Conjugated Systems - University of Texas at Dallasutdallas.edu/~biewerm/13H-conjugated.pdf ·...
Transcript of Conjugated Systems - University of Texas at Dallasutdallas.edu/~biewerm/13H-conjugated.pdf ·...
Conjugated Systems
When the p orbitals of double bonds are on adjacent atoms, the double bonds are said to be conjugated
This conjugation leads to differences in the properties of conjugated dienes
Due to the conjugation the electrons can resonate between all conjugated p orbitals
This resonance cannot occur between isolated double bonds
Energy Differences in Conjugated Systems
As seen with other structures that can resonate, the extra resonance forms lead to a more stable system
Conjugated systems are thus more stable than isolated double bonds
stability
Remember from discussion of alkene stability, more substituted double bonds are more stable due to stability offered by hyperconjugation
Therefore the stability of diene isomers can also be predicted due to conjugation and amount of substitution on the double bonds
Can measure stability by hydrogenation
H2catalyst
The energy required for this hydrogenation indicates the stability of the alkene
28.6 Kcal/mol
57.4 Kcal/mol 55.4 Kcal/mol
Almost double in energy
2 Kcal/mol Conjugation stability
Energy Differences in Conjugated Systems
Conjugated systems are thus always lower in energy than isolated double bonds
Structural Differences in Conjugated Systems
Due to the resonance in conjugated double bonds, the bond distances are not strictly “single” or “double” bond lengths
1.53 Å 1.32 Å
1.47 Å
In order for the double bonds to resonate, however, the p orbitals must be aligned
s-trans s-cis
s-trans is more stable due to sterics with hydrogens with the s-cis conformation
H
H
H
HH
H
HH
HH
H H
Allenes
The shortest possible diene system would be propadiene (called “allene”)
H2C C CH2
The two double bonds of allene though are not conjugated
HH
H
H
The central carbon of allene must form a π bond with both adjacent carbons, thus the p orbitals used must be orthogonal
Allenes are thus less stable than either conjugated or isolated double bonds
Alkyne Isomerization using Allenes
When internal alkynes are reacted with strong base, they isomerize to terminal alkynes
NaNH2NH3
The mechanism for this isomerization is first to abstract a hydrogen adjacent to the alkyne which resonates to an allene anion
NaNH2NH3
HC CH2
NH3C CH2
The generated allene can then react again with base to generate another allene anion
NaNH2
C CHHNH3
HNaNH2
The important point is that once the terminal alkyne is formed, it is quantitatively deprotonated with strong base to drive equilibrium
Molecular Orbitals
We can understand, and predict, many properties of conjugated systems by considering the molecular orbitals
Remember when we discussed bonding in organic compounds we formed bonds by combining atomic orbitals
Either sigma (σ) or pi (π) bonds were formed depending upon the symmetry of the resultant bond upon addition of the atomic orbitals
The same process occurs when considering conjugated dienes
Rules for combining orbitals:
1) Always get the same number of molecular orbitals as number of atomic orbitals used to combine
2) As the number of nodes increase, the energy of the molecular orbital increases
3) The molecular orbitals obtained are the region of space where the electrons reside (on time average)
Molecular Orbitals
First consider an isolated alkene
Simplest is ethylene
We can separate the sigma and pi framework
With alkenes, we are interested in the pi framework since this is what controls the reactivity
First combine two p orbitals to form a π bond
Each p orbital has two lobes with opposite phase
Upon addition, will obtain two MOs with different energy
Energy
Instead of + and -, often represent phases with color
The molecular orbitals obtained computationally appear same as the approximation used by combining atomic p orbitals
π bond π* bond
Molecular Orbitals
Can draw electronic configuration for the π system
Again consider ethylene Since there are 2 π electrons in this molecule, will place 2 electrons in MO diagram
Always place electrons in lowest energy orbital first, each orbital can accommodate two electrons
Molecular Orbitals
E
Molecular Orbitals
Can obtain molecular orbitals for larger conjugated systems using the same procedure
Consider butadiene, 2 double bonds in conjugation corresponding to overlap of 4 adjacent p orbitals
By combining 4 atomic p orbitals, will obtain 4 molecular orbitals that differ in phase of orbitals
0 nodes 1 node 2 nodes 3 nodes
As the number of nodes increases, the energy of the orbital increases
E
Molecular Orbitals for Butadiene
4 electrons are placed in these molecular orbitals by pairing the lowest energy MO’s until all electrons are placed in orbitals
