Polarimeter Concentration: pure liquid in g/mL; solution in g per 100 mL of solvent before after

Polarimeter

))(,(

)(][

ionconcentratdmlength

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


H Br

CH3

Cl H


S

S

CH3

Br H

CH3

H Cl

R

R


CH3

Br H

CH3

Cl H

R

S

CH3

H Br

CH3

H Cl

S

R


Enantiomers

Enantiomers


H Br

CH3

Cl H


S

S

CH3

Br H

CH3

H Cl

R

R


CH3

Br H

CH3

Cl H

R

S

CH3

H Br

CH3

H Cl

S

R


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

Documents

Polarimeter Concentration: pure liquid in g/mL; solution in g per 100 mL of solvent before after