15 15-1 © 2003 thomson learning, inc. all rights reserved general, organic, and biochemistry, 7e...

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15-1© 2003 Thomson Learning, Inc.All rights reserved

General, Organic, and General, Organic, and Biochemistry, 7eBiochemistry, 7e

Bettelheim,Bettelheim,

Brown, and MarchBrown, and March

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Chapter 15Chapter 15

Chirality - the Handedness Chirality - the Handedness of Moleculesof Molecules

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IsomersIsomers• Types of isomers

• in this chapter we study enantiomers and diastereomers

sameconnectivity

Stereoisomers

Chiral

Enantiomers Diastereomers

Constitutional Isomers

Cis-Trans Isomers

withstereocenters

without stereocenters

Achiral

differentconnectivity

Isomers

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EnantiomersEnantiomers• Enantiomers:Enantiomers: nonsuperposable mirror images

• as an example of a molecule that exists as a pair of enantiomers, consider 2-butanol

OH

CH3C CH2CH3

H

HO

CCH3

HCH3CH2

Original molecule Mirror image

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EnantiomersEnantiomers• one way to see that the mirror image of 2-butanol is not

superposable on the original is to rotate the mirror image

Original molecule

OH

CH3C CH2CH3

H

OH

CCH3

HCH3CH2

OH

CH3C H

CH2CH3

Mirror image The mirror imagerotated by 180°

180° rotate by 180°about the

C-OH bond

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EnantiomersEnantiomers• now try to fit one molecule on top of the other so that

all groups and bonds match exactly

• the original and mirror image are not superposable• they are different molecules• nonsuperposable mirror images are enantiomersenantiomers

OH

CH3C CH2CH3

H

OH

CH3C H

CH2CH3

The original molecule

The mirror imageturned by 180°

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EnantiomersEnantiomers• Objects that are not superposable on their mirror

images are chiralchiral (from the Greek: cheir, hand)• they show handedness

• The most common cause of enantiomerism in organic molecules is the presence of a carbon with four different groups bonded to it• a carbon with four different groups bonded to it is

called a stereocenterstereocenter

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EnantiomersEnantiomers• If an object and its mirror image are

superposable, they are identical and there is no possibility of enantiomerism• we say that such an object is achiralachiral (without chirality)

• As an example of an achiral molecule, consider 2-propanol• notice that it has no stereocenter


OH

CH3C CH3

H

OH

CCH3

HH3C

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EnantiomersEnantiomers• to see the relationship between the original and its

mirror image, rotate the mirror image by 120°

• when we do this rotation, we see that all atoms and bonds of the mirror image fit exactly on the original

• this means that the original and its mirror image are the same molecule

• they are just viewed from different perspectives


OH

CH3C CH3

H

OH

CCH3

HH3C

OH

CH3C CH3

H

The mirror imagerotated by 120°

120° rotate by 120°about the

C-OH bond

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EnantiomersEnantiomers• To summarize

• objects that are nonsuperposable on their mirror images are chiralchiral (they show handedness)

• the most common cause of chirality among organic molecules is the presence of a carbon with four different groups bonded to it

• we call a carbon with four different groups bonded to it a stereocenterstereocenter

• objects that are superposable on their mirror images are achiralachiral (without chirality)

• nonsuperposable mirror images are called enantiomersenantiomers• enantiomers always come in pairs

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The R,S SystemThe R,S System• Because enantiomers are different compounds,

each must have a different name• here are the enantiomers of the over-the-counter drug

ibuprofen

• the R,S system is a way to distinguish between enantiomers without having to draw them and point to one or the other

COOH

H CH3

HOOC

H3C H

The active enantiomerThe inactive enantiomerof ibuprofen

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The R,S SystemThe R,S System• The first step in assigning an R or S configuration

to a stereocenter is to arrange the groups on the stereocenter in order of priority• priority is based on atomic number• the higher the atomic number, the higher the priority

