β-Elimination Reactions Overview
dehydration of alcohols:
X = H; Y = OH
Dehydrohalogenation of
Alkyl Halides
dehydrohalogenation of alkyl halides:
X = H; Y = Br, etc.
E2 and E1 Reactions in Detail
X βC
β-Elimination Reactions Overview
+
X
Y
is a useful method for the preparation of alkenes
dehydrohalogenation of alkyl halides:
consumes base
C
Cα Y
C
Dehydrohalogenation
dehydration of alcohols:
acid-catalyzed
X C
β
C
Cα Y
C
Cl
+
X
NaOCH2CH3
ethanol, 55°
55°C
Y
(100 %)
likewise, NaOCH3 in methanol, or KOH in ethanol
Regioselectivity
Dehydrohalogenation
When the alkyl halide is primary,
primary, potassium
terttert-butoxide in dimethyl sulfoxide is the
base/solvent system that is normally used.
Br
CH3(CH2)15CH2CH2Cl
KOC(CH3)3
dimethyl sulfoxide
CH3(CH2)15CH
(86%)
CH2
KOCH2CH3
+
ethanol, 70°
70°C
29 %
71 %
follows Zaitsev's rule
More highly substituted double bond
predominates = More Stable
Zaitsev’s Rule
The more substituted alkene is
obtained when a proton is removed
from the β-carbon that is bonded to
the fewest hydrogens
Conjugated alkenes are preferred !
Steric hindrance effects the product distribution
Stereoselectivity
KOCH2CH3
ethanol
Br
+
(23%)
(77%)
more stable configuration
of double bond predominates
Stereoselectivity
Br
KOCH2CH3
ethanol
Mechanism of the
Dehydrohalogenation of Alkyl Halides:
The E2 Mechanism
+
(85%)
(15%)
more stable configuration
of double bond predominates
Facts
Dehydrohalogenation of alkyl halides
exhibits second-order kinetics
first order in alkyl halide
first order in base
rate = k[alkyl halide][base]
Facts
Rate of elimination depends on halogen
weaker C—
C—X bond; faster rate
rate: RI > RBr > RCl > RF
implies that carbon-halogen bond breaks in
the rate-determining step
implies that rate-determining step
involves both base and alkyl halide;
i.e., it is bimolecular
The E2 Mechanism
concerted (one-step) bimolecular process
single transition state
C—H bond breaks
π component of double bond forms
C—X bond breaks
The E2 Mechanism
The E2 Mechanism
R
.. –
:
O
..
The E2 Mechanism
R
H
C
.. –
:
O
..
H
C
C
C
: X:
..
Reactants
: X:
..
Reactants
The E2 Mechanism
δ–
..
O
..
Transition state
R
The E2 Mechanism
H
R
C
..
O
..
H
C
C
δ–
: X:
..
C
.. –
: X:
..
Products
Stereochemistry of the E2 Reaction
Remember: The bonds to the eliminated groups (H
and X) must be in the same plane and anti to each
other
H
Anti Elimination in E2 Reactions
Stereoelectronic Effects
X
More stable conformation than syn-eclipsed
Regioselectivity
The best orbital overlap of the interacting orbitals is
achieved through back side attack of the leaving
group X as in an SN2 displacement.
Configuration of the Reactant
Elimination from Cyclic Compounds
H
Br
H
Br
Configuration must be trans, which is (anti).
Stereoelectronic effect
Stereoelectronic effect
Br
KOC(CH3)3
(CH3)3COH
(CH3)3C
cis-1Bromo-4-4-tert
tert-cis-1-Bromo
butylcyclohexane
(CH3)3C
(CH3)3C
trans-1Bromo-4-4-tert
tert-trans-1-Bromo
butylcyclohexane
Br
(CH3)3C
KOC(CH3)3
(CH3)3COH
Stereoelectronic effect
cis
Stereoelectronic effect
cis
Br
KOC(CH3)3
(CH3)3COH
(CH3)3C
Br
KOC(CH3)3
(CH3)3COH
(CH3)3C
H H
Rate constant for
dehydrohalogenation
of cis is 500 times
greater than that of
trans
(CH3)3C
Br
(CH3)3C
KOC(CH3)3
(CH3)3COH
trans
(CH3)3C
H that is removed by base must be anti
periplanar to Br
Two anti periplanar H atoms in cis
stereoisomer
Stereoelectronic effect
Stereoelectronic effect
trans
H
Br
(CH3)3C
H
cis
more reactive
KOC(CH3)3
(CH3)3COH
H H
(CH3)3C
H that is removed by base must be anti
periplanar to Br
No anti periplanar H atoms in trans
stereoisomer; all vicinal H atoms are
gauche to Br
Stereoelectronic effect
An effect on reactivity that has its origin in
the spatial arrangement of orbitals or bonds is
called a stereoelectronic effect.
