CHAPTER 12: Elimination Reactions
12.1. Addition vs. Elimination, SN2 and SN1 vs. E2 and E1
Using a variety of reaction conditions, it is possible to add two groups across an
alkene (Scheme 12.1, see Chapter 8). Elimination reactions are simply the reverse
of this, removing two groups to form an alkene.
Scheme 12.1 – Generalized Reaction Equations for Electrophilic Addition
Across an Alkene and Elimination to Form an Alkene.
Nucleophilic substitution reactions are classed into two broad categories
depending on the mechanism they follow: SN2 reactions occur in one step and are
stereospecific, SN1 reactions occur in two steps and are not stereospecific.
Elimination reactions are classed in exactly the same way.
Most elimination reactions follow one of two possible mechanisms. Technically,
more complex elimination mechanisms are possible and sometimes discussed in
advanced texts, but these are specific variations of the two main mechanisms.
Unlike with nucleophilic substitution reactions, it is often extremely difficult to
predict which of the two mechanisms will be followed in a given reaction. The goal
of this chapter is to discuss the two possibilities and give enough context that
students can determine the products for elimination reactions. This text will
specify which mechanism an elimination reaction follows or provide context to
make it easily determinable.
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There are many specifically named elimination reactions. For example, the
formation of an alkene by removing a hydrogen and a halide (see Section 12.6) is
sometimes called dehydrohalogenation. This text will generally avoid using the
specific names, but it is possible that they may be encountered in assignments,
labs, discussions, etc. In these cases, searching the name of the reaction using a
resource such as Wikipedia will be a straightforward way of understanding what is
being discussed.
12.2. Elimination Reactions: E2 Reactions
Elimination reactions can occur with one or two steps in the mechanism.
Reactions that follow the E2 mechanism have one step. The main difference from
their counterpart is that they have a very specific geometric requirement to
occur. This effect affects regioselectivity.
12.2.1. Mechanism
Elimination reactions that follow the E2 mechanism have one step (Scheme
12.2). The base removes a proton, creating a new conjugate acid. This occurs at
the same time that electrons from the old bond form a new π bond to an adjacent
carbon by ejecting the leaving group. The new π bond forms at the same time that
both old bonds break.
Scheme 12.2 – Reaction Mechanism for E2 Elimination of Bromocyclohexane
with Sodium hydroxide.
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Depending on the specific reaction that is occurring there may be additional
steps before or after the substitution step. For example, the nucleophile/base or
leaving group may be activated prior to the substitution, or there may be a
protonation or deprotonation after the elimination. These extra steps do not
change the classification of the mechanism for the elimination step; if the new π
bond forms at the same time the old bonds break, it is still classed as an E2
elimination reaction.
12.2.2. Reaction Coordinate and Rate-Determining Step
There is only one step in an E2 elimination reaction. By definition, it is the rate-
determining step (Figure 12.1). The overall reaction is exergonic.
Figure 12.1 – Reaction Coordinate for E2 Elimination of Bromocyclohexane
with Sodium hydroxide.
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12.2.3. Anti-Bonding Orbital Requirements
Recall that when two orbitals overlap constructively they form a covalent bond
(σ or π; see Section 1.3.1). However, when they overlap deconstructively they
form an anti-bonding orbital (σ* or π*; see Section 1.3.1). Usually, in order to
break a covalent bond electron density must be put into its corresponding anti-
bonding orbital (Figure 12.2). It is only possible for the new π bond to form at the
same time that both old bonds are broken by having the electron density from
the old bond eclipse the anti-bonding orbital of the leaving group. This allows the
electrons that previously made the C-H σ bond to immediately become the
electrons of the new C-C π bond. As a result, the C-H and C-LG σ bonds being
broken must be antiperiplanar to each other.
Figure 12.2 – Representation of the Geometric Constraint of the C-H σ Bond
Eclipsing the C-LG σ* Anti-Bonding Orbital for E2 Reactions.
12.2.4. Regioselectivity – Zaitsev’s Rule
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Many elimination reactions can form multiple products (regioisomers)
depending on which hydrogen is removed with the leaving group (Scheme 12.3).
