CH 06

Chapter 6
Ionic Reactions
Nucleophilic Substitution
and Elimination Reactions
of Alkyl Halides
Created by
Professor William Tam & Dr. Phillis Chang
Copyright 2014 by John Wiley & Sons, Inc. All rights reserved.
About The Authors
These PowerPoint Lecture Slides were created and prepared by Professor
William Tam and his wife, Dr. Phillis Chang.
Professor William Tam received his B.Sc. at the University of Hong Kong in
1990 and his Ph.D. at the University of Toronto (Canada) in 1995. He was an
NSERC postdoctoral fellow at the Imperial College (UK) and at Harvard
University (USA). He joined the Department of Chemistry at the University of
Guelph (Ontario, Canada) in 1998 and is currently a Full Professor and
Associate Chair in the department. Professor Tam has received several awards
in research and teaching, and according to Essential Science Indicators, he is
currently ranked as the Top 1% most cited Chemists worldwide. He has
published four books and over 80 scientific papers in top international journals
such as J. Am. Chem. Soc., Angew. Chem., Org. Lett., and J. Org. Chem.
Dr. Phillis Chang received her B.Sc. at New York University (USA) in 1994, her
M.Sc. and Ph.D. in 1997 and 2001 at the University of Guelph (Canada). She
lives in Guelph with her husband, William, and their son, Matthew.
2014 by John Wiley & Sons, Inc. All rights reserved.

Table of Contents (hyperlinked)
1. Alkyl Halides
2. Nucleophilic Substitution Reactions
3. Nucleophiles
4. Leaving Groups
5. Kinetics of a Nucleophilic Substitution Reaction: An SN2 Reaction
6. A Mechanism for the SN2 Reaction
7. Transition State Theory: Free-Energy Diagrams
8. The Stereochemistry of SN2 Reactions
9. The Reaction of tert-Butyl Chloride with Water: An SN1 Reaction
11. Carbocations
13. Factors Affecting the Rates of SN1 and SN2 Reactions
14. Organic Synthesis: Functional Group Transformations Using SN2
Reactions
15. Elimination Reactions of Alkyl Halides
16. The E2 Reaction
17. The E1 Reaction
18. How to Determine Whether Substitution or Elimination Is Favored
19. Overall Summary
Table of Contents
1. Alkyl Halides
2. Nucleophilic Substitution Reactions
3. Nucleophiles
4. Leaving Groups
5. Kinetics of a Nucleophilic Substitution Reaction: An SN2 Reaction
7. Transition State Theory: Free-Energy Diagrams
9. The Reaction of tert-Butyl Chloride with Water: An SN1 Reaction
11. Carbocations
13. Factors Affecting the Rates of SN1 and SN2 Reactions
14. Organic Synthesis: Functional Group Transformations Using SN2
Reactions
15. Elimination Reactions of Alkyl Halides
16. The E2 Reaction
17. The E1 Reaction
18. How to Determine Whether Substitution or Elimination Is Favored
19. Overall Summary
In this chapter we will consider:
What groups can be replaced (i.e.,
substituted) or eliminated
The various mechanisms by which such

processes occur
The conditions that can promote such

reactions

1. Alkyl Halides
An alkyl halide has a halogen atom
bonded to an sp3-hybridized
(tetrahedral) carbon atom
The carbonchlorine and carbon

bromine bonds are polarized because
the halogen is more electronegative
than carbon

Iodine does not have a permanent
dipole, but the bond is easily
polarizable
Iodine is a good leaving group due to

its polarizability, i.e. its ability to
stabilize a negative charge due to its
large atomic size

C X
X = Cl, Br, I
Halogens are more electronegative

than carbon

Different Types of Organic Halides
Alkyl halides (haloalkanes)
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
Vinyl halides (Alkenyl halides)
sp2
X
Aryl halides
sp2
X
benzene or aromatic ring
Acetylenic halides (Alkynyl halides)

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

HO C Br
R R
transition state (T.S.)

