Organic Chemistry Chirality Lesson

When drawing 2D images of molecules, we can forget that these molecules exist in 3D space. Try drawing 1-bromo-1-chloroethane, it should look something like this:

If we only consider the “raw” drawing, we miss the fact that this is a 3D molecule and therefore, don’t see that the orientation and order of the molecules changes the properties of the principle. In Organic Chemistry, we call this property “Chirality” and there are two designations/configurations:

R Configuration

S Configuration

Let’s take a 3D look at 1-bromo-1-chloro-ethane:

The red ball is Bromine, the green ball is Chlorine, the gray ball with 3 white balls is Carbon with 3 Hydrogens, and the white ball hiding in the back is Hydrogen. Both of these molecules are 1-bromo-1-chloro-ethane but they cannot be superimposed on one another, meaning they are somehow different. Mentally, take Image 2 on the right, and if you rotate it so that Chlorine is on the right hand side of the molecule, it would give you something like this:

While the Bromine, Chlorine, and Methylgroup (Carbon and 3 Hydrogens) line up, the Hydrogen atom in Image 1 (darker image) is going to the back of the page where the Hydrogen atom in Image 2 (transparent image) is coming to the front of the page. This small difference is enough to distinguish between these two molecules, thereby giving them two names:

(1R)-1-bromo-1-chloroethane

(1S)-1-bromo-1-chloroethane

Chiral or Achiral?

Now that we have learned about the idea of chirality, let’s dive into how we determine if a molecule is chiral or achiral (not chiral). First, identify any carbon atoms that have 4 single bonds (including any Hydrogen atoms that may not be shown). A carbon that is part of a double or triple bond will always be achiral (but the molecule itself may still be chiral). In our example, 1-bromo-chloroethane, our 4 single bonds are made with the center Carbon attached to Bromine, Chlorine, Carbon, and Hydrogen. The next step to determine chirality is to evaluate each of the 4 atoms attached to the center Carbon and see if any are the same. If there are 2 of the same atom (2 Hydrogens, 2 Bromine, 2 Chlorine, etc...), the center Carbon will be achiral. However, if there are 2 of the same atom that are also part of different chains, the molecule may be chiral. For example, consider 2-bromobutane:

Here we see the center Carbon bound to Bromine, Hydrogen (not pictured), a Carbon (left), and a second Carbon (right). While there are 2 Carbon molecules attached, they are slightly different; the Carbon on the left has a Carbon bound to it along with 2 Hydrogens, while the Carbon on the right has 3 Hydrogens. That makes these Carbons different and as a result, 2-bromobutane is chiral:

(2R)-2-bromo-butane

(2S)-2-bromo-butane

Now that we have defined the rules to determine if an atom in a molecule is chiral or achiral, we need to establish how we will assign the “R” and “S” designation to an atom.

R or S Configuration?

Let’s go back to our example using 1-bromo-1-chloroethane.

Once we have established that an atom is chiral using the rules above, we must establish whether it is in the R or S configuration. First, list out the atomic weights from largest to smallest:

Atom Name	Atomic Number	Priority
Bromine	35	1
Chlorine	17	2
Carbon (methyl)	6	3
Hydrogen	1	4

Next, write the priority of each atom over the molecule to visualize the priority in 3D space:

We want to draw, with a single line, from 1 to 3 to see what direction the molecule is in. If the line goes in a “clockwise” direction, it is in the R configuration and if the line is “counterclockwise”, the atom is in the S configuration:

In this case, we would call this (1R)-1-bromo-1-chloroethane since it is in the R configuration. If we were to redraw it with the chlorine on the left, the priority would be reversed and we would then have (1S)-1-bromo-chloroethane.

You may also see chemical drawings with stereochemistry incorporated, designated by a solid wedge indicating the molecule is “coming out of the page”, or by a dashed wedge indicating the atom is going away from the viewer or “into the page”:

This can affect how we assign R or S to an atom. When we do our priority numbering, we want to have 1, 2, and 3 all on the page or coming out of the page. Said another way, we want the 4th priority to always have the wedge. This will mean re-orienting the molecule in our minds until we are “looking” at it from a different angle. Let’s start with an easy example:

We see that the top 3 atom sizes are all already either on the page or coming out of the page. The order of 1,2,3 is in a clockwise direction, meaning that this atom is chiral in the R configuration. In fact, because the Hydrogen, or 4th priority atom, is going into the page, the following drawings would also be in the R configuration:

When priority 4 is going in the back of the page, it is easy to know R or S. But what if we changed the stereochemistry and had a different atom going to the back of the page? Take the following example:

For this molecule, the Hydrogen (which has the smallest atomic number) is coming out of the page. We have to re-visualize this molecule and approach it as if we were facing it from the other direction. Imagine walking through the page and looking back at this molecule, from the new angle, the Bromine would be coming towards you and the molecule would look like this:

When we re-visualize the molecule, we see the Chlorine (or 2 priority) is on the left, the Carbon on the right giving us the S configuration, resulting in (1S)-1-bromo-chloroethane:

Summary

 

Chirality determines the 3D configuration of a molecule, denoted by using R or S, depending on the configuration. To determine if an atom in a molecule is chiral, it must have 4 distinct atoms connected to it. To determine if it is R or S, number the atoms 1-4 with the highest atomic number being 1 and the lowest 4. If 2 atoms have the same atomic number, the longer, more substituted chain is given the higher priority. Once all 4 atoms have been assigned a number, draw an imaginary line from atom 1 to atom 2, and atom 2 to 3. If the line is clockwise, it is R configuration. If the line is counterclockwise, it is in the S configuration. When stereochemistry is involved, reorient the molecule so that the lowest atomic number is going into the page (dashed line) and then draw your line between atomic numbers 1,2 and 3 to determine the configuration.