Ethers

Type of physical science: Chemistry

Field of study: Chemical compounds

Ethers are water derivatives in which the two hydrogens are replaced with organic radicals. They are generally inert compounds and have excellent solvent and anesthetic properties.

Overview

Ethers can be considered as disubstituted derivatives of water. Thus, when both hydrogens of water (H2O) are replaced by carbon chains or rings (R), a new family of compounds of general formula R2O arises. When the two R groups are the same, the compound is known as a symmetrical ether; when they are different, the ether is termed unsymmetrical, or mixed. Symmetrical ethers are named by using the prefix di-, the name of the common radical, R, and the word "ether." Thus, (C₂H₅)₂O is called diethyl ether, or, often, simply ethyl ether. In cases of unsymmetrical ethers, the groups are named alphabetically and are followed by the word "ether"; for example, C₂H₅OCH₃ is called ethylmethyl ether.

Ethers are much less soluble in water than alcohols of the same molecular weight because they cannot associate with one another by hydrogen bonding. They are, however, miscible with most common organic solvents and other organic compounds, because they can associate with other polar compounds containing hydrogens that are directly attached to oxygen, nitrogen, or sulfur. Hydrogen bonding is also responsible for the lower melting and boiling points of the low-molecular-weight ethers in comparison to the corresponding alcohols. Thus, as a result of its solubility properties, ethyl ether is routinely employed to extract a compound from an aqueous layer. Solubility and the lower boiling point are the main reasons for the use of ether in the purification of compounds by recrystallization.

Saturated alkyl ethers are inert toward practically all reagents at moderate temperatures, and as a result, they can be used as solvents in chemical manufacture and laboratory research. Thus, the Grignard reagent (probably one of the most versatile intermediates in organic synthesis) is always prepared using ethers (such as ethyl ether or tetrahydrofuran) as solvents.

Ethers are split by the alkali metals and by the halide salts of metalloids at higher temperatures. Hydrogen iodide (or bromide) also splits the ether to alkyl halides and alcohols at room temperature. Often, in complicated syntheses, an alcohol group is protected by conversion into an unreactive ether and is later regenerated when protection is no longer desired. Ultraviolet-light-catalyzed bromination and chlorination of ethers occur faster than with the corresponding hydrocarbons. Of great importance for their storage, however, is their reaction with atmospheric oxygen standing to form dangerous peroxides, which can explode when in high concentration at elevated temperatures.

Unsaturated ethers undergo the reactions associated with a double bond or an aromatic ring. Thus, vinyl ether, (CH₂=CH)₂O, undergoes polymerization upon exposure with acids, and phenyl ether, (C₆H₅)₂O, easily gets nitrated with nitric acid.

Simple symmetrical ethers are generally prepared industrially in the acid-catalyzed dehydration (water loss) of alcohols. The reaction should be temperature controlled; otherwise, dehydration of the alcohol leads to the formation of the corresponding alkene

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The Williamson synthesis, which has been instrumental historically in the developing of the radical theory, involves the reaction of the sodium salt of an alcohol (RONa) and alkyl halide (RX) to produce an unsymmetrical ether RONa + R'X → ROR' + NaX

Cyclic ethers are compounds in which the oxygen atom is part of the ring structure. Some examples are ethylene oxide (oxirane), 1,4-dioxane, furan, and tetrahydrofuran. They are excellent solvents but are much more reactive toward acids than the saturated alkyl ethers. Ethylene oxide is industrially produced by the silver-metal-catalyzed treatment of ethylene with oxygen gas at 300 degrees Celsius. Another method involves the oxidation of ethylene with performic or peracetic acid. Treatment of furfural, a compound isolated from oat hulls, with zinc catalysts produces furan, which yields tetrahydrofuran upon platinum- or palladium-catalyzed hydrogenation.

Crown ethers, such as 18-crown-6, are large-ring polyethers that act as important tools in the development of efficient syntheses. Their ability to complex with the potassium cation, for example, allows inorganic anions to dissolve readily in organic solvents, thereby reducing the reaction time and increasing the yields under mild conditions.

