Elimination Reactions: E1 & E2

Suggested Video: https://www.youtube.com/watch?v=ZOUS0Q_B4fQ

Some of the figures and texts are taken/adopted from libretexts.org.

Please see the last slide of the presentation for individual references.
Elimination & Substitution Reactions: SN1, SN2, E1, E2
Conversion of functional groups using nucleophilic substitution reactions and elimination reactions:

N3-
Alkyl Halide Alkyl Azide RN3
(R-X)
CN-
Nitrile RCN
OH-
Alcohol ROH
OR'- Ether ROR'
SH- Thiol RSH Strong or weak nucleophiles are used.
SR'- Thioether (sulfide) RSR'
R'-C C- Alkyn R'C CR
R'COO- Ester R'COOR
X'-
A different alkyl halide R-X'
E1 & E2
Alkenes Bases are used.
Nucleophiles and Bases (Reminder)

Nucleophiles in protic solvents:

Good nucleophiles: I-, HS-, RS-, Br-, HO-. RO-, CN-, N3-

Fair nucleophiles: Cl-, F-, RCOO-, NH3

Weak nucleophiles: H2O, ROH, RCOOH

Nucleophiles and Bases (Reminder)
▪ Conjugated bases of compounds with very high pKa are strong bases.

For example: For CH3CH2OH, pKa = ~16 (negligible acidity)

For CH3CH2O- (strong base)

▪ Conjugated bases of weak acids are weak bases.

For example: For CH3COOH, pKa = ~5 (weak acid)

For CH3COO-, (weak base)

▪ Conjugated bases of strong acids are very weak bases.

Examples: For HCl, pKa = ~6 (strong acid)

For Cl-, (negligible basicity)

ClO4-, HSO4-, I-, Br-, Cl-, NO3- show negligible basicity and DO NOT ionize water.
Nucleophiles and Bases (Reminder)
▪ Hydroxides (OH-) of group I and II metal ions are strong inorganic bases commonly used in laboratories.

Examples: LiOH, NaOH, KOH, Ca(OH)2, Ba(OH)2 etc..

▪ Amines are weak bases.

Examples: Ammonia: NH3 (weak base)

..

Triethyl amine: (CH3CH2)3N (weak base)

Pyridine: C5H5N (very weak base)

..
Nucleophiles and Bases (Reminder)
▪ Deprotonated amines are very strong bases:

Examples: Azanide (or amide): NH2- (very strong base)

▪ Deprotonated alkanes and deprotonated simple alcohols, hydride ion, amide ion, sulfide ion are very strong bases
which undergo complete base ionization in water:

Examples: CH3- > H- > NH2- > CH3CH2O- > S2- (very strong bases: in order of basicity)
methide hydride azanide ethoxide sulfide

CH3- + H2O CH4 + OH-

▪ A bulky alkoxide (RO-: conjugate base of an alcohol) is a strong base but a weak nucleophile:

Examples: CH3CH2O- (strong base and strong nucleophile)

(CH3)3CO- (strong base and weak nucleophile)
 Substitution and Elimination Reactions: SN2 & E2
CH3OH, 25 °C
+ Br-
CH3ONa

SN2
E2
(CH3)3COH, 55 °C
+ Br- +
(CH3)3CONa

Reaction could go Base

through this
hydrogen atom
as well.
Elimination Reactions: E2
▪ Like SN2 reactions, E2 reactions follow second order kinetics.

Energy diagram and mechanism for E2 reactions

https://commons.wikimedia.org/wiki/File:The_broken_C-H_bond_and_the_leaving_group_in_an_E2_mechanism_are_anti-periplanar.png
https://en.wikipedia.org/wiki/File:Representation_of_co-planar_A-B_and_C-D_bonds_with_a_dihedral_angle_of_180_degrees.jpg
https://commons.wikimedia.org/wiki/File:Newman_projection_showing_A_and_D_anti-periplanar.jpg
Elimination Reactions: E2 Figure is prepare in molview.com
Hβ
For an E2 reaction to occur;
(1) there must be at least one β-hydrogen AND
Cβ
Cα

Hβ
Hα
Hα

(2) the β-hydrogen and the leaving group must have an antiperiplanar relation
(for example, A and D have an antiperiplanar relation):

E2 Mechanism

“(3) A strong base is necessary, especially for primary alkyl halides. Secondary and tertiary alkyl halides will
proceed with E2 in the presence of a base (OH-, RO-, R2N-)” (Adopted from www.libretexts.com)
 Elimination Reactions: E2
If there are more than one alkene product formation possibility, generally the more stable alkene is the major product.

Alkene Stability:
a) More substituted alkenes are more stable than less substituted alkenes

b) Trans alkenes are more stable than cis alkenes

Figures are taken and changed from https://chem.libretexts.org/Bookshelves/Organic_Chemistry/Organic_Chemistry_(McMurry)/07%3A_Alkenes-

_Structure_and_Reactivity/7.07%3A_Stability_of_Alkenes
Elimination Reactions: E2
Having multiple β-hydrogens to be eliminated brings multiple products to the table. Additionally, substitution products may be
observed.

