Elimination

reactions

1
 Learning Outcomes
Predict the outcome of elimination reactions
Predict the dominant mechanism between
elimination and substitution reaction, and the
major and minor products from the reactions
 References
• McMurry : Chapter 10, 11
• Klein: Chapter 10

3
 Outlines
• Introduction
• E2 reaction
• Regiochemical outcome of E2 reaction
• Stereochemical outcome of E2 reaction
• E1 reaction
• Regiochemical outcome of E1 reaction
• Stereochemical outcome of E1 reaction
• Substitution vs Elimination

4
 Introduction
• occur when a single reactant splits into two
products, often with the formation of a small
molecule

Leaving group (LG) is replaced

with a nucleophile.
5

The β-proton is removed

together with the LG, forming
double bond 5
 E2 reaction
• E stands for elimination, the LG is eliminated
• 2 stands for bimolecular, involves both substrate
and base

a. How many steps are there in the reaction? How many arrows are
there in the each of the step? Where are they coming and where
are they going?
b. Compare the final product to the initial product!
c. Compared to substitution reactions, what are the differences and
what are the similarities?
6
 E2 SN2
One step reaction One step reaction

Two chemical entities Two chemical entities

Using a base Using a nucleophile

LG is removed from the LG is substituted by

substrate nucleophile

Tertiary substrates readily Tertiary substrates don’t

undergo E2 undergo SN2
Steps of E2 reaction:

1. Base will take proton from the β position of substrate

Base
Base

2. The negative charge from carbon will be transferred into double bond with neighboring
carbon

3. The negative charge from carbon will be transferred into LG.

Then, why tertiary carbons readily undergo E2 reaction?
These are the steps:
1. Base will take proton from the β position of substrate

If you compare the primary carbon and tertiary carbon, tertiary carbon is less
stable than primary carbon to hold a negative charge due to inductive effect!
( methyl groups are electron donating  making negative charge unstable)
Therefore, the electron transfer will be done very fast!

2. The negative charge from carbon will be transferred into double bond with neighboring
carbon

3. The negative charge from α-carbon will be transferred into LG.

 Factors affecting E2 reaction
1. The substrate
Tertiary substrates undergo E2 reaction more
readily than secondary and primary substrates.
2. The base
The stronger the base, the faster the reaction.
3. The leaving group
The leaving group must be able to withdraw
electron density from C, and capable of stabilizing
the negative charge after being expelled.
10
11
 Regiochemical outcome of an E2
reaction
• In what region of the molecule is the reaction
taking place?

There are 2 ᵦ carbon connected to LG

where does the double bond form?

• Double bonds can have anywhere from 1 to 4
groups attached to them:

Disubstituted

Monosubstituted
In the elimination reaction,
• The more substituted alkene = Zaitsev product (usually the major
product)
• The less substituted alkene = Hofmann product

Zaitsev product: major product

ᵦ carbon is secondary carbon  Neg charge on carbon will be

very unstable because less e- donating groups are attached to the
neg charge destabilizing it fast reaction

Hofmann product: minor product

ᵦ carbon is Primarycarbon  Neg charge on carbon will be more
stable than possibility # 1 reaction will not proceed so fast

There are however exception to the rule

• When more than one alkene isomer can be formed
in an E2 elimination, the more substituted, more
stable alkene isomer is usually formed

15
Reactivity order for E2

16
 • In this exception reaction, Hofmann product is the
major product. Zaitsev product Hofffman product

ᵦ α
ᵦ

Happen when the reaction is performed with a sterically hindered base (e.g. t-
butoxide)!
Base attaching the more
substituted carbon

The Bulkier bases prefer to attack less

substituted carbons due to steric hindrance

Base attaching the Less

substituted carbon
• Example of Bulky bases

The regiochemical outcome of an E2 reaction can

often be controlled by carefully choosing the
base.
 Exercise
Draw the Zaitsev and Hofmann products of the reaction between
the substrates with a base!

