![Interconversion between eclipsed and gauche conformations](https://upload.wikimedia.org/wikipedia/commons/a/a7/Interconversion_between_eclipsed_and_gauche_conformations..png)
In
chemistry, conformational isomerism is a form of
stereoisomerism
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 ...
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
atom
Every atom is composed of a nucleus and one or more electrons bound to the nucleus. The nucleus is made of one or more protons and a number of neutrons. Only the most common variety of hydrogen has no neutrons.
Every solid, liquid, gas, ...
s in a
molecule
A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and bioche ...
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
A potential energy surface (PES) describes the energy of a system, especially a collection of atoms, in terms of certain parameters, normally the positions of the atoms. The surface might define the energy as a function of one or more coordinat ...
are specifically called conformational isomers or conformers.
Conformations that correspond to local maxima on the energy surface are the
transition state
In chemistry, the transition state of a chemical reaction is a particular configuration along the reaction coordinate. It is defined as the state corresponding to the highest potential energy along this reaction coordinate. It is often marked ...
s 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 (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
Half-life (symbol ) is the time required for a quantity (of substance) to reduce to half of its initial value. The term is commonly used in nuclear physics to describe how quickly unstable atoms undergo radioactive decay or how long stable at ...
of interconversion of 1000 seconds or longer), the isomers are termed atropisomers (''see:''
atropisomerism).
The
ring-flip of substituted
cyclohexanes constitutes another common form of conformational isomerism.
Conformational isomers are thus distinct from the other classes of
stereoisomers
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 ...
(i. e.
configurational isomers) where interconversion necessarily involves breaking and reforming of chemical bonds. 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
Chirality is a property of asymmetry important in several branches of science. The word ''chirality'' is derived from the Greek (''kheir''), "hand", a familiar chiral object.
An object or a system is ''chiral'' if it is distinguishable from i ...
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 bond
In chemistry, a double bond is a covalent bond between two atoms involving four bonding electrons as opposed to two in a single bond. Double bonds occur most commonly between two carbon atoms, for example in alkenes. Many double bonds exist betwee ...
s 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
In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula , where R, R', and R″ represent organic groups or hydrogen atoms. The amide group is called a peptide bond when it is ...
, 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.
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.
Conformational analysis also plays an important role in rational, structure-based
drug design
Drug design, often referred to as rational drug design or simply rational design, is the inventive process of finding new medications based on the knowledge of a biological target. The drug is most commonly an organic small molecule that acti ...
.
Types
![Butane conformations and relative energies](https://upload.wikimedia.org/wikipedia/commons/2/22/Butane_conformations_and_relative_energies.svg)
Rotating their carbon–carbon bonds, the molecules ethane and propane have three local energy minima. They are structurally and energetically equivalent, and are called the ''staggered conformers''. For each molecule, the three substituents emanating from each carbon–carbon bond are staggered, with each H–C–C–H
dihedral angle
A dihedral angle is the angle between two intersecting planes or half-planes. In chemistry, it is the clockwise angle between half-planes through two sets of three atoms, having two atoms in common. In solid geometry, it is defined as the un ...
(and H–C–C–CH
3 dihedral angle in the case of propane) equal to 60° (or approximately equal to 60° in the case of propane). The three eclipsed conformations, in which the dihedral angles are zero, are transition states (energy maxima) connecting two equivalent energy minima, the staggered conformers.
The butane molecule is the simplest molecule for which single bond rotations result in two types of nonequivalent structures, known as the ''anti''- and ''gauche-''conformers (see figure).
For example, butane has three conformers relating to its two methyl (CH
3) groups: two ''gauche'' conformers, which have the methyls ±60° apart and are
enantiomeric, and an ''anti'' conformer, where the four carbon centres are coplanar and the substituents are 180° apart (refer to free energy diagram of butane). The energy difference between gauche and anti is 0.9 kcal/mol associated with the
strain
Strain may refer to:
Science and technology
* Strain (biology), variants of plants, viruses or bacteria; or an inbred animal used for experimental purposes
* Strain (chemistry), a chemical stress of a molecule
* Strain (injury), an injury to a mu ...
energy of the gauche conformer. The anti conformer is, therefore, the most stable (≈ 0 kcal/mol). The three eclipsed conformations with dihedral angles of 0°, 120°, and 240° are transition states between conformers.
