Protons in identical electronic environments within a molecule are chemically equivalent and have the same chemical shift. The replacement test is a useful tool to identify chemical equivalence and predict NMR spectra. A substituent replaces each of the protons being examined and the resulting molecules are compared. If the same molecule is obtained, the protons are equivalent or homotopic. Replacement of any hydrogens in ethane by chlorine yields chloroethane because all six protons are rendered homotopic by the rapid rotation of the carbon-carbon bond. Homotopic protons are interchangeable by rotation about an axis of symmetry and yield a single NMR signal.

In chloroethane, however, replacing the alpha- and beta-hydrogens gives 1,1-dichloroethane and 1,2-dichloroethane, respectively. Here, the protons attached to the alpha and beta carbons are non-equivalent with respect to each other and yield distinct NMR signals. Such protons are chemically non-equivalent and called constitutionally heterotopic or just heterotopic.