Chemically equivalent protons in NMR

[663697]

This is from Khan's video on Chemical equivalence in NMR. They say that the 2 circled protons are not chemically equivalent due to being adjacent to a chiral center, but the 3 protons to the left of the chiral center are equivalent. Why is this so?

---

Members don't see this ad.

 

[deleted853480]

Basically a complicated reason that takes too long to explain. I learned about in a 3rd year orgo class. Don't worry about the reason and just remember that rule.

 

[Lawpy]

This is from Khan's video on Chemical equivalence in NMR. They say that the 2 circled protons are not chemically equivalent due to being adjacent to a chiral center, but the 3 protons to the left of the chiral center are equivalent. Why is this so?

Some good resources to check out: 5.2: Chemical equivalence and 3.11: Prochirality

Basically, the carbon atom bonded to the two circled protons is a prochiral carbon atom. What this means is one of the protons can be replaced by a different substituent group to make that carbon atom chiral. For example, if you replace one of those hydrogen atoms with deuterium (hydrogen with a neutron), the carbon atom becomes a chiral center because deuterium and hydrogen differ in atomic mass and are chemically different. Replacing the purple circled proton with deuterium vs replacing the red circled proton with deuterium will result in a chiral center with opposite absolute configurations. Since the other chiral atom (marked by the red dot) is kept unchanged (and so the absolute configuration there is unchanged), replacing either of the proton will result in two new diasteromers. And as a result, the two circled protons are called diastereotopic, have different chemical environments and are not chemically equivalent.

The three protons bonded to the carbon atom are the same because if you replace any of them with deuterium or another substituent, you're not creating a chiral center. These protons are called homotopic and are chemically equivalent.

Now, if you don't have an adjacent chiral center marked by the red dot and you only have one prochiral carbon atom attached to two protons, replacing either of the proton with deuterium will result in two chiral molecules with opposite absolute configurations. But since you are converting an achiral molecule to a chiral molecule with one chiral center, you are creating mirror images of the new chiral molecule and thus creating enantiomers. The protons attached to the prochiral carbon atom are called enantiotopic and are chemically equivalent (unless they are placed in a chiral environment, in which case they are not chemically equivalent and have different chemical shifts)

For more examples, see the following link: Homotopic, Diastereotopic, Enantiotopic — Master Organic Chemistry

 

[rabbott1971]

The protons attached to the prochiral carbon atom are called enantiotopic and are chemically equivalent (unless they are placed in a chiral environment, in which case they are not chemically equivalent and have different chemical shifts)

Isn't that what @Cuttlefish was asking? He said he thought they would be chemically equivalent but the video says they make separate signals? I haven't watched the video, but from the way I learned NMR, those two protons would produce one signal and would not have a different chemical shift.

 

[Lawpy]

Isn't that what @Cuttlefish was asking? He said he thought they would be chemically equivalent but the video says they make separate signals? I haven't watched the video, but from the way I learned NMR, those two protons would produce one signal and would not have a different chemical shift.

The circled protons in the video image have different signals because they are diastereotopic. Replacing the purple circled proton vs replacing red circled proton with something else will result in two diastereomers. Diastereomers have different chemical and physical properties, and so the circled protons are in different chemical environments and have different chemical shifts.

 

[rabbott1971]

The circled protons in the video image have different signals because they are diastereotopic. Replacing the purple circled proton vs replacing red circled proton with something else will result in two diastereomers. Diastereomers have different chemical and physical properties, and so the circled protons are in different chemical environments and have different chemical shifts.

I quoted you as saying they are chemically equivalent, and I agree. Whether or not you could replace them with different things and create chirality does not seem to bear upon whether or not the molecule as given would show one or two signals for the circled protons! If there is a reason why these would show up as separate signals in the given configuration (not hypothesizing deuterium or other substituent) then please let me hear about that. Otherwise I choose to believe in the Lawper of fifteen minutes ago whom I quoted as finding the circled protons chemically equivalent.

 

[Lawpy]

I quoted you as saying they are chemically equivalent, and I agree. Whether or not you could replace them with different things and create chirality does not seem to bear upon whether or not the molecule as given would show one or two signals for the circled protons! If there is a reason why these would show up as separate signals in the given configuration (not hypothesizing deuterium or other substituent) then please let me hear about that. Otherwise I choose to believe in the Lawper of fifteen minutes ago whom I quoted as finding the circled protons chemically equivalent.

? You quoted me in the context of the discussion on enantiotopic protons. This is what I said regarding the problem at hand.