Note that the two eclipsed conformations have different energies: at 0° the two methyl groups are eclipsed, resulting in higher energy (≈ 5 kcal/mol) than at 120°, where the methyl groups are eclipsed with hydrogens (≈ 3.5 kcal/mol).
While simple molecules can be described by these types of conformations, more complex molecules require the use of the
Klyne–Prelog system In stereochemistry, the Klyne–Prelog system (named for William Klyne and Vladimir Prelog) for describing conformations about a single bond offers a more systematic means to unambiguously name complex structures, where the torsional or dihedra ...
to describe the different conformers.
More specific examples of conformational isomerism are detailed elsewhere:
*Ring conformation
**
Cyclohexane conformation
In organic chemistry, 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 ...
s, including with chair and boat conformations among others.
**
Cycloalkane conformations, including medium rings and
macrocycles
Macrocycles are often described as molecules and ions containing a ring of twelve or more atoms. Classical examples include the crown ethers, calixarenes, porphyrins, and cyclodextrins. Macrocycles describe a large, mature area of chemistry.
...
**
Carbohydrate conformation
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 ...
, which includes cyclohexane conformations as well as other details.
*
Allylic strain
250 px , right , Allylic strain in an olefin.
Allylic strain (also known as A1,3 strain, 1,3-allylic strain, or A-strain) in organic chemistry is a type of strain energy resulting from the interaction between a substituent on one end of an olef ...
– energetics related to rotation about the single bond between an sp
2 carbon and an sp
3 carbon.
*
Atropisomerism – due to restricted rotation about a bond.
*
Folding
Fold, folding or foldable may refer to:
Arts, entertainment, and media
* ''Fold'' (album), the debut release by Australian rock band Epicure
* Fold (poker), in the game of poker, to discard one's hand and forfeit interest in the current pot
*Abov ...
, including the secondary and tertiary structure of biopolymers (nucleic acids and proteins).
*
Akamptisomerism – due to restricted inversion of a bond angle.
Free energy and equilibria of conformational isomers
Equilibrium of conformers
![Equillibrium conformers](https://upload.wikimedia.org/wikipedia/commons/9/97/Equillibrium_conformers.jpg)
Conformational isomers exist in a
dynamic equilibrium
In chemistry, a dynamic equilibrium exists once a reversible reaction occurs. Substances transition between the reactants and products at equal rates, meaning there is no net change. Reactants and products are formed at such a rate that the co ...
, where the relative free energies of isomers determines the population of each isomer and the energy barrier of rotation determines the rate of interconversion between isomers:
:
where ''K'' is the equilibrium constant, Δ''G°'' is the difference in standard free energy between the two conformers in kcal/mol, ''R'' is the universal
gas constant
The molar gas constant (also known as the gas constant, universal gas constant, or ideal gas constant) is denoted by the symbol or . It is the molar equivalent to the Boltzmann constant, expressed in units of energy per temperature increment per ...
(1.987×10
−3 kcal/mol K), and ''T'' is the system's temperature in
kelvin
The kelvin, symbol K, is the primary unit of temperature in the International System of Units (SI), used alongside its prefixed forms and the degree Celsius. It is named after the Belfast-born and University of Glasgow-based engineer and phy ...
s. In units of kcal/mol at 298 K,
:
Thus, every 1.36 kcal/mol corresponds to a factor of about 10 in term of equilibrium constant at temperatures around room temperature. (The "1.36 rule" is useful in general for estimation of equilibrium constants at room temperature from free energy differences. At lower temperatures, a smaller energy difference is needed to obtain a given equilibrium constant.)
Three isotherms are given in the diagram depicting the equilibrium distribution of two conformers at different temperatures. At a free energy difference of 0 kcal/mol, this gives an equilibrium constant of 1, meaning that two conformers exist in a 1:1 ratio. The two have equal free energy; neither is more stable, so neither predominates compared to the other. A negative difference in free energy means that a conformer interconverts to a thermodynamically more stable conformation, thus the equilibrium constant will always be greater than 1. For example, the Δ''G°'' for the transformation of butane from the ''gauche'' conformer to the ''anti'' conformer is −0.47 kcal/mol at 298 K. This gives an equilibrium constant is about 2.2 in favor of the ''anti'' conformer, or a 31:69 mixture of ''gauche'':''anti'' conformers at equilibrium. Conversely, a positive difference in free energy means the conformer already is the more stable one, so the interconversion is an unfavorable equilibrium (''K'' < 1). Even for highly unfavorable changes (large positive Δ''G°''), the equilibrium constant between two conformers can be increased by increasing the temperature, so that the amount of the less stable conformer present at equilibrium increases (although it always remains the minor conformer).
