L
TOPIC 7. ELIMINATION REACTIONS
(chapter 7 and parts of chapters 4,6,20)
OBJECTIVES
1. Describe mechanisms for elimination of a leaving group and adjacent
proton to form a pi-bond.
2. Discuss the effect of starting material (“substrate”), leaving group, and
reaction conditions on the course and outcome of a reaction.
3. Describe syntheses of alkenes and alkynes.
4. Use combinations of elimination and substitution reactions in developing
two-step syntheses of value-added compounds.
D.M. Collard 2007
S:7.1-7.4
REVIEW OF ALKENES: STRUCTURE,
NOMENCLATURE, AND STABILITY
Prob:
7.18-21
Preview of Reactivity
Structure
Additions (Topic 8)
C C
H2
Pt or Pd
C C
Cl
Cl
Cl
C C
H
H
C C
H
HBr
H
Cl
H2O
H2SO4
H H
C C
H Br
C C
H OH
C C
Systematic Nomenclature
e.g.,
H3C
F
C C
H
Br
Assign Cahn-Ingold-Prelog priority to substituents on each sp2 carbon
Highest priority on
same side: Z (zusammen=same)
opposite sides: E (entgegen=opposite)
Problem: Name the following compound
H3C
CH2CH(CH3)2
C C
H
CH3
D.M. Collard 2007
Problem: Provide IUPAC names for the following alkenes
Problem: Determine the E/Z configurations of the double bonds in each of the following
alkenes
OH
geraniol
Relative Stability
Heats of Hydrogenation
C4H8 + H2
Pt
C4H10
or Pd
ΔHo < 0
+ H2
ΔHo = -120
kJ/mol
+ H2
+ H2
+H2
+H2
+H2
ΔHH > 0
D.M. Collard 2007
ΔHo = -127
kJ/mol
ΔHo = -115
kJ/mol
Overall Stability
R
R
R
H
R
H
R
H
R
R
R
H
R
R
R
R
R
H
H
R
H
H
H
H
number of
substituents
Number of substituents Ç ⇒
Remember hyperconjugation?
H
C
C
C
H
H
Hyperconjugation accounts for the enhanced stability of cations, radicals
and alkenes with higher degrees of substitution.
H
C
C
H
H
Carbocation
relative
stability
stability
explains
D.M. Collard 2007
H
H
C
C
C
H
Radical
C
H
C
H
Alkene
H
Cycloalkenes
C C
H
H
cyclopropene
cyclobutene
cyclopentene
cyclohexene
cycloheptene
cyclooctene
trans cyclooctene
cis cyclooctene
strain energies:
15 kcal/mol
27 kcal/mol
PREVIEW OF FORMATION OF ALKENES &
ALKYNES BY ELIMINATION REACTIONS
H Br
C C
H OH
C C
base
acid
C C
Zn
Br Br
C C
Br Br
C C
H H
D.M. Collard 2007
base
NaNH2
C C
S:7.5
S:6.15-6.17
L
BASE-PROMOTED
DEHYDROHALOGENATION OF ALKYL HALIDES
CH3
H3C
H2O
Br
CH3
but:
CH3
H3C
NaOH
Br
CH3
ELIMINATION MECHANISMS
Bimolecular Elimination (E2) Reaction
Rate = k[R-L][base]
‡
B
H
Br
D.M. Collard 2007
Unimolecular Elimination (E1) Reaction
Rate = k[R-L], independent of [base]
H
Br
SN2 SUBSTITUTION VERSUS E2
ELIMINATION
S:6.18-6.19
Prob:
6.21,23,29
X
H
L
X
H
L
Substitution and elimination mechanisms might be competitive pathways in a
reaction mixture. The outcome of a reaction depends on:
i. the structure of the substrate (steric hindrance to nucleophilic
attack)
ii. the basicity of the nucleophile
D.M. Collard 2007
Observations and Explanations
CH3
H3C C Br
CH3
CH3CH2 Br
H3C
CH Br
CH2
CH3ONa
or KCN
H3C
C
CH3
CH3ONa
CH3CH2 OCH3
CH3ONa
CH3CH CH2
H3 C
H3 C
CH Br
KCN
H3 C
CH CN
H3 C
H3C
CH3
H3C C OK
CH3CH2 Br
CH3
heat
H2C CH2
Summary
3° substrates only undergo substitution with weakly basic nucleophiles
(ROH, H2O, RCO2H). Stronger bases promote elimination. 1° substrates
generally undergo substitution unless the base itself is sterically crowded
(e.g., t-BuO-).
Substrate
3°
Nucleophile/Base
Mechanism
weak bases:
ROH, H2O, RCO2H
give solvolysis
SN1 (some E1 on heating)
strong bases:
anionic bases (HO-,
RO- NH2-), NH3
E2
No SN2 with 3° substrates
D.M. Collard 2007
Summary
3° substrates only undergo substitution with weakly basic nucleophiles
(ROH, H2O, RCO2H). Stronger bases promote elimination. 1° substrates
generally undergo substitution unless the base itself is sterically crowded
(e.g., t-BuO–).
Substrate Nucleophile/Base
2°
Mechanism
Less basic than HO–:
e.g.., HS–, RS–, NH3,
–CN, RCO –
2
SN2
HO– and more basic:
RO–, NH2–
E2
weak nucleophiles:
ROH, H2O
SN1 (some E1 on heating)
Summary
3° substrates only undergo substitution with weakly basic nucleophiles
(ROH, H2O, RCO2H). Stronger bases promote elimination. 1° substrates
generally undergo substitution unless the base itself is sterically crowded
(e.g., t-BuO–).
