Chapter 5 1

Chapter 5 2

ChiralityChirality

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

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

Chapter 5 3

o g a objec

AchiralAchiral

• Objects that can be superposed are achiralachiral.

Chapter 5 4

ISÓMEROSISÓMEROSTêm a mesma fórmula molecular mas estruturas diferentes

CONSTITUCIONAIS : Diferem na ordem em que át tã li d t ios átomos estão ligados entre si

Chapter 5 5

ESTEREOISÓMEROS: A ligação entre átomos segue a mesma ordemESTEREOISÓMEROS: A ligação entre átomos segue a mesma ordem, mas possuem orientação espacial diferente

Chapter 5 6

StereoisomersStereoisomersEnantiomers: Nonsuperimposable mirror p pimages, different molecules with different properties. p p

Chapter 5 7

Chiral CarbonsChiral Carbons

• Carbons with four different groups attached are chiral.

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

Chapter 5 8

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 the When the images can be superposed the d id i hi lhi l

Chapter 5 9compound is compound is achiralachiral..

Planes of SymmetryPlanes of Symmetry

• A molecule that has a plane of symmetry isA molecule that has a plane of symmetry is achiral.

Chapter 5 10

Cis and Trans Cyclic CompoundsCis and Trans Cyclic Compounds

• Cis-1,2-dichlorocyclohexane is achiral because the molecule has an internal plane of symmetry. Both structures above can be superimposed.p p

• Trans-1,2-dichlorocyclohexane does not have a plane of symmetry so the images are nonsuperimposable and the molecule will have two enantiomers

Chapter 5 11

molecule will have two enantiomers.

(R) and (S) Nomenclature(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)Chapter 5 12

with (R) and (S).

Cahn–Ingold–Prelogg gRules

• Assign a priority number to each group attached to the chiral carbonattached to the chiral carbon.

• Priority is assigned according to atomic number The highest atomic numbernumber. The highest atomic number assigned is the highest priority #1.

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

• Double and triple bonds are treated likeDouble and triple bonds are treated like bonds to duplicate atoms.

Chapter 5 13

Assign (R) or (S)Assign (R) or (S)

• 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.• Clockwise = (R) Counterclockwise = (S)

Chapter 5 14

Clockwise (R), Counterclockwise (S)

Assign PrioritiesAssign Priorities

Atomic number: F > N > C > H

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

Chapter 5 15

Assign PrioritiesAssign Priorities

CounterclockwiseCounterclockwise

((SS))

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)

Chapter 5 16

Examplep

3

OH1

C

CH2CH33

rotateC

CH3CH2CH2H

CH2CH32

3 CCH3CH2CH2

OHH2 4

H4

OH1

ClockwiseClockwiseClockwiseClockwise((RR))

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

Chapter 5 17

Treatment of Multiple BondsTreatment of Multiple Bonds

Chapter 5 18

Example (Continued)p ( )

CH3

33CH3

H11 44

CH3CH2CH=CHCH2CH2CH2CH3

H

2222

CounterclockwiseCounterclockwiseCounterclockwiseCounterclockwise((SS))

Chapter 5 19

Solved Problem 1Draw the enantiomers of 1,3-dibromobutane and label them as (R) and (S). (Making a model

Solved Problem 1

is particularly helpful for this type of problem.)

SolutionThe 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(R) or (S) as shown.

Chapter 5 20

P ti f E tiProperties of EnantiomersS b ili i t lti i t d d it• 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 tienantiomer.

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

Chapter 5 21

Optical ActivityOptical Activity

• Enantiomers rotate the plane of polarized light in opposite directions, but same g pp ,number of degrees.

Chapter 5 22

Polarimeter

Clockwise Clockwise CounterclockwiseCounterclockwise

Dextrorotatory (+) Levorotatory (-)

Not related to (R) and (S)

Chapter 5 23

Specific RotationSpecific RotationObserved rotation depends on the lengthObserved rotation depends on the length of the cell and concentration, as well as the t th f ti l ti it t tstrength of optical activity, temperature,

and wavelength of light.

[α] = α (observed)lc • l

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

Chapter 5 24

length of sample cell in decimeters.

Solved Problem 2

Wh f th ti f 2 b t l i l d i l i t th b d t ti i

Solved Problem 2

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

S l tiSince 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

Solution

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

[ ] 25– 4.05° 13 5°[α] D

25 =(0.15)(2)

= –13.5°

Chapter 5 25

Biological DiscriminationBiological Discrimination

Chapter 5 26

Racemic MixturesRacemic Mixtures

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

and melting point (m. p.) from the enantiomers!