Population distribution of conformers
The fractional population distribution of different conformers follows a
Boltzmann distribution
In statistical mechanics and mathematics, a Boltzmann distribution (also called Gibbs distribution Translated by J.B. Sykes and M.J. Kearsley. See section 28) is a probability distribution or probability measure that gives the probability th ...
:
:
The left hand side is the proportion of conformer ''i'' in an equilibrating mixture of ''M'' conformers in thermodynamic equilibrium. On the right side, ''E''
''k'' (''k'' = 1, 2, ..., ''M'') is the energy of conformer ''k'', ''R'' is the molar ideal gas constant (approximately equal to 8.314 J/(mol·K) or 1.987 cal/(mol·K)), and ''T'' is the
absolute temperature
Thermodynamic temperature is a quantity defined in thermodynamics as distinct from kinetic theory or statistical mechanics.
Historically, thermodynamic temperature was defined by Kelvin in terms of a macroscopic relation between thermodynamic w ...
. The denominator of the right side is the partition function.
Factors contributing to the free energy of conformers
The effects of
electrostatic
Electrostatics is a branch of physics that studies electric charges at rest ( static electricity).
Since classical times, it has been known that some materials, such as amber, attract lightweight particles after rubbing. The Greek word for amb ...
and
steric interactions of the substituents as well as orbital interactions such as
hyperconjugation
In organic chemistry, hyperconjugation (σ-conjugation or no-bond resonance) refers to the delocalization of electrons with the participation of bonds of primarily σ-character. Usually, hyperconjugation involves the interaction of the electron ...
are responsible for the relative stability of conformers and their transition states. The contributions of these factors vary depending on the nature of the substituents and may either contribute positively or negatively to the energy barrier. Computational studies of small molecules such as ethane suggest that electrostatic effects make the greatest contribution to the energy barrier; however, the barrier is traditionally attributed primarily to steric interactions.
![Contributions to Rotational Energy Barrier](https://upload.wikimedia.org/wikipedia/commons/f/f2/Contributions_to_Rotational_Energy_Barrier.png)
In the case of cyclic systems, the steric effect and contribution to the free energy can be approximated by
A value 400px, The A-value for a methyl group is 1.74 as derived from the chemical equilibrium above. This means it costs of energy to have a methyl group in the axial position compared to the equatorial position.
A-values are numerical values used in ...
s, which measure the energy difference when a substituent on cyclohexane in the axial as compared to the equatorial position. In large (>14 atom) rings, there are many accessible low-energy conformations which correspond to the strain-free diamond lattice.
Isolation or observation of the conformational isomers
The short timescale of interconversion precludes the separation of conformational isomers in most cases.
Atropisomers are conformational isomers which can be separated due to restricted rotation. The equilibrium between conformational isomers can be observed using a variety of
spectroscopic techniques.
Protein folding
Protein folding is the physical process by which a protein chain is translated to its native three-dimensional structure, typically a "folded" conformation by which the protein becomes biologically functional. Via an expeditious and reproduc ...
also generates stable conformational isomers which can be observed. The
Karplus equation
The Karplus equation, named after Martin Karplus, describes the correlation between 3J-coupling constants and dihedral torsion angles in nuclear magnetic resonance spectroscopy:
:J(\phi) = A \cos^2 \phi + B \cos\,\phi + C
where ''J'' is the 3''J ...
relates the dihedral angle of
vicinal protons to their
J-coupling
In nuclear chemistry and nuclear physics, ''J''-couplings (also called spin-spin coupling or indirect dipole–dipole coupling) are mediated through chemical bonds connecting two spins. It is an indirect interaction between two nuclear spins that ...
constants as measured by NMR. The equation aids in the elucidation of protein folding as well as the conformations of other rigid
aliphatic
In organic chemistry, hydrocarbons ( compounds composed solely of carbon and hydrogen) are divided into two classes: aromatic compounds and aliphatic compounds (; G. ''aleiphar'', fat, oil). Aliphatic compounds can be saturated, like hexane, ...
molecules. Protein side chains exhibit rotamers, whose distribution is determined by their steric interaction with different conformations of the backbone. This is evident from statistical analysis of the conformations of protein side chains in the
Backbone-dependent rotamer library
In biochemistry, a backbone-dependent rotamer library provides the frequencies, mean dihedral angles, and standard deviations of the discrete conformations (known as rotamers) of the amino acid side chains in proteins as a function of the backb ...
