R2 = alkyl, aryl
Some symmetrical ethers can not be prepared using Williamson either synthesis because, in addition to nucleophilic aliphatic substitution, 1,2-elimination could occur between a substrate bearing beta hydrogens and an alkoxide ion, leading to an alkene as the organic product.
To prepare ether 1 using Williamson ether synthesis, a tert-butyl substrate (2) should be reacted with the tert-butoxide ion (3).
Since alkoxide ions are strongly basic and since the substrate is a tertiary alkyl substrate, the major reaction between 2 and 3 would be 1,2-elimination, giving alkene 4 as the organic product.
Preparation of unsymmetrical ethers using Williamson ether synthesis requires planning because, again, in addition to nucleophilic aliphatic substitution, 1,2-elimination could occur between some substrates and alkoxide ion and could be the dominant process.