Chapter 6

Nucleophilic Substitution
and Elimination Reactions
of Alkyl Halides

Created by
Professor William Tam & Dr. Phillis Chang
Ch. 6
1. Organic Halides

 
 
C X
X = Cl, Br, I

 Halogens are more electronegative

than carbon

Ch. 6
 Carbon-Halogen Bond Lengths
and Bond Strength
H H H H
H C F H C Cl H C Br H C I
H H H H
C–X Bond
Length (Å)
1.39 1.78 1.93 2.14

increase
C–X Bond
Strength 472 350 293 239
(kJ/mol)
decrease Ch. 6
1A. Physical Properties of Organic Halides:
Boiling Point (bp/oC)
Group Fluoride Chloride Bromide Iodide

Me -78.4 -23.8 3.6 42.5

Et -37.7 13.1 38.4 72

Bu 32 78.4 101 130

s
Bu - 68 91.2 120
i
Bu - 69 91 119
t
Bu 12 51 73.3 100(dec)

Ch. 6
Physical Properties of Organic Halides:
Density ()
Group Fluoride Chloride Bromide Iodide

Me 0.84(-60) 0.92 1.73(0) 2.28

Et 0.72 0.91(15) 1.46 1.95

Bu 0.78 0.89 1.27 1.61

s
Bu - 0.87 1.26 1.60
i
Bu - 0.87 1.26 1.60
t
Bu 0.75(12) 0.84 1.22 1.57(0)

Ch. 6
Different Types of Organic Halides
 Alkyl halides (haloalkanes)

C X sp3

Attached to Attached to Attached to

1 carbon atom 2 carbon atoms 3 carbon atoms
C C C

C Cl C Br C I
a 1o chloride a 2o bromide a 3o iodide
Ch. 6
 Vinyl halides (Alkenyl halides)
sp2

X
 Aryl halides
sp2
X

benzene or aromatic ring

 Acetylenic halides (Alkynyl halides)

sp

X Ch. 6
 sp 3
 Prone to undergo
 Nucleophilic Substitutions
 C X (SN) and Elimination
Reactions (E) (the focus
Alkyl halides
of this Chapter)

sp2
sp2 sp
X X X

 Different reactivity than alkyl halides,

and do not undergo SN or E reactions
Ch. 6
2. Nucleophilic Substitution Reactions

 
Nu + C X Nu C + X
(nucleophile) (substrate) (product) (leaving
group)

The Nu⊖ The Nu⊖ uses

The bond The LG
donates between its e⊖ pair to gains the
an e⊖ pair C and LG form a new pair of e⊖
to the breaks, covalent bond originally
substrate giving both with the bonded
e⊖ from the substrate C in the
bond to LG substrate
Ch. 6
Timing of The Bond Breaking & Bond
Making Process
 Two types of mechanisms
● 1st type: SN2 (concerted mechanism)

R
R 
R

   
HO C Br HO C Br HO C
R R
R R
R R
transition state (T.S.)
+ Br-

Ch. 6 -
 ● 2 nd
type: SN1 (stepwise mechanism)
Step (1):
R (k 1) R
R C Br R C + Br
slow
R R
r.d.s.
Step (2) k1 << k2 and k3
R (k2 ) R H
R C + H2 O R C O
R fast R H
Step (3)
R H (k3) R
+
R C O + H 2O +
R C OH H3O
R H fast R Ch. 6 -
3. Nucleophiles
 A reagent that seeks a positive center
 Has an unshared pair of e⊖
e.g.: HO , CH3O , H2N (negative charge)

H2O, NH3 (neutral)

 
 
This is the positive
center that the C X
Nu⊖ seeks
Ch. 6 -
 Examples:
H H H H
HO + C C + Cl
CH3 Cl CH3 OH
(Nu ) (substrate) (product) (L.G.)

H H H H

H
O
H
+ C C H + Cl
CH3 Cl CH3 O
(Nu ) (substrate) H (L.G.)