.
In
cyclohexane derivatives, the two chair conformers interconvert with rapidly at room temperature, with cyclohexane itself undergoing the ring-flip at a rates of approximately 10
5 ring-flips/sec, with an overall energy barrier of 10 kcal/mol (42 kJ/mol), which precludes their separation at ambient temperatures.
However, at low temperatures below the
coalescence
Coalescence may refer to:
* Coalescence (chemistry), the process by which two or more separate masses of miscible substances seem to "pull" each other together should they make the slightest contact
* Coalescence (computer science), the merging of ...
point one can directly monitor the equilibrium by NMR spectroscopy and by dynamic, temperature dependent NMR spectroscopy the barrier interconversion.
The dynamics of conformational (and other kinds of) isomerism can be monitored by
NMR
Nuclear magnetic resonance (NMR) is a physical phenomenon in which nuclei in a strong constant magnetic field are perturbed by a weak oscillating magnetic field (in the near field) and respond by producing an electromagnetic signal with ...
spectroscopy at varying temperatures. The technique applies to barriers of 8–14 kcal/mol, and species exhibiting such dynamics are often called "
fluxional".
Besides NMR spectroscopy,
IR spectroscopy
Infrared spectroscopy (IR spectroscopy or vibrational spectroscopy) is the measurement of the interaction of infrared radiation with matter by absorption, emission, or reflection. It is used to study and identify chemical substances or function ...
is used to measure conformer ratios. For the axial and equatorial conformer of bromocyclohexane, ν
CBr differs by almost 50 cm
−1.
Conformation-dependent reactions
Reaction rates are highly dependent on the conformation of the reactants. In many cases the dominant product arises from the reaction of the ''less prevalent'' conformer, by virtue of the
Curtin-Hammett principle. This is typical for situations where the conformational equilibration is much faster than reaction to form the product. The dependence of a reaction on the stereochemical orientation is therefore usually only visible in
configurational isomers, in which a particular conformation is locked by substituents. Prediction of rates of many reactions involving the transition between sp2 and sp3 states, such as ketone reduction, alcohol oxidation or
nucleophilic substitution
In chemistry, a nucleophilic substitution is a class of chemical reactions in which an electron-rich chemical species (known as a nucleophile) replaces a functional group within another electron-deficient molecule (known as the electrophile). The ...
is possible if all conformers and their relative stability ruled by their
strain
Strain may refer to:
Science and technology
* Strain (biology), variants of plants, viruses or bacteria; or an inbred animal used for experimental purposes
* Strain (chemistry), a chemical stress of a molecule
* Strain (injury), an injury to a mu ...
is taken into account.
One example with configurational isomers is provided by
elimination reaction
An elimination reaction is a type of organic reaction in which two substituents are removed from a molecule in either a one- or two-step mechanism. The one-step mechanism is known as the E2 reaction, and the two-step mechanism is known as the E1 r ...
s, which involve the simultaneous removal of a proton and a
leaving group In chemistry, a leaving group is defined by the IUPAC as an atom or group of atoms that detaches from the main or residual part of a substrate during a reaction or elementary step of a reaction. However, in common usage, the term is often limited ...
from vicinal or ''anti''periplanar positions under the influence of a base.
The mechanism requires that the departing atoms or groups follow antiparallel trajectories. For open chain substrates this geometric prerequisite is met by at least one of the three staggered conformers. For some cyclic substrates such as cyclohexane, however, an antiparallel arrangement may not be attainable depending on the substituents which might set a conformational lock. Adjacent
substituents on a cyclohexane ring can achieve antiperiplanarity only when they occupy trans
diaxial positions (that is, both are in axial position, one going up and one going down).
One consequence of this analysis is that ''trans''-4-''tert''-butylcyclohexyl chloride cannot easily eliminate but instead undergoes substitution (see diagram below) because the most stable conformation has the bulky ''t''-Bu group in the equatorial position, therefore the chloride group is not antiperiplanar with any vicinal hydrogen (it is gauche to all four). The thermodynamically unfavored conformation has the ''t''-Bu group in the axial position, which is higher in energy by more than 5 kcal/mol (see
A value 400px, The A-value for a methyl group is 1.74 as derived from the chemical equilibrium above. This means it costs of energy to have a methyl group in the axial position compared to the equatorial position.