According to the Zaitsev's Rule, in a E1 or E2 reaction the major product is the more stable alkene. The more stable alkene is
the one with the more highly substituted (and trans) carbon-carbon double bound.

The product including the more substituted carbon-carbon double is the major product, meaning that it will have higher
percentage compared to the minor product(s).
Elimination Reactions: E2
Multiple β-hydrogens result in multiple products. According to the Zaitsev's Rule, the more stable product is the major
product.

Minor

Major Using a strong base (OH-) and having a secondary

substrate (and possibly heating) can favor elimination
over substitution.

Minor

Major
Using a strong base (OH-) (and possibly heating) can
favor elimination over substitution. However, minor
substitution products may be observed as well.
Elimination Reactions: E2
Let’s predict the possible elimination products (including only the structural isomers).
Elimination Reactions: E2
▪ Hoffman’s Product (the least substituted product is the major product)

▪ When there is a sterically hindered leaving group, such as a bulky –NR3+, the Hoffmann’s Product is favored.
Elimination Reactions: E2
▪ In E2 reactions, leaving group and the eliminated hydrogen should have antiperiplanar relation.

▪ This antiperiplanar relation may determine the (major) products to expect.

▪ Let's predict the elimination products from 2-bromobutane.

* Large groups are away from each

other in favored conformations.

Conformations of Other Alkanes. (2020, December 30). Retrieved May 1, 2021, from https://chem.libretexts.org/@go/page/31404
Elimination Reactions: E2
Let's predict the elimination products from 2-bromobutane.

CH3CH2O-
30%

cis product

Zaitsev’s Rule
Products
CH3CH2O-
50%

Favored
Conformation trans product

CH3CH2O-
20% Minor Product
Elimination Reactions: E2
▪ This antiperiplanar relation may determine the (major) products to expect.

▪ Larger substituents prefer equatorial positions, but

the reactions requires the antiperiplanar conformation
where large chlorine atom is in axial position. This
(Cl-axial) conformation forms only a small
population of the compound at a given time. As a
result, the reaction is slower.

Zaitsev product

https://commons.wikimedia.org/wiki/File:The_broken_C-H_bond_and_the_leaving_group_in_an_E2_mechanism_are_anti-periplanar.png
https://en.wikipedia.org/wiki/File:Representation_of_co-planar_A-B_and_C-D_bonds_with_a_dihedral_angle_of_180_degrees.jpg
https://commons.wikimedia.org/wiki/File:Newman_projection_showing_A_and_D_anti-periplanar.jpg
Elimination Reactions: E2 vs SN2
▪ Primary alkyl halides:

▪ If a strong base that is not sterically hindered (EtO-) is used at ~55°, the major product may be the SN2 product while
E2 product may remain as a minor product.

▪ Secondary alkyl halides:

▪ If a strong base that is not sterically hindered (EtO-) is used at ~55°, the major product can be the E2 product while SN2
product may still be observed as a minor product.

▪ Tertiary alkyl halides:

▪ No SN2 is expected.

▪ If a strong base that is not sterically hindered (EtO-) is used at ~25°, the major product can be the E2 product. SN1
product may still be observed as a minor product.

▪ If a strong base that is not sterically hindered (EtO-) is used at higher temperature (for example: ~55°), the major
product can be the E2 product and additionally minor E1 products may be observed.
Elimination Reactions: E2 vs SN2
▪ Impact of temperature:

Higher temperatures increases the elimination reaction rates. Higher temperatures can be applied to favor elimination
reactions over nucleophilic substitution reactions.

▪ Base selection:

Use of hydroxide (OH-), alkoxide (OR-), or amide (NH2-) as the base increases the tendency to give E2 reactions.

Use of weak bases or more polarizable ions (RCOO-, Cl-, I-, RS-, etc..) increases the tendency to give SN2 reactions.
 Elimination Reactions: E2 vs SN2
▪ Bulky strong bases:

Bulky bases, such as potassium tert-butoxide [(CH3)3CO-K+], are not good nucleophiles but they can still act as strong bases.
As a result, such bulky bases can be used to favor elimination reactions over nucleophilic substitution reactions.
CH3OH, 65 °C
For example: CH3CH2CH2Br ~1% E2 product + 99% SN2 product
CH3ONa
(CH3)3COH, 40 °C
CH3CH2CH2Br ~85% E2 product + 15% SN2 product
(CH3)3CONa

▪ Use of a bulky base can change the product preference:

Figure is taken from:

https://chem.libretexts.org/Bookshelves/Organic_Chemistry/Book%3A_Basic_Principles_of_Organic_Chemistry_(Roberts_and_Caserio)/08%3A_Nucleophilic_Substitution_and_Elimination_Reac
tions/8.09%3A_The_E2_Reaction
Substitution and Elimination Reactions: SN1 & E1

