Cahn-Ingold-Prelog

1. Effect of the Nucleophile
Author: Dr. Robert D. Craig,

2. This is
Doug Henning!
He performed his first show at the age
of 14 at the birthday party of a friend
and was inspired by his audience's
spellbound reaction

3. He won The Tony Award
 Debuting in December 1975, Doug
Henning's World of Magic captured
the attention of more than 50 million
viewers!

4. Hughes and Sir Christopher
Ingold
In 1935, Edward D. Hughes and
Sir Christopher Ingold studied
nucleophilic substitution reactions of
alkyl halides and related compounds.
They proposed that there were two
main mechanisms at work, both of
them competing with each other.

5. Are just as spectacular!!!!!
The two main mechanisms are the SN
1 reaction and the SN2 reaction.
The “S” stands for chemical
substitution,
And the “N” stands for nucleophilic,
and the number represents the
kinetic order of the reaction.

6. Sir Christopher Ingold
 Known for Organic reaction
mechanisms
 “Cahn-Ingold-Prelog” rules !
He received the Longstaff Medal of the
Royal Society of Chemistry in 1951,
the Royal Medal of the Royal Society
in 1952, and was knighted in 1958

7. Just like Paul Macartney!!!

8. Sir Christopher Ingold
Is one bad dude!!!!!

9. This is how he got down!!!
A graph showing the relative reactivities of the different
alkyl halides towards SN1 and SN2 reactions

10. the SN1 reaction

11. the SN2 reaction

12. Effect of the Nucleophile
 The nucleophile takes part in the
slow step (the only step) of the SN2
reaction but not in the slow step of
the SN1. Therefore, a strong
nucleophile promotes the SN2 but not
the SN1.

13. Effect of the Nucleophile
 Weak nucleophiles fail to promote
the SN2 reaction; therefore, reactions
with weak nucleophiles often go by
the SN1 mechanism if the substrate is
secondary or tertiary

14. Effect of the Nucleophile
 SN1: Nucleophile strength is
unimportant (usually weak).

15. Effect of the Nucleophile
 SN2: Strong nucleophiles are
required.

16. Effect of the Substrate
 The structure of the substrate (the
alkyl halide) is an important factor in
determining which of these
substitution mechanisms might
operate.

17. Effect of the Substrate
 Methyl halides and primary halides
cannot easily ionize and undergo SN1
substitution because methyl and
primary carbocations are high in
energy. They are relatively
unhindered, however, so they make
good SN2 substrates.

18. Tert-butyl-chloride-3D
 Tertiary halides are too hindered to
undergo SN2 displacement, but they
can ionize to form tertiary
carbocations. Tertiary halides
undergo substitution exclusively
through the SN1 mechanism.
Secondary halides can undergo
substitution by either mechanism,
depending on the conditions

19. Tert-butyl-chloride-3D
will exhibit Steric hinderance

20. SN2 substrates
 SN2 substrates:CH3X > 1° > 2°
 (3° is not suitable

21. SN1 substrates
 SN1 substrates: 3° > 2°
(1° and CH3X are unlikely)

22. silver nitrate (AgNO3)
 If silver nitrate (AgNO3) is added to
an alkyl halide in a good ionizing
solvent, it removes the halide ion to
give a carbocation. This technique
can force some unlikely ionizations,
often giving interesting
rearrangements (see Problem 6-29.)

23. Effect of the Solvent
 The slow step of the SN1 reaction
involves formation of two ions.
Solvation of these ions is crucial to
stabilizing them and lowering the
activation energy for their formation.
Very polar ionizing solvents such as
water and alcohols are needed for
the SN1. The solvent may be heated
to reflux (boiling) to provide the
energy needed for ionization

24. Effect of the Solvent
 Less charge separation is generated
in the transition state of the SN2
reaction.
 Strong solvation may weaken the
strength of the nucleophile because
of the energy needed to strip off the
solvent molecules.

25. Effect of the Solvent
 Thus, the SN2 reaction often goes
faster in less polar solvents if the
nucleophile will dissolve. Polar
aprotic solvents may enhance the
strength of weak nucleophiles

26. Effect of the Solvent
The slow step of the SN1 reaction
involves formation of two ions.
Solvation of these ions is crucial to
stabilizing them and lowering the
activation energy for their formation.
Very polar ionizing solvents such as
water and alcohols are needed for
the SN1.

27. Effect of the Solvent
 The solvent may be heated to reflux
(boiling) to provide the energy
needed for ionization

28. This is . . .
 .

29. The same as this . . .

30. the transition state
 Less charge separation is generated in the
transition state of the SN2 reaction. Strong
solvation may weaken the strength of the
nucleophile because of the energy needed
to strip off the solvent molecules. Thus,
the SN2 reaction often goes faster in less
polar solvents if the nucleophile will
dissolve.
 Polar aprotic solvents may enhance the
strength of weak nucleophiles

31. the transition state

32. the transition state
 .

33. aprotic solvents:
 Common characteristics of aprotic
solvents:
 Examples are dimethyl sulfoxide,
dimethylformamide, dioxane and
hexamethylphosphorotriamide,
tetrahydrofuran

34. dimethyl sulfoxide
You might see this later

35. dimethyl sulfoxide
 .

36. tetrahydrofuran
 .

37. tetrahydrofuran
You will definitely need this later.
 .

