Stereoisomerism

Stereoisomerism is a form of isomerism where compounds have the same molecular formula and the same sequence of bonded atoms (connectivity) but differ in the three-dimensional arrangement of their atoms in space. Stereoisomers can significantly impact the physical and chemical properties of compounds, especially in biological systems.

1.0Types of Stereoisomerism

Stereoisomers are compounds with the same molecular formula and sequence of bonded atoms but differ in the three-dimensional arrangement of their atoms. These differences in spatial orientation lead to distinct physical and chemical properties. Stereoisomers can be classified into two broad categories: 

1. Configurational isomers 
2.  Conformational isomers.

2.0Configurational isomers

Configurational isomers are stereoisomers that can only be interconverted by breaking and reforming chemical bonds. They are subdivided into Geometrical isomers and Optical isomers.

1. Geometrical (Cis-Trans) Isomerism
2. Optical Isomerism

Geometrical (Cis-Trans) Isomerism:

Geometrical isomerism arises due to restricted rotation around a bond, typically a double bond (C=C) or in cyclic compounds. In these isomers, the atoms or groups attached to the carbon atoms of the double bond or ring are arranged differently in space.

• Cis Isomer: The same groups or atoms are on the same side of the double bond or ring.
• Trans Isomer: The same groups or atoms are on the opposite sides of the double bond or ring.

Conditions for Geometrical Isomerism:

• Restricted rotation around the double bond or ring structure.
• Different groups must be attached to the carbon atoms involved in the bond or ring. If the two substituents are identical on both carbons, geometrical isomerism does not exist.
• While a double bond often leads to geometrical isomerism (G.I.), it is not a necessary condition. The key requirement for G.I. is restricted rotation around a bond or structure, which can also occur in cyclic compounds where rotation is hindered. Thus, restricted rotation is the critical condition for the existence of geometrical isomers.

Example:

2-Butene:

• Cis-2-butene: CH₃ groups are on the same side of the double bond.
• Trans-2-butene: CH₃ groups are on opposite sides of the double bond.

Physical properties of Cis-Trans Geometrical Isomers:

Optical Isomerism

Optical isomerism occurs when molecules have the same connectivity but differ in how they interact with plane-polarized light. Optical isomers, also known as enantiomers, are non-superimposable mirror images of each other.

Chirality:

The key to optical isomerism is the  presence of chirality. A molecule is said to be chiral if it cannot be superimposed on its mirror image, much like left and right hands. A chiral center (stereocenter) is usually a carbon atom bonded to four different groups.

• Enantiomers: These are two stereoisomers that are mirror images of each other but cannot be superimposed. They have identical physical properties except for their interaction with plane-polarized light and reactions in chiral environments.

Optical Activity:

Optical isomers (enantiomers) rotate the plane of polarized light in different directions:

• Dextrorotatory (d): Rotates light to the right (clockwise).
• Levorotatory (l): Rotates light to the left (counterclockwise).

R and S Nomenclature:

To distinguish enantiomers, the Cahn-Ingold-Prelog system is used to assign R or S configuration to a chiral center. This system ranks the substituents around a chiral carbon based on atomic number, and based on their arrangement, the isomer is classified as either R (rectus) or S (sinister).

• R Configuration: The sequence of priorities follows a clockwise direction.
• S Configuration: The sequence of priorities follows a counterclockwise direction.

Diastereomers:

• Diastereomers are stereoisomers that are not mirror images of each other and are non-superimposable. They differ in physical and chemical properties, unlike enantiomers.
• They can occur when there are two or more chiral centers in a molecule.

Example of Enantiomers:

1. Lactic Acid: Lactic acid has one chiral center and exists as two enantiomers: D-lactic acid and L-lactic acid.
2. Thalidomide: Thalidomide, a drug used in the 1950s, exists as two enantiomers. One enantiomer had therapeutic effects, while the other caused severe birth defects, illustrating the importance of chirality in pharmaceuticals.

Types of Optical Isomers:

Meso Compounds: Meso compounds are stereoisomers that have multiple chiral centers but are superimposable on their mirror image due to an internal plane of symmetry. As a result, meso compounds are optically inactive.

Example:

• Tartaric Acid: It has two chiral centers and exists as two enantiomers (D and L forms) and a meso form.

Key Differences Between Geometrical and Optical Isomerism

3.0Conformational Isomerism

Conformational isomers (or conformers) are stereoisomers that can be interconverted by rotation around single bonds. Unlike configurational isomers, these do not require breaking any bonds to convert from one form to another. Conformers typically occur in alkanes and cycloalkanes due to the free rotation about C–C single bonds.

Key Types of Conformational Isomers:

1. Staggered Conformation:In this conformation, the atoms or groups attached to the two carbons are positioned as far apart as possible, leading to minimized repulsion and maximum stability. Ethane and cyclohexane are common examples that show staggered conformations.
2. Eclipsed Conformation:In this conformation, the atoms or groups are aligned with one another, leading to maximum repulsion and higher energy. This is less stable than the staggered conformation.

Example- Conformation of Propane

4.0Strain related to Conformational Isomers

Strain refers to the instability in a molecule caused by the repulsion or unfavorable interactions between atoms or groups. The strain affects the molecule’s stability and reactivity. There are several types of strain in organic chemistry, each arising from different structural aspects of molecules.