chapter 9 elimination reactions of alkyl halides competition between substitution and

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Chapter 9

Elimination Reactions of Alkyl Halides

Competition Between Substitution and

Elimination

Organic Chemistry 6th Edition

Paula Yurkanis Bruice

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

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The E2 Reaction

Hydroxide cannot act as a nucleophile in this reaction because of the bulky tertiary halide. Rather, hydroxide acts as a base and abstracts a proton.

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The removal of a proton and a halide ion is called dehydrohalogenation:

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An E2 reaction is also called a b-elimination or a 1,2-elimination reaction:

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

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The Regioselectivity of the E2 Reaction

The major product of an E2 reaction is the most stablealkene:

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

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The Zaitsev Rule

The more substituted alkene product is obtained when a proton is removed from the b-carbon that is bondedto the fewest hydrogens

The most stable alkene is generally (but not always) themost substituted alkene

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Conjugated alkene products are preferred over the more substituted alkene product:

Do not use Zaitsev’s rule to predict the major productin these cases

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Bulky bases affect the product distribution resulting in the Hofmann product, the least substituted alkene:

However, it takes a lot of steric hindrance for the less stable product to be the major product:

Hofmann product

Zaitsev product

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Another exception to Zaitsev’s rule

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Consider the elimination of 2-fluoropentane…

A carbanion-like transition state

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Therefore, the major product of an E2 elimination reactionis the more stable alkene except if the reactants aresterically hindered or the leaving group is poor

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The E1 Reaction

A unimolecular reaction:

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The E1 reaction, like the SN1 reaction, involves a carbocation intermediate:

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How does a weak base like water remove a proton froman sp3 carbon?

1) The presence of a positive charge greatly reduces the pKa

2) Hyperconjugation weakens the C-H bond by electron density

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The major product in an E1 reaction is generally themore substituted alkene

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Reaction coordinate diagram for the E1 reaction of2-chloro-2-methylbutane

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Because the first step is the rate-determining step, the rate of an E1 reaction depends both on the ease with which the carbocation is formed and how readily the leaving group leaves

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

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Competition Between E2 and E1 Reactions

An E2 is favored by a high concentration of strong base and an aprotic polar solventAn E1 is favored by a weak base and a protic polar solventReview Section 8.10 24

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Stereochemistry of the E2 Reaction

The bonds to the eliminated groups (H and X) must bein the same plane

The anti elimination is favored over the syn elimination25

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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 26

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Consider the stereoselectivity 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 27

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

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When only one hydrogen is bonded to the b-carbon, themajor product of an E2 reaction depends on the structureof the alkene

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Stereochemistry of the E1 Reaction

The major stereoisomer obtained from an E1 reaction isthe alkene in which the bulkiest substituents are onopposite sides of the double bond

Both syn and anti elimination can occur in an E1 reaction

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Elimination from Cyclic Compounds

In an E2 reaction, groups to be eliminated must be inaxial positions

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The hydrogen that is removed and the leaving group both have to be in the axial position, therefore…

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E1 Elimination from Cyclic Compounds

No axial orientation required for the E1 reaction.39

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Utilization of kinetic isotope effect to study a reactionmechanism

A carbon deuterium bond (C–D) is stronger than a carbon hydrogen bond (C–H)

The deuterium kinetic isotope effect is 7.1, indicating that a C–H (or C–D) bond must be broken in the rate-determining step

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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 a good 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

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Consider the SN2/E2 conditions

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A bulky alkyl halide or a sterically hindered nucleophileencourages elimination over substitution

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A strong or a bulky base encourages elimination oversubstitution

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High temperature favors elimination over substitution:

Why? Because elimination is entropically favorable.

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Tertiary alkyl halides undergo only elimination under SN2/E2 conditions:

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Consider SN1/E1 conditions:

Primary alkyl halides do not form carbocations; thereforethey cannot undergo SN1 and E1 reactions.

The elimination reaction favored at higher temperatures.

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Substitution and Elimination Reactions in Synthesis

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

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

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Hydroxide

Water

The E2 reaction should be used if you want to synthesize an alkene:

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Consecutive E2 Elimination ReactionsRequires a strong base NaNH2. Reaction carried out in liquid ammonia.

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Synthesis Example

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Synthesis Example

Racemic

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Synthesis Example

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Synthesis Example

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