Description
Stereoisomerism
• These differ from each other in the
their atoms are connected, i.e., in
way their
• structures. It’s six types signifying the
• main difference in the of the isomers are:
• structural features
• Chain/ Skeletal/ Nuclear
• Position Isomerism
• Isomerism
• Functional Isomerism
• Metamerism
• Tautomerism
• Ring Chain Isomerism
I. Configurational Isomerism
II. Conformational Isomerism
• Enantiomers are known to possess same physical and chemical properties but differ in the way they interact with
polarised light. they plane Substances which can rotate the plane of
polarised light are said to be optically
active.
• Dextrorotatory (Latin: dextre means right) and is indicated by (+) sign.
Laevorotatory (Latin: laeves mean left) and is indicated by (-) sign.
Those substance which do not rotate the
plane of polarised light are called optically inactive.
• To overcome the problem of D-L system, R.S. Cahn(England), Si Christopher Ingold (England), and V.
Prelog (Zürich) evolved a new and unambiguous system for assigning absolute configuration to chiral molecules.
This system is named as CIP (Cahn, Ingold, Prelog) system after their names. It is called as R-S system as the prefixes R-and S-are used to designate the configuration at a particular chirality centre. A racemic mixture is named as (RS). This system is based on certain rules called as sequence rules and also as CIP rules .
Includes Questions
1. State and explain Recemic mixure and write note on different methods of resolution. (Winter-2020)
2. Give Difference between Enantiomers and Diesteriomers (Winter-2020)
3. Give brief note on Conformation of Cyclohexane. (Winter-2020)
4. State and Explain (Summer-2020)
a) Enantiomers b) Diesteriomers c)Specific rotation
d) Mesomers e) Geometric Isomer
5. Write a Short Note on Geometric Isomerism. (Summer-2020)
6. Explain in brief with suitable example – Stereospecific and Stereoselective reactions. (Summer-2020)
7. Define plane polarized light and discuss optical activity in detail (Summer-2019)
8. Differentiate enantiomers and diastereomers, discuss mesomers (Summer-2019)
9. Explain nomenclature of optical isomers. (Summer-2019)
10. Differentiate stereoselective and stereospecific reactions. (Winter-2019)
11. Give short notes on nomenclature of geometrical isomers. (Winter-2019)
12. Discuss the sequence rule in detail to assign configuration. (Winter-2019)
- Subject:- Organic chemistry 3
- Course:- B.pharm (pharmacy),
- Semester:- 4th sem , sem :- 4
STEREOISOMERISM
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ISOMERISM isos meros
Ethyl alcohol (CH3CH2OH) and
Dimethyl ether (CH3OCH3) are isomers.
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Stereoisomers CONSTITUTIONAL
ISOMERS
Enantiomers or Diastereomers
Optical isomers
Conformational
Geometric Meso Epimers
Ciss/trans Isomers compound
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These differ from each other in the way
their atoms are connected, i.e., in their
structures. It’s six types signifying the
main difference in the structural features
of the isomers are:
I. Chain/ Skeletal/ Nuclear Isomerism
II. Position Isomerism
III. Functional Isomerism
IV. Metamerism
V. Tautomerism
VI. Ring Chain Isomerism
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These have same molecular formula but
different arrangement of carbon chain within
the molecule. CH3
H3C—CH2—CH2—CH3 C4H10 H3C—CH—CH3
n-Butane Same molecular 2-Methylpropane (Isobutane)
(straight chain) formula (Branched chain)
CH 3 CH 2 CH 2 CH 2 CH 3
n-Pentane
CH 3 CH 3
H3 C C CH 3 C 5 H 12 H3 C CH CH 2 CH 3
Same
2-Methylbutane
CH 3 molecular formula
(Iso-pentane)
2, 2-Dimethylpropane
(Neo-pentane)
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differ in the position of attached atoms or
groups or in position of multiple (double or
triple) bonds.
OH
CH 3 CH 2 CH 2 OH CH 3 —CH—CH 3
Propan-1-ol (The OH group atC1) Propan-2-ol (The OH group atC2)
4 3 2 1 4 3 2 1
CH3CH2C CH CH3 C C CH3
But-1-yne (Triple bond at C1) But-2-yne (Triple bond at C2)
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different functional groups.
CH 3 CH 2 OH CH 3 O CH 3
Dimethyl ether
Ethanol
O O
CH3 C OH H C OCH3
Ethanoic acid Methyl methanoate
O O
and
CH3 C CH3 CH3CH2 C H
Propanone (Acetone) Propanal (Propionaldehyde)
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( i. e., -O- , -S-, -NH-, - CO- etc.). Metamerism is
shown by members of the same family, i.e., same
functional groups.
