chapter 4 steriochemistry

8/10/2019 Chapter 4 Steriochemistry

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Introduction To Stereochemistry

Consider two of the compounds we produced while finding all the isomers of C7H16:

2-methylhexame is superimposable with its mirror image

CH3

CH3

2-methylhexane 3-methylhexane

Me

C

Me

2-methylhexane

Me

Me

H

Bu

Me

Me

H

Bu

mirror

rotateMe

Me

H

Bu

H


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CH3

CH3


Et

Me

H

Pr

Et

Me

H

Pr

mirror

rotate

C

Me

3-methylhexane

H

Et

Me

Pr

H


2-methylhexame is superimposable with its mirror image


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!Compounds that are not superimposable with their mirror image are called chiral(in Greek, chiral means

"handed") 3-methylhexane is a chiral molecule.

!Compounds that are superimposable with their mirror image are called achiral. 2-methylhexane is an

achiral molecule.

!An atom (usually carbon) with 4 different substituents is called a stereogenic centeror stereocenter.

CH3

CH3




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Enantiomers

Two compounds that are non-superimposable mirror images (the two "hands") are called enantiomers.

CH3

Et

Me

H

Pr

Et

Me

H

Pr

mirror

3-methylhexane

Et

Me

H

Pr

Et

Me

H

Pr

Me H H Me

enantiomers


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Structural (constitutional) Isomers -Compounds of the same molecular formula with different connectivity

(structure, constitution)

Conformational Isomers - Compounds of the same structure that differ in rotation around one or more

single bonds

Configurational Isomersor Stereoisomers- Compounds of the same structure that differ in one or more

aspects of stereochemistry (how groups are oriented in space - enantiomers or diastereomers)

2-methylpentane 3-methylpentane

Me

HH

HH

Me

Me

HH

MeH

H

Me H H Me


We need a a way to describe the stereochemistry!


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The CIP System Revisited

Me H

H Me

12

3 4

12

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1. Rank each substituent attached to the stereocenter according to the CIP priority system (1 = highest, 4 = lowest)

2. "View" the compound with the lowest priority substituent pointing away from you

Et Pr

Me

H

12

3

4

Pr Et

Me

H

1 2

3

4Me H

12

3 4

3. Draw a circular arrow from connecting substituents 13 from highest to lowest priority. If the arrow movesclockwise, the sterocenter is labeled (R) [this stands for rectus]. If the arrow moves counterclockwise, then thestereocenter is labeled (S) [this stands for sinister].

Et Pr

Me

H

12

3

4Me H H Me

Pr Et

Me

H

1 2

3

4

H Me

12

34

counterclockwise clockwise(S)-3-methylhexane (R)-3-methylhexane


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H3C CH3

Br H

H3C

CH3

F H

H CH3

O

HO CH3

H

H3C

CH3

CH3


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H3C CH3

Br H

H3C

CH3

F H

H CH3

O

HO CH3

H

H3C

CH3

(R)-2-fluorobutane

(S)-4-bromo-2-methyl-1-pentene

(S)-3-tert-butylcyclohexene

(R)-2-hydroxy-2-methyl-butanal

H3C

CH3

F H

1

23

4

1

2

3

4

1

23

4

CH3

1

2 3

4

H

CH3

H3C

1

2 3

4

H3C


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Properties of Chiral Molecules

Chiral objects can only be "recognized" as chiral by another chiral object

O

H

O

H

Carvone

Which is (S) and which is (R)? [Your nose can tell!]

O

H

O

H

Carvone

1

2 3

4

1

23

4

(S)(R)


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Properties of Chiral Molecules

Chiral objects can only be "recognized" as chiral by another chiral object

O

H

O

H

(R)-carvone [odor of spearmint] (S)-carvone [odor of caraway seed]


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Multiple Stereocenters

Me H H Me

(S)-3-methylhexane (R)-3-methylhexane

Me H

Me

Cl

Cl H

Me H

Cl H

Me H

Cl H

Me H

Cl H

3(S), 4(R)-3-chloro-4-methylhexane3(S), 4(S)-3-chloro-4-methylhexane 3(R), 4(R)-3-chloro-4-methylhexane3(R), 4(S)-3-chloro-4-methylhexane

1 stereocenter: 2 stereoisomers

2 stereocenter: 4 stereoisomers


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Stereoisomers that are not enantiomers (non-superimposable mirror images) are called diastereomers

Me H

Cl H

Me H

Cl H

Me H

Cl H

Me H

Cl H

3(S), 4(R)-3-chloro-4-methylhexane

3(S), 4(S)-3-chloro-4-methylhexane 3(R), 4(R)-3-chloro-4-methylhexane

3(R), 4(S)-3-chloro-4-methylhexane

What about these relationships?

enantiomers

enantiomers


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Me

Me

How many stereoisomers for 3,4-dimethylhexane?

Me

H

Me

H H

Me

H

Me

H

Me

Me

H

Me

H

H

Me

enantiomersThe same compound!

(superimposable)

Me H

MeH

H Me

HMe

Me H

HMe

(3S,4S)-3,4-dimethylhexane

H Me

MeH

(3R,4R)-3,4-dimethylhexane??-3,4-dimethylhexane??-3,4-dimethylhexane


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Meso Compounds

Me

Me

3,4-dimethylhexane has 3 stereoisomers!

