Lecture 12 - Stereochemistry

General

Organic ChemistryTwo credits

Second Semester 2009

King Saud bin Abdulaziz University for Health Science

Reference Book: Organic Chemistry: A Brief Course, by Robert C. Atkins and Francis A. CareyThird Edition

Instructor: Rabih O. Al-Kaysi, PhD.

Chapter 7Chapter 7

Stereochemistry Stereochemistry

Lecture 12

7-3Dr. Wolf's CHM 201 & 202

Molecular Chirality: Molecular Chirality: EnantiomersEnantiomers

A molecule is A molecule is chiralchiral if its two mirror image if its two mirror image forms forms are notare not superposable upon one another. superposable upon one another. ASYMMETRIC!ASYMMETRIC!

A molecule is A molecule is achiralachiral if its two mirror image if its two mirror image forms forms areare superposable. SYMMETRIC! superposable. SYMMETRIC!

ChiralityChiralityChiralityChirality

BrBrClCl

HH

FF

Bromochlorofluoromethane is chiralBromochlorofluoromethane is chiralBromochlorofluoromethane is chiralBromochlorofluoromethane is chiral

It cannot be It cannot be superposed point superposed point for point on its for point on its mirror image.mirror image.

BrBrClCl

HH

FF


HH

ClClBrBr

FFTo show To show nonsuperposability, rotate nonsuperposability, rotate this model 180° around a this model 180° around a vertical axis.vertical axis.

BrBrClCl

HH

FF


HH

ClClBrBr

FF

Another lookAnother lookAnother lookAnother look

are enantiomers with respect to each otherare enantiomers with respect to each other

andand

nonsuperposable mirror images are nonsuperposable mirror images are called enantiomerscalled enantiomers

EnantiomersEnantiomersEnantiomersEnantiomers

IsomersIsomersIsomersIsomers

stereoisomersstereoisomersconstitutionalconstitutionalisomersisomers

IsomersIsomersIsomersIsomers

stereoisomersstereoisomersconstitutionalconstitutionalisomersisomers

diastereomersdiastereomersenantiomersenantiomers

ChlorodifluoromethaneChlorodifluoromethane

is is achiralachiral







The two The two structures are structures are mirror images, mirror images, but are not but are not enantiomers, enantiomers, because they because they can be can be superposed on superposed on each other.each other.

The Chirality CenterThe Chirality Center

a carbon atom with foura carbon atom with fourdifferent groups attached to itdifferent groups attached to it

also called:also called:chiral centerchiral centerasymmetric centerasymmetric centerstereocenterstereocenterstereogenic centerstereogenic center

The Chirality CenterThe Chirality Center

ww

xx yy

zz

CC

A molecule with a single chirality center A molecule with a single chirality center is chiral.is chiral.

BromoBromochlorochlorofluorofluoromethanemethane is an example. is an example.

Chirality and chirality centersChirality and chirality centers

ClCl FF

BrBr

HH

CC

A molecule with a single chirality center A molecule with a single chirality center is chiral.is chiral.

2-Butanol is another example.2-Butanol is another example.

Chirality and chirality centersChirality and chirality centers

CHCH33

OHOH

HH

CC CHCH22CHCH33

Examples of molecules with 1 chirality centerExamples of molecules with 1 chirality center

CHCH33

CC

CHCH22CHCH33

CHCH22CHCH22CHCH22CHCH33CHCH33CHCH22CHCH22

a chiral alkanea chiral alkane

Just for general knowledge, will not be tested on


Linalool, a naturally occurring chiral alcoholLinalool, a naturally occurring chiral alcohol

OHOH



1,2-Epoxypropane: a chirality center1,2-Epoxypropane: a chirality centercan be part of a ringcan be part of a ring

OO

HH22CC CHCHCHCH33

attached to the chirality center are:attached to the chirality center are:

——HH

——CHCH33

——OCHOCH22

——CHCH22OO



Limonene: a chirality Limonene: a chirality center can be part of a center can be part of a ringring

CHCH33

HH CC

CHCH33

CHCH22

attached to theattached to thechirality center are:chirality center are:

——HH

——CHCH22CHCH22

——CHCH22CH=CCH=C

——C=CC=CJust for general knowledge, will not be tested on

A molecule with a single chirality centerA molecule with a single chirality centermust be chiral.must be chiral.

But, a molecule with two or more But, a molecule with two or more chirality centers may be chiralchirality centers may be chiral

or it may not or it may not

7-23Dr. Wolf's CHM 201 & 202

Symmetry in Achiral Symmetry in Achiral StructuresStructures

Symmetry tests for Symmetry tests for achiralachiral structures structuresSymmetry tests for Symmetry tests for achiralachiral structures structures

Any molecule with a plane of symmetryAny molecule with a plane of symmetryor a center of symmetry must be or a center of symmetry must be achiralachiral..

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

has a plane of symmetry.has a plane of symmetry.

Plane of symmetryPlane of symmetry

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

1-Bromo-1-chloro-2-fluoroethene has a plane1-Bromo-1-chloro-2-fluoroethene has a planeof symmetry.of symmetry.

