07 lec

1. Chapter 7
Lecture
Alkyl Halides:
Nucleophilic Substitution
and Elimination
© 2013 Pearson Education, Inc.
© 2013 Pearson Education, Inc.

2. Classes of Alkyl Halides
H H
• ___________ halides: H C C Br
Halogen is directly H H
bonded to sp3 carbon.
• Vinyl halides: Halogen H H
is bonded C C
H Cl
to____carbon of
alkene. I
• ______halides:
Halogen is bonded to
sp2 carbon on _______
ring.
© 2013 Pearson Education, Inc.Chapter 6 2

3. IUPAC Nomenclature
4-(2-fluoroethyl)heptane
© 2013 Pearson Education, Inc. Chapter 6 3

4. Common Names
CH2X2 is called methylene halide.
CHX3 is a haloform.
CX4 is carbon tetrahalide.
Common halogenated solvents:
________ is methylene chloride.
_______ is chloroform.
________is carbon tetrachloride.
© 2013 Pearson Education, Inc. Chapter 6 4

5. Compare
classification to
alcohols and amines
© 2013 Pearson Education, Inc. Chapter 6 5

6. Uses of Alkyl Halides
• Industrial and household cleaners.
• Anesthetics:
• CHCl3 used originally as general anesthetic but it
is toxic and carcinogenic.
• CF3CHClBr is a mixed halide sold as Halothane.
• Freons are used as refrigerants and foaming agents.
• Freons can harm the ozone layer, so they have
been replaced by low-boiling hydrocarbons or
carbon dioxide.
• Pesticides such as DDT are extremely toxic to
insects but not as toxic to mammals.
• Haloalkanes can not be destroyed by bacteria, so
they accumulate in the soil to a level that can be
toxic to mammals, especially humans.
© 2013 Pearson Education, Inc. Chapter 6 6

7. Dipole Moments depends on
electronegativity and bond length
• Electronegativities of the halides:
• >>>>
• Bond lengths increase as the size of
the halogen increases:
• >>>>
• Bond dipoles:
C—Cl> C—F > C—Br > C—I
1.56 D 1.51 D 1.48 D 1.29 D
Carbon—halogen bond is polar,
carbon has partial _______ charge
and can be attacked by ____________
© 2013 Pearson Education, Inc. Chapter 6 7

8. Boiling Points and Densities
• 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
73 C 102 C
• Alkyl fluorides and alkyl chlorides (thosewith just one chlorine
atom) are less dense than water (1.00 g/mL).
• Alkyl chlorides with two or more chlorine atoms are denser than
water.
• All alkyl bromides and alkyl iodides are denser than water.
© 2013 Pearson Education, Inc. Chapter 6 8

9. Preparation (synthesis) of
Alkyl Halides
• Free radical halogenation
• _________________more selective than
__________________
• Free radical allylichalogenation
• Halogen is placed on a carbon
________________to the double bond
(allylic).
© 2013 Pearson Education, Inc. Chapter 6 9

10. © 2013 Pearson Education, Inc.

11. Write the mechanism for the free radical
bromination of propane
Chapter 2 11
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12. Synthesis of alkyl halides by
allylicbromination
• Allylic radicals are resonance stabilized.
• Bromination occurs with good yield at the
allylic position (sp3 C next to C C).
© 2013 Pearson Education, Inc. Chapter 6 12

13. Mechanism of allylic bromination
• N-Bromosuccinimide (NBS) is an allylic brominating agent.
• Reacts close to room temperature.
• The mechanism involves an ___________stabilized by
____________. Both allylic radicals can react with bromine.
© 2013 Pearson Education, Inc. Chapter 6 13

14. Major Write mechanism
© 2013 Pearson Education, Inc. Chapter 6 14

15. Reactions of Alkyl Halides
© 2013 Pearson Education, Inc. Chapter 6 15

16. The SN2 Reaction: Substitution
Nucleophilic Bimolecular
• The___________atomon the alkyl halide is replaced with
the ____________(HO-).
• Since the halogen is more electronegative than carbon,
the C—I bond breaks ________________ and the iodide
ion leaves.
© 2013 Pearson Education, Inc. Chapter 6 16

17. Back-Side Attack in the SN2 Reaction
SN2 Energy Diagram
a_) Exergonic
b) ____________
c) Transition state resembles
____hybridization
d) _____species participate in rds
e) Rate law
f) Stereochemistry ______________ 6
© 2013 Pearson Education, Inc. Chapter 17

18. New functional groups synthesized
with the SN2 Reaction or RX
© 2013 Pearson Education, Inc. Chapter 6 18

19. SN2 requires a _______ nucleophile
Stronger nucleophiles give fast SN2
A negatively charged nucleophile is ___________ than its neutral
counterpart:
In the same period, nucleophilicity ____________ from left to right:
__________down periodic table, as size and polarizability increase:
© 2013 Pearson Education, Inc. Chapter 6 19

20. The more polarizable, the
better Nu
Electrons in a larger atom are not as tightly held as the electrons in a
smaller atom and can be used to form a bond much easier
© 2013 Pearson Education, Inc. Chapter 6 20

21. The solvent
Dielectric constant: A measure of a solvent’s ability to insulate
opposite charges from one another: The greater the value of the
dielectric constant of a solvent, the smaller the interaction
between ions of opposite charge dissolved in that solvent.
© 2013 Pearson Education, Inc.

