Topicity

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.

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 stereochemical term diastereotopic refers to the relationship between two groups in a molecule which, if replaced, would generate compounds that are diastereomers.

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).

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.

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).

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).