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It is well-known that the "chair" conformation of cyclohexane is the most stable of its conformers. But is there any cyclohexane derivative where other notable conformers (boat, half-chair) are the most stable?

My own intuition is that if there are 4 very bulky groups in the 1, 2, 4, 5 positions then the boat conformer would be preferred.

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  • $\begingroup$ You don't want your cyclohexane to be a part of a larger polycyclic structure, I guess? $\endgroup$
    – Ivan Neretin
    Feb 7, 2020 at 9:04
  • 1
    $\begingroup$ Yes, I don't want, say, a decaline derivative. $\endgroup$
    – Gopai Mukherjee
    Feb 7, 2020 at 11:10
  • $\begingroup$ How about something where there is a carbonyl group on the ring, forcing a planar bonding geometry at that carbon; exclude that as well? $\endgroup$
    – Oscar Lanzi
    Feb 7, 2020 at 13:47
  • 1
    $\begingroup$ A simple force field optimisation should anwer this question. $\endgroup$
    – Karl
    Feb 7, 2020 at 16:59
  • 2
    $\begingroup$ How about norbonane molecule? $\endgroup$
    – Mathew Mahindaratne
    Feb 7, 2020 at 19:54

1 Answer 1

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TL;DR:

It is highly unlikely that there is a non-multicyclic derivative with a stable boat conformation.
It needs a lot of convincing and quite bulky groups to destabilise the chair conformation and stable another conformation like the twist-boat.

Conformations of cyclohexane

There are quite a few imaginable conformations,[1] but for cyclohexane itself there are only two stable: the chair and the twist-boat conformation. The other ones are transition states, which are given in the comments of the linked question.

chair conformation twist-boat conformation

A related question is Where is bifurcation situated on cyclohexane isomerisation PES? Unfortunately it is not answered. However, more insight is given by the articles of H. Rzepa on his blog and the pdf of some lecture notes.[2]

Below is an animation of the boat conformation's imaginary frequency, which will yield the twist-boat conformation upon relaxation.

imaginary mode of the boat conformation

Why is this actually the case? There is a very intuitive answer: There are eclipsed conformations where they do not have to be, see the image below. This stress can be easily relieved in this twist-boat conformation, in which all bonds are staggered (and the chair conformation, too, as it is the global minimum).

eclipsed highlighted of the boat conformation staggered bonds highlighted of the twist-boat conformation

You can even do a little bit more, for example looking at non-covalent interactions. I have optimised all structures on the RI-BP86/def2-SVP level of theory using ORCA 4.2.0. Then I have used Multiwfn to analyse NCI with promolecular densities.[3,4] You will see that the isosurface extends further to the hydrogens in the boat and twist boat conformations. Note that this is more a visualisation of these properties than actual evidence for their existence. It should help in understanding, but it shouldn't be used as a general argument. There are plenty of sources explaining why staggered conformations are generally lower in energy than eclipsed ones.

NCI analysis of the boat, twist-boat, and chair conformer of cycloxexane

Locking in a boat conformation

You have probably heard of a conformational anchor. Adding groups so that they will lock into a specific conformation. Like when you attach a tert-butyl group in one of the positions, it will rise the energy of the conformation when it is in axial position.

If you do not want to consider extended ring systems to lock the conformation into position, like the earlier mentioned norbornane and derivatives, you'll probably get structures to prefer a twist-boat conformation, but probably not one that will result in an actual boat conformation. I have tried some conformational sampling with CREST on the semiempirical GFN2-xTB level of theory and multiple attempts have failed so far.[5] In my attempts the closest I have gotten was with (1R,2S,3S,4R,5S,6r)‐1,2,3,4,5,6‐hexamethylcyclohexane, where the twist boat conformation is only about $\pu{1 kJ mol-1}$ higher in energy, see the images below (hydrogen omitted for clarity).

boat and chair conformation of (*1R*,*2S*,*3S*,*4R*,*5S*,*6r*)‐1,2,3,4,5,6‐hexamethylcyclohexane

I encourage you to get a molecular viewer and look at the structures yourself.[6] You will quickly see how crowded the ring actually is and that there is not much space to put much larger groups anyway. I believe this illustrates the problem well.

However, I was able to push it further and have found a beast that is predominantly available in the twist-boat conformation. Therefore I have added tert-butyl moieties in 1, 2, 4, and 5 position just as you have proposed, (1R,2S,4R,5S)‐1,2,4,5‐tetra‐tert‐butylcyclohexane. The CREST program found two (very, very similar) conformers within a $\approx\pu{25 kcal mol-1}$ window.[7] There was no chair conformation in this window, and the second structure is barely in the given interval, therefore I will not include it here.[8]

twist-boat conformation of (*1R*,*2S*,*4R*,*5S*)‐1,2,4,5‐tetra‐tert‐butylcyclohexane

Notes & References:

