Stereochemistry: A summary

Table of Contents

• Terminology used in stereochemistry

  • Chiral center

    • Assigning R/S configurations

  • Enantiomers

  • Diastereomers

  • Chiral molecule

  • Meso compound

  • Optical activity

  • Racemic mixture

  • Fischer projections 

Terminology used in stereochemistry

Chiral center

A chiral center, also known as a stereocenter, stereogenic center, or asymmetric center, is an sp³ hybridized carbon atom with four different groups bonded to it.

Understanding chiral centers is crucial in organic chemistry because the spatial arrangement around these centers influences the physical, chemical, and biological properties of molecules, especially in pharmaceuticals.

Assigning R/S configurations

R/S configurations are used to designate the absolute configuration of chiral centers in a molecule. 

1. Identify the chiral center.

2. Assign priorities to the four groups attached to the chiral center based on atomic number (higher atomic number gets higher priority).

3. Orient the molecule so that the group with the lowest priority is pointing away from you.

4. Determine the direction of 1-2-3 sequence .

• If the direction is clockwise, the configuration is R (rectus, right).

• If the direction is counterclockwise, the configuration is S (sinister, left).

Enantiomers

Enantiomers are a pair of stereoisomers that have opposite configurations at all chiral centers.

• Because of this, enantiomers are non-superimposable mirror images of each other. 

• They have identical physical properties (melting point, boiling point) and chemical properties but differ in their optical activity or direction in which they rotate plane-polarized light. 

Diastereomers

Diastereomers are stereoisomers that have opposite configurations at one or more (but not all) of their chiral centers. 

• This means they are not mirror images of each other and are non-superimposable. 

• Unlike enantiomers, diastereomers have different physical and chemical properties. 

Generally, a molecule with n chiral centers can have up to 2ⁿ stereoisomers. 

For example, the amino acid threonine has 2 chiral centers, so there are 4 possible stereoisomers.

Chiral molecule

A molecule that lacks a plane of symmetry. 

• A common feature of chiral molecules is the presence of one or more chiral centers.

• The molecule and its mirror image cannot be aligned perfectly when overlaid. 

• Chiral molecules can rotate plane-polarized light, a property used to distinguish between enantiomers.

Meso compound

A meso compound is an achiral molecule that contains multiple chiral centers. 

• A meso compound can be placed on top of its mirror image and perfectly match.

• Meso compounds do not exhibit optical activity, meaning they do not rotate plane-polarized light. 

Example: Consider tartaric acid (C₄H₆O₆):

Meso-tartaric acid has two chiral centers but an internal plane of symmetry, making it achiral.

Optical activity

Optical activity refers to the ability of a chiral molecule to rotate the plane of plane-polarized light as it passes through a solution of the chiral compound. This property is a direct result of the asymmetry in chiral molecules. The degree of rotation is measured using a device called a polarimeter. 

• Direction of Rotation:

  • Dextrorotatory (D or +): Rotates plane-polarized light to the right (clockwise).

  • Levorotatory (L or -): Rotates plane-polarized light to the left (counterclockwise).

Racemic mixture

A racemic mixture (or racemate) is a mixture that contains equal amounts of two enantiomers of a chiral molecule. Because it has equal parts of both enantiomers, their opposite optical activities cancel each other out, resulting in an optically inactive mixture. 

Consider the drug ibuprofen:

• Pure (S)-ibuprofen is the active form that provides pain relief.

• Pure (R)-ibuprofen is inactive but can be converted to the active form in the body.

A racemic mixture of ibuprofen contains equal parts of (S)-ibuprofen and (R)-ibuprofen. This is how the drug is commonly sold, as the racemic mixture is easier and cheaper to produce.

Fischer projections 

Fischer Projections are a way to represent three-dimensional molecules in two dimensions, especially useful for visualizing and comparing the spatial arrangements of atoms around chiral centers. They are commonly used for sugars and amino acids.

Key Points:

• Horizontal Lines: Represent bonds that come out of the plane of the paper (towards the viewer).

• Vertical Lines: Represent bonds that go behind the plane of the paper (away from the viewer).

• Intersection: The point where the horizontal and vertical lines cross represents a chiral center.

Fischer projections are also helpful for visualizing and comparing the relationship between stereoisomers: