Elimination Reactions ofAlkyl Halides

Chapter 9

“A pessimist finds difficulty in every opportunity. An optimist finds opportunity in

every difficulty.” A. Lincoln

Elimination Reactions

Elimination Rx can be of two types

• E1 mechanism (unimolecular)

• E2 mechanism (bimolecular)

E2 Eliminations

Concerted one step reaction

E2 Eliminations

• Called “dehydrohalogenations”

• Called Eliminiation

• Called 1-2 Elimination

E2 Eliminations

Relative reactivities of RX in an E2 reaction:

(most reactive) RI > RBr > RCl > RF (least reactive))

F- is a better base than Br-

E2 EliminationsSometimes only one elimination product is possible

Sometimes More than one product may result

E2 Eliminations

Kinetic and Thermodynamic Product

(A regioselective reaction !)

Zaitsev’s Rule

The more highly substituted product is obtained when a proton is removed from the -carbon that is bonded to

the fewest hydrogens

Reactivity of Alkyl Halides

• *

Reactivity Considerations• The more substituted product is not always the most

rapidly formed…

That Conjugated Diene thing just keeps showing up…….

Reactivity Considerations• The more substituted product is not always the most

rapidly formed…That Pesky Bulky Base – Changes things……

Reactivity Considerations

• Steric hindrance may dictate removal of a more accessible H

(The most substituted is not formed here.)

• *

(What does this mean?)

Alkyl fluorides• Dehydrohalogenation of R-I, R-Br, R-Cl yield more substituted alkene

• Dehydrohalogenation of RF yields the less

substituted alkene

Elimination of Alkyl fluorides

Elimination of Alkyl fluorides• Fluoride is a strong base• Fluoride is a poor leaving group• A partial negative charge develops on the

carbon that lost the proton (a carbanion)

Carbo - IonsCarbocations are stabilized by alkyl groups

Carbanions are destabilized by alkyl groups

CR’

R”

R

: -3O < 2O < 1O

Increasing stability of Carbanions

Elimination Considerations

• The major product is the more substituted alkene unless…the alkyl halide contains conjugation

the base is large

the alkyl halide is an alkyl fluoride

E1 Mechanism

•

E1 Mechanism

Major product will generally be the more substituted - Zatsev

E1 Mechanism

Product depends on stability of the carbocation

E1 Mechanism

• Because a carbocation is formed – rearrangement is possible

E1 Mechanism

• Because a carbocation is formed – rearrangement is possible

Competition E1 vs. E2

RX Elimination comments

1o alkyl halides E2 only Difficulty in forming 1o carbocations

2o alkyl halides E1 and E2 Favored by same as SN2 conditions

3o alkyl halides E1 and E2 Favored by same as SN2 conditions

Review of SN Reactions

SN1 is Favored ByMore Substituted Carbocation

Weak NucleophilePolar Protic Solvent

SN2 is Favored ByLess Substituted Carbocation

Strong NucleophilePolar AProtic Solvent

Stereochemistry of E2

• In an E2 reaction, 2 groups are eliminated in one step

• The 2 groups MUST be located in the same plane (periplanar)

(syn-periplanar)slower

(anti-periplanar)

faster

E2 is regioselective

E2 Is Stereoselective

•

The conformers that have the bulkiest groups on opposite sides will be the major product.

Stereochemistry of E2

Note: E isomer is major product because bulky groups, methyl and t-butyl, are anti.

Stereochemistry of E2

Important note: use models! E2 for 2-bromo-3-phenylbutane

onlyE isomer

onlyZ isomer

(2S, 3S)

(2S, 3R)

E1 Eliminations

– planar, carbocation intermediate– syn and anti elimination can occur

(Major product is the one with bulkiest groups on opposite sides.)

bulkiest groups on opposite sides

Elimination from Cyclics - E2

– In an E2 reaction, both groups must be periplanar and anti to each other.

– This is NOT the most stable conformer.

Elimination from Cyclics - E2

Elimination from Cyclics - E2

Occurs 200 x faster!More stable conformer has groups equatorial.

Elimination from Cyclics - E2

• In an E2 reaction, the H is removed from the most substituted -carbon unless that hydrogen is not in the axial

Elimination from Cyclics - E1

• In an E1 reaction, the elimination is not concerted.

• Intermediate is a carbocation• Groups do not need to be in the axial position

Elimination from Cyclics - E1

• Carbocation intermediates may rearrange.

(Zaitsev’s rule is followed, but first watch out for a rearrangement.)

Stereochemistry Reviewmechanism products comments

SN1 Both enantiomers formed (more inverted than retained)

Racemization w/ some inversion

•E1Both E and Z formed (more of the stereoisomer with bulkiest groups trans)

Also C+ intermediate

•SN2 Only the inverted product is formed

Inversion

E2 Both enantiomers formed (more of the stereoisomer with bulkiest groups trans)

Using Isotopes In Chemistry

• Look at mechanism

• Look at research handout

• Look at medical questions handout

Substitution vs. Elimination

•

Steps To Deciding

• Decide if it favors Sn2/E2 or Sn1/E1 conditions

• Decide if it favors Substitution or Elemination

…….. That’s all there is to it

From Yahoo Images

Deciding Between First or Second order

• Substrate –1st order – primary and secondary2nd order – secondary and tertiary

• Nucleophile 1st order – weaker nuclephile2nd order – strong nucleophile

• Solvent 1st order – polar protic solvent2nd order – polar aprotic or neutral

2 out of three ain’t bad………… or is that just a long lost song

Deciding Between Sn2 and E2

• Substrate

• Base

• Temperature

From Yahoo Images

Deciding Between Sn2 and E2

• Substrate Sn2 – primary alkyl halide E2 – secondary alkyl halide

Deciding Between Sn2 and E2• Nuclophile Sn2 – Weaker and Smaller

E2 – stronger and Bulkier

Deciding Between Sn2 and E2

• Temperature Sn2 – Lower Temperature E2 – Higher Temperatue

SN1 / E1 Conditions

• All alkyl halides have same order of reactivity for SN1 or E1

• Substitution is favored at lower temperatures

Practice Activity

• Each person create a reaction and conditions

• Have your neighbor decide which mechanism it will undergo

• Switch and do it again

From Yahoo Images

Williamson Ether Synthesis

• Williamson ether synthesis– Alkyl halide with alkoxide (SN2 reaction)

– Alexander Williamson (1850!)– React alcohol with sodium metal or sodium hydride

CH3OH + Na CH3O- + Na+ + 1/2 H2

NaH

Williamson Ether Synthesis

• If you want to prepare n-propyl n-butyl ether, there are two methods.

Williamson Ether Synthesis

• If you want to prepare ethyl t-butyl ether, there are two methods… HOWEVER, if you use t-butyl halide, you will obtain primarily the elimination product.

Alkyne Syntheses• Elimination Reactions involving geminal

dihalides(note: use a very strong base NH2 , not OH-, or

it stops at vicinyl dihalide!)

Synthesis Problems

• Synthesize 1,3-cylcohexadiene from

cyclohexane.

Synthesis Problems

• Synthesis Pathway

Synthesis Problems

• Synthesize trans-1,2-dibromo-1-methylcylcohexane from methylcyclohexane.

Synthesis Problems

• Synthesis Pathway

Synthesis Problems

• Synthesize 2-butanone from 1-bromobutane.

Synthesis Problems

• Retrosynthetic Analysis

Synthesis Problems

• Synthetic pathway

END

“A pessimist finds difficulty in every opportunity. An optimist finds opportunity in every difficulty.”

A. Lincoln