StereochemistryStereochemistry

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Chirality

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

•Mirror-imageMirror-image object is different from the original object.

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AchiralAchiral

•Objects that can be superposed are achiralachiral..

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StereoisomersStereoisomers EnantiomersEnantiomers: Nonsuperimposable mirrorNonsuperimposable mirror images, images,

differentdifferent molecules with different properties molecules with different properties. .

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Chiral CarbonsChiral Carbons

•Carbons attached with four different atoms four different atoms or groupsor groups are are chiralchiral.

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

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Achiral CompoundsAchiral 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 When the images can be superposed the compound is the compound is achiralachiral..

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Planes of SymmetryPlanes of Symmetry

•A molecule that has a plane of symmetry

• is is achiralachiral.

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Cis and Trans Cyclic CompoundsCis and Trans Cyclic Compounds

•CisCis-1,2-dichlorocyclopentane-1,2-dichlorocyclopentane:: IIs achiral because the molecule has an internal plane of symmetry. Both structures above can be superimposed.•Transrans-1,2-dichlorocyclopentane-1,2-dichlorocyclopentane does not have a plane of symmetry so the images are nonsuperimposable and the molecule will have two enantiomers.

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((RR ) )and (and (SS) Nomenclature) Nomenclature

•Different molecules (enantiomersenantiomers) must have different names.•Usually only one enantiomer will be biologically activebiologically active.

•ConfigurationConfiguration around the chiral carbon chiral carbon is specified with (RR) and (SS).

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Cahn–Ingold–PrelogCahn–Ingold–Prelog RulesRules•Assign a prioritypriority number to each group attached to the

chiral carbon.

•PriorityPriority is assigned according to atomic number. The

highest atomic number assigned is the highest priority highest priority

#1.#1.

•In case of ties, look at the next atoms along the In case of ties, look at the next atoms along the

chain.chain.Double and triple bonds are treated like bonds to Double and triple bonds are treated like bonds to

duplicate atomsduplicate atoms.

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Assign (Assign (RR ) or () or (SS ))

•Working in 3-D, rotate the molecule so that the lowest Working in 3-D, rotate the molecule so that the lowest

priority group is in backpriority group is in back..

•Draw an arrow from highest to lowest priority group.Draw an arrow from highest to lowest priority group.

Clockwise = (Clockwise = (RR), Counterclockwise = (), Counterclockwise = (SS) )

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Assign PrioritiesAssign Priorities

Atomic number: F > N > C > HAtomic 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 PrioritiesAssign Priorities

Draw an arrow from Group 1 to Group 22 to Group 33 and back to Group 1. Ignore Group 44.

Clockwise = (R) and Counterclockwise = (SS)

CounterclockwiseCounterclockwise

((SS))

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ExampleExample

C

OH

CH3CH2CH2H

CH2CH3

1

23

4

C

CH2CH3

CH3CH2CH2OH

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.

ClockwiseClockwise ( (RR))

Treatment of Multiple BondsTreatment of Multiple Bonds

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Example (Continued)Example (Continued)

CH3

CH3CH2CH=CH

CH2CH2CH2CH3

H11

22

33

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CounterclockwiseCounterclockwise ( (SS))

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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.

Solved Problem 1Solved Problem 1

SolutionSolution

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Properties of EnantiomersProperties 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 directionsin opposite directions.•Different interaction with other chiral molecules:–Active site of enzymes is selective for a specific Active site of enzymes is selective for a specific enantiomer.enantiomer.–Taste buds and scent receptors are also chiral. Enantiomers may have different smells.

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Optical ActivityOptical Activity

•EnantiomersEnantiomers : : rotate the plane of polarized light in opposite directions, but same number of degrees.