O O
O CH3
CH3CH2—C—CH2CH3 is a metamer of CH3CH2CH2—C—CH3 or
CH3—C—CHCH3
Pentan-3-one Pentan-2-one
(Diethyl ketone) (Methyl n-propyl ketone) 3-Methylbutan-2-one
(Isopropyl methyl ketone)
CH3
CH3CH2—O—CH2CH3 is a metamer of CH3CH2CH2—O—CH3 or CH3CH2CH—O—CH3
Ethoxy ethane 1-Methoxy propane 2-Methoxypropane
(Diethyl ether) (Methyl n-propyl ether) (Isopropyl methyl ether)
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Structural or constitutional isomers existing in
easy and rapid equilibrium by migration of an
tautomers ( keto-enol
tautomerism).
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Open chain and cyclic compounds having
the same molecular formula
CH 3 CH CH 2 and
Propene Cyclopropane
CH 3 C CH and
Propyne Cyclopropene
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formula but differ in the manner their
atoms or groups are arranged in the
space are called stereoisomers. It is of
two types:
I. Configurational Isomerism
II. Conformational Isomerism
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interconverted unless a covalent bond is
broken are called configurational isomers
. These isomers can be separated under
normal conditions.
The configurational isomerism is again of
two types:
a) Optical Isomerism or Enantiomerism
b) Geometrical Isomerism
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which are related to
as an object and its non-
superimposable mirror image are called
optical isomers or enantiomers (Greek:
enantion means opposite).
The optical isomers can also rotate the plane
of polarised light to an equal degree but in
opposite direction.
The property of rotating plane of polarised
light is known as optical activity.
The optical isomers have similar physical
and chemical properties .
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Mirror
COOH COOH
H OH HO H
CH3 CH3
( -) - Lactic acid ( +) - Lactic acid
(Rotates the plane of polarized (Rotates the plane of polarized
light towards left hand side i.e. light towards right hand side i.e.
anticlockwise) clockwise)
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Geometric isomers
These isomers are also called as cis-
trans isomers. For example, molecular
formula C 2H2Cl2 corresponds to two
geometric isomers as follows:
can be
interconverted rapidly at room temperature
without breaking a covalent bond are called
conformational isomers or conformers.
Because such isomers can be readily
interconverted, they cannot be separated
under normal conditions.
Two types of conformational isomers are:
a) Conformational isomers resulting from
rotation about single bond
b) Conformational isomers arising from
amine inversion
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containing single bonds have many
interconvertible conformational
isomers.e.g, 'boat' and 'chair' forms of cyclohexane.
H H H
H H H
H H H
H
H H H H
H H
H H
H
H H H
H
Cyclohexane Cyclohexane
H (Chair form) (Boat form)
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"inside out"
amine
inversion Walden inversion
R3
R3 R1
R2
N R1 N N
R1 R3 R2
R2
Transition state
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Measured with polarimeter
Rotation, in degrees, is []
Clockwise rotation is called dextrorotatory
Anti-clockwise is levorotatory
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The angle between the entrance and exit
planes is the optical rotation.
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specific
rotation,[ ]D
[]D = obser ved rotation
(pathlength x concentration)
= = degrees
Specific rotation is that obser ved for
1 g/mL in solution in cell with a 10
cm path using light from sodium
metal vapor (589 nm)
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Enantiomers are known to possess same
physical and chemical properties but they
differ in the way they interact with plane
polarised light.
Substances which can rotate the plane of
polarised light are said to be optically
active.
Dextrorotatory (Latin: dextre means right)
and is indicated by (+) sign.
Laevorotatory (Latin: laeves mean left) and
is indicated by (-) sign.
Those substance which do not rotate the
plane of polarised light are called optically
inactive. www.remixeducation.in
Angle of rotation ( is the angle
(degrees) by which the analyser is rotated
to get maximum intensity of light. It
depends upon:
(i) Nature of the substance;
(ii) Concentration of the solution in g/ml;
(iii) Length of the polarimeter tube;
(iv) of the incident monochromatic light
(598nm).
(v) Temperature of the sample.
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Enatiomerism depends on whether a
molecule in not superimposable on its
mirror image. If it is superimposable, the
molecule is optically inactive otherwise is
optically active. The most convenient
method of inspecting superimposability is
to determine whether the molecule has
any of the following three elements of
symmetry:
1.Plane of symmetry (s)
2. Centre of symmetry (i)
3.Simple or proper axis of symmetry
(Cn) www.remixeducation.in
an imaginary
plane which divides a molecule in such a way that
one half is mirror image of the other half .
