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Chapter 8
Alkyl Halides and Elimination reactions
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There will be 10 minute quiz on following questions.
On the April 17th (Thursday)
1.
2.
What is Zaitsev rule ?
Which halide undergo elimination reaction faster than others
a) under E1 mechanism?
b) under E2 mechanism?
R3CX,, R2CHX, RCH2X
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An Overview of Functional Groups
Compounds containing C-Z s Bonds
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An Overview of Functional Groups
Hydrocarbons
Hydrocarbons are compounds made up of only the elements carbon
and hydrogen. They may be aliphatic or aromatic.
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Compounds Containing a C=O Group
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Kinds of Organic Reactions
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Alkyl Halides and Nucleophilic Substitution
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Alkyl Halides and Elimination Reactions
General Features of Elimination
It is well known that elimination reactions (E) often compete successfully
with SN reactions, because nucleophiles are also Brønsted-Lowry bases (SN2
versus E2) and carbocations are prone to the elimination of a proton (again
involving a Brønsted-Lowry base: SN1 versus E1).
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Alkyl Halides and Elimination Reactions
General Features of Elimination
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Alkyl Halides and Elimination Reactions
General Features of Elimination
• Removal of the elements HX is called dehydrohalogenation.
• Dehydrohalogenation is an example of  elimination
(1,2-elimination).
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Alkyl Halides and Elimination Reactions
General Features of Elimination
• bases used in elimination reactions : RO¯ ( alkoxides).
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Alkyl Halides and Elimination Reactions
General Features of Elimination
•
How to draw any product of dehydrohalogenation
1.
Find the  carbon.
2.
Identify all  carbons with H atoms.
3.
Remove the elements of H and X from the  and  carbons and form a 
bond.
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Alkyl Halides and Elimination Reactions
Alkenes—The Products of Elimination
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Alkyl Halides and Elimination Reactions
Alkenes—The Products of Elimination
• Alkenes are classified according to the number of carbon atoms
bonded to the carbons of the double bond.
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Alkyl Halides and Elimination Reactions
Alkenes—The Products of Elimination
• rotation about double bonds is restricted.
diastereomers
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Alkyl Halides and Elimination Reactions
Stability of Alkenes
• In general, trans alkenes are more stable than cis
alkenes because the groups bonded to the double bond
carbons are further apart, reducing steric interactions.
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Alkyl Halides and Elimination Reactions
Stability of Alkenes
• The stability of an alkene increases as the number of R
groups bonded to the double bond carbons increases.
• The higher the percent s-character, the more readily an atom
accepts electron density. Thus, sp2 carbons are more able to
accept electron density and sp3 carbons are more able to
donate electron density.
• Consequently, increasing the number of electron donating
groups on a carbon atom able to accept electron density
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makes the alkene more stable.
Alkyl Halides and Elimination Reactions
Stability of Alkenes
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Alkyl Halides and Elimination Reactions
Mechanisms of Elimination
• There are two mechanisms of elimination—E2 and E1,
just as there are two mechanisms of substitution, SN2
and SN1.
• E2 mechanism—bimolecular elimination
• E1 mechanism—unimolecular elimination
• The E2 and E1 mechanisms differ in the timing of bond
cleavage and bond formation, analogous to the SN2 and
SN1 mechanisms.
• E2 and SN2 reactions have some features in common, as
do E1 and SN1 reactions.
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Alkyl Halides and Elimination Reactions
Mechanisms of Elimination—E2
• The most common mechanism for dehydrohalogenation
• second-order kinetics : both the alkyl halide and the
base appear in the rate equation, i.e.,
rate = k[(CH3)3CBr][¯OH]
• One step mechanism : all bonds are broken and formed
in a single step. -- The reaction is concerted
CH3
CH3
C
Br
OH
_
CH3
C
CH2 +
H2O +
Br
_
CH3
CH3
E2 mechanism
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Alkyl Halides and Elimination Reactions
Mechanisms of Elimination—E2
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Alkyl Halides and Elimination Reactions
Mechanisms of Elimination—E2
• There are close parallels between E2 and SN2 mechanisms in
how the identity of the base, the leaving group and the
solvent affect the rate.
• The base appears in the rate equation, so the rate of the E2
reaction increases as the strength of the base increases.
• E2 reactions are generally run with strong, negatively charged
bases like¯OH and ¯OR. Strong sterically hindered (nonnucleophilic) nitrogen bases (DBN and DBU) are also
sometimes used.
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Alkyl Halides and Elimination Reactions
DBN
..
N
..
N
..
N
..
N
DBU
1,5-diazabicyclo[4.3.0]non-5-ene and 1.8-diazobicylco[5.4.0]undec-7-ene
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Alkyl Halides and Elimination Reactions
Mechanisms of Elimination—E2 : the leaving group
the solvent
Acetone, DMF, DMSO
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Alkyl Halides and Elimination Reactions
Mechanisms of Elimination—E2 : nature of R group
Substitution v.s. elimination
i.e. more substitution lowers Ea
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Alkyl Halides and Elimination Reactions
Mechanisms of Elimination—E2
slower
faster
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Alkyl Halides and Elimination Reactions
Mechanisms of Elimination—E2
Table 8.2 summarizes the characteristics of the E2 mechanism.
