Download - Polarimeter Concentration: pure liquid in g/mL; solution in g per 100 mL of solvent before after
Polarimeter
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rotationobservedrotationspecific
Concentration: pure liquid in g/mL; solution in g per 100 mL of solvent
beforeafter
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.
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!!
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)
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?
.16.)40)(70.0(.)40)(30.0(][ mixture
Contribution from R
Contribution from S
• Using the specific rotation to obtain the composition of the mixture.
• For the same two enantiomers ([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)
8. -40.
40.+ (1. – fraction which is R)
Fraction which is R = 40%; fraction which is S is 60%.
Racemic Mixtures, Racemates
• The racemic mixture (racemate) is a 50:50 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.
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.
R R R R R
R R R S S
As before
Specific rotation of mix = 0.80 x 50. + .20 x (-50.)
= 30.
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%.
Look from
this point of
view.
Fischer Projection
HCl
CH3
C2H5
(R)-2-chlorobutane
H,low priority substituent, is closer so CCW is R.
Reposition to
Standard Fischer projection orientation:
vertical bonds recede
horizontal bonds come forward
Standard short notation:Cl H
CH3
C2H5
Cl H
CH3
C2H5
R and S designations may be assigned in Fischer Projection diagrams. Frequently there is an H horizontal making R CCW and S CW.
Cl to Ethyl to Methyl
Manipulating Fischer Projections
Cl H
CH3
C2H5
Even number of swaps yields same structure; odd number yields enantiomer.
1 swap
H Cl
CH3
C2H5
or C2H5 H
CH3
Cl
Cl CH3
H
C2H5
or Etc.
All of these represent the same structure, the enantiomer (different views)!!
R
S
Manipulating Fischer Projections
Cl H
CH3
C2H5
Even number of swaps yields same structure; odd number yields enantiomer.
2 swaps
H CH3
Cl
C2H5
or C2H5 H
Cl
CH3
H Cl
C2H5
CH3
or Etc.
All of these represent the same structure, the original (different views)!!
R
R
H3C H
Cl
C2H5
Rotation of Entire Fischer Diagrams
CH3
H Br
C2H5
Rotate diagram by 180 deg
CH3
HBr
C2H5
Same Structure simply rotated: H & Br still forward; CH3 & C2H5 in back.
CH3
H
Br
C2H5
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 simple rotation is an example of “proper rotation”.
This combination of a simple rotation and reflection is called an “improper rotation”.
Multiple Chiral CentersCH3
H Br
CH3
Cl H
(2S,3S) 2-bromo-3-chlorobutane
S
S
CH3
Br H
CH3
H Cl
R
R
(2R,3R) 2-bromo-3-chlorobutane
Do a single swap on each chiral center to get the enantiomeric molecule.
Each S configuration has changed to R.
CH3
Br H
CH3
Cl H
Now do a single swap on only one chiral center to get a diastereomeric molecule (stereoisomers but not mirror objects).
R
S
CH3
H Br
CH3
H Cl
S
R
(2R,3S) 2-bromo-3-chlorobutane (2S,3R) 2-bromo-3-chlorobutane
Multiple Chiral CentersCH3
H Br
CH3
Cl H
(2S,3S) 2-bromo-3-chlorobutane
S
S
CH3
Br H
CH3
H Cl
R
R
(2R,3R) 2-bromo-3-chlorobutane
CH3
Br H
CH3
Cl H
R
S
CH3
H Br
CH3
H Cl
S
R
(2R,3S) 2-bromo-3-chlorobutane (2S,3R) 2-bromo-3-chlorobutane
Enantiomers
Enantiomers
Multiple Chiral CentersCH3
H Br
CH3
Cl H
(2S,3S) 2-bromo-3-chlorobutane
S
S
CH3
Br H
CH3
H Cl
R
R
(2R,3R) 2-bromo-3-chlorobutane
CH3
Br H
CH3
Cl H
R
S
CH3
H Br
CH3
H Cl
S
R
(2R,3S) 2-bromo-3-chlorobutane (2S,3R) 2-bromo-3-chlorobutane
Diastereomers
Diastereomers
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.
Diastereomers
• Require the presence of two or more chiral centers.
• Have different physical and chemical properties.
• May be separated by physical and chemical techniques.
