lecture recording on 28 February 2025 at 13.52.32 PM

Introduction to Stereochemistry

• Stereochemistry deals with the 3D arrangement of atoms in molecules.

• Isomers can have the same molecular formula but differ in their spatial arrangement.

Types of Stereoisomers

Mirror Images

• Enantiomers: Molecules that are non-superimposable mirror images.

  • Example: Right-handed and left-handed versions of a molecule.

Optical Activity

• Polarized Light: Enantiomers affect plane polarized light differently.

  • Dextrorotatory (+): Rotates light clockwise.

  • Levorotatory (−): Rotates light counterclockwise.

R and S Configuration

• Chiral Centers: Atoms attached to four different groups are termed chiral centers.

• R/S Configuration is determined based on the priority of attached groups according to the Cahn-Ingold-Prelog (CIP) rules.

  • Assign priorities based on atomic number; higher atomic number gets higher priority.

  • To determine configuration:

    1. Identify chiral center with four different groups.

    2. Arrange groups so that the lowest priority is away (on a dash).

    3. Count from 1 to 3 to see if the priority order is clockwise (R) or counterclockwise (S).

Examples of R/S Assignments

Example Chiral Center with Groups: -OH, -Cl, -H, -C

• Assign Priorities: Cl > O > C > H.

  • If H is on a dash, count resulting order to determine configuration.

  • Configuration based on bracket to determine spatial orientation.

Importance of Configuration

• R/S designation helps ensure proper naming of compounds in stereochemistry.

• Importance in pharmaceuticals and chemical reactions - different enantiomers can have drastically different effects.

Handling Different Orientations

Wedges and Dashes

• Wedge: Group coming towards you (3D representation).

• Dash: Group going away from you.

• For configurations, ensure the lowest priority group's orientation (using wedges/dashes) is correct before determining R or S.

Non-Dash Arrangement (Plane of Paper)

• If the lowest priority is in the plane, rotate the entire molecule or apply different conventions to visualize correctly.

Fischer Projections

Purpose

• Fischer projections are used to simplify the representation of stereoisomers with two or more chiral centers.

Creating Fischer Projections

1. Convert the stereoisomer from a Newman projection into eclipsed form.

2. Pull the front up to convert into Fischer format, ensuring horizontal groups are treated as wedges and vertical groups as dashes.

Summary of Configuration Naming

• In compounds with two or more chiral centers, indicate the configuration of each chiral center with corresponding numbering (e.g., 2S, 3R).

• For reactions, the arrangement can lead to various stereochemical outcomes.

Maximum Stereoisomers Formula

• The maximum number of stereoisomers can be calculated using the formula 2^n, where n is the number of chiral centers.

  • Example: 2 chiral centers lead to 4 stereoisomers, 3 chiral centers lead to 8 stereoisomers.

Conclusion

• Understanding the spatial orientation of molecules is critical in predicting their chemical behavior and interactions in various fields, particularly in biochemistry and pharmacology.