Elimination Reactions Organic Chemistry 4th Edition Paula Yurkanis Bruice Chapter 11 Elimination Reactions of Alkyl Halides Competition Between Substitution and Elimination Irene Lee Case Western Reserve University Cleveland, OH ©2004, Prentice Hall

In addition to substitution, an alkyl halide can undergo an elimination reaction

The E2 Reaction

The weaker the base, the better it is as a leaving group

The Regioselectivity of the E2 Reaction The major product of an E2 reaction is the most stable alkene The greater the number of substituents, the more stable is the alkene

Reaction coordinate diagram for the E2 reaction of 2-bromobutane and methoxide ion

The Zaitsev Rule The more substituted alkene product is obtained when a proton is removed from the b-carbon that is bonded to the fewest hydrogens The most stable alkene is generally (but not always) the most substituted alkene

Conjugated alkene products are preferred over the more substituted alkene product Do not use Zaitsev’s rule to predict the major product in these cases

Steric hindrance also affects the product distribution

Another exception to Zaitsev’s rule

Consider the elimination of 2-fluoropentane …

A carbanion-like transition state

Relative stabilities of carbanions tertiary carbanion secondary carbanion primary carbanion methyl anion least stable most stable

The E1 Reaction

Reaction coordinate diagram for the E1 reaction of 2-chloro-2-methylbutane

Because the E1 reaction forms a carbocation intermediate, we need to consider carbocation rearrangement

Competition Between E2 and E1 Reactions

Stereochemistry of the E2 Reaction The bonds to the eliminated groups (H and X) must be in the same plane H X H X the more stable conformation The anti elimination is favored over the syn elimination

Another view of the E2 reaction mechanism The best overlap of the interacting orbitals is achieved through back side attack Anti elimination avoids repulsion of the electron-rich base

Consider the regioselectivity of the E2 reaction The alkene with the bulkiest groups on opposite sides of the double bond will be formed in greater yield, because it is the more stable alkene

Reaction coordinate diagram for the E2 reaction of 2-bromopentane and ethoxide ion

The particular alkene isomer that is formed depends on the configuration of the reactant

Stereochemistry of the E1 Reaction

Elimination from Cyclic Compounds In an E2 reaction, groups to be eliminated must be trans to one another

E1 Elimination from Cyclic Compounds An E1 reaction involves both syn and anti elimination

Utilization of kinetic isotope effect to study a reaction mechanism kH kD A carbon deuterium bond (C–D) is stronger than a carbon hydrogen bond (C–H) The deterium isotope is 7.1, indicating that C–H (or C–D) bond must be broken in the rate-determining step

Competition Between Substitution and Elimination Alkyl halides can undergo SN2, SN1, E2 and E1 1) decide whether the reaction conditions favor SN2/E2 or SN1/E1 SN2/E2 reactions are favored by a high concentration of nucleophile/strong base SN1/E1 reactions are favored by a poor nucleophile/weak base 2) decide how much of the product will be the substitution product and how much of the product will be the elimination product

Consider the SN2/E2 conditions

A bulky base encourages elimination over substitution

A weak base encourages substitution over elimination strong base weak base

Consider SN1/E1 conditions

Substitution and Elimination Reactions in Synthesis

In synthesizing an ether, the less hindered group should be provided by the alkyl halide

However, the most hindered alkyl halide should be used if you want to synthesize an alkene

Consecutive E2 Elimination Reactions

Intermolecular Versus Intramolecular Reactions A low concentration of reactant favors an intramolecular reaction The intramolecular reaction is also favored when a five- or six-membered ring is formed

Three- and four-membered rings are less easily formed Three-membered ring compounds are formed more easily than four-membered ring compounds The likelihood of the reacting groups finding each other decreases sharply when the groups are in compounds that would form seven-membered and larger rings.

Now we can design a synthesis …