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TRANSCRIPT
1-What is Optical Isomerism
2-What is Polarimeter?
3- Chirality
4-Enantiomers and diastereomers
Isomers
Structural isomerism
(Constitutional isomers)
Position of function groups
Skeleton or chain of carbon
Functional group
Stereoisomerism
Optical isomers
(Diastereomers
(Enantiomers
Geometrical
Cis & trans
Conformational
Configurational
Type of Isomerism
Optical isomerism
An isomerism resulting from ability of certain molecules to rotate plane of
polarized light
-- the light is rotated plane-polarized
light to either to the right or left
right ( clockwise ) + d ( dexter ) dextro
left ( anticlockwise ) - l ( laevous ) levo
Any material that rotates the plane
of polarized light.
Optically active compound is non-
superimposable on its mirror image.
C COOHH2N
CH3
H
Types of Optical isomerism
1-Optically active.
If a molecule is super-imposable on
its mirror image, the compound
does not rotate the plane polarized
light.
Example:
Alanine
(amino acid)
2-Optically inactive
B D
C C
D
A
B
MirrorMirror
Mirror imageReal molecule
Mirror image
C
DB
A
C
BD
A Mirror image
C
DB
A
A
DB
C
A
Enantiomers
Have Equal And
Opposite
Rotations
W
C
X Z
Y
W
C X Y
Z
(+) dextrorotatory (-) levorotatory
Enantiomers
All Other
Physical
Properties Are
The Same
Enantiomers (from
Greek enantio,
“opposite” and merso ,
“part”( have opposite
configuration
Optically active.
Enantiomers: isomers
that are
nonsuperimposable
mirror images of each other
Types of Optical isomerism
If one stereoisomer is “right-handed,”
its enantiomer is “left-handed.”
Optical Isomerism
Optically active
Non SuperImposable
(Enantiomers)
Optically inactive
Superimposable
(Diastereomers)
Chirality
And
Chiral Compounds
If a molecule is not superimposable on its
mirror image, it is chiral.
If it is superimposable on its mirror image, it is achiral.
What is chirality?
Chirality (cheir, Greek for hand).
The property of nonsuperimposability of an
object on its mirror image is called chirality.
Things that are
chiral have non
superimposable
mirror images
What is Chiral carbon?
Chiral carbon: It is an sp3-hybridized carbon atom with four different groups attached to it.
Chiral compound exists in a pair of enantiomers.
Chiral carbons have no symmetry they are asymmetric
Chiral center is indicated by an *.
If one stereoisomer is “right-handed,” its enantiomer is “left-
handed.”
Chiral Centers One of the ways a molecule can be chiral is to have a stereocenter.
A point in a molecule where four different groups (or atoms) are attached
to carbon is called a chiral center
also called:
asymmetric center
stereocenter
stereogenic center
• To locate a stereogenic center, examine each tetrahedral carbon atom in a
molecule, and look at the four groups—not the four atoms—bonded to it.
• Always omit from consideration all C atoms that cannot be tetrahedral
stereogenic centers. These include
*CH2 and CH3 groups * Any sp or sp2 hybridized C
Stereogenic Carbons
stereocenter
*
What is the relationship between chirality and enantiomers?
A chiral molecule always has
an enantiomer.
An achiral molecule never has
an enantiomer.
Recall that enantiomers are non-superimposable mirror images.
Enantiomers have identical physical and
chemical properties except in two
important respects: 1. They rotate the plane polarized light in opposite
directions, however in equal amounts.
The isomer that rotates the plane to the left
(anticlockwise) is called the levo isomer and is
designated (-)
While the one that rotates the plane to the right
(clockwise) is called the dextro isomer and
designated (+).
2. They react at different rates with other chiral
compounds.
This is the reason that many compounds
are biologically active while their
enantiomers are not.
They react at the same rates with achiral
compounds.
Summary of the Basic Principles of Chirality:
• Everything has a mirror image. The fundamental question is whether
the molecule and its mirror image are superimposable.
• If a molecule and its mirror image are not superimposable, the
molecule and its mirror image are an enatiomers.
• The terms stereogenic center and chiral molecule are related but
distinct. In general, a chiral molecule must have one or more
stereogenic centers.
• The presence of a plane of symmetry makes a molecule achiral.
