2. Stereochemistry
Part of science which deals with the three-dimensional arrangement of atoms, molecules
and the effect of this on chemical reactions is called as Stereochemistry.
Isomers:
Isomers are molecules that have the same molecular formula but differ from each other in
physical or chemical properties.
Stereoisomers:
When isomerism is caused by the different arrangements of atoms or groups in space, the
phenomenon is called Stereoisomerism.
Stereoisomers:
The Stereoisomers have the same structural formulas but differ in the spatial
arrangement of atoms or groups in the molecule.
Types of stereoisomerism:
• Optical isomerism
• Geometrical or cis-trans isomerism
3. Optical isomerism
Optical isomers are the isomers that are identical in all physical (like melting point, boiling
point, density etc.) and chemical properties except for their action on plane polarized light.
This property which is often referred to as the Optical activity.
Optical activity:
Plane-polarized light is light whose vibrations take place in only one of these possible plane.
Nicole prism:
Ordinary light is turned into plane-polarized light by passing it through a lens made of the
material kirown as Polaroid or more traditionally through pieces of calcite (a particular
crystalline form of CaCO3) so arranged as to constitute what is called a Nicol prism
4. The property of a substance of rotating the plane of polarized light is called optical
activity and the substance possessing it is said to be optically active.
Optical activity in a compound is detected and measured by means of a polarimeter.
• The compound which rotates the plane of polarized light to the right is said to be
dextrorotatory. It is indicated by the sign (+).
• The compound which rotated the plane of polarized light to the left is said to be
levorotatory. It is indicated by the sign (-).
• If the substance does not affect the plane of polarization, light transmission is still at a
maximum and the substance is said to be optically inactive.
Example: lactic acid that is extracted from muscle tissue rotates light to the right, and
hence is known as dextrorotatory lactic acid, or ( +) lactic acid.
Light Source Polarizer Tube Analyzer Eye
5. Specific rotation:
Specific rotation is the number of degrees of rotation observed if a 1 decimeter tube is used,
and the compound being examined is present to the extent of 1 g/mL.
Example: The specific rotation of amyl alcohol (2-methyl-l-butanol at 25°C) is -5.90.
6. Enantiomerism:
The relationship between two stereoisomers having molecule that are mirror images of each
other is called as enantiomerism.
Enantiomers:
Isomers that are mirror images of each other are called enantiomers.
identical physical and chemical properties except for the direction of rotation of the plane of
polarized light and reaction towards optically active reagents.
(+)-2-methyl-1-butanol (-)-2-methyl-1-butanol
Specific rotation +5.90° -5.90°
Boiling point 128.9°C 128.9°C
Relative density 0.8193 0.8193
Refractive index 1.4107 1.4107
7. Distereomerism
The relationship between two stereoisomers having molecules that are not mirror images of
each other is called diestereomerism. Such molecules are called diestereomers.
(I) is the mirror image of (II); (III) is the mirror image of (IV). Thus the four isomers are two
pair of enantiomers. When comparing (I) with (III) and (II) with (IV); they are neither
superimposable nor are the mirror images of each other and hence are called as diestereomers.
• different physical properties (like melting points, boiling points, solubilities in a given
solvent, densities, refractive indexes).
• differ in specific rotation;
• Differences in boiling point and in solubility.
• Can be separated from each other by fractional distillation or fractional crystallization.
• Differences in molecular shape and polarity, they differ in adsorption, can be separated
by chromatography
8. Meso compounds
A compound with two or more chiral carbon atoms but also having a plane of symmetry (a
mirror plane) is called the meso compounds.
Meso Tartaric acid
Recemic modification
• A mixture of equal parts of enantiomers is called a racemic modification.
• A racemic modification is optically inactive: when enantiomers are mixed together, a
rotation caused by a molecule of one isomer is exactly canceled by an equal and opposite
rotation caused by a molecule of its enantiomer.
• The prefix ± is used to specify the racemic nature of the perpendicular sample as, for
example (±)-lactic acid
9. Recemic modification
• The process of conversing an optically active compound (+)- or (-)- into racemic
modification (±) is known as racemization.
CH3
C
H OH
COOH
C
H3
C OH
C OH
O
H
CH3
C
H OH
COOH
+
CH3
C
O
H H
COOH
(+)-Acid Enol (unstable) (+)-Acid (-)-Acid
(Recemic mixture)
Chiral and achiral molecules
• A carbon atom is described as being asymmetric when four different atoms or groups are
bonded to it. Such carbon is called chiral carbon (sometimes it is called chiral centre)
COOH
C
H OH
CH3
Lactic acid
Chiral centre
10. DL system of nomenclature of optical isomers
• Compounds with similar configuration at the asymmetric carbon atom may have opposite
sign of rotations and compounds with different configuration may have same sign of
rotation.