The molecular orbital that is highest in energy that contains electrons is called the highest occupied molecular orbital (HOMO)
The molecular orbital that is lowest in energy that does not contain electrons is called the lowest unoccupied molecular orbital (LUMO)
Highest occupied MO (HOMO)
Lowest unoccupied MO (LUMO)
Reactivity of Conjugated Systems
The π bonds of conjugated systems can react in similar reactions as isolated alkenes
HBr Br
While the products are similar (H and Br in this case adding to a π bond), the rate is different
When considering a nucleophile adding to an electrophile, the higher in energy the HOMO of the nucleophile, the faster is the rate
As learned in UV-vis spectroscopy, as the conjugation increases the HOMO-LUMO gap is smaller
EDue to the higher energy HOMO of butadiene versus an isolated
alkene, butadiene will react faster in an electrophilic alkene addition
ΔE
Reactivity of Conjugated Systems
The difference in rate between conjugated and isolated alkenes can also be explained by the difference in energy for the intermediate in the rate determining step
HBr
HBr
Br
Br
Br
Br
Secondary cation in resonance
Isolated secondary cation
A cation in resonance is more stable than an isolated cation, therefore the reaction of butadiene will have a lower energy of activation than 1-butene and thus the rate will be faster
Thermodynamic Versus Kinetic Control
Another difference between π reactions of conjugated systems versus isolated alkenes are the possibility of different products
When an isolated alkene reacts, only the product from the most stable carbocation intermediate is formed
HBr BrBr
When conjugated alkenes react, however, the carbocation intermediate can resonate
HBr
Each resonance structure can react to form different products
Br Br
Br
Br1, 2 Product 1, 4 Product
Thermodynamic Versus Kinetic Control
Which product is favored (1, 2 versus 1, 4 product) can be controlled by reaction conditions
In the product isomers, however, the more substituted double bond is more favored
A convenient experimental condition to control thermodynamic product is to run the reaction at higher temperature
The electrophile will first add to the double bond to create a resonance stabilized cation
The resonance forms can react with the nucleophile to generate two transition state structures that have partial positive charges as the new bonds are forming
Br
!+
!+Br
!+
!+In positive charged species, the more substituted form
is more stable The more stable
transition state thus leads to the faster rate (kinetically favored)
Br
Br
The more stable product (thermodynamically
favored)
The kinetic product is favored at lower temperature
1, 2 Product (Kinetic) 1, 4 Product
(Thermodynamic)
Molecular Orbitals for Allylic Systems
An allylic system refers to 3 conjugated p orbitals
Allyl cation Allyl radical Allyl anion
All allylic systems have 3 p orbitals in conjugation, but the number of electrons conjugated changes
With 3 conjugated p orbitals, must obtain 3 molecular orbitals
E
0 nodes
1 node
2 nodes
Depending upon number of π electrons the electronic configuration can be determined
Allyl cation has 2 π electrons
Allyl radical has 3 π electrons Allyl anion has 4 π electrons
Implies that excess negative charge of anion is located on the terminal carbons (size of coefficients correlates with probability of electron density)
Similar to resonance description
Molecular Orbitals for Allylic Systems
(with odd number of carbons, nodes can occur at nucleus
unlike systems with even number of carbons)
Reactions with Allylic Systems
An allyl system is observed as an intermediate or transition state in many reaction mechanisms
Consider an SN1 mechanism:
Cl H2O OH
Generates allyl cation intermediate
The relative rates for this reaction with different structures correspond to the stability of intermediate in reaction mechanism
ClCl
Cl Cl Cl
1˚ cation 2˚ cation 1˚/1˚ cation (resonance)
1˚/2˚ cation (resonance)
1˚/3˚ cation (resonance)
Intermediate:
Relative rate: 1 1.7 14.3 1300 1900000
Reactions with Allylic Systems
Consider an SN2 mechanism:
In an SN2 reaction, there is not an intermediate but rather a transition state structure for the rate-determining step
Cl
NUC
Cl !-
!-
nucleophile NUC
Cl
Cl
NUC
nucleophileWhen reacting an allyl halide, the transition state has an allyl structure
which is more stable
Cl ClCl
Electrophilic carbon in Transition state:
Relative rate: (SN2)
1˚ 1˚ in resonance 2˚ in resonance
1 37 1.9
Relative rate of SN2 reaction with ethoxide:
Reactions with Allylic Systems
Consider pKa for allyl systems:
base
pKa = 50-60
Very unstable anion
base
pKa = 43
Anion stabilized by allyl resonance
Allylic positions are much more acidic than unactivated carbons due to the resonance stabilization
of anion formed after deprotonation