  1. For example, see what Geoff demonstrates for pyranose sugars in Conformations of Cyclohexane. There is also a more general article about ring puckering: https://doi.org/10.1021/ja00839a011, pdf via the Internet Archive
  2. The pdf via the Internet Archive
  3. Johnson, E. R.; Keinan, S.; Mori-Sánchez, P.; Contreras-García, J.; Cohen, A. J.; Yang, W. Revealing Noncovalent Interactions. J. Am. Chem. Soc. 2010, 132 (18), 6498–6506. DOI: 10.1021/ja100936w.
  4. I have previously written about it: How to identify hydrogen bonds and other non-covalent interactions from structure considerations?
  5. (a) Mulliken Center for Theoretical Chemistry, xTB on Github, xTB documentation, CREST: Phys. Chem. Chem. Phys. 2020, xTB: J. Chem. Theory Comput. 2017, 13 (5), 1989–2009 & J. Chem. Theory Comput. 2019, 15 (3), 1652–1671
  6. A good open source choice to view the following Cartesian coordinates is Avogadro. 
  36
 GFN2-xTB       -37.96990166 (“chair”)
 C          1.2520828623       -0.5447977556        0.4005613406
 C          2.5529154246       -1.2427641817       -0.0035234170
 H          2.5670950259       -1.4609755375       -1.0683723566
 H          2.6812224740       -2.1742430344        0.5412168974
 H          3.4037282124       -0.6057253357        0.2302177479
 H          1.1934851832       -0.5794558732        1.4947912916
 C          1.2932369007        0.9399180068       -0.0046696921
 C          1.6543517514        1.1471873131       -1.4778364887
 H          1.5052577715        2.1882681334       -1.7560128481
 H          2.7000386472        0.9041963949       -1.6490857234
 H          1.0549606283        0.5311695599       -2.1388312879
 C          0.0004268408        1.6743272530        0.3958681428
 C          0.0003369080        1.9795490247        1.8972278766
 H         -0.8803447484        2.5595415091        2.1655307399
 H          0.0002805364        1.0701573015        2.4915141491
 H          0.8810286139        2.5594814678        2.1656262412
 H          0.0007645822        2.6443828331       -0.1162274411
 C         -1.2926832357        0.9406761004       -0.0050185229
 C         -1.6531427367        1.1479070715       -1.4783512638
 H         -2.6988310362        0.9052087273       -1.6499938197
 H         -1.0536713182        0.5316482470       -2.1390476329
 H         -1.5036207617        2.1889143513       -1.7565761588
 H         -2.1018819331        1.4053817317        0.5738089641
 C         -1.2524695951       -0.5439792518        0.4004522605
 C         -2.5537665456       -1.2411162270       -0.0035423382
 H         -2.5679998358       -1.4596918660       -1.0683148885
 H         -2.6827814315       -2.1722962125        0.5415232111
 H         -3.4041581021       -0.6033840583        0.2298854735
 C         -0.0003947478       -1.2538292818       -0.1423844973
 C         -0.0008645772       -2.7329645415        0.2464953252
 H          0.8741384569       -3.2373492283       -0.1525769397
 H         -0.0008947662       -2.8427074989        1.3295318583
 H         -0.8762127488       -3.2367530896       -0.1525580475
 H         -0.0003167563       -1.1995260135       -1.2346248660
 H         -1.1939183223       -0.5785009660        1.4946918825
 H          2.1024953812        1.4040515111        0.5745201353
  36
 GFN2-xTB       -37.96945643 (“boat”)
 C          1.3009843031        0.3904694151        0.6116442813
 C          2.7523842286        0.8697430480        0.5759961739
 H          3.1370164012        0.8924092382       -0.4400705597
 H          3.3851298683        0.2141081553        1.1682244589
 H          2.8236187015        1.8700221417        0.9985166065
 H          1.0589906677        0.1993477976        1.6630540690
 C          0.3343786187        1.4770082561        0.0930304054
 C          0.8370012219        2.1686754632       -1.1755196945
 H          0.0729240573        2.8439373660       -1.5550562687
 H          1.7313073547        2.7544698863       -0.9832626635
 H          1.0594535849        1.4416329460       -1.9531205354
 C         -1.0843113664        0.9157582793       -0.1622022415
 C         -2.1249907625        1.9785105445        0.1901580387
 H         -3.1130958026        1.6979927608       -0.1639981009
 H         -2.1696260162        2.1243458743        1.2679063910
 H         -1.8631471288        2.9288081963       -0.2704747138
 H         -1.1814251431        0.6916654706       -1.2293744660
 C         -1.3009787861       -0.3905116297        0.6116386064
 C         -2.7523814313       -0.8697957935        0.5761213628
 H         -3.1371030728       -0.8924849595       -0.4399103572
 H         -3.3850864608       -0.2141683561        1.1683995711
 H         -2.8235618371       -1.8700681103        0.9986656463
 H         -1.0588901236       -0.1993916529        1.6630242750
 C         -0.3343953584       -1.4770058647        0.0929158564
 C         -0.8370714193       -2.1686218804       -1.1756271655
 H         -0.0730166306       -2.8438887577       -1.5552044908
 H         -1.7314363652       -2.7543627913       -0.9834449686
 H         -1.0594386262       -1.4414807272       -1.9531506454