Any material which rotates the plane of the polarized light is termed "optically
active.“
Compounds featuring chiral centers are optically active.
An isomer of optically active compound can rotate the plane of polarized light
to the left (levorotatory), in which case it will be designated (l, or -), or to the
right (dextrorotatory) in which case it will be termed (d, or +).
Label the stereogenic centers in each molecule and decide if it is chiral.
a) CH3CH2CH(Cl)CH2CH3
HCl
achiral
b) CH3CH(OH)CH=CH2
H OH
chiral
c) (CH3)2CHCH2CH2CH(CH3)CH2CH3
H CH3
chiral
A molecule that has a plane of symmetry or a
center of symmetry is superimposeabl
◦ Plane of symmetry plane bisect molecule so
one half is the mirror of the other half.
Another test for chirality is to assess whether the object itself has a
mirror plane of symmetry or center of symmetry (point of inversion).
Symmetry
plane of
symmetry
Examples
plane of symmetry :
R. S. Cahn, Sir Christopher Ingold, and V. Prelog
(according to Cahn-Ingold-Prelog)
Absolute Configuration ( AC )
The system that is used was devised by
R. S. Cahn, Sir Christopher Ingold, and
V. Prelog. Called “sequence rule”
1-Need rules for ranking substituents at
stereogenic center in order of decreasing precedence
2-Need convention for orienting molecule so
that order of appearance of substituents can be compared with rank
Absolute Configuration ( AC )
Absolute Configuration ( AC )
1. Rank the substituents at the stereogenic center
according to same rules used in E-Z notation
(Assign each group priority 1-4.)
2. Orient the molecule so that lowest-
ranked substituent points away from
you (lowest priority group (4) is in
the back, look at remaining 3 groups
in a plane.
3. If the order of decreasing precedence traces a
clockwise path, the absolute configuration is
R. If the path is anticlockwise, the
configuration is S.
Sequence Rules
Rotate to the right-hide
the hydrogen, and that
will look like this-------->
1
(S)-Bromochlorofluoromethane (R)-Bromochlorofluoromethane
2
3 4
Absolute Configuration ( AC )
Absolute Configuration ( AC )
First, we assign priorities:
we next make sure that the #4 priority group (the hydrogen) is pointed
back away from ourselves, into the plane of the page (it is already).
Is the actual spatial arrangement of atoms or groups around a chiral
carbon
In 1891 German chemist [ Emil Fisher ]
introduce formula showing the spatial arrangement of atoms
Horizontal lines come out of the page Vertical lines go back into pag
Method to project a tetrahedral carbon onto a flat surface
Tetrahedral carbon represented by two crossed lines
to show configuration at stereogenic center without necessity of
drawing wedges and dashes or using models.
Absolute Configuration ( AC )
Fischer projections
Fischer projections Absolute Configuration ( AC )
Rules
1. Draw Fischer Projection formula
2. Rank the substitution according to the
priority order(1-4)
3-Place the group of lowest priority, usually H, at
the top of the Fischer projection by using one of the
allowed motions The lowest-priority group is thus oriented back away from viewer
4. Draw an arrow from group with highest
priority to second highest priority.
if the arrow is ……
a- clockwise, the configuration is R
b- anti-clockwise, the configuration S
(±)- Ethanolamine CH3CH(OH)NH2
has one chiral carbon, so 2- enantiomers
H2N
CH3
H
OH H2N OH
H
CH3
Mirror
Fischer projection formula
Fischer projections Absolute Configuration ( AC )
Groups are assigned a priority ranking using the same set of
rules as are used in ( E ) and ( Z ) system
CH3CH(OH)NH2
1. Draw Fischer Projection formula
H2N
CH3
OH
H
Fischer projections Absolute Configuration ( AC )
2. Rank the substitution according to the priority order
H2N
CH3
OH
H
OH > NH2 > CH3 > H
1 2
3
Fischer projections Absolute Configuration ( AC )
3. The group (atom) with lowest priority [H] should be away from
the observer , if not do an even number of changes to get H away
from the observer
H2N
CH3
OH
H
1
OH OH
CH3
CH3
H2N H2N
H
H
2
Absolute Configuration ( AC )
Fischer projections
4. Draw an arrow from group with highest priority
( OH ) to second highest priority ( NH2 ) .