19
 Stereochemical outcome of an E2
reaction
• E2 reaction prefer the reaction happen in the
anti-periplanar!
Anti-periplanar is a term used in organic chemistry to describe the bond angle in a
molecule.

saw-horse formula Newman projection

20
 Stereochemical outcome of an E2
reaction

Trans Cis
Have identical proton in
Stereochemistry is RELEVANT! There
the β position, so the
are 2 stereoisomeric alkenes that are
regiochemistry is NOT
possible.
an issue!

Example of stereoselective reaction, because

the substrate produces two stereoisomers in
UNEQUAL amounts
1. Draw Newman projection of that substrate(3-bromopentane)!

Et
H H

Br Antiperiplanar position!
H
Met

2. Eliminate the Leaving Group and Hydrogen to

form double bond
Et
Et
H H
H Et H

H
H Br Met
H
Met
Met Trans: major product!
3. Rotate the Newman projection in order for the LG
and H in the antiperiplanar position!
Et Et
H H H Met

H Br H Br
Met H
4. Eliminate the Leaving Group and Hydrogen to
form double bond
Et
Et
Met Et Met
H Met

HH Br H H
HH Cis: minor product!
Bulky groups opposite Bulky groups close to
each other each other

Et Et
H H H Met

H Br H Br
Met H
Gauche conformation: methyl and
Anti conformation: more stable ethyl groups close to each other 
substrate will be found mostly less stable
in this conformer

Form trans product: Form cis product:

major product minor product

Example of stereoselective reaction, because the

substrate produces two stereoisomers in UNEQUAL
amounts
24
• A stereoselective reaction is one in which one
stereoisomer predominates over another
when two or more may be formed.

25
Another example of reaction:
Not sterically hindered base:
The formation of Zaitsev product is
expected!

More substituted: Less substituted:

Zaitsev product Hofmann product

Only 1 proton in β position! So, this reaction is

stereospecific  produce only one alkene rather
than a mixture of stereoisomeric alkenes.

Stereospecific reaction is a reaction in which the stereochemistry

of the reactant completely determines the stereochemistry of
the product without any other option.
26
1. Draw Newman projection of that substrate!

2. Rotate the Newman projection in order for the LG

and H in the antiperiplanar position!

27
 3. Eliminate the Leaving Group and Hydrogen to
form double bond

Z-stereoisomer
Expected Zaitsev product

Z-stereoisomer

E-stereoisomer
Example of stereospecific reaction,
because the substrate produces only one Because ᵦ carbon has only one
type of product! proton
 Recap steps of E2 reaction
1. Check the expected regiochemical outcome; which one will
you get as a major product, Zaitsev or Hoffman product?
– If the base is not sterically hindered, you will get Zaitsev.
– If the base is sterically hindered, you will get Hoffman.
– If the beta position is identical, the regiochemistry is not an
issue
2. Check the expected stereochemical outcome; is it one
type of product or mixture of stereoisomers?
- Identify the proton at β position. If it is only 1, it is stereospecific
reaction. If it has more than 1, it is stereoselective reaction.
- Draw Newman projection
- Rotate the groups until you get antiperiplanar conformation (H on
the front carbon is 180° away from LG)
- Remove the proton and LG 29
• E2 mechanism: stereo specificity (11.49 min)
• https://www.youtube.com/watch?v=VdpIq3FZ
Cn8

30
 Exercise
Predict the product of these following reactions!

+
10.5. A. Check the expected regiochemical outcome!
Ethoxide ion is not sterically hindered base  Zaitsev product is
the major product!

There are 2 β position. The more substituted Carbon is the major

product (Zaitsev product)

Zaitsev product Hofmann product

32
 10.5. B. Check the expected stereochemical outcome!
There is only 1 H at the β position  stereospecific reaction

Met Met
Turn it slightly so Met H H Et
its easier to see

H Cl H Cl
Et Met

Et Met

Met H
33
Sum up of the reaction:

+ +

major product minor product

Z-stereoisomer
10.6. A. Check the expected regiochemical outcome!
Ethoxide ion is not sterically hindered base  Zaitsev product is
the major product!