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-OH-NH2

-CHO

-CH2OH

-CH2CH3

-CH2H-H

-SH

-COHO

-CH2NH2

-CNH2

O

-I-Br

-Cl

Atom orGroup

oxygen (8)nitrogen (7)

carbon to oxygen, oxygen, then hydrogen (6 ->8, 8, 1)carbon to oxygen (6 -> 8)

carbon to carbon (6 -> 6)carbon to hydrogen (6 -> 1)hydrogen (1)

sulfur (16)

Reason for Priority: First Point of Difference(Atomic numbers)

carbon to oxygen, oxygen, then oxygen (6 ->8, 8, 8)

carbon to nitrogen (6 -> 7)

carbon to oxygen, oxygen, then nitrogen (6 ->8, 8, 7)

bromine (35)

chlorine (17)

iodine (53)

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The R,S SystemThe R,S System• Example:Example: assign priorities to the groups in each set

-CH2OH -CH2CH2OH-CH2CH2OH -CH2NH2(a) (b)and and

-CH2OH -CH2CH2COH

O

-CH2NH2 -CH2COH

O

and(c) (d)and

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The R,S SystemThe R,S System• Example:Example: assign priorities to the groups in each set

-CH2OH -CH2CH2OH-CH2CH2OH -CH2NH2

-CH2OH -CH2CH2OH -CH2CH2OH -CH2NH2

(a) (b)and and

Higher priority Lower priority Higher priorityLower priority

-CH2OH -CH2CH2COH

O-CH2NH2 -CH2COH

O

-CH2OH -CH2CH2COH

O

-CH2NH2 -CH2COH

O

and(c) (d)and

Higher priority Lower priority Higher priority Lower priority

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The R,S SystemThe R,S System• To assign an R or S configuration

1.assign a priority from 1 (highest) to 4 (lowest) to each group bonded to the stereocenter

2.orient the molecule in space so that the group of lowest priority (4) is directed away from you; the three groups of higher priority (1-3) then project toward you

3.read the three groups projecting toward you in order from highest (1) to lowest (3) priority

4. if reading the groups 1-2-3 is clockwise, the configuration is RR; if reading them is counterclockwise, the configuration is SS

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The R,S SystemThe R,S System• example:example: assign an R or S configuration to each

stereocenterOH

CH3C CH2CH3

HH3C COOH

C

HH2N

(a) (b)

2-Butanol Alanine

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The R,S SystemThe R,S System• example:example: assign an R or S configuration to each

stereocenterOH

CH3C CH2CH3

H

R R

1

2

34

(R)-2-Butanol

(a)

H3C COOHC

HH2N R R

1

23

4

(R)-Alanine

(b)

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The R,S SystemThe R,S System• returning to our original three-dimensional drawings of

the enantiomers of ibuprofen

COOH

H CH3

HOOC

H3C H

R S

(S)-Ibuprofen(the active enentiomer)

(R)-Ibuprofen(the inactive enantiomer)

1 12 2

3 3 44

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Two StereocentersTwo Stereocenters• For a molecule with nn stereocenters, the

maximum number of stereoisomers possible is 22nn

• we have already verified that, for a molecule with one stereocenter, 21 = 2 stereoisomers (one pair of enantiomers) are possible

• for a molecule with two stereocenters, a maximum of 22 = 4 stereoisomers (two pair of enantiomers) is possible

• for a molecule with three stereocenters, a maximum of 23 = 8 stereoisomers (four pairs of enantiomers) is possible

• and so forth

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Two StereocentersTwo Stereocenters• 2,3,4-trihydroxybutanal

• two stereocenters; 22 = 4 stereoisomers exist

• diastereomers:diastereomers: stereoisomers that are not mirror images

• (a) and (c), for example, are diastereomers

C

C

H OH

CHO

OH

CH2OH

H

C

C

HHO

CHO

HO

CH2OH

H

C

C

H OH

CHO

H

CH2OH

HO

C

C

HHO

CHO

H

CH2OH

OH

A pair of enantiomers(Erythreose)