H H
(product)
C + H3 O
CH3 OH Ch. 6 -
4. Leaving Groups
 To be a good leaving group, the substituent
must be able to leave as a relatively stable,
weakly basic molecule or ion
e.g.: I⊖, Br⊖, Cl⊖, TsO⊖, MsO⊖, H2O, NH3

O
OTs = O S CH3 (Tosylate)
O
O
OMs = O S CH3 (Mesylate)
O
Ch. 6 -
5. Kinetics of a Nucleophilic Substitution
Reaction: An SN2 Reaction
HO + CH3 Br HO CH3 + Br
-
Rate = k[CH3Br][OH ]

 The rate of the substitution reaction is

linearly dependent on the
concentration of OH⊖ and CH3Br
 Overall, a second-order reaction 
bimolecular
Ch. 6 -
5A. How Do We Measure the Rate of
This Reaction?
e.g.:
H H
HO + C Cl HO C + Cl
H H
(Nu ) H H (leaving
(substrate) (product) group)
 The rate of reaction can be measured by
● The consumption of the reactants
(HO⊖ or CH3Cl) or
● The appearance of the products
(CH3OH or Cl⊖) over time Ch. 6 -
Graphically…

Concentration, M
[CH3Cl] ↓
[CH3OH] ↑

Time, t
Δ[CH3Cl] [CH3Cl]t=t − [CH3Cl]t=0
Rate = =−
Δt Time in seconds
Ch. 6 -
Initial Rate
[CH3Cl]t=0

Concentration, M [CH3Cl]t=t

[CH3Cl]

Time, t

Initial Rate [CH3Cl]t=t − [CH3Cl]t=0

=−
(from slope) Δt
Ch. 6 -
 Example:
60oC
HO + Cl CH3 H2O
HO CH3 + Cl

Initial rate
[OH⊖]t=0 [CH3Cl]t=0 Result
mole L-1, s-1
1.0 M 0.0010 M 4.9 × 10-7

1.0 M 0.0020 M 9.8 × 10-7 Doubled

2.0 M 0.0010 M 9.8 × 10-7 Doubled

2.0 M 0.0020 M 19.6 × 10-7 Quadrupled

Ch. 6 -
 Conclusion:
60oC
HO + Cl CH3 H2O
HO CH3 + Cl

● The rate of reaction is directly

proportional to the concentration of
either reactant.

● When the concentration of either

reactant is doubled, the rate of
reaction doubles.
Ch. 6 -
The Kinetic Rate Expression
60oC
HO + Cl CH3 H2O
HO CH3 + Cl

Rate α [OH⊖][CH3Cl]

Rate = k[OH⊖][CH3Cl]

Initial Rate
k=
[OH⊖][CH3Cl]
= 4.9 × 10-7 L mol-1 s-1
Ch. 6 -
6. A Mechanism for the SN2 Reaction
H
H 
H
  
   
HO C Br HO C Br HO C
H H
H H
H H
transition state (T.S.)
+ Br-
negative OH⊖ O–C bond
brings an e⊖ partially formed; O–C bond
pair to δ+ C; δ– Br C–Br bond formed; Br⊖
begins to move partially broken. departed.
away with an e⊖ Configuration of Configuration
pair C begins to invert of C inverted
Ch. 6 -
7. Transition State Theory:
Free Energy Diagrams
 A reaction that proceeds with a
negative free-energy change (releases
energy to its surroundings) is said to
be exergonic
 A reaction that proceeds with a positive
free-energy change (absorbs energy
from its surroundings) is said to be
endergonic
Ch. 6 -
 At 60oC (333 K)
CH3 Br + OH CH3 OH + Cl

Go = -100 kJ/mol

● This reaction is highly exergonic

Ho = -75 kJ/mol

● This reaction is exothermic

Ch. 6 -
CH3 Br + OH CH3 OH + Cl

● Its equilibrium constant (Keq) is

Go = –RT ln Keq
–Go
ln Keq =
RT
–(–100 kJ/mol)
=
(0.00831 kJ K-1 mol-1)(333 K)
= 36.1

Keq = 5.0 ╳ 1015

Ch. 6 -
A Free Energy Diagram for a Hypothetical SN2
Reaction That Takes Place with a Negative Go

