4
$\begingroup$

Changing one atropisomer to another requires bond breaking (in some cases the removal and reattachement of steric groups, according to my understanding) so how it is possible that according to IUPAC atropisomers are classified as conformers (conformational isomers)?

According to IUPAC:

Atropisomers - A subclass of conformers which can be isolated as separate chemical species and which arise from restricted rotation about a single bond.

Conformers - One of a set of stereoisomers, each of which is characterized by a conformation corresponding to a distinct potential energy minimum.

Conformation - The spatial arrangement of the atoms affording distinction between stereoisomers, which can be inter-converted by rotations about formally single bonds. Some authorities extend the term to include inversion at trigonal pyramidal centres and other polytopal rearrangements.

This definition of "conformation" seems vague to me, but it is often said that changing one conformation to another involves no bond-breaking and changing one configuration to another requires bond-breaking. This is the difference between them.

IUPAC gives examples of atropisomerism: e.g. (E)-cyclooctene (given in Gold Book "planar chirality" entry). This definitely should involve bond-breaking. Other IUPAC examples of atropisomerism include substituted ortho-biphenyls.

$\endgroup$
5
  • 2
    $\begingroup$ Think of the whole bond-breaking narrative in a different way: the bonds in both isomers are exactly the same. $\endgroup$ – Ivan Neretin Sep 24 '18 at 10:03
  • 1
    $\begingroup$ They're conformers, but with very high energy barrier of rotation. $\endgroup$ – Mithoron Sep 24 '18 at 15:56
  • $\begingroup$ @IvanNeretin I don't understand? Bonds are the same in (configurational) chiral centres too, but they are oriented differently and require bond breaking as well as (E/Z)-cyclooctene which supposedly is atropoisomeric. $\endgroup$ – user35715 Sep 25 '18 at 0:22
  • $\begingroup$ @Mithoron Yes, some of them, like (E)-cyclooctene requires a lot of energy to break the double bond temporarily to turn it in to (Z)-cyclooctene, but this bond-breaking is the problem I have trouble understanding. How come you can call something that involves bond-breaking atropisomerism and conformerism? $\endgroup$ – user35715 Sep 25 '18 at 0:27
  • $\begingroup$ @user35715: The transformation of E- to Z-cyclooctene is a configurational change that involves bond breaking be it sigma or pi bonds. But this is not the issue. Think about the E-double bond of cyclooctene "jumping rope with the methylene chain", which interconverts enantiomers. Granted it is difficult for this ring but no bonds need to be broken. $\endgroup$ – user55119 Sep 9 '20 at 14:22
7
+50
$\begingroup$

I think your notation of "Changing one atropisomer to another requires bond breaking (in some cases the removal and reattachement of steric groups, according to my understanding)" is not correct. To my knowledge, the free rotation of one single bond of an atropisomer is not restricted by connecting bond(s). I think you get confused by some literature explaining breaking a bond selectively directed to pair of atropisomers (e.g., Ref.1):

Preparation of atropisomers by breaking a bond

According to your post, IUPAC definition of atropisomers:

Atropisomers - A subclass of conformers which can be isolated as separate chemical species and which arise from restricted rotation about a single bond.

A variety of sources confirm this definition. For instance, Ref.2 and 3 described atropisomers as:

Atropisomers are stereoisomers (rotamers) resulting from hindered rotation about single bonds (having an energy barrier to rotation about a single $\sigma$ bond) usually due to steric hindrance. This energy barrier to rotation is high enough to allow the isolation of the conformers (rotamers).

Nonetheless, the name, coined by German biochemist Richard Kuhn in application to a theoretical concept 1n 1933 (Wikipedia) is derived from Greek (a = not and tropos = turn; thus, atropos meaning "without turn"), which supported the definition. However, the atropisomerism was first detected in 6,6'-dinitro-2,2'-diphenic acid by Cristie, et al. in 1922 (Ref.4):

6,6'-dinitro-2,2'-diphenic acids

It is also important to know the nomenclature of atropisomers (Wikipedia):

Determining the axial stereochemistry of biaryl atropisomers can be accomplished through the use of a Newman projection along the axis of hindered rotation. The ortho, and in some cases meta substituents are first assigned priority based on Cahn–Ingold–Prelog priority rules (Ref.5 & Ref.6). One scheme of nomenclature in based on envisioning the helicity defined by these groups (Ref.7). Starting with the substituent of highest priority in the closest ring and moving along the shortest path to the substituent of highest priority in the other ring, the absolute configuration is assigned $P$ or $\Delta$ for clockwise and $M$ or $\Lambda$ for counterclockwise. Alternately, all four groups can be ranked by Cahn–Ingold–Prelog priority rules, with overall priority given to the groups on the "front" atom of the Newman projection. The two configurations are termed $R_\mathrm{a}$ and $S_\mathrm{a}$ in analogy to the traditional $R/S$ for a traditional tetrahedral stereocenter (Ref.8}:

