By James Ashenhurst
Homotopic, Enantiotopic, Diastereotopic
Last updated: March 27th, 2019
When you have two hydrogens attached to a single carbon, they can have three different types of relationships. We call them “homotopic”, “enantiotopic”, and “diastereotopic”.
First of all, when is this important?
- Certain reactions directly replace hydrogens with other atoms. For example, free radical chlorination replaces C-H bonds with C-Cl bonds. So understanding these principles help in understanding what potential types of products you could obtain from these reactions.
- In Nuclear Magnetic Resonance (NMR) these relationships determine whether or not these hydrogens are in the same “chemical environment”. In other words, whether or not they have the same or different signals.
Take a molecule like ethane. Let’s label (with color) two different hydrogens, blue and red. Next, let’s replace each of these hydrogens in turn with a different atom. In this example it could be chlorine (Cl) but really this can be done with any atom or group (except hydrogen of course).
Replace the red H and the blue H in turn with Cl and compare the molecules that are formed. Ask: how are these molecules related?
In this case they are both chloroethane. Since the two molecules are the same, the two hydrogens are said to be “homotopic”. Replacement of either gives rise to the same product.
Let’s look at butane next; specifically, the second carbon of butane. Replacement of the red H with Cl leads to (R)-2-chlorobutane, while replacement of the blue H with Cl leads to (S)-2-chlorobutane. These hydrogens are therefore not homotopic. Since enantiomers are obtained here, these two protons are therefore enantiotopic.
Note that the CH3 protons of butane are homotopic; it’s only the C-2 (and C-3) hydrogens of butane that are enantiotopic.
It’s also possible to have diastereotopic protons. Look at the alkene below. Replacement of the red H with Cl leads to the E-alkene, while replacement of the blue H with Cl leads to the Z-alkene. What’s the relationship between these two compounds? They’re diastereomers – stereoisomers, but not mirror images. So the two protons are said to be diastereotopic.
There’s another potential situation which can lead to diastereotopic protons. Look at the molecule below – R-2-butanol. Replacement of the red H leads to the (R, R) product. Replacement of the blue H leads to the (R, S) product. Therefore, these two products are diastereomers, and the two protons are diastereotopic.
- In free radical chorination – say, of butane – on the second carbon (C-2), substitution of C-H with Cl will lead to a mixture of stereocenters. It’s important to recognize when this can happen.
- (Most common) – In NMR spectroscopy:
- homotopic protons have the exact same chemical shift
- enantiotopic protons have the same chemical shift in the vast majority of situations. However, if they are placed in a chiral environment (e.g. a chiral solvent) they will have different chemical shifts.
- diastereotopic protons have different chemical shifts in all situations
P.S. I’m writing about this because a reader suggested this topic through my feedback form. Have a suggestion for a post? Send feedback here (anonymous if you like)