Basically, the carbon atom bonded to the two circled protons is a prochiral carbon atom. What this means is one of the protons can be replaced by a different substituent group to make that carbon atom chiral. For example, if you replace one of those hydrogen atoms with deuterium (hydrogen with a neutron), the carbon atom becomes a chiral center because deuterium and hydrogen differ in atomic mass and are chemically different. Replacing the purple circled proton with deuterium vs replacing the red circled proton with deuterium will result in a chiral center with opposite absolute configurations. Since the other chiral atom (marked by the red dot) is kept unchanged (and so the absolute configuration there is unchanged), replacing either of the proton will result in two new diasteromers. And as a result, the two circled protons are called diastereotopic, have different chemical environments and are not chemically equivalent.

Now, if you don't have an adjacent chiral center marked by the red dot and you only have one prochiral carbon atom attached to two protons, replacing either of the proton with deuterium will result in two chiral molecules with opposite absolute configurations. But since you are converting an achiral molecule to a chiral molecule with one chiral center, you are creating mirror images of the new chiral molecule and thus creating enantiomers. The protons attached to the prochiral carbon atom are called enantiotopic and are chemically equivalent (unless they are placed in a chiral environment, in which case they are not chemically equivalent and have different chemical shifts)

The circled protons are not enantiotopic and are not chemically equivalent. They are in different chemical environments. Seeing why that is requires imagining replacing one of the protons with a different substituent and observing the resulting chirality and configuration.

 

[rabbott1971]

Well we must be talking past each other. The molecule in the Khan Academy screen grab, with two circled hydrogens, is prochiral at the carbon with the circled hydrogens. From how I was taught to understand NMR, those two hydrogens are chemically equivalent. From your statements, you indicated they are chemically equivalent. But you go on to give an extensive discussion of stereoisomerism and what can happen, could happen, might happen, etc., and what we would call things in each of those contingencies. I don't understand how that impacts the NMR of the chemical compound shown in the screen grab, in which the circled hydrogens, to my understanding, are chemically equivalent. I'll try to look at the video, but I do not understand your comparisons to what might show up on NMR if you made this or that change to the given molecule.

 

[Lawpy]

Well we must be talking past each other. The molecule in the Khan Academy screen grab, with two circled hydrogens, is prochiral at the carbon with the circled hydrogens. From how I was taught to understand NMR, those two hydrogens are chemically equivalent. From your statements, you indicated they are chemically equivalent. But you go on to give an extensive discussion of stereoisomerism and what can happen, could happen, might happen, etc., and what we would call things in each of those contingencies. I don't understand how that impacts the NMR of the chemical compound shown in the screen grab, in which the circled hydrogens, to my understanding, are chemically equivalent. I'll try to look at the video, but I do not understand your comparisons to what might show up on NMR if you made this or that change to the given molecule.

No I said those protons are not chemically equivalent. For protons to have different chemical signals, they need to be in different chemical environments. Stereoisomerism definitely affects chemical environment (this is why diastereomers have different chemical and physical properties despite having same atoms and same structure but few of the chiral configurations had changed).

At first glance, the circled protons might look the same because they are both bonded to a carbon atom attached to different groups. But closer inspection shows they are not and this can be seen by converting the prochiral carbon into a chiral one by replacing a proton with something else. This conversion is necessary to show why the protons are in different chemical environments.

NMR signals reflect the chemical environment of the protons. Protons that are chemically equivalent will have one signal. Protons that are chemically different will have two or more different signals. Diastereotopic protons, like the circled protons in the video, are of different chemical environments and thus have different signals.

 

[Lawpy]

Here is another resource: 5-HMR-8 Symmetry in NMR Spectra

That said, I don't recall seeing these concepts on the MCAT, but I could see them explained in a difficult passage.

 

[rabbott1971]

OK thanks I looked at a few things and while I do not understand it, I recognize that there is a phenomenon there which accords with what you are saying. I'll have to study on it, but thanks for your patient replies.

 

[Lawpy]

OK thanks I looked at a few things and while I do not understand it, I recognize that there is a phenomenon there which accords with what you are saying. I'll have to study on it, but thanks for your patient replies.

It's an advanced concept but it's still based on a simple underlying theme: different NMR signals = different chemical environments of protons. Chemical equivalence = same chemical environment of protons = one NMR signal.

The substitution test for prochirality is a useful method for determining chemical equivalence of protons. It's based on the idea that molecular symmetry can affect chemical environment.

 

[663697]

Here is another resource: 5-HMR-8 Symmetry in NMR Spectra

That said, I don't recall seeing these concepts on the MCAT, but I could see them explained in a difficult passage.

In your opinion, would you say learning this rule is worth it with less than ~10 days left? Feels like I'd have to find a bunch of practice questions to get it down.

 

[Lawpy]

In your opinion, would you say learning this rule is worth it with less than ~10 days left? Feels like I'd have to find a bunch of practice questions to get it down.

