Topicity

Last updated

In stereochemistry, topicity is the stereochemical relationship between substituents and the structure to which they are attached. Depending on the relationship, such groups can be heterotopic, homotopic, enantiotopic, or diastereotopic.

Contents

Homotopic

Homotopic groups in a chemical compound are equivalent groups. Two groups A and B are homotopic if the molecule remains the same (including stereochemically) when the groups are interchanged with some other atom (such as bromine) while the remaining parts of the molecule stay fixed. Homotopic atoms are always identical, in any environment. Homotopic NMR-active nuclei have the same chemical shift in an NMR spectrum. For example, the four hydrogen atoms of methane (CH4) are homotopic with one another, as are the two hydrogens or the two chlorines in dichloromethane (CH2Cl2).

Enantiotopic

The stereochemical term enantiotopic refers to the relationship between two groups in a molecule which, if one or the other were replaced, would generate a chiral compound. The two possible compounds resulting from that replacement would be enantiomers.

For example, the two hydrogen atoms attached to the second carbon in butane are enantiotopic. Replacement of one hydrogen atom (colored blue) with a bromine atom will produce (R)-2-bromobutane. Replacement of the other hydrogen atom (colored red) with a bromine atom will produce the enantiomer (S)-2-bromobutane.

Enantiotopic1.png Enantiotopic3.png Enantiotopic2.png
Butane(R)-2-bromobutane(S)-2-bromobutane

Enantiotopic groups are identical and indistinguishable except in chiral environments. For instance, the CH2 hydrogens in ethanol (CH3CH2OH) are normally enantiotopic, but can be made different (diastereotopic) if combined with a chiral center, for instance by conversion to an ester of a chiral carboxylic acid such as lactic acid, or if coordinated to a chiral metal center, or if associated with an enzyme active site, since enzymes are constituted of chiral amino acids. Indeed, in the presence of the enzyme LADH, one specific hydrogen is removed from the CH2 group during the oxidation of ethanol to acetaldehyde, and it gets replaced in the same place during the reverse reaction. The chiral environment needs not be optically pure for this effect.

Enantiotopic groups are mirror images of each other about an internal plane of symmetry. A chiral environment removes that symmetry. Enantiotopic pairs of NMR-active nuclei are also indistinguishable by NMR and produce a single signal.

Enantiotopic groups need not be attached to the same atom. For example, two hydrogen atoms adjacent to the carbonyl group in cis-2,6-dimethylcyclohexanone are enantiotopic; they are related by an internal plane of symmetry passing through the carbonyl group, but deprotonation on one side of the carbonyl group or on the other will generate compounds that are enantiomers. Similarly, the replacement of one or the other with deuterium will generate enantiomers.

Diastereotopic

The stereochemical term diastereotopic refers to the relationship between two groups in a molecule which, if replaced, would generate compounds that are diastereomers. Diastereotopic groups are often, but not always, identical groups attached to the same atom in a molecule containing at least one chiral center.

For example, the two hydrogen atoms of the CH2 moiety in (S)-2-bromobutane are diastereotopic. Replacement of one hydrogen atom (colored blue) with a bromine atom will produce (2S,3R)-2,3-dibromobutane. Replacement of the other hydrogen atom (colored red) with a bromine atom will produce the diastereomer (2S,3S)-2,3-dibromobutane.

Diastereotopic1.png Diastereotopic3.png Diastereotopic2.png
(S)-2-bromobutane(2S,3R)-2,3-dibromobutane(2S,3S)-2,3-dibromobutane

In chiral molecules containing diastereotopic groups, such as in 2-bromobutane, there is no requirement for enantiomeric or optical purity; no matter its proportion, each enantiomer will generate enantiomeric sets of diastereomers upon substitution of diastereotopic groups (though, as in the case of substitution by bromine in 2-bromobutane, meso isomers have, strictly speaking, no enantiomer).

Diastereotopic groups are not mirror images of one another about any plane. They are always different, in any environment, but may not be distinguishable. For instance, both pairs of CH2 hydrogens in ethyl phenylalaninate hydrochloride (PhCH2CH(NH3+)COOCH2CH3 Cl−) are diastereotopic and both give pairs of distinct 1H-NMR signals in DMSO-d6 at 300 MHz, [1] but in the similar ethyl 2-nitrobutanoate (CH3CH2CH(NO2)COOCH2CH3), only the CH2 group next to the chiral center gives distinct signals from its two hydrogens with the same instrument in CDCl3. [2] Such signals are often complex because of small differences in chemical shift, overlap and an additional strong coupling between geminal hydrogens. On the other hand, the two CH3 groups of ipsenol, which are three bonds away from the chiral center, give separate 1H doublets at 300 MHz and separate 13C-NMR signals in CDCl3, [3] but the diastereotopic hydrogens in ethyl alaninate hydrochloride (CH3CH(NH3+)COOCH2CH3 Cl−), also three bonds away from the chiral center, show barely distinguishable 1H-NMR signals in DMSO-d6. [4]

Figure 1. Diastereotopic hydrogens in achiral compounds. DIASTERE.png
Figure 1. Diastereotopic hydrogens in achiral compounds.

