Physical Organic Chemistry -Chapter...
Transcript of Physical Organic Chemistry -Chapter...
Course code : CHEM 43244
Course title : Advanced Organic Chemistry I
Physical Organic Chemistry (15 h)
Dr. Dinesh Pandithavidana
E-mail: [email protected]
Mobile: 0777-745-720
Office: B1 222/3
Stereochemical Principles
Stereoselective Reactions:
• A stereoselective reaction can produce multiple stereoisomers theoretically, but
more of some produced than others
Br Br
+
(2R)-2-bromo-1,1-dimethylcyclohexane
base
(1Z)-3,3-dimethylcyclohexene(2R)-2-bromo-1,1-dimethylcyclohexane
+(2S)-2-bromo-1,1-dimethylcyclohexane
(1Z)-3,3-dimethylcyclohexene
no E (trans) isomer is formed
Stereospecific Reactions:
• A stereospecific reaction produces different stereoisomer products from
different stereoisomer reactants.
SN2 mechanism
stereospecific
SN1 mechanism
non-stereospecific
Regioselective Reactions:
• A regioselective reaction is one
in which multiple constitutional
isomers possible, but more of
some formed than others.
HBr
Br Br
+
major product no measurable quantity formed
DefinitionsProchiral:
• A molecule is prochiral if the addition of a new group or an exchange of one
group on the molecule would create a new stereocenter and, therefore, a chiral
molecule. A prochiral atom must be bonded to three different groups before any
change is made.
O
The molecule on the left is prochiral because a new stereocenter can be made by
replacing one group on the carbon marked with an asterisk (*) with a new one.
The molecule on the right is prochiral because a new stereocenter can be made
by adding a new group to the carbon marked with an asterisk.
* *
Proton Equivalence
• Proton NMR is much more sensitive than 13C and the active nucleus (1H) is
nearly 100 % of the natural abundance.
• Shows how many kinds of nonequivalent hydrogens are in a compound.
• Theoretical equivalence can be predicted by seeing if replacing each H with
“X” gives the same or different outcome.“X” gives the same or different outcome.
• Equivalent H’s have the same signal while nonequivalent are “different” and
as such may cause additional splitting (diastereotopic effect).
– There are degrees of nonequivalence
Nonequivalent Hydrogens
• Replacement of each H with “X” gives a different constitutional isomer.
• Then the Hydrogens are in constitutionally heterotopic environments
and will have different chemical shifts – they are nonequivalent under all
circumstances.
Equivalent Hydrogens
• Two H’s that are in identical environments (homotopic) have the same NMR signal.
• Test by replacing each with X
– if they give the identical result, they are equivalent
– Protons are considered homotopic
Enantiotopic Distinctions
• If Hydrogens are in environments that are mirror images of each other, they are
enantiotopic.
• Replacement of each H with X produces a set of enantiomers.
• The Hydrogens have the same NMR signal in the absence of chiral materials
(optically active solvents, co-solvents or Lewis acids)
Diastereotopic Distinctions
• In a chiral molecule, paired hydrogens can have different environments and different shifts.
• Replacement of a pro-R hydrogen with X gives a different diastereomer than replacement of the pro-S hydrogen.
• Diastereotopic hydrogens are distinct chemically and spectrocopically.
Symmetry in NMR Spectra
• Protons and other nuclei in NMR spectra can be classified as heterotopic,
diastereotopic, enantiotopic and homotopic.
• Heterotopic and diastereotopic protons will have different chemical shifts and
couplings to neighboring magnetic nuclei.
• Enantiotopic and homotopic protons will have identical chemical shifts. They may or
may not have identical couplings to other nuclei.
• Distinction can be made by the substitution test.
The Substitution Test for Equivalance of Protons:
For a pair of protons to be tested, replace one with another group
(which is not present in the molecule). Compare the two structures formed:
• If they are identical, the protons are homotopic,
• If they are enantiomers, the protons are enantiotopic.
• If they are diastereomers then the protons are diastereotopic.
• If they are structural isomers, the protons are heterotopic.
Correlation of Structures with Reactivity
• The structural changes which are used to bring about electronic perturbations are
substituent groups, which may be introduced , near to the reaction center and
which do not themselves take part directly in the reaction being considered.
