Polarimeter

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Polarimeter
before
after
Concentration pure liquid in g/mL solution in g
per 100 mL of solvent
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Optical Activity

• Optically Active compounds rotate plane polarized
  light. Chiral compounds (compounds not
  superimposable on their mirror objects) are
  expected to be optically active.
• Optically Inactive compounds do not rotate plane
  polarized light. Achiral compounds are optically
  inactive.

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Problems

• If the specific rotation of pure R 2-bromobutane
  is 48 degrees what is the specific rotation of
  the pure S enantiomer?

The pure S enantiomer has a specific rotation of
-48 degrees. Equal but opposite!!
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Mixtures of Enantiomers

• These are high school mixture problems.
• If you know the specific rotation of the pure
  enantiomers and the composition of a mixture then
  the specific rotation of the mixture may be
  predicted. And conversely the specific rotation
  of the mixture may be used to calculate the
  composition of the mixture.

Specific rotation of mixture (fraction which is
R)(specific rotation of R) (fraction which
is S)(specific rotation of S)
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Example

• Mixture of 30 R and 70 S enantiomer.
• The pure R enantiomer has a specific rotation of
  -40 degrees.
• What is the specific rotation of the mixture?

Contribution from R
Contribution from S
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• Using the specific rotation to obtain the
  composition of the mixture.
• For the same two enantiomers (a of R -40) ,
  suppose the specific rotation of a mixture is 8.
  degrees what is the composition?

Specific rotation of mixture (fraction which is
R)( specific rotation of R) (fraction which
is S)( specific rotation of S)
-40.
8.
40.
(1. fraction which is R)
Fraction which is R 40 fraction which is S is
60.
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Racemic Mixtures, Racemates

• The racemic mixture (racemate) is a 5050 mixture
  of the two enantiomers.
• The specific rotation is zero.
• The racemic mixture may have different physical
  properties (m.p., b.p., etc.) than the
  enantiomers.

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Optical Purity, Enantiomeric Excess
Consider a mixture which is 80 R (and 20 S).
Assume the specific rotation of the pure R
enantiomer is 50 degrees.
As before Specific rotation of mix 0.80 x 50.
.20 x (-50.) 30.
R R R R R R R R S S
Now, recall that a racemic mixture is 50 R and
50 S. Mixture is 60 R and 40 racemic.
Specific rotation of mix 0.60 x 50. .40 x
(0.) 30.
The optical purity (or enantiomeric excess) is
60.
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Fischer Projection
Cl to Ethyl to Methyl
Reposition to
Look from this point of view.
Standard Fischer projection orientation vertical
bonds recede horizontal bonds come forward
H,low priority substituent, is closer so CCW is R.
R and S designations may be assigned in Fischer
Projection diagrams. Frequently there is an H
horizontal making R CCW and S CW.
Standard short notation
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Manipulating Fischer Projections
Even number of swaps yields same structure odd
number yields enantiomer.
1 swap
or
R
or
Etc.
S
All of these represent the same structure, the
enantiomer (different views)!!
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Manipulating Fischer Projections
Even number of swaps yields same structure odd
number yields enantiomer.
2 swaps
or
R
or
Etc.
R
All of these represent the same structure, the
original (different views)!!
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Rotation of Entire Fischer Diagrams
Rotate diagram by 180 deg
Same Structure simply rotated H Br still
forward CH3 C2H5 in back.
This simple rotation is an example of proper
rotation.
Rotation by 90 (or 270) degrees.
Enantiomers. Non superimposable structures! Not
only has rotation taken place but reflection as
well (back to front). For example, the H is now
towards the rear and ethyl is brought forward.
This combination of a simple rotation and
reflection is called an improper rotation.
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Multiple Chiral Centers
S
R
Do a single swap on each chiral center to get the
enantiomeric molecule.
S
R
Each S configuration has changed to R.
Now do a single swap on only one chiral center to
get a diastereomeric molecule (stereoisomers but
not mirror objects).
R
S
S
R
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Multiple Chiral Centers
S
R
S
R
R
S
S
R
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Multiple Chiral Centers
S
R
Diastereomers
S
R
R
S
Diastereomers
S
R
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Diastereomers

• Everyday example shaking hands. Right and Left
  hands are mirror objects
• R --- R is enantiomer of L --- L
• and have equivalent fit to each other.
• R --- L and L --- R are enantiomeric, have
  equivalent fit, but fit differently than R
  --- R or L L.

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Diastereomers

• Require the presence of two or more chiral
  centers.
• Have different physical and chemical properties.
• May be separated by physical and chemical
  techniques.