• Thus D-L-system has been used to specify the configuration at the asymmetric carbon
atom. In this system, the configuration of an enantiomer is related to a standard,
glyceraldehyde.
COOH
C
H OH
CH3
COOH
C H
O
H
CH3
d-Lactic acid
+3.82°
l-Lactic acid
– 8.25°
H OH
CHO
CH2OH
* H
O
H
CHO
CH2OH
*
(+) Glyceraldehyde
D configuration
(-) Glyceraldehyde
L configuration
12. RS system of specifying configuration
• R. S. Calm, C. K. Ingold and V. Prelog
• Step I: Assigning a sequence of priority to the four atoms or groups of atoms attached to the
chiral centre. For example in Bromochloriodomethane. Priority is I (53), Br (35), Cl (17), H (01).
• Step II: Visualization of molecule: The configuration is specified as R (Latin: rectus, right); if
counterclockwise, the configuration is specified as S (Latin: sinister, left).
R and S configuration of bromochloroiodomethane
13. Sequence rules:
Sequence rule 1: For example, in Chloroiodomethanesulfonic acid the sequence is
I, Cl, S, H; in -Deuterioethyl bromide it is Br, C, D, H.
Sequence rule 2:
Sequence rule 3:
14. Sequence rules:
Sequence rule 3:
Assymetric synthesis:
• Asymmetric synthesis is a reaction in which an achiral unit in a substrate a molecule is
converted into a chiral unit in such a manner that unequal amounts of stereoisomers
(enantiomers or diastereomers) are produced.
• When a compound containing an asymmetric carbon (CHIRAL) is synthesized by
conventional laboratory methods from an achiral compound the product is a racemic mixture.
• If such a synthesis carried out under chiral influence (optically active reagent), only one
of optically active isomer will form preferentially over the other.
15. Mehods of Assymetric synthesis:
Partial assymetric synthesis: "a method for preparing optically active compounds from
symmetric compounds by use of optically active intermediates but, without the requirement
of resolution".
• Both the active isomers, (+)− and (−)− are invariably produced simultaneously but one of
these is obtained in excess and often (but not always) it has the same sign of rotation as the
active reagent employed.
16. Total (Absolute) assymetric synthesis: Preparing optically active products from optically
inactive substances without the intermediate use of optically active reagents, but just by
irradiating it by right or left circularly polarized light is called as Total (Absolute) Asymmetric
Synthesis or Absolute Asymmetric Decomposition
17. Reactions of chiral molecules:
Bond breaking:
no bond breaking takes place to the chiral center….. the spatial arrangement about the chiral
center is unchanged.
Mechanism: the reaction that does not involve the breaking of a bond to a chiral center
proceeds with retention of configuration about that chiral center.
18. Reactions of chiral molecules:
Relative configuration:
• Configuration of a particular enantiomer - X-ray diffraction (procedure is difficult and
time-consuming and can be applied to certain compounds).
• Due to this limitation, configurational relationship between two optically active
compounds can be determined by converting one into the other by reactions that do not
involve breaking of a bond to a chiral center.
(The carbon oxygen bond is the one that is broken. No bond to the chiral center is broken, and
therefore configuration is retained with CH2Cl occupying the same relative position in the
product that was occupied by CH2OH in the reactant.
19. Oxidation of (−)-2-methyl-1-butanol with potassium permanganate, leads to the formation of
the acid 2-Methylbutanoic acid - no bond to the chiral center is broken.
The three compounds all happen to be specified as S, but this is simply because CH2Cl and
COOH happen to have the same relative priority as CH2OH.
In sec-Butylchloride and 1,2-Dichlorobutane, one is S and the other is R; here, a group (CH3)
that has a lower priority than −C2H5 is converted into a group (CH2Cl) that has a higher
priority.
20. Generation of secondary chiral centre:
Free radical chlorination of sec-Butyl chloride can also lead to the formation of compound
with a second chiral centre: 2,3-Dichlorobutane. This compound, can exists as three
stereoisomers, meso and a pair of diestereomers.
Since no bonds to the original chiral center - C-2, are broken, its configuration is retained in
all the products. This must be applied in all the cases where second chiral centre is generated
21. Example:
• Resolution of organic acids, like racemic acid, (±)-HA with the help of alkaloid produced by
the plants (cocaine, morphine, strychnine and quinine). Most alkaloids are produced by
plants in only one of two possible enantiomeric forms, and hence they are optically active.
Biochemical resolution:
When certain bacteria or moulds are added to a solution of racemic mixture they bring about
the decomposition of one of the optically active forms more rapidly than the other.
Example: Penicillium glaucum decomposes (+)-Tartaric acid more rapidly than the (−)-
Tartaric acid so that the later can be obtained from the residue after treatment with the mould