Diastereotopic groups also arise in achiral molecules. For instance, any one pair of CH2 hydrogens in 3-pentanol (Figure 1) are diastereotopic, as the two CH2 carbons are enantiotopic. Substitution of any one of the four CH2 hydrogens creates two chiral centers at once, and the two possible hydrogen substitution products at any one CH2 carbon will be diastereomers. This kind of relationship is often easier to detect in cyclic molecules. For instance, any pair of CH2 hydrogens in cyclopentanol (Figure 2) are similarly diastereotopic, and this is easily discerned as one of the hydrogens in the pair will be cis to the OH group (on the same side of the ring face) while the other will be trans to it (on the opposite side).

The term diastereotopic is also applied to identical groups attached to the same end of an alkene moiety which, if replaced, would generate geometric isomers (also falling in the category of diastereomers). Thus, the CH2 hydrogens of propene are diastereotopic, one being cis to the CH3 group, and the other being trans to it, and replacement of one or the other with CH3 would generate cis- or trans--2-butene.

Figure 2. Diastereotopic hydrogens in a chiral metal complex. DIASTER2.png
Figure 2. Diastereotopic hydrogens in a chiral metal complex.

Diastereotopicity is not limited to organic molecules, nor to groups attached to carbon, nor to molecules with chiral tetrahedral (sp3-hybridized) centers: for instance, the pair of hydrogens in any CH2 or NH2 group in tris(ethylenediamine)chromium(III) ion (Cr(en)33+), where the metal center is chiral, are diastereotopic (Figure 2).

The terms enantiotopic and diastereotopic can also be applied to the faces of planar groups (especially carbonyl groups and alkene moieties). See Cahn-Ingold-Prelog priority rule.

Heterotopic

Heterotopic groups are those that when substituted are structurally different. They are neither diastereotopic or enantiotopic nor homotopic. [5]

See also

Related Research Articles

Cahn–Ingold–Prelog priority rules

The Cahn–Ingold–Prelog (CIP) sequence rules, named for organic chemists Robert Sidney Cahn, Christopher Kelk Ingold, and Vladimir Prelog — alternatively termed the CIP priority rules, system, or conventions — are a standard process used in organic chemistry to completely and unequivocally name a stereoisomer of a molecule. The purpose of the CIP system is to assign an R or S descriptor to each stereocenter and an E or Z descriptor to each double bond so that the configuration of the entire molecule can be specified uniquely by including the descriptors in its systematic name. A molecule may contain any number of stereocenters and any number of double bonds, and each usually gives rise to two possible isomers. A molecule with an integer n describing the number of its stereogenic centers will usually have 2n stereoisomers, and 2n−1 diastereomers each having an associated pair of enantiomers. The CIP sequence rules contribute to the precise naming of every stereoisomer of every organic and organometallic molecule with all atoms of ligancy of fewer than 4.

Monosaccharides, also called simple sugars, are the simplest forms of sugar and the most basic units (monomers) from which all carbohydrates are built.

In chemistry, a structural isomer of a compound is another compound whose molecule has the same number of atoms of each element, but with logically distinct bonds between them. The term metamer was formerly used for the same concept.

Stereoisomerism 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.

Hexose

In chemistry, a hexose is a monosaccharide (simple sugar) with six carbon atoms. The chemical formula for all hexoses is C6H12O6, and their molecular weight is 180.156 g/mol.

A carbanion is an anion in which carbon is trivalent and bears a formal negative charge.

Diastereomer Molecules which are non-mirror image, non-identical stereoisomers


In stereochemistry, diastereomers are a type of stereoisomer. Diastereomers are defined as non-mirror image, non-identical stereoisomers. Hence, they occur when two or more stereoisomers of a compound have different configurations at one or more of the equivalent (related) stereocenters and are not mirror images of each other. When two diastereoisomers differ from each other at only one stereocenter they are epimers. Each stereocenter gives rise to two different configurations and thus typically increases the number of stereoisomers by a factor of two.

Diethyl malonate Chemical compound

Diethyl malonate, also known as DEM, is the diethyl ester of malonic acid. It occurs naturally in grapes and strawberries as a colourless liquid with an apple-like odour, and is used in perfumes. It is also used to synthesize other compounds such as barbiturates, artificial flavourings, vitamin B1, and vitamin B6.

Unsaturated hydrocarbon

Unsaturated hydrocarbons are hydrocarbons that have double or triple covalent bonds between adjacent carbon atoms. The term "unsaturated" means more hydrogen atoms may be added to the hydrocarbon to make it saturated. The configuration of an unsaturated carbons include straight chain, such as alkenes and alkynes, as well as branched chains and aromatic compounds.

Chirality (chemistry) 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.