2nd 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 (k 2 ) R H
R C + H 2O R C O
R fast R H
fast
3. Nucleophiles
A reagent that seeks a positive center
Nucleophile nucleus loving
phile derived from the Greek word

philia meaning loving

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

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 + H3O
CH3 OH
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
5. Kinetics of a Nucleophilic
Substitution Reaction:
An SN2 Reaction
The rate of the substitution reaction is

linearly dependent on the
concentration of HO and CH3Br
Overall, a second-order reaction
bimolecular
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
Graphically
Concentration, M
[CH3Cl]
[CH3OH]
Time, t
[CH3Cl] [CH3Cl]t=t [CH3Cl]t=0
Rate = =
t Time in seconds
Initial Rate
[CH3Cl]t=0
Concentration, M [CH3Cl]t=t
[CH3Cl]
Time, t
Initial Rate [CH3Cl]t=t [CH3Cl]t=0

=
(from slope) t
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

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.
The Kinetic Rate Expression
60oC
HO + Cl CH3 H2O
HO CH3 + Cl
Rate [OH][CH3Cl]
Rate = k[OH][CH3Cl]
Initial Rate
k=
[OH][CH3Cl]
= 4.9 10-7 L mol-1 s-1
5B. What is the Order of This
Reaction?
This reaction is said to be second
order overall
We also say that the reaction is
bimolecular
We call this kind of reaction an SN2
reaction, meaning substitution,
nucleophilic, bimolecular

6. A Mechanism for the SN2
Reaction
H
H

HO C Br HO C Br
H H H
H
transition state (T.S.)
negative HO
brings an e pair OC bond
partially formed; OC bond
to +C; Br formed; Br
begins to move CBr bond
partially broken. departed.
away with an e Configuration
pair Configuration of
C begins to invert of C inverted
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
At 60oC (333 K)
DGo = -100 kJ/mol

This reaction is highly exergonic
DHo = -75 kJ/mol
This reaction is exothermic

Its equilibrium constant (Keq) is
DGo = RT ln Keq
DGo
ln Keq =
RT
(100 kJ/mol)
=
(0.00831 kJ K-1 mol-1)(333 K)
= 36.1
Keq = 5.0 x 1015
A Free Energy Diagram for a Hypothetical SN2
Reaction That Takes Place with a Negative DGo

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 (DG) for
the reaction is the difference in energy
between the reactants and the transition
state
The free energy change for the
reaction (DGo) is the difference in energy
between the reactants and the products
A Free Energy Diagram for a Hypothetical
Reaction with a Positive Free-Energy Change

7A. Temperature & Reaction Rate
A 10C increase
in temperature
will cause the
reaction rate to
double for many
Distribution of energies at two reactions taking
different temperatures. The number
of collisions with energies greater place near room
than the free energy of activation is
indicated by the corresponding temperature
shaded area under each curve.

The relationship
between the rate
constant (k) and DG
is exponential :
DG/RT
k = k0 e
e = 2.718, the base of
natural logarithms
k0 = absolute rate
Distribution of energies at two constant, which equals
different temperatures. The number
of collisions with energies greater the rate at which all
than the free energy of activation is transition states proceed
indicated by the corresponding
to products (At 25oC,
k0 = 6.2 1012 s1 )
A reaction with a
lower free energy of
activation (DG) will
occur exponentially
faster than a
reaction with a
higher DG, as
dictated by
DG/RT
Distribution of energies at two
different temperatures. The number k = k0 e
of collisions with energies greater
than the free energy of activation is
indicated by the corresponding

Free Energy Diagram of SN2 Reactions
T.S.
DG = free energy of
Free Energy
DG activation
HO- + CH3Br DGo = free energy
change
DGo
CH3OH + Br-
Reaction Coordinate
Exothermic (DGo is negative)