 C          1.0843324761       -0.9157815011       -0.1622407002
 C          2.1250455546       -1.9784641695        0.1902373202
 H          2.1696137891       -2.1242687584        1.2679947854
 H          1.8631584859       -2.9287608420       -0.2703581429
 H          3.1131889321       -1.6980202130       -0.1638895009
 H          1.1815268495       -0.6916894600       -1.2294091391
 H         -0.2613905266       -2.2395020738        0.8774919294
 H          0.2613017165        2.2394206185        0.8776918141
  1. The default is actually $\pu{6 kcal mol-1}$, but I refuse to give in to these medieval units.
  2. Cartesian coordinates of the lowest structure of (1R,2S,4R,5S)‐1,2,4,5‐tetra‐tert‐butylcyclohexane:
  66
 GFN2-xTB       -69.56788868 (“twist-boat”)
 C          1.2637535413       -0.4535845271       -0.7036170298
 H          0.8234262820       -0.3514280493       -1.7011134458
 C          0.2874611950       -1.2968906916        0.1262691467
 H          0.4862260613       -1.1072837877        1.1760079950
 H          0.4711152326       -2.3509422427       -0.0576548430
 C         -1.2138745760       -1.0160032197       -0.1668918408
 H         -1.5059514690       -1.6533453308       -1.0111946700
 C         -2.0580638654       -1.5542451449        1.0386873052
 C         -3.5291500453       -1.7879146105        0.6673596086
 H         -4.0389307694       -2.2795212021        1.4949415613
 H         -3.6040044082       -2.4413551590       -0.2001570459
 H         -4.0628013225       -0.8693626960        0.4623391177
 C         -1.5380651982       -2.9543377210        1.4269474062
 H         -1.4806005503       -3.6016258516        0.5545295073
 H         -2.2263828398       -3.4107111998        2.1359237707
 H         -0.5631185572       -2.9193311608        1.9023111302
 C         -1.9997742111       -0.6828458212        2.2953624607
 H         -2.6171623926       -1.1292449936        3.0737145663
 H         -2.3680382876        0.3190177054        2.1083809564
 H         -0.9863340848       -0.6190135645        2.6836308403
 C         -1.2637584056        0.4535847074       -0.7036134097
 H         -0.8234213043        0.3514344229       -1.7011060021
 C         -0.2874690577        1.2968787699        0.1262850454
 H         -0.4862254771        1.1072466416        1.1760203260
 H         -0.4711273811        2.3509334181       -0.0576150207
 C          1.2138643519        1.0160021804       -0.1668873426
 H          1.5059281496        1.6533459288       -1.0111931129
 C          2.0580613014        1.5542510848        1.0386835495
 C          3.5291313266        1.7879648142        0.6673219595
 H          4.0628193815        0.8694121253        0.4623879257
 H          4.0388969819        2.2796720426        1.4948537541
 H          3.6039479309        2.4413286270       -0.2002563066
 C          1.5380254724        2.9543167424        1.4269934992
 H          0.5630890040        2.9192624252        1.9023748186
 H          1.4805221407        3.6016312375        0.5545978702
 H          2.2263377642        3.4106933389        2.1359728252
 C          1.9998372135        0.6828176443        2.2953360365
 H          2.3681483571       -0.3190197145        2.1083145750
 H          0.9864074015        0.6189230717        2.6836201429
 H          2.6172202830        1.1292244475        3.0736878514
 C         -2.5734381625        1.2159695783       -1.0649400350
 C         -3.4459088573        0.3435906290       -1.9774479664
 H         -3.6675713251       -0.6208273126       -1.5422795084
 H         -4.3867433184        0.8479997186       -2.1893090423
 H         -2.9342730730        0.1735856167       -2.9232393678
 C         -2.1913064757        2.4425123599       -1.9212170334
 H         -1.7500553845        3.2379982242       -1.3271846647
 H         -3.0851290926        2.8470606980       -2.3920018369
 H         -1.4898086285        2.1738538773       -2.7080018465
 C         -3.3790378509        1.7599694390        0.1164846666
 H         -3.8515396128        0.9790436919        0.6998702684
 H         -2.7421665034        2.3465041110        0.7744832021
 H         -4.1670675305        2.4137947017       -0.2548140206
 C          2.5734370335       -1.2159683519       -1.0649370663
 C          3.3790279628       -1.7599706209        0.1164927971
 H          3.8516735927       -0.9790428294        0.6997637198
 H          2.7421180248       -2.3463565373        0.7745861394
 H          4.1669484076       -2.4139382233       -0.2547885352
 C          3.4459325455       -0.3435930502       -1.9774226323
 H          4.3867849824       -0.8479910147       -2.1892312850
 H          3.6675602100        0.6208308804       -1.5422534239
 H          2.9343365617       -0.1736062497       -2.9232383093
 C          2.1913055807       -2.4425004188       -1.9212296089
 H          3.0851285923       -2.8470461925       -2.3920160549
 H          1.7500476265       -3.2379922732       -1.3272105313
 H          1.4898131110       -2.1738289364       -2.7080150254
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