Chapter7-6-Chem207

Chem 207 B. R. Kaafarani 1

Chapter 7Stereochemistry


Chirality

A molecule is chiral if its two mirror image formsare not superimposable upon one another.

A molecule is achiral if its two mirror imageforms are superimposable.


BrCl

H

F

Bromochlorofluoromethane is chiral

It cannot besuperimposedpoint for pointon its mirrorimage.


BrCl

H

F


H

ClBr

F

To show nonsuperimposability,rotate this model 180 around avertical axis.


BrCl

H

F


H

ClBr

F


are enantiomers with respect to each other!

and

nonsuperimposable mirror images are called enantiomers

Enantiomers


Isomers

stereoisomersconstitutionalisomers

diastereomersenantiomers

Different connectivity Same connectivity;different arrangementof atoms in space

same molecular formula

Nonsuperimposable mirror images

Not enantiomers


7.2. The Chirality Center

w

x y

z

C

A carbon atom with four differentgroups attached to it

Also called:Chiral centerAsymmetric centerStereocenterStereogenic center


Chirality and Chirality Centers

Cl F

Br

H

C

A molecule with a single chirality center is chiral. Bromochlorofluoromethane & 2-butanol are examples.

CH3

OH

H

C CH2CH3

CH3

C

CH2CH3

CH2CH2CH2CH3CH3CH2CH2Chiral alkane


Examples of Molecules With 1 Chirality Center

Linalool, a naturally occurring chiral alcohol

OH



1,2-Epoxypropane: chirality center can be part of a ring.

O

H2C CHCH3

Attached to the chirality center are:HCH3OCH2CH2O



Limonene: a chiralitycenter can be part of a ring. CH3

H C

CH3

CH2

Attached to thechirality center are:HCH2CH2CH2CH=C=



Chiral as a result of isotopic substitution.

CH3CD

T

H

D: Deuterium (2H)T: Tritium (3H)


7.3. Symmetry in Achiral Structures

A molecule with a single chirality centermust be chiral.

But, a molecule with two or more chirality centers may be chiral or it may not (Sections 7.11-7.13).

Symmetry tests for achiral structures

Any molecule with a plane of symmetryor a center of symmetry must be achiral.


A plane of symmetry bisects a molecule into two mirror image halves. Chlorodifluoromethane

has a plane of symmetry.

Plane of Symmetry


Center of Symmetry

A point in the center ofthe molecule is a center ofsymmetry if a line drawnfrom it to any element,when extended an equaldistance in the oppositedirection, encounters anidentical element.


A substance is optically active if it rotates theplane of polarized light.

In order for a substance to exhibit optical activity,it must be chiral and one enantiomer must bepresent in excess of the other.

7.4. Properties of Chiral Molecules:Optical Activity


Light

Has wave properties. Periodic increase and decrease in amplitude of wave.


Light

Optical activity is usually measured using light having a wavelength of 589 nm. This is the wavelength of the yellow light from a sodium lamp and is called the D line of sodium.


Polarized light

Ordinary (nonpolarized)light consists of manybeams vibrating in differentplanes.

Plane-polarized lightconsists of only thosebeams that vibrate in thesame plane.


Nicol prism

Polarization of Light


Rotation of Plane-Polarized Light


Polarimeter


Specific Rotation []

100 cl

concentration = g/100 mLlength in decimeters

[] =

Observed rotation () depends on the number of molecules encountered and is proportional to:

Path length (l), and concentration (c)

Therefore, define specific rotation [] as:


Racemic Mixture

A mixture containing equal quantities of enantiomers is called a racemic mixture.

A racemic mixture is optically inactive ( = 0).

A sample that is optically inactive can be either achiral substance or a racemic mixture.


Optical Purity

An optically pure substance consists exclusively of a single enantiomer.

Enantiomeric excess = % one enantiomer % other enantiomer

% Optical purity = enantiomeric excess


Relative configuration compares the arrangementof atoms in space of one compound with those ofanother.

until the 1950s, all configurations were relative.

Absolute configuration is the precise arrangementof atoms in space.

We can now determine the absolute configuration ofalmost any compound!