if the arrow is ……
a- clockwise, the configuration is R
b- anti-clockwise, the configuration S
HO
H
NH2
CH3
(R)-ethanolamine
(+)- ethanolamine
Absolute Configuration ( AC )
Fischer projections
Draw the formulas for the two enantiomers of each of the
following compunds
then assign each as Ror S
CH
Br
CH3
OH
CH
CH3H3CH2Ca- b-
H .W
A Fischer projection can have one group held steady while the
other three rotate in either a clockwise or a counterclockwise
direction
◦ Effect is to simply rotate around a single bond
Absolute Configuration ( AC )
Fischer projections
Rules for manipulating Fischer projections:
A Fischer projection can be rotated on the page by 180°, but not
by 90° or 270° ◦ Only a 180° rotation maintains the Fischer convention by keeping
the same substituent groups going into and coming out of the
plane
Absolute Configuration ( AC )
Fischer projections
A 90° rotation breaks the Fischer convention by exchanging the
groups that go into and come out of the plane
◦ A 90° or a 270° rotation changes the representation to the
enantiomer
Absolute Configuration ( AC )
Fischer projections
Determination of Number of Enantiomers
2n where n = number of chiral
carbons
n = zero no possible stereoisomers
1 2 enantiomers are possible
2 4 ~ ~ ~ ~ ~ ~ ~
3 8 ~ ~ ~ ~ ~ ~
4 16 ~ ~ ~ ~ ~ ~
5 32 ~ ~ ~ ~ ~ ~
Optical isomerism
Diastereomers Diastereomers are stereoisomers that are not mirror images of one another and are non-
superimposable on one another.
Stereoisomers with two or more stereocenters can be diastereomers.
It is sometimes difficult to determine whether or not two molecules are diastereomers
Example:2-bromo-3-chlorobutane
(±)- CH3CH(Cl)CH(Br)NH2
n = 2 ….. So No. of stereoisomer 4
CH3
H Cl
NH2
H Br
CH3
Cl H
NH2
Br H
CH3
H Cl
NH2
Br H
CH3
Cl H
NH2
H Br
1 2 3 4
Enantiomers Enantiomers
mirror mirror
1,3 and 1,4
2,3 and 2,4
are diastereoisomers
Optical isomerism
Diastereomers
Determination of Absolute configuration(AC) in enatiomer 1
a. At C1 :
H
NH2
C2
C2 NH2
H
Br
Br
2
1
So , AC at C1 is S
Br > NH2 > C2 > H
Diastereomers
Optical isomerism
a. At C2:
H
C1
CH3
Cl CH3
H
Cl
C1
2
1
AC at C2 is S
Cl > C1 > CH3 > H
Determination of (AC) in enatiomer 1
Diastereomers
Optical isomerism
So for overall
1 ( 1S, 2S )
2 ( 1R, 2R )
Similarly:
3 ( 1R, 2S )
4 ( 1S, 2R )
Louis Pasteur discovered that sodium ammonium salts of tartaric acid crystallize into right handed and left handed forms
The solutions contain mirror image isomers, called enantiomers and they crystallized in distinctly different shapes
A (50:50) racemic mixture of both crystal types dissolved together was not optically active
The optical rotations of equal concentrations of these forms have opposite optical rotations
the effect of each molecule is cancelled out
by its enantiomer
Racemic mixture Optical isomerism
*It is optically inactive as it shows no rotation of PP light(because the
rotation by each enantiomer is cancelled)
*It is often designated as being (±) or (dl) or (RS).
*A solution of either a racemic mixture or of achiral compound said to be
optically inactive
* Can be separated (resolved) into 2 optically active enantiomers .
a sample that is optically inactive can be either an achiral substance or
a racemic mixture
Racemic mixture
Thus
Optical isomerism
Resolution of racemic mixture
1- Treat the mixture with microorganism
N
N
H
CH3
N
N
H
CH3
(R,S) nicotine (R)
PseudomonasPutida
( R) RCOOH ( R) RCOO- (S) R’NH3
+
+ ( R) R’NH2
( S) RCOOH ( R) RCOO- (R) R’NH3+
Racemic mixture
2- Using chiral reagent
Optical isomerism
The pure compounds need to be separated or resolved from the mixture (called a racemate)
Using a Chiral amine changes the relationship of the products
Now we can separate the Diastereomeric Salts
*To separate components of a racemate (reversibly) we make a derivative of each with a chiral substance that is free of its enantiomer (resolving agent) *This gives Diastereomers that are separated by their differing solubility *The resolving agent is then removed
Optical isomerism
Meso-compound A meso compound is an achiral compound that has chiral centers. It is
superimposed on its mirror image and is optically inactive although it contains two or more stereocenters.