Applications

The introduction of anesthetics into the practice of surgery has probably done more to relieve the suffering of patients than any other single innovation. The mechanism of anesthesia is believed to involve the partitioning of the anesthetic between the aqueous and nonpolar body fluids. Thus, nonpolar body fluids that include membranes, such as nerve endings where nerve impulses are transmitted, swell upon exposure to the anesthetic, thereby preventing nerve transmission. High levels of anesthesia, however, may have fatal results because of the increasing risk of blocking the autonomous nerve transmissions to the heart, which leads to cardiac arrhythmia and death.

Its nonpolar character and the availability of ethyl ether established it as one of the most important anesthetics during the nineteenth century. Its low boiling point (34 to 36 degrees Celsius) gives it a high degree of volatility, which allows its easy introduction into the lungs and the blood stream via breathing. At the same time, the induction and recovery times are much shorter.

Since ethers are rather inert substances, the mode of action is limited to solubility into the membranes; any unwanted reactions are not possible. Similar, if not more rapid, results are observed with divinyl ether, (CH₂=CH)₂O, otherwise known as Vinethene, which can also be easily synthesized. Both compounds are excellent anesthetics because they act as depressants on the central nervous system while keeping the pulse rate, respiration rate, and blood pressure of the patient at, or slightly above, normal. Moreover, the danger of overdose is much less with ethyl ether than with other anesthetics.

There are several disadvantages that led to the gradual phasing out of ether in the operating room. First, ether's side effects include nausea, irritation of the respiratory passages, and the possibility of postoperative pneumonia. Of greater importance, however, are its large degree of flammability and the explosiveness of ether-air mixtures. Ethyl ether's vapors are 2.6 times denser than air, resulting in the accumulation of a heavy layer along a laboratory bench or floor. Consequently, its subsequent ignition, even from a remote source, is very likely to occur. Ethyl ether's flash point is very low (-45 degrees Celsius), as are the flash points of most popular ethers ,-dioxane, 12 degrees Celsius; tetrahydrofuran, -14 degrees Celsius). Good safety precaution, therefore, demands that a steam or hot-water bath be used for heating them. Moreover, all ethers' (especially vinyl ether's) ability to form peroxides upon long exposure to air on standing in an open container is greatly significant, since their presence can be particularly harmful to the patient.

The solubility properties and inertness of ethers are of great importance to research. Ethyl ether, for example, can be used as a recrystallizing solvent, and its volatility is important in its easy removal from the purified compound. An exceptionally good solvent, 1,4-dioxane can, itself, dissolve many macromolecules. As a result, it is often used by biologists to prepare paraffin-impregnated tissue sections. The ability of unsaturated and cyclic ethers to polymerize gives them great significance as row materials in industry. Thus, ethylene oxide is largely used in the preparation of nonionic emulsifying agents, plastics, plasticizers, synthetic textiles, and synthetic rubber. Similarly, vinyl ether is largely used in polymerization and copolymerization processes to yield a variety of synthetic polymers. A variety of cellulose, called ethyl cellulose, is an ether prepared via the Williamson synthesis.

Aromatic ethers (ethers in which at least one group is a benzene ring) occur frequently in nature and are often used in everyday life. Eugenol, for instance, is a compound found in oil of clove that acts as an antiseptic and an anesthetic, and is used as a pain reliever for toothaches. A mixture of eugenol and zinc oxide forms a plasterlike material that is used in dentistry to make impressions and temporary fillings. Many aromatic ethers display a great effect to the human nervous system. These include mephenesin (a skeletal muscle relaxant), reserpine (a tranquilizer), mescaline (a hallucinogen), morphine (a narcotic pain-killer), and quinine (a cardiac depressant). Finally, phenacetin, the active ingredient in pain relievers such as Tylenol, is also an aromatic ether. In all cases, though, the ether part does not serve as the main functional group of the compound.

Context

Ethyl ether's use as a solvent in organic synthesis was quickly recognized because of its inertness toward most chemicals. The ease with which it could be obtained from readily available materials such as ethyl alcohol and sulfuric acid, as well as its excellent solubility properties, made it historically one of the most popular solvents. As new techniques and synthetic variations were developed, more and more ethers (such as tetrahydrofuran, 1,4-dioxane and dibutyl ether) were being used both in commercial and in experimental applications, such as reaction and extraction procedures. The discovery of crown ethers in the 1970's gave a new dimension to the efficient and high-yield syntheses.

