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In order to draw chemical structures I use ChemBioDraw Ultra.

As an exercise I've to draw the most stable conformation.

enter image description here

I expect a twist-boat like structure (instead of usual chair conformation for substituted dioxanes)

Is there a freeware or an easy computer online tool to check if my propose (right side picture) is correct?

When I go to >Edit > Get 3D Model the program gives me a small picture with a 3D-Model: enter image description here

By double-clicking this small image it opens ChemBio3DUltra and I can rotate this molecule: enter image description here

@Martin: Is this correct (I've expected a twisted cyclic ring)?

@Martin I draw the structure at right with i-Bu and H exchanged in Chemdraw and do >Edit > Get 3D Model

enter image description here

The reason why I first thought it should be twist boat like was that one C-O is pointing up and the other pointing down. May be someone knows why people gives this stereoinformation inside the cyclic ring?

enter image description here

As I've drawn it as a twist boat I get exactly the same with ChemBioDraw. Is there a way to calculate by how many kcal/mol the first one is more stable then the second one with ChemBioDraw?

What's interesting: I searched for a structure in which the twist-boat conformation is the most favorable one and found one:

However, when there are two large substituents in the cis-1,4 arrangement on a cyclohexane ring, neither of which will go easily into an axial position, then it appears that the twist-boat conformation (Section 12-3A) is most favorable [http://authors.library.caltech.edu/25034/13/BPOCchapter12.pdf, page 458]

(The A-value of a tert-Butyl is in the range of 5 kcal/mol which is around the value of the energy difference between cyclohexane in twist-boat and chair conformation. I've drawn cis-1,4-di-tert-butyl-cyclohexane with ChemDraw and used >Edit>Get 3D Model and ChemBioDraw gave me the structure which is NOT the energetical most suitable one! Why?

enter image description here

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  • $\begingroup$ If you drew it with ChemBioDraw already, why don't you also check it with the Chem3D implementation? $\endgroup$
    – Martin - マーチン ♦
    Commented Oct 7, 2014 at 12:47
  • $\begingroup$ Well the program might only give you its best estimate, which is clearly basing it on chair conformations. So you might have to edit your molecule to be a twisted conformer.// On a second view, your stereochemistry in the right hand picture is at least ambiguous, if not wrong (as it says R, S).// I also would not have expected a twisted conformer, but I can be wrong on this one. $\endgroup$
    – Martin - マーチン ♦
    Commented Oct 7, 2014 at 13:27
  • $\begingroup$ You can use programs like Avogadro to get the molecular mechanics energy of different force fields. I believe Chem3D also supports MMFF or MM3 or similar force field evaluations. I agree with @Martin that you will need to test the twist-boat conformation and you will likely need to edit the 3D structure for that. $\endgroup$
    – Geoff Hutchison
    Commented Oct 7, 2014 at 13:40
  • $\begingroup$ Is whatever forcefield you are using correctly parametrized for cyclic acetals? If you have access to the CSD, why not use actual data? $\endgroup$
    – Abel Friedman
    Commented Oct 7, 2014 at 15:31
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    $\begingroup$ For your recent update (i.e., for cis-t-butyl) I don't know how ChemDraw and Chem3D generate the 3D structures. That's a tech support question. I doubt they do a significant force field minimization or test multiple ring conformations. Very few programs evaluate ring conformers automatically. $\endgroup$
    – Geoff Hutchison
    Commented Oct 7, 2014 at 19:36

2 Answers 2

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Short answer: yes, the dioxane has a minimum when it's in a twist-boat form.

I use Avogadro which offers a "auto-optimize" tool. You can grab atoms and throw them around to force rings into different conformations while the force field is minimizing.

So here's what I did.