Pericyclic Reactions
Reactions involving concerted bond formation, or bond breakage, with a ring of interacting orbitals
Ring of interacting orbitals -Orbitals must form a continuous loop
Therefore each orbital must be able to interact with the adjacent orbital
Electrons are located in Molecular Orbitals (MO’s)
When two molecules react, a molecular orbital on one molecule interacts with a molecular orbital on the second molecule which causes an energy gain
(if reaction is favorable)
With conjugated π systems we can consider only the π framework
Energy Gain in a Reaction
Remember that these molecular orbitals on two molecules combine to form new orbitals in a reaction
Consider the interaction of HOMO and LUMO orbitals on different molecules
HOMO HOMO
If two HOMO orbitals react then two new MO’s will be obtained
(one lower and one higher in energy)
The 4 electrons will be placed and thus there is no energy gain
LUMOLUMO
If two LUMO orbitals react then also obtain two new MO’s,
but since there are no electrons, there is no change in energy
HOMO LUMOThe only energy gain is when a HOMO from one molecule reacts with a LUMO
from the other molecule
In order for the HOMO of one molecule to interact with the LUMO of another molecule the SYMMETRY of the orbitals must be correct
If the symmetry is wrong, then we cannot have interacting orbitals
Consider butadiene reacting with ethylene
Butadiene HOMO
Ethylene LUMO
The symmetry of the interacting orbitals is correct, therefore butadiene reacting with ethylene is symmetry allowed
Pericyclic Reactions
Ethylene, however, cannot react with itself
The orbitals cannot align themselves with proper symmetry
Therefore this reaction is symmetry forbidden
Ethylene LUMO
Ethylene HOMO
Pericyclic Reactions
Alkenes thus do not react thermally
! No Reaction
E
Excitation
Photolysis (if the energy of light is correct!) can excite an electron to a higher MO
This process changes the symmetry of the HOMO
Therefore a reaction can be made “symmetry allowed” by photolysis
Alkenes, for example, will react under photolysis but not thermally
h!
h!
Similar to process observed in UV-vis
spectroscopy
Diels-Alder reaction is one type of pericyclic reaction
The reaction between butadiene and ethylene is called a Diels-Alder reaction
Obtain cyclohexene functional units after a Diels-Alder reaction
Pericyclic Reactions
-Will always obtain a cyclohexene ring after a Diels-Alder reaction, finding this ring in a product structure will allow proper prediction
of what compounds are needed in a Diels-Alder reaction
Diels-Alder Reaction is favored by a lower HOMO-LUMO energy gap
In addition to requiring the correct symmetry, the energy gap between the HOMO and LUMO orbitals determines the amount of energy gain in a reaction
As the energy gap between the HOMO and LUMO becomes smaller the reaction rate is favored
Pericyclic Reactions
HOMO
LUMO
Energy gain HOMO
LUMO
Energy gain
Adjusting molecular orbital energy levels
Electron withdrawing groups lower the energy of a molecular orbital, Electron donating groups raise the energy of a molecular orbital
Usually the butadiene reacts through the HOMO and ethylene reacts through the LUMO, therefore a Diels-Alder reaction is favored with electron withdrawing groups on ethylene and
electron donating groups on butadiene
Pericyclic Reactions
Methyl groups are donating, thus the diene on the right will have a higher energy HOMO
than butadiene
NO2
Nitro groups are electron withdrawing, thus the alkene on the right will have a lower
energy LUMO than ethylene
Overall therefore with these compounds, the fastest rate will be the Diels-Alder between the methyl substituted diene and the nitro substituted alkene
Reaction Products
Always try to find the cyclohexene unit in the product, this will indicate what was the initial butadiene and ethylene parts
CN CN
O
O
OCH3 O
O
OCH3
When one of the starting materials is already a ring, the product will be a bicyclic compound
(in this case a bridged bicyclic)
O
OH3CO
A bridged bicyclic compound is often best viewed in a perspective drawing to indicate stereochemistry
Break cyclohexene at carbon positions
adjacent to alkene to allow butadiene and ethylene formation
Stereochemistry of Addition
Butadiene must be in a s-cis conformation, not s-trans conformation for a Diels-Alder reaction
Therefore the rate of the reaction will be affected by diene substituents
s-cis (reactive conformer)
s-trans (does not react)
> >
Locked in s-cis Most stable in s-cis, but can convert
to s-trans
Not stable in s-cis, sterics of methyl
groups favor s-trans
Orientation Between the Diene and Alkene
With substituents on the diene and dienophile, the two components can react to form two different stereoproducts
These two products are diastereomers
Which is favored?