Barring other factors (see Sections 12.2.4.1-12.2.4.3) the major regioisomer will
be the one where the alkene has the most substituents.
Scheme 12.3 – Regioselectivity in Elimination Reactions.
This is sometimes referred to as Zaitsev’s Rule (the major regioisomer formed
will be the most thermodynamically stable one [the one that is lower in energy]).
Generally, the more substituents an alkene has the more thermodynamically
stable it is. Why this is true is beyond the scope of this text. Technically there are
many reactions that do not follow Zaitsev’s Rule. However, at an introductory
level only the two main causes of exceptions will be considered (see Sections
12.2.4.2 and 12.2.4.3).
12.2.4.1. Effects from Resonance
Alkenes are more stabilized by having additional conjugation/delocalization and
resonance forms than by having more substituents (Scheme 12.4). As a result, if
conjugation is possible the major product will have it rather than additional
substituents. This is consistent with Zaitsev’s Rule because it is the relative
stability of the products that dictates regioselectivity.
Scheme 12.4 – Regioselectivity in Elimination Reactions Where Conjugation is
Possible.
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12.2.4.2. Effects from Sterically Bulky Bases
If the base is very large, with a large amount of steric bulk/interactions, then
regioselectivity can be reversed and the major regioisomer will be the one where
the alkene has the fewest substituents (Scheme 12.5). The change in
regioselectivity is the result of steric strain between the two molecules affecting
the two possible acid-base reactions differently. This is almost always done by
using a t-butoxide base. Other bases, with more complex structures, may work
but are not normally discussed at an introductory level.
Scheme 12.5 – Example of the Change in Regioselectivity by Using Sodium
Hydroxide, a Small Base, or Sodium t-Butoxide, a Large Base, for Selectively
Undergoing One of Two Competing Reactions with 2-Bromobutane.
Often this approach does not work well; steric interactions normally do not
affect acid-base reactions, which are a component of elimination mechanisms. At
an introductory level, assume t-butoxide bases will change regioselectivity in
elimination reactions.
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12.2.4.3. Effects from Chair Conformations
By far the most important exceptions to Zaitsev’s Rule are in E2 elimination
reactions involving six-membered rings. In order for E2 eliminations to occur the
hydrogen and leaving group involved must be antiperiplanar to each other (see
Section 12.2.3). This is only possible if the leaving group is axial (Scheme 12.6). In
chair conformations where the leaving group is equatorial its corresponding σ*
anti-bonding orbital points directly into the centre of the ring. As a result, it is not
geometrically possible for any C-H σ bond to eclipse it.
Scheme 12.6 – Orbital Overlaps Demonstrating Requirement for Leaving
Group Being Axial in Six-Membered Rings.
Depending on the relative location and configuration of any other substituents
on the ring it may or may not be possible for the more substituted alkene to be
formed (Scheme 12.7). If it is possible, then that will still be the major product.
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However, if it is not possible then the E2 elimination still occurs but the other
regioisomer is generated.
Scheme 12.7 – Example of Effects from Relative Configuration of Adjacent
Groups on Regioselectivity for E2 Eliminations in Six-Membered Rings.
12.2.5. Stereoselectivity
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Reactions that follow the E2 elimination mechanism are stereoselective for the
formation of alkenes where the largest groups on either end of the alkene are
trans relative to each other. Usually this means they selectively form E-alkenes.
The stereochemistry of the alkene can be predicted by considering the Newman
projections along the bond that will become the alkene (Figure 12.3).
Figure 12.3 – Example of Determining Stereoselectivity in E2 Eliminations by
Examining Possible Conformations.
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Because E2 elimination is only possible when the C-H and C-LG bonds are
antiperiplanar to each other, only certain conformations need to be considered. If
there are multiple conformations to be considered, the most stable one will lead
to the major product. This is the conformation with the smallest amount of
steric/torsional strain.
12.3. Elimination Reactions: E1 Reactions
Elimination reactions can occur with one or two steps in the mechanism.
Reactions that follow the E1 mechanism have two steps. The main difference
from their counterpart is that they do not have a geometric requirement to occur.