It's good to know but definitely not required. NMR questions are among the hardest on the MCAT, and these concepts on stereoisomerism make it only harder. You could see them in a difficult passage but you'll have the information there to support it.

 

[rabbott1971]

I personally think the chemical shift idea Lawper described is beyond MCAT level base of knowledge. The stereoisomerism principles in general are better use of your time, but the NMR aspect is beyond the pale.

 

[rlaboss]

This is from Khan's video on Chemical equivalence in NMR. They say that the 2 circled protons are not chemically equivalent due to being adjacent to a chiral center, but the 3 protons to the left of the chiral center are equivalent. Why is this so?

I will try to explain the best I can. No matter how the central C2-C3 bond is rotated you would be able to identify which hydrogen was circled in purple. If it is in this /\/ spacial arrangement (as shown), you know the purple H is coming out of the screen. If you rotate the C-C bond between C2 and C3 180 degrees and have a spatial orientation that is like an upside down boat (picture \_/ upside down), you can be certain that the hydrogen circled in purple is now going into the page. Now the 3 terminal hydrogens. When the C1-C2 bond is rotated, there's no way to tell which hydrogen is which. In E2 reactions, it is often more favourable for the antiperiplanar proton to be removed. Because the spatial structure shown in more stable than the 'upsidedown' boat spatial conformation, in an E2 reaction where the antiperiplanar proton is more favourable to remove, the proton circled in red will more likely be removed in the E2 elimination. Therefore the two hydrogens circled are not chemically equivalent.

 

[rlaboss]

Basically a complicated reason that takes too long to explain. I learned about in a 3rd year orgo class. Don't worry about the reason and just remember that rule.

I will try to explain the best I can. No matter how the central C2-C3 bond is rotated you would be able to identify which hydrogen was circled in purple. If it is in this /\/ spacial arrangement (as shown), you know the purple H is coming out of the screen. If you rotate the C-C bond between C2 and C3 180 degrees and have a spatial orientation that is like an upside down boat (picture \_/ upside down), you can be certain that the hydrogen circled in purple is now going into the page. Now the 3 terminal hydrogens. When the C1-C2 bond is rotated, there's no way to tell which hydrogen is which. In E2 reactions, it is often more favourable for the antiperiplanar proton to be removed. Because the spatial structure shown in more stable than the 'upsidedown' boat spatial conformation, in an E2 reaction where the antiperiplanar proton is more favourable to remove, the proton circled in red will more likely be removed in the E2 elimination. Therefore the two hydrogens circled are not chemically equivalent.

 

[aldol16]

These effects are more easily rationalized with a physical organic chemistry background and are beyond the scope of the MCAT. The MCAT isn't testing you on whether you have highly technical knowledge of NMR and the physical meaning of chemical coupling - it's testing you on whether you can apply basic concepts to more complicated problems, which is what medicine is all about. So don't worry about this - know your basic NMR skills and you will do fine. The chance of you encountering a problem having to do with diastereotopic protons on the MCAT is miniscule. Even the chemistry GRE wouldn't test on these abstract concepts.

 

[663697]

These effects are more easily rationalized with a physical organic chemistry background and are beyond the scope of the MCAT. The MCAT isn't testing you on whether you have highly technical knowledge of NMR and the physical meaning of chemical coupling - it's testing you on whether you can apply basic concepts to more complicated problems, which is what medicine is all about. So don't worry about this - know your basic NMR skills and you will do fine. The chance of you encountering a problem having to do with diastereotopic protons on the MCAT is miniscule. Even the chemistry GRE wouldn't test on these abstract concepts.

So for the purposes of the MCAT would we most likely treat those 2 protons as chemically equivalent (unless the passage specifically introduces this topic)?

 

[aldol16]

So for the purposes of the MCAT would we most likely treat those 2 protons as chemically equivalent (unless the passage specifically introduces this topic)?

The MCAT probably won't touch on this topic - they wouldn't want you to erroneously assign these protons so you would likely get a simpler spectrum. This one is too complex.

 

[663697]

Sort of unrelated question but still on the topic of NMR:

One of the Khan practice questions said this structure has 2 triplets but I'm not sure if they are actually correct about this one. The 2 protons don't seem equivalent, so wouldn't it be a doublet of doublets?

 

[aldol16]

One of the Khan practice questions said this structure has 2 triplets but I'm not sure if they are actually correct about this one. The 2 protons don't seem equivalent, so wouldn't it be a doublet of doublets?

Depending on what R and X are, the two protons you show here are not equivalent. The one on the left will couple with the para proton (with respect to X) and be a doublet whereas the one on the right will couple with the para proton and the ortho proton for a doublet of doublets. The doublet of doublets could show up as a triplet depending on the coupling constants. You could also have long-range coupling which could complicate the spectrum.