A meso compound, should have :
*two or more stereocenters,
* an internal plane,
*the stereochemistry should be R and S.
*They are diastereomers of the (R,R) and (S,S)
isomer.
*Only 3 stereoisomers
It is a general rule that any molecule with at least one stereocenter is
chiral – but as with most rules, there is an exception. Some molecules
have more than one stereocenter but are actually achiral – these are
called meso compounds. Tartaric acid, a byproduct of the wine-making
process, provides a good example
With two stereocenters, there should, in theory, be
four stereoisomers of tartaric acid. In fact, there are
only three. First of all, there is a pair of enantiomers
with (2R,3R) and (2S, 3S) stereochemistry
Now, carefully consider a (2S, 3R)
stereoisomer. You may notice that, when
it is rotated into just the right
conformation, this isomer has a plane of
symmetry passing through the C2-C3bond
That means that this molecule is not chiral, even though it has two stereocenters! It also means
that (2R,3S) tartaric acid and (2S,3R) tartaric acid are not enantiomers, as we might have
expected – they are in fact the very same molecule, meso-tartaric acid. This achiral molecule is,
however, still a diastereomer of both R,R and S,S tartaric acid. Notice that the two
‘stereocenters’ of (meso)-tartaric acid have the same four substituents – this is a prerequisite for
meso compounds; otherwise there would be no plane of symmetry
Meso-compound Optical isomerism
48
Tartaric acid has two chiral centers and one diastereomeric forms
One form is chiral and one is achiral, but both have two chiral centers
The two structures on the right in the figure are identical so the compound (2R, 3S) is
achiral
Identical substitution on both chiral centers.
Optical isomerism Meso-compound
Applications
of isomersem
In living organisms, virtually every
molecule that contains a chiral center is
found as a single enantiomer, not a racemic
mixture.
At the molecular level, our bodies are chiral
and interact differently with the individual
enantiomers of a particular compound.
For example, the two enantiomers of
carvone produce very different responses in
humans:
(−)-carvone is the substance responsible
for the smell of spearment oil,
and (+)-carvone—the major flavor
component of caraway seeds—is
responsible for the characteristic aroma of
rye bread.
Chirality in Nature
The sedative thalidomide, was sold in Europe from 1956 to the early 1960s.
It was prescribed to treat nausea during pregnancy, but unfortunately only the
(+) enantiomer was safe for that purpose.
The (−( enantiomer was discovered to be a relatively potent teratogen,
which caused the children of many women who had taken thalidomide to be
born with missing or undeveloped limbs.
As a result, thalidomide was quickly banned for this use. It is currently used to
treat leprosy, however, and it has also shown promise as a treatment for AIDS
(acquired immunodeficiency syndrome).
A racemic mixture
Ibuprofen, a common analgesic and anti-
inflammatory agent that is the active
ingredient in pain relievers
The drug is sold as a racemic mixture that
takes approximately 38 minutes to achieve
its full effect in relieving pain and swelling
in an adult human.
Because only the (+) enantiomer is active
in humans, however, the same mass of
medication would relieve symptoms in
only about 12 minutes if it consisted of
only the (+) enantiomer.
Unfortunately, isolating only the (+)
enantiomer would substantially increase
the cost of the drug. Conversion of the (−(
to (+) enantiomer in the human body
accounts for the delay in feeling the full
effects of the drug
A pharmaceutical example of a chiral compound
Extra examples
Step 1: Hold the molecule so that
1-The chiral center is on the plane of
the paper,
2-Two bonds are coming out of the
plane of the paper and are on a
horizontal plane,
3-The two remaining bonds are
going into the plane of the paper and
are on a vertical plane
To convert this stereoformula into a Fischer
projection use the following proced
Steps
Step 2: Push the two bonds coming out of the plane of the paper onto the plane of the
paper
Step 3: Pull the two bonds going into the plane of the paper onto the plane of the
paper.
