STEREOISOMERS

ARRANGEMENTS IN 3D-SPACE

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Isomers

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Physiological Properties of Stereoisomers(Enantiomers)

Enantiomers can have very different physiological properties.

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found in oranges found in lemons

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Chirality

“Handedness”: Right glove doesn’t fit the left hand.

Mirror-image object is different from the original object.

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Achiral

Objects that can be superposed are achiral.

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StereoisomersEnantiomers: Nonsuperimposable mirror

images, different molecules with different properties.

Chiral Molecules

Chiral molecules have an asymmetric center.

An asymmetric center is an atom that is

attached todifferent groups.

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Chiral Carbons

• Carbons with four different groups attached are chiral.

• It’s mirror image will be a different compound (enantiomer).

Enantiomers are nonsuperimposable mirror images.

Enantiomers

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Enantiomers

The two isomers are called enantiomers.

Enantiomers are different compounds: they can be separated.

Enantiomers have the same physical and chemical properties.

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Achiral Compounds

Take this mirror image and try to superimpose it on the one to the left matching all the atoms. Everything will

match.

When the images can be superposed the compound is achiral.

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Planes of Symmetry

A molecule that has a plane of symmetry is achiral.

Chiral and Achiral Molecules

Chiral compounds have nonsuperimposablemirror images.

Achiral compounds have superimposable mirror images(they are identical molecules).

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Asymmetric Center versusStereocenter

Asymmetric center: an atom attached to fourdifferent groups.

Stereocenter: an atom at which the interchange of two groupsproduces a stereoisomer.

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(R) and (S) Nomenclature

• Different molecules (enantiomers) must have different names.

• Usually only one enantiomer will be biologically active.

• Configuration around the chiral carbon is specified with (R) and (S).

Rule 1:

• Look at the four atoms directly attached to the chirality center, and rank them according to atomic number.

• With the lowest priority group pointing away, look at remaining 3 groups in a plane

• Clockwise is designated R (from Latin word for “right”)

• Counterclockwise is designated S (from Latin word for “left”)

Cahn–Ingold–Prelog RulesSequence Rules (IUPAC)

Rule 2:

• If a decision cannot be reached by ranking the first atoms in the substituents, look at the second, third, or fourth atoms until difference is found

Sequence Rules (Continued)

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Rule 3:

• Multiple-bonded atoms are equivalent to the same number of single-bonded atoms

Sequence Rules (Continued)

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Assign (R) or (S)

• Working in 3-D, rotate the molecule so that the lowest priority group is in back.

• Draw an arrow from highest to lowest priority group.• Clockwise = (R), Counterclockwise = (S)

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Assign Priorities

Atomic number: F > N > C > H

Once priorities have been assigned, the lowest priority group (#4) should be moved to the back if necessary.

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Assign Priorities

Draw an arrow from Group 1 to Group 2 to Group 3 and back to Group 1. Ignore Group 4.

Clockwise = (R) and Counterclockwise = (S)

Counterclockwise

(S)

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Example

C

OH

CH3CH2CH2

H

CH2CH3

1

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4

C

CH2CH3

CH3CH2CH2

OH

H

1

2

3

4

rotate

When rotating to put the lowest priority group in the back, keep one group in place and rotate the other three.

Clockwise(R)

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Example (Continued)

CH3

CH3CH2CH=CH

CH2CH2CH2CH3

H1

2

3

4

Counterclockwise(S)

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Draw the enantiomers of 1,3-dibromobutane and label them as (R) and

(S). (Making a model is particularly helpful for this type of problem.)

The third carbon atom in 1,3-dibromobutane is asymmetric. The bromine atom receives first

priority, the (–CH2CH2Br) group second priority, the methyl group third, and the hydrogen

fourth. The following mirror images are drawn with the hydrogen atom back, ready to assign

(R) or (S) as shown.

Example

Solution

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Properties of Enantiomers

• Same boiling point, melting point, and density.

• Same refractive index.

• Rotate the plane of polarized light in the same magnitude, but in opposite directions.

• Different interaction with other chiral molecules: – Active site of enzymes is selective for a specific

enantiomer.

– Taste buds and scent receptors are also chiral. Enantiomers may have different smells.

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Optical Activity

Enantiomersrotate the plane of polarized light in opposite directions, but same number of degrees.

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Polarimeter

Clockwise

Dextrorotatory (+)

Counterclockwise

Levorotatory (-)

Not related to (R) and (S)

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Specific Rotation

Observed rotation depends on the length of the cell and concentration, as well as the strength of optical activity, temperature, and wavelength of light.

[] = (observed)

c l

Where (observed) is the rotation observed in the polarimeter, c is concentration in g/mL and l is length of sample cell in decimeters.

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When one of the enantiomers of 2-butanol is placed in a polarimeter, the observed rotation is

4.05° counterclockwise. The solution was made by diluting 6 g of 2-butanol to a total of 40

mL, and the solution was placed into a 200-mm polarimeter tube for the measurement.

Determine the specific rotation for this enantiomer of 2-butanol.

Since it is levorotatory, this must be (–)-2-butanol The concentration is 6 g per 40 mL = 0.15

g/mL, and the path length is 200 mm = 2 dm. The specific rotation is

[]D25 =

– 4.05°

(0.15)(2)= –13.5°

Example

Solution

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Biological Discrimination

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Racemic Mixtures

• Equal quantities of d- and l- enantiomers.• Notation: (d,l) or ()• No optical activity.• The mixture may have different boiling point (b. p.) and melting

point (m. p.) from the enantiomers!

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Racemic Products

If optically inactive reagents combine to form a chiral molecule, a racemic mixture is formed.

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Optical Purity

• Optical purity (o.p.) is sometimes called enantiomeric excess (e.e.).

