Williamson's synthesis is a versatile method for the synthesis of both symmetrical and unsymmetrical ethers. However, for the synthesis of unsymmetrical ethers, a proper choice of reactants is necessary. Since Williamson's synthesis occurs by $\mathrm{S}_{\mathrm{N}} 2$ mechanism and primary alkyl halides are most reactive in $\mathrm{S}_{\mathrm{N}} 2$ reaction, therefore, best yields of unsymmetrical ethers are obtained when the alkyl halides are primary and the alkoxide may be primary, secondary or tertiary. For example, tertbutylethyl ether is prepared by treating ethyl bromide with sodium tert-butoxide.


The above ether cannot be prepared by treating sodium ethoxide with tert-butyl chloride or bromide since under these condition an alkene, i.e., isobutylene is the main product.

Aryl and vinyl halides cannot be used as substrates because they are less reactive in nucleophilic substitution.