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PolarimeterPolarimeter

ClockwiseClockwise

Dextrorotatory (+)

CounterclockwiseCounterclockwise

Levorotatory (-)

Not related to (R) and (S)

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Specific RotationSpecific Rotation

Observed 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 Where (observed (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°

Solved Problem 2Solved Problem 2

SolutionSolution

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Biological DiscriminationBiological Discrimination

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Racemic MixturesRacemic Mixtures

•Equal quantities 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 ProductsRacemic Products

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

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Optical PurityOptical Purity

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

•One enantiomer One enantiomer is present in greater amounts.

observed rotation

rotation of pure enantiomerX 100o.p. =

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Calculate % CompositionCalculate % 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 the mixture is -3.18.

3.18

15.90X 100o.p. = = 20%

2l = 120% l = 60% d = 40%

Sign is from the enantiomer in excess: levorotatory.Sign is from the enantiomer in excess: levorotatory.

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Chirality of ConformersChirality of Conformers

•If equilibrium exists between two chiral

conformers, the molecule is not chiral.

•Judge chirality Judge chirality by looking at the most symmetrical

conformer.

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

average.

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Chirality of Conformational IsomersChirality of Conformational Isomers

The two chair conformations of ciscis-1,2--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 ConformersNonmobile Conformers

•The planar conformation of the biphenyl derivative is too sterically crowded. The compound has no rotation around the central CC——CC bond and thus it is conformationally locked. •The staggered conformations are chiral: They are nonsuperimposable mirror images.They are nonsuperimposable mirror images.

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Allen'sAllen's

•Some allen's 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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2,32,3--Pentadiene Is ChiralPentadiene Is Chiral

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Fischer ProjectionsFischer Projections•Flat representation of a 3-D moleculea 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 (Continu.)Fischer Projections (Continu.)

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Fischer RulesFischer 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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180180°° RotationRotation

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

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9090°° RotationRotation

•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 chiral centers.

CH3

H Cl

Cl H

CH3

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Fischer (Fischer (RR) and () and (SS))

•Lowest priority (usually H) comes forwardforward, so assignment rules are backwardsbackwards!•Clockwise 1-2-3 is (S) and counterclockwise 1-2-3 is (R).•Example:Example:

(S)

(S)

CH3

H Cl

Cl H

CH3

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DiastereomersDiastereomers•Molecules with two or more chiral carbons.Molecules with two or more chiral carbons.•StereoisomersStereoisomers that are that are notnot mirror images mirror images.

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AlkenesAlkenes

•Cis-transCis-trans isomers are not mirror images, so these are diastereomers.

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Two or More Chiral CarbonsTwo or More Chiral Carbons

•When compounds have two or more chiral centers they have enantiomersenantiomers, diastereomersdiastereomers, or meso isomersmeso isomers.•EnantiomersEnantiomers have opposite configurations at each corresponding chiral carbonchiral carbon.•DiastereomersDiastereomers have some matching, some opposite configurations.•Meso compounds Meso compounds have internal mirror planes.•Maximum number of isomers is 22nn, where nn = the = the number of chiral carbons. 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 StructuresComparing Structures

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•Meso compounds have a plane of symmetry.Meso compounds have a plane of symmetry.•If one image was rotated 180If one image was rotated 180°, then it could be °, then it could be superimposed on the other image.superimposed on the other image.•Meso compounds are achiral even though they have Meso compounds are achiral even though they have chiral centerschiral centers.

Meso CompoundsMeso Compounds

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Number of StereoisomersNumber of Stereoisomers

The 2n rule will not apply to compounds that may have a plane of symmetry. 2,3-dibromo butane has only 3 stereoisomers:

(±) diastereomer and the meso diastereomer.

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Properties of DiastereomersProperties of Diastereomers•Diastereomers have Diastereomers have different physical properties, so they can be easily separated.•Enantiomers differ Enantiomers differ only in reaction with other chiral molecules and the direction in which polarized light is rotated.•EnantiomersEnantiomers are difficult to separate.•Convert enantiomersConvert enantiomers into diastereodiastereo- - mers mers to be able to separate them.

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Resolution of EnantiomersResolution of Enantiomers

React the racemic mixture with a pure

chiral compound, such as tartaric acid, to

form diastereomers, then separate them.

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ChromatographicChromatographicResolution of Resolution of EnantiomersEnantiomers