1. Fischer-Rosanoff Convention
Before 1951, only relative configurations could be known.
Sugars and amino acids with same relative configuration as (+)-glyceraldehyde were assigned D and same as (-)-glyceraldehyde were assigned L.
With X-ray crystallography, now know absolute configurations: D is (R) and L is (S).
No relationship to dextro- or levorotatory =>

2. D and L Assignments * * *
=>

3. Properties of Diastereomers
Diastereomers have different physical properties: m.p., b.p.
They can be separated easily.
Enantiomers differ only in reaction with other chiral molecules and the direction in which polarized light is rotated.
Enantiomers are difficult to separate =>

4. Resolution of Enantiomers
React a racemic mixture with a chiral compound to form diastereomers, which can be separated.
=>

5. Chromatographic Resolution of Enantiomers
=>

7. Chapter 6 Alkyl Halides: Nucleophilic Substitution and Elimination
Organic Chemistry, 5th Edition L. G. Wade, Jr.
Chapter 6 Alkyl Halides: Nucleophilic Substitution and Elimination

8. Classes of Halides
Alkyl: Halogen, X, is directly bonded to sp3 carbon.
Vinyl: X is bonded to sp2 carbon of alkene.
Aryl: X is bonded to sp2 carbon on benzene ring.
Examples:
=>

9. Polarity and Reactivity
Halogens are more electronegative than C.
Carbon-halogen bond is polar, so carbon has partial positive charge.
Carbon can be attacked by a nucleophile.
Halogen can leave with the electron pair =>

10. Classes of Alkyl Halides
Methyl halides: only one C, CH3X
Primary: C to which X is bonded has only one C-C bond.
Secondary: C to which X is bonded has two C-C bonds.
Tertiary: C to which X is bonded has three C-C bonds =>

11. Classify These:
=>

12. Dihalides
Geminal dihalide: two halogen atoms are bonded to the same carbon
Vicinal dihalide: two halogen atoms are bonded
to adjacent carbons.
=>

13. IUPAC Nomenclature Name as haloalkane.
Choose the longest carbon chain, even if the halogen is not bonded to any of those C’s.
Use lowest possible numbers for position.
=>

14. Systematic Common Names
Name as alkyl halide.
Useful only for small alkyl groups.
Name these:
=>

15. “Trivial” Names CHX3 is a haloform. CX4 is carbon tetrahalide.
CH2X2 called methylene halide. .
CHX3 is a haloform.
CX4 is carbon tetrahalide.
Examples:
CH2Cl2 is methylene chloride
CHCl3 is chloroform -CHI3 is iodoform
CCl4 is carbon tetrachloride

16. Preparation of RX Free radical halogenation (Chapter 4) - REVIEW
Free radical allylic halogenation
produces alkyl halide with double bond on the neighboring carbon. LATER =>

17. Substitution Reactions
The halogen atom on the alkyl halide is replaced with another group.
Since the halogen is more electronegative than
carbon, the C-X bond breaks heterolytically and
X- leaves.
The group replacing X- is a nucleophile. =>

18. Elimination Reactions
The alkyl halide loses halogen as a halide ion, and also loses H+ on the adjacent carbon to a base.
The alkyl halide loses halogen as a halide ion, and
also loses H+ on the adjacent carbon to a base.
A pi bond is formed. Product is alkene.
Also called dehydrohalogenation (-HX).

19. Ingold

20. Father of Physical Organic Chemistry
Sir Christopher
Ingold
Father of Physical Organic Chemistry
Coined such names and symbols as:
SN1, SN2, E1, E2, nucleophile, electrophile
resonance effect, inductive effect/
In print, he often attacked enemies vigorously and sometimes in vitrolic manner.

21. SN2 Mechanism Both reactants are involved in RDS
Rate is first order in each reactant
Both reactants are involved in RDS
Note: one-step reaction with no intermediate
Bimolecular nuleophilic substitution.
Concerted reaction: new bond forming
and old bond breaking at same time
INVERSION OF CONFIGURATION

22. SN2 Energy Diagram One-step reaction.
Transition state is highest in energy. =>

23. Uses for SN2 Reactions Synthesis of other classes of compounds.
Halogen exchange reaction.
=>

24. SN2: Nucleophilic Strength
Stronger nucleophiles react faster.
Strong bases are strong nucleophiles, but not all strong nucleophiles are basic.
=>

25. Trends in Nuc. Strength
Of a conjugate acid-base pair, the base is stronger: OH- > H2O, NH2- > NH3
Decreases left to right on Periodic Table. More
electronegative atoms less likely to form new bond:
OH- > F-, NH3 > H2O
Increases down Periodic Table, as size and polarizability
increase: I- > Br- > Cl-

