4 4-1 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Introduction to Organic Chemistry 2 ed William H. Brown

44

4-1Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.

Introduction to Introduction to Organic Organic

ChemistryChemistry2 ed2 ed

William H. BrownWilliam H. Brown

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ChiralityChiralityChapter 4Chapter 4

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StereoisomersStereoisomers• Have the same molecular formula and the same

order of attachment of their atoms (the same connectivity), but different three-dimensional orientations of their atoms in space.• example: the cis-trans isomers of cycloalkanes

cis-1,4-Dimethyl- cyclohexane

and

H

CH3

CH3

HCH3

H

CH3

Htrans-1,4-Dimethyl- cyclohexane

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StereoisomersStereoisomers• Are divided into enantiomers and diastereomers

Stereoisomers

Diastereomers(Stereoisomers whose

molecules arenot mirror images

Enantiomers(Stereoisomers whose

molecules are nonsuperposable mirror images)

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ChiralityChirality• ChiralChiral: objects that are not superposable on

their mirror images are said to be chiralchiral; that is, they show handedness

• AchiralAchiral: objects that are superposable on their mirror images are said to be achiralachiral; that is, they do not show handedness. • an object is achiral if it possesses a plane of symmetry

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Plane of SymmetryPlane of Symmetry• Plane of symmetryPlane of symmetry: an imaginary plane dividing

an object such that one half is the mirror image of the other half

Br

Cl HH

Plane of symmetryharder to see

H

C

H

ClBr

Plane of symmetryeasy to see

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Plane of SymmetryPlane of Symmetry

HO OH

mirrorplane

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ChiralityChirality• Lactic acid is chiral; that is

• it and its mirror image are nonsuperposable• it and its mirror image are enantiomers

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StereocenterStereocenter• The most common (but not the only ) cause of

chirality in organic molecules is the presence of a stereocenter

• StereocenteStereocenter: an atom in a molecule at which interchange of two atoms or groups of atoms bonded to it gives a stereoisomer• the most common type of stereocenter is a

tetrahedral carbon atom with four different groups bonded to it.

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StereocenterStereocenter• 2-Chlorobutane has one stereocenter and exists

as a pair of enantiomers

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R,S - Priority RulesR,S - Priority Rules• Each atom bonded to the stereocenter is

assigned a priority

1. Priority is based on atomic number; the higher the atomic number, the higher the priority

(53)(35)(17)(16)(8)(7)(6)(1)

Increasing priority

-H -CH3 -NH2 -OH -SH -Cl -Br -I

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R,S - Priority RulesR,S - Priority Rules2. If priority cannot be assigned on the basis of

atoms bonded directly to the stereocenter, look to the next set of atoms and continue until priority is assigned

Increasing priority

(8)(7)(6)(1)-CH2-OH-CH2-NH2-CH2-CH3-CH2-H

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R,S - Priority RulesR,S - Priority Rules3. Atoms participating in a double bond are

considered to be bonded to an equivalent number of similar atoms by single bonds

CC

O

-CH=CH2 -CH-CH2

-CH

O

H

C

C

O

is treated as

is treated as

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R or S ConfigurationR or S Configuration1. Locate th stereocenter, identify its four

substituent, and assign each a priority from 1 (highest) to 4 (lowest)

2. Orient the molecule so that the group of lowest priority (4) is directed away from you

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

4. If reading is clockwise, configuration is R (from the Latin rectus); if it is counterclockwise, configuration is S (from the Latin sinister)

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R or S ConfigurationR or S Configuration• (S)-2-Chlorobutane

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R or S ConfigurationR or S Configuration• (R)-3-Chlorocyclohexene

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Two or More StereocentersTwo or More Stereocenters• For a molecule with n stereocenters, a

maximum of 2n stereoisomers are possible• with 1 stereocenter, 21 = 2 stereoisomers are

possible• with 2 stereocenters, a maximum of 22 = 4

stereoisomers are possible• etc.

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Two or More StereocentersTwo or More Stereocenters• 2,3,4-Trihydroxybutanal

• two stereocenters; 22 = 4 stereoisomers exist

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)

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Two or More StereocentersTwo or More Stereocenters• 2,3-Dihydroxybutanedioic acid (tartaric acid)

• 2n = 4, but only three stereoisomers exist

• Meso compoundMeso compound: an achiral compound possessing two or more stereocenters

C

C

H OH

CO2H

OH

CO2H

H

C

C

HHO

CO2H

HO

CO2H

H

C

C

H OH

CO2H

H

CO2H

HO

C

C

HHO

CO2H

H

CO2H

OH

A pair of enantiomers A meso compound(plane of symmetry)

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Two or More StereocentersTwo or More Stereocenters• 2-Methylcyclopentanol

H H

CH3 HO

H H

OHH3C

H HO

CH3 H

OH H

H H3C

cis-2-Methylcyclopentanol (a pair of enantiomers)

trans-2-Methylcyclopentanol (a pair of enantiomers)

diastereomers

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Two or More StereocentersTwo or More Stereocenters• 1,2-Cyclopentanediol

