1. Reaction mechanisms

2. Ionic Reactions

3. Ionic Reactions

4. Ionic Reactions

5. Ionic Reactions

6. Bond Polarity
Partial charges

7. Nucleophiles and Electrophiles

8. Leaving Groups

9. Radical Reactions

10. Type of Reactions

11. Nucleophilic reactions: nucleophilic substitution (SN)
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

12. Nucleophilic Substitution
Some nucleophilic substitution reactions

13. Mechanism
Chemists propose two limiting mechanisms for nucleophilic displacement
a fundamental difference between them is the timing of bond breaking and bond forming steps
At one extreme, the two processes take place simultaneously; designated SN2
S = substitution
N = nucleophilic
2 = bimolecular (two species are involved in the rate-determining step)
rate = k[haloalkane][nucleophile]
In the other limiting mechanism, bond breaking between carbon and the leaving group is entirely completed before bond forming with the nucleophile begins. This mechanism is designated SN1 where
S = substitution
N = nucleophilic
1 = unimolecular (only one species is involved in the rate-determining step)
rate = k[haloalkane]

14. SN2 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

15. SN2 An energy diagram for an SN 2 reaction
there is one transition state and no reactive intermediate

16. SN1 reaction: unimolecular nucleophilic substitution
SN1 is illustrated by the solvolysis of tert-butyl bromide
Step 1: ionization of the C-X bond gives a carbocation intermediate

17. SN1
Step 2: reaction of the carbocation (an electrophile) with methanol (a nucleophile) gives an oxonium ion
Step 3: proton transfer completes the reaction

18. SN1
An energy diagram for an SN1 reaction

19. SN1
For an SN1 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
OCH 3 CH O
(R)-Enantiomer
(S)-Enantiomer

20. Effect of variables on SN 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

21. Effect of substituents on SN2

22. Effect of substituents on SN1

23. Effect of substituents on SN reactions
governed by electronic factors, namely the relative stabilities of carbocation intermediates
relative rates: 3° > 2° > 1° > methyl
SN2 reactions
governed by steric factors, namely the relative ease of approach of the nucleophile to the site of reaction
relative rates: methyl > 1° > 2° > 3°

24. Effect of substituents on SN reactions
Effect of electronic and steric factors in competition between SN1 and SN2 reactions

25. Nucleophilicity
Nucleophilicity: 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

26. Nucleophilicity

27. Nucleophilicity

28. Leaving Group

29. Leaving Group

30. The Leaving Group
the best leaving groups in this series are the halogens I-, Br-, and Cl-
OH-, RO-, and NH2- are such poor leaving groups that they are rarely if ever displaced in nucleophilic substitution reactions

31. Solvent Effect Protic solvent: a solvent that contains an -OH group
these solvents favor SN1 reactions; the greater the polarity of the solvent, the easier it is to form carbocations in it

32. Solvent Effect Aprotic solvent: does not contain an -OH group
it is more difficult to form carbocations in aprotic solvents
aprotic solvents favor SN2 reactions

33. Summary of SN1 and SN2

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

35. b-Elimination
There are two limiting mechanisms for β-elimination reactions
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: 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

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

37. 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

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

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

40. Substitution vs Elimination
Many nucleophiles are also strong bases (OH- and RO-) and SN and E reactions often compete
the ratio of SN/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

41. SN1 versus E1
Reactions of 2° and 3° haloalkanes in polar protic solvents give mixtures of substitution and elimination products

42. SN2 versus E2
It is considerably easier to predict the ratio of SN2 to E2 products

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

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

45. Summary of S vs E for Haloalkanes
Examples: predict the major product and the mechanism for each reaction
Elimination, strong base, high temp.
SN2, weak base, good nucleophil
SN1 (+Elimination), strong base, good nucleophil, protic solvent
No reaction,
I is a weak base (SN2)
I better leaving group than Cl

46. 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

47. Carbocation rearrangements in SN + E reactions

48. Carbocation rearrangements in SN + 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)

49. Carbocation rearrangements in Electrophilic addition reactions