Ch. 6 -
 The reaction coordinate indicates the
progress of the reaction, in terms of the
conversion of reactants to products
 The top of the energy curve corresponds to
the transition state for the reaction
 The free energy of activation (G‡) for
the reaction is the difference in energy
between the reactants and the transition
state
 The free energy change for the
reaction (Go) is the difference in energy
between the reactants and the products
Ch. 6 -
A Free Energy Diagram for a Hypothetical
Reaction with a Positive Free-Energy Change

Ch. 6 -
7A. Temperature, Reaction Rate,
and the Equilibrium Constant
 A 10°C increase
in temperature
will cause the
reaction rate to
double for many
Distribution of energies at two
reactions taking
different temperatures. The number place near room
of collisions with energies greater
than the free energy of activation is temperature
indicated by the corresponding
shaded area under each curve.
Ch. 6 -

Distribution of energies at two
different temperatures. The number
of collisions with energies greater
than the free energy of activation is
indicated by the corresponding
shaded area under each curve.
 The relationship
between the rate
constant (k) and G‡
is exponential :
G‡/RT
k = k0 e
e = 2.718, the base of
natural logarithms
k0 = absolute rate
constant, which equals
the rate at which all
transition states proceed
to products (At 25oC,
k0 = 6.2 ╳ 1012 s1 )
Ch. 6 -
  A reaction with a
lower free energy of
activation (G‡) will
occur exponentially
faster than a
reaction with a
higher G‡, as
dictated by
G‡/RT
Distribution of energies at two k = k0 e
different temperatures. The number
of collisions with energies greater
than the free energy of activation is
indicated by the corresponding
shaded area under each curve.
Ch. 6 -
Free Energy Diagram of SN2 Reactions

T.S.
G = free energy of
Free Energy

G activation
HO- + CH3Br Go = free energy
change
Go
CH3OH + Br-
Reaction Coordinate

 Exothermic (Go is negative)

 Thermodynamically favorable process
Ch. 6 -
8.The Stereochemistry of SN2 Reactions
 Inversion of configuration

CH3
HO + C Br
H (inversion)
CH2CH3
(R) CH3
HO C + Br
H
(S) CH2CH3
Ch. 6 -
 Example:
Nu⊖ attacks from the TOP face.

CH3 I +
OCH3

(inversion of configuration)

CH3 OCH3
+I
Ch. 6 -
 Example:

Nu⊖ attacks from the BACK face.

+ CN + Br
Br CN
(inversion of
configuration)

Ch. 6 -
9. The Reaction of tert-Butyl Chloride
with Hydroxide Ion: An SN1 Reaction
CH3 CH3
CH3 C Br + H2O CH3 C OH + HBr
CH3 CH3
 The rate of SN1 reactions depends only on
concentration of the alkyl halide and is
independent on concentration of the Nu⊖
Rate = k[RX]
In other words, it is a first-order reaction
 unimolecular nucleophilic substitution
Ch. 6 -
 9A. Multistep Reactions & the Rate-
Determining Step
 In a multistep reaction, the rate of the
overall reaction is the same as the rate
of the SLOWEST step, known as the
rate-determining step (r.d.s)
 For example:
k1 k2 k3
Reactant Intermediate Intermediate Product
(slow) (fast) (fast)
1 2

k1 << k2 or k3 Ch. 6 -
  The opening A is
much smaller than
openings B and C
 The overall rate at
which sand reaches
A
to the bottom of
the hourglass is
B limited by the rate
at which sand falls
C through opening A
 Opening A is
analogous to the
rate-determining
step of a multistep
reaction Ch. 6 -
10. A Mechanism for the SN1 Reaction
 A multistep process
Step (1):

CH3 (k1) CH3

CH3 C Br CH3 C + Br
CH3 slow CH3
r.d. step
(ionization
of alkyl
halide)
Ch. 6 -
 Free Energy Diagram of SN1 Reactions
T.S. (1)
T.S. (2)
Free Energy

T.S. (3)
(CH3)3C
+ Br-
G1 (CH3)3C -OH2
-
+ Br
(CH3)3CBr intermediate (CH3)3C-OH
+ H 2O -
+ Br
Reaction Coordinate
Ch. 6 -
Step (2)