12.3.1. Mechanism
Elimination reactions that follow the E1 mechanism have two steps (Scheme
12.8). The leaving group leaves, generating a carbocation. This greatly increases
its acidity. Then, the base removes a proton, creating a new conjugate acid and
forming a new π bond to the adjacent carbon. The old bond to the leaving group
breaks before the new π bond forms.
Scheme 12.8 – Reaction Mechanism for E1 Elimination of Bromocyclohexane
with Water.
Depending on the specific reaction that is occurring there may be additional
steps before or after the substitution step. For example, the nucleophile/base or
leaving group may be activated prior to the substitution, or there may be a
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protonation or deprotonation after the elimination. These extra steps do not
change the classification of the mechanism for the elimination step; if the new π
bond forms after the old bond to the leaving group breaks, it is still classed as an
E1 elimination reaction.
12.3.2. Reaction Coordinate and Rate-Determining Step
The first step, carbocation formation, requires a large amount of energy and is
the rate-determining step (Figure 12.4). The overall reaction is slightly exergonic.
Figure 12.4 – Reaction Coordinate for E1 Elimination of Bromocyclohexane
with Water.
12.3.3. Regioselectivity – Zaitsev’s Rule
As with E2 eliminations, E1 eliminations follow Zaitsev’s Rule: the major
regioisomer formed will be the most thermodynamically stable one. Generally,
the more substituents an alkene has the more thermodynamically stable it is.
Gaining additional stabilization through delocalization/resonance still applies (see
Section 12.2.4.1). Theoretically, regioselectivity in E1 elimination reactions can be
altered by use of a very bulky base (see Section 12.2.4.2). In practice this works
exceptionally poorly in almost all cases; this text will not feature examples of
these types of reactions.
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A major difference between E2 eliminations and E1 eliminations is in the
regioselectivity of eliminations from six-membered rings. Reactions that follow E2
mechanisms can have altered regioselectivity as a result of the geometric
constraint placed on them (see Section 12.2.4.3). Because the first step in E1
mechanisms is the formation of a trigonal planar carbocation there is no
geometric constraint placed on which hydrogen(s) can be removed (Scheme 12.9).
As a result, E1 eliminations from six-membered rings can always selectively form
the more stable alkene.
Scheme 12.9 – Contrasting Regioselectivity in Elimination Reactions from Six-
Membered Rings Through E2 and E1 Mechanisms.
12.3.4. Stereoselectivity
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Reactions that follow the E1 elimination mechanism are stereoselective for the
formation of alkenes where the largest groups on either end of the alkene are
trans relative to each other. Usually this means they selectively form E-alkenes.
However, these reactions are typically less stereoselective than E2 eliminations;
depending on the exact structure of the starting material, the selectivity can be
very close to 1:1 E:Z. The reasons for this are a competition between kinetic and
thermodynamic factors, which lies outside the scope of this text. Unless otherwise
indicated, assume reactions that follow E1 mechanisms have the same
stereoselectivity as those that follow E2 mechanisms.
12.4. Determining if a Reaction Follows an E2 or E1 Mechanism
Because of the similarities between them, usually factors that favour SN2 also
favour E2 and factors that favour SN1 also favour E1 (see Section 11.4). However,
there are far more exceptions and deviations from these trends in elimination
reactions than in nucleophilic substitution reactions.
The two mechanisms, E1 and E2, are distinct. However, for many compounds
the two reaction pathways have similar activation energies. In these cases some
of the molecules follow the E1 mechanism and some follow the E2 mechanism. It
is usually not possible to accurately predict which pathway will be preferred, or by
how much, for a given compound. It is important to recognize that in most cases
the major product will be the same regardless of which elimination mechanism
occurs. If the mechanism could affect the structure of the major product this text
will clearly indicate which mechanism is followed to allow the student to
accurately predict the product.
There are some compounds for which the elimination mechanism can be
accurately predicted. If following an E1 mechanism would generate a primary
carbocation without resonance stabilization, then the mechanism will instead
always be E2 (Figure 12.5).
