Transcript Document

Dehydrohalogenation of
Alkyl Halides
E2 and E1 Reactions in Detail
b-Elimination Reactions Overview
dehydration of alcohols:
X = H; Y = OH
dehydrohalogenation of alkyl halides:
X = H; Y = Br, etc.
X
C
b
Ca Y
C
C
+
X
Y
b-Elimination Reactions Overview
dehydration of alcohols:
acid-catalyzed
dehydrohalogenation of alkyl halides:
consumes base
X
C
b
Ca Y
C
C
+
X
Y
Dehydrohalogenation
is a useful method for the preparation of alkenes
Cl
NaOCH2CH3
ethanol, 55°C
(100 %)
likewise, NaOCH3 in methanol, or KOH in ethanol
Dehydrohalogenation
When the alkyl halide is primary, potassium
tert-butoxide in dimethyl sulfoxide is the
base/solvent system that is normally used.
CH3(CH2)15CH2CH2Cl
KOC(CH3)3
dimethyl sulfoxide
CH3(CH2)15CH
(86%)
CH2
Regioselectivity
KOCH2CH3
Br
+
ethanol, 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 b-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
+
(85%)
(15%)
more stable configuration
of double bond predominates
Mechanism of the
Dehydrohalogenation of Alkyl Halides:
The E2 Mechanism
Facts
Dehydrohalogenation of alkyl halides
exhibits second-order kinetics
first order in alkyl halide
first order in base
rate = k[alkyl halide][base]
implies that rate-determining step
involves both base and alkyl halide;
i.e., it is bimolecular
Facts
Rate of elimination depends on halogen
weaker C—X bond; faster rate
rate: RI > RBr > RCl > RF
implies that carbon-halogen bond breaks in
the rate-determining step
The E2 Mechanism
concerted (one-step) bimolecular process
single transition state
C—H bond breaks
p component of double bond forms
C—X bond breaks
The E2 Mechanism
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The E2 Mechanism
R
.. –
O
.. :
H
C
C
: X:
..
Reactants
The E2 Mechanism
R
.. –
O
.. :
H
C
C
: X:
..
Reactants
The E2 Mechanism
R
d–
..
O
..
H
Transition state
C
C
d–
: X:
..
The E2 Mechanism
R
..
O
..
H
C
C
.. –
: X:
..
Products
Anti Elimination in E2 Reactions
Stereoelectronic Effects
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
X
More stable conformation than syn-eclipsed
The best orbital overlap of the interacting orbitals is
achieved through back side attack of the leaving
group X as in an SN2 displacement.
Regioselectivity
Configuration of the Reactant
Elimination from Cyclic Compounds
H
Br
H
Br
Configuration must be trans, which is (anti).
Stereoelectronic effect
Br
KOC(CH3)3
(CH3)3COH
(CH3)3C
cis-1-Bromo-4-tertbutylcyclohexane
(CH3)3C
Stereoelectronic effect
(CH3)3C
trans-1-Bromo-4-tertbutylcyclohexane
Br
(CH3)3C
KOC(CH3)3
(CH3)3COH
Stereoelectronic effect
cis
Br
KOC(CH3)3
(CH3)3COH
(CH3)3C
Rate constant for
dehydrohalogenation
of cis is 500 times
greater than that of
trans
(CH3)3C
Br
(CH3)3C
trans
KOC(CH3)3
(CH3)3COH
Stereoelectronic effect
cis
Br
KOC(CH3)3
(CH3)3COH
(CH3)3C
H H
(CH3)3C
H that is removed by base must be anti
periplanar to Br
Two anti periplanar H atoms in cis
stereoisomer
Stereoelectronic effect
trans
H
Br
H
(CH3)3C
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
cis
more reactive
trans
less reactive
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.
E2 in a cyclohexane ring
E2 in a cyclohexane ring
H3 C
Cis or trans?
Axial or equatorial?
CH3
Cl
neomenthyl
Cl
e,e  a,a
+
CH3
menthyl
H3 C
CH3
+
CH3 CH2 O-
CH3
CH3
CH3
a,e  e,a
+
H3 C
H3 C
CH3
CH3
80%
H3 C
CH 3
20%
CH3 CH2 O-
CH 3
100%
Can you explain
predict the
the products?
products?
Cyclohexane Stereochemistry Revisited
http://www.csir.co.za/biochemtek/newsletter/aug/menthol.html
How many stereoisomers are possible for menthol?
l-menthol
http://www.library.ucsf.edu/tobacco/batco/html/9000/9036/
A Different Mechanism for Alkyl
Halide Elimination:
The E1 Mechanism
Example
CH3
CH3
CH2CH3
C
Br
Ethanol, heat
H3C
CH3
H2C
+
C
CH2CH3
(25%)
H
C
C
CH3
H3C
(75%)
The E1 Mechanism
1. Alkyl halides can undergo elimination in
absence of base.
2. Carbocation is intermediate
3. Rate-determining step is unimolecular
ionization of alkyl halide.
CH3
Step 1
CH3
CH2CH3
C
: Br:
..
slow, unimolecular
CH3
C
CH3 + CH2CH3
.. –
: Br :
..
CH3
Step 2
CH3
C
+
CH2CH3
– H+
CH3
CH2
+
C
CH3
CH2CH3
C
CH3
CHCH3
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
Summary & Applications (Synthesis)
SN1 / E1 vs. SN2 / E2
E2 and E1 Reactions
Substitution vs. Elimination
Alkyl halides can undergo SN2, SN1, E2 and E1 Reactions
1) Which reaction conditions favor SN2/E2 or SN1/E1?
•SN2/E2 reactions are favored by a high
concentration of nucleophile/strong base
•SN1/E1 reactions are favored by a poor
nucleophile/weak base
2) What will be the relative distribution of substitution product
vs. elimination product?
Consider the Substrate
NOTE: a bulky base encourages elimination over substitution
Returning to Sn2 and E2:
Considering the differences
Br
+
CH3 O-
O
+
CH3Br
OCH3
Can you explain
predict the
the products?
products?
Substitution and Elimination Reactions
in Synthesis
A hindered alkyl halide should be used if you
want to synthesize an alkene
Which reaction produces an ether?
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
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.
Designing a synthesis …
?
CH3
?
CH3
Br
Br