Chapter 8:

Elimination
Reactions
Elimination Reactions
- E2
- Analogue to the SN2
- Bimolecular rate law: rate = k[Base][S.M.]
- Requires strong bases
- Leaving group must be anti to the H that is removed
- E1
- Analogue to the SN1
- Unimolecular rate law: rate = k[S.M.]
- Reagents usually are heat + H2SO4
- Preference for 3° > 2° >>> 1°
E2 Reaction Mechanism

- Concerted reaction (everything happens in one step)

- The hydrogen on the alpha carbon (carbon next to a leaving group) is acidic
- Acid/base reaction
- The alkene product is the conjugate base, and H-Base is the conjugate acid
E2 Reaction Coordinate Diagram
E1 Reaction Mechanism

- 2-step reaction
- The hydrogen on the alpha carbon (carbon next to a carbocation) is acidic
- Acid/base reaction
- The alkene product is the conjugate base, and H-Base is the conjugate acid
E1 Reaction Coordinate Diagram
Summary of E1 and E2

E1 E2

Mechanism Two-step mechanism (one One-step mechanism (zero

intermediate, 2 transitions intermediates, 1 transition
states) state)

Rate Unimolecular Bimolecular

Rate = k [S.M.] Rate = k[S.M.][base]

Bases *No preference Strong bases

(heat + H2SO4)

Solvent Polar protic solvents Polar aprotic, non-polar

protic

Steric 3° and 2° No preference

E1CB Mechanism
- When the leaving group is very bad leaving group, the preferred route is the E1 CB mechanism

- This is the normally how elimination reactions are drawn when the hydrogen being removed is
on the alpha position with respect to a carbonyl group (in worksheet #7!)
Species that ALWAYS Act as Bases
Strong Bases Weak Bases
E2: H and LG Must be Anti
- What do we mean when we say that the hydrogen being removed by the base and
the leaving group must be anti to one another?
- We are talking about the way their orbitals are aligned with respect to one another

- σC-H must be parallel to σ*C-LG

- In order to form the π interaction between the two
carbons, the electrons sitting in σC-H move to σ*C-LG
- This transfer of electrons establishes the π
interaction which forms the double bond
- Remember: double bond = 1 σ bond + 1 π bond
E2: H and LG Must be Anti
- Basically, the molecule takes two sigma bonds (σ C-H and σ*C-LG) and transforms those

orbitals into 1 π bond (πC-C)

σC-H
σ*C-H
E2: H and LG Must be Anti
- In order for the molecule to to convert σC-H and σ*C-LG into πC-C , the σC-H and σ*C-LG
orbitals must be parallel to one another and facing in opposite directions
- This orientation is called “anti” or “anti-periplanar”

σC-H

σ*C-H
E1: H and LG Do Not Need to be Anti
- In the E1 mechanism, the location of the hydrogen with respect to the leaving group is
irrelevant. Why?
- Once the carbocation is generated (sp2 hybridized), the orientation of the σC-H bond does

not matter (no longer constrained by the formation of πC-C from σ*C-H)

σC-H
σ*C-H
E2: H and LG Must be Anti
- For linear molecules, choosing the hydrogen that is anti to the leaving group is less
of a concern
- In linear molecules the directionality of hydrogen is usually ignored, and the reader
will assume you’re eliminating the hydrogen that is anti to the LG

Groups highlighted in green

are anti to one another
E2 in Cyclic Molecules
- In cyclic molecules, the student must be more careful in choosing which hydrogen
can be removed for the E2 mechanism
- Certain hydrogens are able to be removed for the E2 reaction (because they are
anti) while others are not
- This is easiest to see in the chair conformation
E2 in Cyclic Molecules
- In cyclic molecules, you must be more careful in choosing which hydrogen can be
removed for the E2 mechanism
- Certain hydrogens are able to be removed for the E2 reaction (because they are
anti) while others are not
- This is easiest to see in the chair conformation
E2 in Cyclic Molecules: Example

Hydrogen that are on the alpha carbons are

highlighted in blue
E2 in Cyclic Molecules: Example

Only one of these hydrogens are anti to the

leaving group (in this case Br)