There are 2 β position. The more substituted Carbon is the major

product (Zaitsev product)

Zaitsev product Hofmann product

10.6. B. Check the expected stereochemical outcome!
There is only 1 H at the β position  stereospecific reaction

Et
Isopropyl H Isopropyl
Et
Cl H
Et Et H
Sum up of the reaction:

+ +

major product minor product

Z-stereoisomer
 E1 reaction
• E stands for elimination, the LG is eliminated
• 1 stands for unimolecular, involves substrate only

a. How many steps are there in the reaction? How many arrows are
there in the each of the step? Where are they coming and where
are they going?
b. Compare the final product to the initial product!
c. Compare with substitution reactions, what are the differences
and what are the similarities?
38
 E1 SN1
Two steps reaction Two steps reaction
Substrate as the rate Substrate as the rate
determining step determining step

Tertiary halides reacting more Tertiary halides reacting more

readily than secondary halides; readily than secondary halides;
primary halides don’t undergo primary halides don’t undergo
E1. SN1.
Using a base Using a nucleophile

LG is removed from the LG is substituted by

substrate nucleophile

39
 SN1

E1

Notes:
E1 reaction is generally accompanied by a competing SN1 reaction,
and a mixture of product is generally obtained.
Means that it will be a mixture of substitution and elimination
products in the solution
Steps of E1 reaction:

The following steps are not real Just for understanding

1. Leaving group (LG) will take electrons from neighboring carbon, results in the formation
of carbocation.

2. Base will snatch Hydrogen from β-position carbon and the electrons from C-H bond
move into C.

3. The negative charge from carbon will be transferred into carbocation.

 Factors affecting E1 reaction
1. The substrate (carbocation)
Tertiary substrates undergo E1 reaction more readily
than secondary substrates. Primary substrates don’t
undergo E1 reaction.
2. The base
The strength of the base will not really affecting the
speed of the reaction (not a rate determining step)
3. The leaving group
The leaving group must be able to withdraw electron
density from C, and capable of stabilizing the
negative charge after being expelled.
42
Example of E1 reaction:

Bad LG!

t-butyl alcohol undergo elimination reaction to form 2-methyl propene

We need to protonate OH- group with a strong acid to give a better leaving group.

43
 Regiochemical outcome of an E1
reaction

Zaitsev product Hofmann product

More substituted
alkene ( Tri-substituted)

• Difference with E2 reaction:

The regiochemical outcome of an E1 reaction cannot be
controlled by choosing the base (sterically hindered or not
sterically hindered)  Zaitsev product is ALWAYS a major
product for E1 reaction.
 Exercise
Draw the major and minor products that are expected
when these substances are heated in the presence of
concentrated H2SO4 to give an E1 reaction!

1°
2°
1°

2°
1°

2°
 Stereochemical outcome of an E1
reaction
• E1 reactions do not require anti-periplanarity in order for the
reaction to occur. E2 LG andH must be in opposite side
E1 carbocation must leave first)

• E1 reactions are stereoselective, in which they prefer the

formation of trans stereoisomer compared to cis.
So if we have this reaction of elimination of water molecules from 3-hydroxyl
pentane, it will form trans and cis product, with trans as the major product.

Decreased steric
hindrance
• E1 mechanism: stereo selectivity (9.30 min)
• https://www.youtube.com/watch?v=4fdEhh6Y
NE4

47
 Substitution vs Elimination
• Substitution and elimination reactions are almost
always in competition with each other  predict
which mechanism win the competition!
• Ex of one clear winner:

• Substrate is tertiary  SN2 is impossible (due to steric hindrance )

• The base is very strong base (OH-)  compete the process of E1 and SN1
reaction (which depends on the loss of LG)but SN1 and E1 favors
Weak nucleophile/base not strong bases
• Product is only from E2 reaction!
48
• Ex of more than 1 winner:

• Substrate is tertiary  SN2 is impossible

• The base is weak base (MeOH)  too weak to undergoes
E2 reaction.
• Product is the mixture between E1 and SN1 reactions!
Goal:
Predict all of the products and predict which products
are major and which are minor.

