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Ether

Ether, commonly known as or simply ether, is a colorless, volatile organic liquid with the (CH₃CH₂)₂O, consisting of an oxygen atom bonded to two ethyl groups, and it serves as the prototypical member of the ether class of compounds. It has a characteristic sweet, pungent odor and is highly flammable, with a of 34.6°C and a of 0.713 g/cm³ at 20°C, making it less dense than and slightly soluble in it (6.05 g/100 mL at 25°C). Historically, ether revolutionized as the first widely used , enabling pain-free following its public demonstration in , though its use has largely been supplanted by safer alternatives due to risks like flammability and potential for explosive formation. In chemistry, ethers are a broad class of compounds characterized by a general structure R–O–R', where R and R' are alkyl or aryl groups, and exemplifies this due to its simple symmetric structure (ethoxyethane in IUPAC ). These compounds are generally inert and nonpolar, which contributes to their utility as solvents in , extractions, and laboratory procedures, as they dissolve a wide range of nonpolar substances like fats, oils, waxes, and alkaloids without reacting with them. 's low reactivity stems from the absence of a readily abstractable hydrogen on the oxygen, unlike alcohols, allowing it to act as a stable medium for Grignard reagents and other moisture-sensitive syntheses. Synthesized first in 1540 by German botanist Valerius Cordus through the reaction of and , ether's anesthetic properties were explored recreationally in the early before its medical adoption. The landmark event occurred on October 16, 1846, when American dentist successfully administered it to a at , marking the birth of modern surgical and earning the day the moniker "Ether Day." Today, while no longer used clinically for in developed countries due to superior agents like and , remains valuable industrially as a for engines, a , and a in pharmaceutical production and . Safety concerns dominate ether's handling protocols, as it forms explosive peroxides upon exposure to air and , necessitating stabilizers like BHT in commercial grades and storage under inert atmospheres. Its vapors are heavier than air, posing risks in confined spaces, and can cause , , or , with an OSHA of 400 as an 8-hour time-weighted average. Despite these hazards, ether's legacy endures in scientific and historical contexts, symbolizing a pivotal advancement in and chemistry.

Structure and bonding

General structure

Ethers are organic compounds characterized by an oxygen atom bonded to two carbon atoms, forming the . The general formula for ethers is R-O-R', where R and R' are alkyl, aryl, or other carbon-based groups that may be identical or different. Symmetric ethers occur when R = R', such as in , while asymmetric or mixed ethers have distinct R and R' groups. The defining structural feature is the C-O-C linkage, as illustrated by the simplest ether, dimethyl ether (CH_3-O-CH_3), where two methyl groups flank the oxygen. Ethers are classified into acyclic (open-chain) and cyclic types based on whether the oxygen is incorporated into a ring./15:_Alcohols_and_Ethers/15.12:_Cyclic_Ethers) The smallest cyclic ether is oxirane, also known as , which forms a strained three-membered ./Ethers/Properties_of_Ethers/Epoxides) Structural isomerism arises in ethers when different carbon chain arrangements satisfy the same molecular formula. For C_4H_{10}O, representative ether isomers include diethyl ether (CH_3CH_2-O-CH_2CH_3, symmetric) and methyl isopropyl ether (CH_3-O-CH(CH_3)_2, asymmetric).

Bonding characteristics

In ethers, the central oxygen atom adopts sp³ hybridization, utilizing four equivalent sp³ hybrid orbitals: two to form sigma bonds with adjacent carbon atoms and two to accommodate lone pairs of electrons. This hybridization results in a tetrahedral electron geometry around oxygen. The C-O sigma bonds in ethers have a typical length of approximately 143 pm, shorter than the standard C-C bond length of about 154 pm due to the higher electronegativity of oxygen. The C-O-C bond angle measures 110–112°, slightly less than the ideal tetrahedral angle of 109.5° owing to repulsion between the oxygen lone pairs, a phenomenon similar to that observed in the H-O-H angle of water./Ethers/Properties_of_Ethers/Physical_Properties_of_Ether) Ethers exhibit polarity arising from the electronegative oxygen atom, which polarizes the C-O bonds and imparts a net ; for example, has a dipole moment of 1.15 D. This dipole is lower than that of comparable alcohols (e.g., 1.69 D for ) because ethers lack the highly polar O-H bond./Ethers/Properties_of_Ethers/Physical_Properties_of_Ether) The , denoted as R–O–R with two lone pairs on oxygen, demonstrates notable , particularly resistance to under neutral or basic conditions, in contrast to esters which readily undergo ./Ethers/Properties_of_Ethers/Chemical_Properties_of_Ethers) Compared to peroxides (R–O–O–R), ethers possess stronger C-O bonds with dissociation energies around 358 /, whereas the O-O bond in peroxides is significantly weaker at approximately 150 /, rendering peroxides far less and more prone to .

