Williamson ether synthesis

[5]The Williamson reaction is of broad scope, is widely used in both laboratory and industrial synthesis, and remains the simplest and most popular method of preparing ethers.

In the case of asymmetrical ethers there are two possibilities for the choice of reactants, and one is usually preferable either on the basis of availability or reactivity.

Since the conditions of the reaction are rather forcing, protecting groups are often used to pacify other parts of the reacting molecules (e.g. other alcohols, amines, etc.)

Yields for these ether syntheses are traditionally low when reaction times are shortened, which can be the case with undergraduate laboratory class periods.

This method has proved to be highly selective and especially helpful in production of aromatic ethers such as anisole which has increasing industrial applications.

[7] Since alkoxide ions are highly reactive, they are usually prepared immediately prior to the reactions or are generated in situ.

In laboratory chemistry, in situ generation is most often accomplished by the use of a carbonate base or potassium hydroxide, while in industrial syntheses phase transfer catalysis is very common.

However, if an unreactive alkylating agent is used (e.g. an alkyl chloride) then the rate of reaction can be greatly improved by the addition of a catalytic quantity of a soluble iodide salt (which undergoes halide exchange with the chloride to yield a much more reactive iodide, a variant of the Finkelstein reaction).

Finally, phase transfer catalysts are sometimes used (e.g. tetrabutylammonium bromide or 18-crown-6) in order to increase the solubility of the alkoxide by offering a softer counter-ion.