Stereochemistry of Addition
NO2 NO2 NO2
Endo Rule
The Diels-Alder reaction favors the endo product
Endo means “inside” the pocket formed by the Diels-Alder reaction, exo is “outside” of this pocket
O2NH
HNO2
When the substituted ethylene approaches the butadiene, the substituent (nitro in this example) could either be pointing towards the sp2 hybridized
carbons of butadiene (endo) or away from these carbons (exo)
Endo orientation
Exo orientation
O2NH
HNO2
As the bonds form in the Diels-Alder reaction, the orientation of the substituents determines the stereochemistry of the product formation
O2NH
H
HNO2
H
NO2
NO2
Endo product
Exo product
=
=
Energetic Basis of Endo Rule
This stereochemical preference is due to ENERGY
In the endo position the orbitals on the electron withdrawing group can favorably interact with the orbitals of the diene
In exo orientation this interaction is not present
NC H
Endo position
CN
In endo position, orbitals on alkene substituents can interact with p orbitals of butadiene
Exo position
Favorable interaction
Regiochemistry of Unsymmetrically Substituted Diels-Alder Products
When a monosubstituted butadiene and a monosubstituted alkene react, different regioproducts can be obtained
Can predict favored product by understanding location of charge in molecules
OCH3 OCH3 OCH3
Consider resonance forms Negative charge is located on C2 and C4
OCH3NO2 !
OCH3NO2
OCH3
NO2
or
123
4
NO
O
Consider resonance forms
NO
O
Positive charge located on C2
12
The negative charge will react preferentially with the positive charge to obtain one regioproduct
Using this analysis we can predict regioproducts
A Diels-Alder reaction can therefore control both regio- and stereochemistry depending upon the structure of the diene and dienophile
Pericyclic Reactions
OCH3NO2
OCH3NO2 Will observe both regio- and
stereocontrol of reaction product
H3CO NO2 H3CO
NO2
Observe regiocontrol, but with only one stereocenter
with this product can not obtain diastereomers
Natural Rubber
Natural rubber is an alkene polymer produced by many sources, the most common being the “rubber” tree
Originally named by Joseph Priestly due to its ability to “rub” out pencil marks, therefore rubber is named due to its eraser properties
Natural rubber is a result of a polymerization from conjugated isoprene units
Natural rubber obtained from tree is called “latex”, it is too soft and is later hardened by a process called vulcanization (heating with sulfur) to cross link the chains
Double bonds in product are key for the rubber to be deformed and return to original shape – they cause kinks in polymer so neighboring chains have difficulty packing
Isoprene 2-methyl-1,3-butadiene
Polyisoprene (has Z alkenes in natural rubber)
Isoprene Rule
Instead of polymerizing a large number of isoprene units to form a polymer, isoprene is a common precursor in naturally occurring materials
Isoprene is first reacted once to create an alcohol,
OH O PO
OO P
O
OOHHO P
O
OO P
O
OOH
and then the alcohol is reacted with diphosphoric acid
The diphosphate compound can then be equilibrated to generate a compound that has the good diphosphate leaving group in an allylic position
OPP enzyme OPP
Isoprene Rule
The allylic diphosphate isoprene compound can react through an SN1 reaction to couple two isoprene units
OPP
OPP OPP OPP
Many naturally occurring compounds are simply multiples of the simple isoprene starting material (called isoprene rule)
Two isoprene units form terpenes, three isoprene units form sesquiterpenes, four isoprene units form diterpenes and so on
O
Limonene Camphor Pinene
Steroids
Isoprenes are also used in biochemical reactions to produce steroid structures
OPP
Two compounds with three isoprene units (Farnesyl-OPP) are coupled in a head-to-tail fashion to create squalene
OPP
Farnesyl-OPP Squalene
O
Steroids
A terminal alkene of the symmetrical squalene molecule is then reacted biochemically to form an epoxide
Realize that the squalene oxide is not in a linear conformation in the enzyme, but rather is folded into a more compact spherical shape
This conformation of the squalene allows the adjacent double bonds to first react with the epoxide and then sequential alkenes react with carbocations to form the 6-6-6-5 ring junction
HO
All steroids have this same 6-6-6-5 ring junction, the substituents can be modified by other enzymes to create “different” steroids