1. Chapter 6 Alkyl Halides: Nucleophilic Substitution and Elimination
Organic Chemistry, 6h Edition L. G. Wade, Jr.
Chapter 6 Alkyl Halides: Nucleophilic Substitution and Elimination

2. 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:
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Chapter 6

3. 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 =>
Chapter 6

4. 6-2 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.
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5. Systematic Common Names
Name as alkyl halide.
Useful only for small alkyl groups.
Name these:
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6. “Trivial” Names CH2X2 called methylene halide. CHX3 is a haloform.
CX4 is carbon tetrahalide.
Examples:
CH2Cl2 is methylene chloride
CHCl3 is chloroform
CCl4 is carbon tetrachloride =>
Chapter 6

7. 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 =>
Chapter 6

8. Classify These:
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9. Dihalides
Geminal dihalide: two halogen atoms are bonded to the same carbon
Vicinal dihalide: two halogen atoms are bonded to adjacent carbons.
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10. 6-3 Uses of Alkyl Halides Solvents - degreasers and dry cleaning fluid
Reagents for synthesis of other compounds
Anesthetics: Halothane is CF3CHClBr
CHCl3 used originally (toxic and carcinogenic)
Freons, chlorofluorocarbons or CFC’s
Freon 12, CF2Cl2, now replaced with Freon 22, CF2CHCl, not as harmful to ozone layer.
Pesticides - DDT banned in U.S =>
Chapter 6

11. Dipole Moments
m = 4.8 x d x d, where d is the charge (proportional to DEN) and d is the distance (bond length) in Angstroms.
Electronegativities: F > Cl > Br > I
Bond lengths: C-F < C-Cl < C-Br < C-I
Bond dipoles: C-Cl > C-F > C-Br > C-I D D D D
Molecular dipoles depend on shape, too! =>
Chapter 6

12. 6-5 Physical Properties of RX Boiling Points
Greater intermolecular forces, higher b.p.
dipole-dipole attractions not significantly different for different halides
London forces greater for larger atoms
Greater mass, higher b.p.
Spherical shape decreases b.p (CH3)3CBr CH3(CH2)3Br C C =>
Chapter 6

13. Densities Alkyl fluorides and chlorides less dense than water.
Alkyl dichlorides, bromides, and iodides more dense than water =>
Chapter 6

14. 6-6 Preparation of RX Free radical halogenation (Chapter 4)
produces mixtures, not good lab synthesis
unless: all H’s are equivalent, or
halogenation is highly selective.
Free radical allylic halogenation
produces alkyl halide with double bond on the neighboring carbon =>
Chapter 6

15. Halogenation of Alkanes
All H’s equivalent. Restrict amount of halogen to prevent di- or trihalide, etc formation
Highly selective: bromination of 3 C
Chapter 6

16. Allylic Halogenation Allylic radical is resonance stabilized.
Bromination occurs with good yield at the allylic position (sp3 C next to C=C).
Avoid a large excess of Br2 by using N-bromosuccinimide (NBS) to generate Br2 as product HBr is formed.
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Chapter 6

17. Reaction Mechanism Free radical chain reaction
initiation, propagation, termination.
Chapter 6

18. 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. =>
Chapter 6

19. Elimination Reactions
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) =>
Chapter 6

20. SN2 Mechanism Bimolecular nucleophilic substitution.
Concerted reaction: new bond forming and old bond breaking at same time.
Rate is first order in each reactant.
Inversion of configuration =>
Chapter 6

21. SN2 Energy Diagram One-step reaction.
Transition state is highest in energy. =>
Chapter 6

22. 6-9 Generality of SN2 RXN Synthesis of other classes of compounds.
Halogen exchange reaction.
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Chapter 6

23. 6-10 Factors Affecting SN2: Nucleophilic Strength
Stronger nucleophiles react faster.
Strong bases are strong nucleophiles, but not all strong nucleophiles are basic.
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Chapter 6

