Core Concepts-Absolute Configuration
In this tutorial, you will learn about what absolute configuration is, along with how to determine the absolute configuration of a molecule.
Topics Covered in Other Articles
- What are Organic Compounds?
- Constitutional Isomers
- Stereoisomers and Chiral Centers
- Enantiomers vs. Diastereomers
- IUPAC Naming of Organic Compounds
What is Absolute Configuration?
We use absolute configuration for chiral molecules in stereochemistry to describe the 3D orientation of the molecule. The absolute configuration of a molecule refers to the spatial arrangement of atoms around a chirality center. R and S are the terms used to refer to the absolute configuration of a molecule. To determine the absolute configuration of a molecule, we use the Cahn-Ingold-Prelog (CIP) sequence rules, named after R.S Cahn, C.K Ingold, and Vladimir Prelog.
Determining Absolute Configuration
Before we get into determining absolute configuration, I want to remind you that wedged lines represent bonds pointing toward you, while the dashed lines represent bonds pointing away from you.
When the Lowest Priority is a Dash
For this example, we are going to be looking at the amino acid alanine.
To begin assigning absolute configuration, we need to find the chirality center within the molecule. A chirality center is an atom with three or more different attachments; carbon is a common chirality center with four different attachments. In our example, the chirality center is the carbon with an asterisk.
Next, we will rank the atoms connected to the chiral carbon. They are ranked based on their atomic number; the higher the atomic number, the higher the priority. In our example, nitrogen is priority one because it has the highest atomic number of 7. Next, the two carbons connected to the chiral center are the atoms with the highest atomic number. We will look at the atoms further branching off these carbons to determine priority between the two. The carbon on the left has three hydrogens attached, while the one on the right has two oxygens attached. Oxygen has a higher atomic number than hydrogen; therefore, the carbon on the right has second priority. The carbon on the left has third priority, leaving hydrogen at the lowest priority.
Start by drawing an arrow from priority one going to priority two and then three.
If the arrow is going clockwise, like in this example, the configuration is R. On the contrary, if the arrow is going counterclockwise, the configuration is S. If you are struggling to remember which direction is R and which is S, you could think about the direction you write the beginning portions of these letters.
When the Lowest Priority is a Wedge
Ideally, the lowest priority atom is a dashed line, like in the example above. When the lowest priority atom is a wedge, the steps we follow are essentially the same as before but with a twist at the end. We will use the amino acid alanine again for this example.
Find the chirality center in the molecule. In this example, the same carbon as before is our chirality center.
Assign priority to the atoms connected to the chiral carbon based on their atomic number. Though some atoms have moved, they still have the same priority that they were assigned previously.
Draw an arrow from priority one going to priority two and then three.
This looks very similar to the previous example, but this last twist is very important to determine the molecule’s absolute configuration. The arrow in this example is going clockwise, so it appears to have an R configuration. But, because the lowest priority atom is a wedge, we will flip the configuration, making this molecule have an S configuration.
When the Lowest Priority is a Line
If the lowest priority atom is in the same plane as the paper, we can then temporarily switch it with whichever atom is pointing away.
With the molecule flipped, we assign its configuration the same way we have in previous examples. On our molecule, the arrow is moving clockwise, indicating an R configuration. But, because we switched the two atoms, the configuration of the original molecule is flipped and therefore has an S configuration.
Absolute Configuration Practice Examples
1: S configuration (I > Br > OH > H)
2: R configuration (OH > CN > CH2NH2 > H). Remember to switch the lowest priority atom to the back of the molecule.
3: Neither. This molecule is achiral.