22. SN2 reactions proceed faster in
aprotic solvents that “free” the Nu
Polar aprotic solvents
________have acidic
protons and therefore
________ hydrogen
bond and Nu is “free”
to attack
• Polar protic solvents ________
acidic hydrogens (O—H or N—
H) that can solvate the
nucleophile, _________ their
nucleophilicity.
• Nucleophilicity in protic solvents
increases as the size of the
atom increases
© 2013 Pearson Education, Inc. Chapter 6 22

23. Crown ethers solvate the cation, so the
nucleophilic strength of the anion
increases (“Free” to attack)
• Fluoride becomes a
good nucleophile.
© 2013 Pearson Education, Inc. Chapter 6 23

24. A good leaving group is required in
substitution and elimination
reactions
The best leaving groups are:
• Electron-withdrawing, to polarize the carbon atom.
• Stable (not a strong base) once they have left.
• Polarizable, to stabilize the transition state.
© 2013 Pearson Education, Inc. Chapter 6 24

25. Relative rates for SN2 depends on structure of
substrate (RX, electrophile)
Nucleophile approaches from
the back side; It must overlap
the back lobe of the C—X sp3
orbital.
CH3X1°2°3°
• Tertiary halides do not react via the SN2 mechanism,
due to _________________hindrance.
© 2013 Pearson Education, Inc. Chapter 6 25

26. Stereochemistry of SN2
SN2 reactions will result in an inversion of
configuration also called a Walden inversion.
The SN2 reaction is a ___________ nucleophilic substitution.
It is a ______________ reaction
Rate =____________________
_____________ of configuration occurs.
© 2013 Pearson Education, Inc. Chapter 6 26

27. Write the mechanism for the reaction
or (S)-2-Chlorobutane with iodide ion
Chapter 6 27
© 2013 Pearson Education, Inc.

28. The SN1 Reaction
• The SN1 reaction is a ______________
nucleophilic substitution.
• _____________It has a ____________
intermediate.
• Racemization ___________
• Rate =____________ 6
© 2013 Pearson Education, Inc.
Chapter 28

29. SN1 Mechanism
Step 1: Formation of the
carbocation (rate-determining step)
Step 2: Attack of the nucleophile.
If the nucleophile is an uncharged molecule like water or an alcohol, the positively
charged product must lose a proton to give the final uncharged product.
© 2013 Pearson Education, Inc. Chapter 6 29

30. Step 3: If the nucleophile was neutral, a third step
(deprotonation) will be needed.
SN1 Energy Diagram
______________
Forming the carbocation is
______________
Step 2 is _______ with a
______activation energy.
If the product is chiral a
_____________is
obtained
Rate =
© 2013 Pearson Education, Inc. Chapter 6 30

31. Stereochemistry of SN1
enantiotopic phases of the carbocation
• Carbocations are_______hybridized and have ________
geometry. The lobes of the empty p orbital are
perpendicular to the trigonal plane above and below.
• Nucleophilic attack can occur from either side, producing
mixtures of retention and inversion of configuration if the
carbon is chiral.
© 2013 Pearson Education, Inc. Chapter 6 31

32. Stereochemistry of SN1
The SN1 reaction produces mixtures of enantiomers. There
is usually slightly _______inversion than retention of
configuration.
© 2013 Pearson Education, Inc. Chapter 6 32

33. examples of complete racemization have been observed, but
partial racemization with a slight excess of inversion is more
common.
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34. Factors that favor SN1 reactions
a) Nature of the electrophile (RX)
b) A better leaving group will increase the rate of the reaction.
c) Polar protic solvent is best because it can solvate both ions
strongly through hydrogen bonding stabilizing the
carbocation. This reactions usually are solvolysis.
© 2013 Pearson Education, Inc. Chapter 6 34

35. Rearrangements can occur
• Carbocations can rearrange to form a more stable
carbocation: 1,2 Hydride shift: H-, 1,2- Methyl shifts:
CH3- or phenyl Ph- shifts.
© 2013 Pearson Education, Inc. Chapter 6 35

36. Write mechanism for the following reaction
© 2013 Pearson Education, Inc. Chapter 6 36

37. SN1 or SN2 Mechanism?
SN2 SN1
CH3X > 1º> 2º 3º> 2º
Strong nucleophile Weak nucleophile (may
also be used as solvent)
Polar aprotic solvent Polar protic solvent
Rate = k[alkyl halide][Nuc] Rate = k[alkyl halide]
Inversion at chiral carbon Racemization
No rearrangements Rearranged products
© 2013 Pearson Education, Inc. Chapter 6 37

38. Exercises
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39. © 2013 Pearson Education, Inc.

40. © 2013 Pearson Education, Inc.