Meso CompoundsCH3
H Cl
CH3
Cl H
S
S
CH3
Cl H
CH3
H Cl
R
R
CH3
Cl H
CH3
Cl H
R
S
CH3
H Cl
CH3
H Cl
S
R
Must have same set of substituents on corresponding chiral carbons.
As we had before here are the four structures produced by
systematically varying the configuration at each chiral carbon.
Meso CompoundsCH3
H Cl
CH3
Cl H
S
S
CH3
Cl H
CH3
H Cl
R
R
CH3
Cl H
CH3
Cl H
R
S
CH3
H Cl
CH3
H Cl
S
RMirror images! But superimposable via a 180 degree rotation. Same compound.
Enantiomers
Mirror images, not superimposable.
Diastereomers.
Meso
What are the stereochemical relationships?
Meso Compounds: Characteristics
CH3
Cl H
CH3
Cl H
R
S
Meso
Can be superimposed on mirror object, optically inactive.
CH3
H Cl
CH3
H Cl R
Has at least two chiral carbons. Corresponding carbons are of opposite configuration.
S
Can demonstrate mirror plane of symmetry
Molecule is achiral. Optically inactive. Specific rotation is zero.
Can be superimposed by 180 deg rotation.
Meso Compounds: Recognizing
CH3
Cl H
CH3
Cl H
R
S
Meso
Cl
H CH3
CH3
Cl H
R
S
What of this structure? It has chiral carbons. Is it optically active? Is it meso instead?
Assign configurations.
Looks meso. But no mirror plane.
Rearrange by doing even number of swaps on upper carbon.
H
Cl CH3
CH3
Cl H
CH3
Cl H
CH3
Cl H
Now have mirror plane.
Original structure was meso compound. In checking to see if meso you must attempt to establish the plane of symmetry.
Cl
H CH3
CH3
Cl H
Cycloalkanes
Based on these planar ring diagrams we observe reflection plane and expect optical inactivity….
But the actual molecule is not planar!! Examine cyclohexane.
Look for reflection planes!
This plane of symmetry (and two similar ones) are still present. Achiral. Optically inactive. The planar diagrams predicted correctly.
There are other reflection planes as well. Do you see them?
Horizontal reflection plane.
Vertical reflection plane.
Substituted cyclohexanes
(1S,2R)-1,2-dimethylcyclohexane
cisThe planar diagram predicts achiral and optically inactive. But again we know the structure is not planar.
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. 50:50 mixture. Racemic mixture. Optically Inactive. Planar structure predicted correctly
Mirror objects!!
More…
trans 1,2 dimethylcyclohexane
(1R,2R)-1,2-dimethylcyclohexane
No mirror planes. Predicted to be chiral, optically active.
(1S,2S)-1,2-dimethylcyclohexane
Ring Flips??????
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.
R,R R,R
trans
Enantiomer.
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.
Chirality in the Biological World
– A schematic diagram of an enzyme surface capable of binding with (R)-glyceraldehyde but not with (S)-glyceraldehyde.
All three substituents match up with sites on the enzyme.
If two are matched up then the third will fai!
Acids and Bases
Different Definitions of Acids and Bases
• Arrhenius definitions for aqueous solutions.
acidacid:: a substance that produces H+ (H3O+) ions aqueous solution
basebase:: a substance that produces OH- ions in aqueous solutionH+(aq) + H2O(l) H3O
+(aq)Hydronium ion
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.
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.
H
O
H
H+
H
O
H
H
base
acid
lone pairs pi bonding electrons sigma bonding electrons
Energy
Basicity
Types of electrons:
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.
Acid – Base Eqilibria
Same equilibrium with electron pushing (curved arrows).
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.
An example: pi electrons as bases
Bronsted Lowry Acid
Bronsted Lowry Base
The carbocations are conjugate acids of the alkenes.
For the moment, just note that there are two possible carbocations formed.
Sigma bonding electrons as bases. Much more unusual!!
Super acid
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.
Trends for Relative Acid Strengths
Totally ionized in aqueous solution.
Aqueous Solution
Totally unionized in aqueous solution
Example
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?
pKa = 9.95
Stronger acid
H2O + PhOH H3O+ + PhO-
Ka = [H3O+][PhO-]/[PhOH] = 10-9.95
OH
phenol, PhOH
CH3CH2OH
ethanol, EtOH
Recall
H2O + EtOH H3O+ + EtO-
Ka = [H3O+][EtO-]/[EtOH] = 10-15.9
pKa = 15.9
Weaker acid
Stronger base
Weaker base.