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Meso Compounds
Must have same set of substituents on
corresponding chiral carbons.
S
R
R
S
As we had before here are the four structures
produced by systematically varying the
configuration at each chiral carbon.
S
R
S
R
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Meso Compounds
What are the stereochemical relationships?
S
R
Enantiomers Mirror images, not superimposable.
R
S
Diastereomers.
S
R
S
R
Mirror images! But superimposable via a 180
degree rotation. Same compound.
Meso
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Meso Compounds Characteristics
Has at least two chiral carbons. Corresponding
carbons are of opposite configuration.
Can be superimposed on mirror object, optically
inactive.
Can demonstrate mirror plane of symmetry
Molecule is achiral. Optically inactive.
Specific rotation is zero.
R
S
S
R
Meso
Can be superimposed by 180 deg rotation.
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Meso Compounds Recognizing
What of this structure? It has chiral carbons.
Is it optically active? Is it meso instead?
Assign configurations. Looks meso. But no mirror
plane.
R
S
Rearrange by doing even number of swaps on upper
carbon.
Now have mirror plane.
R
Original structure was meso compound. In checking
to see if meso you must attempt to establish the
plane of symmetry.
S
Meso
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Cycloalkanes
Vertical reflection plane.
Horizontal reflection plane.
Look for reflection planes!
There are other reflection planes as well. Do you
see them?
Based on these planar ring diagrams we observe
reflection plane and expect optical inactivity.
But the actual molecule is not planar!! Examine
cyclohexane.
This plane of symmetry (and two similar ones) are
still present. Achiral. Optically inactive. The
planar diagrams predicted correctly.
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Substituted cyclohexanes
The planar diagram predicts achiral and optically
inactive. But again we know the structure is not
planar.
cis
Mirror objects!!
This is a chiral structure and would be expected
to be optically active!!
But recall the chair interconversion.
Earlier we showed that the two structures have
the same energy. Rapid interconversion. 5050
mixture. Racemic mixture. Optically Inactive.
Planar structure predicted correctly
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More
trans
No mirror planes. Predicted to be chiral,
optically active.
Enantiomer.
Ring Flips??????
R,R
R,R
trans 1,2 dimethylcyclohexane
Each structure is chiral. Not mirror images! Not
the same! Present in different amounts. Optically
active!
Other isomers for you 1,3 cis and trans, 1,4
cis and trans.
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Resolution of mixture into separate enantiomers.
Mixtures of enantiomers are difficult to separate
because the enantiomers have the same boiling
point, etc. The technique is to convert the pair
of enantiomers into a pair of diastereomers and
to utilize the different physical characteristics
of diastereomers.
Formation of diastereomeric salts. Racemic
mixture of anions allowed to form salts with pure
cation enantiomer.
Racemic mixture reacted with chiral enzyme. One
enantiomer is selectively reacted.
Racemic mixture is put through column packed with
chiral material. One enantiomer passes through
more quickly.
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Chirality in the Biological World
All three substituents match up with sites on
the enzyme.
If two are matched up then the third will fai!

• A schematic diagram of an enzyme surface capable
  of binding with (R)-glyceraldehyde but not with
  (S)-glyceraldehyde.

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Acids and Bases
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Different Definitions of Acids and Bases

• Arrhenius definitions for aqueous solutions.
• acid a substance that produces H (H3O) ions
  aqueous solution
• base a substance that produces OH- ions in
  aqueous solution