• It is the change in reaction, brought about by substitution, which are of interest, so
structural changes must be determined relative to some standard substituent
which is electronically neutral. Hydrogen is normally adopted as the “zero”
substituent. substituent.
• This is because that most reactions studied, occur at carbon as one reaction
center, and the electronegativities of carbon & hydrogen are almost equal. So that
C ̶ H bond has no polarity. Furthermore, the hydrogen substituent has no
unshared pairs of π-electrons.
O
O
X
H
O
H
H
O
O
X O
H
H
H+ +
ka
• We can measure the ionization of substituted benzoic acid in water and then
determine equilibrium constant, Ka.
O
O
X
H
O
H
H
O
O
X O
H
H
H+ +
ka
X NO2 CN Cl H CH3 OCH3
Log Ka -3.45 -3.56 -4.00 -4.20 -4.37 -.4.47
Ka has been increased by substitution of H for an electron-withdrawing groups which
weakens the O-H bond, and conversely decreased by an electron donating group.
This reveals the carboxylic acid acts as a the electrophile and water acts as the nucleophile.
Relative to hydrogen, in this series, electron withdrawing sustituents increase the acidity and
electron donating susbtituents decrease the acidity.
Log Ka -3.45 -3.56 -4.00 -4.20 -4.37 -.4.47
σ +0.75 +0.64 +0.2 0.00 -0.17 -0.27
• Quantitatively, the effect of each substituent, relative to that of hydrogen,
may be obtained by a comparison of ∆G for dissociation constants of
substituted benzoic acid (KX) with that of the parent compound (non
substituted benzoic acid) KH.
• Substituent effect =
• σ is called substituent constant because it’s value depends on the nature of
substituent.
σ=
=∆−∆
H
X
HX
K
KGG log
Energy
O
O-
O
O-
O2N
HG∆
XG∆
• For Hydrogen, as a reference point; σ = 0.0
Because if so if there is no substituent, 01loglog ==
H
H
K
K
O H O H
H
X
K
Klog
.. .
.m-Br, Cl
p-NO2
m-CNO
O
X
H
O
H
H
O
O
X O
H
H
H+ +
ka
σ
..
..
...
.. .
m-OMe
m-I
p-F
m-Mep-OMe
p-I
p-Cl
m-Br, Cl
p-Br
H
electron withdrawing groupselectron donating groups
Gradient = 1
Let’s see the hydrolysis of methyl benzoate and ionization of phenyl acetic
acid with compared to ionization of benzoic acid.
O
O CH3
O
O
OH
X X
Rates are evidently increased by electron withdrawing substituents on the ester,
which must accordingly be the electrophiles.which must accordingly be the electrophiles.
In case of phenyl acetic acid, ionization center, COOH and benzene ring with the
substituent have been isolated by the –CH2- group. So the reaction is less
sensitive to substituents than benzoic acid ionization reaction.
X O
H
H
X+
ka
O
O
H
O
O
H
X
K
Klog
for Benzoic acid (m = 1)
for Methyl benzoate (m > 1)
Hammett Plot
σelectron withdrawing groupselectron donating groups
for Phenyl acetate (m < 1)
*** This σ corresponds to ionization of Benzoic
acid which is our standard reaction
• Now it is evident that the linear relationship of previous plots implies;
• Introducing a constant of proportionality, ρ , known as the reaction constant.
ασ
H
X
K
Klog
σρ.log =
H
X
K
K
• Introducing a constant of proportionality, ρ , known as the reaction constant.
The Hammett Equation:
The equation describing the straight line correlation between a series of reactions
with substituted aromatics and the hydrolysis of benzoic acids with the same
substituents is known as the Hammett Equation.
The reaction constant, ρ, describes the susceptibility of the reaction to
substituents, compared to the ionization of benzoic acid. It is equivalent to the
slope of the Hammett plot. Information on the reaction and the associated
mechanism can be obtained based on the value obtained for ρ.
If the value of:
• ρ>1, the reaction is more sensitive to substituents than benzoic acid and
negative charge is built during the reaction (or positive charge is lost).
• 0<ρ<1 , the reaction is less sensitive to substituents than benzoic acid
and negative charge is built (or positive charge is lost).
• ρ=0, no sensitivity to substituents, and no charge is built or lost.
• ρ<0, the reaction builds positive charge (or loses negative charge).