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Alkyl Halides and Elimination Reactions
Mechanisms of Elimination—E2
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Alkyl Halides and Elimination Reactions
The Zaitsev (Saytzeff) Rule
• The major product is the more stable product—the one with
the more substituted double bond.
• This phenomenon is called the Zaitsev rule. (1875)
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Alkyl Halides and Elimination Reactions
The Zaitsev (Saytzeff) Rule
• The Zaitsev rule: the major product in  elimination has the more
substituted double bond.
• A reaction is regioselective when it yields predominantly or
exclusively one constitutional isomer when more than one is
possible. Thus, the E2 reaction is regioselective.
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If the stereochemistry is known,
the outcome is not always the same.
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Alkyl Halides and Elimination Reactions
cf. stereoselective
• When a mixture of stereoisomers is possible from a
dehydrohalogenation, the major product is the more stable
stereoisomer.
• A reaction is stereoselective when it forms predominantly or
exclusively one stereoisomer when two or more are possible.
• The E2 reaction is stereoselective because one stereoisomer
is formed preferentially.
Why?
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Alkyl Halides and Elimination Reactions
Stereochemistry of the E2 Reaction
• In the transition state of an E2 reaction all involved atoms should
be aligned in the same plane.
one hydrogen atom, two carbon atoms, the leaving group (X)
There are two ways for the C—H and C—X bonds to be coplanar.
• E2 elimination occurs most often in the anti periplanar geometry.
This is all about orbital alignment.
This arrangement allows the molecule to react in the lower energy
staggered conformation, and allows the incoming base and
leaving group to be further away from each other.
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Alkyl Halides and Elimination Reactions
Stereochemistry of the E2 Reaction
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Alkyl Halides and Elimination Reactions
Stereochemistry of the E2 Reaction
• In cyclic compounds, the stereochemical requirement of an anti
periplanar geometry in an E2 reaction has important
consequences.
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• For E2 elimination, the C-Cl bond must be anti periplanar to the
C—H bond on a  carbon, and this occurs only when the H and
Cl atoms are both in the axial position. The requirement for trans
diaxial geometry means that elimination must occur from the
less stable conformer, B.
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Alkyl Halides and Elimination Reactions
Stereochemistry of the E2 Reaction
• The cis isomer
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Alkyl Halides and Elimination Reactions
Stereochemistry of the E2 Reaction
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Alkyl Halides and Elimination Reactions
Stereochemistry of the E2 Reaction
• The trans isomer.
This is not predicted by the Zaitsev rule.
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If the stereochemistry is known,
the outcome is not always the same.
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Alkyl Halides and Elimination Reactions
Mechanisms of Elimination— E1 mechanism
CH3
CH3
C
H2O
CH3
CH3
C
CH2
+
+
H3O +
I
_
CH3
I
E1 mechanism
• An E1 reaction exhibits first-order kinetics:
rate = k[(CH3)3CCI]
• The E1 reaction proceeds via a two-step mechanism: the
bond to the leaving group breaks first before the  bond is
formed. The slow step is unimolecular, involving only the
alkyl halide.
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Alkyl Halides and Elimination Reactions
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Alkyl Halides and Elimination Reactions
E1 Mechanisms
CH3
CH3
C
H2O
CH3
CH3
C
CH2
+
+
H3O +
I
_
CH3
I
E1 mechanism
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Alkyl Halides and Elimination Reactions
Other characteristics of E1 reactions
• The rate of an E1 reaction increases as the number of R groups on the
carbon with the leaving group increases.
• The strength of the base usually determines whether a reaction follows the
E1 or E2 mechanism. Strong bases like ¯OH and ¯OR favor E2 reactions,
whereas weaker bases like H2O and ROH favor E1 reactions.
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Alkyl Halides and Elimination Reactions
E1 Mechanisms
• E1 reactions are regioselective, favoring formation of the more
substituted, more stable alkene.
• Zaitsev’s rule applies to E1 reactions also.
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Alkyl Halides and Elimination Reactions
Mechanisms of Elimination—E1
Table 8.3 summarizes the characteristics of the E1 mechanism.
No need of antiperiplanar arrangement
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Alkyl Halides and Elimination Reactions
SN1 and E1 Reactions
• SN1 and E1 reactions have exactly the same first step—formation
of a carbocation. They differ in what happens to the carbocation.
• Because E1 reactions often occur with a competing SN1 reaction, E1 reactions of
alkyl halides are much less useful than E2 reactions.
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Alkyl Halides and Elimination Reactions
SN1 and E1 Reactions
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Alkyl Halides and Elimination Reactions
When is the Mechanism E1 or E2?
• Strong bases favor the E2 mechanism.
• Weak bases favor the E1 mechanism.
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Alkyl Halides and Elimination Reactions
E2 Reactions and Alkyne Synthesis
• A single elimination reaction produces a  bond of an
alkene. Two consecutive elimination reactions produce
two  bonds of an alkyne.
