Ring flip

Last updated
The conformer of methylcyclohexane with equatorial methyl is favored by 1.74 kcal/mol (7.3 kJ/mol) relative to the conformer where methyl is axial. MeC6H11conformers.svg
The conformer of methylcyclohexane with equatorial methyl is favored by 1.74 kcal/mol (7.3 kJ/mol) relative to the conformer where methyl is axial.

In organic chemistry, a ring flip (also known as a ring inversion or ring reversal) is the interconversion of cyclic conformers that have equivalent ring shapes (e.g., from a chair conformer to another chair conformer) that results in the exchange of nonequivalent substituent positions. [1] The overall process generally takes place over several steps, involving coupled rotations about several of the molecule's single bonds, in conjunction with minor deformations of bond angles. Most commonly, the term is used to refer to the interconversion of the two chair conformers of cyclohexane derivatives, which is specifically referred to as a chair flip, although other cycloalkanes and inorganic rings undergo similar processes.

Contents

Chair flip

As stated above, a chair flip is a ring inversion specifically of cyclohexane (and its derivatives) from one chair conformer to another, often to reduce steric strain. The term, "flip" is misleading, because the direction of each carbon remains the same; what changes is the orientation. A conformation is a unique structural arrangement of atoms, in particular one achieved through the rotation of single bonds. [2] A conformer is a conformational isomer, a blend of the two words.

Cyclohexane

There exist many different conformations for cyclohexane, such as chair, boat, and twist-boat, but the chair conformation is the most commonly observed state for cyclohexanes because it requires the least amount of energy. [3] The chair conformation minimizes both angle strain and torsional strain by having all carbon-carbon bonds at 110.9° and all hydrogens staggered from one another. [2]

The conformational changes that occur in a cyclohexane ring flip take place over several stages. Structure D (10.8 kcal/mol) is the highest energy transition state of the process. Cyclohexane ring flip and relative conformation energies.svg
The conformational changes that occur in a cyclohexane ring flip take place over several stages. Structure D (10.8 kcal/mol) is the highest energy transition state of the process.

The molecular motions involved in a chair flip are detailed in the figure on the right: The half-chair conformation (D, 10.8 kcal/mol, C2 symmetry) is the energy maximum when proceeding from the chair conformer (A, 0 kcal/mol reference, D3d symmetry) to the higher energy twist-boat conformer (B, 5.5 kcal/mol, D2 symmetry). The boat conformation (C, 6.9 kcal/mol, C2v symmetry) is a local energy maximum for the interconversion of the two mirror image twist-boat conformers, the second of which is converted to the other chair confirmation through another half-chair. At the end of the process, all axial positions have become equatorial and vice versa. The overall barrier of 10.8 kcal/mol corresponds to a rate constant of about 105 s–1 at room temperature.

Note that the twist-boat (D2) conformer and the half-chair (C2) transition state are in chiral point groups and are therefore chiral molecules. In the figure, the two depictions of B and two depictions of D are pairs of enantiomers.

As a consequence of the chair flip, the axially-substituted and equatorially-substituted conformers of a molecule like chlorocyclohexane cannot be isolated at room temperature. However, in some cases, the isolation of individual conformers of substituted cyclohexane derivatives has been achieved at low temperatures (–150 °C). [4]

Axial and equatorial positions

As noted above, by transitioning from one chair conformer to another, all axial positions become equatorial and all equatorial positions become axial. Substituent groups in equatorial positions roughly follow along the equator of the cyclohexane ring and are perpendicular to the axis, while substituents in axial positions roughly follow the imaginary axis of the carbon ring and are perpendicular to the equator. [5]

Diaxial interactions or axial-axial interactions is what the steric strain between an axial substituent and another axial group, typically a hydrogen, on the same side of a chair conformation ring. The interaction is labeled by the carbon number they come from. A 1,3-diaxial interaction happens between the atoms connected to the first and third carbons. The more interactions the more strain on the molecule and the conformations with the most strain are less likely to be seen. An example is cyclopropane which, because of its planar geometry, has six fully eclipsed carbon and axial hydrogen bonds making the strain 116 kJ/mol (27.7 kcal/mol). [5] Strain can also be decreased when the carbon-carbon bond angles are close or at the preferred bond angle of 109.5°, meaning a ring having six tetrahedral carbons is typically lower than that of most rings.  