SN1
E1
CH3CH2OH, 55 °C
CH3CH2ONa CH3CH2O:-
Base

+ Br- + CH3CH2OH
 Substitution and Elimination Reactions: E1

E1 reactions does NOT require a very strong base and acidic conditions may favor an E1 reaction.

https://chem.libretexts.org/Bookshelves/Organic_Chemistry/Book%3A_Organic_Chemistry_with_a_Biological_Emphasis_v2.0_(Soderberg)/14%3A_Electrophilic_Reactions/14.03%3A_Elimin
ation_by_the_E1_Mechanism#:~:text=E1%20eliminations%20can%20occur%20at,it%20a%20viable%20leaving%20group.
Elimination Reactions: E1

CH3CH2OH, 55 °C
CH3CH2ONa CH3CH2O:-
Base

+ Br- + CH3CH2OH
E1
▪ Since E1 reactions proceeds with a carbocation, factors affecting SN1 affect E1 as well.

▪ SN1 and E1 products are usually observed together. Usually, SN1 products are favored at low temperatures.

▪ Higher temperatures may increase the E1 product amount. However, we can’t easily favor E1 over SN1 reactions.
 Elimination Reactions: E1
▪ Both SN1 and E1 reaction types favor tertiary alkyl halides. For example: dehydration of tertiary alcohols by a bulky
acid (for example: phosphoric acid or sulfuric acid) may follow E1 mechanism.

E1

▪ When an elimination reactions is desired for a tertiary alkyl halide, instead of E1 reactions, E2 type eliminations can be
more practical by using a strong base.

https://chem.libretexts.org/Bookshelves/Organic_Chemistry/Supplemental_Modules_(Organic_Chemistry)/Reactions/Elimination_Reactions/E1_Reactions
https://chem.libretexts.org/Bookshelves/Organic_Chemistry/Book%3A_Basic_Principles_of_Organic_Chemistry_(Roberts_and_Caserio)/08%3A_Nucleophilic_Substitution_and_Elimination_Reac
tions/8.09%3A_The_E2_Reaction
Elimination Reactions: E1 & E2
For elimination reactions, which would be more plausible mechanism: E1 or E2?
Possible elimination products?

1) good leaving group,

2) secondary alkyl substate,
3) strong and bulky base: E2

(CH3)3COK, 45°C
(CH3)3COH
Elimination Product

H3PO4

Major Elimination Product Minor Elimination Product

-OH is a bad leaving group. However, it is protonated under acidic conditions: -H2O+
1) -H2O is a good leaving group.
2) Tertiary alkyl substate may favor carbocation formation.
3) Weak base (H2PO4-): E1
Elimination Reactions: E1 & E2
References
1) Elimination Reactions- Zaitsev’s Rule. (2020, August 11). Retrieved May 15, 2021, from https://chem.libretexts.org/@go/page/31511
2) The E2 Reaction and the Deuterium Isotope Effect. (2020, August 11). Retrieved May 15, 2021, from
https://chem.libretexts.org/@go/page/31512
3) The E2 Reaction and Cyclohexane Conformation. (2020, August 11). Retrieved May 15, 2021, from
https://chem.libretexts.org/@go/page/31513
4) The E1 and E1cB Reactions. (2021, January 18). Retrieved May 15, 2021, from https://chem.libretexts.org/@go/page/31515
5) Biological Elimination Reactions. (2020, August 11). Retrieved May 15, 2021, from https://chem.libretexts.org/@go/page/31516
6) A Summary of Reactivity - SN1, SN2, E1, E1cB, and E2. (2020, August 11). Retrieved May 15, 2021, from
https://chem.libretexts.org/@go/page/31517
7) Reactions of Alkyl Halides - Nucleophilic Substitutions and Eliminations (Summary). (2020, August 11). Retrieved May 15, 2021, from
https://chem.libretexts.org/@go/page/210489
8) https://commons.wikimedia.org/wiki/File:The_broken_C-H_bond_and_the_leaving_group_in_an_E2_mechanism_are_anti-periplanar.png
9) https://en.wikipedia.org/wiki/File:Representation_of_co-planar_A-B_and_C-D_bonds_with_a_dihedral_angle_of_180_degrees.jpg
10) https://commons.wikimedia.org/wiki/File:Newman_projection_showing_A_and_D_anti-periplanar.jpg
11) Solomons, G. T. W., Fryhle, C. B., & Snyder, S. A. (2017). Solomons’ Organic Chemistry (Global ed.). John Wiley & Sons.
Elimination Reactions: E1 & E2

This summary is taken from:A Summary of Reactivity - SN1, SN2, E1, E1cB, and E2. (2020, August 11). Retrieved May 15, 2021, from https://chem.libretexts.org/@go/page/31517