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Figure 12.5 – Using the Structure of the Potential Carbocation Intermediate to
Predict the Mechanism of Elimination.
12.5. Reaction: Elimination of H-OH (Dehydration)
Two types of elimination reactions occur very frequently in synthesis.
Dehydration, the elimination of water (H-OH), is a very common elimination
reaction (Scheme 12.10). It is possible for this reaction to occur without catalysis,
or with base catalysis. However, in the overwhelming majority of cases chemists
prefer to use acid catalysis for dehydration reactions.
Scheme 12.10 – Generalized Reaction Equation for Acid-Catalyzed Elimination
of H-OH to Form an Alkene.
12.5.1. Mechanism Using Acid Catalysis
Depending on the structure of the starting material this reaction may proceed
through an E2 or E1 mechanism. For comparison to hydration (addition of H-OH
across an alkene, see Section 8.6.1) an example following the E1 mechanism is
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shown. The mechanism for this reaction is the exact opposite order of steps as the
addition of H-OH across an alkene (Scheme 12.11; see Scheme 8.9). The strong
acid reacts with water to form hydronium (not shown). This is the active catalyst.
First, the leaving group (alcohol) gets activated by the catalyst. This greatly
increases its leaving group ability. The activated leaving group leaves, generating
a carbocation and water. Finally, another equivalent of water removes a proton,
generating the final product and regenerating the catalyst.
Scheme 12.11 – Reaction Mechanism for Acid-Catalyzed Elimination of H-OH
to Form the Alkene of (E)-But-2-ene.
12.5.2. Controlling Equilibrium
Although the reaction equations imply that they are irreversible both hydration
and dehydration are fully reversible and may be catalyzed by the same catalyst.
As a result, the alkene and the alcohol are in equilibrium. It is possible to control
the equilibrium using Le Chatelier’s principle. The strong acid catalysts used for
these reactions, such as hydrochloric acid (HCl) or sulfuric acid (H 2SO4), are
dissolved in water (H2O). As a result, lowering the concentration of the acid
catalyst also adds water to the reaction. Because water lies on one side of the
equilibrium, changing the concentration of the acid catalyst can shift equilibrium
to favour either the alkene or the alcohol (Scheme 12.12).
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Scheme 12.12 – Controlling Equilibrium in Hydration/Dehydration Reactions.
12.6. Reaction: Elimination of H-X (Dehydrohalogenation)
Two types of elimination reactions occur very frequently in synthesis.
Dehydrohalogenation, the elimination of a strong halogen acid (H-X), is a very
common elimination reaction (Scheme 12.13). It is possible for this reaction to
occur with (Lewis) acid catalysis. However, in the overwhelming majority of cases
chemists prefer to simply use a strong base such as sodium hydroxide. Note that
although H-X is formally eliminated it will not actually be a product of the
reaction; the strong base will form water (or an alcohol) and a salt.
Scheme 12.13 – Generalized Reaction Equation for Elimination of H-X to Form
an Alkene.
12.6.1. Mechanism
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Depending on the structure of the starting material it is possible for this
reaction to proceed through an E2 or E1 mechanism. However, when using a
strong base often the E2 mechanism is faster for these reactions. The mechanism
for this reaction is the same as a standard E2 elimination (Scheme 12.14; see
Scheme 12.2). The strong base (NaOH) removes a proton, creating a new
conjugate acid (water). This occurs at the same time that electrons from the old
bond form a new π bond to an adjacent carbon by ejecting the leaving group (the
halide). Recall that while most halides are excellent leaving groups, fluorine is an
exception; this reaction will not work with a fluoride (F-) leaving group.
Scheme 12.14 – Reaction Mechanism for E2 Elimination of 2-Bromobutane
with Sodium hydroxide.
12.7. Oxidation of Alcohols via Elimination
Recall that in organic chemistry, oxidation and reduction are commonly
associated with the loss or gain of hydrogens (see Section 7.4). For example, the
conversion of a carbonyl to an alcohol is considered a reduction reaction, while
the reverse would be considered an oxidation reaction.
Some oxidation reactions, typically those of alcohols and hydrates, are
equivalent to elimination reactions (Scheme 12.15).