Nomenclature of atropisomers

Atropisomers are also found in nature. The main pigment of cotton seeds, gossypol is an atropisomer, which exists in both form of $(R_\mathrm{a})$- and $(S_\mathrm{a})$-conformations. Most commercial Upland (Gossypium hirsutum) cottonseeds have an $(R_\mathrm{a})$- to $(S_\mathrm{a})$-gossypol ratio of ~$2:3$, but some Pima (Gossypium barbadense) seeds have an excess of $(R_\mathrm{a})$-gossypol. Between two isomers, $(R_\mathrm{a})$-gossypol is more toxic and exhibits significantly greater anticancer activity than its $(S_\mathrm{a})$-atropisomer:

(Ra)- and (Sa)-Gossypols

Two fun facts about atropisomers are (KU.edu):

  • Atropisomers are detectable by $\mathrm{NMR}$ if half lives exceed $\pu{10^{-2} s}$.
  • Atropisomers are isolatable if the half-life is above $\pu{10^3 s}$.

References:

  1. Gerhard Bringmann, Thomas Hartung, “Atropo-enantioselective biaryl synthesis by stereocontrolled cleavage of configuratively labile lactone-bridged precursors using chiral H-nucleophiles,” Tetrahedron 1993, 49(36), 7891-7902 (https://doi.org/10.1016/S0040-4020(01)88014-5).
  2. Alan R. Katritzky, Christopher A. Ramsden, John A. Joule, Viktor V. Zhdankin, In Handbook of Heterocyclic Chemistry, Third Edition; Elsevier Limited: Amsterdam, The Netherlands, 2010 (ISBN: 978-0-08-095843-9).
  3. Jonathan Clayden, “Atropisomerism,” Tetrahedron 2004, 60(20), 4335 (https://doi.org/10.1016/j.tet.2004.03.002).
  4. George Hallatt Christie, James Kenner, "LXXI.—The molecular configurations of polynuclear aromatic compounds. Part I. The resolution of $\gamma$-6 : 6′-dinitro- and 4 : 6 : 4′ : 6′-tetranitro-diphenic acids into optically active components," Journal of the Chemical Society, Transactions 1922, 121, 614–620 (https://doi.org/10.1039/CT9222100614).
  5. R. S. Cahn, Christopher Ingold, V. Prelog, “Specification of Molecular Chirality,” Angew. Chem. Internat. Ed. Engl. 1966, 5(4), 385-415 (https://doi.org/10.1002/anie.196603851) and Corrigendum: Angew. Chem. Internat. Ed. Engl. 1966, 5(5), 511-511 (https://doi.org/10.1002/anie.196605111).
  6. G. P. Moss, "Basic terminology of stereochemistry: IUPAC Recomendations 1996," Pure and Applied Chemistry 1996, 68(12), 2193-2222 ()(PDF).
  7. http://goldbook.iupac.org/terms/view/H02763: IUPAC. Compendium of Chemical Terminology, 2nd ed. (the "Gold Book"). Compiled by A. D. McNaught and A. Wilkinson. Blackwell Scientific Publications, Oxford (1997). Online version (2019-) created by S. J. Chalk. ISBN 0-9678550-9-8. https://doi.org/10.1351/goldbook.
  8. http://goldbook.iupac.org/terms/view/A00547: IUPAC. Compendium of Chemical Terminology, 2nd ed. (the "Gold Book"). Compiled by A. D. McNaught and A. Wilkinson. Blackwell Scientific Publications, Oxford (1997). Online version (2019-) created by S. J. Chalk. ISBN 0-9678550-9-8. https://doi.org/10.1351/goldbook.
$\endgroup$
3
$\begingroup$

While the user seems to have vanished, its worth pointing out the misconception they are having. Its not that the (E) and (Z) enantiomers of cyclooctene are atropisomers. Rather, (E)-cyclooctene has two atropisomeric conformations, which can be interconverted with out breaking the double bond. Rotation is hindered around this bond, but it can still occur due to rotation of the two surrounding single bonds. A very nice depiction of this can be found on Henry Rzepa's old website

(In case the link breaks, here is the DOI for the main hub of the site) DOI: http://doi.org/10042/a3uy9

$\endgroup$

Your Answer

By clicking “Post Your Answer”, you agree to our terms of service, privacy policy and cookie policy