Elimination Reactions

In addition to substitution, alkyl halides can also undergo elimination reactions, which lead to the formation of alkenes.

As with substitution reactions, elimination reactions come in two mechanistic types:E1 eliminations (a two-step process involving an intermediate carbocation)E2 eliminations (a one-step process involving a concurrent abstraction of a proton, from an adjacent carbon, and extrusion of the leaving group)

(E1)

(E2)

Et

Br

EtH

Et

Et

H

Et

Etslow

Et

Br

EtH

Et

EtEtO-

-H+

+ EtOH + Br-

+ Br-

E1 Elimination

In this, two-step process, the rate of the reaction is dependent on the rate of ionization of the substrate (as was the case in the SN1 reaction)

Et

Br

EtH

Et

Et

H

Et

Etslow -H+

+ Br-

(rate-determining step)r.d.s.

R OH

Rate = k[R-X]

Et

Br

EtH

Et

Et

H

Et

Et

slow

+ Br-

(rate-determining step)r.d.s.

R OH

Et

OR

Et

Et

As shown below, the intermediate carbocation may distribute itself between elimination and substitution (and also rearrangement, not shown).

Et

Br

EtH

Et

Et

H

Et

Etslow -H+

+ Br-

(rate-determining step)r.d.s.

R OH

In the case of E1 elimination, as was the case with SN1 substitution, the base (nucleophile for SN1) does not need to be strong. The slow step is formation of the carbocation, and subsequent reactions occur rapidly.

Regiochemistry of E1 Reaction

In cases where more than one regioisomeric double bond is possible, the more substituted double bond may predominate (Zaitsev’s Rule).

H3C

X

CH3

CH3

H2C

HCH3

CH3H H

-X-

CH3

CH3

H3CCH3

CH3

H2C

HCH3

CH3H H

=

(More Substitued Double Bond)Favored

-H+

-H+

E2 EliminationLike the SN2 substitution, the E2 elimination is a one-step process.Like the SN2 substitution, the E2 elimination often requires stronger bases (nucleophiles for SN2).Like the SN2 substitution, the E2 elimination exhibits bimolecular kinetics.

Et

Br

EtH

Et

EtEtO-

+ EtOH + Br-

Rate = k[R-X][B-]

Geometry of E2 Elimination

Like the SN2 substitution (which requires backside attack), the E2 elimination reaction has a geometric preference for an anti-coplanar orientation of the H-C-C-X bonds.In some cases, this may result in a stereospecific reaction, where one stereoisomer of the halide results in one geometric isomer of the alkene and the opposite stereoisomer of the halide produces the opposite geometric isomer of the alkene.

PhMe

H

Br

Pht-Bu

B:-

Me

Ph

t-Bu

Ph

+ BH + Br-

MePh

H

Br

Pht-Bu

B:-

Ph

Me

t-Bu

Ph

+ BH + Br-

(Z-alkene)

(E-alkene)

S

R

Commonly utilized bases to effect elimination reactions

(i-pr)N

(i-pr)Li Lithium Diisopropylamide (LDA)

Me C

Me

Me

O-K+ Potassium tert-Butoxide (KO-t-Bu)

N

NDiazabicycloundecene (DBU)

Et3N Triethylamine (TEA)

N Pyridine (pyr)

pKa of Conjugate Acid

40

17

11

12

5.2

Incr

easi

ng B

asic

ity o

f C

onju

gate

Bas

e

(i-pr)2NEt Diisopropylethylamine (DIEA, Hunig's Base)

11

A third mechanistic type of elimination reactions: E1cb (E1 conjugate base)

Recall:

E1 elimination: intermediate carbocation (forms slowly)E2 elimination: concerted, one step, requires coplanar arrangement of H-C-C-X bonds

In the E1cb mechanistic type, the intermediate is a carbanion.

The E1cb mechanism tends to be operative when there is a carbanion-stabilizing group (electron withdrawing group = EWG) present and when there is a relatively poor leaving group.

H

XR1

EWG R3R2

B:

XR1

EWGR3

R2

R1

EWG

R3

R2

-X--BH

Dehydration of Alcohols

Since hydroxide is a poor leaving group, it is common to first protonate the oxygen of the alcohol with a strong acid. The leaving group is thus the (neutral) water molecule as shown.

H

OR2

R1 R4R3

H

H

OR2

R1 R4R3

H

H

+H+ -H+

-H2OR2

R1

R4

R3

Dehydration of Alcohols

Alternatively, one can convert the O-H group to a better leaving group as shown below.

Debromination of Vicinal Dibromides

X

XR2

R1 R4R3

R2

R1

R4

R3

Zn: