Meso compoundFrom Wikipedia, the free encyclopediaJump to: navigation, search

A meso compound or meso isomer is a non-optically active member of a set of stereoisomers, at least two of which are optically active.[1][2] This means that despite containing two or more stereocenters (chiral centers) it is not chiral. A meso compound is superimposable on its mirror image, and it does not produce a "(+)" or "(-)" reading when analyzed with a polarimeter.[3]

For example, there are 3 isomers of tartaric acid (depicted below), there is a meso compound (the 2R,3S and 2S,3R isomers are equivalent) and the optically active pair of levotartaric acid (D-(S,S)-(−)-tartaric acid) and dextrotartaric acid (L-(R,R)-(+)-tartaric acid). In the meso compound an internal plane of symmetry exists, bisecting the molecule which is not present in the non-meso compounds. That is, on rotating the meso compound by 180° on a plane perpendicular to the screen, the same stereochemistry is obtained, again this is not seen in the non-meso tartaric acid. (see Fischer projection).[3]

It is a requirement for two of the stereocenters in a meso compound to have at least two substituents in common (though having this characteristic does not necessarily mean that the compound is meso). For example, in 2,4-pentanediol, both the second and fourth carbons, which are stereocenters, have all four substituents in common.

Since a meso isomer has a superimposable mirror image, a compound with a total of n stereocenters cannot have 2n stereoisomers if at least one of the stereoisomers is meso.[4]

[edit] Cyclic meso compounds

1,2-substituted cyclopropane has a meso cis-isomer (molecule has a mirror plane) and two trans-enantiomers:

The two cis stereoisomers of 1,2-substituted cyclohexanes behave like meso compounds at room temperature in most cases. At room temperature, most 1,2-disubstituted cyclohexanes undergo rapid ring flipping (exceptions being rings with bulky substituents), and as a result, the two cis stereoisomers behave chemically identically with chiral reagents. At low temperatures, however, this is not the case, as the activation energy for the ring-flip cannot be overcome, and they therefore behave like enantiomers. In nearly all cases at room temperature, the two cis stereoisomers of 1,2-disubstituted cyclohexanes can be treated as chemically equivalent. [5] Also noteworthy is the fact that when a cyclohexane undergoes a ring flip, the absolute configurations of the sterocenters do not change.

DiastereomerFrom Wikipedia, the free encyclopedia  (Redirected from Diasteromer)Jump to: navigation, search Erythro redirects here. For the fictional planet, see Erythro (Asimov).

Diastereomers (diastereoisomers) are stereoisomers that are not enantiomers.[1]

Diastereomerism occurs when two or more stereoisomers of a compound have different configurations at one or more (but not all) of the equivalent (related) stereocenters and are not mirror images of each other.[2] When two diastereoisomers differ from each other at only one stereocenter they are epimers. Each stereocenter gives rise to two different configurations and thus to two different stereoisomers.

Diastereomers

D-Threose D-Erythrose

Diastereomers differ from enantiomers in that the latter are pairs of stereoisomers which differ in all stereocenters and are therefore mirror images of one another.[3] Enantiomers of a compound with more than one stereocenter are also diastereomers of the other stereoisomers of that compound that are not their mirror image. Diastereomers have different physical properties and different reactivity, unlike enantiomers.

Cis-trans isomerism and conformational isomerism are also forms of diastereomerism.

Diastereoselectivity is the preference for the formation of one or more than one diastereomer over the other in an organic reaction.

Contents

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1 Erythro / threo 2 Multiple stereocenters 3 Example 4 Applications 5 See also 6 References

[edit] Erythro / threo

Two common prefixes used to distinguish diastereomers are threo and erythro. When drawn in the Fischer projection the erythro isomer has two identical substituents on the same side and the threo isomer has them on opposite sides. The names are derived from the diastereomeric aldoses erythrose (a syrup) and threose (melting point 126 °C).

Another threo compound is threonine, one of the essential amino acids. The erythro diastereomer is called allo-threonine.

 L-Threonine (2S,3R) and D-Threonine (2R,3S)

 L-allo-Threonine (2S,3S) and D-allo-Threonine (2R,3R)

[edit] Multiple stereocenters

If a molecule contains two asymmetric carbons, there are up to 4 possible configurations, and they cannot all be non-superimposable mirror images of each other. The possibilities continue to multiply as there are more asymmetric centers in a molecule. In general, the number of configurational isomers of a molecule can be determined by calculating 2n, where n = the number of chiral centers in the molecule. This holds true except in cases where the molecule has meso forms.

[edit] Example

Tartaric acid contains two asymmetric centers, but two of the "isomers" are equivalent and together are called a meso compound. This configuration is not optically active, while the remaining two isomers are D- and L- mirror images, i.e., enantiomers. The meso form is a diastereomer of the other forms.

(natural) tartaric acidL-(+)-tartaric aciddextrotartaric acid

D-(-)-tartaric acidlevotartaric acid

mesotartaric acid

(1:1)DL-tartaric acid"racemic acid"

The families of 4, 5 and 6 carbon carbohydrates contain many diastereomers because of the large numbers of asymmetric centres in these molecules.

[edit] Applications

As stated, two enantiomers will have identical physical properties, while diastereomers will not. This knowledge is harnessed in chiral synthesis to separate a mixture of enantiomers. This is the principle behind chiral resolution. After preparing the diastereomers, they are separated by chromatography or recrystallization.

Cis–trans isomerism

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(Redirected from Cis-trans isomerism)

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Cis-2-butene

Trans-2-butene

In organic chemistry, cis-trans isomerism or geometric isomerism or configuration isomerism or E-Z isomerism is a form of stereoisomerism describing the orientation of functional groups within a molecule. In general, such isomers contain double bonds, which cannot rotate, but they can also arise from ring structures, wherein the rotation of bonds is greatly restricted. Cis and trans isomers occur both in organic molecules and in inorganic coordination complexes.

The terms cis and trans are from Latin, in which cis means "on the same side" and trans means "on the other side" or "across". The term "geometric isomerism" is considered an obsolete synonym of "cis-trans isomerism" by IUPAC.[1] It is sometimes used as a synonym for general stereoisomerism (e.g., optical isomerism being called geometric isomerism); the correct term for non-optical stereoisomerism is diastereomerism.

Contents

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1 In organic chemistry o 1.1 Comparison of physical properties

1.1.1 Stability o 1.2 E/Z notation

2 Inorganic coordination complexes 3 See also 4 References 5 External links

[edit] In organic chemistry

When the substituent groups are oriented in the same direction, the diastereomer is referred to as cis, whereas, when the substituents are oriented in opposing directions, the diastereomer is referred to as trans. An example of a small hydrocarbon displaying cis-trans isomerism is 2-butene.

Alicyclic compounds can also display cis-trans isomerism. As an example of a geometric isomer due to a ring structure, consider 1,2-dichlorocyclohexane:

trans-1,2-dichlorocyclohexane cis-1,2-dichlorocyclohexane

[edit] Comparison of physical properties

Cis isomers and trans isomers often have different physical properties. Differences between isomers, in general, arise from the differences in the shape of the molecule or the overall dipole moment.

cis-2-pentene trans-2-pentene

cis-1,2-dichloroethene trans-1,2-dichloroethene

cis-butenedioic acid(maleic acid)

trans-butenedioic acid(fumaric acid)

Oleic acid Elaidic acid

These differences can be very small, as in the case of the boiling point of straight-chain alkenes, such as 2-Pentene, which is 37°C in the cis isomer and 36°C in the trans isomer.[2] The differences between cis and trans isomers can be larger if polar bonds are present, as in the 1,2-dichloroethenes. The cis isomer in this case has a boiling point of 60.3°C, while the trans isomer has a boiling point of 47.5°C.[3] In the cis isomer the two polar C-Cl bond dipole moments combine to give an overall molecular dipole, so that there are intermolecular dipole-dipole forces (or Keesom forces) which add to the London dispersion forces and raise the boiling point. In the trans isomer on the other hand, this does not occur because the two C-Cl bond moments cancel and the molecule is non-polar.

The two isomers of butenedioic acid have such large differences in properties and reactivities that they were actually given completely different names. The cis isomer is called maleic acid and the trans is named fumaric acid. Polarity is key in determining relative boiling point as it causes increased intermolecular forces, thereby raising the boiling point. In the same manner, symmetry is key in determining relative melting point as it allows for better packing in the solid state, even if it does not alter the polarity of the molecule. One example of this is the relationship between oleic acid and elaidic acid; oleic acid, the cis isomer, has a melting point of 13.4 degrees Celsius, making it a liquid at room temperature, while the trans isomer, elaidic acid, has the much higher melting point of 43 degrees Celsius, due to the straighter trans isomer being able to pack more tightly, and is solid at room temperature.

Thus, trans-alkenes which are less polar and more symmetrical have lower boiling points and higher melting points and cis-alkenes, which are generally more polar and less symmetrical have higher boiling points and lower melting points.

In the case of geometric isomers that are a consequence of double bonds, and, in particular, when both substituents are the same, some general trends usually hold. These trends can be attributed to the fact that the dipoles of the substituents in a cis isomer will add up to give an overall molecular dipole. In a trans isomer, the dipoles of the substituents will cancel out[citation needed] due to their being on opposite site of the molecule. Trans isomers also tend to have lower densities than their cis counterparts.[citation needed]

March[4] observes that, as trans alkenes, in general, have more symmetry than cis alkenes, the trans alkenes also tend to have higher melting points and lower solubility in inert solvents.

Vicinal coupling constants (3JHH), measured by NMR spectroscopy, are larger for trans- (range: 12–18 Hz, typical: 15 Hz) than for cis- (range: 0–12 Hz, typical: 8 Hz) isomers.[5]

[edit] Stability

Usually, trans isomers are more stable than the cis isomers. This is partly due to their shape; the straighter shape of the trans isomer leads to hydrogen intermolecular forces that make the isomer more stable[citation needed]. According to Jerry March, trans isomers also have a lower heat of

combustion, indicating higher thermochemical stability. In the Benson Heat of formation group additivity, dataset cis isomers suffer a 1.10 kcal/mol stability penalty. Exceptions to this rule exist. For instance, for 1,2-difluoroethylene, 1,2-difluorodiazene (FN=NF), and several other halogen- and oxygen-substituted ethylenes. In this case, the cis isomer is more stable than the trans isomer.[6] This phenomenon is called the cis effect.[7]

[edit] E/Z notation

Bromine has a higher CIP priority than chlorine, so this alkene is the Z isomer

Main article: E-Z notation

The cis/trans system for naming isomers is not effective when there are more than two different substituents on a double bond. The E/Z notation should then be used. Z (from the German zusammen) means together and corresponds to the term cis; E (from the German entgegen) means opposite and corresponds to the term trans.

Whether a molecular configuration is designated E or Z is determined by the Cahn-Ingold-Prelog priority rules (higher atomic numbers are given higher priority). For each of the two atoms in the double bond, it is necessary to determine which of the two substituents is of a higher priority. If both of the substituents of higher priority are on the same side, the arrangement is Z; if they are on opposite sides, the arrangement is E.

[edit] Inorganic coordination complexes

In inorganic coordination complexes with octahedral or square planar geometries, there are also cis isomers in which similar ligands are closer together and trans isomers in which they are further apart.

The two isomeric complexes, cisplatin and transplatin

For example, there are two isomers of square planar Pt(NH3)2Cl2, as explained by Alfred Werner in 1893. The cis isomer, whose full name is cis-diamminedichloroplatinum(II), was shown in 1969 by Barnett Rosenberg to have antitumor activity and is now a chemotherapy drug known by the short name cisplatin. In contrast, the trans isomer (transplatin) has no useful anticancer activity. Each isomer can be synthesized using the trans effect to control which isomer is produced.

cis-[Co(NH3)4 Cl2]+ and trans-[Co(NH3)4 Cl2]+

For octahedral complexes of formula MX4Y2, two isomers also exist. (Here M is a metal atom, and X and Y are two different types of ligands.) In the cis isomer, the two Y ligands are adjacent to each other at 90o, as is true for the two chlorine atoms shown in green in cis-[Co(NH3)4Cl2]+, at left. In the trans isomer shown at right, the two Cl atoms are on opposite sides of the central Co atom.

A related type of isomerism in octahedral MX3Y3 complexes is facial-meridional (or fac-mer) isomerism, in which different numbers of ligands are cis or trans to each other.

StereoisomerismFrom Wikipedia, the free encyclopediaJump to: navigation, search

Stereoisomers are isomeric molecules that have the same molecular formula and sequence of bonded atoms (constitution), but which differ only in the three-dimensional orientations of their atoms in space.[1][2] Structural isomers share the same molecular formula, but the bond

connections and/or their order between different atoms/groups differs. In stereoisomers, the order and bond connections of the constituent atoms remains the same, but their orientation in space differ.

Contents

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1 Enantiomers 2 Diastereomers 3 Cis-trans and E-Z isomerism 4 Conformers 5 More definitions 6 References

[edit] Enantiomers

Main article: Enantiomer

Enantiomers are two stereoisomers that are related to each other by a reflection: they are mirror images of each other, which are non-superimposable. Human hands are a macroscopic example of stereoisomerism. Every stereogenic center in one has the opposite configuration in the other. Two compounds that are enantiomers of each other have the same physical properties, except for the direction in which they rotate polarized light and how they interact with different optical isomers of other compounds. For this reason, pure enantiomers exhibit the phenomenon of optical activity and can be separated only with the use of a chiral agent. In nature, only one enantiomer of most chiral biological compounds, such as amino acids (except glycine which is achiral), is present. As a result, different enantiomers of a compound may have substantially different biological effects.

[edit] Diastereomers

Main article: Diastereomer

Diastereomers are stereoisomers not related through a reflection operation. They are not mirror images of each other. These include meso compounds, cis-trans (E-Z) isomers, and non-enantiomeric optical isomers. Diastereomers seldom have the same physical properties. In the example shown below, the meso form of tartaric acid forms a diastereomeric pair with both levo and dextro tartaric acids, which form an enantiomeric pair.

(natural) tartaric acidL-(+)-tartaric aciddextrotartaric acid

D-(-)-tartaric acidlevotartaric acid

mesotartaric acid

(1:1)DL-tartaric acid"racemic acid"

It should be carefully noted here that the D- and L-labeling of the isomers above is not the same as the d- and l-labeling more commonly seen, explaining why these may appear reversed to those only familiar with the latter naming convention. Please refer to Chirality for more information regarding the D- and L-labels.

[edit] Cis-trans and E-Z isomerism

Main articles: Cis-trans isomerism and E-Z notation

Stereoisomerism about double bonds arises because rotation about the double bond is restricted, keeping the substituents fixed relative to each other. If the substituents on either end of a double bond are the same, it is not considered a stereo bond.

Traditionally, double bond stereochemistry was described as either cis (Latin, on this side) or trans (Latin, across), in reference to the relative position of substituents on either side of a double bond. The simplest examples of cis-trans isomerism are the 1,2-disubstituted ethenes, like the dichloroethene (C2H2Cl2) isomers shown below.

Molecule I is cis-1,2-dichloroethene and molecule II is trans-1,2-dichloroethene. Due to occasional ambiguity, IUPAC adopted a more rigorous system wherein the substituents at each end of the double bond are assigned priority based on their atomic number. If the high priority substituents are on the same side of the bond it is assigned Z (Ger. zusammen, together). If they are on opposite sides it is E (Ger. entgegen, opposite). Since chlorine has a larger atomic number

than hydrogen it is the highest priority group. Using this notation to name the above pictured molecules, molecule I is (Z)-1,2-dichloroethene and molecule II is (E)-1,2-dichloroethene. It is not the case Z and cis or E and trans are always interchangeable. Consider the following fluoromethylpentene:

The proper name for this molecule is either trans-2-fluoro-3-methylpent-2-ene because the alkyl groups that form the backbone chain (i.e. methyl and ethyl) reside across the double bond from each other, or (Z)-2-fluoro-3-methylpent-2-ene because the highest priority groups on each side of the double bond are on the same side of the double bond. Fluoro is the highest priority group on the left side of the double bond and ethyl is the highest priority group on the right side of the molecule.

The terms cis and trans are also used to describe the relative position of two substituents on a ring; cis if on the same side, otherwise trans.

[edit] Conformers

Main article: Conformational isomerism

Conformational isomerism is a form of isomerism that describes the phenomenon of molecules with the same structural formula having different shapes due to rotations about one or more bonds. Different conformations can have different energies, can usually interconvert, and are very rarely isolatable. For example, cyclohexane can exist in a variety of different conformations including a chair conformation and a boat conformation, but for cyclohexane itself, these can never be separated. The boat conformation represents an energy maximum (and not a transition state) on the conformational itinerary between the two equivalent chair forms. There are some molecules that can be isolated in several conformations, due to the large energy barriers between different conformations. 2,2,2',2'-Tetrasubstituted biphenyls can fit into this latter category.

[edit] More definitions

A configurational stereoisomer is a stereoisomer of a reference molecule that has the opposite configuration at a stereocenter (e.g. R- vs S- or E- vs Z-). This means that configurational isomers can only be interconverted by breaking covalent bonds to the stereocenter, for example by inverting the configurations of some or all of the stereocenters in a compound.

Enantiomer

From Wikipedia, the free encyclopediaJump to: navigation, search This article is about the concept in chemistry. For a discussion of enantiomers in mathematics, see Chirality (mathematics).

(S)-(+)-lactic acid (left) and (R)-(–)-lactic acid (right) are nonsuperposable mirror images of each other

In chemistry, an enantiomer is one of two stereoisomers that are mirror images of each other that are "non-superposable" (not identical), much as one's left and right hands are "the same" but opposite. [1] The term, pronounced /ɨˈnæntɪ.ɵmər/, is derived from the Greek 'ἐνάντιος', opposite, and 'μέρος', part or portion.Enantiopure compounds refer to samples having, within the limits of detection, molecules of only one chirality.[2]

Enantiomers have, when present in a symmetric environment, identical chemical and physical properties except for their ability to rotate plane-polarized light (+/−) by equal amounts but in opposite directions (nevertheless it's important to note that the polarized light can be considered an asymmetric media). A mixture of equal parts of an optically active isomer and its enantiomer is termed racemic and has a net rotation of plane-polarized light of zero.

Enantiomers of each other often show different chemical reactions with other substances that are also enantiomers. Since many molecules in the body of living beings are enantiomers themselves, there is often a marked difference in the effects of two enantiomers on living beings. In drugs, for example, the working substance is often one of two enantiomers, while the other one is responsible for adverse effects.

Contents

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1 Examples 2 Enantioselective preparations 3 Enantiopure medications 4 See also 5 References

[edit] Examples

Enantiomers of mecoprop, 2-(4-chloro-2-methylphenoxy)propanoic acid

Enantiomers of Citalopram. The top is ( S )-Citalopram and the bottom is (R)-Citalopram

An example of such an enantiomer is the sedative Thalidomide. It was sold in a number of countries across the world from 1957 until 1961 when it was withdrawn from the market after being found to be a cause of birth defects.

In the herbicide Mecoprop, the carboxyl group and the hydrogen atom on the central C-atom are exchanged (with the screen as plane of symmetry). After rotating one of the isomers 180 degrees (in the same plane), the two are still mirror images of each other. The mirror image of each enantiomer is superposable on the other enantiomer.

Another example are the antidepressant drugs Escitalopram (aka Lexapro) and Citalopram (aka Celexa). Citalopram is a racemate [1:1 mixture of (S)-Citalopram and (R)-Citalopram]; Escitalopram [(S)-Citalopram] is a pure enantiomer. The dosages for Escitalopram are typically 1/2 of those for Citalopram, and there are fewer side effects, suggesting that most side effects come from the (R)-enantiomer.[citation needed]

[edit] Enantioselective preparations

See also: chiral resolution and asymmetric synthesis

There are two main strategies for the preparation of enantiopure compounds. The first is known as chiral resolution. This method involves preparing the compound in racemic form, and separating it into its isomers. In his pioneering work, Louis Pasteur was able to isolate the isomers of tartaric acid because they crystallize from solution as crystals each with a different symmetry. A less common method is by enantiomer self-disproportionation.

The second strategy is asymmetric synthesis: the use of various techniques to prepare the desired compound in high enantiomeric excess. Techniques encompassed include the use of chiral starting materials (chiral pool synthesis), the use of chiral auxiliaries and chiral catalysts, and the application of asymmetric induction. The use of enzymes (biocatalysis) may also produce the desired compound.

Enantioconvergent synthesis is the synthesis of one enantiomer from a racemic precursor molecule utilizing both enantiomers. Thus, the two enantiomers of the reactant produce a single enantiomer of product.

[edit] Enantiopure medications

Main article: Enantiopure drug

Advances in industrial chemical processes have made it economical for pharmaceutical manufacturers to take drugs that were originally marketed as a racemic mixture and market the individual enantiomers. In some cases, the enantiomers have genuinely different effects. In other cases, there may be no clinical benefit to the patient. Single-enantiomer drugs are separately patentable from the racemic mixture. It is possible that both enantiomers are active. Or, it may be that only one is active, in which case separating the mixture has no objective benefits, bu

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