26. Polarizability Effect
=>

27. Bulky Nucleophiles
Sterically hindered for attack on carbon, so weaker nucleophiles.
=>

28. Solvent Effects (1)
Polar protic solvents (O-H or N-H) reduce the strength of the nucleophile. Hydrogen bonds must be broken before nucleophile can attack the carbon.
=>

29. Solvent Effects (2)
Polar aprotic solvents (no O-H or N-H) do not form hydrogen bonds with nucleophile
Examples:

30. Crown Ethers
Solvate the cation, so nucleophilic strength of the anion increases.
Fluoride anion becomes a
good nucleophile

31. SN2: Reactivity of Substrate
Carbon must be partially positive.
Must have a good leaving group
Carbon must not be sterically hindered.
=>

32. Leaving Group Ability Stable once it has left (not a strong base)
Electron-withdrawing
Stable once it has left (not a strong base)
Polarizable to stabilize the transition state.
=>

33. Structure of Substrate
Relative rates for SN2: CH3X > 1° > 2° >> 3°
Tertiary halides do not react via the SN2 mechanism, due to steric hindrance =>

34. Effect of Beta Branching
Isobutyl
bromide
Neopentyl
bromide
Propyl
bromide
NOTE: ALL ABOVE ARE PRIMARY

35. Miscellaneous Substrate
All have sterically hindered
backsides - No SN2 reactivity

36. Stereochemistry of SN2
Walden inversion
=>

37. EXAMPLES S R

38. EXAMPLES 2
MESO

39. EXAMPLE 3

40. How would you prepare the following from an alkyl halide?
EXAMPLE 4
How would you prepare the
following from an alkyl halide?
retrosynthetic
analysis

41. SN1 Reaction Two step reaction with carbocation intermediate.
Unimolecular nucleophilic substitution.
Two step reaction with carbocation intermediate.
Rate is first order in the alkyl halide,
zero order in the nucleophile.
Racemization occurs.

42. Formation of carbocation (slow)
SN1 Mechanism (1)
Formation of carbocation (slow)
=>

43. SN1 Mechanism (2)
Nucleophilic attack
Loss of H+ (if needed)
=>

44. SN1 Energy Diagram Forming the carbocation is endothermic
Carbocation intermediate is in an energy well =>

45. Rates of SN1 Reactions
3° > 2° > 1° >> CH3X
Order follows stability of carbocations (opposite to SN2)
More stable ion requires less energy to form
Better leaving group, faster reaction (like SN2)
Polar protic solvent best: It solvates ions strongly with hydrogen
bonding

46. Stereochemistry of SN1
Racemization: inversion and retention
=>

47. Rearrangements
Carbocations can rearrange to form a more stable carbocation.
Hydride shift: H- on adjacent carbon bonds with C+.
Methyl shift: CH3- moves from adjacent carbon
if no H’s are available.

48. Hydride Shift
=>

49. Methyl Shift
=>

50. Interesting Rearrangement = PUSH PULL
-AgBr
push pull

51. SN2 or SN1? Primary or methyl Tertiary
Weak nucleophile (may also be solvent)
Strong nucleophile
Polar protic solvent, Ag+
Polar aprotic solvent
Rate = k[halide]
Rate = k[halide][Nuc]
Inversion at chiral carbon
Racemization of optically active compound
No rearrangements
Rearranged products

52. E1 Reaction Two groups lost (usually X- and H+)
Unimolecular elimination
Two groups lost (usually X- and H+)
Nucleophile acts as base)
Also have SN1 products (mixture
SN1 and E1 have common first step.

53. E1 EXAMPLES +

54. E1 Mechanism Halide ion leaves, forming carbocation.
Base removes H+ from adjacent carbon.
Pi bond forms.

55. A Closer Look
=>

56. E1 Energy Diagram
=>
Note: first step is same as SN1

57. E2 Reaction Bimolecular elimination Requires a strong base
Halide leaving and proton abstraction happens
simultaneously - no intermediate

58. E2 Examples

59. E2 Mechanism
=>

60. Saytzeff’s Rule
If more than one elimination product is possible, the most-substituted alkene is the major product (most stable).
R2C=CR2>R2C=CHR>RHC=CHR>H2C=CHR tetra > tri > di > mono
=>
minor
major

61. E2 Stereochemistry
=>

62. E1 or E2? Tertiary > Secondary Tertiary > Secondary Weak base
Good ionizing solvent
Rate = k[halide]
Saytzeff product
No required geometry
Rearranged products
Tertiary > Secondary
Strong base required
Solvent polarity not important
Rate = k[halide][base]
Saytzeff product
Coplanar leaving groups (usually anti)
No rearrangements =>

63. End of Chapter 6