Query: What makes for strong (or weak) acids?
K = 10-9.95 / 10-15.9 = 106.0
What affects acidity?1. Electronegativity of the atom holding the negative charge.
CH3OH CH3O - + H+
CH3NH2 CH3NH - + H+
CH3CH3 CH3CH2- + H+
Increasing electronegativity of atom bearing negative charge. Increasing stability of anion.
Increasing acidity.
Increasing basicity of anion.
2. Size of the atom bearing the negative charge in the anion.
CH3OH CH3O - + H+; pKa = 16
CH3SH CH3S - + H+; pKa = 7.0
Increasing size of atom holding negative charge. Increasing stability of anion.
Increasing acidity.
Increasing basicity of anion.
OO
What affects acidity? - 23. Resonance stabilization, usually of the anion.
OH
phenol, PhOH
OO
ethanol, EtOHCH3CH2OH CH3CH2O
- + H+
Increasing resonance stabilization. Increased anion stability.
Aci
dit
y
Increasing basicity of the anion.
No resonance structures!!
OH OH
etc.
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.
An example: competitive Bases & Resonance
• Two different bases or two sites in the same molecule may compete to be protonated (be the base).
O
O H
acetic acid
H+O
O H
HH+
O
O H
H
Acetic acid can be protonated at two sites.
Which conjugate acid is favored?
The more stable one! Which is that?
Recall resonance provides additional stability by moving pi or non-bonding electrons.
Pi bonding electrons converted to non-bonding.
O
O H
H
O
O H
H
Non-bonding electrons converted to pi bonding.
No valid resonance structures for this cation.
An example: competitive Bases & Resonance
H+O
O H
H
O
O H
H
O
O H
H
O
O H
acetic acid
All atoms obey octet rule!
All atoms obey octet rule!
The carbon is electron deficient – 6 electrons, not 8.
Lesser importance
Comments on the importance of the resonance structures.
What affects acidity? - 34. Inductive and Electrostatic Stabilization.
F3CCH2O - + H+
H3CCH2O - + H+H3CCH2OH
F3CCH2OH
Due to electronegativity of F small positive charges build up on C resulting in stabilization of the anion.
Increasing anion stability.Acidity.Increasing anion basicity.
Effect drops off with distance. EtOH pKa = 15.9
What affects acidity? - 45. 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.
Incr
easi
ng
Aci
dit
y o
f H
A
Incr
easi
ng
B
asic
ity
of
A-
Note. The NH2-
is more basic than the RCC-
ion.
Know this order.
Example of hybridization Effect.
RCCH + AgNO3 AgCCR (ppt)
acid base
terminal alkyne
non-terminal alkyne
RCCR + LiCH2CH2CH2CH3 No Reaction
RCCH + LiCH2CH2CH2CH3 HCH2CH2CH2CH3 + RCCLi
RCCR + AgNO3 NR
What affects acidity? - 5
6. Stabilization of ions by solvents (solvation).
H
O RO R + H
H
O
H
H
O
HH
OH
Solvation provides stabilization.
OH
ethanol
OH
propan-2-ol
OH
2-methylpropan-2-olCrowding inhibiting solvation
Solvation, stability of anion, acidity
pKa = 15.9 17 18
(CH3)3CO -, crowded
Comparison of alcohol acidities.
Example
Para nitrophenol is more acidic than phenol. Offer an explanation
OH
OH
N
O O
O
O
N
O O
+ H
+ H 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.
A B
OH
N
O O
Examine the equilibrium for p-nitrophenol. How does the nitro group increase the acidity?
O
N
O O
+ H
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
OH
N
O O
OH
N
O O
OH
N
O O
OH
N
O O
A B C D
Structure D occurs only due to the nitro group. The stability it provides will slightly decrease 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.
OH
N
O O
O
N
O O
+ H
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
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.
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.
O
N
O O
O
N
O O
O
N
O O
O
N
O O
A B C D
3. (3 pts) Which is the stronger base and why?
HNvs
HN O
Sample Problem
H2N H2N O H2N O