Plane of symmetryPlane of symmetry

A point in the center of theA point in the center of themolecule is a center of molecule is a center of symmetry if a line drawn symmetry if a line drawn from it to any element, from it to any element, when extended an equal when extended an equal distance in the opposite distance in the opposite direction, encounters an direction, encounters an identical element. identical element.

Center of symmetryCenter of symmetry


7-28Dr. Wolf's CHM 201 & 202

Properties of Chiral Molecules:Properties of Chiral Molecules:

Optical ActivityOptical Activity

7-29Dr. Wolf's CHM 201 & 202

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

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

Optical ActivityOptical ActivityOptical ActivityOptical Activity


7-30Dr. Wolf's CHM 201 & 202

LightLightLightLight

has wave propertieshas wave properties

periodic increase and decrease in amplitude of periodic increase and decrease in amplitude of wavewave


7-31Dr. Wolf's CHM 201 & 202

LightLightLightLight

optical activity is usually measured using light optical activity is usually measured using light having a wavelength of 589 nmhaving a wavelength of 589 nmthis is the wavelength of the yellow light from a this is the wavelength of the yellow light from a sodium lamp and is called the D line of sodiumsodium lamp and is called the D line of sodium


Polarized lightPolarized light

ordinary ordinary (nonpolarized) (nonpolarized) light consists of light consists of many beams many beams vibrating in vibrating in different planesdifferent planes

plane-polarized plane-polarized light consists of light consists of only those beams only those beams that vibrate in the that vibrate in the same planesame plane


Nicol prismNicol prism

Polarization of lightPolarization of light


Rotation of plane-polarized lightRotation of plane-polarized light


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

path length (path length (ll), ), andand concentration ( concentration (cc))

therefore, define specific rotation [therefore, define specific rotation [] as:] as:

Specific rotationSpecific rotation

100 100

clcl

concentration = g/100 mLconcentration = g/100 mLlength in decimeterslength in decimeters

[[] =] =


a mixture containing equal quantities a mixture containing equal quantities of enantiomers is called a of enantiomers is called a racemic mixtureracemic mixture

a racemic mixture is a racemic mixture is optically inactiveoptically inactive(( = 0) = 0)

a sample that is optically inactive can bea sample that is optically inactive can beeither an achiral substance or a racemiceither an achiral substance or a racemicmixturemixture

Racemic mixtureRacemic mixture


7-37Dr. Wolf's CHM 201 & 202

an an optically pure optically pure substance consists exclusively substance consists exclusively of a single enantiomerof a single enantiomer

enantiomeric excess enantiomeric excess = = % one enantiomer – % other enantiomer% one enantiomer – % other enantiomer

% optical purity % optical purity = = enantiomeric excess enantiomeric excess

e.g. 75% (-) – 25% (+) = 50% opt. pure (-)e.g. 75% (-) – 25% (+) = 50% opt. pure (-)

Optical purityOptical purityOptical purityOptical purity


7-38Dr. Wolf's CHM 201 & 202

Absoluteand

Relative Configuration

7-39Dr. Wolf's CHM 201 & 202

Relative configurationRelative configuration compares the compares the arrangement of atoms in space of one compound arrangement of atoms in space of one compound with those of another.with those of another.

until the 1950s, all configurations were relativeuntil the 1950s, all configurations were relative

Absolute configurationAbsolute configuration is the precise is the precise arrangement of atoms in space.arrangement of atoms in space.

we can now determine the absolute we can now determine the absolute configuration of almost any compoundconfiguration of almost any compound

ConfigurationConfigurationConfigurationConfiguration

7-40Dr. Wolf's CHM 201 & 202

No bonds are made or broken at the stereogenic centerNo bonds are made or broken at the stereogenic center

in this experiment. Therefore, when (+)-3-buten-2-ol in this experiment. Therefore, when (+)-3-buten-2-ol

and (+)-2-butanol have the same sign of rotation, the and (+)-2-butanol have the same sign of rotation, the

arrangement of atoms in space is analogous. The twoarrangement of atoms in space is analogous. The two

have the same relative configuration.have the same relative configuration.

CHCH33CHCHCHCH22CHCH33

OHOH

HH22,, PdPd

[[] + 33.2°] + 33.2° [[] + 13.5°] + 13.5°

Relative configurationRelative configurationRelative configurationRelative configuration

CHCH33CHCHCHCH

OHOH

CHCH22

7-41Dr. Wolf's CHM 201 & 202

HHHOHO

HH OHOH HH22, Pd, Pd

HHHOHOHH22, Pd, Pd

HH OHOH

Two possibilitiesTwo possibilitiesTwo possibilitiesTwo possibilities

But in the absence of additional information, we can't tell But in the absence of additional information, we can't tell which structure corresponds towhich structure corresponds to(+)-3-buten-2-ol, and which one to (–)-3-buten-2-ol.(+)-3-buten-2-ol, and which one to (–)-3-buten-2-ol.

7-42Dr. Wolf's CHM 201 & 202

HHHOHO


HHHOHOHH22, Pd, Pd

HH OHOH

Two possibilitiesTwo possibilitiesTwo possibilitiesTwo possibilities

Nor can we tell which structure corresponds toNor can we tell which structure corresponds to(+)-2-butanol, and which one to (–)-2-butanol.(+)-2-butanol, and which one to (–)-2-butanol.