Numbered six carbon ring demonstrating the changes made axially and equatorially when a ring is "flipped."In the left side representation, red hydrogens are equatorial, then become axial upon ring flip. Ring flip.png
Numbered six carbon ring demonstrating the changes made axially and equatorially when a ring is "flipped."In the left side representation, red hydrogens are equatorial, then become axial upon ring flip.

Examples

The H NMR spectrum of titanocene pentasulfide features two signals at room temperature, a consequence of its relative rigidity. Cp2TiS5dynamics.png
The H NMR spectrum of titanocene pentasulfide features two signals at room temperature, a consequence of its relative rigidity.
Bicycloalkane with two "bridgehead carbons" Coloratano - numeracion.png
Bicycloalkane with two "bridgehead carbons"

Cyclohexane is a prototype for low-energy degenerate ring flipping. Two 1H NMR signals should be observed in principle, corresponding to axial and equatorial protons. However, due to the cyclohexane chair flip, only one signal is seen for a solution of cyclohexane at room temperature, as the axial and equatorial proton rapidly interconvert relative to the NMR time scale. The coalescence temperature at 60 MHz is ca. –60 °C. [6] As a consequence of the chair flip, the axially-substituted and equatorially-substituted conformers of a molecule like chlorocyclohexane cannot be isolated at room temperature.

However, in some cases, the isolation of individual conformers of substituted cyclohexane derivatives has been achieved at low temperatures (–150 °C).

Most compounds with nonplanar rings engage in degenerate ring flipping. One well-studied example is titanocene pentasulfide, where the inversion barrier is high relative to cyclohexane's. Hexamethylcyclotrisiloxane on the other hand is subject to a very low barrier.

Bicycloalkanes are alkanes containing two rings that are connected to each other by sharing two carbon atoms. Orientation within bicycloalkanes is dependent on the cis or trans orientation of the hydrogen shared by the different rings instead of the methyl groups present in the rings. [7]

Tetrodotoxin is one of the world's most potent toxins. It is made up of multiple six member rings set in chair conformations, with each ring but one containing an atom other than carbon.

Skeletal structures of 1,8-dimethylnaphthalene and 4,5-dimethylphenanthrene annotated with the steric effects between the two methyl groups. Napthalene phenanthraene methyl-methyl strain.png
Skeletal structures of 1,8-dimethylnaphthalene and 4,5-dimethylphenanthrene annotated with the steric effects between the two methyl groups.

See also

Related Research Articles

<span class="mw-page-title-main">Stereoisomerism</span> When molecules have the same atoms and bond structure but differ in 3D orientation

In stereochemistry, stereoisomerism, or spatial isomerism, is a form of isomerism in which molecules have the same molecular formula and sequence of bonded atoms (constitution), but differ in the three-dimensional orientations of their atoms in space. This contrasts with structural isomers, which share the same molecular formula, but the bond connections or their order differs. By definition, molecules that are stereoisomers of each other represent the same structural isomer.

<span class="mw-page-title-main">Structural formula</span> Graphic representation of a molecular structure

The structural formula of a chemical compound is a graphic representation of the molecular structure, showing how the atoms are possibly arranged in the real three-dimensional space. The chemical bonding within the molecule is also shown, either explicitly or implicitly. Unlike other chemical formula types, which have a limited number of symbols and are capable of only limited descriptive power, structural formulas provide a more complete geometric representation of the molecular structure. For example, many chemical compounds exist in different isomeric forms, which have different enantiomeric structures but the same molecular formula. There are multiple types of ways to draw these structural formulas such as: Lewis Structures, condensed formulas, skeletal formulas, Newman projections, Cyclohexane conformations, Haworth projections, and Fischer projections.

<span class="mw-page-title-main">Cycloalkane</span> Saturated alicyclic hydrocarbon

In organic chemistry, the cycloalkanes are the monocyclic saturated hydrocarbons. In other words, a cycloalkane consists only of hydrogen and carbon atoms arranged in a structure containing a single ring, and all of the carbon-carbon bonds are single. The larger cycloalkanes, with more than 20 carbon atoms are typically called cycloparaffins. All cycloalkanes are isomers of alkenes.

Cyclohexane is a cycloalkane with the molecular formula C6H12. Cyclohexane is non-polar. Cyclohexane is a colourless, flammable liquid with a distinctive detergent-like odor, reminiscent of cleaning products. Cyclohexane is mainly used for the industrial production of adipic acid and caprolactam, which are precursors to nylon.

