Download Properties of Enantiomers

Properties of Enantiomers
Achiral Properties
Any pair of enantiomers are physically and chemically
indistinguishable by most techniques in achiral environments.
Enantiomers have identical achiral properties such as:
 melting point,
 boiling point,
 density,
 solubility in water,
 spectroscopic properties (NMR, IR, UV)
 same rate of reaction with achiral reagents
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Properties of Enantiomers
Achiral Properties of Mandelic Acid
Mandelic acid is isolated from sweet and bitter almonds
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Enantiomers
Chiral Properties: Optical Activity
Chiral molecules rotate plane-polarised monochromatic light
either clockwise or counterclockwise. This phenomenon
is
called optical activity.
This property is inherent in the interaction between light and
the individual molecules through which it passes.
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Chiral molecules are thus optically active.
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Enantiomers
Measurement of Optical Rotation
The degree of rotation of plane-polarized light is measured
using a polarimeter.
The source light passes through a polarizer and then is
detected at an analyzer.
The angle between the entrance and exit planes is the optical
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rotation, a.
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Enantiomers
Measurement of Optical Rotation
Optical rotation a is measured in degrees.
A clockwise rotation is called dextrorotatory or (+), while
a counterclockwise rotation is levorotatory or (-).
The optical rotation a is not very useful for direct comparative
purposes since it depends on the path length the light
traverses, the concentration of the analyte, the analyte itself
and the wavelength of the light.
The more useful property is the specific rotation [a]D that is
standardized for concentration and path length.
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Enantiomers
Calculation of Specific Rotation
Specific rotation [α] is a standardized physical constant for the
degree that a solution rotates plane-polarized light.
Specific rotation is the optical rotation observed for 1 g/mL
of an analyte in solution in a cell of 10 cm (1 dm) path
length using light of the sodium D line of wavelength 589
nm.
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The temperature is maintained at 25
oC
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Enantiomers
Sample Calculation of Specific Rotation
The optical rotation of a solution of 0.497 g of valine dissolved
in 5 ml of ethanol measured in a cell of path length 2 decimeter
is +6.58o.
Calculate the specific rotation, [a]D, of the amino acid valine .
Remember to include its sign (+ or -).
Specific Rotation = Observed Rotation / (conc,g/ml) x (length of
sample tube, decimeters)
0.497g / 5 mL = 0.0994 g/mL
+6.58 / (0.0994 g/mL x 2 dm) = +33.1o
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Enantiomers
Stereochemical Terminology vs Optical Activity
Enantiomerically pure or enantiopure: Comprises of exclusively
one enantiomer.
Racemic
mixture:
Comprises
of
an
equal
mixture
of
enantiomers.
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Enantiomers
Stereochemical Terminology vs Optical Activity
Dextrorotatory (+): an optically active compound that rotates
plane polarized light in a clockwise direction. Usually
represented with d (lower case).
Levorotatory (-): an optically active compound that rotates
plane polarized light in a counterclockwise direction. Usually
represented with l (lower case).
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Enantiomers
Stereochemical Terminology vs Optical Activity
D/L vs d/l Notations
The D/L notation is unrelated to (+)/(−) or d/l; it does not
indicate which enantiomer is dextrorotatory and which is
levorotatory.
The
D/L
notations simply indicates that a compound's
stereochemistry is related to the dextrorotatory or levorotatory
enantiomer of glyceraldehyde. The dextrorotatory isomer of
glyceraldehyde is, in fact, the D- isomer.
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Enantiomers
Chiral Properties: Optical Activity
Enantiomers differ only in the properties that are chiral:
 direction of rotation of plane polarized light,
 their rate of reaction with chiral reagents,
 biological activity and taste.
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Isolated from Sweet and Bitter almonds
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Enantiomers
Chiral Properties: Optical Activity and Aroma
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Enantiomers
Chiral Properties: Biological Activity
Stereochemistry is important in biological systems because
most body reactions are stereospecific. Receptors on cells
accept only molecules with specific spatial arrangements. Other
configurations of the same chemical may not elicit a favorable
response or be toxic.
Enantiomers of a chiral drug interact with the biological
environment as depicted below.
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Enantiomers
Biological Activity: The Tragic Case of Thalidomide
Thalidomide was once hailed as a "wonder drug" that provided
a "safe, sound sleep". It was considered an effective sedative
for pregnant women to combat many of the symptoms
associated with morning sickness.
However, thalidomide later became notorious as the killer and
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Enantiomers
Biological Activity: The Tragic Case of Thalidomide
The R enantiomer fits the active site of a specific enzyme (like a
“key” for a specific “lock”) producing the desired effect
(sedative).
The S enantiomer cannot interact with the same site due to the
different arrangement of atoms (3D shape). Instead, it fits a
different enzyme active pocket triggering a different biological
effect (toxic).
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Enantiomers
Chiral Properties: Taste
Although there are individual variations between enantiomers,
there are now well-recognized taste differences between
enantiomers of many compounds.
For example, D-asparagine has a sweet taste, while the natural
L-asparagine is tasteless.
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Enantiomers
Chiral Properties: Kinetics of Enantiomers
Enantiomers react at different rates with chiral reagents.
