1. 1 Reaction mechanisms

2. 2 Bond Polarity Partial charges

3. 3

4. 4 Type of Reactions

5. 5

6. 6 Nucleophiles and Electrophiles

7. 7

8. 8

9. 9 Leaving Groups

10. 10

11. 11 Radical Reactions

12. 12

13. 13

14. 14

15. 15 Nucleophilic reactions: Nucleophilic substitution: -> reagent is nucleophil -> nucleophil replaces leaving group -> competing reaction (elimination + rearrangements) in the following general reaction, substitution takes place on an sp3 hybridized (tetrahedral) carbon 1. nucleophilic substitution (S N )

16. 16 Some nucleophilic substitution reactions

17. 17 Mechanism Chemists propose two limiting mechanisms for nucleophilic displacement –a fundamental difference between them is the timing of bond breaking and bond forming steps S N 2 At 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]

18. 18 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]

19. 19 S N 2 reaction: bimolecular nucleophilic substitution –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

20. 20 SN2SN2 An energy diagram for an S N 2 reaction –there is one transition state and no reactive intermediate

21. 21 S N 1 is illustrated by the solvolysis of tert-butyl bromide –Step 1: ionization of the C-X bond gives a carbocation intermediate S N 1 reaction: unimolecular nucleophilic substitution

22. 22 SN1SN1 –Step 2: reaction of the carbocation (an electrophile ) with methanol (a nucleophile) gives an oxonium ion –Step 3: proton transfer completes the reaction

23. 23 An energy diagram for an S N 1 reaction SN1SN1

24. 24 For an S N 1 reaction at a stereocenter, the product is a racemic mixture the nucleophile attacks with equal probability from either face of the planar carbocation intermediate + A racemic mixture Cl C 6 H 5 C 6 H 5 COCH 3 H CH 3 OC H Cl (R)-Enantiomer(S)-Enantiomer SN1SN1

25. 25 Effect of variables on S N Reactions –the nature of substituents bonded to the atom attacked by nucleophile –the nature of the nucleophile –the nature of the leaving group –the solvent effect

26. 26 Effect of substituents on S N 2

27. 27 Effect of substituents on S N 1

28. 28 S N 1 reactions electronic factors –governed by electronic factors, namely the relative stabilities of carbocation intermediates –relative rates: 3° > 2° > 1° > methyl S N 2 reactions steric factors –governed by steric factors, namely the relative ease of approach of the nucleophile to the site of reaction –relative rates: methyl > 1° > 2° > 3° Effect of substituents on SN reactions

29. 29 Effect of substituents on S N reactions Effect of electronic and steric factors in competition between S N 1 and S N 2 reactions

30. 30 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 Two important features: - An anion is a better nucleophile than a uncharged conjugated acid - strong bases are good nucleophiles

31. 31 Nucleophilicity

32. 32 Nucleophilicity

33. 33

34. 34 Leaving Group

35. 35

36. 36 Leaving Group

37. 37 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

38. 38 Solvent Effect Protic solventProtic solvent: a solvent that contains an -OH group –these solvents favor S N 1 reactions; the greater the polarity of the solvent, the easier it is to form carbocations in it

39. 39 Solvent Effect Aprotic solventAprotic solvent: does not contain an -OH group –it is more difficult to form carbocations in aprotic solvents –aprotic solvents favor S N 2 reactions

40. 40 Summary of S N 1 and S N 2

41. 41  Competing Reaction: Elimination  - Elimination  - Elimination: removal of atoms or groups of atoms from adjacent carbons to form a carbon-carbon double bond dehydrohalogenation –we study a type of  - elimination called dehydrohalogenation (the elimination of HX)

42. 42  - Elimination There are two limiting mechanisms for β-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

43. 43 E2 Mechanism A one-step mechanism; all bond-breaking and bond-forming steps are concerted

44. 44 E1 Mechanism –Step 1: 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 Nucleophile -> acting as a strong base

45. 45 Elimination Saytzeff rule:Saytzeff rule: the major product of a elimination is the more stable (the more highly substituted) alkene

46. 46 Elimination Reactions Summary of E1 versus E2 Reactions for Haloalkanes

47. 47 Substitution vs Elimination Many nucleophiles are also strong bases (OH - and RO - ) and S N and E reactions often compete –the ratio of S N /E products depends on the relative rates of the two reactions What favors Elimination reactions: - attacking nucleophil is a strong and large base - steric crowding in the substrate - High temperatures and low polarity of solvent

48. 48 S N 1 versus E1 Reactions of 2° and 3° haloalkanes in polar protic solvents give mixtures of substitution and elimination products

49. 49 S N 2 versus E2 It is considerably easier to predict the ratio of S N 2 to E2 products

50. 50 Summary of S vs E for Haloalkanes –for methyl and 1°haloalkanes

51. 51 Summary of S vs E for Haloalkanes –for 2° and 3° haloalkanes

52. 52 Summary of S vs E for Haloalkanes –Examples: predict the major product and the mechanism for each reaction Elimination, strong base, high temp. S N 2, weak base, good nucleophil S N 1 (+Elimination), strong base, good nucleophil, protic solvent No reaction, I is a weak base (S N 2) I better leaving group than Cl

53. 53 Penataan ulang via Carbocation (Rearrangements) Also 1,3- and other shifts are possible The driving force of rearrangements is -> to form a more stable carbocation !!! Happens often with secondary carbocations -> more stable tertiary carbocation

54. 54 Via Carbocation S N + E reactions Rearrangement

55. 55 Via S N + E reactions -> Wagner – Meerwein rearrangements Rearrangement of a secondary carbocations -> more stable tertiary carbocation Plays an important role in biosynthesis of molecules, i.e. Cholesterol -> (Biochemistry)

56. 56 Via Electrophilic addition reactions

57. 57 Ionic Reactions

58. 58 Ionic Reactions

59. 59 Ionic Reactions

60. 60 Ionic Reactions