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.

 Homotopic

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.

Enantiotopic

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.

Diastereotopic

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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{ 11 comments… read them below or add one }

azmanam April 17, 2012 at 9:04 pm

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.

:)

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mevans April 17, 2012 at 9:57 pm

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

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azmanam April 18, 2012 at 3:56 pm

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…

/troll

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james April 17, 2012 at 10:36 pm

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

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BRSM April 21, 2012 at 9:44 am

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

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Emeryville Pharmaceuticals August 9, 2012 at 12:21 am

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.

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james August 9, 2012 at 2:25 pm

Good suggestion. thanks!

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Shelby December 14, 2012 at 11:43 am

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!

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minette February 8, 2013 at 1:08 am

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. :)

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Sajani November 4, 2013 at 4:40 pm

THANK YOU SO MUCH! You are awesome!!

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razaullah October 23, 2014 at 8:27 am

if those examples are illustrated the it would be very nice

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