Unit 6: Stereoisomerism

Introduction to Stereoisomerism

Stereoisomerism is a fundamental concept in organic chemistry, describing molecules with the same molecular formula and connectivity but different spatial arrangements. This unit covers the main types of stereoisomers: enantiomers, diastereomers, meso compounds, and geometric (E/Z) isomers. Understanding these isomers is essential for predicting chemical behavior, especially in biological systems.

Types of Isomers

Classification Flowchart

Isomers are classified based on molecular formula, connectivity, and spatial arrangement. The following flowchart summarizes the process:

Enantiomers

Definition and Properties

Enantiomers are pairs of molecules that are non-superimposable mirror images of each other. They have identical physical properties (boiling point, melting point, solubility) and chemical properties except in chiral environments.

• Chirality: A molecule is chiral if its mirror image is not superimposable. This typically requires a carbon atom bonded to four different groups (a chiral center).

• Optical Activity: Enantiomers rotate plane-polarized light in opposite directions. A sample is optically active if it rotates light; a 1:1 mixture (racemic mixture) is not optically active.

• Enantiomeric Excess (%ee): Quantifies the purity of one enantiomer over the other.

Formula for Optical Rotation:

Where is the specific rotation, is the observed rotation, is concentration (g/mL), and is path length (dm).

Formula for Enantiomeric Excess:

Example: If a sample has 84% of the main enantiomer and 8% of the other, %ee = 76%.

Importance of Chirality

• Many drugs and biomolecules are chiral; only one enantiomer may be biologically active.

• Thalidomide tragedy: One enantiomer was therapeutic, the other caused birth defects.

Assigning R/S Configuration

Cahn-Ingold-Prelog (CIP) Priority Rules

To assign absolute configuration (R or S) to a chiral center:

1. Assign priority to each group attached to the chiral carbon based on atomic number (highest = 1).

2. If a tie, compare atoms at the next level outward.

3. Multiple bonds are treated as if atoms are duplicated.

4. Orient the molecule so the lowest priority group is in the back.

5. Trace a path from highest (1) to lowest (3) priority. Clockwise = R, counterclockwise = S.

Example: (S)-2-butanol and (R)-2-butanol are enantiomers.

Diastereomers

Definition and Properties

Diastereomers are stereoisomers that are not mirror images. They occur in molecules with multiple chiral centers and have different physical and chemical properties.

• Number of possible stereoisomers: , where is the number of chiral centers.

• Often, symmetry reduces the number of unique isomers (see meso compounds).

Meso Compounds

Definition and Properties

Meso compounds contain chiral centers but are achiral due to an internal plane of symmetry. They do not exhibit optical activity.

• Example: Tartaric acid has three isomers—two enantiomers and one meso compound.

• If a molecule can be divided into two mirror-image halves, it is meso.

Geometric Isomers (E/Z)

Definition and Assignment

Geometric isomers (cis/trans or E/Z) arise from restricted rotation around double bonds. The E/Z system uses CIP priority rules:

• If the highest priority groups on each end of the double bond are on the same side, the isomer is Z (zusammen, together).

• If on opposite sides, the isomer is E (entgegen, opposite).

Example: 2-bromo-2-pentene can be E or Z depending on the position of Br and CH3 groups.

Fischer Projections

Usage and Manipulation

Fischer projections are a way to represent 3D molecules in 2D. Vertical lines represent bonds going behind the plane; horizontal lines come out of the plane.

• Rotating a Fischer projection by 180° does not change configuration.

• Switching two groups inverts configuration (creates a diastereomer).

Summary Table: Types of Stereoisomers

Key Concepts for Exam Preparation

• Assigning and identifying isomers

• Recognizing mirror images and optical activity

• Calculating enantiomeric excess

• Using Fischer projections

• Naming alkenes and assigning E/Z configuration

Additional info: The notes reference the importance of chirality in drug design and biological systems, and mention historical context (Pasteur's chiral resolution, Prelog's CIP rules).