Conformational isomerism

Rotation about single bond of butane to interconvert one conformation to another. The gauche conformation on the right is a conformer, while the eclipsed conformation on the left is a transition state between conformers. Above: Newman projection; below: depiction of spatial orientation.

In chemistry, conformational isomerism is a form of stereoisomerism in which the isomers can be interconverted just by rotations about formally single bonds (refer to figure on single bond rotation). While any two arrangements of atoms in a molecule that differ by rotation about single bonds can be referred to as different conformations, conformations that correspond to local minima on the potential energy surface are specifically called conformational isomers or conformers.[1] Conformations that correspond to local maxima on the energy surface are the transition states between the local-minimum conformational isomers. Rotations about single bonds involve overcoming a rotational energy barrier to interconvert one conformer to another. If the energy barrier is low, there is free rotation[2] and a sample of the compound exists as a rapidly equilibrating mixture of multiple conformers; if the energy barrier is high enough then there is restricted rotation, a molecule may exist for a relatively long time period as a stable rotational isomer or rotamer (an isomer arising from hindered single-bond rotation). When the time scale for interconversion is long enough for isolation of individual rotamers (usually arbitrarily defined as a half-life of interconversion of 1000 seconds or longer), the isomers are termed atropisomers (see: atropisomerism).[1][3][4] The ring-flip of substituted cyclohexanes constitutes another common form of conformational isomerism.

Conformational isomers are thus distinct from the other classes of stereoisomers (i. e. configurational isomers) where interconversion necessarily involves breaking and reforming of chemical bonds.[5] For example, L/D- and R/S- configurations of organic molecules have different handedness and optical activities, and can only be interconverted by breaking one or more bonds connected to the chiral atom and reforming a similar bond in a different direction or spatial orientation. They also differ from geometric (cis/trans) isomers, another class of stereoisomers, which require the π-component of double bonds to break for interconversion. (Although the distinction is not always clear-cut, since certain bonds that are formally single bonds actually have double bond character that becomes apparent only when secondary resonance contributors are considered, like the C–N bonds of amides, for instance.) Due to rapid interconversion, conformers are usually not isolable at room temperature.

The study of the energetics between different conformations is referred to as conformational analysis.[6] It is useful for understanding the stability of different isomers, for example, by taking into account the spatial orientation and through-space interactions of substituents. In addition, conformational analysis can be used to predict and explain product selectivity, mechanisms, and rates of reactions.[7] Conformational analysis also plays an important role in rational, structure-based drug design.

  1. ^ a b Moss, GP (1996-01-01). "Basic terminology of stereochemistry (IUPAC Recommendations 1996)". Pure and Applied Chemistry. 68 (12): 2193–2222. doi:10.1351/pac199668122193. ISSN 1365-3075. S2CID 98272391.
  2. ^ IUPAC, Compendium of Chemical Terminology, 2nd ed. (the "Gold Book") (1997). Online corrected version: (1996) "Free rotation (hindered rotation, restricted rotation)". doi:10.1351/goldbook.F02520
  3. ^ Ōki, Michinori (1983) Recent Advances in Atropisomerism, in Topics in Stereochemistry, Vol. 14 (N. L. Allinger, E. L. Eliel and S. H. Wilen, Eds.), Hoboken, NJ:John Wiley & Sons, pp. 1-82; published online in 2007, DOI: 10.1002/9780470147238.ch1, see [1] and [2][permanent dead link], accessed 12 June 2014.
  4. ^ Alkorta, Ibon; Jose Elguero; Christian Roussel; Nicolas Vanthuyne; Patrick Piras (2012). Atropisomerism and Axial Chirality in Heteroaromatic Compounds. Advances in Heterocyclic Chemistry. Vol. 105. pp. 1–188. doi:10.1016/B978-0-12-396530-1.00001-2. hdl:10261/62060. ISBN 9780123965301.
  5. ^ Hunt, Ian. "Stereochemistry". University of Calgary. Retrieved 28 October 2013.
  6. ^ Anslyn, Eric; Dennis Dougherty (2006). Modern Physical Organic Chemistry. University Science. p. 95. ISBN 978-1891389313.
  7. ^ Barton, Derek (1970). "The Principles of Conformational Analysis". Nobel Media AB 2013. 169 (3945). Elsevier Publishing Co.: 539–44. Bibcode:1970Sci...169..539B. doi:10.1126/science.169.3945.539. PMID 17746022. Retrieved 10 November 2013.