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Tröger’s Base Tautomerization Reactions
Contributors: Charleville, S.W*, Sargent, K*, Winikoff, S.G; all from Truman State University
Contributors: Charleville, S.W*, Sargent, K*, Winikoff, S.G; all from Truman State University
Uploaded files:Hi Sami! Great poster! Your research looks very interesting and I think the way that you presented the information was very effective. I was wondering if you could explain to me how the large carbamoyl substituents drown out the methanol coordination effects, favoring the exo-product. Does this mean that although methanol faces less steric hinderance by approaching from the top face, the exo-product is ultimately favored because there is less steric interference within the molecule? I was also curious as to the choice of base used for deprotonation. Is there a specific reason this base was chosen and have other possibilities been tried? Thank you for your time and I really enjoyed your poster!
Hi Sami! Great poster! Your research looks very interesting and I think the way that you presented the information was very effective. I was wondering if you could explain to me how the large carbamoyl substituents drown out the methanol coordination effects, favoring the exo-product. Does this mean that although methanol faces less steric hinderance by approaching from the top face, the exo-product is ultimately favored because there is less steric interference within the molecule? I was also curious as to the choice of base used for deprotonation. Is there a specific reason this base was chosen and have other possibilities been tried? Thank you for your time and I really enjoyed your poster!
Hi!
This is an interesting poster. I have a question about Figure 3. Do you have any theories on why the exo structure is so much higher in energy than the endo structure for step two of the reaction coordinate?
Thanks,
Ellie
Hi!
This is an interesting poster. I have a question about Figure 3. Do you have any theories on why the exo structure is so much higher in energy than the endo structure for step two of the reaction coordinate?
Thanks,
Ellie
Thank you so much for your questions!
Maggie, your intuition is absolutely correct. The methanol faces less steric hindrance as it approaches from the top face, but this forces the carbamoyl group into a high-steric position, which counteracts any stabilizing effects.
In fact, this effect also answers Ellie’s question. The endo product is lower by step 2 because the methanol, approaching from the top face, stabilizes the negative charge, driving down the energy to be lower than the exo structure. However, by step 3, in which the proton is transferred to the enolate, the carbamoyl group is forced into an unfavorable position, which drives the endo energy back up again.
As for the base that we used (di-isopropylamine), the reasoning behind this base was due to experimental data collected by the Harmata group at the University of Missouri. They found that the deprotonation occurred with the highest yield when DIPA was used, as compared to diethylamine, for example, so we’re trying to replicate their conditions as best as possible computationally.
Thank you so much for your questions!
Maggie, your intuition is absolutely correct. The methanol faces less steric hindrance as it approaches from the top face, but this forces the carbamoyl group into a high-steric position, which counteracts any stabilizing effects.
In fact, this effect also answers Ellie’s question. The endo product is lower by step 2 because the methanol, approaching from the top face, stabilizes the negative charge, driving down the energy to be lower than the exo structure. However, by step 3, in which the proton is transferred to the enolate, the carbamoyl group is forced into an unfavorable position, which drives the endo energy back up again.
As for the base that we used (di-isopropylamine), the reasoning behind this base was due to experimental data collected by the Harmata group at the University of Missouri. They found that the deprotonation occurred with the highest yield when DIPA was used, as compared to diethylamine, for example, so we’re trying to replicate their conditions as best as possible computationally.
Thank you for this poster. This is a really interesting molecule and I love that you are connecting this work directly to experimental work. Really useful! I have two questions:
- The y-axes of Figs 2 and 3 are labeled Relative Gibbs. Does mean that you've got entropy included in the energies that are shown? If so, this is very tricky -- I'm curious how you went about including entropy effects.
- I was a little surprised to see in Figure 2 that the last step of the reaction is uphill. So then I'm wondering, why does the HDIPA leave? Why doesn't it just remain coordinated to the base?
Thank you for this poster. This is a really interesting molecule and I love that you are connecting this work directly to experimental work. Really useful! I have two questions:
- The y-axes of Figs 2 and 3 are labeled Relative Gibbs. Does mean that you've got entropy included in the energies that are shown? If so, this is very tricky -- I'm curious how you went about including entropy effects.
- I was a little surprised to see in Figure 2 that the last step of the reaction is uphill. So then I'm wondering, why does the HDIPA leave? Why doesn't it just remain coordinated to the base?
This is a really interesting poster! How do you think the sterics on the amide are effecting the transition state to ensure that tautomerization is happening?
Thanks,
Emma
This is a really interesting poster! How do you think the sterics on the amide are effecting the transition state to ensure that tautomerization is happening?
Thanks,
Emma
Thank you for this poster. This is a really interesting molecule and I love that you are connecting this work directly to experimental work. Really useful! I have two questions:
- The y-axes of Figs 2 and 3 are labeled Relative Gibbs. Does mean that you've got entropy included in the energies that are shown? If so, this is very tricky -- I'm curious how you went about including entropy effects.
- I was a little surprised to see in Figure 2 that the last step of the reaction is uphill. So then I'm wondering, why does the HDIPA leave? Why doesn't it just remain coordinated to the base?
Hi Brent! Thank you for your questions!
- Yes, we've obtained these units using uncorrected Gibbs free energy from frequency calculations, which accounts for entropy.
- This is a really great question, and it's something that we would like to know ourselves! Right now, we think it's an artifact from a calculation error (probably from DIPA), so we're rerunning jobs to look into it.
Very good questions, thank you!
Thank you for this poster. This is a really interesting molecule and I love that you are connecting this work directly to experimental work. Really useful! I have two questions:
- The y-axes of Figs 2 and 3 are labeled Relative Gibbs. Does mean that you've got entropy included in the energies that are shown? If so, this is very tricky -- I'm curious how you went about including entropy effects.
- I was a little surprised to see in Figure 2 that the last step of the reaction is uphill. So then I'm wondering, why does the HDIPA leave? Why doesn't it just remain coordinated to the base?
Hi Brent! Thank you for your questions!
- Yes, we've obtained these units using uncorrected Gibbs free energy from frequency calculations, which accounts for entropy.
- This is a really great question, and it's something that we would like to know ourselves! Right now, we think it's an artifact from a calculation error (probably from DIPA), so we're rerunning jobs to look into it.
Very good questions, thank you!