<span class="mw-page-title-main">Chirality (chemistry)</span> Geometric property of some molecules and ions

In chemistry, a molecule or ion is called chiral if it cannot be superposed on its mirror image by any combination of rotations, translations, and some conformational changes. This geometric property is called chirality. The terms are derived from Ancient Greek χείρ (cheir) 'hand'; which is the canonical example of an object with this property.

<span class="mw-page-title-main">Cyclohexane conformation</span> Structures of cyclohexane

Cyclohexane conformations are any of several three-dimensional shapes adopted by molecules of cyclohexane. Because many compounds feature structurally similar six-membered rings, the structure and dynamics of cyclohexane are important prototypes of a wide range of compounds.

<span class="mw-page-title-main">Conformational isomerism</span> Different molecular structures formed only by rotation about single bonds

In chemistry, conformational isomerism is a form of stereoisomerism in which the isomers can be interconverted just by rotations about formally single bonds. 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. 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 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. When the time scale for interconversion is long enough for isolation of individual rotamers, the isomers are termed atropisomers. The ring-flip of substituted cyclohexanes constitutes another common form of conformational isomerism.

In chemistry, a molecule experiences strain when its chemical structure undergoes some stress which raises its internal energy in comparison to a strain-free reference compound. The internal energy of a molecule consists of all the energy stored within it. A strained molecule has an additional amount of internal energy which an unstrained molecule does not. This extra internal energy, or strain energy, can be likened to a compressed spring. Much like a compressed spring must be held in place to prevent release of its potential energy, a molecule can be held in an energetically unfavorable conformation by the bonds within that molecule. Without the bonds holding the conformation in place, the strain energy would be released.

<span class="mw-page-title-main">Decalin</span> Chemical compound

Decalin, a bicyclic organic compound, is an industrial solvent. A colorless liquid with an aromatic odor, it is used as a solvent for many resins or fuel additives.

<span class="mw-page-title-main">Ring strain</span> Instability in molecules with bonds at unnatural angles

In organic chemistry, ring strain is a type of instability that exists when bonds in a molecule form angles that are abnormal. Strain is most commonly discussed for small rings such as cyclopropanes and cyclobutanes, whose internal angles are substantially smaller than the idealized value of approximately 109°. Because of their high strain, the heat of combustion for these small rings is elevated.

<span class="mw-page-title-main">Hyperconjugation</span> Concept in organic chemistry

In organic chemistry, hyperconjugation refers to the delocalization of electrons with the participation of bonds of primarily σ-character. Usually, hyperconjugation involves the interaction of the electrons in a sigma (σ) orbital with an adjacent unpopulated non-bonding p or antibonding σ* or π* orbitals to give a pair of extended molecular orbitals. However, sometimes, low-lying antibonding σ* orbitals may also interact with filled orbitals of lone pair character (n) in what is termed negative hyperconjugation. Increased electron delocalization associated with hyperconjugation increases the stability of the system. In particular, the new orbital with bonding character is stabilized, resulting in an overall stabilization of the molecule. Only electrons in bonds that are in the β position can have this sort of direct stabilizing effect — donating from a sigma bond on an atom to an orbital in another atom directly attached to it. However, extended versions of hyperconjugation can be important as well. The Baker–Nathan effect, sometimes used synonymously for hyperconjugation, is a specific application of it to certain chemical reactions or types of structures.

<span class="mw-page-title-main">Anomeric effect</span>

In organic chemistry, the anomeric effect or Edward-Lemieux effect is a stereoelectronic effect that describes the tendency of heteroatomic substituents adjacent to a heteroatom within a cyclohexane ring to prefer the axial orientation instead of the less hindered equatorial orientation that would be expected from steric considerations. This effect was originally observed in pyranose rings by J. T. Edward in 1955 when studying carbohydrate chemistry.

<span class="mw-page-title-main">Cyclic compound</span> Molecule with a ring of bonded atoms

A cyclic compound is a term for a compound in the field of chemistry in which one or more series of atoms in the compound is connected to form a ring. Rings may vary in size from three to many atoms, and include examples where all the atoms are carbon, none of the atoms are carbon, or where both carbon and non-carbon atoms are present. Depending on the ring size, the bond order of the individual links between ring atoms, and their arrangements within the rings, carbocyclic and heterocyclic compounds may be aromatic or non-aromatic; in the latter case, they may vary from being fully saturated to having varying numbers of multiple bonds between the ring atoms. Because of the tremendous diversity allowed, in combination, by the valences of common atoms and their ability to form rings, the number of possible cyclic structures, even of small size numbers in the many billions.