CH3 (k 2 ) CH3 H
CH3 C + H2O CH3 C O
fast
CH3 CH3 H

Ch. 6 -
 Free Energy Diagram of SN1 Reactions
T.S. (1)
T.S. (2)
Free Energy

T.S. (3)
(CH3)3C
+ Br-
G1 (CH3)3C -OH2
-
+ Br
(CH3)3CBr intermediate (CH3)3C-OH
+ H 2O -
+ Br
Reaction Coordinate
Ch. 6 -
Step (2)

CH3 (k 2 ) CH3 H
CH3 C + H2O CH3 C O
fast
CH3 CH3 H

Step (3)

CH3 H (k 3 ) CH3
CH3 C O + H2O CH3 C OH
fast
CH3 H CH3
+ H3O+ Ch. 6 -
 Free Energy Diagram of SN1 Reactions
T.S. (1)
T.S. (2)
Free Energy

T.S. (3)
(CH3)3C
+ Br-
G1 (CH3)3C -OH2
-
+ Br
(CH3)3CBr intermediate (CH3)3C-OH
+ H 2O -
+ Br
Reaction Coordinate
Ch. 6 -
Step (2)

CH3 (k 2 ) CH3 H
CH3 C + H2O CH3 C O
fast
CH3 CH3 H

Step (3) k1 << k2 and k3

CH3 H (k 3 ) CH3
CH3 C O + H2O CH3 C OH
fast
CH3 H CH3
+ H3O+ Ch. 6 -
 2 intermediates and 3 transition states
(T.S.)
 The most important T.S. for SN1
reactions is T.S. (1) of the rate-
determining step (r.d.s.)
CH3
 
CH3 C Br
CH3
Ch. 6 -
11. Carbocations
11A. The Structure of Carbocations
 Carbocations are
trigonal planar
 The central carbon
atom in a carbocation
H3 C is electron deficient; it
C CH3 has only six e⊖ in its
valence shell
H 3C  The p orbital of a
carbocation contains
no electrons, but it can
accept an electron pair
sp2-sp3  bond when the carbocation
undergoes further
reaction
Ch. 6 -
11B. The Relative Stabilities of
Carbocations
 General order of reactivity (towards SN1
reaction)
● 3o > 2o >> 1o > methyl

 The more stable the carbocation

formed, the faster the SN1 reaction

Ch. 6 -
 Stability of cations
most stable (positive inductive effect)
R R R H
> > >
C C C C
R R R H H H H H

 Resonance stabilization of allylic and

benzylic cations

CH2 CH2
etc.
Ch. 6 -
12. The Stereochemistry of SN1 Reactions
Ph Ph Ph
CH3OH CH3OH
C CH3 C OCH3
CH3 Br
CH2CH3 CH3 CH2CH3 CH2CH3
(S) (trigonal planar) (R) and (S)
racemic mixture

CH3OH CH3OH
attack from left 50:50 attack from right
chance
Ph Ph

CH3O CH3 CH3 OCH3

CH2CH3 (1 : 1) CH2CH3
(R) ( S)
Ch. 6 -
  Example: racemic mixture
( 1 : 1 )
(R) H2O (R) (S)
+
(SN1)
Br OH OH
(one enantiomer)
attack from H2 O
slow TOP face H2 O
r.d.s.
H2 O O
H H

H2O attack from O

H H
(carbocation) BOTTOM face
Ch. 6 -
  Example:
I OMe Me
t
Bu Me MeOH tBu Me +tBu OMe

MeOH
slow Me H MeOH
O
r.d.s.
t
Bu Me
MeOH
Me
 CH3
t t H
Bu  Bu O
MeOH Me
trigonal planar
Ch. 6 -
13. Factors Affecting the Rates of
SN1 and SN2 Reactions

 The structure of the substrate

 The concentration and reactivity of the

nucleophile (for SN2 reactions only)

 The effect of the solvent

 The nature of the leaving group Ch. 6 -

13A. The Effect of the Structure of the Substrate

 General order of reactivity (towards SN2

reaction)

