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Reaction of π Bonds
Remember discussion of reaction of alkenes using orbital analysis,
π bonds are far more reactive than σ bonds and they generally react as the nucleophile
σ* C-C
π* C-C
C (p)
C (sp3)
C (p)
C (sp3)
π C-C
σ C-C
C-C single bonds are relatively unreactive
due to large overlap of sp3 hybridized
orbital and energy match, therefore very
low HOMO and high LUMO energy
Atomic p orbital is higher in energy than sp3
(less s character) and the overlap for p orbitals
is much less to form π bond
Therefore orbitals do not mix as well for π bond
and thus HOMO does not lower in energy nor
LUMO raise in energy as much as σ bond
(already had seen this with weaker π bond)
C-C π bond will thus be far more reactive, and it will react preferentially as the nucleophile due to higher HOMO level
Electrophilic Addition to Alkenes
Alkenes generally react in an addition mechanism
(addition – two new species add to a molecule and none leave)
If hydrogen halides react, then a H and Cl add to the two ends of the double bond
H3C
CH3
Cl
!+ !H Cl
CH3
H3C
H
Since H-Cl is polarized, the H will be partially positively charged and Cl partially negative
The alkene is thus the nucleophile and the proton is the electrophile
The reaction is thus a two step reaction
The first step will generate a carbocation as a reactive intermediate
H3C
CH3
!+ !H Cl
Cl
CH3
H3 C
H
Cl
CH3
H3 C
H
And the second step will have the carbocation react with the chloride to yield the product
(the chloride is the nucleophile and the carbocation is the electrophile)
Since the carbocation is the most unstable structure, the first step is the rate determining step for this reaction
Regiochemistry of Alkene Additions
When E-2-butene was reacted with HCl, only one product can be obtained
H3C
CH3
!+ !H Cl
CH3
H3 C
Cl
Cl
CH3
H3 C
H
H
When an unsymmetrical alkene, however, like propene is reacted, two possible products are obtained (2-chloropropane or 1-chloropropane) (resulting from H and Cl adding to different ends of alkene)
Cl
Cl
!+ !H Cl
H3C
H3C
H3C
Cl
H3 C
H3 C
Cl
Since the carbocation is the high energy structure along the reaction coordinate, the energy of
activation will be determined by the stability of the possible carbocations in the first step
Since 2˚ carbocations are more stable than 1˚, 2-chloropropane is the only product obtained
Regiochemistry of Alkene Additions
Hammond postulate is used to predict the relative rates of propene addition, because the cation is the high energy structure along the reaction coordinate the transition state for this reaction closely resembles the cation structure, thus has a high amount of positive charge on the carbon
!+
H3C
!H Cl
H
H3 C
!Cl
!+
H3 C
H3 C
H3 C
Reaction Coordinate
Similar to a 2˚ cation is more stable than a 1˚ cation, a partial positive charge on a 2˚ carbon is more stable than a partial positive charge on a 1˚ carbon
Regiochemistry of Alkene Additions
The hydrogen halide reactions with alkenes follow “Markovnikov” addition
Markovnikov addition – in an electrophilic addition, the heavier atom adds to the more
substituted carbon
The physical meaning behind the Markovnikov addition is the electrophile adds in such a
way to generate the most stable intermediate
What does this imply for a hydrogen halide reaction?
(remember that the first step is the creation of a carbocation)
Cl
Cl
!+ !H Cl
H3C
Cl
H3 C
Markovnikov product
H3C
H3C
H3 C
Cl
Anti-Markovnikov
product
Regiochemistry of Alkene Additions
When considering an addition to an alkene, need to look at the two possible intermediate structures and compare their energies (the more stable one will therefore react with a faster rate)
Some factors that could influence stability:
Resonance effects
We have observed previously that especially with charged species, structures that can
resonate the charge onto multiple atoms are more stable than compounds that isolate the
charge on a single atom
pKa
~16
H3 C
H2
C
O
O
O
4.8
H3C
O
H3C
O
Regiochemistry of Alkene Additions
The same effect can be observed in the carbocation intermediates for alkene additions
Cl
CH3
H3C
Cl
CH3
H3 C
H Cl
or
Which is favored?