The hydrogen that is anti to Br is highlighted

in red
E2 in Cyclic Molecules: Example

- Here there is only one possible product because only one hydrogen is anti to Br
- In cases where there are multiple possible products, the majority product is usually the Zaitsev product (most
substituted alkene)
- When the base + S.M. are sterically hindered, the Hoffman product is favored (least substituted alkene)
E2 in Cyclic Molecules: Shorthand
- On an exam when time is limited, its difficult to draw out the chair structure and correctly
identify which hydrogen can be eliminated
- There is trick for choosing the correct one…
- In cyclohexane derivatives the wedged bond indicates the substituents is pointed up,
whereas the dashed line indicates it is going down
- Because of this pattern, hydrogens must always have the opposite bond type of the leaving
group in order to be eliminated

Pointing up
This ring has no H that
are anti to the LG
Pointing down Pointing down
 E2 in Cyclic Molecules: Shorthand

Pointing up

=
Pointing down Pointing down

This ring has no H that are anti to the LG

 E2 in Cyclic Molecules: Shorthand

Pointing up

Pointing up Pointing up =

Pointing down
Pointing down

This ring has 2 H that are anti to the LG

Reaction SN1 SN2 E1 E2

Mechanism Two-step One-step Two-step One-step

mechanism (one mechanism (zero mechanism (one mechanism (zero
intermediate, 2 intermediates, 1 intermediate, 2 intermediates, 1
transitions states) transition state) transitions states) transition state)

Rate rate = k [S.M.] rate = k [S.M.][nuc] rate = k [S.M.] rate = k [S.M.][base]

Nucleophile/base Nucleophile: no Strong nucleophiles Base: no preference Strong bases

preference *heat + H2SO4

Solvent Polar protic solvents Polar aprotic, non- Polar protic solvents Polar aprotic, non-
polar protic polar protic

Steric 2° or 3° carbon 1° or 2° carbon 2° or 3° carbon 1° or 2° carbon

Leaving group Good LG No preference Good LG No preference

What makes a Good Leaving Group?
- Look at how well the leaving group can carry negative charge once it detaches from the starting
material
- Usually, the weaker the base generated from the leaving group, the better the leaving group
- Example 1: bromine
- When bromine leaves, it generates Br-
- HBr is an incredibly strong acid (Pka = -8.7)
- Br- is therefore an incredibly weak conjugate base, which makes it a fantastic leaving
group
- Example 2: alcohols
- When -OH leaves it generates -OH
- -OH is a very strong base
- Alcohols make terrible leaving groups, which is why they are usually protonated with acid
before leaving (-+OH2 is a fantastic leaving group)
Good and Bad Leaving Groups
How to Decide (SN1, SN2, E1, E2)
- The biggest factor in deciding between substitution (SN1, SN2) and elimination (E1, E2) is
whether the reagent is a nucleophile or a base
Nucleophilicity vs. Basicity
- What do we mean when we say something is a strong base versus being a strong nucleophile?
Nucleophilicity vs. Basicity
- Nucleophilicity is defined as the rate of the following reaction:

Nucleophilicity is a measure of chemical kinetics

Nucleophilicity vs. Basicity
- Basicity is defined as the equilibrium constant of the following reaction:

Ka = equilibrium constant in forward direction = [A-][H3O+]/[HA] = 1/Kb

Kb = equilibrium constant in reverse direction = [HA]/[A -][H3O+] = 1/Ka

Basicity is a measure of chemical thermodynamics (equilibrium)

Nucleophilicity
- What factors affect the strength of a nucleophile, what makes a nucleophile strong versus weak?
1) Charge
2) Electronegativity
3) Steric hindrance
4) Solvent
- Important: because nucleophilicity is the measure of a reaction rate, it is not an inherent
property of a specific species, the medium that the nucleophile is in + the molecule it is attacking
plays a part in how nucleophilic it is
- Different from basicity, which is a measure of an inherent property based on thermodynamics
Nucleophilicity: Charge
- Species that have a higher concentration of electrons (higher lying HOMOs) are more nucleophilic
- For this reason, the conjugate base of any species will be more nucleophilic
Nucleophilicity: Electronegativity
- Species that have a larger electronegativity are less nucleophilic (within a row)
- Because the species will hold more tightly onto its valence electrons (lower lying HOMO)

Strongest nucleophile Weakest nucleophile

Element Carbon Nitrogen Oxygen Fluorine

Electronegativity 2.55 3.04 3.44 3.98

Nucleophilicity: Steric Hindrance
- Nucleophilicity is a measure of reaction rate, so the speed at which a nucleophile can access its
electrophilic target matters