● Methyl > 1o > 2o >> 3o > vinyl or aryl

DO NOT
undergo
SN2 reactions
Ch. 6 -
 For example:
R Br + HO R OH + Br
Relative Rate (towards SN2)
CH3 CH3
CH3 Br CH3CH2 Br CH3CH Br CH3 C CH2Br CH3 C Br
CH3 CH3 CH3

methyl 1o 2o neopentyl 3o
6 4
2  10 4  10 500 1 <1
Most Least
reactive reactive
Ch. 6 -
 Compare
H    H
HO C Br HO C + Br
faster H
H
H H

H 
  H
HO C Br HO C + Br
slower CH3
CH3
CH3 CH3
Ch. 6 -
 H 
  H
HO C Br HO C + Br
t very t
Bu
Bu slow
H CH3

CH3  
 CH3
HO C Br HO C + Br
extremely
CH3 CH3
slow
CH3 CH3
Ch. 6 -
 Note NO SN2 reaction on sp2 or sp
carbons
e.g. sp2
H I
+ Nu No reaction
H H
sp2
I
+ Nu No reaction
sp

I + Nu No reaction
Ch. 6 -
Reactivity of the Substrate in SN1
Reactions
 General order of reactivity (towards SN1
reaction)
● 3o > 2o >> 1o > methyl

 The more stable the carbocation

formed, the faster the SN1 reaction

Ch. 6 -
 Stability of cations
most stable (positive inductive effect)
R R R H
> > >
C C C C
R R R H H H H H

 Allylic halides and benzylic halides also

undergo SN1 reactions at reasonable
rates I
Br
an allylic bromide a benzylic iodide
Ch. 6 -
 Resonance stabilization for allylic and
benzylic cations

CH2 CH2
etc.

Ch. 6 -
13B. The Effect of the Concentration
& Strength of the Nucleophile

 For SN1 reaction

Recall: Rate = k[RX]
● The Nu⊖ does NOT participate in the
r.d.s.
● Rate of SN1 reactions are NOT
affected by either the concentration
or the identity of the Nu⊖

Ch. 6 -
 For SN2 reaction
Recall: Rate = k[RX][RX]
● The rate of SN2 reactions depends
on both the concentration and
the identity of the attacking Nu⊖

Ch. 6 -
 Identity of the Nu⊖
● The relative strength of a Nu⊖ (its
nucleophilicity) is measured in
terms of the relative rate of its SN2
reaction with a given substrate
rapid
CH3O + CH3I CH3OCH3 + I
Good Nu⊖
Very
CH3OH + CH3I CH3OCH3 + I
slow
Poor Nu⊖
Ch. 6 -
 The relative strength of a Nu⊖ can be
correlated with 3 structural features
● A negatively charged Nu⊖ is always a
more reactive Nu⊖ than its conjugated
acid
 e.g. HO⊖ is a better Nu⊖ than H2O
and RO⊖ is better than ROH
● In a group of Nu⊖s in which the
nucleophilic atom is the same,
nucleophilicities parallel basicities
 e.g. for O compounds,
RO⊖ > HO⊖ >> RCO2⊖ > ROH > H2O
Ch. 6 -
● When the nucleophilic atoms are
different, then nucleophilicities may
not parallel basicities
 e.g. in protic solvents HS⊖, CN⊖,
and I⊖ are all weaker bases than
HO⊖, yet they are stronger Nu⊖s
than HO⊖
HS⊖ > CN⊖ > I⊖ >
HO⊖

Ch. 6 -
13C. Solvent Effects on SN2
Reactions:
Polar Protic & Aprotic
 Classification of solvents
Solvents
Non-polar solvents
(e.g. hexane,
benzene)
Solvents Polar protic solvents
(e.g. H2O, MeOH)
Polar
solvents
Polar aprotic solvents
(e.g. DMSO, HMPA)
Ch. 6 -
 SN2 Reactions in Polar Aprotic Solvents
● The best solvents for SN2 reactions
are
 Polar aprotic solvents, which
have strong dipoles but do not
have OH or NH groups
 Examples
O
CH3 O
O
H N P NMe
S Me2N NMe2 2
CH3 CH3 CH3 CH3CN
(DMSO) (DMF) (HMPA) (Acetonitrile)
Ch. 6 -
  Polar aprotic solvents tend to
solvate metal cations rather than
nucleophilic anions, and this
results in “naked” anions of the
Nu⊖ and makes the e⊖ pair of
the Nu⊖ more available

