1. ORGANOHALIDES + Nucleophilic Reactions (SN1/2, E1/E2/E1cB)
CH21 PS CLASS

2. Preparation of Organohalides
From ALKENES C=C [just review old lessons]
FOR TERTIARY ALCOHOLS, we can simply use H-X (gas) X=Cl,Br in ether, 0°C

3. Preparation of Organohalides
FOR TERTIARY ALCOHOLS, we can simply use H-X (gas) X=Cl,Br in ether, 0°C
Follows SN1 so a carbocation is formed,
be careful with rearrangements!

4. Preparation of Organohalides
FOR PRIMARY/SECONDARY ALCOHOLS: SOCl2 / PBr3

5. Practice

6. Alkyl Fluorides
Also from ALCOHOLS +
HF / Pryidine
(CH3CH2)2NSF3

7. Grignard Reagents
Reaction of R-X with Mg over ether/THF to form R-Mg-X organometallic compound.

8. Grignard Reagents: reduction of R-X

9. More samples:

10. Nucleophilic Reactions
R-X, alkyl halides are ELECTROPHILES (positive or electron-poor)
They react with NUCLEOPHILES/BASES (negative or electron-rich)
Either substitution
C-C-X becomes C-C-blah + X-
or elimination reactions
C-C-X becomes C=C + X-

11. SUBSTITUTION REACTIONS
S – substitution: R-X + Nu  R-Nu + X-
N – Nucleophilic
1 or 2  unimolecular or bimolecular rates
INVERSION (change of stereochemistry) CAN HAPPEN!

12. Try this first…

13. SN2  BIMOLECULAR
Bimolecular simply refers to the rate depending on BOTH reactants because of the nature of the mechanism
Rate = k[RX][Nu]
Rate depends on both because there is
ONE SINGLE COLLISION BETWEEN RX and Nu to form a Nu-R-X transition state

14. SN2  BIMOLECULAR 100% INVERSION OF STEREOCHEMISTRY OCCURS! SUBSTRATE
LEAVING GROUP

15. Factors that affect SN2 RXNS:
STERIC EFFECTS TO INCOMING Nu:
C=C-X (vinylic) and Ar-X (aryl) TOTALL UNREACTIVE

16. Factors that affect SN2 RXNS:
THE NUCLEOPHILE

17. Factors that affect SN2 RXNS:
THE LEAVING GROUP
should be stable on its own as a free anion
Comparing halides, we go down the column

18. Factors that affect SN2 RXNS:
Alcohols and fluorides usually do not undergo SN2 because OH- and F- aren’t good leaving groups
This is why we use SOCl2 and PBr3 … THEY CONVERT THE –OH INTO A BETTER LEAVING GROUP

19. Factors that affect SN2 RXNS:
Reaction SOLVENT can also affect the reaction.
We prefer POLAR APROTIC SOLVENTS
POLAR but no –OH or –NH in the molecule (no H2O, NH3, etc…)
Polar protic solvents form a CAGE around Nu

20. Practice

21. Practice

22. Practice

23. Practice

24. SN1  UNIMOLECULAR
Unimolecular: rate depends only on the substrate (mechanism), almost opposite of SN2
Rate = k[RX]
Rate is only dependent on the slowest step which is the spontaneous dissociation of your leaving group. (molecules just don’t easily dissociate!)

25. SN1  UNIMOLECULAR

26. SN1  UNIMOLECULAR

27. SN1  UNIMOLECULAR
STEREOCHEM IS LOST, A RACEMATE FORM IS MADE, but usually not 50:50

28. SN1  UNIMOLECULAR
STEREOCHEM IS LOST, A RACEMATE FORM IS MADE, but usually not 50:50
An ION PAIR BLOCKS THE OTHER SIDE!

29. Factors that affect SN1 RXNS:
SUBSTRATE:

30. Factors that affect SN1 RXNS:
LEAVING GROUP:
An –OH in acidic medium can become –OH2+ and leave as H2O which is very favorable

31. Factors that affect SN1 RXNS:
NUCLEOPHILE: no effect, almost at all.

32. Factors that affect SN1 RXNS:
SOLVENT: rates increase if you stabilize carbocation transition state.
POLAR PROTIC!

33. Factors that affect SN1 RXNS:
SOLVENT: rates increase if you stabilize carbocation transition state.
POLAR PROTIC!

34. PRACTICE

35. PRACTICE

36. PRACTICE

37. PRACTICE

38. PRACTICE

39. PRACTICE

40. PRACTICE

41. Elimination Reactions
More compliated (different mechanisms)
The loss of H-X can lead to a MIXTURE of alkene products (C-C-X  C=C + HX)
But we can predict the most stable/major poduct
ZAITZEV’S RULE: base-induced eliminations will form more stable alkene

42. E2 elimination
Again, bimolecular so a single collision between your Base B: and the alkyl halide.

43. E2 elimination
Anti-periplanar is favored for transition state

44. E2 elimination
Anti-periplanar is favored for transition state

45. Practice

46. Practice

47. Practice

48. Practice

49. E1 reaction
Unimolecular, ALSO spontaneously forms carbocation, but then followed by loss of H+ (taken by a base B: and not an attack by Nu:)
COMPETES WITH SN1 reactions!

50. E1 reaction

51. E1 reactions
No need for anti periplanar geometry

52. PRACTICE

53. PRACTICE

54. E1cB
Unimolecular, but this time CARBANION formed because a proton H+ is first removed by a base.
cB stands for “conjugate base” because you deprotonate your carbon C-H into a C- and H+
Usually favored for poor leaving groups (e.g. –OH)
Carbanion can be stabilized with C=O groups nearby

55. E1cB

56. E1cB
PRESENCE OF C=O NEARBY CAN GIVE
RESONANCE STABILIZATION!

57. PREDICTING WHAT PREDOMINATES:

58. Slight Clarifications: BASE vs. NUCLEOPHILE
Affinity for a PROTON
Strong base like R-O- or OH-
Usually a LEWIS BASE
In this context, how attracted to a CARBON

59. PRACTICE

60. PRACTICE

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68. PRACTICE