24. Trends in Nucleophilic 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 =>
Chapter 6

25. Polarizability Effect
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Chapter 6

26. Steric Effect Bulky Nucleophiles
Sterically hindered for attack on carbon, so weaker nucleophiles.
Chapter 6

27. 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.
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Chapter 6

28. Solvent Effects (2)
Polar aprotic solvents (no O-H or N-H) do not form hydrogen bonds with nucleophile
Examples:
Chapter 6

29. Crown Ethers
Solvate the cation, so nucleophilic strength of the anion increases.
Fluoride becomes a good nucleophile.
Chapter 6

30. Leaving Group Ability Electron-withdrawing
Stable once it has left (not a strong base)
Polarizable to stabilize the transition state.
Chapter 6

31. Structure of Substrate
Relative rates for SN2: CH3X > 1° > 2° >> 3°
Tertiary halides do not react via the SN2 mechanism, due to steric hindrance.
Chapter 6

32. Steric Hindrance Nucleophile approaches from the back side.
It must overlap the back lobe of the C-X sp3 orbital.
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Chapter 6

33. Walden inversion or Inversion of Configuration
Stereochemistry of SN2
Walden inversion or Inversion of Configuration
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34. SN1 Reaction Unimolecular nucleophilic substitution.
Two step reaction with carbocation intermediate.
Rate is first order in the alkyl halide, zero order in the nucleophile.
Racemization occurs =>
Chapter 6

35. SN1 Mechanism
Chapter 6

36. Chapter 6

37. SN1 Energy Diagram Forming the carbocation is endothermic
Carbocation intermediate is in an energy well =>
Chapter 6

38. 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 =>
Chapter 6

39. Stereochemistry of SN1 Racemization: inversion and retention =>
Chapter 6

40. SN2 or SN1? Primary or methyl Strong nucleophile Polar aprotic solvent
Rate = k[halide][Nuc]
Inversion at chiral carbon
No rearrangements
Tertiary
Weak nucleophile (may also be solvent)
Polar protic solvent, silver salts
Rate = k[halide]
Racemization of optically active compound
Rearranged products =>
Chapter 6

41. E1 Reaction Unimolecular elimination
Two groups lost (usually X- and H+)
Nucleophile acts as base
Also have SN1 products (mixture) =>
Chapter 6

42. E1 Mechanism Halide ion leaves, forming carbocation.
Base removes H+ from adjacent carbon.
Pi bond forms =>
Chapter 6

43. A Closer Look
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44. Example
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45. E1 Energy Diagram
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Note: first step is same as SN1
Chapter 6

46. Zaitsev’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
Chapter 6

47. Example
Chapter 6

48. E2 Reaction Bimolecular elimination Requires a strong base
Halide leaving and proton abstraction happens simultaneously - no intermediate =>
Chapter 6

49. E2 Mechanism Order of reactivity: 3° > 2 ° > 1°
Mixture may form, but Zaitsev product predominates.
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50. Example
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51. Example (2)
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52. E2 Stereochemistry
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53. Chapter 6

54. E1 or E2? Tertiary > Secondary Tertiary > Secondary Weak base
Good ionizing solvent
Rate = k[halide]
Zaitsev product
No required geometry
Rearranged products
Tertiary > Secondary
Strong base required
Solvent polarity not important
Rate = k[halide][base]
Zaitsev product
Coplanar leaving groups (usually anti)
No rearrangements =>
Chapter 6

55. Substitution or Elimination?
Strength of the nucleophile determines order: Strong nucleophile, bimolecular, SN2 or E2.
Primary halide usually SN2.
Tertiary halide mixture of SN1, E1 or E2
High temperature favors elimination.
Bulky bases favor elimination.
Good nucleophiles, but weak bases, favor substitution =>
Chapter 6

56. Secondary Halides?
Mixtures of products are common.
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Chapter 6

57. End of Chapter 6
Chapter 6