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Subject Chemistry

Paper No and Title Paper-9, Organic Chemistry-III (Reaction Mechanism-2)

Module No and Title Module-24, The E1cB Elimination

Module Tag CHE_P9_M24

CHEMISTRY PAPER No. 9 : Organic Chemistry-III (Reaction Mechanism-2)

Module-24: The E1cB Elimination
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TABLE OF CONTENTS
1. Learning Outcomes
2. Introduction

3. The E1cB elimination: Detailed Mechanism

3.1 Mechanistic aspects
3.2 Regio- and Stereo-selectivity in E1cB Elimination
3.3 Kinetics of E1cB mechanism

4. Comparison of E1cB elimination with E1 and E2 mechanisms

4.1 The Variable Transition State Theory for Elimination Reactions

5. Summary

CHEMISTRY PAPER No. 9 : Organic Chemistry-III (Reaction Mechanism-2)

Module-24: The E1cB Elimination
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1. Learning Outcomes
After studying this module, you shall be able to

• Know what is meant by E1cB elimination reactions

• Acquaint with the E1cB mechanism
• Predict Regio- and stereo-chemical outcomes of E1cB elimination
• Differentiate between the E1cB and E1 / E2 mechanism

2. Introduction
E1cB elimination stands for (Elimination, Unimolecular from conjugate Base). The E1cb
mechanism, like the E1, involves two steps, but the order is reversed. Thus, an E1cB elimination
reaction, in general, proceeds by a fast removal of a proton from the β-carbon resulting in the
formation of a carbanion intermediate which then loses the leaving group in the second slower
step. So, in the E1cB mechanism the C—H bond is broken first, by deprotonation with a base and
the conjugate base (cB) of the substrate is produced. Subsequently, the C—Het bond breaks.
Hence, the overall rate of the reaction depends upon the concentration of the conjugate base of
the substrate (carbanion intermediate) which is accountable for the designation of this
mechanism. The reaction is termed unimolecular because the rate determining step involves only
a single molecular entity (the conjugate base).

For example below, is a β-hydroxy carbonyl compound (I). Dehydration of alcohols is normally
catalysed by acids. Here, compound (I) suffers dehydration (1,2-elimination) even with acids. But
substrates are said to follow E1cb mechanism. The carbanion intermediate readily expels OH to
form delocalized conjugated carbonyl unit (II).

CHEMISTRY PAPER No. 9 : Organic Chemistry-III (Reaction Mechanism-2)

Module-24: The E1cB Elimination
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For elimination reaction to proceed via the E1cB mechanistic pathway, there are two main
requirements:

1. The compound must have an acidic hydrogen β- to the EWG and C-H at C2(α- to the
carbonyl group, C-H at C2) and,
2. a relatively poor leaving group on the α- carbon.

Also, stronger bases promote E1cB mechanism in addition to the above two conditions.

3. The E1cB elimination: Detailed Mechanism

3.1 Mechanistic aspects

As discussed, the first step of E1cB elimination involves the deprotonation of the β-carbon, which
results in the formation of an anionic transition state (such as carbanion). So, for the elimination
to proceed via an E1cB pathway, the stability of this transition state matters the most. This
transition state can be stabilized via delocalization of the electron lone pair through resonance or
via inductive effect. So, the substituents that can stabilize the carbanion intermediate are
important. This mechanism is not observed with simple alkyl halides or sulfonates. The E1cb
mechanism is only observed when there is at least one good electron-withdrawing group (EWG)
adjacent to the C-H bond to be cleaved. The effect of an electron withdrawing group is to increase
the Brønsted acidity of adjacent C-H bonds, or in other words, to stabilize their conjugate bases.
Hence, it is more likely to be involved when the leaving group is at β-­‐position to a carbonyl,
nitro, cyano, sulfinyl, or other carbanion-stabilizing group. E1cb reactions generally require both
carbanion stabilization and a relatively poor leaving group.

Another example is shown below where the carbanion intermediate is stabilized by both inductive
and delocalization effects.

CHEMISTRY PAPER No. 9 : Organic Chemistry-III (Reaction Mechanism-2)

Module-24: The E1cB Elimination
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The E1cB mechanism is not limited to carbon-based eliminations. It has been observed with other
heteroatoms, such as nitrogen as shown below:

3.2 Regio- and Stereo-selectivity in E1cB Elimination

For the E1cB reaction, the regioselectivity is easier to predict as the location of the double bond
will depend upon the position of: (i) the acidic proton and (ii) the leaving group. Further, the
acidity of the β-proton depends upon the resonance effects of adjacent substituents, and on the
degree of steric hindrance to approach of base to the proton. Hence, preferential proton
abstraction from less-substituted carbons leads to the formation of the less-substituted alkene
(Hoffman product). This can also be attributed to the fact that carbanion stability is of the order:
primary > secondary > tertiary. Similarly, substituents that stabilize the carbanion-intermediate
control the regiochemistry of E1cb eliminations by favoring deprotonation at the most acidic
carbon which leads to a more stable carbanion TS.

As with E1 mechanism, as the E1cB reactions also occur stepwise, they lose all their
stereochemistry during the formation of the carbanion-intermediate. However,
considering the geometrical isomerism, the E1cB reactions may be stereoselective in the
formation of the E-alkene product (which is again less-hindered) as exemplified by the
double E1cB reaction in the substrate below:

4. Comparison of E1cB elimination with E1 and E2 mechanisms

E1cb eliminations are different than the E1 and E2 eliminations in the timing of the deprotonation
at the α- carbon and the loss of the leaving group. While E2 elimination is a concerted process
which involves simultaneous deprotonation, formation of double bond and loss of the leaving
group, the E1 and E1cB reactions occur in a stepwise manner. However, the order of
deprotonation and removal of leaving group is reversed in these two elimination mechanisms.
While in the E1 reaction the leaving group is lost first to generate a carbocation followed by
subsequent deprotonation to yield the product, the order is reversed in E1cB elimination with an
intermediate carbanion resulting first due to deprotonation and which is subsequently converted
to the alkene by loss of the leaving group. The same is depicted in the figure below.