DMSO
CH3O Na CH3O + DMSO Na
"naked anion"

Ch. 6 -
  Tremendous acceleration in SN2
reactions with polar aprotic
solvent
CH3Br + NaI CH3I + NaBr

Solvent Relative Rate

MeOH 1

DMF 106

Ch. 6 -
 SN2 Reactions in Polar Protic Solvents
● In polar protic solvents, the Nu⊖
anion is solvated by the surrounding
protic solvent which makes the e⊖
pair of the Nu⊖ less available and
thus less reactive in SN2 reactions
OR
H
RO H Nu H OR
H
OR
Ch. 6 -
 Halide Nucleophilicity in Protic Solvents
● I⊖ > Br⊖ > Cl⊖ > F⊖
  OR OR
RO   H
H H
 
RO H F -
H OR RO H I-
 
H H
RO OR H
OR
(strongly solvated) (weakly solvated)
 Thus, I⊖ is a stronger Nu⊖ in protic
solvents, as its e⊖ pair is more available
to attack the substrate in the SN2 reaction.
Ch. 6 -
 Halide Nucleophilicity in Polar Aprotic
Solvents (e.g. in DMSO)
● F⊖ > Cl⊖ > Br⊖ > I⊖
 Polar aprotic solvents do not solvate
anions but solvate the cations

 The “naked” anions act as the Nu⊖

 Since F⊖ is smaller in size and the

charge per surface area is larger than
I⊖, the nucleophilicity of F⊖ in this
environment is greater than I⊖
Ch. 6 -
13D. Solvent Effects on SN1 Reactions:
The Ionizing Ability of the Solvent
 Solvent plays an important role in SN1
reactions but the reasons are different
from those in SN2 reactions

 Solvent effects in SN1 reactions are due

largely to stabilization or destabilization
of the transition state

Ch. 6 -
 Polar protic solvents stabilize the
development of the polar transition
state and thus accelerate this rate-
determining step (r.d.s.):
 OR
H
CH3 H3 C  
slow  
CH3 C Cl CH3 C Cl
r.d.s.
CH3  CH3 
R O H
H OR
CH2
-
Cl + CH3 C
CH3
Ch. 6 -
13E. The Nature of the Leaving Group
 The better a species can stabilize a
negative charge, the better the LG in
an SN2 reaction
SN1 Reaction:

slow  
C X C X C + X
r.d.s.

SN2 Reaction:
 
slow  
C X Nu C X Nu C +X
r.d.s.
Nu: Ch. 6 -
 Examples of the reactivity of some X⊖:
CH3O + CH3–X  CH3–OCH3 + X
Relative Rate:
OH, Worst X ⊖ Best X ⊖

NH2, <<F < Cl < Br < I < TsO

RO
~0 1 200 10,000 30,000 60,000

 Note: Normally R–F, R–OH, R–

NH2, R–OR’ do not undergo SN2
reactions. Ch. 6 -
 Nu
R OH  R Nu + OH
a poor a strong
leaving group basic anion
H

H Nu
R O R Nu H 2O
✔
+
H
a good weak
leaving group base
Ch. 6 -
14. Organic Synthesis: Functional Group
Transformation Using SN2 Reactions

OH

CN CN HO Me

MeO
Br
MeS
HS

SMe SH
Ch. 6 -
 Me

I Me C C O Me
I
MeCOO
Br

N3
Me3N

N3 NMe3 Br
Ch. 6 -
 Examples:

NaOEt,??DMSO
Br O

I SMe
NaSMe,?? DMSO

Ch. 6 -
 Examples:
??