The preference for an anti periplanar
arrangement of H and Br in the transition
state for E2 dehydrohalogenation is an
example of a stereoelectronic effect.
effect.
trans
less reactive
E2 in a cyclohexane ring
Cyclohexane Stereochemistry Revisited
E2 in a cyclohexane ring
H3 C
Cis or trans?
Axial or equatorial?
CH3
H3 C
CH3
+
CH3
neomenthyl
CH3
Cl
e,e ↔ a,a
+
+
CH3 CH2 O-
CH3
CH3
CH3
80%
H3 C
CH3
20%
CH3 CH2 O-
CH3
menthyl
H3 C
a,e ↔ e,a
Cl
H3 C
http://www.csir.co.za/biochemtek/newsletter/aug/menthol.html
CH3
100%
Can you predict
explain the
the products?
products?
How many stereoisomers are possible for menthol?
l-menthol
http://www.library.ucsf.edu/tobacco/batco/html/9000/9036/
Example
CH3
CH3
C
CH2CH3
Br
A Different Mechanism for Alkyl
Halide Elimination:
The E1 Mechanism
Ethanol, heat
H 3C
CH3
H 2C
+
C
H
C
CH2CH3
H 3C
(25%)
The E1 Mechanism
C
CH3
(75%)
CH3
Step 1
CH3
C
CH2CH3
:
: Br
..
1. Alkyl halides can undergo elimination in
absence of base.
2. Carbocation is intermediate
3. Rate-determining step is unimolecular
ionization of alkyl halide.
slow, unimolecular
CH3
CH3
C
+ CH2CH3
.. –
:
: Br
..
CH3
Step 2
CH3
C
+
CH2CH3
– H+
CH3
CH2
CH3
C
+
CH2CH3
CH3
C
CHCH 3
Which alkene is more stable and why?
Reaction coordinate diagram for the E1 reaction of
2-chloro-2-methylbutane
Must consider possible carbocation rearrangement
Stereochemistry of the E1 Reaction
E1 Elimination from Cyclic Compounds
E1 mechanism involves both syn and anti elimination
E2 and E1 Reactions
Summary & Applications (Synthesis)
SN1 / E1 vs. SN2 / E2
Substitution vs. Elimination
Alkyl halides can undergo S N2, S N1, E2 and E1 Reactions
1) Which reaction conditions favor S N2/E2 or S N1/E1?
•S N2/E2 reactions are favored by a high
concentration of nucleophile/strong base
•S N1/E1 reactions are favored by a poor
nucleophile/weak base
2) What will be the relative distribution of substitution product
vs. elimination product?
Consider SN1/E1 vs. S N2/E2
NOTE: a bulky base encourages elimination over substitution
Consider the Substrate
Substitution and Elimination Reactions
in Synthesis
Returning to Sn2 and E2:
Considering the differences
Br
+
CH3 O-
O
+
CH3Br
OCH3
Can you predict
explain the
the products?
products?
Which reaction produces an ether?
A hindered alkyl halide should be used if you
want to synthesize an alkene
CH3
CH3CH2Br + CH3COCH3
CH3
CH3CH2O- + CH3CBr
CH3
Consecutive E2 Elimination Reactions:
Alkynes
Intermolecular vs. Intramolecular Reactions
• A low concentration of reactant favors an intramolecular
reaction
• The intramolecular reaction is also favored when a fiveor six-membered ring is formed
Designing a synthesis …
Three- and four-membered rings are less easily formed
Three-membered ring compounds are formed more
easily than four-membered ring compounds
The likelihood of the reacting groups finding each other
decreases sharply when the groups are in compounds
that would form seven-membered and larger rings.
CH3
?
CH3
Br
Br
?