A pair of enantiomers(Threose)

(a) (b) (c) (d)

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StereoisomersStereoisomers• example:example: mark all stereocenters in each molecule and

tell how many stereoisomers are possible for each

CH3

CH3

OH

OH

CH2=CHCHCH2CH3

OH

NH2

OHHO

HO

COOH

NH2

OH

NH2

OH

O

(a) (b) (c)

(d) (e) (f)

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StereoisomersStereoisomers• example:example: mark all stereocenters in each molecule and

tell how many stereoisomers are possible for each• solution:solution:

CH3

CH3

OH

OH

CH2=CHCHCH2CH3

OH

NH2

OHHO

HO

COOH

NH2

OH

NH2

OH

O

(a) (b) (c)

(d) (e) (f)

21 = 2

22 = 4

22 = 4

21 = 2

21 = 2

22 = 4

** *

**

* *

*

*

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StereoisomersStereoisomers• The 2n rule applies equally well to molecules with

three or more stereocenters

HO

Cholesterol has 8 stereocenters;256 stereoisomers are possible

HO

H3C

H3C

This is the stereoisomer found in human metabolism

** * * *

*

H

H

H

*

H3CH

H

*H

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Optical ActivityOptical Activity• Ordinary light:Ordinary light: light waves vibrating in all planes

perpendicular to its direction of propagation• Plane-polarized light:Plane-polarized light: light waves vibrating only in

parallel planes• Polarimeter:Polarimeter: an instrument for measuring the

ability of a compound to rotate the plane of plane-polarized light

• Optically active:Optically active: showing that a compound rotates the plane of plane-polarized light

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PolarimeterPolarimeter

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Optical ActivityOptical Activity• Dextrorotatory:Dextrorotatory: clockwise rotation of the plane of

plane-polarized light• Levorotatory:Levorotatory: counterclockwise rotation of the plane of

plane-polarized light• Specific rotation:Specific rotation: the observed rotation of an optically

active substance at a concentration of 1 g/mL in a sample tube 10 cm long

DD

H3CC

OHH

COOH

CH3

C

HOH

COOH

[]21 = -2.6°= +2.6°21

[]

(R)-(-)-Lactatic acid(S)-(+)-Lactic acid

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Chirality in BiomoleculesChirality in Biomolecules• Except for inorganic salts and a few low-

molecular-weight organic substances, the molecules in living systems, both plant and animal, are chiral• although these molecules can exist as a number of

stereoisomers, almost invariably only one stereoisomer is found in nature

• instances do occur in which more than one stereoisomer is found, but these rarely exist together in the same biological system

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Chirality in BiomoleculesChirality in Biomolecules• Enzymes (protein bio-catalysts) all have many

stereocenters• an example is chymotrypsin, an enzyme in the

intestines of animals that catalyzes the digestion of proteins

• chymotrypsin has 251 stereocenters• the maximum number of stereoisomers possible is 2251!• only one of these stereoisomers is produced and used

by any given organism• because enzymes are chiral substances, most either

produce or react with only substances that match their stereochemical requirements

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Chirality in BiomoleculesChirality in Biomolecules• how an enzyme distinguishes between a molecule and

its enantiomer

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Chirality in BiomoleculesChirality in Biomolecules• because interactions between molecules in living

systems take place in a chiral environment, a molecule and its enantiomer or one of its diastereomers elicit different physiological responses

• as we have seen, (S)-ibuprofen is active as a pain and fever reliever, while its R enantiomer is inactive

• the S enantiomer of naproxen is the active pain reliever, but its R enantiomer is a liver toxin!

HOOC

H3C H

HOOC

H3C H

OCH3(S)-Ibuprofen (S)-Naproxen

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End End Chapter 15Chapter 15

ChiralityChirality

15 15-1 © 2003 thomson learning, inc. all rights reserved general, organic, and biochemistry, 7e...

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