Significance of ρ
Resonance Effect (R)
Reaction center is perturbed by the substituents through,
1) Inductive effect
2) Resonance effect
3) Filed effect
The effect is described as a +R effect, if it results in donation of electrons from
substituent to reaction center.
And a – R effect, if a withdrawal of electron results.And a – R effect, if a withdrawal of electron results.
Donor groups typically possess unshared π-electron pairs or electrons on an atom
directly attached to the ring.
E.g.
These groups are all capable of exerting +R effect which stabilizes an acceptor
center when they are at ortho- or para- positions.
-NR2 , -OR, -SR, -PR2, -X , HC CH2
Stabilization via +R effect
� Substituents which have π-acceptor center, adjacent to the ring, which can act
as electron acceptors.
E.g:
C
OCH3
C
OCH3
C N C NE.g:
C
C
C
CO O
Stabilization via -R effect
CO
CO
C N C N
• In case of Resonance Effect, many substituents give rise to a perturbation
which is greater when they are located at ortho- or para- than they are at
meta- position.
This is because little interactions
between donor and acceptor centers
will occur, if they are located at meta,
so resonance structures cannot be
drawn due to the presence of high
energy.
C C
O
CH3
O
CH33 3
Inductive Effect & Field Effect
• Inductive effect is caused by differences in electronegativity which polarize
both σ and π bonds. This also depends on number of bonds between the
reaction center and substituent.
Me3N
C
CField effect
Inductive effect +δ
+δδ
• The Field effect is propagated through space and depends more for its
intensity and proximity than on the number of bonds between the reaction
center and substituent.
• When inductive effect is there, field effect is also should be associated with
it.
Field effect
Can you explain differences of σ values?
σ = 0.15 σ = 0.34
F C
O
O
C
O
O
F
HO C
O
O
C
O
O
HO
σ = - 0.4 σ = + 0.12
Deviations from Linearity in Hammett Plots
Modified Substituent Constants σ_
Scale:
• We can develop new σ values for these substrates by separating out these through-
conjugation effects from inductive effects.
• Develop line with ρ value based on m-substituents only, which cannot exhibit
resonance effects. The amount by which certain substituents deviate from the line
can be added to their σ values to produce a new scale of σ_
value.
Substituent effect by the enhanced resonance = ( σ͞ ̶ σ)
Modified Substituent Constants σ+
Scale:
• Similarly, in some cases,we find that strongly electron-donating substituents don’t fall
on the line predicted by the Hammett correlation.
Example: SN1
solvolysis of p-substituted tertiary halides
Substituent effect by the enhanced resonance = ( σ+ ̶ σ)
Uses of Hammett Plots
(1) Calculation of k or K for a specific reaction of a specific compound:
If we know ρ for a particular reaction, then we can
calculate the rate or equilibrium constant for any substituent relative to that
for the unsubstituted compound (because we also know σ for the
σρ.log =
H
X
K
K
for the unsubstituted compound (because we also know σ for the
substituent).
(2) To provide information about reaction pathways:
� Magnitude and sign of ρ tell about development of charge at reaction
centre.
� If σ+ or σ͞ gives a better correlation than σ , then we know we have
a reaction where through conjugation is important.
The Hammond Postulate
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The Hammond PostulateG
• In an endothermic reaction, the transition state resembles the products more than the
reactants, so anything that stabilizes the product stabilizes the transition state also. Thus,
lowering the energy of the transition state decreases Ea, which increases the reaction rate.
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• If there are two possible products in an endothermic reaction, but one is more stable than
the other, the transition state that leads to the formation of the more stable product is lower
in energy, so this reaction should occur faster.
The Hammond PostulateG.
• In the case of an exothermic reaction, the transition state resembles the reactants
more than the products. Thus, lowering the energy of the products has little or no effect
on the energy of the transition state.
• Since Ea is unaffected, the reaction rate is unaffected.
• The conclusion is that in an exothermic reaction, the more stable product may or may
not form faster, since Ea is similar for both products.
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• The Hammond postulate estimates the relative energy of transition states,
and thus it can be used to predict the relative rates of two reactions.
• According to the Hammond postulate, the stability of the carbocation
determines the rate of its formation.
The Hammond Postulate:
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Energy diagram for
carbocation
formation in two
different SN1 reactions