Cahn–Ingold–Prelog priority rules

From Canonica AI

Introduction

The Cahn–Ingold–Prelog (CIP) priority rules are a set of guidelines used in stereochemistry to name the spatial arrangement of atoms around a chiral center or double bond. Named after chemists Robert Sydney Cahn, Christopher Kelk Ingold, and Vladimir Prelog, these rules provide a consistent and systematic method for designating the configuration of stereoisomers.

A 3D model of a chiral molecule with labels indicating the priority of each substituent according to the Cahn–Ingold–Prelog rules.
A 3D model of a chiral molecule with labels indicating the priority of each substituent according to the Cahn–Ingold–Prelog rules.

Principles of Cahn–Ingold–Prelog Priority Rules

The CIP priority rules are based on atomic number, isotope mass, and the sequence of atoms in a molecule. The rules are applied in the following order:

  1. The atom directly attached to the chiral center or double bond with the highest atomic number is given the highest priority.
  2. If there is a tie in atomic number, the tie is broken by considering the atoms attached to the tied atoms. The atom with the highest atomic number among these second atoms is given higher priority.
  3. If there is still a tie, the process is repeated until the tie is broken.
  4. If the atoms tied for priority are isotopes, the isotope with the greater atomic mass is given higher priority.
  5. If a multiple bond is present, the atom(s) involved in the bond are duplicated for the purpose of assigning priority.

Application in Stereochemistry

In stereochemistry, the CIP rules are used to assign absolute configurations to chiral centers and double bonds in molecules. The rules are applied as follows:

  1. Identify the chiral center or double bond.
  2. Assign priorities to the four groups attached to the chiral center or the two groups attached to each side of the double bond using the CIP rules.
  3. Arrange the molecule so that the group with the lowest priority is pointed away from you.
  4. If the remaining groups decrease in priority in a clockwise direction, the configuration is R (from the Latin rectus, meaning right). If they decrease in priority in a counterclockwise direction, the configuration is S (from the Latin sinister, meaning left).

For double bonds, if the two highest priority groups are on the same side of the bond, the configuration is Z (from the German zusammen, meaning together). If they are on opposite sides, the configuration is E (from the German entgegen, meaning opposite).

Limitations and Exceptions

While the CIP rules are widely used and generally reliable, they do have some limitations and exceptions. For example, they do not always yield unambiguous results for molecules with multiple chiral centers or complex cyclic structures. In these cases, additional rules or conventions may be needed to assign absolute configurations.

See Also