Ether
An ether is a functional group characterized by an oxygen atom attached on each side to an alkyl, alkenyl, alkynyl, or aryl group. The reactivity and properties of dialkyl ethers are significantly different from those that contain one or more alkenyl, alkynyl, or aryl groups.
Nomenclature
Ethers commonly are named using the formula “alkoxyalkane” in which the alkoxy and alkane components of the name are derived from the alkyl groups attached to the ether oxygen. An alkyl chain attached to an oxygen atom can also be referred to as an alkoxy substituent when the group acts as a substituent.
Physical Properties
In general ethers have relatively low polarity. The C-O-C bond angle is approximately 110o. The individual C-O dipoles are largely opposed and the resulting dipole moment is relatively small compared to other oxygen-containing organic compounds.
Ether moieties are unable to form hydrogen bonds to other ethers. While the oxygen atom of an ether is a good hydrogen bond acceptor, the group is unable to act as a hydrogen bond donor. Ethers are relatively soluble in solvents that are able to act as hydrogen bond donors such as water and lower alcohols; for example, tetrahydrofuran and 1,4-dioxane are totally miscible with water. Ethers are capable of solvating metal ions and can act as ligands in transition metal complexes.
Reactions
Ethers are generally relatively unreactive. As protective groups they are able to withstand a wider range of conditions than esters or other common alcohol protective groups. Their relative stability often makes their removal more difficult however. Ethers undergo the following reactions:
- Nucleophilic displacement
Strained ethers such as epoxides (three membered ring cyclic ethers) are far more susceptible to fragmentation by nucleophiles, generally with retention of configuration. Displacement can occur under both basic and acidic conditions.
- Peroxide formation
Primary and secondary ethers can form peroxides in the presence of oxygen. These compounds are highly explosive and become concentrated when the solvent is evaporated. It is therefore important to handle ethereal solvents carefully and to avoid evaporating ether solvents to dryness and, if possible, to handle them under an inert atmosphere.
- Hydrolysis
Ethers typically are hydrolyzed with relatively strong Lewis acids such as boron tribromide or heating in hydrobromic acid. Hydrolysis will occur slowly upon treatment with lower halogen mineral acids such as hydrochloric acid. Ethers react with hydrobromic acid and hydroiodic acid at a higher rate. Certain aryl ethers can undergo cleavage under relatively milder conditions, such as treatment with aluminum trichloride.
- Reduction to alkene
Epoxides can undergo deoxygenation to the corresponding alkene via treatment with tungsten hexachloride. The reaction generally proceeds with retention of configuration.
Synthesis
Ethers can be prepared in the laboratory in several different ways.
R-O- + R-X → R-O-R + X-
This reaction involves the nucleophilic displacement of a halide ion from an alkyl halide with an alkoxide. An alkoxide is treated with a compound possession a good leaving group that is susceptible to nucleophilic displacement. Suitable leaving groups (X) include sulfonates, bromides, and iodides. The reaction proceeds in competition with elimination and can therefore give a mixture of substitution and elimination products. The Finkelstein Reaction is commonly employed to prepare alkyl iodide compounds for use in the Williamson Ether synthesis from the corresponding chlorides and bromides.
Reactions in which the leaving group resides on a benzylic carbon atom are particularly facile because the positive charge on the carbon atom bearing the leaving group in the transition state is stabilized by conjugation with the phenyl ring.
- Electrophilic addition of alcohols to alkenes
This reaction proceeds under Lewis acidic conditions. Mercury trifluoroacetate frequently is used as a Lewis acid catalyst. The resulting ether proceeds via anti addition and affords the ether possessing Markovnikov regiochemistry.
Epoxides (three membered ring cyclic ethers) can be prepared by the following methods:
- By the base-promoted intramolecular displacement of a good leaving group (e.g. halogen, OTs) by a hydroxyl moiety on a carbon atom adjacent to the leaving group.
- MCPBA oxidation of an alkene (affords syn addition product).