Why is S-Ethyl 3-hydroxybutanoate SO MUCH more stable than its R enantiomer?

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Discussion Overview

The discussion centers on the stability and boiling points of the enantiomers S-ethyl 3-hydroxybutanoate and R-ethyl 3-hydroxybutanoate, exploring the reasons behind the observed differences in their properties and the implications for reactions involving these compounds.

Discussion Character

  • Debate/contested
  • Technical explanation
  • Experimental/applied

Main Points Raised

  • One participant notes a significant difference in boiling points between the R and S enantiomers, questioning how such a difference can exist for what is essentially the same molecule.
  • Another participant challenges the initial claim, stating that enantiomers typically have the same boiling point under normal conditions and suggests that the data may be misinterpreted or sourced incorrectly.
  • A participant acknowledges a correction regarding the spelling of the compound and expresses confusion about the stability of the R enantiomer in the context of a reduction reaction using alcohol dehydrogenase.
  • One participant explains that the preference for one enantiomer over the other in enzymatic reactions is due to the lack of symmetry in the enzyme's active site, rather than stability differences.
  • Another participant proposes that the observed predominance of the S enantiomer in their reaction is due to the enzyme's ability to interact more favorably with the S form, while the formation of the R enantiomer is attributed to an induced fit model that occurs less efficiently.
  • A later reply confirms the explanation provided regarding the enzyme's interaction with the substrate.

Areas of Agreement / Disagreement

Participants express disagreement regarding the boiling points of the enantiomers, with some asserting that enantiomers should have the same boiling point while others present data suggesting otherwise. The discussion on the enzymatic reaction indicates some consensus on the role of enzyme symmetry, but the overall topic remains unresolved.

Contextual Notes

There are limitations regarding the assumptions made about boiling points and the conditions under which the data were obtained. The discussion also highlights the dependence on specific experimental setups and definitions related to enantiomer stability.

ericvon11
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The boiling point for R-ethyl 3-hyrdoxybutanoate is about 75 C
The boiling point for S-ethyl 3-hyrdoxybutanoate is about 180 C

How!?
How is the same molecule that much more stable just by rearrangement of the hydroxy group. I'm trying to explain how some R enantiomer may boil off along with ether if heated enough but I'd like to explain why it is that the R enantiomer is less stable
 
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This must be wrong (the spelling of the substance name is also wrong by the way). Enantiomers have the same boiling point under normal conditions. Were it true you'd have a wonderful business opportunity separating the enantiomes and selling them. I checked the data at Sigma Aldrich and I suspect that is where you have got your data because I find the same odd difference. The racemate is stated to have a bp of 170 oC so the higher value is probably true.
 
Woops! I meant hydroxy. Hm, maybe I read this was under pressure. My lab book says 180-182 for the s enantiomer. I'm still confused as to why the re face of ethyl acetoacetate is so much more favorable in my reduction reaction using alcohol dehydrogenase. Any clue?
 
Yes, with the dehydrogenase it has nothing to do with stability. It is related to the lack of symmetry in the enzyme active site. If I remember correctly there are some rules of thumb to predict which enantiomer that predominates for a new substrate but the thumb of those rules tend to be rather thick so often you get what you get.
At pdb there are lots of structures here is a relevant one showing an inhibitor bound to the active site: http://www.rcsb.org/pdb/explore/explore.do?structureId=1AXE
 
cool, that helps. Basically, I've taken it that the reason why I got 92 percent S in this reaction of yeast alcohol dehydrogenase and acetoacetate is because NADH can only donate to the acetoacetate from one side that fits (the S). And the small amount of R would likely be from induced fit model meaning that the enzyme changes to fit some si faced acetoacetates making R enantiomers. This however must take longer than the S and thus is less. Does that sound right, to your knowledge?
Edit: Fits from one side (re face creating an S)
 
Exactly!
 
Thank you so much. I've been trying to explain this lab for the entire day and couldn't quite get it. I appreciate the help!
 

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