A molecule with atleast a plane of symmetry can
be superimposed on its mirror image and is achiral.
A molecule that does not have a plane of symmetry
is usually chiral; it cannot be superimposed upon
its mirror image COOH
•A plan of symmetry H OH
may pass through Plane
of
atoms, between symmetry
H OH
atoms or both.
COOH
meso-Tartaric acid
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The plane has
the same thing
on both sides
for the flask
There isnomirror
planefor a hand
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42
A molecule that has a plane of
symmetr y is achiral.
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CHRIAL
- ral) [Greek : Cheir 'Handedness'] and the
property of non- superimposability is
called chirality. Thus our hands are chiral.
Similarly, alphabets R, F,J are chiral and A, M, O
are achiral.
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RR
Chiral objects
A A M M O O
(Achiral objects)
Chiral objects - human hand, gloves, shoes, etc.
Achiral objects - a sphere, a cube, a button,
socks without thumb, etc.
Chirality or molecular dissymmetry is the
necessary and sufficient condition for a
molecule to be optically active.
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• achiral
• chiral
• Enantiomers: nonsuperimposable mirror
images, different molecules.
• One enantiomeric form of limonene smells
like oranges, while its mirror image smells like
• lemons. The one enantiome r of carvone is the
essence of caraway, and the other, the
• essence of spearmint.
Most molecules in the plant and animal world are
chiral and usually only one form of then enantiomer
• is found.
Nineteen of the twenty known amino acids are
chiral, and all of them are classified as left handed.
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D and L Conversation:-
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▪ The relative configuration of the compound were established
by obtaining them by a series of reactions from either D (+)
glyceraldehyde or L(-) glyceraldehyde. These do not involve
the breaking of a bond on chiral atom, the configuration about
the chiral atom is retained. For example ,;acetic acid obtained
from L-glyceraldehyde by a series of step has L-configuration
and that obtained from D-glyceraldehyde has D-
configuration.
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▪ The relative lactic acid also produced from D-glyceraldehyde
is the same but it is levo-rotatory, while glyceraldehyde it self
is dextro rotatory,
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▪ It should be noted that the notations D and L refer to the
relative configuration, while d or(+) and l of (-) refer to
the sign of optical rotation. A compound with D-
configuration can be dextrorotatory [D(+)] levorotatory
[D(-)].similarly a compound with L-configuration can be
either [L(+)] or [L(-)].Thus the sign of rotation is not an
indication of D(+) glyceraldehyde. In fact there are large
number of compounds which have similar configurations
but different signs of rotation.
▪ In 1951 X-ray diffraction results were employed to
ascertain the absolute configuration of the molecules,
which gave the same configuration to D-glyceraldehyde
,as was assigned by Emil Fiscer.
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To overcome the problem of D-L system, R.S. Cahn
(England), Sir Christopher Ingold (England), and V.
Prelog (Zürich) evolved a new and unambiguous system
for assigning absolute configuration to chiral molecules.
This system is named as CIP (Cahn, Ingold, Prelog)
system after their names. It is called as R-S system as
the prefixes R-and S-are used to designate the
configuration at a particular chirality centre. A racemic
mixture is named as (RS). This system is based on
certain rules called as sequence rules and also as CIP
rules .
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Cahn, Ingold and Prelog helped in introducing a new system
for assigning the configurational form to the molecule. The
system replaced the DL system. This system, adopted by
IUPAC, is called the RS convention or the sequence rule
system.
In the sequence rule system, the four atoms or groups directly
attached to the asymmetric carbon atom, are to be ranked and
to be placed in a priority order. Use of the following rules was
made to decide the priority order of the groups attached to the
asymmetric carbon atom.
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◦ Each atom bonded to the stereocenter is assigned a priority, based on
atomic number. The higher the atomic number, the higher the priority.
◦ Of the four atoms directly attached to the asymmetric carbon atom, the
atom with the highest atomic number was given the highest priority and
the atom with the lowest atomic number the lowest priority.
1 6 7 8 16 17 35 53
H CH3 NH2 OH SH Cl Br I
Increasing Priority
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61
◦ If priority cannot be assigned on the basis of the atoms
bonded to the stereocenter, look to the next set of atoms.
Priority is assigned at the first point of difference.