Me

H

Me

H H

Me

H

Me

H

Me

Me

H

Me

H

H

Me

Enantiomers (chiral)AMesoCompound (achiral)

Me H

MeH

H Me

HMe

Me H

HMe

(3S,4S)-3,4-dimethylhexane

H Me

MeH

(3R,4R)-3,4-dimethylhexanemeso-3,4-dimethylhexanemeso-3,4-dimethylhexane


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Meso Compounds

The best way to identify a meso compound is to prove that it is superimposable with its mirror

image. However, a quick test is to see if it contains a plane of symmetry:

Compounds containing a planeof symmetry are achiral!

No plane of symmetry

(3S,4S)-3,4-dimethy lhexane (3R,4R)-3,4-dimethylhexanemeso-3,4-dimethylhexane

Me

H

Me

H

plane of symmetry

H

Me

Me

H

Me

H

H

Me


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The Isomers of C3H4Cl2, Revisited

CH3

Cl

CH2

Cl

Cl

Cl

Cl

Cl

Cl

Cl

CH3

Cl

Cl

Cl Cl

Cl

Cl

Cl

Cl

Cl

Cl

Cl

Cl


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The Isomers of C3H4Cl2, Revisited

CH3

Cl

CH2

Cl

Cl

Cl

Cl

Cl

Cl

Cl

CH3

Cl

Cl

Cl Cl

Cl

Cl

Cl

Cl

Cl

Cl

Cl

Cl

Cl

Cl


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Racemic Mixtures

A 50:50 mixture of 2 enantiomers is called a racemic mixtureor a racemate.

H3C

(E)-2-butene

HBr

2-bromobutane

achiral chiral

But do we get (R) or (S)?

We get both!

CH3H3C

50% (S)-2-bromobutane (R)-2-bromobutane

H Br

CH3H3C

Br H

50%

addition reactionCH3

H

H

H3C

CH3

H

H

H

Br


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Racemic Mixtures In Medicine

CH3

CH3

CH3

O

HO

CH3

CH3

CH3

O

HO

(R)-ibuprofen(inactive)

(S)-ibuprofen(active)

N

NH

O

O

O

O

H

N

NH

O

O

O

O

H

(S)-Thalidomide(teratogenic)

(R)-Thalidomide(analgesic)

Prescribed worldwide from 1957-1961 for morning sickness and as a sleep aid


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Optical Rotation and Polarimetry

Chiral molecules will rotate polarized light:

monochromatic light source

randomly oriented light

optical polarizer - only allows "vertical" light to pass through

optical polarizer - only allows "horizontal" light to pass through

No light emitted



optical polarizer - only allows "vertical" light to pass through optical polarizer - only allows "horizontal" light to pass through

chiral materialdetector


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optical polarizer - only allows "vertical" light to pass through optical polarizer - only allows "horizontal" light to pass through





optical polarizer

chiral material

detector

The maximum signal will be optained if the second polarizer is rotated to match the light rotation:

maximum signal



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optical polarizer


maximum signal

The amount (in degrees) that a chiral material will rotate light is called the optical rotation. Different chiral

molecules will have optical rotations that vary in direction and size of the optical rotation. Enantiomers will

always have equal optical rotations but in opposite directions.

The optical purityof a substance can be measured by comparing the optical rotation of the sample to the

known optical rotation of a single entantiomer of that compound. Optical purity is usually reported in percent

entantiomeric excess (%ee).

Enantiomeric excess is the % of the sample that is non-racemic. For example, 80% ee means that there is

90% of one enantiomer and 10% of the other.

%ee =single enantiomer rotation

sample rotation

X 100



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Vocabulary

(R) or (S): identifies the configuration of a stereocenter using the CIP priority system

d- or (+): indicates that a (chiral) compound rotates light in a clockwise direction (this

has no correlation with S or R)

lor (-): indicates that a (chiral) compound rotates light in a counterclockwise direction

(this has no correlation with S or R)

dlor (+/-) or rac-: indicates a racemate


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Resolution of Enantiomers

(R)-compound X

(S)-compound X

react or somehow associate with:

(R)-compound Y

(R)-compound X (R)-compound Y(R)-compound Y(S)-compound X

Separate by some technique (chromatography,

crystallization, distillation, etc.)

(R)-compound X (R)-compound Y

(R)-compound Y(S)-compound X

somehow remove compound Y

(R)-compound X(S)-compound X

racemic mixtureof enantiomers

Single

enantiomer

mixture of 2

diastereomers

singlediastereomer

singlediastereomer

singleenantiomer

singleenantiomer


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O

OH

Cl

Me

O

OH

Cl

Me

this hydrogenis acidic

(S)-2-chloroproprionic acid

(R)-2-chloroproprionic acid

H2N

Me(R)-!-methylbenzylamine

this hydrogenis acidic

H3N

Me

O

O

Cl

Me

O

O

Cl

Me

H3N

Me

this nitrogen lonepair is basic

(R)-!-methylbenzylamine

The R,S-diastereomer of the salt

The R,R-diastereomer of the salt

separate

O

OH

Cl

Me

H2N

Me

this nitrogen lonepair is basic

O

O

Cl

MeH3N

Me

acidify

(R)-2-chloroproprionic acid

H3N

MeO

O

Cl

Me

acidifyO

OH

Cl

Me

(S)-2-chloroproprionic acid

Resolution of Enantiomers


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H

H H

H

mirror plane

NO2

Me

O2N

Me

mirror plane

O2N

Me

NO2

Me

mirror plane

There is hindered rotationaround this bond!

Chirality Without Stereocenters


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Chirality Without Stereocenters

C

Me

Me H

H

Why is 1,3-dimethylallane (1,3-dimethyl-2,3-pentadiene) chiral?

chapter 4 steriochemistry

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