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Scheme 12.15 – Comparison of Generalized Reaction Mechanisms for
Elimination and Some Oxidation Reactions.
12.7.1. Reaction: Oxidation using X-X and a Base
It is possible to oxidize an alcohol to an aldehyde or ketone using a dihalide (X 2)
and a weak base. The most common pairing is bromine (Br2) and sodium
bicarbonate (NaCO3H). After activation this reaction follows an E2 mechanism
(Scheme 12.16). First, the alcohol (nucleophile) attacks the dihalide (electrophile).
This creates a new O-X bond and a salt. Second, the base removes a proton,
creating the activated intermediate. Finally, another equivalent of base removes a
proton to cause the elimination/oxidation step.
Scheme 12.16 – Reaction Mechanism for Oxidation of Propan-1-ol Using
Bromine and Sodium Bicarbonate.
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This oxidation works well for simple molecules but is not commonly used in
complex syntheses; because a dihalide, water, and a base are present other
simple reactions, such as additions across alkenes, can also occur.
12.7.2. Reaction: Oxidation using CrO3 (Jones Oxidation)
It is possible to oxidize an alcohol to a carboxylic acid or ketone using an acid
and chromium trioxide (CrO3). This is sometimes referred to as Jones Oxidation.
The actual chromium compound needed for the reaction (HCrO3+) can be
generated several ways (Scheme 12.17); mixing chromium trioxide (CrO3),
chromic acid (H2CrO4), or sodium dichromate (Na2Cr2O7) with sulfuric acid (H2SO4)
will form the required intermediate. The mechanism for the reaction with sodium
dichromate is straightforward but time consuming; at an introductory level it is
important only to know that this reaction is possible with this chromium source.
Some texts show the sulfuric acid directly reacting with the chromium trioxide,
chromic acid, or sodium dichromate to form the protonated chromium trioxide.
Since water is present, this is unlikely to be accurate.
Scheme 12.17 – Formation of Activated Chromium Trioxide Using Sulfuric
Acid and Chromium Trioxide, Chromic Acid, or Sodium Dichromate.
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12.7.2.1. Mechanism
After formation of the activated chromium trioxide (not shown) this reaction
follows an E2 mechanism (Scheme 12.18). First, the alcohol (nucleophile) attacks
the activated chromium trioxide (HCrO3+; electrophile). This creates a new O-Cr
bond and a salt. Second, the base (water) removes a proton, creating the
activated intermediate. Finally, another equivalent of water removes a proton to
cause the elimination/oxidation step.
Scheme 12.18 – Reaction Mechanism for Oxidation of Butan-2-ol Using
Protonated Chromium Trioxide in Water.
12.7.2.2. The Role of Water
It is important to remember that sulfuric acid (H2SO4) is always contaminated
with at least a small amount of water (H2O). When water, acid, and
aldehydes/ketones are present they will combine to form hydrates (see Section
7.5.2). With ketones this is not a problem, however with aldehydes the hydrate
can undergo another oxidation (Scheme 12.19). As a result, any Jones oxidation
reaction that has water in it will oxidize primary alcohols twice, into carboxylic
acids, instead of forming the aldehyde. The mechanism for the second oxidation is
identical to that of the first; drawing the complete mechanism for a Jones
oxidation of a primary alcohol to a carboxylic acid is more tedious than
challenging.
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Scheme 12.19 – Reaction Mechanism for Oxidation of Propan-1-ol Using
Protonated Chromium Trioxide in Water.
12.7.2.3. Solving Problems Using Special Reagents - PCC
It is possible to stop the oxidation of primary alcohols as aldehydes by
rigorously excluding water. This can be accomplished by changing the way the
activated chromium trioxide (HCrO3+) is formed. The most common approach is to
use pyridinium chlorochromate (PCC) instead of combining a chromium source
with sulfuric acid (Scheme 12.20).
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Scheme 12.20 – Reaction Equation for Oxidation of Propan-1-ol Using
Pyridinium Chlorochromate (PCC).
PCC is stable while a solid. When dissolved in a solvent PCC spontaneously
forms activated chromium trioxide in equilibrium with itself (Scheme 12.21).