Unsaturated ethers

Unsaturated ethers feature an oxygen atom bonded to a carbon chain containing one or more multiple bonds, which introduces distinct effects compared to their saturated counterparts through partial conjugation. These compounds exhibit modified and reactivity due to the between the ether oxygen and the unsaturated system, often leading to enhanced at the multiple bond and altered . Vinyl ethers, a prominent subclass of ethers, possess the general structure CH₂=CH–OR, where the oxygen is directly attached to a sp²-hybridized carbon of the . The on oxygen donates electrons into the π system of the C=C bond via , resulting in a weakened C=C bond and increased reactivity toward electrophiles. A representative example is methyl vinyl ether (CH₂=CH–OCH₃), commonly used in reactions. The involves two key structures: the neutral form CH₂=CH–OR and the zwitterionic form ⁺CH₂–CH=OR⁻, imparting partial character to the C–O linkage and shortening the C–O bond to approximately 136 pm, compared to 143 pm in saturated ethers like . This resonance stabilization also contributes to the instability of ethers, particularly under acidic conditions, where protonation of the oxygen facilitates . For instance, ethers readily undergo acid-catalyzed to form poly( ethers), a process exploited in synthetic . Allyl ethers, with the structure CH₂=CH–CH₂–OR, position the double bond one carbon removed from the oxygen, resulting in less direct conjugation than in ethers. The allylic arrangement allows for some hyperconjugative interaction between the C=C π and the C–O σ , but without the strong π-donation seen in ethers, leading to relatively greater and different reactivity profiles, such as in Claisen rearrangements. Acetylenic ethers, represented by R–C≡C–OR, are comparatively rare owing to their inherent instability arising from the high strain and reactivity of the adjacent to the oxygen. An example is ethyl ethynyl ether (CH₃CH₂–O–C≡CH), which tends to decompose thermally or hydrolyze readily, limiting its practical applications despite potential use in chemistry.

Nomenclature

Systematic nomenclature

In the IUPAC system of nomenclature, ethers are primarily named using substitutive nomenclature, treating them as alkoxy or aryloxy derivatives of a parent hydride, such as an or arene. The preferred method identifies the longest continuous carbon chain as the parent , with the shorter alkyl chain expressed as an alkoxy . For example, the compound with the CH₃–O–CH₂CH₃ is named methoxy, where serves as the parent chain and methoxy as the , rather than ethoxymethane, to prioritize the longer chain. This approach, outlined in IUPAC recommendations P-63.2 and P-65.6.3.1, ensures systematic and unambiguous naming for unsymmetrical acyclic ethers. For symmetrical ethers, where both alkyl groups are identical, the IUPAC preferred name follows the same alkoxyalkane convention, using a single alkoxy prefix attached to the parent chain derived from one of the groups. For instance, CH₃CH₂–O–CH₂CH₃ is , as specified in rule P-63.2.1. Although functional class nomenclature (e.g., ) is retained for general use, substitutive names like ethoxyethane are designated as preferred IUPAC names (PINs) for indexing and unambiguous communication. Numbering in acyclic ethers begins from the end of the parent chain that yields the lowest for the alkoxy , in accordance with general rules for prefixes (P-14.4). For example, CH₃–O–CH₂CH₂CH₃ is named 1-methoxypropane, assigning the oxygen-attached carbon the position 1 to minimize the . If additional substituents are present, locants are chosen to give the lowest set of numbers overall, prioritizing the principal function if applicable. Cyclic ethers are named using retained heteromonocyclic names under the Hantzsch-Widman system, with oxygen indicated by the prefix 'oxa-' and specific suffixes based on ring size. The three-membered ring is oxirane (P-22.2.2.1), the five-membered ring is oxolane (P-22.2.2.1), and the six-membered ring is oxane (P-22.2.2.1); for example, the saturated five-membered cyclic ether is oxolane, a PIN also known commonly as tetrahydrofuran. In these names, the heteroatom (oxygen) is assigned position 1, and substituents receive the lowest possible locants (P-25.3.3.1.1). For mixed alkyl-aryl ethers, the parent structure is selected based on seniority rules, typically favoring the aromatic ring as the parent when it is senior to the aliphatic chain (P-44.1 and P-58.2). Thus, C₆H₅–O–CH₃ is named methoxybenzene (P-63.2.2), while longer alkyl chains may lead to aryloxyalkane names, such as phenoxyethane for C₆H₅–O–CH₂CH₃, ensuring the senior parent is chosen. These rules extend the alkoxyalkane method to hybrid systems, maintaining consistency in substitutive .