• One enantiomer is present in greater amounts.

observed rotation

rotation of pure enantiomerX 100o.p. =

Enantiomeric Excess

Enantiomeric excess tells us how much of an excess of one enantiomeris in a mixture.

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Calculate % Composition

The specific rotation of (S)-2-iodobutane is +15.90. Determine the % composition of a mixture of (R)- and (S)-2-iodobutane if the specific rotation of theMixture is -3.18.

3.18

15.90X 100o.p. = = 20%

l = 60% d = 40%

Sign is from the enantiomer in excess: levorotatory.

R and S Versus (+) and (–)

Some Renantiomers are (+) and some are (–).

Some Senantiomers are (+) and some are (–).

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If One Enantiomer Is (+), the Other Is (–)

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Chirality of Conformers

• If equilibrium exists between two chiralconformers, the molecule is not chiral.

• Judge chirality by looking at the most symmetrical conformer.

• Cyclohexane can be considered to be planar, on average.

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Chirality of Conformational Isomers

The two chair conformations of cis-1,2-dibromocyclohexane are nonsuperimposable, but the interconversion is fast and the molecules are in equilibrium. Any sample would be racemic and, as such, optically inactive.

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Nonmobile Conformers

• The planar conformation of the biphenyl derivative is too sterically crowded. The compound has no rotation around the central C—C bond and thus it is conformationally locked.

• The staggered conformations are chiral: They are nonsuperimposable mirror images.

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Allenes

• Some allenes are chiral even though they do not have a chiral carbon.

• Central carbon is sp hybridized.

• To be chiral, the groups at the end carbons must have different groups.

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2,3-Pentadiene Is Chiral

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Fischer Projections

• Flat representation of a 3-D molecule.

• A chiral carbon is at the intersection of horizontal and vertical lines.

• Horizontal lines are forward, out-of-plane.

• Vertical lines are behind the plane.

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Fischer Projections (Continued)

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Fischer Rules

• Carbon chain is on the vertical line.

• Highest oxidized carbon is at top.

• Rotation of 180 in plane doesn’t change molecule.

• Do not rotate 90!

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180° Rotation

• A rotation of 180° is allowed because it will not change the configuration.

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90° Rotation

• A 90° rotation will change the orientation of the horizontal and vertical groups.

• Do not rotate a Fischer projection 90°.

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Fischer Mirror Images

• Fisher projections are easy to draw and make it easier to find enantiomers and internal mirror planes when the molecule has 2 or more chiralcenters.

C H 3

H C l

C l H

C H 3

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Fischer (R) and (S)

• Lowest priority (usually H) comes forward, so assignment rules are backwards!

• Clockwise 1-2-3 is (S) and counterclockwise 1-2-3 is (R).

• Example:(S)

(S)

C H 3

H C l

C l H

C H 3

Compounds with Two Asymmetric CentersDiastereomers

1 and 2 are enantiomers. 3 and 4 are enantiomers.

Diastereomers are stereoisomers that are not enantiomers.

1 and 3 are diastereomers.

1 and 4 are diastereomers.

2 and 3 are diastereomers.

2 and 4 are diastereomers.

Diastereomers have different physical and chemical properties. 50

A Meso Compound Has a Superimposable Mirror Image

Meso compounds are optically inactive even though they have asymmetric centers.

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Two Asymmetric Centers: Three Stereoisomers

(a meso compound and a pair of enantiomers)

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Number of Stereoisomers

The 2n rule will not apply to compounds that may have a plane of symmetry. 2,3-dibromobutane has only 3 stereoisomers: (±) enantiomerand the mesodiastereomer.

A Meso Compound

A compound with two asymmetric centers that have the same four groups bonded to each asymmetric center will have three stereoisomers:

a meso compound and a pair of enantiomers.54

Two Asymmetric Centers, Four Stereoisomers

The cisstereoisomers are a pair of enantiomers.

The trans stereoisomersare a pair of enantiomers.

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Identifying an Asymmetric Center

An asymmetric center is attached to four different groups.

two asymmetric centers, four stereoisomers56

No Asymmetric Centers

There are only two stereoisomers: cis and trans.

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There are only two stereoisomers: cis and trans

A Meso Compound

For cyclic compounds with the same substituent bonded to two asymmetric centers,

cis = a meso compoundand

trans = a pair of enantiomers. 58

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Two or More Chiral Carbons• When compounds have two or more chiral

centers they have enantiomers, diastereomers, or meso isomers.

• Enantiomers have opposite configurations at each corresponding chiral carbon.

• Diastereomers have some matching, some opposite configurations.

• Meso compounds have internal mirror planes.

• Maximum number of isomers is 2n, where n = the number of chiral carbons.

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Are the structures connected the same?Are the structures connected the same?

yesyes nono

Are they mirror images?Are they mirror images? Constitutional IsomersConstitutional Isomers

yesyes nono

EnantiomersEnantiomersAll chiral centers will All chiral centers will

be opposite between them.be opposite between them.

Is there a plane of symmetry?Is there a plane of symmetry?

yesyes nono

DiastereomersDiastereomersMesoMesosuperimposablesuperimposable

Comparing Structures

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Properties of Diastereomers

• Diastereomers have different physical properties, so they can be easily separated.

• Enantiomers differ only in reaction with other chiral molecules and the direction in which polarized light is rotated.

• Enantiomers are difficult to separate.

• Convert enantiomers into diastereomers to be able to separate them.

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Resolution of Enantiomers

React the racemic mixture with a pure chiralcompound, such as tartaric acid, to form diastereomers, then separate them.

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ChromatographicResolution of Enantiomers

Separating Enantiomers

separating by hand

separating by chromatography64

Physical Properties of Stereoisomers

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Nitrogen and Phosphorus Can Be Asymmetric Centers

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