Substrate Nucleophile/Base
1°
Mechanism
All except t-BuO–
SN2
t-Bu-O–
E2
(hindered strong base)
Me
D.M. Collard 2007
all
SN2
STEREOCHEMISTRY AND
REGIOCHEMISTRY
Regiochemistry: Zaitev Elimination
EtOK
EtOH
Br
Zaitsev’s Rule: _______ substituted (stable) alkene is formed
ΔG
Reaction coordinate
Anti-Zaitsev Elimination
1. Use of bulky bases can lead to formation of “anti-Zaitsev” products
t-BuOK
t-BuOH
Br
H
H
H H
D.M. Collard 2007
H
H
H
Br
H
S:7.6;
20.13
Prob:
7.22a-b,
23a-b,29,
30,34,35
20.30h,
40(r,s,t)
2. Formation of “anti-Zaitsev” products via the Hofmann Elimination
Br
N(CH3)3
(CH3)3N
N(CH3)3 HO
Br
Ag2O
H2 O
Ag2Br
150 oC
(+5% 2-isomer)
Mechanistic explanation
δ
HO
δ
HO
H
H
δ
N(CH3)3
Br
δ
Concerted E2 of alkyl bromide
Developing alkene character
in the transition state is stabilized by
hyperconjugation, giving Zaitsev product
Hofmann elimination
Developing carbanionic character in transition
state (facilitated by the N+) is
destabilized by alkyl substitutents, giving
anti-Zaitzev product
Orientation of E2 Eliminations
Antiperiplanar: preferred orientation for elimination
H
B
Cl
H
H
Cl
Cl
Synperiplanar: slower elimination
H
Cl
B
H
D.M. Collard 2007
Cl
H
Cl
Explain the observation that cis-4-t-butyl cyclohexyl chloride undergoes
elimination with a strong base 500 times faster than the trans isomer
Cl
Cl
t-BuOK
t-BuOK
t-Bu
t-Bu
t-Bu
trans
cis
cis reacts 500 times faster than trans
Cl
H
Cl
t-Bu
H
t-Bu
H
H
H
DEHYDROBROMINATION AND
DEBROMINATION OF VICINAL
DIBROMIDES
Br Br
C C
H H
Br Br
C C
D.M. Collard 2007
2 eq. NaNH2
Zn
C C
C C
S:7.9
Prob:7.22e
Problem. Why does treatment of 1,2-dibromocyclohexane give 1,3cyclohexadiene, not an alkyne?
Br
NaNH2
Br
L
ACID-PROMOTED DEHYDRATION OF
ALCOHOLS
Acid-Promoted Elimination
H OH
C C
acid
C C
Ease of dehydration:
3° > 2° >> 1°
Proceeds under relatively
mild conditions
85 °C
20% aq. H2SO4
D.M. Collard 2007
Requires relatively
harsh conditions
180 °C
conc. H2SO4
S:7.7-7.8
Prob:
7.22c-d,
23c,26,
32,33,36
Ease of Formation of Carbocations: Kinetics vs.
Thermodynamics
Stability of starting material and products of a reaction relates to
thermodynamics (equilibrium). The relative energy of the starting material and
transition state relates to the rate of the reaction (kinetics).
i-Pr+,
H2O
t-Bu+,
H2O
H
i-PrOH, H+
t-BuOH, H+
reaction coordinate
reaction coordinate
Mechanism: Dehydration of 2° and 3° Alcohols by E1
CH3
H3C C O
CH3 H
D.M. Collard 2007
H OH2
Mechanism: Dehydration of 1° Alcohols by E2
H OSO3H
CH3 CH2 O
H
Rearrangement of Carbocations During Elimination
not:
OH
H
H3PO4
Δ
H
H-OPO3H2
Carbocations rearrange by hydride or alkyl shifts: 2o → 3o
D.M. Collard 2007
A SUMMARY OF REACTIONS
H
C C
C C
Br2, hν
ns
io
ut
tit
bs
su
We’ve added a few more reactions
(eliminations) to your chart of reactions….
….we’ll add a few more in the next topic.
H
C C
H
Elim'n
Br
Ad
H2/Pt
Br Br
n
d' n Subst'n Subst'n
'
im
l
E
Add'n
Elim'n
C C
Elim'n
H
C C
OH
s
SYNTHETIC STRATEGIES: TWO (OR MORE)
STEP SYNTHESES
s
ub
tit
You need to recognize that there is a single intermediate which can:
1. be made from the starting material,
and 2. be transformed into the desired product
D.M. Collard 2007
ns
Prob:
7.24a-c,f,g,j,k,
31
At the end of Topic 6 you were challenged to recognize one-step synthetic
transformations. But not all transformations can be achieved in one step.
For example, there is no method to dehydrogenate (i.e., remove H2)
alkanes. So how would you bring about the following transformation?
???
io
ut
Problem: What two-step process can be used to achieve the
following overall transformation?
Br
Problem: This process can, of course, be extended to longer sequences of
reactions. How could you prepare decane from bromohexane, bromoethane
and ethyne?
from
Br
D.M. Collard 2007
Br
HC CH
Problem: Reaction of trans-1-bromo-2-methylcyclohexane with sodium
ethoxide, a non-bulky base, results in formation of 3-methylcyclohexene, the
anti-Zaitzev product. Explain.
CH3
Br
EtONa
EtOH
CH3
TOPIC 7 ON EXAM 4
Types of Questions
- Describe elimination reaction mechanisms
- Predict the products of elimination reactions
- Describe some simple reactions of alkenes (hydrogenation) and alkynes
(acidity, hydrogenation)
The problems in the book are good examples of the types of problems on the
exam.
Preparing for Exam 4:
- Work as many problems as possible.
- Work in groups.
- Do the “Learning Group Problem” at the end of the chapter.
- Work through the practice exam
D.M. Collard 2007