- The bulkier a species is, the

slower it attacks an
electrophilic carbon,
Strongest nucleophile Weakest nucleophile therefore it is less nucleophilic
- The effect is called steric
hindrance
Nucleophilicity: Solvent
- As mentioned earlier, nucleophilicity is not an inherent property, rather it is a function dependent
on the medium in which a molecule exists
- For this reason, the solvent of a reaction plays an important role in nucleophilicity
- Why?→Intramolecular bonds
Nucleophilicity: Solvent
- Hydrogen bond = an attractive intermolecular interaction that occurs between a hydrogen atom
connected to some donor molecule (D-H) and an acceptor atom (:A)

D 一 H ・・・・・ A

- Example: Hydrogen bonding in DNA

Nucleophilicity: Solvent
- Most important hydrogen bonding in the world: water!
Nucleophilicity: Solvent
- Certain solvents have the ability to engage in hydrogen bonds with the nucleophile
- Example: -OCH3 in H2O

- The negatively charged methoxide anion forms

intermolecular hydrogen bonds with the water
molecule
- This generates steric bulk around the nucleophile
and slows down the rate of the reaction, therefore
making methoxide less nucleophilic
Nucleophilicity: Solvent
- Certain solvents have the ability to engage in hydrogen bonds with the nucleophile
- Solvents that can engage in hydrogen bonding with nucleophiles
- Polar protic solvents: water, alcohols, carboxylic acids
Nucleophilicity: Solvent
- Certain solvents have the ability to engage in hydrogen bonds with the nucleophile
- Solvents that cannot engage in hydrogen bonding with nucleophiles
- Polar aprotic solvents: acetone, dimethylformamide (DMF), acetonitrile (ACN),
dimethyl sulfoxide (DMSO)
Nucleophilicity: Solvent
- Certain solvents have the ability to engage in hydrogen bonds with the nucleophile
- Solvents that cannot engage in hydrogen bonding with nucleophiles
- Nonpolar solvents: cyclohexane, hexanes, benzene, carbon tetrachloride
Nucleophilicity: Solvent
- Effect of Solvent on Trends in Nucleophilicity
- When there is no effect of solvent on nucleophile (polar aprotic/nonpolar solvent)...
- Going down a row, we expect nucleophilicity trends to align with basicity

Strongest nucleophile Weakest nucleophile

In polar aprotic or nonpolar solvent

Nucleophilicity: Solvent
- Effect of Solvent on Trends in Nucleophilicity
- When the nucleophiles are in polar protic solvents, the trend reverses
- This is because F- is the strongest H-acceptor, and so it becomes the most “crowded”

Weakest nucleophile Strongest nucleophile

In polar protic solvent

Nucleophilicity
- Remember, the SN2 mechanism is bimolecular
- Rate = k[S.M.][nucleophile]
- Strong nucleophiles are said to prefer SN2, but it's not really a matter of “preference”
- The reason strong nucleophiles usually undergo SN2 reactions is b/c the strong nucleophile
attack the carbon center more quickly than the leaving group can leave
- Strong nucleophile = fastest nucleophile
- The fact that a strong nucleophile favors SN2 is entirely due to kinetics
- Remember, the SN1 mechanism is unimolecular
- When the nucleophile is weak, the reaction pathway where the nucleophile attacks the
electrophile is much more slow, therefore the leaving group has the opportunity to leave
first
- Additionally, when there is a lot of steric hindrance (3°), the leaving group has the
opportunity to leave first because the nucleophilic attack is slowed down
SN1 or SN2?
We would say this rxn is SN2
because CN- is a strong
nucleophile, but what does that
really mean?

rate: r1
Note: r1, r1’, and r2 are rates of reaction,
SN2: not equilibrium constants

rate: r1’ rate: r2

SN1:
 rate: r1
- r1 = k1[S.M.][nucleophile]
SN2:
- r1’ = k1’[S.M.]
- r2 = k2[carbocation][nucleophile]

rate: r1’ rate: r2

SN1:
Slow step

- Strong nucleophiles prefer SN2 because r1 >>>>> r1’

- The SN2 mechanistic route, on average, will happen before the first step
of the SN1 mechanism can occur
- So, the majority of the products will be the result of the SN2 pathway
SN1 or SN2?
We would say this rxn is SN1 because
the tertiary carbon is too hindered for
even a strong nucleophile like CN-, but
what does that really mean?

rate: r1 Note: r1, r1’, and r2 are rates of reaction,

SN2: not equilibrium constants

rate: r1’ rate: r2

SN1:
 rate: r1 Note: r1, r1’, and r2 are rates of reaction,
SN2: not equilibrium constants

rate: r1’ rate: r2

SN1:

- 3° carbons prefer SN1 because r1’ >>>>> r1

- The first step of the SN1 mechanistic route, on average, will happen before the first
step of the SN2 mechanism can occur
- This is because steric bulk on the electrophilic carbon severely hinders the
nucleophile’s access, therefore the speed of that step slows down
- The second step of the SN1 mechanism (r2) is very fast and so it doesn’t play a role
SN1 or SN2?