1 6 7 8
CH2 H CH2 CH3 CH2 NH2 CH2 OH
Increasing Priority
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2. In case, the molecule has more than one group, having the same atom
through which the groups are attached to the asymmetric carbon atom,
then to decide the priority order between the groups the next atoms
attached to the first atom are taken into consideration. For example in 2-
butanol, CH3CHOHC2H5, the four different groups attached are –
CH3,
-C2H5, -OH and H. The highest priority group would be –OH and the
lowest priority group would be H. As both the groups –CH3 and –C2H5,
are attached to the asymmetric carbon atom through carbon therefore to
decide the priority between these two the next atoms attached in the
groups are to be taken into consideration. In –CH3 the next atoms are
hydrogen whereas in –C2H5 the next atoms are one carbon and two
hydrogens; therefore the priority goes to the ethyl group.
◦ Atoms participating in a double or triple bond are
considered to be bonded to an equivalent number
of similar atoms by single bonds
H H
C O C O
O C
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1.
2. Assign a priority to each substituent from 1 (highest)
to 4 (lowest)
3. Orient the molecule so that the group of lowest
priority (4) is directed away from you
4. Read the three groups projecting toward you in order from
highest (1) to lowest priority (3)
5. 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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clockwise 1 2 2 counter
1 clockwise
C C
4 4
3 3
view with
substituent of
lowest priority
in back
R (rectus) S (sinister)
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I1 I1
F C C
4 4F
Br Cl
Cl 2 Br
3 3
2
R Enantiomers S
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1. -OH HO
H
COOH HOOC
H
OH
C
2. -COOH C
3. -CH3 CH3 CH3
4. -H (R)-(-)-lactic acid (S)-(+)-lactic acid
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3 2
4 F COOH
H 2 1
Br
3H C 1
1 2 Cl 3 OH
Br Cl
H4 4
F3 H
R-configuration R-configuration S-configuration
Lowest priority 4 on horizontal li
3
2 CH3
CHO 4 1
4 1 H OH
H OH
2 CH2CH3
3 CH2OH
R-configuration S-configuration
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CHO CHO CHO
H HO H H OH
HO
H H OH HO H
HO
CH2OH CH2OH CH2OH
L-Erythrose D-Threose L-Threose
(2S, 3S) (2S, 3R) (2R, 3S)
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A 50:50 mixture of two chiral or enantiomers
compounds that are mirror images does not rotate
light – called a racemic mixture (named for “racemic
acid” that was the double salt of (+) and (-) tartaric acid
The pure compounds need to be separated or
resolved from the mixture (called a racemate)
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
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Racemic mixture, also called racemate, a mixture of
equal quantities of two enantiomers, or substances that
have dissymmetric molecular structures that are mirror
images of one another. Each enantiomer rotates the plane
of polarization of plane-polarized light through a
characteristic angle, but, because the rotatory effect of
each component exactly cancels that of the other, the
racemic mixture is optically inactive. The name is derived
from racemic acid. Racemic acid, or, more properly,
racemic tartaric acid, is a mixture of equal amounts of
dextrorotatory and levorotatory tartaric acids; it is
customarily designated D- or L-, or (+)- or (–)-,
respectively, tartaric acid.
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1. Physical methods:
- Spontaneous resolution
- Inclusion compounds
- Chromatography
2. Chemical methods:
- Diastereomeric salt formation
3. Biochemical methods:
- Enzymatic decomposition
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Usual methods of separation such as fractional
distillation, fractional crystallization or adsorption
techniques cannot be used for the separation of
enantiomers. Therefore, some special procedures are
needed for resolution of racemic mixtures. Some of
the more important methods are:
1 Preferential Crystallization
2 Biochemical Method
3 Resolution through the formation of
diastereomers: The Chemical Method
Chromatographic Method
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crystallization is closely related
to mechanical separation of crystals.
A supersaturated solution of the racemic
mixture is inoculated with a crystal of one of the
enantiomers or an isomorphous crystal of another
chiral compound. For example, when the saturated
solution of (±) sodium ammonium tartarate is seeded
with the crystal of one of the pure enantiomer or a
crystal of (–) asparagine, (–) sodium ammonium
tartarate crystalises out first.
This method is also called as entrainment
and the seed cystal is called entrainer.
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Microorganisms or enzymes are highly
stereoselective.
Fermentation of (±) tartaric acid in presence of yeast or a
mold, e.g., Pencillium glaucum . The (+) tartaric acid is
completely consumed leaving behind (–) tartaric acid.
(±) Amino acids can be separated using hog- kidney acylase
until half of acetyl groups are hydrolysed away, only acetyl
derivative of L- amino acid is hydrolysed leaving behind
acetyl derivative of D-amino acid.
Limitations:
(i)) These reactions are to be carried out in dilute solutions, so
isolation of products becomes difficult.