In chemistry and molecular physics, fluxionalmolecules are molecules that undergo dynamics such that some or all of their atoms interchange between symmetry-equivalent positions. Because virtually all molecules are fluxional in some respects, e.g. bond rotations in most organic compounds, the term fluxional depends on the context and the method used to assess the dynamics. Often, a molecule is considered fluxional if its spectroscopic signature exhibits line-broadening due to chemical exchange. In some cases, where the rates are slow, fluxionality is not detected spectroscopically, but by isotopic labeling and other methods.

<span class="mw-page-title-main">Allylic strain</span> Type of strain energy in organic chemistry

Allylic strain in organic chemistry is a type of strain energy resulting from the interaction between a substituent on one end of an olefin with an allylic substituent on the other end. If the substituents are large enough in size, they can sterically interfere with each other such that one conformer is greatly favored over the other. Allylic strain was first recognized in the literature in 1965 by Johnson and Malhotra. The authors were investigating cyclohexane conformations including endocyclic and exocylic double bonds when they noticed certain conformations were disfavored due to the geometry constraints caused by the double bond. Organic chemists capitalize on the rigidity resulting from allylic strain for use in asymmetric reactions.

Methylcyclohexane (cyclohexylmethane) is an organic compound with the molecular formula is CH3C6H11. Classified as saturated hydrocarbon, it is a colourless liquid with a faint odor. Methylcyclohexane is used as a solvent. It is mainly converted in naphtha reformers to toluene. Methylcyclohexane is also used in some correction fluids (such as White-Out) as a solvent.

A-values are numerical values used in the determination of the most stable orientation of atoms in a molecule, as well as a general representation of steric bulk. A-values are derived from energy measurements of the different cyclohexane conformations of a monosubstituted cyclohexane chemical. Substituents on a cyclohexane ring prefer to reside in the equatorial position to the axial. The difference in Gibbs free energy (ΔG) between the higher energy conformation and the lower energy conformation is the A-value for that particular substituent.

<span class="mw-page-title-main">Isomer</span> Chemical compounds with the same molecular formula but different atomic arrangements

In chemistry, isomers are molecules or polyatomic ions with identical molecular formula – that is, same number of atoms of each element – but distinct arrangements of atoms in space. Isomerism refers to the existence or possibility of isomers.

Carbohydrate conformation refers to the overall three-dimensional structure adopted by a carbohydrate (saccharide) molecule as a result of the through-bond and through-space physical forces it experiences arising from its molecular structure. The physical forces that dictate the three-dimensional shapes of all molecules—here, of all monosaccharide, oligosaccharide, and polysaccharide molecules—are sometimes summarily captured by such terms as "steric interactions" and "stereoelectronic effects".

Macrocyclic stereocontrol refers to the directed outcome of a given intermolecular or intramolecular chemical reaction, generally an organic reaction, that is governed by the conformational or geometrical preference of a carbocyclic or heterocyclic ring, where the ring containing 8 or more atoms.

References

  1. ↑ IUPAC , Compendium of Chemical Terminology , 2nd ed. (the "Gold Book") (1997). Online corrected version: (2006–) " ring reversal (ring inversion) ". doi : 10.1351/goldbook.LR05397
  2. 1 2 Brown, William H., et al. Organic Chemistry. 8th ed., Cengage Learning, 2018.
  3. ↑ Kang, S., Noh, C., Kang, H., Shin, J. Y., Kim, S. Y., Kim, S., ... & Lee, Y. (2021). Dynamics and Entropy of Cyclohexane Rings Control pH-Responsive Reactivity. JACS Au, 1(11), 2070-2079.
  4. ↑ Jensen, Frederick R.; Bushweller, C. Hackett (1969). "Separation of conformers. II. Axial and equatorial isomers of chlorocyclohexane and trideuteriomethoxycyclohexane". Journal of the American Chemical Society. 91 (12): 3223–3225. doi:10.1021/ja01040a022.
  5. 1 2 Brown, William H., et al. Organic Chemistry. 8th ed., Cengage Learning, 2018.
  6. ↑ D., Nasipuri (1994). Stereochemistry of organic compounds : principles, and applications (2nd ed.). New Delhi: Wiley Eastern. ISBN   8122405703. OCLC   31526399.[ page needed ]
  7. ↑ Brown, William H., et al. Organic Chemistry. 8th ed., Cengage Learning, 2018.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.