After completing this section, you should be able to
- write the mechanism of a typical E2 reaction.
- sketch the transition state of a typical E2 reaction.
- discuss the kinetic evidence that supports the proposed E2 mechanism.
- discuss the stereochemistry of an E2 reaction, and explain why the anti periplanar geometry is preferred.
- determine the structure of the alkene produced from the E2 reaction of a substrate containing two chiral carbon atoms.
- describe the deuterium isotope effect, and discuss how it can be used to provide evidence in support of the E2 mechanism.
Make certain that you can define, and use in context, the key terms below.
- anti periplanar
- deuterium isotope effect
- E2 reaction
- syn periplanar
An E2 reaction is a bimolecular elimination reaction; thus, two molecules are involved in the rate-limiting step. In this section, we are concerned with E2 reactions involving an alkyl halide and a base.
Use molecular models to assist you to understand the difference between syn periplanar and anti periplanar, and to appreciate why E2 eliminations are stereospecific.
Note that when deuterium is used the kinetic isotope effect (KIE) is referred to as the deuterium isotope effect. A C–H bond is about 5 kJ/mol weaker than a C–D bond. So if the rate-limiting step involves a breaking of this bond as it does at the E2 transition state there will be a substantial difference in reaction rates when comparing deuterated and non-deuterated analogues. Indeed, the reaction of 2-bromopropane with sodium ethoxide (NaOEt) is 6.7 times faster than its deuterated counterpart, providing evidence consistent with an E2 mechanism.
E2, bimolecular elimination, was proposed in the 1920s by British chemist Christopher Kelk Ingold. Unlike E1 reactions, E2 reactions remove two subsituents in a single concerted reaction step, also resulting in an alkene.
E2 reactions are typically seen with secondary and tertiary alkyl halides, but a hindered base is necessary with a primary halide. The mechanism by which it occurs is a single step concerted reaction with one transition state. The rate at which this mechanism occurs is second order kinetics, and depends on both the base and alkyl halide. A good leaving group is required because it is involved in the rate determining step. The leaving groups must be coplanar in order to form a pi bond; carbons go from sp3 to sp2 hybridization states.
To get a clearer picture of the interplay of these factors involved in a a reaction between a nucleophile/base and an alkyl halide, consider the reaction of a 2º-alkyl halide, isopropyl bromide, with two different nucleophiles. In one pathway, a methanethiolate nucleophile substitutes for bromine in an SN2 reaction. In the other (bottom) pathway, methoxide ion acts as a base (rather than as a nucleophile) in an elimination reaction. As we will soon see, the mechanism of this reaction is single-step, and is referred to as the E2 mechanism.
Below is a mechanistic diagram of an elimination reaction by the E2 pathway:
An E2 reaction has certain requirements to proceed:
- A strong base is necessary especially necessary for primary alkyl halides. Secondary and tertirary primary halides will procede with E2 in the precesence of a base (OH-, RO-, R2N-)
- Both leaving groups should be on the same plane, this allows the double bond to form in the reaction. In the reaction above you can see both leaving groups are in the plane of the carbons.
- Follows Zaitsev's rule, the most substituted alkene is usually the major product.
- Hofmann's Rule, if a sterically hindered base will result in the least substituted product.
E2 Reaction Coordinate
In this reaction Ba represents the base and Br representents a leaving group, typically a halogen. There is one transition state that shows the concerted reaction for the base attracting the hydrogen and the halogen taking the electrons from the bond. The product be both eclipse and staggered depending on the transition states. Eclipsed products have a synperiplanar transition states, while staggered products have antiperiplanar transition states. Staggered conformation is usually the major product because of its lower energy confirmation.
The Leaving Group Effect in E2 Reactions
As Size Increases, The Ability of the Leaving Group to Leave Increases: Here we revisit the effect size has on basicity. If we move down the periodic table, size increases. With an increase in size, basicity decreases, and the ability of the leaving group to leave increases. The relationship among the following halogens, unlike the previous example, is true to what we will see in upcoming reaction mechanisms.
Kinetic Isotope Effects
Kinetic Isotope Effects (KIEs) are used to determine reaction mechanisms by determining rate limiting steps and transition states and are commonly measured using NMR to detect isotope location or GC/MS to detect mass changes. In a KIE experiment an atom is replaced by its isotope and the change in rate of the reaction is observed. A very common isotope substitution is when hydrogen is replaced by deuterium. This is known as a deuterium effect and is expressed by the ratio kH/kD (as explained above). Normal KIEs for the deuterium effect are around 1 to 7 or 8. Large effects are seen because the percentage mass change between hydrogen and deuterium is great. Heavy atom isotope effects involve the substitution of carbon, oxygen, nitrogen, sulfur, and bromine, with effects that are much smaller and are usually between 1.02 and 1.10. The difference in KIE magnitude is directly related to the percentage change in mass. Large effects are seen when hydrogen is replaced with deuterium because the percentage mass change is very large (mass is being doubled) while smaller percent mass changes are present when an atom like sulfur is replaced with its isotope (increased by two mass units).
Primary kinetic isotope effects are rate changes due to isotopic substitution at a site of bond breaking in the rate determining step of a reaction.
Consider the bromination of acetone: kinetic studies have been performed that show the rate of this reaction is independent of the concentration of bromine. To determine the rate determining step and mechanism of this reaction the substitution of a deuterium for a hydrogen can be made.
When hydrogen was replaced with deuterium in this reaction a kH/kD of 7 was found. Therefore the rate determining step is the tautomerization of acetone and involves the breaking of a C-H bond. Since the breaking of a C-H bond is involved, a substantial isotope effect is expected.
What is the product of the following molecule in an E2 reaction? What is the stereochemistry?
The stereochemistry is (Z) for the reaction.
Contributors and Attributions
Prof. Steven Farmer (Sonoma State University)
- Layne Morsch (University of Illinois Springfield)