Thermodynamically favorable process
8. The Stereochemistry of SN2
Reactions
Inversion of configuration
CH3
HO + C Br
H (inversion)
CH2CH3
(R) CH3
HO C + Br
H
(S) CH2CH3
Example: Nu attacks from the TOP face.
CH3 I
+ OCH3
(inversion of configuration)
CH3 OCH3
+I

Example:
Nu attacks from the BACK side.
(inversion of
configuration)

9. The Reaction of tert -Butyl
Chloride with Water:
An SN1 Reaction

The rate of SN1 reactions depends only
on concentration of the alkyl halide and
is independent of concentration of the
Nu
Rate = k[tBuCl]
In other words, it is a first-order
reaction
unimolecular nucleophilic substitution
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
The opening A is
Fig. 6.5 much smaller than
openings B and C
The overall rate at
which sand reaches
A to the bottom of the
hourglass is limited
by the rate at which
B
sand falls through
opening A
C Opening A is
analogous to the
rate-determining
step of a multistep
reaction
10. A Mechanism for the SN1
Reaction
A multistep process
slow
r.d.s.

intermediate

Step (2)
CH3 (k2) CH3 H

CH3 C + H2O CH3 C O
fast
CH3 CH3 H

intermediate

Step (2)
CH3 (k2) CH3 H

CH3 C + H2O CH3 C O
fast
CH3 CH3 H
fast

intermediate

Step (2)
CH3 (k2) CH3 H

CH3 C + H2O CH3 C O
fast
CH3 CH3 H
k1 << k2 and k3
fast

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
11. Carbocations
11A. The Structure of Carbocations
Carbocations are
trigonal planar
The central carbon
atom in a carbocation
H3C is electron deficient; it
C CH3 has only six e in its
valence shell
H3C The p orbital of a
carbocation contains
no electrons, but it can
accept an electron pair
when the carbocation
undergoes further
reaction
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

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.

12. 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
(1 : 1)
Example: racemic mixture
( 1 : 1 )
(R) H2O (R) (S)
+
(SN1)
Br OH OH
(one enantiomer)
attack from H2O
slow TOP face H2O
r.d.s.
H2O O
H H
H2O attack from O

H H
(carbocation) BOTTOM face
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
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

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
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
o o o
methyl 1 2 neopentyl 3
6 4
2 10 4 10 500 1 <1
Most Least
reactive reactive
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
H
HO C Br
t very
Bu slow
H
CH3
CH3
HO C Br HO C + Br
extremely CH3
CH3 slow
CH3 CH3
Note NO SN2 reaction on sp2 or sp carbons
sp2
sp2
sp

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

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

Resonance stabilization for allylic and
benzylic cations

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
For SN2 reaction
Recall: Rate = k[Nu][RX]
The rate of SN2 reactions depends
on both the concentration and
the identity of the attacking Nu

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
Good Nu
Very
slow
Poor Nu:
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 conjugate
acid
e.g. HO is a better Nu than H2O
and RO is better than ROH
In a group of Nus in which the
nucleophilic atom is the same,
nucleophilicities parallel basicities
e.g. for O compounds,
RO > HO >> RCO2 > ROH > H2O
When the nucleophilic atoms are
different, then nucleophilicities may
not parallel basicities
e.g. in protic solvents HS, NC,
and I are all weaker bases than
HO, yet they are stronger Nus
than HO
HS > NC > I > HO

13C. Solvent Effects in SN2 & SN1
Reactions
SN2 reactions are favored by polar
aprotic solvents (e.g., acetone, DMF,
DMSO)
SN1 reactions are favored by polar

protic solvents (e.g., EtOH, MeOH,
H2O)

Classification of 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)

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)
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"

Tremendous acceleration in SN2
reactions with polar aprotic
solvent
CH3Br + NaI CH3I + NaBr
Solvent Relative Rate
MeOH 1
DMF 106

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
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.
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
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

Polar protic solvents stabilize the
development of the polar transition
state and thus accelerate this rate-
determining step (r.d.s.):