Cl
Cl
CH3
H3 C
H3C
CH2CH3
CH3
Cl
CH3
The chlorine atom has lone pair of electrons which can delocalize into empty p orbital of cation for resonance stabilization
The reaction of Z-2-butene with HCl thus only yields 2,2-dichlorobutane
Cl
H3 C
CH3
Cl
H Cl
H3 C
Cl Cl
CH3
H3 C
CH3
Regiochemistry of Alkene Additions
Any atom with lone pair of electrons adjacent to empty p orbital can stabilize cation through resonance, realize though that resonance can only occur with orbital alignment between adjacent atoms
OCH3
H+
OCH3
OH
H2O
OCH3
OCH3
The proton adds in the first step to generate the carbocation adjacent to the oxygen due to
resonance from the lone pair stabilizing the cation, thus directing the regiochemistry
Because the cation is more stable with resonance, the relative rate compared to alkenes without the possibility of resonance is higher
Relative Rate (25˚C)
H+/H2O
OCH3
OH
OCH3
H+/H2O
OH
5 x 1014
1
Regiochemistry of Alkene Additions
Resonance can also occur with extended p orbitals on adjacent carbon atoms
We observed the reaction of butadiene in discussing kinetic versus thermodynamic reactions
Isolated 1˚ cation
H+
or
2˚ cation in resonance
!+
OH2
H2 O
OH
!+
!+
OH2
OH
!+
Partial charge on 2˚ carbon
more stable than 1˚ carbon,
therefore top pathway is the
kinetic pathway
More substituted double
bond is more stable,
therefore bottom pathway is
the thermodynamic pathway
In practice, kinetic pathway is favored at low temperatures and thermodynamic pathway is favored at high temperatures
Effect of Hyperconjugation on Carbocation Stability
We have already observed that cations with more alkyl substituents are more stable than cations with less alkyl substituents
CH3
H3C
H
CH3
H3 C
H
CH3
H3 C
H
H
H
H
Stability
The reason is due to a type of resonance with the neighboring C-H bond called
“hyperconjugation”
H
H
H2C
CH3
CH3
The electrons in the neighboring C-H
bond stabilize the empty p orbital by
donating electron density
This effect can only occur with a
neighboring carbon, therefore 3˚ > 2˚ > 1˚ > methyl cation
H
H
H
H
H
H
H
H
The interaction is similar, but
different, than the interaction between
two p orbitals in an alkene
(less interaction due to further
distance in hyperconjugation)
Inductive Effects on Carbocation Stability
In addition to resonance and hyperconjugation, inductive effects can alter carbocation stability
Inductive means “through bond”
Both resonance and hyperconjugation occur through overlap of orbitals, not through the σ bond
H
H
H
H
H
Overlap of p
orbitals
H
H
H
H
Hyperconjugation
!-Cl
H!+
H
H
H
Inductive
Inductive effects, therefore, are due to dipoles caused by differences in electronegativity
Inductive Effects on Carbocation Stability
Inductive effects can either stabilize a carbocation (if electron donating towards cation) or destabilize a carbocation (if electron withdrawing from a cation)
Consider the electrophilic reaction of an allyl chloride Cl
Cl
HCl
Cl
Cl
!+
The dipole of C-Cl bond causes a
partial positive charge to be
placed adjacent to carbocation,
therefore destabilizing the cation
Relative Rates (25 ˚C)
CH3
1
OCH3
Cl
Cl
2 x 106
5 x 1014
1 x 10-4
Faster than 1
hyperconjugation
resonance
inductive
resonance
Resonance effect outweighs the inductive effect for these examples
Rearrangements in Alkene Additions
Rearrangements can occur whenever a carbocation is formed as an intermediate in a reaction
We observed carbocation intermediates in both E1 and SN1 reactions
Electrophilic addition of HX or H+/H20 to alkenes also form carbocation intermediates and thus
rearrangements may occur if a more stable carbocation can be formed after rearrangement
H3C CH3
HCl
H3 C
CH3
H3C CH3
CH3
H3C
H3C
H3C Cl
CH3
H3 C
CH3
CH3
As with all rearrangements, whether a hydride shift or alkyl shift, the orbitals must be aligned to allow the rearrangement to occur
CH3
H3 C
H3 C
H
CH3
H
CH3
H
No overlap of orbitals, rearrangement cannot occur
Rearrangements in Alkene Additions
In addition to the energy gain from going to a more substituted carbocation through
rearrangements, a shift could be energetic driven by formation of a more stable ring system
OH
OH
H+, H2O
4-membered ring
5-membered ring
(more stable)
Can also observe rearrangements to form smaller rings
(would need some other energy driving force)
OH
H+, H2O
OH
OH
OH
Resonance stabilized Need to have a vicinal diol
(called Pinacol rearrangement)
O
Hydroboration of Alkenes