  • File -> Import -> Fetch by chemical name: (2R,4R)-2-isobutyl-4-methyl-1,5-dioxaspiro[5.5]undecane. This grabs the 3D geometry from the NIH Resolver (i.e., PubChem)
  • Auto-Optimize Tool: Force Field MMFF94

Then I started minimizing and looking at the energies. I pulled various atoms around to try to minimize steric clashes and flip rings from chair to boat, etc.

For the figures that follow, I've removed the hydrogens for clarity, but they exist as far as the energies and minimization. I just removed them to save the graphic.

Chair/Chair: 24 kJ/mol

chair-chair form

Twist-boat/Chair: 14 kJ/mol

twist-chair

So yes, there's a decent stabilization in the twisted form of the twist-boat. You have to get the hydrogens right, or you'll end up with a bunch of eclipsed interactions between the dioxane oxygens and hydrogens on the cyclohexane.

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  • $\begingroup$ This is a very useful description! When I optimize I get a value of 402.258 kJ/mol for the optimal configuration. Is there a way to directly see the 24kJ/mol or have you used a calculator? "Chair/Chair: 24 kJ/mol" means that this chair is 24 kJ/mol higher in energy as the normal cyclohexane chair? $\endgroup$
    – laminin
    Commented Oct 8, 2014 at 13:57
  • $\begingroup$ What force field are you using? The default is UFF, but I switched to MMFF94 which is designed for organic molecules. UFF is less accurate but defined for all elements and strange geometries. $\endgroup$
    – Geoff Hutchison
    Commented Oct 8, 2014 at 13:59
  • $\begingroup$ I used MMFF94. See my screenshot: dropbox.com/s/gz6jyz5raezlc4u/avogadro.PNG?dl=0 $\endgroup$
    – laminin
    Commented Oct 8, 2014 at 14:12
  • $\begingroup$ I'd be happy to move this to chat. I don't see hydrogens, and your structure is completely planar, so of course the energy is higher. $\endgroup$
    – Geoff Hutchison
    Commented Oct 8, 2014 at 15:06
  • $\begingroup$ Thank you. I'd like to move this to chat too, but how? I just imported by name, clicked AutoOptimization, MMFF94 and pulled on some bonds still the value gets smaller. Is there a easy way to know which bonds I have to pull? Now I recognized that for optimization I have to display the hydrogens. Now I recognized that for optimization I have to display the hydrogens. I got a value of 12.6463 kJ/mol which makes more sense. $\endgroup$
    – laminin
    Commented Oct 8, 2014 at 15:48
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It's tough to see in your Chem3D picture (try turning off display of H's), but the dioxane is in a chair conformation. Truthfully, I don't think you need a 3D package to determine this, although using the energy minimization can confirm your hypothesis.

My approach is to assume that the dioxane is going to be in a chair conformation. I'm much better at converting six membered rings to the chair if I start with the ring completely in the plane. In this case, that means redrawing the original so that the oxygens are in the plane and the isobutyl and methyl groups are viewed as substituents off the dioxane (left side of figure). Now it becomes clear that the substituents should be in a trans-1,3 relationship. (Note that you have an error in your ChemDraw pics that these groups are cis. The R/S designation even changes at the isobutyl group.) Next, I draw a chair and place the oxygens. I like to number the atoms to avoid mistakes, although many people are better at this than me and can skip this step. In my first chair drawing, I see that the isobutyl group is placed axially, and interacts with the fused cyclohexane. Going through a ring flip puts the isobutyl equatorial and the methyl axial. There's no way to avoid 1,3-diaxial interactions completely, so I would predict that the right chair structure is the most favorable.

enter image description here

Where the 3D packages can really help is to see how much the chairs are distorted toward a twist conformation, but for a first guess, I think the hand drawn structures are useful.

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  • $\begingroup$ Thank you for this very helpful answer! I guess that the equilibrium is only a very tiny shifted towards the right one because i-Bu is like a Me because of avoiding interaction of the i-Pr attached on the first carbon atom. $\endgroup$
    – laminin
    Commented Oct 8, 2014 at 14:00

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