Learning outcomes

1
Learning outcomes

• Explain nucleophilic substitution reaction of
  haloalkanes
• Explain SN1 and SN2 mechanisms.
• Compare the relative reactivities of 1?, 2? and
  3? haloalkanes toward hydrolysis.

V 1 Intro
2
Previously The SN1 Mechanism
CH3
1)
CH3
..
-
slow

CH3
Br
CH3
C
CH3


CH3
C
..

Br


..
3
SN1 mechanism involving rearrangement of
carbocation

• Carbocations can rearrange to form a more stable
  carbocation.
• Rearrangement occurs in two ways
• Hydride shift(1,2-H-) H- on adjacent(1,2) carbon
  bonds with C.
• Methyl shift(1,2--CH3) CH3- moves from
  adjacent(1,2) carbon if no Hs are available.
• Rearrangement is a serious side reaction when
  there is carbocation formation involved in the
  reactions!
  

4
Rearrangement - Methyl shift(1,2--CH3)

• Example 1 Write the mechanism for the following
  reaction.
• Step 1 Formation of carbocation

5

• Rearrangement - Methyl shift(1,2--CH3)
• the migration of a methyl group together with its
  pair of electrons - more stable tertiary
  carbocation is formed.
• Step 2 Nucleophilic attack on the carbocation

6
Rearrangement - Hydride Shift (1,2-H-)

• Step 1 Formation of carbocation

H
H
1,2-H- shift
C
H
C
C
C
H
C
H
C
C
C
H
3
3
3
3
H
C
H
H
C
H
3
3

• the hydride shift converts the initially formed
  secondary carbocation to a more stable tertiary
  carbocation.

7
Rearrangement - Hydride Shift (1,2-H-)

• Step 1 Formation of carbocation

H
H
1,2-H- shift
C
H
C
C
C
H
C
H
C
C
C
H
3
3
3
3
H
C
H
H
C
H
3
3

• Step 2 Nucleophilic attack on the carbocation

8

• Exercise 2 (Mac 2002)
• The structure of compound A is as follows
• i. Give IUPAC name for A
• ii. Compound A react with OH- forming an alcohol.
  Write the mechanism for the formation of this
  alcohol and name the reaction.

9
Bimolecular Nucleophilic Substitution Reaction
(SN2)

• The term bimolecular means that the transition
  state of the rate limiting step involves the
  collision of two molecules.
• Example of SN2 reaction

60oC
HO- CH3 Br
CH3 OH Br-
H2O / NaOH
to make it happen CH3Br OH-must collide, a
bimolecular reaction ? An SN2 reaction
substitution, nucleophilic, bimolecular
10
Bimolecular Nucleophilic Substitution Reaction
(SN2)

• General Mechanism
• Single step with no intermediate
• Concerted reaction new bond forming and old bond
  breaking at same time.
• The mechanism of SN2 occurs in a single step.

H
transition state
V5 SN2 mech.
11
Bimolecular Nucleophilic Substitution Reaction
(SN2)

• General Mechanism
• The rate of reaction involves two reactants.
• The rate of reaction depends on the
  concentration of the haloalkane and the
  concentration of nucleophile.
• rate k R-X Nu-
• SN2 is a second order reaction.

H
transition state
12
SN2 Bimolecular Nucleophilic Substitution

• SN2 reactions always lead to inversion of
  configuration
• In SN2 reaction, the nucleophile attacks from
  the back side of the electrophilic carbon, that
  is, from the side directly opposite bonded to the
  halogen.

13
SN2 Bimolecular Nucleophilic Substitution
Back-side attack causes the product formed has
inverse configuration from the original
configuration. turns the tetrahedron of the
carbon atom inside out, like umbrella caught by
the wind.
14
SN2 Bimolecular Nucleophilic Substitution
?
C
Nu
X
?
Nu
C
X
Nu
C
X
15
SN2 Bimolecular Nucleophilic Substitution
?
Nu
C
X
A Transition State
?
Nu
C
X
Nu
C
X
16
SN2 Bimolecular Nucleophilic Substitution
?
backside attack
Nu
C
X
Inversion occurs at carbon
?
Nu
C
X
Nu
C
X
17
SN2 Bimolecular Nucleophilic Substitution
?
Nu
C
X
A Transition State

• The transition state involves partial bonding
  between the attacking nucleophile and the
  haloalkane.

?
Nu
C
X
Nu
C
X
18

• Another example
• Reaction of ethyl bromide with aqueous sodium
  hydroxide.
• SN2 Mechanism

transition state
19
Relative Reactivities of Unimolecular
Nucleophilic Substitution Reaction (SN2)

• The reactivity on SN2 reaction depends on the
  size of the groups attached to the C - X atom
  that being attacked.

• Relative reactivities of haloalkanes in an SN2
  reaction (opposite to SN1)
• R3-C-Xltltlt R2-C-X lt R-C-X lt CH3-X
• 3o 2o
  1o
• increasing reactivity

V2 V3 V4 class
20
Relative Reactivities of Unimolecular
Nucleophilic Substitution Reaction (SN2)

• The reaction will be fast when the groups are
  small, and will slow considerably when larger
  groups are attached. The presence of bulky alkyl
  groups will prevent the nucleophilic attack.

SN2 Reactivity of Substrate on hydrolysis
reaction.
21
SN2 Reactivity of Substrate on hydrolysis
reaction.
22
Relative Reactivities of Unimolecular
Nucleophilic Substitution Reaction (SN2)

• SN2 reactions are governed mainly by steric
  factors (steric effect).
• The more alkyl groups connected to the reacting
  carbon, the slower the reaction.

V6 steric Hind.
23
Relative Reactivities of Unimolecular
Nucleophilic Substitution Reaction (SN2)

• Carbon must not be sterically hindered.
• Tertiary halides do not react via the SN2
  mechanism, due to steric hindrance.

24
Relative Reactivities of Unimolecular
Nucleophilic Substitution Reaction (SN2)

• Steric hindrance
• - the spatial arrangement of the groups near the
  reacting site hinders(retards) a reaction
• -Large groups can often hinder the formation
• Steric effect
• - is an effect on relative rates caused by the
  space-filling properties of those parts of a
  molecule attached at or near to the reacting site.

25
Relative Reactivities of Unimolecular
Nucleophilic Substitution Reaction (SN2)

• NOTE 1o haloalkanes with large alkyl groups (e.g
  (CH3)3CCH2Br) will not undergo SN2 reaction due
  to steric hidrance.

V7 SN1 for 1o
26

• Exercise 1 (Feb 2003)
• Write a reasonable structures of products formed
  when 1-iodobutane reacts with
• i. KCN
• ii. NaOH/H2O
• iii. excess NH3
• Write the mechanism for the reaction in (ii).

V8 HX -CN
27
Comparison of SN1 and SN2 Reactions
V9 SN1 SN2