Enzymes being chiral, the enzyme D-amino acid oxidase
catalyzes only the reaction of the R enantiomer and leaves the S
enantiomer unchanged.
The enzyme typically binds only one enantiomer since as
expected “only the right hand fits the right-hand glove”.
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Molecular Structure Relationships
The Roadmap
There are various categories of isomeric relationships that exist
between compounds of the same chemical formula. The family
tree below illustrates these relationships.
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Diastereomers
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Diastereomers
A General Introduction
Diastereomers are stereoisomers that are not mirror images of
each other.
Diastereomers can be divided into two categories:
(a) Configurational Diastereomers: These are stereoisomers of a
chiral molecule, but ones that are not enantiomers.
(b) Cis-Trans Diastereomers: These are stereoisomers, that
usually arise due to restricted rotation within a molecule;
commonly at a carbon-carbon double bond.
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Diastereomers
Configurational Diastereomers
Configurational diastereoisomerism occurs in molecules that
have more than one chiral center.
Generally, a molecule with n chiral centers can have a maximum
of 2n stereoisomers.
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Diastereomers
Configurational Diastereomers (Exceptions)
Occasionally, exceptions occur. For example, whereas tartaric
acid has 2 chiral centers and expected to have a maximum of 4
stereoisomers, it has only 3 stereoisomers.
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Diastereomers
Meso Compound
A meso compound or meso isomer is an achiral member of a
set of stereoisomers, at least two of which are chiral.
Since a meso isomer has a superposable mirror image, a
compound with a total of n stereocenters cannot have 2n
stereoisomers if at least one of the stereoisomers is meso.
Although a meso compound passes the tests of same molecular
formula, same connectivity of atoms, having a chiral centre and
mirror image, It fails the test of non-superimposability since it is
superimposable on its mirror image.
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Diastereomers
Meso Compounds
Other examples of stereoisomers that have corresponding meso
compounds include:
(a) 1,2-substituted cyclopropane has a meso cis-isomer.
(b) cis-1,2-disubstituted cycloalkanes are meso if the two
substituents are identical. cis stereoisomers of 1,2substituted cyclohexanes behave like meso compounds
since they can undergo rapid ring flipping.
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Diastereomers
Assignment
Determine which of the following compounds are chiral and
which ones are not. Give reasons to support each choice you
make.
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Diastereomers
Properties of Configurational Diastereomers
Configurational diastereomers have different chiral and achiral
properties in any environment and are thus different
compounds.
They have different:
Spectroscopic characteristics (NMR, IR, UV),
 Solubility and ease of crystallization,
Chromatographic retention times,
 Melting and boiling points
 Specific rotations.
Rates of reactions with any reagents
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Biological properties
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Diastereomers
Properties of Configurational Diastereomers
Compare the listed properties of the two diastereomers of
tartaric acid (dextrotartaric and mesotartaric acid) and note the
differences in magnitude.
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Diastereomers
Separation of Diastereomers
Being different compounds, diastereomers can be separated
through conventional techniques such as distillation, selective
crystallization and chromatography.
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Molecular Structure Relationships
The Roadmap
There are various categories of isomeric relationships that exist
between compounds of the same chemical formula. The family
tree below illustrates these relationships.
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Diastereoisomers
Cis-Trans Diastereomers (Geometric Isomers)
Cis-Trans diastereomers or geometric isomers usually arise
when there is restricted rotation in a molecule; commonly at a
carbon-carbon double bond.
Due to the restricted rotation at the double bond, groups
attached to it could be positioned on the same or opposite sides
of the alkene leading to stereoisomerism.
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Diastereoisomers
Assigning Configuration of Geometric Isomers
By applying the CIP rules, the configuration of a double bond is
specified with a prefix (E or Z) based on whether the high
priority substituents are on opposite or same side of the double
bond.
If both high priority substituents are on the same side of the
double bond, then the stereoisomer is assigned a Z or
Zusammen configuration.
If, by contrast they are on opposite sides, then the stereoisomer
is assigned an E or Entgegen configuration.
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Types of Diastereoisomers
Assigning Configuration of Geometric Isomers
Z comes from the German word Zusammen for 'together‘, while
E is derived from the word Entgegen meaning 'in opposition to'.
Note that for fumaric and maleic acid, the stereochemistry of
the compounds is implied in their names.
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Diastereoisomers
Assigning Configuration of Geometric Isomers
By determining the symbol generated in the movement, highlow-high-low, one can identify the developing symbol (E or Z)
The application of the CIP rules allows for the assignment of a
configuration that can be used in the systematic name of the
alkene.
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Diastereoisomers
Physical Properties of Geometric Isomers
Cis-trans diastereomers are different compounds. They have
different physical, chemical and biological properties. For
example, the cis and trans isomers of butenedioic acid show
large differences in their melting points.
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Diastereoisomers
Chemical Properties of Geometric Isomers
They also have different chemical properties. Whereas maleic
acid readily undergoes dehydration, fumaric acid is resistant to
dehydration.
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Diastereoisomers
Biological Activity of Geometric Isomers
Cis-trans diastereomers have different biological properties.
Triprolidine, an antihistamine drug used to combat symptoms
associated with allergies and provides general relief for flu-like
symptoms, is more effective in the E-configuration.
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