A-values are numerical values used in ...
).
As a result, the ''t''-Bu group "locks" the ring in the conformation where it is in the equatorial position and substitution reaction is observed. On the other hand, ''cis''-4-''tert''-butylcyclohexyl chloride undergoes elimination because antiperiplanarity of Cl and H can be achieved when the ''t''-Bu group is in the favorable equatorial position.
The repulsion between an axial ''t''-butyl group and hydrogen atoms in the 1,3-diaxial position is so strong that the cyclohexane ring will revert to a
twisted boat conformation. The strain in cyclic structures is usually characterized by deviations from ideal
bond angles
Molecular geometry is the three-dimensional arrangement of the atoms that constitute a molecule. It includes the general shape of the molecule as well as bond lengths, bond angles, torsional angles and any other geometrical parameters that deter ...
(
Baeyer strain
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 s ...
), ideal
torsional angles (
Pitzer strain
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 ...
) or
transannular
In organic chemistry annulation (from the Latin ''anellus'' for "little ring"; occasionally annelation) is a chemical reaction in which a new ring is constructed on a molecule.
:
Examples are the Robinson annulation, Danheiser annulation and cer ...
(Prelog ) interactions.
Alkane stereochemistry
Alkane conformers arise from rotation around sp
3 hybridised carbon–carbon
sigma bond
In chemistry, sigma bonds (σ bonds) are the strongest type of covalent chemical bond. They are formed by head-on overlapping between atomic orbitals. Sigma bonding is most simply defined for diatomic molecules using the language and tools of s ...
s. The smallest alkane with such a chemical bond,
ethane
Ethane ( , ) is an organic chemical compound with chemical formula . At standard temperature and pressure, ethane is a colorless, odorless gas. Like many hydrocarbons, ethane is isolated on an industrial scale from natural gas and as a petroc ...
, exists as an infinite number of conformations with respect to rotation around the C–C bond. Two of these are recognised as energy minimum (
staggered conformation
In organic chemistry, a staggered conformation is a chemical conformation of an ethane-like moiety abcX–Ydef in which the substituents a, b, and c are at the maximum distance from d, e, and f; this requires the torsion angles to be 60°. It ...
) and energy maximum (
eclipsed conformation
In chemistry an eclipsed conformation is a conformation in which two substituents X and Y on adjacent atoms A, B are in closest proximity, implying that the torsion angle X–A–B–Y is 0°. Such a conformation can exist in any open chain ...
) forms. The existence of specific conformations is due to hindered rotation around sigma bonds, although a role for
hyperconjugation
In organic chemistry, hyperconjugation (σ-conjugation or no-bond resonance) refers to the delocalization of electrons with the participation of bonds of primarily σ-character. Usually, hyperconjugation involves the interaction of the electron ...
is proposed by a competing theory.
The importance of energy minima and energy maxima is seen by extension of these concepts to more complex molecules for which stable conformations may be predicted as minimum-energy forms. The determination of stable conformations has also played a large role in the establishment of the concept of
asymmetric induction and the ability to predict the
stereochemistry of reactions controlled by steric effects.
In the example of staggered
ethane
Ethane ( , ) is an organic chemical compound with chemical formula . At standard temperature and pressure, ethane is a colorless, odorless gas. Like many hydrocarbons, ethane is isolated on an industrial scale from natural gas and as a petroc ...
in
Newman projection
A Newman projection is a drawing that helps visualize the 3-dimensional structure of a molecule. This projection most commonly sights down a carbon-carbon bond, making it a very useful way to visualize the stereochemistry of alkanes. A Newman pro ...
, a hydrogen atom on one carbon atom has a 60° torsional angle or torsion angle with respect to the nearest hydrogen atom on the other carbon so that
steric hindrance
Steric effects arise from the spatial arrangement of atoms. When atoms come close together there is a rise in the energy of the molecule. Steric effects are nonbonding interactions that influence the shape ( conformation) and reactivity of ions ...
is minimised. The staggered conformation is more stable by 12.5
kJ/
mol than the
eclipsed conformation, which is the energy maximum for ethane. In the eclipsed conformation the torsional angle is minimised.
In
butane, the two staggered conformations are no longer equivalent and represent two distinct conformers:the anti-conformation (left-most, below) and the gauche conformation (right-most, below).