Chapter 5 27

Racemic ProductsRacemic Products

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

Chapter 5 28

Optical PurityOptical Purity

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

• One enantiomer is present in greater amounts.

observed rotation

rotation of pure enantiomerX 100o.p. =

rotation of pure enantiomer

Chapter 5 29

Calculate % CompositionCalculate % CompositionTh ifi t ti f (S) 2 i d b t i +15 90°The specific rotation of (S)-2-iodobutane is +15.90°. Determine the % composition of a mixture of (R)-

d (S) 2 i d b t if th ifi t ti f thand (S)-2-iodobutane if the specific rotation of the mixture is -3.18°.

Sign is from the enantiomer in excess: levorotatory.

3.18

15.90X 100o.p. = = 20% D + L =80 → 40 + 40

Ltotal = 20 + 40 = 60

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

totalD = 40

Chapter 5 30

Chirality of ConformersChirality of Conformers

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

• Judge chirality by looking at the most symmetrical conformersymmetrical conformer.

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

Chapter 5 31

Chirality of Conformational yIsomers

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

i d h ti ll i tiChapter 5 32

racemic and, as such, optically inactive.

Chapter 5 33

Nonmobile ConformersNonmobile 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 conformationallythe central C C bond and thus it is conformationally locked.

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

Chapter 5 34

nonsuperimposable mirror images.

Fischer ProjectionsFischer ProjectionsFl t t ti f 3 D l l• 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.p• Vertical lines are behind the plane.

Chapter 5 35

Fischer Projections (Continued)j ( )

Chapter 5 36

Fischer RulesFischer Rules

• Carbon chain is on the vertical line.Hi h t idi d b i t t• Highest oxidized carbon is at top.

• Rotation of 180° in plane doesn’tRotation of 180 in plane doesn t change molecule.D t t t 90°!• Do not rotate 90°!

Chapter 5 37

180° Rotation180 Rotation

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

Chapter 5 38

90° Rotation90 Rotation

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

• Do not rotate a Fischer projection 90°• Do not rotate a Fischer projection 90 .

Chapter 5 39

Fischer Mirror ImagesFischer 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 ClH ClCl H

CH3

Chapter 5 40

Fischer (R) and (S)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)CH

( )CH3

H ClCl H

(S)

Cl HCH3

Chapter 5 41

DiastereomersDiastereomers

• Molecules with two or more chiral carbons.• Stereoisomers that are not mirror images• Stereoisomers that are not mirror images.

Chapter 5 42

Chapter 5 43

AlkenesAlkenes

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

Chapter 5 44

T M Chi l C bTwo or More Chiral Carbons• When compounds have two or more chiral• When compounds have two or more chiral

centers they have enantiomers, diastereomers, or meso isomers.,

• Enantiomers have opposite configurations at each corresponding chiral carbon.p g

• Diastereomers have some matching, some opposite configurations.pp g

• Meso compounds have internal mirror planes.• Maximum number of isomers is 2n where n =Maximum number of isomers is 2 , where n

the number of chiral carbons.

Chapter 5 45

Comparing StructuresA th t t t d th ?A th t t t d th ?

Comparing StructuresAre 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

EnantiomersEnantiomersEnantiomersEnantiomersAll 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 nonoyy nono

DiastereomersDiastereomersMesoMesosuperimposablesuperimposable

Chapter 546

superimposablesuperimposable

M C dMeso Compounds

• Meso compounds have a plane of symmetry.p p y y• If one image was rotated 180°, then it could be

superimposed on the other image.• Meso compounds are achiral even though they have

chiral centers.

Chapter 5 47

Number of StereoisomersNumber of Stereoisomers

The 2n rule will not apply to compounds that may have a l f t 2 3 dib b t h l 3plane of symmetry. 2,3-dibromobutane has only 3

stereoisomers: (±) diastereomer and the meso diastereomer.

Chapter 5 48

CH3H Br BrH

BrH

CH CHH

H H

CH2CH3H

CH3A B

Br H

C

H

D

Chapter 5 49

Properties of Diastereomers• Diastereomers have different physical

properties so they can be easily separatedproperties, so they can be easily separated.• Enantiomers differ only in reaction with other

chiral molecules and the direction in whichchiral molecules and the direction in which polarized light is rotated.E ti diffi lt t t• Enantiomers are difficult to separate.

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

Chapter 5 50

Resolution of EnantiomersResolution of Enantiomers

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

Chapter 5 51