13D. The Nature of the Leaving Group
Leaving groups depart with the

electron pair that was used to bond
them to the substrate
The best leaving groups are those that

become either a relatively stable anion
or a neutral molecule when they depart

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:
Examples of the reactivity of some X:
CH3O + CH3X CH3OCH3 + X
Relative Rate:
HO , Worst X
Best X
H2N, <<F < Cl < Br < I < TsO

RO
~0 1 200 10,000 30,000 60,000
Note: Normally RF, ROH, RNH2,
ROR do not undergo SN2
reactions.

a poor a strong
leaving group basic anion
H Nu
R O R Nu + H2O
H
a good
weak
leaving group base
Other weak bases that are good
leaving groups:

14. Organic Synthesis: Functional
Group Transformation Using
SN2 Reactions
OH
CN HO
MeO
Br
MeS
HS
SMe SH
Me
I Me C C O Me
I
MeCOO
Br
N3
Me3N
N3 NMe3 Br
Examples:
NaOEt,??DMSO
Br O
I SMe
NaSMe,?? DMSO

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
??
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.)
14A. The Nonreactivity 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

Examples
NaCN
Br No Reaction
DMSO
I NaSMe
No Reaction
HMPA

15. Elimination Reactions of Alkyl
Halides
Substitution
Elimination

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%

15A. Dehydrohalogenation
hydrogen
H carbon
C C
carbon
X halide as LG
Br
LG t
BuOK t
t o + KBr + BuOH
BuOH, 60 C
H
hydrogen
OtBu

15B. Bases Used in Dehydro-
halogenation
Conjugate base of alcohols is often used
as the base in dehydrohalogenations
Na
RO + Na + H2
ROH
NaH
RO + Na + H2

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
Mechanism for an E2 Reaction
Et O Et O
H CH3 H CH3
H CH3
C C H C C H C C
H H H H
H Br H Br +
EtO removes a Partial bonds in Et OH + Br

b proton; CH the transition C=C is fully
breaks; new p state: CH and formed and
bond forms and CBr bonds the other
Br begins to break, new p products are
depart CC bond forms EtOH and Br
Free Energy Diagram of E2 Reaction
T.S.
E2 reaction has ONE
DG
Free Energy
transition state
CH3CHBrCH3
-
+ EtO CH2=CHCH3
-
+ EtOH + Br
Reaction Coordinate
Rate = k[CH3CHBrCH3][EtO]
Second-order overall bimolecular
17. The E1 Reaction
E1: Unimolecular elimination
CH3 CH3 CH3
H 2O
CH3 C Cl CH3 C OH + CH2 C
CH3 CH3 CH3
slow (major (SN1)) (minor (E1))
r.d.s
CH3 H2O as H2O as
CH3 C nucleophile base
CH3
Mechanism of an E1 Reaction
carbon
hydrogen
H
H2O
+ H3O
slow fast
r.d.s. (E1 product)
fast H2O
H HO
2
O OH + H3O
H
(SN1 product)

Step (1):
CH3 H 2O CH3
CH3 C Cl CH3 C + Cl
(k 1 )
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

Step (2)
H 3C H H 3C
(k 2 )
C C H + H 2O CH2
fast H 3C
H 3C H
H
H2O molecule removes one of
the b 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 b and hydronium ion
carbon atoms
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

18A. SN2 vs. E2
(a) H C
+X
(b) S N2 Nu C
H C
Nu
C X
(a) (b) C
+ Nu H + X
E2 C

Primary Substrate
With a strong base, e.g. EtO
Favor SN2
OEt
SN2: 90%
NaOEt
Br EtOH +
E2: (10%)

Secondary Substrate
Favor E2 +
E2: 80%
NaOEt
+
Br EtOH
OEt
SN2: 20%
Tertiary Substrate
E2 is highly favored
NaOEt
+
EtOH
Br OEt
E2: 91% SN1: 9%

