Synthesis of Alkenes I
Reading: Wade chapter 7, sections 7-9- 7-11
Study Problems: 7-38, 7-39, 7-40, 7-41, 7-45, 7-46, 7-48, 7-53
Key Concepts and Skills:
•
Predict the products of dehydrohalogenation of alkyl halides, dehalogenation of
dibromides, and dehydration of alcohols, including major and minor products.
•
Propose mechanisms for dehalogenation, dehydrohalogenation, and dehydration
reactions.
•
Predict and explain the stereochemistry of E2 eliminations to form alkenes.
Predict the products of E2 reactions on cyclohexene systems.
Lecture Topics:
I.
Synthesis of alkenes via E1 and E2 mechanisms
A. Unimolecular Elimination (E1)
•The E1 reaction is a first-order process that has the same slow step as the SN1 reaction
 a rate-limiting ionization step to produce an intermediate carbocation.
• E1 reaction usually takes place in a good ionizing solvent like alcohols and water
without a strong nucleophile or base present.
•The alkyl halide substrate is usually a 2° or a 3° halide
•The carbocation intermediate can undergo a deprotonation by a weak base to form an
alkene or it may undergo substitution by that weak base acting as a nucleophile.
• Rearrangements are common when carbocations are intermediates
H
CH3
Br
EtOH
heat
CH3
H
H
H
SN1
E1
CH3
CH3
hydride
shift
E1
E1
CH3
CH3
E1
CH2
SN1
CH3
OEt
OEt
5 products!
B. Dehydration of alcohols
Dehydration of alcohols is an acid-catalyzed reversible process occurring by an E1
mechanism with a carbocation intermediate
water- a good leaving group
H
H
H
OH
H2SO4
O
O
H
H
H
H
fast
slow
carbocation
intermediate
fast
Reverse process, hydration of alkenes,
provides a practical synthesis of alcohols
To drive the equilibrium in the direction of alkene
production, less volatile alkene is distilled from
reaction mixture to shift equilibrium
+ H3O+
•again, rearrangements are possible, since carbocations are intermediates:
H2SO4
OH
+
CH3
heat
+
CH3
CH3
CH2
C. E2 elimination
E2 elimination provides a more practical synthesis of alkenes.
• alcohols can be used either as precursors of alkyl halides via their aryl and alkane
sulfonates, which are good leaving groups. Alternatively, alkane/aryl sulfonates can be
used in place of alkyl halides for SN2 and E2 reactions
O
Cl
S
good leaving group
O
Tosyl chloride
OH
O
O
S
O
pyridine
NaI
OTos
OTos
Ar
I
acetone
NC-
CN
I
NaI
OTos
(CH3)3CO-
+
• Alkyl halides must be poor SN2 substrates (2° or 3°) for E2 elimination to predominate.
• Concerted mechanism: strong base abstracts a proton from a neighboring carbon atom
as the leaving group departs; excellent yields are obtained with bulky halides:
OH
H
H3C
HO-
H
H 3C
CH2
H 3C
H 3C
CH2
H3C
Br
H3C
Br
+ H2O
+ Br-
•For 2° halides which are prone to SN2 substitution, a bulky base can minimize the
amount of substitution; large alkyl groups hinder its approach to carbon, yet it can still
attack a proton
E2 bases:
CH3
H
N
O-
H3C
N
H 3C
N
N
CH3
N
CH3
t-butoxide ion
diisopropyl amine
Br
triethyl amine
2,6-lutidine
H2
N
diisopropylamine
DBU
Br-
+
Thus, bulky bases can abstract protons, but are too large to undergo SN2 substitution
D. Dehydrohalogenation: Saytzeff vs. Hoffman elimination
Steric hindrance on an alkyl halide substrate will prevent abstraction of the proton
leading to the most highly substituted alkene (Saytzeff product) when a bulky base is
used. In this case, the Hoffman product (less highly-substituted alkene) predominates.