CHEMISTRY PAPER No. 9 : Organic Chemistry-III (Reaction Mechanism-2)

Module-24: The E1cB Elimination
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The reaction co-ordinates for these three types of elimination mechanisms are depicted below:

4.1 The Variable Transition State Theory for Elimination Reactions

With regards to the various types of elimination mechanisms depicted above, it is not possible to
specify a particular type of mechanism for each and every elimination reaction. Several

CHEMISTRY PAPER No. 9 : Organic Chemistry-III (Reaction Mechanism-2)

Module-24: The E1cB Elimination
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elimination reactions occur via mechanisms that are difficult to restrict to the listed 3 mechanistic
types (E2, E1 or E1cB) but are actually intermediary between them. This is described as the
variable transition state theory which says that elimination reactions may not proceed via pure
E1 or E2 or E1cB mechanisms but by intermediate mechanisms/transition states such as E1-like
or E1cb-like etc., depending upon the relative ease of breaking of the C—H or C—X bonds (and
concurrent stabilization of the resulting transition-states) as illustrated below:

The factors that affect the course of the reaction to follow one or another pathway are:

1. Nature of leaving group.

2. Electronic and steric effect of substituents in the substrate.

3. Nature of the base.

4. Solvent effects.

Different combinations of various aspects which favour any of the limiting types of elimination
mechanisms can lead to a reaction proceeding with a variant-type of mechanism. For example,
many substrates containing poor leaving groups such as –Fluoro, which were originally thought
to proceed by an E2 mechanism, may show E1cB-like transition-state.

E1 E2 E1cB
No effect of base. Stronger, bulky and concentrated Strongly basic media
Sometimes requires base favours E2
strongly acidic media.
Good leaving groups Leaving groups. Poor leaving groups.
The leaving group must be trans
to the Hydrogen involved
Less acidic α-carbon Acidic α-carbon More acidic α-carbon
Carbocation Single step, concerted process. Carbanion intermediate.
intermediate involved; Conditions stabilizing it
factors stabilising it. favour E1cB.

CHEMISTRY PAPER No. 9 : Organic Chemistry-III (Reaction Mechanism-2)

Module-24: The E1cB Elimination
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Consider the TS of an E2 reaction having an E1cb character. A highly developed bond is present
between the proton and the base. The poor leaving group remains tightly bound to the carbon, and
hence there is relatively lesser development of the carbon-carbon double bond. Thus, C—H bond
breaking is faster than that of C—X bond, imparting the reaction an E1cB-like character.

Similarly, an E1-like TS is characterized by well-advanced cleavage of the C−X bond and a

largely intact C−H bonds. Further, it is envisaged that E2 eliminations proceeding through an
“E1cb-like” TS will show regioselectivity similar to E1cb reactions and E2 elimination
proceeding through an “E1-like” TS will have the regiochemistry of E1 eliminations. So, in
E1cB-like E2 eliminations, less-substituted alkene usually dominates while E1-like TS for E2
reactions leads to formation of the more highly substituted alkene.

In some cases, the steric and conformational constraints at the substrate also play an important
role. For example, the cis- and trans- isomers of 1-fluoro-2-bromocyclohexane follow different
pathways. The trans isomer has an anti β-hydrogen accessible for E2 elimination and the reaction
proceeds with tert-butoxide. However, the cis isomer must use a syn hydrogen in the E1cb-like
process that causes loss of HF, and needs amide as a stronger base.

CHEMISTRY PAPER No. 9 : Organic Chemistry-III (Reaction Mechanism-2)

Module-24: The E1cB Elimination
____________________________________________________________________________________________________

5. Summary

• E1cB elimination (Elimination, Unimolecular from conjugate Base) involves 2 steps:

Ø Removal of a proton from the β-carbon resulting in the formation of a carbanion
intermediate
Ø Loss of leaving group from the carbanion intermediate leading to the alkene
product.
• The compound must have an acidic hydrogen on its β-carbon and, a relatively poor
leaving group on the α-carbon for E1cB elimination to occur.
• The E1cb mechanism is only observed when there is at least one good electron-
withdrawing group (EWG) adjacent to the C-H bond to be cleaved. The effect of an
electron-withdrawing group is to increase the Brønsted acidity of adjacent C-H bonds, or
in other words, to stabilize their conjugate bases.
• Generally, less substituted alkene product is favoured via E1cB mechanism.
• Also, less hindered E-geometry is prefferd in the alkene product.
• The difference between the E1, E2 or E1cB elimination pathways can be summed up in
their order of breaking of the C—H and C—X bonds in the substrate.
• It is difficult to limit all elimination reactions to the E1, E2 or E1cB mechanisms. The
variable transition state theory suggests that the transition states of the reaction may shoe
E1-like or E1cB-like characteristics in between that of pure E1/E2 or E1cB pathways
depending upon the relative ease of breaking of the C—H or C—X bonds (and
concurrent stabilization of the resulting transition-states).
• The regio- and stereo-chemical outcome of the E2 eliminations proceeding through an
“E1cb-like” TS will be similar to E1cb reactions and of E2 elimination proceeding
through an “E1-like” TS will be similar to that of E1 eliminations.

CHEMISTRY PAPER No. 9 : Organic Chemistry-III (Reaction Mechanism-2)

Module-24: The E1cB Elimination