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%
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%
Tertiary Halides: SN1 vs. E1 & E2
EtO OEt
+
(strong
base) E2: 100% SN1: 0%
Br
EtOH OEt
+
heat
E1 + E2: 20% SN1: 80%
19. Overall Summary
SN1 SN2 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;
RCHX
e.g. with H2O;
e.g. with CH3COO e.g. with RO, HO
MeOH
R' Very favorable

Strong bases
RCX with weak bases;
e.g. with H2O;

Always competes
with SN1
promote E2;
e.g. with RO, HO
MeOH
R"
Review Problems
CN
t
Bu
SN2 with inversion
(2)
O
H NaH
I O Et2O
I O
Intramolecular SN2
(3) CH3
OH HCl
t
Bu
Cl attacks Cl attacks
from top face from bottom
CH3
H
face
CH3
O
H
t t
Bu Bu sp2 hybridized
carbocation
SN1 with racemization

END OF CHAPTER 6

CH 06

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

CH 06

Uploaded by

Copyright:

Available Formats

Chapter 6

2014 by John Wiley & Sons, Inc. All rights reserved.

The various mechanisms by which such

The conditions that can promote such

2014 by John Wiley & Sons, Inc. All rights reserved.

The carbonchlorine and carbon

2014 by John Wiley & Sons, Inc. All rights reserved.

Iodine is a good leaving group due to

2014 by John Wiley & Sons, Inc. All rights reserved.

Halogens are more electronegative

2014 by John Wiley & Sons, Inc. All rights reserved.

Attached to Attached to Attached to

benzene or aromatic ring

Acetylenic halides (Alkynyl halides)

Different reactivity than alkyl halides,

2014 by John Wiley & Sons, Inc. All rights reserved.

Nucleophile nucleus loving

phile derived from the Greek word

2014 by John Wiley & Sons, Inc. All rights reserved.

H2O, NH3 (neutral)

2014 by John Wiley & Sons, Inc. All rights reserved.

The rate of the substitution reaction is

Initial Rate [CH3Cl]t=t [CH3Cl]t=0

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

2014 by John Wiley & Sons, Inc. All rights reserved.

The rate of reaction is directly

When the concentration of either

2014 by John Wiley & Sons, Inc. All rights reserved.

DGo = -100 kJ/mol

DHo = -75 kJ/mol

This reaction is exothermic

2014 by John Wiley & Sons, Inc. All rights reserved.

2014 by John Wiley & Sons, Inc. All rights reserved.

2014 by John Wiley & Sons, Inc. All rights reserved.

2014 by John Wiley & Sons, Inc. All rights reserved.

2014 by John Wiley & Sons, Inc. All rights reserved.

Exothermic (DGo is negative)

2014 by John Wiley & Sons, Inc. All rights reserved.

Nu attacks from the BACK side.

2014 by John Wiley & Sons, Inc. All rights reserved.

2014 by John Wiley & Sons, Inc. All rights reserved.

2014 by John Wiley & Sons, Inc. All rights reserved.

2014 by John Wiley & Sons, Inc. All rights reserved.

CH3 (k2) CH3 H

2014 by John Wiley & Sons, Inc. All rights reserved.

2014 by John Wiley & Sons, Inc. All rights reserved.

CH3 (k2) CH3 H

2014 by John Wiley & Sons, Inc. All rights reserved.

2014 by John Wiley & Sons, Inc. All rights reserved.

CH3 (k2) CH3 H

2014 by John Wiley & Sons, Inc. All rights reserved.

The more stable the carbocation

2014 by John Wiley & Sons, Inc. All rights reserved.

2014 by John Wiley & Sons, Inc. All rights reserved.

H2O attack from O

The concentration and reactivity of the

The effect of the solvent

The nature of the leaving group

General order of reactivity (towards

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

2014 by John Wiley & Sons, Inc. All rights reserved.