Enantioselective synthesis Form of chemical synthesis

Enantioselective synthesis, also called asymmetric synthesis, is a form of chemical synthesis. It is defined by IUPAC as "a chemical reaction in which one or more new elements of chirality are formed in a substrate molecule and which produces the stereoisomeric products in unequal amounts."

Octahedral molecular geometry Molecular geometry

In chemistry, octahedral molecular geometry describes the shape of compounds with six atoms or groups of atoms or ligands symmetrically arranged around a central atom, defining the vertices of an octahedron. The octahedron has eight faces, hence the prefix octa. The octahedron is one of the Platonic solids, although octahedral molecules typically have an atom in their centre and no bonds between the ligand atoms. A perfect octahedron belongs to the point group Oh. Examples of octahedral compounds are sulfur hexafluoride SF6 and molybdenum hexacarbonyl Mo(CO)6. The term "octahedral" is used somewhat loosely by chemists, focusing on the geometry of the bonds to the central atom and not considering differences among the ligands themselves. For example, [Co(NH3)6]3+, which is not octahedral in the mathematical sense due to the orientation of the N−H bonds, is referred to as octahedral.

Asymmetric induction

In stereochemistry, asymmetric induction describes the preferential formation in a chemical reaction of one enantiomer or diastereoisomer over the other as a result of the influence of a chiral feature present in the substrate, reagent, catalyst or environment. Asymmetric induction is a key element in asymmetric synthesis.

Chiral derivatizing agent

A chiral derivatizing agent (CDA) also known as a chiral resolving reagent, is a chiral auxiliary used to convert a mixture of enantiomers into diastereomers in order to analyze the quantities of each enantiomer present within the mix. Analysis can be conducted by spectroscopy or by chromatography. The use of chiral derivatizing agents has declined with the popularization of chiral HPLC. Besides analysis, chiral derivatization is also used for chiral resolution, the actual physical separation of the enantiomers.

Absolute configuration Stereochemistry term

Absolute configuration refers to the spatial arrangement of atoms within a chiral molecular entity and its resultant stereochemical description. Absolute configuration is typically relevant in organic molecules, where carbon is bonded to four different substituents. This type of construction creates two possible enantiomers. Absolute configuration uses a set of rules to describe the relative positions of each bond around the chiral center atom. The most common labeling method uses the descriptors R or S is based on the Cahn–Ingold–Prelog priority rules. R and S refer to Rectus and Sinister, which are Latin for right and left, respectively.

Pirkles alcohol Chemical compound

Pirkle's alcohol is an off-white, crystalline solid that is stable at room temperature when protected from light and oxygen. This chiral molecule is typically used, in nonracemic form, as a chiral shift reagent in nuclear magnetic resonance spectroscopy, in order to simultaneously determine absolute configuration and enantiomeric purity of other chiral molecules. The molecule is named after William H. Pirkle, Professor of Chemistry at the University of Illinois whose group reported its synthesis and its application as a chiral shift reagent.

Isomer Chemical compounds with the same molecular formula but different atomic arrangements

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

2-Bromobutane is an isomer of 1-bromobutane. Both compounds share the molecular formula C4H9Br. 2-Bromobutane is also known as sec-butyl bromide or methylethylbromomethane. Because it contains bromine, a halogen, it is part of a larger class of compounds known as alkyl halides. It is a colorless liquid with a pleasant odor. Because the carbon atom connected to the bromine is connected to two other carbons the molecule is referred to as a secondary alkyl halide. 2-Bromobutane is chiral and thus can be obtained as either of two enantiomers designated as (R)-(−)-2-bromobutane and (S)-(+)-2-bromobutane.

Dimethylphenylphosphine Chemical compound

Dimethylphenylphosphine is an organophosphorus compound with a formula P(C6H5)(CH3)2. The phosphorus is connected to a phenyl group and two methyl groups, making it the simplest aromatic alkylphosphine. It is colorless air sensitive liquid. It is a member of series (CH3)3-n(C6H5)2P that also includes n = 0, n = 2, and n = 3 that are often employed as ligands in metal phosphine complexes.

Enantioselective ketone reductions convert prochiral ketones into chiral, non-racemic alcohols and are used heavily for the synthesis of stereodefined alcohols.

References

  1. ↑ 300 MHz 1H-NMR spectrum of ethyl phenylalaninate hydrochloride in DMSO-d6 from Sigma-Aldrich Co.
  2. ↑ 300 MHz 1H-NMR spectrum of ethyl 2-nitrobutanoate in CDCl3 from Sigma-Aldrich Co.
  3. ↑ Silverstein, R. et al.: Spectrometric Identification of Organic Compounds, 7th ed., John Wiley & Sons, 2005
  4. ↑ 300 MHz 1H-NMR spectrum of ethyl alaninate hydrochloride in DMSO-d6 from Sigma-Aldrich Co.
  5. ↑ Hans J. Reich. "Symmetry in NMR Spectra". University of Wisconsin.
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.