7.5. Absolute and Relative Configuration


CH3CHCH2CH3

OH

H2, Pd

[] + 33.2 [] + 13.5

Relative configuration

CH3CHCH

OH

CH2

No bonds are made or broken at the chirality center in thisexperiment. Therefore, when (+)-3-buten-2-ol and (+)-2-butanol have the same sign of rotation, the arrangement ofatoms in space is analogous. The two have the samerelative configuration.


Two possibilities

But in the absence of additional information, we can't tellwhich structure corresponds to (+)-3-buten-2-ol, and whichone to ()-3-buten-2-ol. Nor can we tell which structure corresponds to (+)-2-butanol, and which one to ()-2-butanol.


CH3CH2CHCH2Br

CH3

HBr

[] -5.8 [] + 4.0

Relative configuration

CH3CH2CHCH2OH

CH3

Not all compounds that have the same relativeconfiguration have the same sign of rotation. No bonds aremade or broken at the chirality center in the reaction shown,so the relative positions of the atoms are the same. Yet thesign of rotation changes.


1. Rank the substituents at the chirality center.2. Orient the molecule so that lowest-ranked

substituent points away from you.

3. If the order of decreasing precedence tracesa clockwise path, the absolute configurationis R. If the path is counterclockwise, theconfiguration is S.

7.6. The Cahn Ingold PrelogR-S Notational System

The Cahn-Ingold-Prelog (CIP) Rules


12

3

4

Example

1 2

3

4

Order of decreasing rank:1 > 2 > 3 > 4


CIP Rules

HC

Br

CH3

F

1 (highest)

2

3

4 (lowest)

(1) Higher atomic number outranks lower atomic number

(2) When two atoms are identical, compare the atomsattached to them on the basis of their atomic numbers.Precedence is established at the first point of difference.

CH2CH3 outranks CH3H3C

CBr

CH2CH3

F

1 (highest)

2

3

4 (lowest)


CH(CH3)2 outranks CH2CH2OH

C(C,C,H) C(C,H,H)

CBr

CH2CH2OH

F

1 (highest)

23

4 (lowest)

H3C

CH3

(3) Work outward from the point of attachment, comparing allthe atoms attached to a particular atom before proceedingfurther along the chain.


CH2OH outranks C(CH3)3

C(O,H,H) C(C,C,C)

(4) Evaluate substituents one by one. Don't add atomic numbers within groups.

HOH2CC

H

C(CH3)3

CH3

1 (highest)

2

3

4 (lowest)


CH=O outranks CH2OH

C(O,O,H) C(O,H,H)

(5) An atom that is multiply bonded to another atom isconsidered to be replicated as a substituent on that atom.

HOH2CC

H

CH

CH3

1 (highest)

2

3

4 (lowest)

O


12

3

4

Example

1 2

3

4

Order of decreasing rank:1 2 3

clockwiseR

counterclockwiseS


C OH

H3C

HCH3CH2

Enantiomers of 2-butanol

CHO

CH3

HCH2CH3

(S)-2-Butanol (R)-2-Butanol


Very important! Two different compounds with the same sign of rotation need not have the same

configuration.


HH3C

H

H

Chirality center in a ring

R

CH2C=C > CH2CH2 > CH3 > H


Purpose of Fischer projections is to showconfiguration at chirality center without necessity ofdrawing wedges and dashes or using models.

7.7. Fischer Projections

Rules for Fischer projections

Arrange the molecule so that horizontal bonds atchirality center point toward you and vertical bondspoint away from you.

Br Cl

F

H


Rules for Fischer Projections

Projection of molecule on page is a cross. Whenrepresented this way it is understood that horizontal bondsproject outward, vertical bonds are back.

F

Br Cl

H

Br Cl

F

H


Same:Melting point, boiling point, density, etc.

Different:Properties that depend on shape of molecule(biological-physiological properties) can be different.

7.8. Properties of Enantiomers


O O

CH3 CH3

H3C H3CCH2 CH2

Odor

()-Carvonespearmint oil

(+)-Carvonecaraway seed oil

(-)-Nicotine is much more toxic than (+)-nicotine. (+)-Adrenaline is more active than (-)-adrenaline in constricting blood vessels. (-)-Thyroxine is an amino acid of the thyroid gland that speeds up metabolism

whereas (+)-thyroxine was used to be given to patients to lower their cholesteroleffects.