I CN
(optically active, chiral) (optically active, chiral)

● Need SN2 reactions to control

stereochemistry
● But SN2 reactions give the inversion of
configurations, so how do you get the
“retention” of configuration here??
● Solution:
“double inversion”  “retention”
Ch. 6 -
 ??

I CN
(optically active, chiral) (optically active, chiral)

NaBr NaCN
DMSO DMSO
(SN2 with Br (SN2 with
inversion) inversion)
(Note: Br⊖ is a stronger Nu than
I⊖ in polar aprotic solvent.)
Ch. 6 -
14A. The Unreactivity of Vinylic and
Phenyl Halides
X
C C
X
vinylic halide phenyl halide

 Vinylic and phenyl halides are generally

unreactive in SN1 or SN2 reactions

Ch. 6 -
 Examples

NaCN
Br No Reaction
DMSO

I NaSMe
No Reaction
HMPA

Ch. 6 -
15. Elimination Reactions of Alkyl
Halides
 Substitution
H OCH3 H OCH3
-
C C C C + Br
(acts as a
Br Nu )
 Elimination
H OCH3 -
C C (acts as a C C + CH3OH + Br
H
Br base)
Ch. 6 -
 Substitution reaction (SN) and
elimination reaction (E) are processes
in competition with each other

e.g.
t
BuOK t
I O Bu +
t
BuOH
SN2: 15% E2: 85%

Ch. 6 -
15A. Dehydrohalogenation

β hydrogen
H α carbon
C C
β carbon
X halide as LG

Br
LG t
BuOK t
β α t + KBr + BuOH
BuOH, 60oC
H
β hydrogen
⊖
OtBu Ch. 6 -
 15B. Bases Used in Dehydrohalogenation
 Conjugate base of alcohols is often used
as the base in dehydrohalogenations
Na
R−O⊖ + Na⊕ + H2
R−O−H
NaH
R−O⊖ + Na⊕ + H2
e.g.
t
EtO Na BuO K
sodium ethoxide potassium tert-butoxide
Ch. 6 -
16. The E2 Reaction
Br
EtO + + EtOH + Br
H
 Rate = k[CH3CHBrCH3][EtO⊖]

 Rate determining step involves both

the alkyl halide and the alkoxide anion

 A bimolecular reaction
Ch. 6 -
Mechanism for an E2 Reaction
Et O Et O
H CH3 H CH3
α  H CH3
C C H C C H C C
H β H  H H
H Br H Br +

⊖ Et OH + Br
EtO removes Partial bonds in
a  proton; the transition C=C is fully
C−H breaks; state: C−H and formed and
new  bond C−Br bonds the other
forms and Br break, new  products are
begins to C−C bond forms EtOH and Br⊖
depart Ch. 6 -
Free Energy Diagram of E2 Reaction
T.S.
E2 reaction has ONE
G ‡
Free Energy

transition state
CH3CHBrCH3
-
+ EtO CH2=CHCH3
-
+ EtOH + Br
Reaction Coordinate

Rate = k[CH3CHBrCH3][EtO⊖]
 Second-order overall  bimolecular
Ch. 6 -
17. The E1 Reaction
 E1: Unimolecular elimination
CH3 CH3 CH
H 2O 3
CH3 C Cl CH3 C OH + CH2 C
CH3 CH3 CH3
slow (major (SN1)) (minor (E1))
r.d.s
CH3 H 2 O as H 2 O as
CH C nucleophile base
3
CH3
Ch. 6 -
Mechanism of an E1 Reaction
α carbon
β hydrogen
H
H2O H2O
Cl + H 3O
slow fast
r.d.s. (E1 product)
fast H2O

H HO
2
O OH + H3O
H
(SN1 product) Ch. 6 -
 Free Energy Diagram of E1 Reaction
T.S. (1)
T.S. (2)
Free Energy

(CH3)3C
-
+ Cl
G1
(CH3)2C=CH2
-
+ H3O + Cl
(CH3)3CCl
+ H 2O

Reaction Coordinate
Ch. 6 -
Step (1):

