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 110^o. 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.

• Williamson Ether Synthesis

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).

Esters are a class of functional groups and chemical compounds. Esters consist of an organic or inorganic acid in which the -OH group of the acid is replaced by an -OR group. Cyclic esters are usually called lactones. Some acids that are commonly esterified are carboxylic acids, phosphoric acid, nitric acid, and sulfuric acid. Volatile esters, particularly carboxylate esters, often have a pleasant smell and are found in essential oils, perfumes, and pheromones, and give many fruits their characteristic scent. Methyl acetate and ethyl acetate are important solvents; phosphoesters form the backbone of DNA molecules; fats and lipids are the esters of fatty acids; and polyesters are important synthetic fabrics and plastics. Esters can be synthesized in a condensation reaction between an acid and an alcohol in a reaction known as esterification.

Nomenclature

An ester is named according to the two parts that make it up: the part from the alcohol and the part from the acid (in that order), for example ethyl ethanoate (see image below).

For esters derived from the simplest carboxylic acids, the traditional name for the acid constituent is generally retained; for example, formate, acetate, propionate, butyrate. For esters from more complex carboxylic acids, the systematic name for the acid is used, followed by the suffix -oate. For example, methyl formate is the ester of methanol and methanoic acid (formic acid). It could also be called methyl methanoate.

Physical properties

Esters participate in hydrogen bonds as hydrogen-bond acceptors, but unlike their parent alcohols cannot act as hydrogen-bond donors. This ability to participate in hydrogen bonding makes them more water-soluble than their parent hydrocarbons; however, the limitations on their hydrogen bonding also make them more hydrophobic than either their parent alcohols or their parent acids. Their lack of hydrogen-bond-donating ability means that ester molecules cannot hydrogen-bond to each other, which, in general, makes esters more volatile than a carboxylic acid of similar molecular weight. This property makes them very useful in organic analytical chemistry: Unknown organic acids with low volatility can often be esterified into a volatile ester, which can then be analyzed using mass spectrometry, gas chromatography, or gas liquid chromatography. Many esters have distinctive odors and are used as artificial fragrances and flavorings.

Reactions

• Saponification (basic hydrolysis)
• Hydrolysis - the breakdown of an ester by water. This process can be catalyzed by both acids and bases. The base-catalyzed process is called saponification. The hydrolysis yields an alcohol and a carboxylic acid or its carboxylate salt.
• Reaction with primary or secondary amines to form amides.
• Phenyl esters react to form hydroxyarylketones via the Fries rearrangement.
• Esters are converted to isocyanates through intermediate hydroxamic acids in the Lossen rearrangement.
• Di-ester enolates such as diethyl malonate react as nucleophiles with alkyl halides in the malonic ester synthesis.
• Certain esters are functionalized with an α-hydroxyl group via the Chan rearrangement.
• Esters with β-hydrogen atoms can be converted to alkenes via pyrolysis.

Synthesis

Methods of preparing esters include:

• Transesterification.
• Dieckmann condensation or Claisen condensation.
• Favorskii rearrangement of α-haloketones in the presence of base.
• Pinner reaction of a nitrile with an alcohol.
• Nucleophilic displacement of alkyl halides with carboxylic acid salts.
• Nucleophilic displacement of acyl halides with alcohols.
• Baeyer-Villiger oxidation of ketones with peroxides.

A benzyl group is a substituent or molecular fragment possessing the structure C₆H₅CH₂-. The abbreviation “Bn” is commonly used in nomenclature and structural depictions of chemical compounds.

The term is also used in reference to the anion, carbocation, and free radical moieties featuring a benzene ring attached to a CH₂ group, in which the CH₂ group bears a negative charge, a positive charge, or a single unpaired electron respectively. In each case, the charge or radical electron is delocalized throughout the aromatic ring. The corresponding species is therefore much more stable than that of an ordinary primary anion, carbocation, or free radical.

This enhanced stability is observed in the Finkelstein reaction. Benzyl chloride has the same rate of reaction toward iodide as methyl chloride despite that methyl chloride is significantly more susceptible to S_N2 nucleophilic attack. While both benzyl chloride and n-butyl chloride are primary alkyl halides, the rate of reaction of benzyl chloride is 179 times greater.

Protective Groups

Benzyl groups frequently can be introduced to alcohol and carboxylic acids and subsequently removed easily and in high yield; therefore they are frequently used in organic synthesis as protective groups.

The following are two common methods for the protection of alcohols as the corresponding benzyl ethers:

• reaction of an alcohol with benzyl bromide and a strong base via Williamson ether synthesis.
• reaction of alcohol with an imidate such as benzyl trichloroacetimidate (C₆H₅CH₂OC(CCl₃)=NH) promoted by trifluoromethanesulfonic acid.

The following is an example of the use of a p-methoxybenzyl (PMB) ether in total synthesis:

The group can be removed readily by hydrogenation or by using CAN, DDQ, or magnesium bromide–dimethyl sulfide.

The following example demonstrates the use of a benzyl pyridinium salt as a benzyl donor for alcohols:

The solvent is α,α,α-trifluorotoluene and MgO is an acid scavenger. The reaction is believed to proceed via an S_N1 mechanism because Friedel-Crafts reaction side products are observed when toluene is used as a solvent.