(ii)) There is loss of one enantiomer which is consumed by the
microorganism. Hence only half of the compound is isolat d (
partially destructive method) .
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Basic Principle
Step 1.
optically pure reagent (+) or (–)-B to give amixture of two
products which are diastereomers. The reagent (+) or (–)-B
is called the resolving agent.
(±) - A + (+)-B ,(+)A(+)B + (-)A(+)B
Step 2. The mixture of diastereomers obtained
above can be separated using the methods of
Fractional distillation, fractional crystallization, etc.
Step 3. The pure diastereomers are then decomposed
each into the corresponding enantiomer and the
original optically active reagent, which are
then separated.
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(±) - Tartaric acid + ()-Cinchonidine
(Racemic modification) (Resolving agent)
(+) - Tartaric acid - () - cinchonidine Diastereomers
+
() - Tartaric acid - () - cinchonidine (separable)
Separated by crystallization
(+) - Tartaric acid - () - cinchonidine () - Tartaric acid - () - cinchonidin
Dil.H 2 SO 4 Dil.H2 SO4
(+) - Tartaric acid () - Tartaric acid
(crystallizes out) (crystallizes out)
Similarly resolution of a (±) base with an optically active acid.
HO
(+) - base (+) - (+) - salt (+) - base
+ (+) - acid HO
() - base () - (+) - salt () - base
Diastereom ers
Racemic (separable) www.remixeducation.in
m odification
widely
used both the
enantiomers are obtained.
successful if the following conditions are
fulfilled:
(i) The resolving agent should be
optically pure.
(ii) The substrate (racemic mixture) and the
resolvingagent should have suitable
functional groups for reaction to occur.
(iii) The resolving agent should be cheap and
be capable of regeneration and
recycling.
(iv) The resolving agent should be such which
produces easily crysta llizable
diastereomeric products.
Asymetric synthesis:
▪ Whenever the achiral compound is treated with an achiral
reagent it results in the formation of racemic mixture. This is
due to the reason that there are equal probabilities for the
formation of the two enantiomers. For example when pyruvic
acid is reacted with hydrogen and nickel the product is racemic
lactic acid. This is due to the fact carbonyl group is planar and
the addition of hydrogen from either side of the carbonyl group
is equally possible, As a result, we get 1:1 mixture of
enantiomers and hence racemic mixture is obtained.
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▪ However, if pyruvic acid is first esterified with an optically
active alcohol such as (-) methyl alcohol and the optically active
thus obtained is first reduced and then hydrolysed, we get
predominantly (-) lactic acid. This is due to the fact that the
direction of attack by the reagent is determined both the chiral
centre already present in the molecule.
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▪ Thus, a method of directly preparing an optically
active isomer from an achiral molecule under the
influence of some other optically active substance
is called asymmetric synthesis.
▪ It may be mentioned here that even in asymmetric
synthesis both (+) and (-) enantiomers are formed
but one of these is obtained in predominating
amounts so that the product exhibits a net optical
rotation.
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1. Retention : Bond at chiral carbon do not break : Configuration
of substrate and product remains same
2. Inversion : Follows SN2 Mechanism. Isomer gets converted to
other form
3. Racemisation : Second chiral center forms Diasteromer (SS ,
RS)
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Stereoisomers - Compounds that have the same molecular formula and
the same connectivity, but different arrangement of the atoms in 3-
dimensional space.
Stereoisomers cannot be converted into each other without breaking
bonds. Stereoisomers can be subdivided into two general categories:
enantiomers and diastereomers.
Enantiomers are Stereoisomers whose molecules are non super
imposable mirror images of each other.
Diastereomers - Stereoisomers which are not enantiomers (or mirror
images). Chiral or asymmetric carbon - A tetrahedral carbon atom
bearing four different substituents.
Chirality centers, or stereocenters - Asymmetrically substituted
atoms in a molecular structure.
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Meso compounds, or meso forms - Symmetric, or achiral molecules that contain
stereocenters. Meso compounds and their mirror images are not stereoisomers, since
they are identical.
Optical activity - The ability of chiral substances to rotate the plane of polarized light
by a specific angle.
Dextrorotatory - Ability of chiral substances to rotate the plane of polarized light to the
right.
Levorotatory - Ability of chiral substances to rotate the plane of polarized light to the
left.
Specific rotation - The measured angle of rotation of polarized light by a pure chiral
sample under specified standard conditions.
Racemic mixture, racemic modification, or racemate - A mixture consisting of equal
amounts of enantiomers. A racemic mixture exhibits no optical activity because the
activities of the individual enantiomers are equal and opposite in value, therby canceling
each other out. www.remixeducation.in
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