Both conformations are free of torsional strain, but, in the gauche conformation, the two
methyl groups are in closer proximity than the sum of their van der Waals radii. The interaction between the two methyl groups is repulsive (
van der Waals strain Van der Waals strain is strain resulting from Van der Waals repulsion when two substituents in a molecule approach each other with a distance less than the sum of their Van der Waals radii.
Van der Waals strain is also called Van der Waals repul ...
), and an
energy barrier
In chemistry and physics, activation energy is the minimum amount of energy that must be provided for compounds to result in a chemical reaction. The activation energy (''E''a) of a reaction is measured in joules per mole (J/mol), kilojoules pe ...
results.
A measure of the
potential energy stored in butane conformers with greater steric hindrance than the 'anti'-conformer ground state is given by these values:
* Gauche, conformer – 3.8 kJ/mol
* Eclipsed H and CH
3 – 16 kJ/mol
* Eclipsed CH
3 and CH
3 – 19 kJ/mol.
The eclipsed
methyl group
In organic chemistry, a methyl group is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms, having chemical formula . In formulas, the group is often abbreviated as Me. This hydrocarbon group occurs in ma ...
s exert a greater steric strain because of their greater
electron density
In quantum chemistry, electron density or electronic density is the measure of the probability of an electron being present at an infinitesimal element of space surrounding any given point. It is a scalar quantity depending upon three spatial va ...
compared to lone
hydrogen
Hydrogen is the chemical element with the symbol H and atomic number 1. Hydrogen is the lightest element. At standard conditions hydrogen is a gas of diatomic molecules having the formula . It is colorless, odorless, tasteless, non-toxic ...
atoms.
400px, center, Relative energies of conformations of butane with respect to rotation of the central C-C bond.
The textbook explanation for the existence of the energy maximum for an eclipsed conformation in ethane is
steric hindrance
Steric effects arise from the spatial arrangement of atoms. When atoms come close together there is a rise in the energy of the molecule. Steric effects are nonbonding interactions that influence the shape ( conformation) and reactivity of ions ...
, but, with a C-C
bond length
In molecular geometry, bond length or bond distance is defined as the average distance between nuclei of two bonded atoms in a molecule. It is a transferable property of a bond between atoms of fixed types, relatively independent of the rest of ...
of 154 pm and a
Van der Waals radius
The van der Waals radius, ''r'', of an atom is the radius of an imaginary hard sphere representing the distance of closest approach for another atom.
It is named after Johannes Diderik van der Waals, winner of the 1910 Nobel Prize in Physics, ...
for hydrogen of 120 pm, the hydrogen atoms in ethane are never in each other's way. The question of whether steric hindrance is responsible for the eclipsed energy maximum is a topic of debate to this day. One alternative to the steric hindrance explanation is based on
hyperconjugation
In organic chemistry, hyperconjugation (σ-conjugation or no-bond resonance) refers to the delocalization of electrons with the participation of bonds of primarily σ-character. Usually, hyperconjugation involves the interaction of the electron ...
as analyzed within the Natural Bond Orbital framework. In the staggered conformation, one C-H
sigma bonding orbital
In theoretical chemistry, the bonding orbital is used in molecular orbital (MO) theory to describe the attractive interactions between the atomic orbitals of two or more atoms in a molecule. In MO theory, electrons are portrayed to move in waves. ...
donates electron density to the
antibonding orbital
In chemical bonding theory, an antibonding orbital is a type of molecular orbital that weakens the chemical bond between two atoms and helps to raise the energy of the molecule relative to the separated atoms. Such an orbital has one or more no ...
of the other C-H bond. The energetic stabilization of this effect is maximized when the two orbitals have maximal overlap, occurring in the staggered conformation. There is no overlap in the eclipsed conformation, leading to a disfavored energy maximum. On the other hand, an analysis within quantitative
molecular orbital theory
In chemistry, molecular orbital theory (MO theory or MOT) is a method for describing the electronic structure of molecules using quantum mechanics. It was proposed early in the 20th century.
In molecular orbital theory, electrons in a molecul ...
shows that 2-orbital-4-electron (steric) repulsions are dominant over hyperconjugation. A
valence bond theory study also emphasizes the importance of steric effects.