Chiral Receptor

Chiral receptor sites: chiral recognition


Chiral Drugs

CH2CH(CH3)2

HH3C

CO

C

HO

Ibuprofen is chiral, but normally sold as racemicmixture. The S enantiomer is the one responsible forits analgesic and antiinflammatory properties.


7.10. Reactions That Create a ChiralityCenter

It is important to recognize, however, that if all ofthe components of the starting state (reactants,catalysts, solvents, etc.) are achiral, any chiralproduct will be formed as a racemic mixture.

This generalization can be more simply stated as"Optically inactive starting materials can't giveoptically active products" (Remember: In order for asubstance to be optically active, it must be chiral andone enantiomer must be present in greater amountsthan the other.)


Example

CH3CH CH2CH3COOH

O

H3C

O

CH2C

H

Chiral, but racemicAchiral

Prochiral structural unit


Epoxidation from this direction gives R epoxide

R

Epoxidation from this direction gives S epoxide

S50%

50%


Top and bottom faces: Prochiral faces

R

Relationship between the two faces: Enantiotopic

S50%

50%


Example

CH3CH CH2

Chiral, but racemic

Br2, H2O CH3CHCH2Br

OHAchiral


Example

CH3CH CHCH3

Chiral, but racemic

HBrCH3CHCH2CH3

Br

Achiral


Many reactions convert chiralreactants to chiral products

However, if the reactant is racemic, theproduct will be racemic also.

Remember: "Optically inactive startingmaterials can't give optically active products."


Example

Chiral, but racemic

HBrCH3CHCH2CH3

OH

CH3CHCH2CH3

Br

Chiral, but racemic

* *


7.11. Chiral Molecules withTwo Chirality Centers

How many stereoisomers when a particular molecule contains two

chirality centers?


2,3-Dihydroxybutanoic acid

What are all the possible R and S combinations of the two chirality centers in this molecule?

O

CH3CHCHCOH

HO OH

23

Carbon-2 R R S SCarbon-3 R S R S

4 Combinations = 4 Stereoisomers

What is the relationship between these stereoisomers?



O

CH3CHCHCOH

HO OH

23


Enantiomers: 2R,3R and 2S,3S2R,3S and 2S,3R


Isomers

StereoisomersConstitutionalisomers

DiastereomersEnantiomers


H O H

C O 2 H

O HH

C H 3

R

R

H O H

C O 2 H

HH O

C H 3

S

S

H O H

C O 2 H

HH O

C H 3

S

R

H O H

C O 2 H

O HH

C H 3

R

S

[] = + 9.5

[] = - 9.5

[] = - 17.8

[] = + 17.8

Enantiomers

Enantiomers



O

CH3CHCHCOH

HO OH

23


But not all relationships are enantiomeric. Stereoisomers that are not enantiomers are diastereomers.


H O H

C O 2 H

O HH

C H 3

R

R

H O H

C O 2 H

HH O

C H 3

S

S

H O H

C O 2 H

HH O

C H 3

S

R

H O H

C O 2 H

O HH

C H 3

R

S

[] = + 9.5

[] = - 9.5

[] = - 17.8

[] = + 17.8

Enantiomers

Enantiomers

Diastereomers


S SR R

Two chirality centers in a ring

Nonsuperimposable mirror images; enantiomers.

trans-1-Bromo-1-chlorocyclopropane


S RS R


Nonsuperimposable mirror images; enantiomers.

cis-1-Bromo-2-chlorocyclopropane


S SS R


Stereoisomers that are notenantiomers; diastereomers

cis-1-Bromo-2-chloro-cyclopropane

trans-1-Bromo-2-chloro-cyclopropane


7.12. Achiral Moleculeswith Two Chirality Centers

It is possible for a molecule to have chirality centers yet be achiral!?


2,3-Butanediol

Consider a molecule with two equivalentlysubstituted chirality centers such as 2,3-butanediol.

CH3CHCHCH3

HO OH

32


Three stereoisomers of 2,3-butanediol

2R,3R 2S,3S

chiral chiral

2R,3S

achiral



2R,3R 2S,3Schiral chiral

These two areenantiomers



2R,3Sachiral

The third structure issuperimposable on itsmirror image.



