ether

The general structure for an ether

Ether is a class of organic compounds that contain an ether group — an oxygen atom connected to two alkyl or aryl groups — of general formula R–O–R.^[1] A typical example is the solvent and anesthetic diethyl ether, commonly referred to simply as "ether" (CH₃-CH₂-O-CH₂-CH₃). Ethers are common in organic chemistry and pervasive in biochemistry, as they are common linkages in carbohydrates and lignin.

Structure and bonding

Ethers feature C-O-C linkage defined by a bond angle of about 120° and C-O distances of about 1.5 Å. The barrier to rotation about the C-O bonds is low. The bonding of oxygen in ethers, alcohols, and water is similar. In the language of valence bond theory, the hybridization at oxygen is sp³.

Oxygen is more electronegative than carbon, thus the hydrogens alpha to ethers are more acidic than in simple hydrocarbons. They are far less acidic than hydrogens alpha to ketones, however.

Nomenclature

The names for simple ethers (i.e. those with none or few other functional groups) are a composite of the two substituents followed by "ether." Methyl ethyl ether (CH₃OC₂H₅), diphenylether (C₆H₅OC₆H₅). IUPAC rules is often not followed for simple ethers. As for other organic compounds, very common ethers acquired names before rules for nomenclature were formalized. Diethyl ether is simply called "ether," but was once called sweet oil of vitriol. Methyl phenyl ether is anisole, because it was originally found in aniseed. The aromatic ethers include furans. Acetals (Éø-alkoxy ethers R-CH(-OR)-O-R) are another class of ethers with characteristic properties.

In the IUPAC nomenclature system, which is rarely encountered, ethers are named using the general formula "alkoxyalkane", for example CH₃-CH₂-O-CH₃ is methoxyethane. If the ether is part of a more complex molecule, it is described as an alkoxy substituent, so -OCH₃ would be considered a "methoxy-" group. The simpler alkyl radical is written in front, so CH₃-O-CH₂CH₃ would be given as methoxy(CH₃O)ethane(CH₂CH₃). The nomenclature of describing the two alkyl groups and appending "ether", e.g. "ethyl methyl ether" in the example above, is a trivial usage.

Polyethers

Polyethers are compounds with more than one ether group. The term generally refers to polymers like polyethylene glycol and polypropylene glycol. The crown ether are examples of low-molecular polyethers.

Related compounds, not classified as ethers

Many classes of compounds with C-O-C linkages are not considered ethers: Esters (R-C(=O)-O-R), hemiacetals (R-CH(-OH)-O-R), carboxylic acid anhydrides (RC(=O)-O-C(=O)R).

Physical properties

Ether molecules cannot form hydrogen bonds amongst each other, resulting in a relatively low boiling point compared to that of the analogous alcohols. The difference, however, in the boiling points of the ethers and their isometric alcohols become smaller as the carbon chains become longer, as the van der waals interactions of the extended carbon chain dominate over the presence of hydrogen bonding.

Ethers are slightly polar, as the COC bond angle in the functional group is about 110 degrees, and the C-O dipoles do not cancel out. Ethers are more polar than alkenes but not as polar as alcohols, esters, or amides of comparable structure. However, the presence of two lone pairs of electrons on the oxygen atoms makes hydrogen bonding with water molecules possible, causing the solubility of alcohols (for instance, butan-1-ol) and ethers (ethoxyethane) to be quite dissimilar.

Cyclic ethers such as tetrahydrofuran and 1,4-dioxane are miscible in water because of the more exposed oxygen atom for hydrogen bonding as compared to aliphatic ethers.

Reactions

Structure of the polymeric diethyl ether peroxide

Ethers in general are of low chemical reactivity but they are more reactive than alkanes. Epoxides are unrepresentative and are discussed separately. Imporant reactions are listed below.^[2]

Ether cleavage

Ethers resist hydrolysis. Mineral acids containing a halogen, such as Hydrobromic acid and hydroiodic acid cleave ethers at a use rate. Hydrogen chloride cleaves ethers only slowly. Some ethers rapidly cleave with boron tribromide to give the alkyl bromide. Certain aryl ethers can be cleaved by aluminium chloride.

Peroxide formation

Primary and secondary ethers with a CH group next to the ether oxygen form peroxides, e.g. diethyl ether peroxide. The reaction requires oxygen (or air) and is accelerated by light, metal catalysts, and aldehydes. The resulting peroxides can be explosive. For this reason, diisopropyl ether and THF are often avoided as solvents.

As Lewis bases

Ethers serve as Lewis bases and Bronsted bases. Strong acids protonate the oxygen to give "onium ions." For instance, diethyl ether forms a complex with boron compounds, such as boron trifluoride diethyl etherate (BF₃^.OEt₂). Ethers also coordinate to magnesium in Grignard reagents (RMgBr). Polyethers, including many antibiotics, bind alkali metal ions particularly strongly.