We have already observed that alkenes can be converted to alcohols by reacting with acidic water
OH
H+, H2O
H3C
H3 C
H3C
CH3
CH3
A carbocation is formed as an intermediate which drives the reaction to Markovnikov product
Alcohols can also be formed from alkenes using a hydroboration route
Boron is less electronegative than carbon and thus can react as an electrophile
H3C
1) BH3•THF
2) H2O2, NaOH
H3 C
The reaction yields a different regioproduct (Anti-Markovnikov)
OH
Hydroboration of Alkenes
Boron is to the left of carbon in the periodic table
B
C
N
O
F
*therefore boron is electropositive compared to carbon
The neutral form of boron, BH3, is unstable
(it only has 6 electrons in the outer shell)
Boron often is complexed with an oxygen containing species to offer stability
O
Tetrahydrofuran
(THF)
BH3
!+ !O BH3
BH3•THF
Hydroboration of Alkenes
Due to the electropositive character of BH3, it will act as an electrophile in alkene reactions
H3C
BH3•THF
H3C
BH3
H3C !+
H !BH2
H
H3 C
BH2
A free carbocation is not formed however as the reaction never rearranges regardless of structure of the alkene
A cyclic transition state occurs instead where one of the B-H bonds is transferred to the
carbon, this process stabilizes the structure as the carbon never bears a full positive charge
The regiochemistry occurs which places the partial positive charge on the carbon better able
to stabilize the charge, after the transition state is passed and the hydrogen has been
transferred, the boron is located on the least substituted carbon and the hydrogen on the more
H3C CH3
H3C
1) BH3•THF
2) H2O2, NaOH
H3C CH3
H3 C
OH
Hydroboration of Alkenes
The boron can then be removed in a second step with basic hydrogen peroxide
H
H3 C
BH2 H3C
H
H3C
BR2
OH
O
BR2
OOH
H3 C
H3 C
The boron can react 2 more times with alkene
The oxidized boron then rearranges to a boronic ester [B(OR)3]
The boronic ester becomes hydrolyzed under the same basic aqueous conditions to generate the Anti-Markovnikov alcohol
H3 C
OBR2
NaOH
H2 O
H3 C
OH
OBR2
Hydroboration of Alkenes
Due to the boron and hydrogen adding in a cyclic transition state, both must attach to the same side of the double bond
(SYN addition)
BH3•THF
BH2
H
Upon oxidation, the alcohol replaces the boron in the same stereochemical position, therefore the alcohol and the H added in the first step are in a SYN orientation
BH2
H
H2O2, NaOH
OH
H
Formation of Alcohols from Alkenes
The methods shown can create different regio- and stereoproducts from alkenes
H+, H2O
OH
Acidic aqueous conditions forms the Markovnikov product, carbocation is formed which can rearrange if possible
1) BH3•THF
2) H2O2, NaOH
H
OH
Hydroboration/Oxidation conditions forms the Anti-Markovnikov product, no free carbocation is formed and addition occurs in a SYN manner
Methanol versus Ethanol Biochemically
Ethanol (which is known to lower inhibitions and cause a lightheadedness) is oxidized biochemically to acetaldehyde
O
H
alcohol
dehydrogenase
aldehyde
dehydrogenase
O
H
O
OH
The physiological side effects of consuming ethanol are due to the buildup of acetaldehyde
(causes nausea, dizziness, sweating, headaches, lower blood pressure)
The acetaldehyde is then oxidized biochemically to acetic acid
Some people have a nonfunctioning aldehyde dehydrogenase enzyme
-these people experience the side effects of acetaldehyde with low ethanol consumption
Methanol versus Ethanol Biochemically
Methanol also gets oxidized by the same enzyme
O
H
alcohol
dehydrogenase
O
H
H
But due to one less carbon, this oxidation creates formaldehyde not acetaldehyde
Formaldehyde is toxic to the body because it disrupts other essential enzymes form working properly
Ethanol is consumed ~25 times faster than methanol by this enzyme
Cationic Polymerization
Alkenes can also react to form polymers
(suffix –mer comes from Greek word meros, meaning “part”)
CH3
CH3
CH3
H3C
CH3
H+
H3 C
H3C
CH3
Initially form most stable carbocation
H3C CH3CH3
H3C
H3 C
CH3
If neither nucleophile
or base are present,
This carbocation could react carbocation can react
with nucleophiles (SN1) with another alkene to
or have a hydrogen
form a “dimer”
abstracted with base (E1)
n
Polyisobutylene
The 3˚ cation of the
dimer structure can
continue to react with
alkenes to form a
polymer structure
Polymerization will continue until the concentration of alkene becomes low and competes with either SN1 or E1 which will terminate the polymerization