Nomenclature
Naming alkanes per standards listed in the
IUPAC Gold Book
The International Union of Pure and Applied Chemistry publishes many books which contain its complete list of definitions. The definitions are divided into seven "colour books": Gold, Green, Blue, Purple, Orange, White, and Red. There is also an e ...
is done according to the
Klyne–Prelog system In stereochemistry, the Klyne–Prelog system (named for William Klyne and Vladimir Prelog) for describing conformations about a single bond offers a more systematic means to unambiguously name complex structures, where the torsional or dihedra ...
for specifying angles (called either torsional or
dihedral angles
A dihedral angle is the angle between two intersecting planes or half-planes. In chemistry, it is the clockwise angle between half-planes through two sets of three atoms, having two atoms in common. In solid geometry, it is defined as the uni ...
) between substituents around a single bond:
* a torsion angle between 0° and ± 90° is called syn (s)
* a torsion angle between ± 90° and 180° is called anti (a)
* a torsion angle between 30° and 150° or between –30° and –150° is called clinal (c)
* a torsion angle between 0° and ± 30° or ± 150° and 180° is called periplanar (p)
* a torsion angle between 0° and ± 30° is called
synperiplanar
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 molec ...
(sp), also called syn- or cis- conformation
* a torsion angle between 30° to 90° and –30° to –90° is called synclinal (sc), also called gauche or skew
* a torsion angle between 90° and 150° or –90° and –150° is called anticlinal (ac)
* a torsion angle between ± 150° and 180° is called
antiperiplanar (ap), also called anti- or trans- conformation
Torsional strain or "Pitzer strain" refers to resistance to twisting about a bond.
Special cases
In
''n''-pentane, the terminal
methyl groups experience additional
pentane interference.
Replacing hydrogen by
fluorine in
polytetrafluoroethylene changes the stereochemistry from the zigzag geometry to that of a
helix
A helix () is a shape like a corkscrew or spiral staircase. It is a type of smooth space curve with tangent lines at a constant angle to a fixed axis. Helices are important in biology, as the DNA molecule is formed as two intertwined helic ...
due to electrostatic repulsion of the fluorine atoms in the 1,3 positions. Evidence for the helix structure in the crystalline state is derived from
X-ray crystallography
X-ray crystallography is the experimental science determining the atomic and molecular structure of a crystal, in which the crystalline structure causes a beam of incident X-rays to diffract into many specific directions. By measuring the angles ...
and from
NMR spectroscopy
Nuclear magnetic resonance spectroscopy, most commonly known as NMR spectroscopy or magnetic resonance spectroscopy (MRS), is a spectroscopic technique to observe local magnetic fields around atomic nuclei. The sample is placed in a magnetic fie ...
and
circular dichroism in solution.
[''Conformational Analysis of Chiral Helical Perfluoroalkyl Chains by VCD'' Kenji Monde, Nobuaki Miura, Mai Hashimoto, Tohru Taniguchi, and Tamotsu Inabe ]J. Am. Chem. Soc.
The ''Journal of the American Chemical Society'' is a weekly peer-reviewed scientific journal that was established in 1879 by the American Chemical Society. The journal has absorbed two other publications in its history, the ''Journal of Analytic ...
; 2006; 128(18) pp 6000–6001
Graphical abstract
/ref>
See also
* Anomeric effect
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 instea ...
* Backbone-dependent rotamer library
In biochemistry, a backbone-dependent rotamer library provides the frequencies, mean dihedral angles, and standard deviations of the discrete conformations (known as rotamers) of the amino acid side chains in proteins as a function of the backb ...
* Cycloalkane
* Cyclohexane
** Cyclohexane conformation
In organic chemistry, 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 ...
s.
* Gauche effect
* Isomer
* Klyne–Prelog system In stereochemistry, the Klyne–Prelog system (named for William Klyne and Vladimir Prelog) for describing conformations about a single bond offers a more systematic means to unambiguously name complex structures, where the torsional or dihedra ...
* Macrocyclic stereocontrol
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 heterocyc ...
* Molecular configuration The molecular configuration of a molecule is the ''permanent'' geometry that results from the spatial arrangement of its bonds. The ability of the same set of atoms to form two or more molecules with different configurations is stereoisomerism. ...
* Molecular modelling
Molecular modelling encompasses all methods, theoretical and computational, used to model or mimic the behaviour of molecules. The methods are used in the fields of computational chemistry, drug design, computational biology and materials sci ...
*
* Steric effects
* Strain (chemistry)
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 ...
References
{{Authority control
Isomerism
Physical organic chemistry
Stereochemistry