Chapter 9

Elimination reactions

E2 and E1 reactionsCompetition between SN and E

Elimination reactions elimination and/or substitution

2 mechanisms ~ E2 and E1

Ch 9 #2

bimolecular

mechanism ~ concerted

1,2-elimination or β-elimination

leaving group effect

E2: bimolecular elimination rxn

no substitution?

Ch 9 #3

E2: regioselectivity (1) ~ Zaitsev’s rule

Zaitsev’s rule “The more substituted alkene product is obtained

when a proton is removed from the β-carbon that is bonded to the fewest hydrogens.”

a product [thermodynamic] control

Ch 9 #4

Generally,

1° > 2° (no 3°) for SN2 Nu: attacks C3° > 2° > 1° for E2 (and E1, except 1°) B: attacks [takes] H

Ch 9 #5

E2: regioselectivity (2) ~ resonance Resonance-stabilized alkene [conjugated diene] is more

stable. It may not be the more-substituted.

Ch 9 #6

E2: regioselectivity (3) ~ steric Ch 9 #7

E2: regioselectivity (4) ~ leaving group

F is the poorest leaving group.

alkene-like TS carbanion-like TS

Ch 9 #8

stability of carbanion

Effect of leaving group on E2 product

Major product of E2 rxn is the more stable alkene. exceptions ~ steric reactant(s), (very) poor leaving group

Ch 9 #9

E1: unimolecular elimination reaction

unimolecular

mechanism

weak base takes H from sp3 C? C+ accepts e of C: + hyperconjugation

no substitution?

Ch 9 #10

E1: reactivity C+ stability

trend same to SN1

trend same to E2

leaving group effect

trend same to SN2, SN1, and E2

Ch 9 #11

E1: regioselectivity more substituted product ~ Zaitsev’s rule

Ch 9 #12

E1: C+ rearrangement Ch 9 #13

Competition betw E2 and E1

E2 is favored by (high concentration of) strong base (like HO–, RO–), and

in aprotic polar solvent (like DMF, DMSO).

E1 is favored by weak base (like H2O, ROH), and

in protic polar solvent (like H2O, ROH).

SN2 is favored by good Nu: in aprotic polar solvent.

SN1 is favored by poor Nu: in protic polar solvent.

Ch 9 #14

Stereochemistry of E2 and E1 E2 is an anti-elimination rxn. 4 atoms [H, C, C, X] must be periplanar [coplanar] to form C=C double bond.

anti-periplanar (highly) favored over syn-periplanar

Ch 9 #15

E2 is stereoselective when 2 β-H’s 2 products (stereoselective)

Ch 9 #16

when 1 β-H 1 product

stereospecific? (2R,3S) ?

Ch 9 #17

E1 also is stereoselective.

2 β-H’s 2 products (stereoselective)

1 β-H’s 2 products (stereoselective)

Ch 9 #18

Elimination from substituted cx E2 must be anti-periplanar.

E2 of menthyl chloride is slow.

H and X must be trans-diaxial.

Ch 9 #19

E2 of neomenthyl chloride is rather fast.

+

Ch 9 #20

E1 need not be periplanar.

+

Cl

CH3OH

CH3O

2 SN + 2 E products

1 product

Ch 9 #21

Stereochemistry of SN and E Ch 9 #22

Kinetic isotope effect

kH = 7.1 kD C–D stronger than C–H (why?)

(deuterium) kinetic isotope effect = kH/kD = 7.1

supports E2 (concerted) mechanism, not E1

Ch 9 #23

Competition betw SN and E

SN2/E21. 1° favors SN2 over E2.

why? above comparison? just observed.

SN2/E2 is favored by good Nu:/strong B: in aprotic polar solvent.

SN1/E1 is favored by poor Nu:/weak B: in protic polar solvent.

X XX

Ch 9 #24

SN2/E2 (cont’d)2. Steric hindrance favors E2 over SN2.

Ch 9 #25

SN2/E2 (cont’d)3. Stronger B: [Nu:] favors E2 over SN2.

why? just observed.

RCOO– ~ a medium baseH3O+ > RCOOH > H2O

Ch 9 #26

SN2/E2 (cont’d)4. High temperature favors E2 over SN2.

why? T∆S

Ch 9 #27

SN2/E2 (cont’d)5. 3° undergoes E2 only.

Ch 9 #28

SN1/E1 hard to control the ratio of SN1 to E1

no SN1/E1 for 1°

more SN1 over E1 for 3° why? no SN2 for 3°? just observed.

Ch 9 #29

Ch 9 #30

Using SN in synthesis Williamson (ether) synthesis

SN2

preparation of RO–

need very strong base for alcohol

need less strong base for phenol

Ch 9 #31

Williamson (ether) synthesis (cont’d) Substrate [RX] should be 1°.

SN1 (using ROH) for 2° or 3° substrate

no SN, no ether

(b) is (much) better (a) gives E2 product also

Ch 9 #32

alkynes from acetylide ion

SN2

Substrate [RX] better be 1°.

Ch 9 #33

Using E in synthesis preparation of alkene

E2(/SN2) rather than E1(/SN1)

2° better, more hindered better

more E2 by using t-BuO– instead of –OH, high temperature

Ch 9 #34

preparation of alkyne from dihalides

need very strong base (–NH2 > –OH) vinyl halide

from alkene

Ch 9 #35

Designing synthesis II Ex 1>

direct hydrocyanation? possible, using catalyst

using SN/E

CN– ~ stronger B: than Br–, weaker B: than OH–

SN2 over E2 (or maybe SN1/E1)

Ex 2>

pKa of HCN = 9.1

E2, no SN2 anti-Markovnikov, syn

Ch 9 #36

Ex 3>

Ex 4>

E2, no SN2not BH3

not BH3SN2 (low E2)

Ch 9 #37

Chapter 9���Elimination reactionsElimination reactionsE2: bimolecular elimination rxnE2: regioselectivity (1) ~ Zaitsev’s rule슬라이드 번호 5E2: regioselectivity (2) ~ resonanceE2: regioselectivity (3) ~ stericE2: regioselectivity (4) ~ leaving group슬라이드 번호 9E1: unimolecular elimination reactionE1: reactivityE1: regioselectivityE1: C+ rearrangement Competition betw E2 and E1Stereochemistry of E2 and E1슬라이드 번호 16슬라이드 번호 17슬라이드 번호 18Elimination from substituted cx슬라이드 번호 20슬라이드 번호 21Stereochemistry of SN and EKinetic isotope effectCompetition betw SN and E슬라이드 번호 25슬라이드 번호 26슬라이드 번호 27슬라이드 번호 28슬라이드 번호 29슬라이드 번호 30Using SN in synthesis 슬라이드 번호 32슬라이드 번호 33Using E in synthesis 슬라이드 번호 35Designing synthesis II슬라이드 번호 37