Organic chemistry I

Zdenk Friedl

Chapter 4

Stereochemistry

Solomons & Fryhle: Organic

Chemistry 8th Ed., Wiley 2004
R:\STUDENTI\1.rocnik\Organic chemistry I\Miscellaneous\

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 Stereochemistry

isomerism: constitutional isomers and stereoisomers

chirality, stereogenic center
R,S nomenclature of enantiomers
optical activity
chiral drugs
molecules with more stereogenic centers
threo, erythro and meso compounds
Fischer projection formulas
D,L nomenclature of enantiomers
relative and absolute configuration

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The isomerism of organic compounds

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Constitutional isomers

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 Stereoisomers

ENANTIOMERS DIASTEREOMERS

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 Chirality
Left and right hand are not superposable - are chiral

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Chiral and achiral molecules

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 Stereogenic center

tetrahedral stereogenic center

tetrahedral stereogenic carbon
(asymmetric carbon)

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The pair of enantiomers

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Test for chirality: plane of symmetry
2-chloropropane vs. 2-chlorobutane

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Nomenclature of enantiomers
The R,S-system I

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Nomenclature of enantiomers
The R,S-system II

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Properties of enantiomers: optical activity

The behavior of enantiomers toward plane-polarized light e

optically active compounds

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Passing the plane-polarized light through an optically
active compound

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The origin of optical activity

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Specific rotation []

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Correlation between the configurations of enantiomers
and the direction []

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 Racemic mixture
e an equimolar mixture of two enantiomers
()-2-butanol

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The stereochemistry of chlorination at C2 of pentane

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 Chiral drugs I

Generally the ()-ibuprofene racemate is used (Brufen, Ibalgin),

but only (S)-enantiomer has the anti-inflammatory action

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 Chiral drugs II
Stereoselective synthesis of (S)-Naproxene
[ Nalgesin S ]

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 Absolute configuration vs. biological activity I

* COOH
H2N CH Asparagine R- sweet
CH2 CONH2
S- bitter

O * N
OH H
Propranolol R- contraceptive
S- antihypertensive

OH H
N O
* * Chloramfenikol R,R- antibiotic
O2 N HO Cl Cl S,S- inactive
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 Absolute configuration vs. biological activity II

O O H
N
N O Thalidomide R- inactive
*
S- extremely
O teratogenic

* N Ethambutol R,R- blinding agent

H3C
2
S,S- tuberculostatic
OH

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Molecules with more than one stereogenic center
the total number of stereoisomers = 2n
where n is equal to the number of tetrahedral stereogenic centers

erythro threo
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 The stereochemistry of chlorination at C3
of (S)-2-chloropentane
a The two diastereomers are not produced in equal amounts

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 Meso compounds
The achiral molecules even though they contain stereogenic centers
a they have a plane of symmetry

threo

erythro meso
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Fischer projection formulas I

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Fischer projection formulas II

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 Nomenclature of enantiomers
The D,L-system

CH=O COOH
H *C OH H2N *C H
CH2OH CH2OH
D-(+)-Glyceraldehyde L-(-)-Ser ine

(R)-(+)-Glyceraldehyde (S)-(-)-Serine

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Stereoisomerism of cyclic compounds

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 Relative configuration I
When no bonds to the stereogenic carbon are broken
a the reaction proceed with retention of configuration

[ reaction with retention of R,S- nomenclature ]

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 Relative configuration II
When no bonds to the stereogenic carbon are broken
a the reaction proceed with retention of configuration

[ reaction with change of R,S- nomenclature ]

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Resolution of enantiomers

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Basics of stereochemistry

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