Dehydrohalogenation of Alkyl Halides E2 and E1 Reactions in Detail

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Dehydrohalogenation of Alkyl Halides E2 and
E1 Reactions in Detail
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b-Elimination Reactions Overview

• dehydration of alcohols X H Y OH
• dehydrohalogenation of alkyl halides X H Y
  Br, etc.

Y
X
a
b
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b-Elimination Reactions Overview

• dehydration of alcohols acid-catalyzed
• dehydrohalogenation of alkyl halides consumes
  base

Y
X
a
b
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Dehydrohalogenation

• is a useful method for the preparation of alkenes

NaOCH2CH3
ethanol, 55C
(100 )
likewise, NaOCH3 in methanol, or KOH in ethanol
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Dehydrohalogenation

• When the alkyl halide is primary,
  potassiumtert-butoxide in dimethyl sulfoxide is
  the base/solvent system that is normally used.

KOC(CH3)3
CH3(CH2)15CH2CH2Cl
dimethyl sulfoxide
(86)
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Regioselectivity

71
29

• follows Zaitsev's rule
• More highly substituted double bond predominates
  More Stable

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Zaitsevs Rule
The more substituted alkene is obtained when a
proton is removed from the b-carbon that is
bonded to the fewest hydrogens
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Conjugated alkenes are preferred !
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Steric hindrance effects the product distribution
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Stereoselectivity
Br

(23)
(77)

• more stable configurationof double bond
  predominates

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Stereoselectivity

(85)
(15)

• more stable configurationof double bond
  predominates

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Mechanism of theDehydrohalogenation of Alkyl
HalidesThe E2 Mechanism
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Facts

• Dehydrohalogenation of alkyl halides
  exhibits second-order kinetics
• first order in alkyl halide first order in
  base rate kalkyl halidebase
• implies that rate-determining step involves
  both base and alkyl halide i.e., it is
  bimolecular

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Facts

• Rate of elimination depends on halogen
• weaker CX bond faster rate rate RI gt
  RBr gt RCl gt RF
• implies that carbon-halogen bond breaks in the
  rate-determining step

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The E2 Mechanism

• concerted (one-step) bimolecular process
• single transition state
• CH bond breaks
• p component of double bond forms
• CX bond breaks

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The E2 Mechanism
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The E2 Mechanism

O
Reactants
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The E2 Mechanism

O
Reactants
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The E2 Mechanism
d
..
H
O
R
..
Transition state
C C
d
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The E2 Mechanism
..
H
O
R
..
C C
Products
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Anti Elimination in E2 Reactions

• Stereoelectronic Effects

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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
More stable conformation than syn-eclipsed
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The best orbital overlap of the interacting
orbitals is achieved through back side attack of
the leaving group X as in an SN2 displacement.
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Regioselectivity
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Configuration of the Reactant
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Elimination from Cyclic Compounds
Configuration must be trans, which is (anti).
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Stereoelectronic effect
KOC(CH3)3(CH3)3COH
cis-1-Bromo-4-tert- butylcyclohexane
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Stereoelectronic effect
trans-1-Bromo-4-tert- butylcyclohexane
KOC(CH3)3(CH3)3COH
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Stereoelectronic effect
cis
KOC(CH3)3(CH3)3COH

• Rate constant for dehydrohalogenation of cis is
  500 times greater than that of trans

KOC(CH3)3(CH3)3COH
trans
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Stereoelectronic effect
cis
KOC(CH3)3(CH3)3COH
H
H

• H that is removed by base must be anti
  periplanar to Br
• Two anti periplanar H atoms in cis stereoisomer

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Stereoelectronic effect
trans
KOC(CH3)3(CH3)3COH

• 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

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Stereoelectronic effect
cis
more reactive
trans
less reactive
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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.

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E2 in a cyclohexane ring
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E2 in a cyclohexane ring
Cis or trans? Axial or equatorial?
a,e ? e,a
e,e ? a,a
Can you predict the products?
Can you explain the products?
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Cyclohexane Stereochemistry Revisited
http//www.csir.co.za/biochemtek/newsletter/aug/me
nthol.html
How many stereoisomers are possible for menthol?
l-menthol
http//www.library.ucsf.edu/tobacco/batco/html/900
0/9036/
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A Different Mechanism for Alkyl Halide
EliminationThe E1 Mechanism
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Example
CH3
CH2CH3
CH3
Br
Ethanol, heat

(75)
(25)
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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.

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Step 1
slow, unimolecular
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Step 2
H
CH3
CH2

C
C
CHCH3
CH3
CH2CH3
CH3
Which alkene is more stable and why?
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Reaction coordinate diagram for the E1 reaction
of 2-chloro-2-methylbutane
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Must consider possible carbocation rearrangement
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Stereochemistry of the E1 Reaction
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E1 Elimination from Cyclic Compounds
E1 mechanism involves both syn and anti
elimination
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Summary Applications (Synthesis) SN1 / E1 vs.
SN2 / E2
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E2 and E1 Reactions
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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?
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Consider SN1/E1 vs. SN2/E2
Consider the Substrate
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NOTE a bulky base encourages elimination over
substitution
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Returning to Sn2 and E2Considering the
differences
Can you predict the products?
Can you explain the products?
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Substitution and Elimination Reactions in
Synthesis
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A hindered alkyl halide should be used if you
want to synthesize an alkene
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Which reaction produces an ether?
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Consecutive E2 Elimination Reactions Alkynes
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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

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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.
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Designing a synthesis
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