STEREOISOMERISM / STEREOISOMERISM PDF

 1.1INTRODUCTION 

 Stereochemistry helps to define the structure of a molecule and orientation of the atoms and functional groups present, in three dimensions. Stereoisomers possess the same molecular and structural formulae and the same functional groups but differ in the threedimensional spatial orientation of these atoms or groups within the molecule. Due to the difference in orientation of the functional group and geometry of the molecule, stereoisomers differ in their physical, chemical, physicochemical and biochemical properties. Based on symmetry and energy criteria, stereoisomers are divided into three classes. 

 (a) Geometrical isomers 

 (b) Optical isomers 

 (c) Conformational isomers. (a) Geometrical isomers (cis-trans isomerism): Maleic acid (m.p. 130°C) and fumaric acid (m.p. 287°C) have the same molecular formula but differ in the arrangement of functional groups around double bond. They have different physical and, to some extent, chemical properties. This type of isomerism is known as geometrical isomerism.

The presence of a carbon-carbon double bond restricts the freedom of rotation about double bond. The designation cis (Latin word: same side), is used to denote the presence of like atoms or groups on the same side and trans (Latin word, across) is used when they are on opposite sides. Isomerism seen in non-cyclic, open-chain compound due to the presence of a double bond, is called as π diastereoisomerism while when it occurs in a cyclic skeleton lacking a double bond, it is termed as σ diastereoisomerism.

(b) Optical Isomerism (enantiomerism): In 1815, Biot found that a number of organic and inorganic compounds in the solution form, have the ability to rotate the plane of polarized light in opposite directions but in identical amplitude, passing through them. Optical isomerism is seen in compounds that can rotate plane polarised light. A carbon atom connected to four chemically different functional groups is known as asymmetric or chiral carbon and the presence of at least one asymmetric carbon atom in the structure is the prerequirement for a molecule to show optical isomerism. If there is one asymmetric carbon then two optically active isomers are possible. 

Isomer rotating plane of polarized light to the right is said to be dextrorotatory (Latin, dexter : right) while isomer showing rotation to the left is known as laevorotatory (Latin, laevus : left). Both isomers are mirror images of each other yet are not superimposable. They are called as enantiomers and the pair of enantiomers is called as enantiomorph. An enantiomer does not possess a plane or center of symmetry. For example

When the enantiomers are present together in equal concentration, the rotation of plane polarized light caused by laevo isomer will be neutralized by a dextro rotating isomer and the mixture will be optically inactive. Such mixtures are called as racemic mixtures. The conversion of an enantiomer into a racemic form is called as racemization. While the separation of racemic mixture into individual enantiomers is called as resolution. The maximum number of optically active isomers possible for a molecule having more than one asymmetric carbon atoms may be given by the formula

With the exception of rotation of plane-polarised light, enantiomers have identical physical and chemical properties like boiling point, melting point, solubility. Their chemical properties are same towards achiral reagents, solvents and conditions. Towards chiral reagents, solvents and catalysts, enantiomers react at different rates.

Forms (I) and (II) are identical and symmetrical. In these forms, the upper half is the mirror image of the lower half. This makes the molecule optically inactive through internal compensation. Such identical and symmetrical stereoisomers are called as meso-isomers. 

 Forms (III) and (IV) are mirror images of each other but are not superimposable. They are enantiomeric forms. While if you compare (III) with (I) or (IV) with (I), these are not enantiomeric pairs. They are neither mirror images nor superimposable. Only one of the two halves of their molecules are identical while the remaining halves are mirror images. Such stereoisomers which are not mirror images and are non-superimposable are called as diastereomers. They have different physical and chemical properties, with both achiral and chiral reagents. The rates are different and the product may be different.

