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Chapter 5Stereochemistry

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ISOMERS

2

Compounds with thesame molecular formula

ConformationalIsomers

rotation aboutsingle bonds

with chiral centers

Stereoisomers

MesoCompounds

Enantiomers

ConstitutionalIsomers

Cis,Trans (E,Z) Isomers(can be calleddiastereomers)

Conformations

rotation restricted

differentconnectivity

Diastereomers

stereocentersbut no chiral centers

Enantiomers

one chiral centerm ore than

one chiral center

chiralachiral

not mirror images

mirror images

Atropisomers

sameconnectivity

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Achiral: Objects, molecules, that contain elements of symmetry

Chapter 5 3

HO OH

mirrorplane

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Planes of Symmetry

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

Chapter 5 4

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Chirality: Handedness”: An object, molecule that lacks elements of

symmetry.

Chapter 5 5

Right-hand glove does not fit the left hand, it is chiral, its mirror image is different from the original

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Enantiomers: a type of stereoisomers

Compounds that are __________________mirror images.

Chapter 5 6

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Stereocenters: chirality centers, stereogenic atom

• Chiral or asymmetric carbon bonded to ______ different groups is the most common type of a chirality center

• Its mirror image will be _________compound (enantiomer).

Chapter 5 7

The double-bonded carbon atoms in cis-trans isomers are the most common types of stereocenters.

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Examples of Chirality Centers: stereocenters

Chapter 5 8

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Cis Cyclic Compounds

• Cis-1,2-dichlorocyclohexane is _______ because the molecule _______internal plane of symmetry. Both structures above are _______________

Chapter 5 9

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Trans Cyclic Compounds

• Trans-1,2-dichlorocyclopentane _________have a plane of symmetry so the images are ______________and the molecules above are _______________

Chapter 5 10

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• • Only one enantiomer of alanine is biologically active

(only the left enantiomer can be metabolized by the enzyme)

• Need a way to distinguish between them.

Chapter 5 11

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( ) and ( ) Absolute configuration; The Cahn–Ingold–Prelog Convention

• Assign a relative “priority” to each group bonded to the asymmetric carbon according to Z

I Br Cl S F O N 13C 12C 2H 1H

Chapter 5 12

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In case of ties, use the next atoms along the chain of each group as tiebreakers.

Chapter 5 13

If the atoms are the same triple bonds takes priority over double and double over single

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• Lowest priority group goes to the back.

• Draw an arrow from highest to lowest priority group.

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

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Determine absolute configuration

Chapter 5 15

CH(CH3)2

CHSH2CH2C

ClH2C CF3

CN

CCH2OH

HH2NH2C

CH2Br

CIH2CH2C

ClCH2CH3

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Assign Absolute Configuration

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OH

C

O

OHCH3

H

OH

C

O

OHCH3

H

C

CH2

CH3

OH H

CH3

C

CH2

CH3

OHH

CH3

C

CH2

CH3

Cl

H

CH3

C

CH2

CH3

ClH

CH3

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

Chapter 5 17

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18

OH

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Properties of Enantiomers• Same boiling point, melting point, and density,

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.

Chapter 5 19

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Optical Activity: the rotation of the angle of polarized light

Chapter 5 20

Clockwise Counterclockwise Clockwise Counterclockwise

Dextorotatory (+) Levorotatory (-)

Not related to (R) and (S)

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Specific Rotation Observed rotation depends on temperature, wavelength of

light, _________________________________________

Normalize:

[] = (observed) c l

(observed) is the rotation observed in the polarimeter

c is concentration in g/mL,

l is length of sample cell in decimeters.

Chapter 5 21

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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.

Chapter 5 22

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Biological Discrimination

Chapter 5 23

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____________ Mixtures

• Equal quantities of + and – ; Old notation (d,l); new (). No optical activity.• Can be formed from reactions of achiral compounds

Chapter 5 24

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Optical Purity (o.p.) sometimes called enantiomeric excess (e.e.)

observed rotation

rotation of pure enantiomerX 100o.p. =

Chapter 5 25

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.

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A commercial synthesis of naproxen, a nonsteroidal anti-inflammatory drug (NSAID),

gives the S enantiomer in 97% eeCalculate the percentages of the R and S

enantiomers in this mixture.

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H3CO

COOH

CH3

(S)-Naproxen

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Chiral compounds that do not posses a chiral carbon

A) Atropisomers

• 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 ____________: They are non-superimposable mirror images.

Chapter 5 27

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B) Allenes: Some allenes are chiral even though they do not have a chiral carbon

Build the model

Chapter 5 28

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Fischer Projections: Flat representation of a 3-D molecule

A _________________is at the intersection of horizontal and vertical lines.

_____________ lines are forward, towards you.

___________ lines are behind the plane. Away from you

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Stereoisomers or same compounds?

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CH3

CH2CH3

Cl

CH3

ClCH2CH3

H H

CH2CH3

CH3

H Cl

CH2CH3

CH3

HCl

H

CH2CH3

CH3Cl

CH2CH3

H

CH3Cl

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Stereoisomers = 2n maximum

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3-chloro-2-butanol: Identify enantiomers and diasteromers

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2,3-dihydroxybutandioic (tartaric acid). The 2n rule will not apply to compounds that

have a plane of symmetry: a meso compound

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Assign absolute configuration to each stereocenter

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Meso Compounds are achiral even though they have chiral centers because they have

_____________________

Chapter 5 33

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

Judge chirality by looking at the most symmetrical conformer. Cyclohexane can be considered to be planar,

on average.

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

Chapter 5 34

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Cyclic molecules• 2-methylcyclopentanol (4)

• 1,3-cyclopentanediol (3, cis is meso)

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Disubstituted derivatives of cycloehexane

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Methylcyclohexanols (2 Methylcyclohexanol = 4)

4-methylcyclohexanol (2)

3-methyl cyclohexanol (4)

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Disubstituted derivatives of cycloehexane

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Cyclohexanediol cis-1,2 rapid interconversion = meso

1,3-cyclohexanediol (3)

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Physical properties• Enantiomers have identical physical and chemical properties in achiral

environments (except one)• Diastereomers are different compounds and have different physical and chemical

properties.

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CH OH

COOH

C

COOH

HHOCH OH

COOH

C

COOH

HHO CH OH

COOH

C

COOH

OHH

(S,S)-Tartaric acid

0-12.7+12.7specific rotation

4.824.344.34

3.232.982.98

1251391391.6601.75981.7598

146-148171-174171-174

pK1 (25°C)solubility in water at 20°C (g/100 mL)density at 20°C (g/cm3)

melting point (°C)

Meso tartaric acid

pK2 (25°C)

(R,R)-Tartaric acid

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Diastereomers: Cis-trans Isomerism on Double Bonds

• These stereoisomers are not mirror images of each other, so they are not ___________. They are diastereomers.

Chapter 5 39

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Diastereomers: Cis-trans Isomerism on Rings

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

Chapter 5 40

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Comparing Structures

Chapter 5 41

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Resolution (separation) of enantiomers

• In 1848, Louis Pasteur noticed that a salt of racemic (±)-tartaric acid crystallizes into mirror-image crystals.

• Using a microscope and a pair of tweezers, he physically separated the enantiomeric crystals.

• Pasteur had accomplished the first artificial resolution of enantiomers.

Chapter 5 42

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Chemical Resolution of Enantiomers

React the _______________with a ______ chiral compound, such as tartaric acid, to form _________________, then separate them.

Chapter 5 43

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Resolution of (R)- and (S)-2-butanol

Chapter 5 44

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Chromatographic____________of Enantiomers

Chapter 5 45