Step 4: Omit the chiral atom symbol for convenience
To determine the absolute configuration of a chiral center in a
Fisher projection, use the following two-step procedure.
Step 1: Assign priority numbers to the four ligands on the chiral cente
Step 2:
If the lowest priority ligand is on a vertical bond, meaning that it is pointing away from
the viewer, trace the three highest-priority ligands starting at the highest-priority ligand
If the lowest-priority ligand is on a horizontal bond, meaning that it is pointing toward
the viewer, trace the three highest-priority ligands starting at the highest-priority
ligand
A Fischer projection restricts a three-
dimensional molecule into two
dimensions. Consequently, there are
limitations as to the operations
that can be performed on a Fischer projection
without changing the
absolute configuration at chiral centers. The
operations that do not
change the absolute configuration at a chiral
center in a Fischer
projections can be summarized as two rules.
Rule 1: Rotation of the Fischer projection by
180º in either
direction without lifting it off the plane of
the paper does not change
the absolute configuration at the chiral center.
Rule 2: Rotation of three
ligands on the chiral center in
either
direction, keeping the
remaining ligand in place,
does not change the
absolute configuration at the
chiral center.
The operations that do change the absolute configuration at a chiral
center in a Fischer projection can be summarized as two rules.
Rule 1: Rotation of the Fischer projection by 90º in either direction changes the absolute configuration at the chiral center.
Rule 2: Interchanging any two ligands on the chiral center changes the absolute configuration at the chiral center.
Assign R or S configuration to
the following Fischer projection of alanine
Strategy
Follow the steps listed in the text
1. Assign priorities to the four substituents on the chiral
carbon
2. Manipulate the Fischer projection to place the group of
lowest priority at the top by carrying out one of the
allowed motions
3. Determine the direction 1→2→3 of the remaining
three group
Configuration of alanine
Absolute Configuration ( AC )
Solution
The priorities of the groups are (1) –NH2, (2) –CO2H, (3) –CH3, and (4) –H
To bring the lowest priority (–H ) to the top we might want to hold the –CH3 group steady while rotating the other three groups counterclockwise
Absolute Configuration ( AC )
Configuration of alanine
Draw the formulas for the two enantiomers of each of the
following compunds
then assign each as Ror S
CH
Br
CH3
OH
CH
CH3H3CH2Ca- b-
Examine the following structural formulas and select those that are chiral.
Label the stereogenic centers in each molecule and decide if it is chiral.
a) CH3CH2CH(Cl)CH2CH3
HCl
achiral
b) CH3CH(OH)CH=CH2
H OH
chiral
c) (CH3)2CHCH2CH2CH(CH3)CH2CH3
H CH3
chiral
How many stereogenic centers does each molecule have?
a)
Br
Br
b)
HC CH2CH3
CH3CHCOH
NH2
O
O
CH
CH
CH2OH
HO
CH3CCH2CH
Cl
Br
CHCH3
a.
c.
b.
d.
Practice Exercise
How many chiral carbon atoms are there in the open-chain form
of fructose
Answer: three
Solve: The carbon atoms numbered 2, 3, 4, and 5 each
have four different groups attached to them, as indicated
here:
How many chiral carbon atoms are there in the open-chain form
of glucose
CH3 C
CH2OH
CH3
CH2 CH CH
CH3
CH3
OH*
Identify the stereocenters (chiral carbon atoms) in the following
molecule?
*
OH
C CH2OH
Br
H
CH3
CH3
C CO2H
NH2
H
CH(CH3)2
C
C CO2H
Cl
H
NH2
C CH3
CH2CH2CH3
H
O
CH3
H
CH2CH3
CO2H
NH2
H
ValineAlanine
**
2-aminopentane2-Chloro- propanoic acid
2-Bromo-2- hydroxyethanol
*
***
Carvone (caraway)
Amino acids
http://chemwiki.ucdavis.edu/Organic_Chemistry/Chirality/Absolute_Config
uration,_R-S_Sequence_Rules
http://www2.chemistry.msu.edu/faculty/reusch/VirtTxtJml/sterism3.htm
http://catalog.flatworldknowledge.com/bookhub/4309?e=averill_1.0-
ch24_s02
http://colapret.cm.utexas.edu/courses/Nomenclature_files/Stereochemistry.htm