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Alkyl Halides and Elimination Reactions
E2 Reactions and Alkyne Synthesis
• Two elimination reactions are needed to remove two
moles of HX from a dihalide substrate.
• Two different starting materials can be used—a vicinal
dihalide or a geminal dihalide.
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Alkyl Halides and Elimination Reactions
E2 Reactions and Alkyne Synthesis
• Stronger bases are needed to synthesize alkynes by
dehydrohalogenation than are needed to synthesize alkenes.
• Because sp2 hybridized C—H bonds are stronger than sp3
hybridized C—H bonds. As a result, a stronger base is needed
to cleave this bond.
• The typical base used is ¯NH2 (amide), used as the sodium salt
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of NaNH2. KOC(CH3)3 can also be used with DMSO as solvent.
Alkyl Halides and Elimination Reactions
E2 Reactions and Alkyne Synthesis
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Alkyl Halides and Elimination Reactions
Predicting the Mechanism from the Reactants—SN1,
SN2, E1 or E2.
t-BuOK
t-BuOH
H3C
H2
C Br
NaI
MeOH
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Alkyl Halides and Elimination Reactions
Predicting the Mechanism from the Reactants—SN1,
SN2, E1 or E2.
• Good nucleophiles that are weak bases favor
substitution over elimination —Certain anions generally
give products of substitution because they are good
nucleophiles but weak bases. These include I¯, Br¯, HS¯,
¯CN, and CH3COO¯.
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Alkyl Halides and Elimination Reactions
Predicting the Mechanism from the Reactants—SN1,
SN2, E1 or E2.
• Bulky nonnucleophilic bases favor elimination over
substitution —KOC(CH3)3, DBU, and DBN are too
sterically hindered to attack tetravalent carbon, but are
able to remove a small proton, favoring elimination over
substitution.
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Alkyl Halides and Elimination Reactions
Predicting the Mechanism from the Reactants—SN1, SN2, E1 or E2.
Tertiary Alkyl Halides
2-methylpropene
C2H5O-Na+
C2H5OH
CH3
CH3
C
CH3
OC2H5
3%
CH3
C
CH2
CH3
CH3
CH3
C
and
97%
Br
CH3
CH3
2-bromo-2-methyl-propane
CH3
C2H5OH
heat
C
OC2H5 and
CH3
80%
CH3
C
CH2
CH3
20%
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2-ethoxy-2-methylpropane
Alkyl Halides and Elimination Reactions
Predicting the Mechanism from the Reactants—SN1, SN2, E1 or E2.
Tertiary Alkyl Halides
E2 will occur preferentially if a strong base is used (OH-, OR-). Reaction in neutral
(weakly basic) conditions leads to a mixture of SN1 and E1 products, with usually
the SN1 product favored.
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Alkyl Halides and Elimination Reactions
Predicting the Mechanism from the Reactants—SN1, SN2, E1 or E2.
Primary Alkyl Halides
SN2 is favored by use of a good nucleophile (RS-, I-, CN-, Br-) and polar aprotic
solvent. E2 is favored by use of a strong, hindered base (tert-butoxide).
t-BuO-K+
Na+CNCH3CH2CH2CH2
CN
pentanenitrile (90%)
CH3CH2CH2CH2
THF-HMPA
1-bromobutane
Br
CH3CH2CH
CH2
1-butene (85%)
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Alkyl Halides and Elimination Reactions
Predicting the Mechanism from the Reactants—SN1, SN2, E1 or E2.
Secondary Alkyl Halides
SN2 and E2 compete.
If a weakly basic strong nucleophile (CH3COO-, Br-, I-) and polar aprotic solvent is
used, SN2 dominates.
If a strong base (OR-) in a protic solvent is used, E2 is dominant.
OOCCH3
CH3CHCH3
2-propyl acetate
(100%)
CH3CH
propene
OC2H5
CH3COO-Na+
C2H5O-Na+
CH3CHCH3
DMSO
CH2
Br
CH3CHCH3
2-ethoxypropane (20%)
C2H5OH
2-bromopropane
CH3CH
CH2
propene (80%)
(0%)
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Alkyl Halides and Elimination Reactions
Predicting the Mechanism from the Reactants—SN1, SN2, E1 or E2.
Secondary Alkyl Halides
If only a weak nucleophile or base is present then SN1 competes with E1 and it is
difficult to predict which will be favored.
This is a situation that is best avoided.
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Homework
8.18, 8.22, 8.24, 8.31, 8.33,
8.40, 8.41, 8.45, 8.49, 8.50,
8.53, 8.54, 8.57
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Preview of Chapter 9
Alcohols, Ethers and Epoxides
Preparation of alcohols, ethers, and epoxides
Another example of substitution
Reactions of alcohols, ethers and epoxides
Dehydration – carbocation -- rearrangement
-Alcohols to alkyl halides
- opening of epoxides
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there will be the 3rd quiz
On April 25th (Friday)!
Covering chapters 7and 8
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