H H

OH HO

H H

OH HO

H HO

OH H

OH H

H HO

cis-1,2-Cyclopentanediol (a meso compound)

trans-1,2-Cyclopentanediol (a pair of enantiomers)

diastereomers

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Two or More StereocentersTwo or More Stereocenters• cis-3-Methylcyclohexanol

OHH3C HO CH3

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Two or More StereocentersTwo or More Stereocenters• trans-3-Methylcyclohexanol

OH

H3C

HO

CH3

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Properties of StereoisomersProperties of Stereoisomers• Enantiomers have identical physical and

chemical properties in achiral environments• Diastereomers are different compounds and

have different physical and chemical properties

• Meso-tartaric acid, for example, has different physical and chemical properties from its enantiomers (see Table 4.1)

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Plane Polarized LightPlane Polarized Light• Ordinary lightOrdinary light: consists of waves vibrating in all

planes perpendicular to its direction of propagation• Plane polarized lightPlane polarized light: consists of waves vibrating

only in parallel planes• PolarimeterPolarimeter: a device for measuring the extent of

rotation of plane polarized light• Observed rotationObserved rotation: the number of degrees, ,

through which a compound rotates the plane of polarized light

• Dextrorotatory (+Dextrorotatory (+): rotation of the plane of polarized light to the right

• Levorotatory (-)Levorotatory (-): rotation of the plane of polarized light to the left

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Optical ActivityOptical Activity• Specific rotationSpecific rotation: observed rotation of the plane of

polarized light when a sample is placed in a tube 1.0 dm in length and at a concentration of 1 g/mL

length (dm) x concentration (g/mL)observed rotation (degrees)=

λT[] =Specific rotation

λT[]

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Optical ActivityOptical Activity• For a pair of enantiomers, the value of the

specific rotation of each is the same, but opposite in sign

[]25D

-13.52 +13.52D25

[α]

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

C

OH

CH3CH3CH2

HC

HO

H3C CH2CH3

H

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ResolutionResolution• Racemic mixtureRacemic mixture: an equimolar mixture of two

enantiomers• because a racemic mixture contains equal numbers of

dextrorotatory and levorotatory molecules, its specific activity is zero

• ResolutionResolution: the separation of a racemic mixture into its enantiomers

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ResolutionResolution• One means of resolution is to convert the pair

of enantiomers into two diastereomers • diastereomers are different compounds and have

different physical properties, which can be used to separate them

• A common reaction for chemical resolution is salt formation

• after separation of the diastereomers, the enantiomerically pure acids are recovered

(RR')-Salt + (SR')-Salt)(R')-Base(R,S)-Carboxylicacid

+ RCO2-

RCO2H B HB+

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ResolutionResolution• Examples of enantiomerically pure bases

= -165D25

[]

(-)-Quinine

= +228D23

[α]

(+)-Cinchonine

H

N

N

HCH2 =CH

HHO HHO

CH2 =CH

N

N

CH3 O

H H

H

H

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ResolutionResolution• Naproxen resolved by way of its ethyl ester

H3CO

C

H CH3

OCH2CH3

H3CO

C

H3C H

OCH2CH3

Ethyl ester of (S)-naproxen

Ethyl ester of (R)-naproxen(not affected by the esterase)

2. HCl, H2O

1. esterase, NaOH

O

O

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ResolutionResolution

H3CO

C

H CH3

OH+ CH3CH2OH

(S)-Naproxen

O

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Chirality in the Biological WorldChirality in the Biological World• Except for inorganic salts and a few low-

molecular-weight organic substances, the molecules of living systems are chiral

• Although these molecules can exist as a number of stereoisomers, generally only one is produced and used in a given biological system

• It is a chiral world!

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Chirality in the Biological WorldChirality in the Biological World• Consider chymotrypsin, a protein-digesting

enzyme in the digestive system of animals• chymotrypsin contains 251 stereocenters• the maximum number of stereoisomers possible is 2251

• There are only 238 stars in our galaxy!

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Chirality in the Biological WorldChirality in the Biological World• Enzymes are like hands in a handshake

• the substrate fits into a binding site on the enzyme surface

• a left-handed molecule will only fit into a left-handed binding site and

• a right-handed molecule will only fit into a right-handed binding site

• enantiomers have different physiological properties because of the handedness of their interactions with other chiral molecules in living systems

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Chiral DrugsChiral Drugs• Some chiral drugs are sold as racemic mixtures,

others as a single enantiomer

(S)-Ibuprofen

C

(S,S)-Captopril

NC

CO2 H

CCH2SH

CH3

H

H

(CH3)2CHCH2

CO2H

HCH3

O

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Chiral DrugsChiral Drugs

HO

HO

CO2H

H NH2

(S)-3,4-Dihydroxyphenylalanine (L-DOPA)

enzyme-catalyzeddecarboxylation

HO

HO NH2

Dopamine

+ CO2

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ChiralityChiralityEnd of Chapter 4End of Chapter 4

Documents

4 4-1 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Introduction to Organic Chemistry 2 ed William H. Brown