Structurally Equivalent Atoms and Groups

We noted earlier that not all methyl (or methylene or methyne) groups in a molecule are necessarily the same (structurally equivalent). Depending on the molecular constitution and configuration, similar atoms or groups of atoms may occupy different structural environments. The symmetry of a molecule is helpful in evaluating structural equivalence, since groups that are interchanged by a symmetry operation must have a characteristic relationship. As illustrated by the following examples, atoms or groups that are structurally interchanged by a rotational symmetry operation other than C₁ are classified as homotopic and are considered structurally equivalent (e.g. the hydrogens in dichloromethane). Ligands that are not homotopic may be referred to generally as heterotopic. If a pair of atoms or groups are interchanged by a reflective symmetry operation they are termed enantiotopic (e.g. the hydrogens in bromochloromethane). It is instructive to confirm these assignments by considering the result of a hypothetical substitution. If homotopic groups are replaced in turn by an X substituent the products will be identical. However, if enantiotopic groups are similarly substituted the products are enantiomers. Enantiotopic atoms or groups are structurally equivalent in a symmetrical environment or in reactions with symmetrical reagents. By clicking on the name of each example shown below, the symmetry operation and hypothetical substitution will be displayed in greater detail. The "Restore" button returns the original display.

In the case of bromoethane (the 2nd example) the three methyl hydrogens are not structurally equivalent in a frozen conformation, but become so as this group rapidly rotates about its C–C sigma bond. This equivalence remains even when the methyl is bonded to a chiral center. The last two examples on the right illustrate a diastereotopic relationship of atoms. In these cases H_a and H_b are not interchanged by a symmetry operation, and substitution of each gives diastereomers as products. Although diastereotopic atoms or groups are similar, they are structurally nonequivalent and often exhibit different properties, such as nmr chemical shifts or reaction rates. A diagram summarizing this classification will be displayed by pressing the "Chart" button.
In evaluating the structure and configuration of molecular components, it is useful to define the concept of prostereoisomerism. An atom bonded to heterotopic ligands may be considered a prostereogenic center. If the ligands are enantiotopic, as in the case of bromochloromethane shown above, the center is called prochiral, since replacement of one of the atoms (or groups) with a different substituent would convert the carbon to a chiral center. Cases in which the ligands are diastereotopic, rather than enantiotopic, are described to by the general term prostereogenic.
Planar sp²-carbon functions having three different substituents at one carbon are similarly considered to have prochiral faces. Thus addition of hydride to the achiral ketone, 2-butanone, produces the chiral alcohol 2-butanol. In this case the planar carbonyl carbon has three different substituents (oxygen, methyl and ethyl), and therefore has prochiral faces (commonly designated re and si).