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5.5
Sequence Rules for Specifying
Configuration
Configuration
•
The three-dimensional arrangement of substituents
at a chirality center
Sequence rules to specify the configuration of a chirality
center:
Look at the four atoms directly attached to the chirality center
and assign priorities in order of decreasing atomic number
1.
•
•
The atom with the highest atomic number is ranked first; the
atom with the lowest atomic number (usually hydrogen) is ranked
fourth
Heavier isotopes of the same element rank higher than the
lighter isotopes
Sequence Rules for Specifying Configuration
2.
If a decision cannot be reached by ranking the first atoms
in the substituents, look at the second, third, or fourth
atoms outward until a difference is found
Sequence Rules for Specifying Configuration
3.
Multiple-bonded atoms are equivalent to the same
number of single-bonded atoms
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Sequence Rules for Specifying Configuration
Sequence Rules for Specifying Configuration
Stereochemical configuration around the carbon
•
Once priorities have been assigned to the four groups attached
to the chiral carbon, orient the molecule so that the group of
lowest priority (4) points directly back
• Look at the three remaining substituents
•
•
R configuration
• If a curved arrow drawn from highest to lowest priority (1→2→3)
through substituents is clockwise
S configuration
• If a curved arrow drawn from highest to lowest priority (1→2→3)
through substituents is counterclockwise
Sequence Rules for Specifying Configuration
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Sequence Rules for Specifying Configuration
(-)-Lactic acid
Rule 1
•
-OH has priority 1
• -H has priority 4
Rule 2
•
-CO2H is higher in priority
than –CH3
•
O (the highest second
atom in –CO2H)
outranks H (the highest
second atom in –CH3)
Sequence Rules for Specifying Configuration
(-)-Glyceraldehyde
• S configuration
(+)-Alanine
• S configuration
Both have the S configuration, although one is levorotatory and the other is
dextrorotatory
•
The sign of optical rotation, (+) or (-) is not directly correlated to the R,S
designation
Sequence Rules for Specifying Configuration
Absolute configuration
• The exact three-dimensional structure of a chiral
molecule
• They are specified verbally by the Cahn-IngoldPrelog R,S convention
• In 1951, an X-ray spectroscopic method for
determining the absolute spatial arrangement of
atoms in a molecule was found
•
Based on these results, it can be said with a
certainty that the R,S conventions are correct
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Worked Example 5.3
Assigning Configuration to Chirality Centers
Orient each of the following drawings so that the lowest-priority
group is toward the rear, and then assign R or S
configuration:
Worked Example 5.4
Drawing the Three-Dimensional Structure of an
Enantiomer
Draw the tetrahedral representation of
(R)-2-chlorobutane.
5.6 Diastereomers
Molecules with more than one chirality center
• A molecule with n chirality centers can have up to 2n
stereoisomers (although it may have fewer)
• Amino acid threonine (2-amino-3-hydroxybutanoic acid)
CH3CH(OH)CH(NH2)COOH
•
•
Two chirality centers (C2 and C3)
Four possible stereoisomers
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Diastereomers
The four stereoisomers of 2-amino-3-hydroxybutanoic acid
Diastereomers
The four stereoisomers of 2-amino-3-hydroxybutanoic acid can
be grouped into two pairs of enantiomers
• The 2R, 3R stereoisomer is the mirror image of 2S, 3S
• The 2R, 3S stereoisomer is the mirror image of 2S, 3R
Diastereomers
• Stereoisomers that are not mirror images
•
•
•
Enantiomers have opposite configurations at all chirality
centers
Diastereomers have opposite configurations at one or more of
the chirality centers but the same configuration at others
2R, 3R stereoisomer and 2R, 3S stereoisomer are
diastereomers because they have the same configuration at
C2 but different configurations at C3.
Diastereomers
• Of the four stereoisomers of threonine, only the 2S,
3R isomer [ ]D = -28.3 occurs naturally in plants and
animals and is an essential human nutrient
• Most biological molecules are chiral, and usually only
one stereoisomer is found in nature
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Diastereomers
Epimers
• Two diastereomers that differ at only one chirality center but
are the same at all the others
•
Cholestanol and coprostanol are both found in human feces
and both have nine chirality centers
•
•
Eight of the nine chirality centers are identical, but the one at
C5 is different
Cholestanol and coprostanol are epimeric at C5
5.7 Meso Compounds
Tartaric acid
• A compound with more than one chirality center
Meso Compounds
• 2R, 3R and 2S, 3S structures represent a pair of
enantiomers because they are not identical
• 2R, 3S and 2S, 3R structures are identical
• The molecule has a plane of symmetry
• Achiral
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Meso Compounds
Meso compounds
• Molecule that are achiral, yet contain chirality centers
• Tartaric acid exists as only three stereoisomers: two
enantiomers and one meso form
Meso Compounds
The (+)- and (-)-tartaric acids
•
Have identical melting points, solubilities, and densities
Differ in sign of their rotation of plane-polarized light
• The meso isomer is diastereomeric with the (+) and (-) forms
• It has no mirror-image relationship to (+)- and (-)-tartaric acids
• Is a different compound
• Has different physical properties
•
Worked Example 5.5
Distinguishing Chiral Compounds from Meso
Compounds
Does cis-1,2-dimethylcyclobutane have any chirality centers?
Is it chiral?
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5.8 Racemic Mixtures and the Resolution of
Enantiomers
Racemate or racemic mixture
• Denoted by either the symbol ( ) or the prefix d,l to
indicate an equal mixture of dextrorotatory and
levorotatory forms
• Show no optical rotation because the (+) rotation form one
enantiomer exactly cancels the (-) rotation from the other
• Pasteur started with a 50 : 50 mixture of the two chiral
tartaric acid enantiomers
•
He was able to resolve, or separate, the racemic tartaric
acid into its (+) and (-) enantiomers
Racemic Mixtures and the Resolution of
Enantiomers
The most common method of resolution uses an acid-base reaction
between the racemate of a chiral carboxylic acid (RCO2H) and an
amine base (RNH2) to yield an ammonium salt
•
Reaction of the
racemate of a chiral
acid, lactic acid, and
an achiral amine base,
methylamine, CH3NH2
•
The product is an
unresolvable 50 : 50
mixture of
methylammonium (+)lactate and
methylammonium
(-)-lactate
Racemic Mixtures and the Resolution of
Enantiomers
Reaction of the racemate of lactic acid and a single enantiomer of a
chiral amine base (R)-1-phenylethylamine
•
(+)- and (-)-lactic acids react with (R)-1-phenylethylamine to give an
R,R ammonium salt and an S,R ammonium salt
• Ammonium salts are separated as two different diastereomers with
different chemical and physical properties
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