Because PCC does not include water, the hydrate cannot form and further
oxidation cannot occur. The mechanism for the oxidation is identical to other
Jones oxidation reactions.
Scheme 12.21 – Mechanism for Formation of HCrO3+ from Pyridinium
Chlorochromate (PCC).
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Chapter 12 Learning Outcomes
Learning Outcomes are summarized lists of the main ideas/skills that students
should take away from a chapter. “Learning Outcomes” lists are not exhaustive;
there may be other ideas/skills covered in the chapter that are also useful but not
necessarily the main focus.
For Chapter 12 the Learning Outcomes are:
1. Draw mechanisms for E1 and E2 elimination reactions.
2. Predict the major products formed from elimination reactions, including
regiochemistry and stereochemistry.
3. Predict the products of alcohol oxidation reactions.
Chapter 12 Practice Problems
Answers for these practice problems are in the next section.
A good approach is to answer all of the questions on a piece of paper and then
check your answers. This avoids accidentally seeing the answer(s) for questions
you have not done yet.
Because this chapter’s primary emphasis is reaction outcomes (instead of
concepts) the style of questions has adjusted to match.
Q12.1: Deep, Eli, and Fatma want to practice elimination reactions. They
performed two (below) and generated Compounds B and E. They now want to
selectively make Compounds C and F using the same starting materials. Write a
brief discussion (small sets of bullet points) rationalizing if it is possible and how it
could (or could not) be achieved for each. You may assume reactions would
proceed as discussed in the textbook and that Deep, Eli, and Fatma know what
they are doing.
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Note: This question is meant to be semi-challenging and force you to think
critically about multiple factors for both cases; considering what mechanism(s)
is/are possible based on the results is only the first step.
Q12.2: Assume each of the following is an elimination (or elimination-like
oxidation) reaction. For each reaction draw the expected major organic
product(s). The products must be drawn as line-angle structures. Clearly indicate
the appropriate stereochemistry using hashed and wedged bonds where
necessary. If the product(s) is/are formed as more than one diastereomer, draw
all diastereomers formed. If the product(s) is/are formed as a racemate (racemic
mixture) draw only one enantiomer and write the word “racemic”
beneath/beside it. Do not write “racemic” if it does not apply.
Remember that it is common but not required to indicate which mechanism is
taking place in elimination reactions. Most commonly the information is omitted
when both E1 and E2 mechanisms generate the same product.
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Q12.3: A reaction equation is given below. Propose a reasonable mechanism for
the reaction. Show all necessary intermediates, curved arrows, lone pairs, and
formal charges.
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Chapter 12 Practice Problems - Answers
Q12.1: Deep, Eli, and Fatma want to practice elimination reactions. They
performed two (below) and generated Compounds B and E. They now want to
selectively make Compounds C and F using the same starting materials. Write a
brief discussion (small sets of bullet points) rationalizing if it is possible and how it
could (or could not) be achieved for each. You may assume reactions would
proceed as discussed in the textbook and that Deep, Eli, and Fatma know what
they are doing.
Note: This question is meant to be semi-challenging and force you to think
critically about multiple factors for both cases; considering what mechanism(s)
is/are possible based on the results is only the first step.
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Q12.2: Assume each of the following is an elimination (or elimination-like
oxidation) reaction. For each reaction draw the expected major organic
product(s). The products must be drawn as line-angle structures. Clearly indicate
the appropriate stereochemistry using hashed and wedged bonds where
necessary. If the product(s) is/are formed as more than one diastereomer, draw
all diastereomers formed. If the product(s) is/are formed as a racemate (racemic
mixture) draw only one enantiomer and write the word “racemic”
beneath/beside it. Do not write “racemic” if it does not apply.
Note: Remember that it is common but not required to indicate which mechanism
is taking place in elimination reactions.
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Q12.3: A reaction equation is given below. Propose a reasonable mechanism for
the reaction. Show all necessary intermediates, curved arrows, lone pairs, and
formal charges.
Must show E2 mechanism. E1 is incorrect. See Section 12.4.
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