2R,3S

achiral

Therefore, thisstructure and its mirrorimage are the same.

It is called a mesoform.

A meso form isachiral molecule thathas chirality centers.



2R,3Sachiral

Meso forms have a plane of symmetry and/or a center of symmetry.

Plane of symmetry is most common case.

Top half of molecule is mirror image of bottom half.


S RRR

chiralmeso

There are three stereoisomers of 1,2-dichloro-cyclopropane; the achiral (meso) cis isomerand two enantiomers of the trans isomer.

Cyclic compounds


Maximum number of stereoisomers = 2n.

where n = number of structural units capable of stereochemical variation.

Structural units include chirality centers and cisand/or trans double bonds.

Number is reduced to less than 2n if meso forms are possible.

How many stereoisomers?

7.13. Molecules with Multiple Chirality Centers


Example

4 chirality centers16 stereoisomers

O

HOCH2CHCHCHCHCH

OH OH OH OH


HO OH

H

H

HO

H3C

H

HCH2CH2CO2H

CH3

H

CH3

11 chirality centers 211 = 2048stereoisomers.

One is "natural" cholic acid;another is the enantiomer ofnatural cholic acid.

2046 are diastereomers ofcholic acid.

Cholic acid (Figure 7.11)


3-Penten-2-ol

HO H

E R

H OH

E S

HHO

Z R

H OH

S

How many stereoisomers?

Z


Stereochemistry of Addition to Alkenes

C C + EY C CE Y

In order to understand stereochemistry of product, you need to know two things:

(1) stereochemistry of alkene (cis or trans; Z or E).(2) stereochemistry of mechanism (syn or anti).


Br2

R

S R

S

meso

Anti addition to trans-2-butene gives a meso form.

Bromine Addition to trans-2-Butene


Br2

R

R S

S

50% 50%

Bromine Addition to cis-2-Butene

+

Anti addition to cis-2-butene gives racemic mixture of chiral enantiomers.


RCO3H

R

R S

S

syn addition to trans-2-butene gives racemic mixture of chiral enantiomers.

Epoxidation of trans-2-ButeneProblem 7.20

50% 50%

+


R

S R

S

Epoxidation of cis-2-ButeneProblem 7.20

syn addition to cis-2-butene gives a meso form.

RCO3H

meso


Stereospecific Reaction

Of two stereoisomers of a particular startingmaterial, each one gives different stereoisomeric formsof the product.

Related to mechanism: terms such as syn additionand anti addition refer to stereospecificity.


trans-2-butene

cis-2-butene

trans-2-butene

cis-2-butene bromination anti 2R,3R + 2S,3S

bromination

epoxidation

epoxidation

anti

syn

syn

meso

meso

2R,3R + 2S,3S

Stereospecific reaction


+

CH368% 32%

Stereoselective Reaction

CH3

CH2

HCH3

H

CH3H

CH3

H

H

H2

Pt

A single starting material can give two or morestereoisomeric products, but gives one of themin greater amounts than any other.


+

68% 32%

CH3

CH2

H CH3

H

CH3H

CH3

H

CH3

H

H2

Pt

CH3H* Prochiral faces

Diastereotopic


7.15 Resolution of Enantiomers

Separation of a racemic mixture into its two enantiomeric forms.


Enantiomers

C(+) C(-)

2P(+)

C(+)P(+) C(-)P(+)

Diastereomers

C(+)P(+)

C(-)P(+)

P(+)

P(+)

C(+)

C(-)

Strategy


7.16Stereoregular Polymers

AtacticIsotactic

Syndiotactic


Atactic Polypropylene

Random stereochemistry of methyl groups attached to main chain (stereorandom).

Properties not very useful for fibers etc. Formed by free-radical polymerization.


Isotactic Polypropylene

Stereoregular polymer; all methyl groups onsame side of main chain.

Useful properties. Prepared by coordination polymerization under

Ziegler-Natta conditions.


Syndiotactic Polypropylene

Stereoregular polymer; methyl groups alternateside-to-side on main chain.

Useful properties. Prepared by coordination polymerization under

Ziegler-Natta conditions.

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Chapter7-6-Chem207