38. Effect of the Solvent
 Polar Protic Solvents
 Let's start with the meaning of the adjective
protic. In the context used here, protic refers to a
hydrogen atom attached to an electronegative
atom. For our purposes that electronegative atom
is almost exclusively oxygen.
 In other words, polar protic solvents are
compounds that can be represented by the
general formula ROH. The polarity of the polar
protic solvents stems from the bond dipole of the
O-H bond.

39. Effect of the Solvent
 The large difference in electronegativities of the
oxygen and the hydrogen atom, combined with
the small size of the hydrogen atom, warrant
separating molecules that contain an OH group
from those polar compounds that do not.
 Examples of polar protic solvents are water (H2O),
methanol (CH3OH), and acetic acid (CH3CO2H).

40.  http://myphlip.pearsoncmg.com/altprod

41. The slow step
 The slow step of the SN1 reaction
involves formation of two ions.
Solvation of these ions is crucial to
stabilizing them and lowering the
activation energy for their formation.
Very polar ionizing solvents such as
water and alcohols are needed for
the SN1.

42. The slow step
 The solvent may be heated to reflux
(boiling) to provide the energy
needed for ionization.

43. The slow step
 Less charge separation is generated in the
transition state of the SN2 reaction.
Strong solvation may weaken the strength
of the nucleophile because of the energy
needed to strip off the solvent molecules.

44. less polar solvents
 Thus, the SN2 reaction often goes
faster in less polar solvents if the
nucleophile will dissolve. Polar
aprotic solvents may enhance the
strength of weak nucleophiles.

45. SN1
 SN1: Good ionizing solvent required.

46. SN2
 SN2: May go faster in a less polar
solvent

47. Kinetics
 The rate of the SN1 reaction is
proportional to the concentration of
the alkyl halide but not the
concentration of the nucleophile. It
follows a first-order rate equation.

48. Kinetics
 The rate of the SN2 reaction is
proportional to the concentrations of
both the alkyl halide [R—X] and the
nucleophile [Nuc: −]. It follows a
second-order rate equation.

49. Kinetics
 SN1 rate = kr[R—X]
 SN2 rate = kr[R—X][Nuc: −]

50. Stereochemistry
 The SN1 reaction involves a flat
carbocation intermediate that can be
attacked from either face. Therefore,
the SN1 usually gives a mixture of
inversion and retention of
configuration

51. Stereochemistry
 The SN2 reaction takes place
through a back-side attack, which
inverts the stereochemistry of the
carbon atom. Complete inversion of
configuration is the result.

52. Stereochemistry
 SN1 stereochemistry:
 Mixture of retention and inversion;
racemization.

53. Stereochemistry
 SN2 stereochemistry
 Complete inversion

54. Rearrangements
 The SN1 reaction involves a
carbocation intermediate. This
intermediate can rearrange, usually
by a hydride shift or an alkyl shift, to
give a more stable carbocation.

55. Rearrangements
 The SN2 reaction takes place in one
step with no intermediates.
 No rearrangement is
possible in the SN2
reaction.

56. rearrangement reaction

57. An example of a reaction taking place with
an SN1 reaction mechanism is the
hydrolysis of tert-butyl bromide with water
forming tert-butyl alcohol

58. a tert-butyl carbocation
 Formation of a tert-butyl carbocation
by separation of a leaving group (a
bromide anion) from the carbon
atom: this step is slow and
reversible!

59. http://en.wikipedia.org/wiki/SN1_re
action

60. The hydride shift
 The mechanism for hydride shift
occurs in multiple steps that includes
various intermediates and transition
states. Below is the mechanism for
the given reaction above:


61. The hydride shift

62. The hydride shift

63. rearrangement reaction
 A rearrangement reaction is a broad
class of organic reactions where the
carbon skeleton of a molecule is
rearranged to give a structural isomer of
the original molecule [1] . Often a
substituent moves from one atom to
another atom in the same molecule. In the
example below the substituent R moves
from carbon atom 1 to carbon atom 2

64. Rearrangements
 SN1: Rearrangements are common.

65. Rearrangements
 SN2: Rearrangements are impossible

66. Nucleophillic substitutions
SN1: SN2:
Promoting factors weak nucleophiles are strong nucleophile
needed
OK
Nucleophile
3° > 2° CH3X > 1° >3° >2°
substrate (RX) good ionizing solvent wide variety of
needed solvents
Solvent good ionizing solvent wide variety of
needed
solvents
leaving group
good one required good one required
Other
***AgNO3
You will use this!
force ionization!

67. the nucleophile competes . . .
 In both reactions, the nucleophile competes with
the leaving group. Because of this, one must
realize what properties a leaving group should
have, and what constitutes a good nucleophile.
For this reason, it is worthwhile to know which
factors will determine whether a reaction follows
an SN1 or SN2 pathway.

68. good leaving groups
 Very good leaving groups, such as
triflate, tosylate and mesylate,
stabilize an incipient negative
charge. The delocalization of this
charge is reflected in the fact that
these ions are not considered to be
nucleophilic

69. good leaving groups
 Very good leaving groups, such as
triflate, tosylate and mesylate,
stabilize an incipient negative
charge. The delocalization of this
charge is reflected in the fact that
these ions are not considered to be
nucleophilic

70. good leaving groups

71. good leaving groups
 Hydroxide and alkoxide ions are not
good leaving groups; however, they
can be activated by means of Lewis
or Brønsted acids