Steps:
1. Determine the function of the reagent.
2. Analyze the substrate and determine the
expected mechanism(s).
3. Consider regiochemical and stereochemical
requirements.
1. Determine the function of the reagent.
Basic rules:
Base  elimination reaction How to
Nucleophile  substitution reaction determine?
Strong base ≠ Strong nucleophile!
It is possible for a reagent to be a strong nuc and a
weak base or weak nuc and strong base.
Basicity and nucleophilicity DO NOT ALWAYS parallel
each other!

51
# Basicity and nucleophilicity parallel each other
when comparing atoms in the same row of the
periodic table.

Ex: NH2- and OH-.

O is more electronegative than N, so OH- will be more stable than NH2-
 NH2- will be a stronger base by give away its electron to an acid.
NH2- will also be stronger nuc than OH-. Stronger base
Stronger Nuc

52
# Basicity and nucleophilicity DO NOT parallel each
other when comparing atoms in the same column of
the periodic table.

Ex: HS- and OH-.

S is larger than O  stabilize a charge better than O  OH- will be a stronger base
by give away its electron to an acid; but a weaker nuc.
When S approaches an electrophile, the electron density of S gets polarized and
makes some part of S more δ-  increases the force of attraction between nuc and
electrophile  increase the rate of attack  means S atom is very nucleophilic 
HS- act as nucleophile and rarely act as a base.

Stronger base

Stronger Nuc
53
Reminder:

Nucleophilicity vs. Basicity

https://www.youtube.com/watch?v=Mx7KM-
k2MMo
Basicity vs Nucleophilicity - Steric Hindrance
https://www.youtube.com/watch?v=3vyeQ8DC_D8

54
 • Sulfur, halides (Cl, Br, I) are function exclusively as
nucleophiles due to large size  undergo
substitution reactions.
• 4 categories of reagents:

Function as:
Strong nuc Strong base Strong base Weak base
Weak base Weak nuc Strong nuc Weak nuc

Substitution reaction Elimination reaction SN2 and E2 SN1 and E1

55
 Notice that tert-butoxide appears in
both the second and third categories.
Technically, it is a strong nucleophile and a strong base, so it
belongs in the third category. But practically, tert-butoxide is
sterically hindered, which prevents it from functioning as a
nucleophile in most cases. Therefore, it is often used as a base,
to favor E2 over SN2.

56
Strength of an acid Strength of a base

Electronegativity Nucleophilicity

57
 Exercise
Identify the function of each of the following reagents. Whether they are
(a) strong nucleophile and weak base;
(b) weak nucleophile and strong base;
(c) strong nucleophile and strong base;
(d) d) weak nucleophile and weak base

Weak nuc and weak base

Strong nuc and Strong base

Strong nuc and weak base

Strong nuc and weak base

58
Goal:
Predict all of the products and predict which products
are major and which are minor.

Steps:
1. Determine the function of the reagent.
2. Analyze the substrate and determine the
expected mechanism(s).
3. Consider regiochemical and stereochemical
requirements.
 2. Analyze the substrate
• Substrate can be either 1◦, 2◦, 3◦ substrate.

When the reagent functions exclusively as a

nucleophile (and not as a base), only
substitution reactions occur. The substrate
determines which mechanism operates. SN2
predominates for primary and secondary
substrates, and SN1 predominates for tertiary
substrate.

When the reagent is a strong nucleophile only,

most of substrates undergo SN2 reaction, unless if
the substrate is tertiary.
60
 When the reagent functions exclusively as a
base (and not as a nucleophile), only
elimination reactions occur. Such reagents are
generally strong bases, resulting in an E2
process. This mechanism is not sensitive to
steric hindrance, and can occur for primary,
secondary and tertiary substrates

When the reagent is a strong base only, all

substrates undergo E2 reaction!
 For primary substrates, SN2 predominates over E2,
unless t-Butoxide is used as the reagent, in which
case E2 predominates.
For secondary substrates, E2 predominates, because
E2 is not sensitive to steric considerations, while
SN2 is extremely sensitive to steric consideration.
For tertiary substrates, only E2 is observed, because the
SN2 pathway is too sterically hindered to occur.