Alpha-halogenation

This reactivity is akin to the tendency of ethers with alpha hydrogen atoms to form peroxides. Chlorine gives alpha-chloroethers.

Synthesis

Ethers can be prepared in the laboratory in several different ways.

Dehydration of alcohols

The Dehydration of alcohols affords ethers:

2 R-OH → R-O-R + H₂O

This direct reaction requires elevated temperatures (about 125 °C). The reaction is catalyzed by acids, usually sulfuric acid. The method is effective for generating symmetrical ethers, but not unsymmetrical ethers. Diethyl ether is produced from ethanol by this method. Cyclic ethers are readily generated by this approach. Such reactions must compete with dehydration of the alcohol:

R-CH₂-CH₂(OH) → R-CH=CH₂ + H₂O

The dehydration route often requires conditions incompatible with delicate molecules. Several milder methods exist to produce ethers.

Williamson ether synthesis

Nucleophilic displacement of alkyl halides by alkoxides

R-ONa + R'-X → R-O-R' + X^-

This reaction is called the Williamson ether synthesis. It involves treatment of a parent alcohol with a strong base to form the alkoxide, followed by addition of an appropriate aliphatic compound bearing a suitable leaving group (R-X). Suitable leaving groups (X) include iodide, bromide, or sulfonates. This method usually does not work well for aryl halides (e.g. bromobenzene (see Ullmann condensation below). Likewise, this method only gives the best yields for primary halides. Secondary and tertiary halides are prone to undergo E2 elimination on exposure to the basic alkoxide anion used in the reaction due to steric hindrance from the large alkyl groups.

In a related reaction, alkyl halides undergo nucleophilic displacement by phenoxides. The R-X cannot be used to react with the alcohol. However, phenols can be used to replace the alcohol, while maintaining the alkyl halide. Since phenols are acidic, they readily react with a strong base like sodium hydroxide to form phenoxide ions. The phenoxide ion will then substitute the -X group in the alkyl halide, forming an ether with an aryl group attached to it in a reaction with an SN2 mechanism.

C₆H₅OH + OH^- → C₆H₅-O^- + H₂O

C₆H₅-O^- + R-X → C₆H₅OR

Ullmann condensation

The Ullmann condensation is similar to the Williamson method except that the substrate is an aryl halide.

Electrophilic addition of alcohols to alkenes

Alcohols add to electrophilically activated alkenes.

R₂C=CR₂ + R-OH → R₂CH-C(-O-R)-R₂

Acid catalysis is required for this reaction. Often, mercury trifluoroacetate (Hg(OCOCF₃)₂) is used as a catalyst for the reaction, geneating an ether with Markovnikov regiochemistry. Using similar reactions, tetrahydropyranyl ethers are used as protective groups for alcohols.

Preparation of epoxides

Epoxides are typically prepared by oxidation of alkenes. The most important epoxide in terms of industrial scale is ethylene oxide, which is produced by oxidation of ethylene with oxygen. Other epoxides are produced by one of two routes:

• By the oxidation of alkenes with a peroxyacid such as m-CPBA.
• By the base intramolecular nuclephilic substitution of a halohydrin.

Important ethers

	Ethylene oxide	The smallest cyclic ether.
	Dimethyl ether	An aerosol spray propellant. A potential renewable alternative fuel for diesel engines with a cetane rating as high as 56-57.
	Diethyl ether	A common low boiling solvent (b.p. 34.6°C), and an early anaesthetic.
	Dimethoxyethane (DME)	A high boiling solvent (b.p. 85°C):
	Dioxane	A cyclic ether and high boiling solvent (b.p. 101.1°C).
	Tetrahydrofuran (THF)	A cyclic ether, one of the most polar simple ethers that is used as a solvent.
	Anisole (methoxybenzene)	An aryl ether and a major constituent of the essential oil of anise seed.
	Crown ethers	Cyclic polyethers that are used as phase transfer catalysts.
	Polyethylene glycol (PEG)	A linear polyether, e.g. used in cosmetics and pharmaceuticals.

References

This article needs additional citations for verification. Please help improve this article by adding reliable references. Unsourced material may be challenged and removed. (December 2007)

1. ^ International Union of Pure and Applied Chemistry. "ethers". Compendium of Chemical Terminology Internet edition.
2. ^ Wilhelm Heitmann, Günther Strehlke, Dieter Mayer "Ethers, Aliphatic" in Ullmann's Encyclopedia of Industrial Chemistry" Wiley-VCH, Weinheim, 2002. doi:10.1002/14356007.a10_023

External links

• ILPI page about ethers.
• An Account of the Extraordinary Medicinal Fluid, called Aether, by M. Turner, circa 1788, from Project Gutenberg