Alkyl Halides

Elimination Reactions of Alkyl Halides

E1 and E2 Reactions

Elimination reactions are reactions where a leaving group (usually a halide) on the alpha carbon and a hydrogen atom on the beta carbon are replaced with a double bond in the presence of a base. E2 reactions are bimolecular, and E1 reactions are unimolecular.

Alkyl halides are very good leaving groups. In substitution reactions, a leaving group is replaced by a nucleophile. Another reaction involving a leaving group is an elimination reaction. An elimination reaction (or 1,2-elimination) is a chemical reaction in which the removal of two atoms (usually a hydrogen and a leaving group) forms a pi bond, a bond formed when two orbitals overlap side by side on the same plane.

Nucleophilic reagents, chemicals added to a reactant, yield substitution reactions, reactions where one functional group is replaced by another. Elimination reactions predominate when strong bases are used as the reagent. Elimination reactions are also known as 1,2-eliminations or beta eliminations. The electrophilic carbon with the halogen is known as the alpha carbon. The beta carbon is the carbon adjacent to the alpha carbon. In an elimination reaction, the bonds between the alpha carbon and leaving group plus the bond between the beta carbon and hydrogen are broken and replaced with a pi bond between the alpha carbon and the beta carbon. Most often, there is a single bond between the alpha and the beta carbon in the original molecule, which leads to the formation of a double bond when the new pi bond forms.

Elimination Reaction

Adding a strong base, such as sodium methoxide (NaOMe or NaOCH3) to a substrate with a leaving group will cause an elimination reaction to occur. The leaving group and a beta hydrogen will be removed and replaced with a pi bond.
Just like there are two mechanisms for substitution reactions (SN1 and SN2), there are two mechanistic pathways to form an elimination product—the E1 and E2 mechanisms. In E1 elimination mechanisms, tertiary alkyl halides react fastest, followed by secondary alkyl halides and then primary alkyl halides. In E2 reactions, the rate is dependent on the concentrations of the substrate and the base used. Stereochemistry is not a major concern with elimination reactions, because a functional group is removed and is replaced with a double bond, which often eliminates the stereochemistry from the molecule. However, in certain cases, the stereochemistry of the alpha and beta carbons can dictate the stereochemistry of the alkene that is formed. In most elimination reactions, regiochemistry is more important than stereochemistry. Regiochemistry is the process that favors bond formation at one atom (or location) over another. If there is more than one beta carbon with a hydrogen available for elimination, regiochemistry will determine where the double bond forms.

Regiochemistry of E1 and E2 Reactions

When more than one beta carbon with hydrogen is available, a mixture of products may form. If one location is favored over another, that reaction exhibits regiochemistry and is called a regioselective reaction, which is a reaction that forms one stereoisomer in preference to another stereoisomer.
Elimination reactions are characterized by the following:
  • Substrate, which is a reactant molecule with an electrophilic carbon attached to a halogen
  • β\beta-hydrogen on the substrate
  • Leaving group, which is the halogen attached to the electrophilic carbon
  • Base, which is an electron-rich reagent that is usually an ionic compound that is more basic than nucleophilic

Examples of bases include alkoxide bases (hydroxide, methoxide, ethoxide, and so on) and nitrogen bases (sodium amide, ammonia, and so on).

Elimination Reaction Outcomes

E1 mechanisms are multistep mechanisms, and E2 mechanisms are concerted mechanisms. E2 reactions form the Zaitsev product with most bases but form the Hofmann product with sterically hindered bases such as KOtBu. E2 mechanisms predominate with all substrates when a base is used. E1 mechanisms are usually only seen with tertiary leaving groups, a solvent, and heat.

There are two mechanistic pathways to form an elimination product—the E1 and E2 mechanisms. E2 mechanisms are concerted (all in one step) and bimolecular (same as SN2). The rate of the reaction is determined by two substances—the base and the substrate. E1 mechanisms are stepwise (more than one step) and unimolecular (same as SN1), where the substrate determines the rate of the reaction. E1 reaction rates are not based on the concentration of the base, just like SN1 reaction rates are not based on the concentration of the nucleophile.

For an E2 reaction, the base removes the beta hydrogen from the alkyl halide, and the leaving group leaves. The two steps happen at the same time, which is called a concerted mechanism. In an E1 reaction, the mechanism steps are:

1. Leaving group leaves, forming a carbocation intermediate

2. Base removes a beta hydrogen, forming an alkene

Comparing E1 and E2 Mechanisms

In the presence of a base, an E2 mechanism occurs, where the base attacks a beta hydrogen and removes it and the leaving group to form a pi bond. In the absence of a base and with the presence of heat, a tertiary leaving group will undergo an E1 mechanism. First, the leaving group leaves to form a carbocation, and then beta elimination produces a pi bond.
When more than one beta carbon has a hydrogen available for elimination, regiochemistry will determine where the double bond forms. Regiochemistry refers to processes in which the production of one structural isomer is favored over the others.

With all bases (NaOH, NaOMe, NaOEt, KOH, and so on) except for sterically hindered bases (big and bulky bases), such as potassium tert-butoxide (KOtBu), the elimination favors the more substituted product. It is called the Zaitsev product and comes from Zaitsev's rule, a rule that states that the alkene formed is more highly substituted because it is more stable. The rule can be used to predict the favored alkene product of an elimination reaction.

If a sterically hindered base, such as potassium tert-butoxide (KOtBu), is used, the less substituted product will form. It is called the Hofmann product and comes from Hofmann's rule, a rule that states that steric effects have the most influence on outcomes, specifically the loss of a beta hydrogen from the least substituted position. Since sterically hindered bases are too big and bulky to easily remove a hydrogen atom from a more substituted beta carbon, the hydrogen atom is selectively removed from a less statically hindered beta carbon and a Hofmann product is formed.

Comparing Hofmann and Zaitsev Products

Elimination of β1\beta_1-hydrogen and bromine (leaving group) leads to the more substituted Zaitsev product. Elimination of β2\beta_2-hydrogen and bromine (leaving group) leads to the less substituted Hofmann product. Sterically hindered bases, with bulky groups attached to the molecule, favor Hofmann; other bases favor the more substituted Zaitsev.
When strong bases are used, E2 reactions are favored for all leaving groups (tertiary, secondary, and primary leaving groups). E1 reactions do not occur with primary leaving groups. E1 reactions occur with secondary structures in the presence of very weak bases and with tertiary structures when poor nucleophiles or solvents are used.

Comparing E1 and E2 Reactions

Conditions E1 Reaction E2 Reaction
Kinetics Unimolecular Bimolecular
Substrate 3° and 2° 1°, 2°, and 3°
Base Very weak base or no base (solvent only) Strong base
Temperature Heat favors elimination over substitution. Heat favors elimination over substitution.
Regiochemistry Zaitsev with sterically hindered base (KOtBu)

Hofmann with all other bases
Zaitsev with sterically hindered base (KOtBu)

Hofmann with all other bases
Stereochemistry No effect No effect
Solvent Polar protic Polar protic
Leaving group Required Required

If a strong base is used in elimination reactions, regardless of the substrate, the process favors E2 eliminations, eliminations with concerted mechanisms. E1 eliminations, which have stepwise mechanisms, are only favored with weak bases (or no base) and heat on 2o and 3o leaving groups. The type of base will favor one regiochemistry over the other.