dehydrohalogenation of alkyl halides e2 and e1 reactions ... · dehydrohalogenation of alkyl...
TRANSCRIPT
Dehydrohalogenation of
Alkyl Halides
E2 and E1 Reactions in Detail
X Y
dehydration of alcohols:
X = H; Y = OH
dehydrohalogenation of alkyl halides:
X = H; Y = Br, etc.
abC CC C + X Y
b-Elimination Reactions Overview
X Y
dehydration of alcohols:
acid-catalyzed
dehydrohalogenation of alkyl halides:
consumes base
abC CC C + X Y
b-Elimination Reactions Overview
is a useful method for the preparation of alkenes
(100 %)
likewise, NaOCH3 in methanol, or KOH in ethanol
NaOCH2CH3
ethanol, 55°C
Dehydrohalogenation
Cl
CH3(CH2)15CH2CH2Cl
When the alkyl halide is primary, potassium
tert-butoxide in dimethyl sulfoxide is the
base/solvent system that is normally used.
KOC(CH3)3
dimethyl sulfoxide
(86%)
CH2CH3(CH2)15CH
Dehydrohalogenation
Br
29 % 71 %
+
Regioselectivity
follows Zaitsev's rule
More highly substituted double bond
predominates = More Stable
KOCH2CH3
ethanol, 70°C
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
more stable configurationof double bond predominates
Stereoselectivity
KOCH2CH3
ethanol
Br
+
(23%) (77%)
more stable configurationof double bond predominates
Stereoselectivity
KOCH2CH3
ethanol
+
(85%) (15%)
Br
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
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
The E2 Mechanism
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–
OR..
.. :
C C
H
X..::
Reactants
The E2 Mechanism
–
OR..
.. :
C C
H
X..::
Reactants
The E2 Mechanism
C C
d–
OR..
..H
X..::d–
Transition state
The E2 Mechanism
OR..
..H
C C
–X..
::..
Products
The E2 Mechanism
Stereoelectronic Effects
Anti Elimination in E2 Reactions
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
XMore 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
Configuration must be trans, which is (anti).
H
Br
H
Br
(CH3)3C
(CH3)3C
Br
KOC(CH3)3
(CH3)3COH
cis-1-Bromo-4-tert-
butylcyclohexane
Stereoelectronic effect
(CH3)3C
(CH3)3C
Br KOC(CH3)3
(CH3)3COH
trans-1-Bromo-4-tert-
butylcyclohexane
Stereoelectronic effect
(CH3)3C
(CH3)3C
Br
(CH3)3C
Br
KOC(CH3)3
(CH3)3COH
KOC(CH3)3
(CH3)3COH
cis
trans
Rate constant for
dehydrohalogenation
of cis is 500 times
greater than that of
trans
Stereoelectronic effect
(CH3)3C
(CH3)3C
Br
KOC(CH3)3
(CH3)3COH
cis
H that is removed by base must be anti
periplanar to Br
Two anti periplanar H atoms in cis
stereoisomer
HH
Stereoelectronic effect
(CH3)3C
KOC(CH3)3
(CH3)3COH
trans
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
HH
(CH3)3C
BrH
H
Stereoelectronic effect
cis
more reactive
trans
less reactive
Stereoelectronic effect
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
Cl
C
H
3
C
H
3
C
H
3
C
H
3
C
H
3
C
H
3
Cl
C
H
3
C
H
2
O
-
C
H
3
C
H
2
O
-
+
+
menthyl
neomenthyl
Can you predict the products?
Cis or trans?
Axial or equatorial?
a,e e,a
e,e a,a
C
H
3
C
H
3
C
H
3
C
H
3
C
H
3
C
H
3
+
80% 20%
Can you explain the products?
C
H
3
C
H
3
C
H
3
100%
Cyclohexane Stereochemistry Revisited
http://www.csir.co.za/biochemtek/newsletter/aug/menthol.html
l-menthol
http://www.library.ucsf.edu/tobacco/batco/html/9000/9036/
How many stereoisomers are possible for menthol?
A Different Mechanism for Alkyl
Halide Elimination:
The E1 Mechanism
CH3 CH2CH3
Br
CH3
Ethanol, heat
+
(25%) (75%)
C
H3C
CH3
C C
H3C
H
CH2CH3
CH3
CH2C
Example
1. Alkyl halides can undergo elimination in
absence of base.
2. Carbocation is intermediate
3. Rate-determining step is unimolecular
ionization of alkyl halide.
The E1 Mechanism
slow, unimolecular
CCH2CH3CH3
CH3
+
CH3 CH2CH3
Br
CH3
C
:..
:
:..
: Br.. –
Step 1
CCH2CH3CH3
CH3
+
CCH2CH3CH3
CH2
+ CCHCH3CH3
CH3
– H+
Step 2
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
Can you predict the products?
Br
O
C
H
3
B
r
C
H
3
O
-
+
+
O
C
H
3
Can you explain the 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?
CH3CH2Br CH3CO-
CH3
CH3
+
CH3CH2O- CH3CBr
CH3
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 five-
or 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