CH3 H 2O CH3
CH3 C Cl CH3 C + Cl
(k1)
CH3 CH3
slow
Aided by the r.d. step Produces relatively
polar solvent, a stable 3o carbocation
chlorine departs and a Cl⊖. The ions
with the e⊖ pair are solvated (and
that bonded it to stabilized) by
the carbon surrounding H2O
molecules
Ch. 6 -
 Free Energy Diagram of E1 Reaction
T.S. (1)
T.S. (2)
Free Energy

(CH3)3C
-
+ Cl
G1
(CH3)2C=CH2
-
+ H3O + Cl
(CH3)3CCl
+ H 2O

Reaction Coordinate
Ch. 6 -
Step (2)
H3C H H3C
(k2 )
C C H + H2O CH2
fast H3C
H3 C H
H
H2O molecule removes one of
the  hydrogens which are
+ H O
acidic due to the adjacent H
positive charge. An e⊖ pair
moves in to form a double Produces alkene and
bond between the  and  hydronium ion
carbon atoms
Ch. 6 -
18. How To Determine Whether
Substitution or Elimination Is Favoured

 All nucleophiles are potential bases and

all bases are potential nucleophiles

 Substitution reactions are always in

competition with elimination reactions

 Different factors can affect which type

of reaction is favoured
Ch. 6 -
18A. SN2 vs. E2

(a) H C
+X
(b) SN2 Nu C
H C
Nu
C X
(a) (b) C
+ Nu H + X
E2 C

Ch. 6 - 1
Primary Substrate
 With a strong base, e.g. EtO⊖
● Favor SN2

OEt
SN2: 90%
NaOEt
Br EtOH +

E2: (10%)

Ch. 6 - 1
Secondary Substrate
 With a strong base, e.g. EtO⊖
● Favor E2 +

E2: 80%
NaOEt
+
Br EtOH

OEt
SN2: 20%
Ch. 6 - 1
Tertiary Substrate
 With a strong base, e.g. EtO⊖
● E2 is highly favored

NaOEt
+
EtOH
Br OEt
E2: 91% SN1: 9%

Ch. 6 - 1
Base/Nu⊖: Small vs. Bulky
 Unhindered “small” base/Nu⊖
NaOMe +
Br MeOH OMe
SN2: 99% E2: 1%

 Hindered “bulky” base/Nu⊖

t
KO Bu +
t
Br t O Bu
BuOH SN2: 15% E2: 85%
Ch. 6 - 1
Basicity vs. Polarizability
O
O
O CH3
CH3 C O
+
(weak base)
Br SN2: 100% E2: 0%

OEt
EtO +
(strong base)
SN2: 20% E2: 80%
Ch. 6 - 1
Tertiary Halides: SN1 vs. E1 & E2

EtO OEt
+
(strong
base) E2: 100% SN1: 0%
Br

EtOH OEt
+
heat
E1 + E2: 20% SN1: 80%
Ch. 6 - 1
19. Overall Summary

S N1 S N2 E1 E2
CH3X ─ Very fast ─ ─

Hindered bases give

RCH2X ─ Mostly ─ mostly alkenes;
e.g. with tBuO⊖

R' Very little;

Solvolysis possible;
Mostly SN2 with
weak bases; Very little
Strong bases
promote E2;
e.g. with H2O;
RCHX MeOH
e.g. with CH3COO⊖ e.g. with RO⊖, HO⊖

R' Very favorable

Strong bases
RCX
with weak bases; Always competes
─ promote E2;
e.g. with H2O; with SN1
e.g. with RO⊖, HO⊖
R"
MeOH

Ch. 6 - 1
Review Problems
(1) Br
Na CN CN
o
t DMF, 25 C
Bu t
SN2 with inversion Bu

(2)
O
H NaH
I O Et2O

H⊖
I O
Intramolecular SN2 Ch. 6 - 1
(3) CH3 CH3 Cl
OH HCl Cl CH3
+
t t t
Bu Bu Bu
( 50 : 50)

Cl⊖ attacks Cl⊖ attacks

from top face from bottom
CH3 face
H CH3
O
H
t t
Bu Bu sp2 hybridized
carbocation
SN1 with racemization
Ch. 6 - 1
 END OF CHAPTER 6 

Ch. 6 - 1