IMPORTANCE OF OPTICAL ISOMERISM

Nearly all naturally occurring substances having asymmetric carbon atoms are in either the d or the l form rather than as racemic mixtures. In drugs and pharmaceuticals, most of the adverse effects and low potency may be related to the utilization of the drug in the form of its racemic mixture. Since, enantiomer in its pure form, is more active and selective, there is now an increasing interest to present the drug in the market in its active enantiomeric form instead of its racemic form. Optical isomerism has also been successfully utilized in elucidating the mechanism of many chemical reactions. The enantiomer that rotates a beam of polarised light in the clockwise direction is indicated by the prefix (+), formerly d (+) or dextro (–), the other enantiomer rotates light in a counter clockwise direction and is indicated by the prefix (–), formerly l(–) or levo. They have identical chemical and physical properties in an achiral environment but form different products when reacted with other chiral molecules and exhibit optical activity. 

1.3 DIASTERIOISOMERISM

Stereoisomers with two or more asymmetric or chiral carbons (stereocenter) will show diasterioisomerism. The stereoisomers that are neither mirror images of one another nor are superimposable, are known as diasterioisomers.

Each stereocenter gives to two different configurations. It means if a molecule contains two asymmetric carbons, there are upto four possible conformations. When two diastereoisomers differ from each other at only one stereocenter they are known as epimers. e.g., D-threose and D-erythrose are epimers of each other. Unlike enantiomers, diastereoisomers have different physical and chemical properties.  

In case of 3-bromo-2-butanol, we have four possible combinations as SS, RR, SR and RS. Out of these, two molecules SS and RR are enantiomers of each other while the configurations RS and SR are diastereomers of SS and RR configurations.

Thus in diastereoisomers, the chemical formula and atom connectivity remain the same but the three dimensional orientation or shape of the molecule is different e.g., 2-bromo-3- chloro ethane

The molecules are different in the configuration of chlorine atoms but same with the bromine atoms hence they are diastereomers. Similarly in cyclic compound 3-ethyl-1- chlorocyclohexane, ethyl groups have same configuration but the chlorine atoms have opposite configuration. Hence, these molecules are diastereomers. Configurations differ at some stereocenters but not at others can not create mirror images. So they are not enantiomers, but are diastereomers.

The dihydrotestosterone molecule contains seven stereocenters. Applying 2N rule, gives 128 possible configurations. Out of these, only one is enantiomeric pair while rest are diastereomers

When multiple stereocenters present in a molecule create an internal plane of symmetry, it leads to meso compounds. Tartaric acid contains two asymmetric centers which give rise to four configurations. But there are really only three stereoisomers of tartaric acid: a pair of chiral molecules (enantionmers of each other) and the achiral meso compound. In meso compound, we have internal mirror plane that splits the molecule into two symmetrical sides, the stereochemistry of both left and right side should be opposite to each other. This leads to auto cancellation of stereo activity of each other resulting into optical inactivity. Hence, meso compounds can not be assigned with either dextrorotatory (+) or levorotatory (–) designation. The internal mirror plane is simply a line of symmetry that bisects the molecule. Each half is a mirror image of the other half. Each half must contain a stereocenter in order to be a meso compound. These stereocenters must also have different absolute

MESO COMPOUNDS   

When multiple stereocenters present in a molecule create an internal plane of symmetry, it leads to meso compounds. Tartaric acid contains two asymmetric centers which give rise to four configurations. But there are really only three stereoisomers of tartaric acid: a pair of chiral molecules (enantionmers of each other) and the achiral meso compound. In meso compound, we have internal mirror plane that splits the molecule into two symmetrical sides, the stereochemistry of both left and right side should be opposite to each other. This leads to auto cancellation of stereo activity of each other resulting into optical inactivity. Hence, meso compounds can not be assigned with either dextrorotatory (+) or levorotatory (–) designation. The internal mirror plane is simply a line of symmetry that bisects the molecule. Each half is a mirror image of the other half. Each half must contain a stereocenter in order to be a meso compound. These stereocenters must also have different absolute

configurations. Due to internal symmetry, they meso molecule is achiral. Hence, this configuration is not optically active. The meso form is also a type of diastereomer. The remaining two isomers are enantiomeric pair (D-and L-form).

The melting point of both enantiomers of tartaric acid is about 170°C while the mesotartaric acid has the melting point of 145°C. A meso compound is 'superimposable' on its mirror image. Examples in cyclic meso compounds include

 ELEMENTS OF SYMMETRY