6a”s8 ghaya0e0ae1%otaeaecan2ooh 入。入 prepared by intramolecular ta or the wilmo -0 the Wtat.thngcbsuresbasaedonbothenthalocandentrog Relative Rates of Cvclic Ether Formation 77 Three-dimensional analogs of crown ethers are polyethers called cryptands. These are highly selective in alkali and other metal cation binding. 9-6 Williamson Ether Synthesis Ethers are prepared by SN2 reactions. Ethers can be prepared by the reaction of an alkoxide with a primary haloalkane or sulfonate ester under SN2 conditions. The parent alcohol of the alkoxide can be used as the solvent, however other polar solvents are often better, such as DMSO (dimethyl sulfoxide) or HMPA (hexamethylphosphoric triamide). The use of alkoxides in ether synthesis is restricted to primary unhindered alkylating agents, otherwise significant amounts of E2 products are formed. Cyclic ethers can be prepared by intramolecular Williamson synthesis. Haloalcohols serve as the starting point for the Williamson synthesis of cyclic ethers. The intramolecular reaction is usually much faster than the intermolecular reaction. If necessary, the intermolecular reaction can be suppressed by using a high dilution of the haloalcohol. Cyclic ethers of even small rings can be prepared using the Williamson synthesis. Ring size controls the speed of cyclic ether formation. The rate of ring closure is based on both enthalpic and entropic contributions. These rate differences can be explained based on the interplay between strain, entropy, and proximity. Entropy reduction (due to ring closure) increases with increasing ring size. (Reaction rate decrease with increasing ring size.) Ring strain decreases with increasing ring size. (Reaction rate increase with increasing ring size.) Transition-state strain is reduced in the 2-haloalkoxides because the 2-haloalkoxide is already strained by the proximity of the halide and hydroxyl. (Reaction rate increase for the 2-haloalkoxides.)