We would say this rxn is SN1 because

the polar protic solvent severely
weakens the nucleophile

We would say this rxn is SN2 because the nucleophile is very strong
Summary of SN1 and SN2

SN1 SN2

Mechanism Two-step mechanism (one One-step mechanism (zero

intermediate, 2 transitions intermediates, 1 transition
states) state)

Rate Unimolecular Bimolecular

Rate = k [S.M.] Rate = k[S.M.][nucleophile]

Stereochemistry Racemic mixture Walden inversion

Nucleophiles No preference Strong nucleophiles

Solvent Polar protic solvents Polar aprotic, non-polar

protic

Steric 3° and 2° 1° and 2°

What Makes Something Basic?
- Basicity is a measure of thermodynamics
- Much like how the strongest acid is the one which produced the weakest conjugate base,
the strongest conjugate base is one which produces the weakest acid
- Equilibrium always favors the weaker acid/base, because those species are more
thermodynamically stable
- Example: for each rxn is Keq greater than or less than 1? Is the base strong or weak?

K <<<<<<< 1
Reactants favored, I- is a terrible base

K >>>>>>> 1
Products favored, H- is a super base
 What Makes Something Basic?

Basicity is a measure of thermodynamics

- Basicity is oftentimes measure with pKb

- -log10(Kb)
- Much like pKa, a lower pKb implied a
stronger base
Species that ALWAYS Act as Bases
How to Decide (SN1, SN2, E1, E2)
- The biggest factor in deciding between substitution (SN1, SN2) and elimination (E1, E2) is
whether the reagent is a nucleophile or a base
How to Decide (SN1, SN2, E1, E2)
- The questions on the exam will make it obvious as to what mechanism is preferred
- Or the question will ask you to justify why a particular mechanism is preferred
- Let’s do an example from the 2019 Exam #2B

“(95 points) Explain why the alkyl halide CH3CH2OCH2Cl reacts rapidly with
CH3CH2OH under SN1 conditions. Provide a step by step mechanism.”
 “(95 points) Explain why the alkyl halide CH3CH2OCH2Cl reacts rapidly with CH3CH2OH
under SN1 conditions. Provide a step by step mechanism.” [Exam 2B, 2019)

Even though the carbon attached to the leaving group is 1°, it is resonance stabilized by the neighboring oxygen
(remember resonance provides the most stability). This stabilization allows the starting material to react
efficiently under SN1 conditions. The SN1 conditions are provided by the weak nucleophile, ethanol.
 “(90 points) Explain why the following alkyl bromide does not undergo any
elimination reaction by any mechanism.” [Exam 2A, 2019]

Regardless of the mechanism, or the hydrogen removed, an elimination reaction would result in the formation
of an sp2 carbon at the bridge-head position of this cyclic molecule. Due to the geometry of this molecule and its
rigid nature, the carbon sitting in the bridge-head position must be sp3 (tetrahedral).
“(90 points) What is the major product of the following reaction. Explain
and draw a mechanism.” [Exam 2A 2018]

Decide between SN1, SN2, E1, and E2

 “(90 points) What is the major product of the following reaction. Explain
and draw a mechanism.” [Exam 2A 2018]

- HI is the strongest acid in organic chemistry (pKa = -9), therefore I- is a super, super weak base, it actually
does not act as a base at all→we can eliminate E2 and E1
- I- is a decent nucleophile (Iodine is not super electronegative so it doesn’t hold onto its valence
electrons tightly, and it is negatively charged)
- All signs point to SN2
“(90 points) What is the major product of the following reaction. Explain
and draw a mechanism.” [Exam 2A 2018]

Mechanism:
Mechanism Problems
Explain the formation of both products A and B mechanistically.
Formation of Product A
Formation of Product B
Mechanism Problems
Explain the formation of both products A and B mechanistically.

Empirically, how would I know which product is the majority product?

The mechanism leading to product A
generates H2, which is a gas at room
temperature. If product A is the favored
product, you would expect a balloon placed
over the rxn flask to inflate very quickly.
Mechanism Problems
Draw the mechanism for the following transformation.
Mechanism Problems