When the reagent is both a strong base and strong nucleophile,

almost all substrates undergo both SN2 and E2, unless for 3◦
substrates undergo E2 only due to steric hindrance.
If substrates are 1◦ no steric hindrance  SN2 predominates
(unless the reagent is t-butoxide which has steric hindrance: E2
predominates)
If substrates are 2◦  steric hindrance  E2 predominates.
62
When the reagent is both a weak base and weak nucleophile,
generally almost all substrates will undergo E1 and SN1 reactions,
except:
1. 1◦ substrates  can’t undergo E1 and SN1 due to instable
carbocation  E2 and SN2 (very slow)
2. 2◦ substrates  undergo E1, SN1, E2, SN2 (very slow)

63
• Unique reaction:
Secondary and tertiary alcohols will undergo E1
reaction when treated with sulfuric acid and heat.

When carbocations are formed,

• At low temperatures, the SN1 pathway will dominate over the E1 pathway.

• At higher temperatures, more E1 products will be formed.

64
 Exercise
Identify the mechanism(s) expected to occur in
each of the following cases.
EtO- (strong base, strong Nuc) : E2 and SN2.
Substrate is primary  SN2 predominates.

H2SO4 neither base nor Nuc. Substrate is

secondary alcohol  E1 reaction

H2O (weak base, weak Nuc): E1,SN1,E2,SN2.

Substrate is tertiary  E1 and SN1

Br (strong Nuc, weak base): SN1 or SN2

Substrate is primary  SN2
65
3. Consider regiochemical and
stereochemical requirements

66
67
 Exercise
Predict the product(s) of the following reaction, and
identify the major and minor products:

Steps:
1. Check the reagent. Reagent is MeO- (strong base, strong Nuc)  SN2 and E2.
2. Check the substrate. Substrate is secondary carbon  E2 predominates over SN2 (due to
steric hindrance).
3. Consider regiochemistry  elimination reaction takes the H at the β position. There are
2 β position. Reaction will produce more Zaitsev (more substituted carbon) as the
product. Since we don’t use sterically hindered base.so the base will take H from the
more substituted carbon
4. Consider stereochemistry  The β carbon has 2 H
 stereoselective  trans will be favored than cis.

5. Consider the SN2 product. The stereochemical

outcome is the inversion of the configuration.

In summary:

69
 Exercise

Steps:
1. Check the reagent. Reagent is OH- (strong base, strong Nuc)  SN2 and E2.
2. Check the substrate. Substrate is primary carbon  SN2 predominates over E2.
3. Consider regiochemistry  nucleophile attacks the α carbon (electrophile).
4. Consider stereochemistry The stereochemical outcome is the inversion of the
configuration.

70
5. Consider the E2 product. There is only one C at
the β position  regiochemistry not applicable

6. Consider the stereochemistry of E2  only

monosubstitution  not applicable
Summary:
From SN2 reaction From E2 reaction

71
 Take home assignment
Please write your answer on the paper with your
handwriting. Scan or take a picture of your
answer and upload it into ACIS under tab of
Assignment of session 9 before your next week
schedule.
Make sure your picture is clear enough.
 Take home assignment
Predict the product(s) of the following reaction, and identify
the major and minor products, together with the
considerations and the arrow pushing:

73
 SUMMARY
• E1 consists of 2 steps reaction, E2 consists of 1 step reaction
• Factors affecting E1 and E2: substrate, base and leaving group
• Regiochemical outcomes of E1 and E2 reaction: Zaitsev and
Hofmann products
• Stereochemical outcomes of E1: stereoselective for trans.
Stereochemical outcomes of E2: can be stereoselective for trans
or stereospecific.
• Steps for determining elimination or substitution reaction:
Steps:
1. Determine the function of the reagent.
2. Analyze the substrate and determine the expected
mechanism(s).
3. Consider regiochemical and stereochemical requirements.
• https://www.khanacademy.org/science/organic-chemistry/substitution-
elimination-reactions#e1-e2-tutorial
78