41. In general, strong bases are strong
nucleophiles,
but not all strong nucleophiles are basic.
• Basicity is defined by the equilibrium constant
for abstracting a proton.
• Nucleophilicity is defined by the rate of attack
on the electrophilic carbon atom
© 2013 Pearson Education, Inc. Chapter 6 41

42. Elimination Reactions
• Elimination reactions produce double bonds.
• Also called dehydrohalogenation (-HX).
© 2013 Pearson Education, Inc. Chapter 6 42

43. The E1 Reaction “Nucleophile” acts as base.
• __________ elimination.
• Stepwise. ___________ intermediate.
• Solvolysis reaction
• Rate =
• The E1 and SN1 reactions have the same conditions so a
mixture of products will be obtained.
© 2013 Pearson Education, Inc. Chapter 6 43

44. E1 Mechanism
Step 1: The leaving group leaves to form a ____________
Step 2: Solvent abstracts a proton to form an __________
© 2013 Pearson Education, Inc. Chapter 6 44

45. In elimination reactions, the major product of
the reaction is the more stable, more
substituted double bond: Zaitsev’s rule.
tetrasubstituted trisubstituted disubstituted monosubstituted
© 2013 Pearson Education, Inc. Chapter 6 45

46. E1 and SN1occur in solvolysis
• Substitution results from _________attack on thecarbocation
• Ethanol serves as a ___________ in the elimination and as a
______________ in the substitution.
A carbocation can:
React with its own leaving group to return to the reactant.
React with a nucleophile to form a substitution product (SN1).
Lose a proton to form an elimination product (E1).
Rearrange to give a more stable carbocation, then react further.
© 2013 Pearson Education, Inc. Chapter 6 46

47. The E2 Reaction
• ___________________.
• Requires a __________ base.
• This is a _________________ reaction: The proton
is abstracted, the double bond forms, and the
leaving group leaves, all in one step.
© 2013 Pearson Education, Inc. Chapter 6 47

48. The E2 Reaction
• Reactivity for alkyl halides:
3° > 2 ° > 1°
• Mixture may form, but
Zaitsevproduct
predominates
• The halide and the proton
to be abstracted must be
anti-coplanar ( = 180º)
(orbitals aligned so they can
begin to form a pi bond in
the transition state and
steric hindrance between the
base and the leaving group
is minimized)
© 2013 Pearson Education, Inc. Chapter 6 48

49. E1 or E2 Mechanism?
• Tertiary > secondary • Tertiary > secondary
• Base strength usually • Strong base required
weak. Solvolysis
• Good ionizing solvent • Polar aprotic solvent
(polar protic)
• Rate = k[alkyl halide] • Rate =k[alkylhalide][base]
• Zaitsevproduct • Zaitsevproduct
• No required geometry • Coplanar leaving groups
(usually anti)
• Rearranged products
• No rearrangements
© 2013 Pearson Education, Inc. Chapter 6 49

50. Substitution or Elimination?
• Strength of the nucleophile determines
order: Strong nucleophiles or bases
promote bimolecular reactions.
• 10 halides usually undergo SN2.
• 30halides are a mixture of SN1, E1, or
E2. They cannot undergo SN2.
• High temperature and bulky bases favor
elimination.
© 2013 Pearson Education, Inc. Chapter 6 50

51. 20 halides: strong nucleophiles will promote SN2/ Strong bases E2.
Weak nucleophiles/ bases promote SN1/E1.
• Bromide and iodide are good examples of strong
nucleophiles, weak bases
• Ethoxide/ethanol is a better base than a nucleophile
• Terbutoxide/terbutyl alcohol can not act as a
nucleophile
• Ethanol (polar protic solvent solvolysis
© 2013 Pearson Education, Inc. Chapter 6 51

52. Predict the mechanisms and products of the
following. reaction
© 2013 Pearson Education, Inc. Chapter 6 52

53. Predict the mechanisms and products of the
following reaction.
© 2013 Pearson Education, Inc. Chapter 6 53

54. 54
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55. 55
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