Bronsted-Lowry definitions for aqueous and
non-aqueous solutions. Conjugate acid base
pair molecules or ions interconverted by
transfer of a proton. acid transfers the
proton. base receives the proton.
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Lewis Acids and Bases
Focuses on the electrons not the H. An acid
receives electrons from the base making a new
bond. Acid electron receptor. Base electron donor.
Types of electrons
Energy
lone pairs pi bonding electrons
sigma bonding electrons
Basicity
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Acid Base Eqilibria
The position of the equilibrium is obtained by
comparing the pKa values of the two acids.
Equivalently, compare the pKb values of the two
bases.
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Acid Base Eqilibria
Same equilibrium with electron pushing (curved
arrows).
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Lone Pair acting as Base.
Note the change in formal charges. As reactant
oxygen had complete ownership of lone pair. In
product it is shared. Oxygen more positive by
1. Similarly, B has gained half of a bonding
pair more negative by 1.
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An example pi electrons as bases
Bronsted Lowry Base
Bronsted Lowry Acid
For the moment, just note that there are two
possible carbocations formed.
The carbocations are conjugate acids of the
alkenes.
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Sigma bonding electrons as bases. Much more
unusual!!
A very, very electronegative F!! A very
positive S!! The OH becomes very acidic because
that would put a negative charge adjacent to the
S.
Super acid
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Trends for Relative Acid Strengths
Totally ionized in aqueous solution.
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Example
pKa 15.9 Weaker acid
pKa 9.95 Stronger acid
H2O PhOH H3O PhO-
H2O EtOH H3O EtO- Ka
H3OEtO-/EtOH 10-15.9
Ka H3OPhO-/PhOH 10-9.95
Ethanol, EtOH, is a weaker acid than phenol,
PhOH. It follows that ethoxide, EtO-, is a
stronger base than phenolate, PhO-. For reaction
PhOH EtO- PhO- EtOH where does
equilibrium lie?
Weaker base.
Stronger base
K 10-9.95 / 10-15.9 106.0
Query What makes for strong (or weak) acids?
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What affects acidity?
1. Electronegativity of the atom holding the
negative charge.
Increasing electronegativity of atom bearing
negative charge. Increasing stability of anion.
Increasing acidity.
2. Size of the atom bearing the negative charge
in the anion.
Increasing size of atom holding negative charge.
Increasing stability of anion.
Increasing acidity.
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What affects acidity? - 2
3. Resonance stabilization, usually of the anion.
Increasing resonance stabilization. Increased
anion stability.
Increasing basicity of the anion.
Acidity
No resonance structures!!
Note that phenol itself enjoys resonance but
charges are generated, costing energy, making the
resonance less important. The more important
resonance in the anion shifts the equilibrium to
the right making phenol more acidic.
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An example competitive Bases Resonance

• Two different bases or two sites in the same
  molecule may compete to be protonated (be the
  base).

Acetic acid can be protonated at two sites.
Pi bonding electrons converted to non-bonding.
Which conjugate acid is favored? The more stable
one! Which is that? Recall resonance provides
additional stability by moving pi or non-bonding
electrons.
No valid resonance structures for this cation.
Non-bonding electrons converted to pi bonding.
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An example competitive Bases Resonance
Comments on the importance of the resonance
structures.
All atoms obey octet rule!
The carbon is electron deficient 6 electrons,
not 8. Lesser importance
All atoms obey octet rule!
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What affects acidity? - 3
4. Inductive and Electrostatic Stabilization.
Increasing anion stability.
Increasing anion basicity.
Acidity.
d
d
Due to electronegativity of F small positive
charges build up on C resulting in stabilization
of the anion.
Effect drops off with distance. EtOH pKa 15.9
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What affects acidity? - 4
Note. The NH2- is more basic than the RCC- ion.
5. Hybridization of the atom bearing the charge.
H-A ? H A-.
sp3 sp2 sp
More s character, more stability, more
electronegative, H-A more acidic, A- less
basic.
Increasing Acidity of HA
Increasing Basicity of A-
Know this order.
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Example of hybridization Effect.
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What affects acidity? - 5
6. Stabilization of ions by solvents (solvation).
Solvation provides stabilization.
Comparison of alcohol acidities.
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18
pKa 15.9
Crowding inhibiting solvation
(CH3)3CO -, crowded
Solvation, stability of anion, acidity
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Example
Para nitrophenol is more acidic than phenol.
Offer an explanation
The lower lies further to the right.
Why? Could be due to destabilization of the
unionized form, A, or stabilization of the
ionized form, B.
B
A
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Examine the equilibrium for p-nitrophenol. How
does the nitro group increase the acidity?
Examine both sides of equilibrium. What does the
nitro group do? First the unionized acid.
Note carefully that in these resonance structures
charge is created on the O and in the ring
or on an oxygen. This decreases the importance of
the resonance.
Structure D occurs only due to the nitro group.
The stability it provides will slightly decrease
acidity.
Resonance structures A, B and C are comparable to
those in the phenol itself and thus would not be
expected to affect acidity. But note the to
attraction here
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Now look at the anion. What does the nitro group
do? Remember we are interested to compare with
the phenol phenolate equilibrium.
In these resonance structures charge is not
created. Thus these structures are important and
increase acidity. They account for the acidity
of all phenols.
Structure D occurs only due to the nitro group.
It increases acidity. The greater amount of
significant resonance in the anion accounts for
the nitro increasing the acidity.
Resonance structures A, B and C are comparable to
those in the phenolate anion itself and thus
would not be expected to affect acidity. But
note the to attraction here
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Sample Problem