The anesthetic properties of ether were first noticed by Paracelsus in the sixteenth century and were rediscovered by Michael Faraday in 1818. The idea of using ethyl ether as an anesthetic was first conceived by Charles W. Jackson, a Boston chemist, who became unconscious from the inhalation of ether in 1842. In September, 1846, William G. T. Morton, a Boston dentist, successfully used ether as an anesthetic after consulting with Jackson. The term "anesthesia" (from the Greek word meaning "without sensitivity") was suggested to Morton by Oliver Wendell Holmes. Earlier in 1842, Crawford W. Long of Jefferson, Georgia, performed the first surgery using ether as an anesthetic, but the results were never published. The use of ethyl ether in major surgery was widely used for the first time by J. C. Warren at the Massachusetts General Hospital in 1847. Because of its drawbacks, such as flammability and the formation of peroxides, as well as the explosiveness of ether-air mixtures, the use of ether has been slowly phased out of the operating room in practically all Western countries.

Ethers, nevertheless, will always serve as good solvents because the formation of peroxides can be controlled by the presence of free-radical inhibitors such as hydroquinone or butylated hydroxytoluene (BHT), and precautions can be taken to avoid flames and spark formation, as well as distillations to dryness. The presence of peroxides can be tested easily with an aqueous potassium iodide extraction; the formation of a yellow tinge is indicative of their presence. Alternatively, a sample of the suspect solvent can be shaken with ferrous sulfate and the solution tested with thiocyanate ion. A deep-red coloration indicates the presence of peroxides. Peroxides can be eliminated by distillation using lithium aluminum hydride, or by passing the solvent through a column of activated alumina. Ethyl ether is still the active ingredient in the "starter fluid" used to start automotive engines on very cold mornings. The spark from the spark plug is enough to ignite the ether, which ignites the gasoline.

Principal terms:

ANESTHETIC: a chemical compound that causes loss of sensation in a specific part or in the whole body

CROWN ETHER: a cyclic polyether whose oxygens are coordinated to a centrally located metal atom; such compounds have strong complexing behavior and are used in high-yield organic syntheses

FLASH POINT: the minimum temperature at which a liquid or volatile solid has vapor pressure sufficient to form an ignitable mixture with the air that is in contact with the surface of the liquid or volatile solid

HYDROGEN BOND: an attractive force that occurs in polar compounds in which a hydrogen atom of one molecule is attracted to two unshared electrons of another; they are found in compounds containing strongly electronegative atoms such as nitrogen, oxygen, or sulfur

SATURATED COMPOUND: a compound in which all available valence bonds of an atom (such as carbon) are attached to other atoms

Bibliography

Allinger, Norman L., et al. ORGANIC CHEMISTRY. 2d ed. New York: Worth, 1976. A textbook for the organic chemistry student, with several sections on ethers. Section 4.11 gives the nomenclature, and 4.12 the properties of ethers, with a detailed account of the history of ether as an anesthetic.

Holum, John R. ELEMENTS OF GENERAL AND BIOLOGICAL CHEMISTRY. 6th ed. New York: Wiley, 1983. A good introductory book in general, organic, and biochemistry. Section 10.3 is a small section dedicated to ethers that also includes a paragraph on anesthetics.

Loudon, G. Marc. ORGANIC CHEMISTRY. Reading, Mass.: Addison-Wesley, 1984. A more advanced book in organic chemistry that discusses, mechanistically, the different organic families. Section 19.11 is a detailed report on the uses and safety hazards of ethers.

Matta, Michael S., and A. C. Wilbraham. GENERAL, ORGANIC, AND BIOLOGICAL CHEMISTRY. 2d ed. Menlo Park, Calif.: Benjamin/Cummings, 1986. An excellent introductory textbook, with several sections titled "Closer Look" in which applications of phenomena and laws in everyday events are highlighted. Section 12-7, "Ethers," discusses in detail the physical process of anesthesia.

Stacy, Gardner, W., and C. C. Wamser. ORGANIC CHEMISTRY: A BACKGROUND FOR THE LIFE SCIENCES. 2d ed. Dubuque, Iowa: Kendall/Hunt, 1985. A good introductory text. Sections 10.4 through 10.6 discuss ethers and epoxide formation. Includes an excellent "Highlight" section on anesthetics.

Reaction yielding tetrahydrofuran