7-43Dr. Wolf's CHM 201 & 202

HHHOHO


HHHOHOHH22, Pd, Pd

HH OHOH

Absolute configurationsAbsolute configurationsAbsolute configurationsAbsolute configurations

[[] +13.5°] +13.5°[[] +33.2°] +33.2°

[[] –33.2°] –33.2° [[] –13.5°] –13.5°

7-44Dr. Wolf's CHM 201 & 202

Not all compounds that have the same relativeNot all compounds that have the same relative

configuration have the same sign of rotation. No bondsconfiguration have the same sign of rotation. No bonds

are made or broken at the stereogenic center in theare made or broken at the stereogenic center in the

reaction shown, so the relative positions of the atoms reaction shown, so the relative positions of the atoms

are the same. Yet the sign of rotation changes.are the same. Yet the sign of rotation changes.

CHCH33CHCH22CHCHCHCH22BrBr

CHCH33

HBrHBr

[[] -5.8°] -5.8° [[] + 4.0°] + 4.0°

Relative configurationRelative configurationRelative configurationRelative configuration

CHCH33CHCH22CHCHCHCH22OHOH

CHCH33

7-45Dr. Wolf's CHM 201 & 202

The Cahn-Ingold-Prelog The Cahn-Ingold-Prelog

R-SR-S

Notational SystemNotational System

7-46Dr. Wolf's CHM 201 & 202

1. 1. need rules for need rules for rankingranking substituents at substituents at stereogenic center in order of decreasing stereogenic center in order of decreasing precedenceprecedence

2. 2. need convention for need convention for orientingorienting molecule so molecule so that order of appearance of substituents that order of appearance of substituents can be compared with rank can be compared with rank

The system that is used was devised by The system that is used was devised by R. S. Cahn, Sir Christopher Ingold, and R. S. Cahn, Sir Christopher Ingold, and V. Prelog.V. Prelog.

Two requirements for a systemTwo requirements for a systemfor specifying absolute configurationfor specifying absolute configuration

Two requirements for a systemTwo requirements for a systemfor specifying absolute configurationfor specifying absolute configuration

7-47Dr. Wolf's CHM 201 & 202

1. Rank the substituents at the stereogenic 1. Rank the substituents at the stereogenic center according to same rules used in center according to same rules used in EE--ZZ notation. notation.

2. Orient the molecule so that lowest-ranked 2. Orient the molecule so that lowest-ranked substituent points away from you. substituent points away from you.

The Cahn-Ingold-Prelog RulesThe Cahn-Ingold-Prelog Rules(Table 7.1)(Table 7.1)


7-48Dr. Wolf's CHM 201 & 202

43

2

1

ExampleExampleExampleExample

4 3

2

1

Order of decreasing rank:Order of decreasing rank:44 > > 33 > 2 > > 2 > 11

7-49Dr. Wolf's CHM 201 & 202

• 1. Rank the substituents at the stereogenic 1. Rank the substituents at the stereogenic center according to same rules used in center according to same rules used in EE--ZZ notation. notation.

• 2. Orient the molecule so that lowest-ranked 2. Orient the molecule so that lowest-ranked substituent points away from you.substituent points away from you.

• 3. If the order of decreasing precedence traces 3. If the order of decreasing precedence traces a clockwise path, the absolute configuration a clockwise path, the absolute configuration is is RR. If the path is anticlockwise, the . If the path is anticlockwise, the configuration is configuration is SS..



7-50Dr. Wolf's CHM 201 & 202

43

2

1

ExampleExampleExampleExample

4 3

2

1

Order of decreasing rank:Order of decreasing rank:44 33 2 2

clockwiseclockwiseRR

anticlockwiseanticlockwiseSS

7-51Dr. Wolf's CHM 201 & 202

((SS)-2-Butanol)-2-Butanol

CC OHOH

HH33CC

HHCHCH33CHCH22

Enantiomers of 2-butanolEnantiomers of 2-butanolEnantiomers of 2-butanolEnantiomers of 2-butanol CCHOHO

CHCH33

HHCHCH22CHCH33

((RR)-2-Butanol)-2-Butanol

7-52Dr. Wolf's CHM 201 & 202

Very important!Very important!Very important!Very important!

Two different compounds with the Two different compounds with the same sign of rotation need not have same sign of rotation need not have the same configuration.the same configuration.

Verify this statement by doing Problem 7.7 on page 291. Verify this statement by doing Problem 7.7 on page 291. All four compounds have positive rotations. What are their All four compounds have positive rotations. What are their configurations according to the Cahn-Ingold-Prelog rules?configurations according to the Cahn-Ingold-Prelog rules?

7-53Dr. Wolf's CHM 201 & 202

HHHH33CC

HH

HH

Chirality center in a ringChirality center in a ringChirality center in a ringChirality center in a ring

RR

——CHCH22C=C > —CHC=C > —CH22CHCH2 2 > > —CH—CH33 > —H > —H

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Lecture 12 - Stereochemistry