbenes are simultaneously nucleophilic and electrophilic 9.8 Carbenes and Carbenoids 64

65 Cyclopropane Forma2on from Carbenes 9.8 Carbenes and Carbenoids 65

66 Cyclopropane Forma2on from Carbenes Due to the concerted mechanism the stereochemistry of the star8ng alkene is preserved 9.8 Carbenes and Carbenoids 66

67 The Simmons Smith Reac2on Cyclopropanes without halogens can also be prepared A carbenoid is a reagent that is not a free carbene but has carbene like reac8vity 9.8 Carbenes and Carbenoids 67

68 The Simmons Smith Reac2on Similarly, the stereochemistry of the star8ng alkene is preserved 9.8 Carbenes and Carbenoids 68