Homotopic, Enantiotopic, Diastereotopic

by James

in Nomenclature, Stereochemistry

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?

  1.  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.
  2. In Nuclear Magnetic Resonance (NMR) these relationships determine whether or not you 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.

When does it matter?

Two situations:

  1. 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.
  2.  (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)



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{ 14 comments… read them below or add one }


Finally, we dip our toes into NMR!

I actually don’t recommend my students use chlorine in their substitution exercise… The molecule might already have a chlorine in it – confusing the situation. Do the substitution exercise on C2 of 1-chloroethane… then what happens?

I use some ridiculous transition metal (for personal reasons, my favorite choice is element 76)… or I have them do the substitution exercise with something nonsensical like a smiley face. We can still name the results and compare their relationship… It’s (R)-2-smileyfacebutane and (S)-2-smileyfacebutane.




The foolproof method is to use something achiral that’s not even an element, like Q. Or a cat… :-P



But the letter Q is chiral… (was it you who tweeted the achiral letters a while ago?)

And as James has shown, cats can be chiral, too…




dipping a little end of my pinky toe into NMR. Still reluctant to talk about it yet.
thanks for the suggestion re: replacing Cl.



This is a good explanation of a topic that several PhD students in my group could definitely grasp a bit better…


Emeryville Pharmaceuticals

Definitely put together otherwise confusing NMR terms well. I’ll be sure to direct my junior level chemists to this next time it comes up.



Good suggestion. thanks!



Hi! This definitely helped- I have a quiz on this stuff today, so this will hopefully help me out! One suggestion- maybe you could include heterotopic ones as well? I get a little confused with those, and we’re learning about those in tandem with the ones you have listed. Great Website!



Hi, thanks for the examples on homotopic, enantiotopic and diastereotopic but i don’t get the difference between the enantiotopic and second example of diastereotopic. I will really appreciate it if you could explain it to me. Thanks. :)



We look at the hydrogens in pairs. An enantiotopic pair of protons will produce different chiral configurations on substitution. Looking at the example above, substitution of one of the protons creates an R center; substitution of the other creates an S center. We either have an R center or an S center. These are both opposite chiral configurations of each other, which means enantiomers.

For the diasteretopic set, let’s start with the first example of a double bond. Chirality doesn’t apply to a single double bond, so going like above, upon substitution of either hydrogen we end up with two stereoisomers–the Z and E configurations. To confirm they are stereoisomers, try flipping either isomer around, and you will see you can’t get them to match. Simply establishing that stereoisomers are created on a substitution of a single double bond means we have diastereotopic protons.

Moving on to the second example of diastereotopic protons: we are examining the proton set next to the chirality center. Diastereomers are two molecules that have the same formula, but their chirality centers have different configurations. If their configurations are completely opposite, we have enantiomers. In the case above, we end up with either an R,S or R,R product of chlorobutanol. These are two molecules with the same formula, but their chirality configurations are different; hence, they are diastereomers. If they were enantiomers, they would need to be complete opposites, eg. an R,S product and an S,R product.

So to check for diastereotopic protons, the first thing you do is substitute each proton in turn and compare the resulting products. Remember your goal specifically is to identify a product’s chirality. If you have diastereomers (different chiral configurations), they are diastereotopic; if enantiomers (opposite chiral configurations), enantiotopic; if the same molecule (no change in chiral configuration), homotopic.



epic response. Thanks Blaise.



THANK YOU SO MUCH! You are awesome!!



if those examples are illustrated the it would be very nice



Thank you so much for all of your articles. They’re so clear and well-written, and as a science student at mcgill I can confirm that you’re a lot easier to understand than many of my org chem profs! We’re learning IR/NMR/MS identification stuff right now and I’m up to my neck in confusing slides and this article was the best thing that’s ever happened to me!


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