Hoffmann
Saytzeff
H
H
CH3
H2
C
CH3CH2OH
+
Br
more hindered
H
71%
H
CH3
H2
C
27%
(CH3)3COH
+
Br
least
hindered
28%
Saytzeff
E. E2 eliminations are stereospecific
72%
Hoffmann
•E2 elimination requires a coplanar arrangement of orbitals in the transition state.
Remember: anti coplanar arrangement is lower in energy than syn-coplanar arrangement
due to both steric and electrostatic repulsion.
B:
B:
X
H
H
R
R'
R
H
RR
X
180° anti H-X
steric and electrostatic
repulsion
H R'
0° syn H-X
staggered
eclipsed
low energy conformer
high-energy conformer
• E2 elimination is stereospecific: different isomers of the starting materials produce
different isomers of products:
-OCH
3
Ph
NaOCH3
H
H
Br
S
CH3
Ph
Ph
CH3
H
Ph
trans phenyl
R
-OCH
3
H
H
Br
Ph
Ph
CH3
H
NaOCH3
CH3
Ph
Ph
R
cis phenyl
R
F. E2 reactions in cyclohexanes
A trans-diaxial arrangement of H-X is preferred for elimination, which means that both H
and X must be axial on the chair.
Example:
CH3
NaOCH3
CH3
CH3
+
Br
96%
0%
Br
CH3
CH3
Br
H
CH3O-
CH3
CH3
Trans-decalin ring systems are rigid and therefore cannot undergo a ring flip. Explain
why the anti bromo-methyl isomer below can undergo elimination, while the synbromomethyl isomer cannot:
H
Br
NaOCH3
CH3
H
H
H
H3C
Br
CH3
-OCH
3
H
H
NaOCH3
no reaction
Br
H
H3C
CH3 Br
G. Dehalogenation of Vicinal Dihalides
Dehalogenation of vicinal dihalides by iodide ion occurs stereospecifically and
concertedly via an E2 mechanism. An anti-coplanar arrangement of both bromine atoms
is required:
IBr
NaI
H
Ph
H
H
Ph
Ph
Ph
H
acetone
Br
IBr
R
R'
R
H
Br
180° anti Br-Br
staggered
Reduction of vicinal dibromides by zinc metal proceeds by way of oxidative insertion of
Zn(0) into a C-Br bond, producing an organozinc species which undergoes
dehalogenation:
Zn(0)
CH3
CH3
Br
H 3C
H 3C
BrZn
H 3C
H 3C
Br
CH3
CH3
H 3C
Br
H3C
CH3
CH3
+ ZnBr2
ZnBr
H 3C
H 3C
CH3
CH3
Br
H. Dehydrogenation of Alkanes
Dehydrogenation of alkanes is an entropically favored but enthalpically disfavored
process
Thus, at room temperature, the reverse reaction predominates; at 500°C, however, the
forward reaction takes place to give an industrial synthesis of alkenes.
H
H
catalyst
+
H2
ΔS>0
ΔH>0
Additional Problems for practice:
1.) Predict the major alkene product from each of the following eliminations:
EtO-
CH3COOH
CH3
H3C
Br
H3C
Br
H 3C
CH3
EtO-
CH3
Br
H 3C
H 3C
(CH3)3CO-
CH3
Br
H3C
heat
H 3C
2.) Show the structure and stereochemistry of the alkenes that result from
elimination of the following 3-phenyl-2 butanol tosylates:
CH3
H 3C
CH3CH3O-
H
H
OTos
2R, 3S
CH3CH3O2R, 3R
CH3CH3O2S, 3R
CH3CH3O2S, 3S
3.) Optically active 2-butanol slowly racemizes on standing in dilute
sulfuric acid. Propose a mechanism to account for this observation
4) Account for the different outcomes when menthyl chloride is subjected to the
following conditions:
NaOEt
EtOH,
100°C
H3C
H3C
Cl
EtOH
160°
+
H 3C
H3C