Common and trivial names

In , ethers are often referred to by trivial or common names, particularly for simple structures, which prioritize ease of use over strict systematic rules. The term "ether" itself originates from the word aithēr (αἰθήρ), denoting the clear upper sky or heavens, as described by philosophers like ; this name was later applied to volatile, colorless liquids due to their light, evaporative qualities. The first such compound, (Et₂O), was synthesized in 1540 by German botanist Valerius Cordus, who named it oleum dulce vitrioli ("sweet oil of "), but the modern name "ether" was coined in 1730 by August Sigmund Frobenius to reflect its airy volatility. This stuck for the archetypal ether, influencing common for similar compounds. Simple symmetrical ethers typically use the format of listing the twice followed by "ether." For instance, (Me₂O) refers to CH₃OCH₃, a gas used as a and , while (Et₂O), or simply "ether," is the well-known volatile and historical . Mixed ethers, containing different alkyl groups, are named by alphabetically ordering the substituents before "ether," such as ethyl methyl ether for CH₃OCH₂CH₃, which is more intuitive in everyday chemical discourse than the systematic "methoxyethane." Aromatic ethers also retain trivial names, including for C₆H₅OCH₃ (retained name for general ; PIN: methoxybenzene), one of several ether names retained by IUPAC for general use, such as and . Phenetole, denoting C₆H₅OCH₂CH₃ (ethoxybenzene), is a widely used trivial name in literature and industry despite not being formally retained by IUPAC. Another prominent example is methyl tert-butyl ether (MTBE), CH₃OC(CH₃)₃, a gasoline additive named for its alkyl components. These trivial names facilitate quick recognition but can lead to ambiguities in complex molecules with multiple functional groups or isomers, where systematic IUPAC is preferred to specify exact structures and positions unambiguously.

Polyethers and cyclic ethers

Polyethers are polymers containing multiple ether linkages in their backbone, and their nomenclature follows polymer chemistry conventions established by the International Union of Pure and Applied Chemistry (IUPAC). For instance, (PEG), with the repeating structure HO–(CH₂CH₂O)ₙ–H, is systematically named poly(oxyethylene) in structure-based nomenclature or poly(ethylene oxide) in source-based nomenclature. Crown ethers represent a subclass of cyclic polyethers designed for host-guest complexation, named using the "x-crown-y" convention where x denotes the total ring atoms and y the number of oxygen atoms; the systematic name employs nomenclature, such as 1,4,7,10,13,16-hexaoxacyclooctadecane for 18-crown-6. Cyclic ethers, which incorporate the ether oxygen within a ring, are named using heterocyclic , where the "oxa-" indicates oxygen in the cycle. Small rings have retained specific names: oxirane for the three-membered ring, for four-membered, oxolane for five-membered (as in ), and oxane for six-membered. Larger cyclic ethers adopt the general form "oxacycloalkane," specifying the ring size and oxygen position. In heterocyclic nomenclature, unsaturated cyclic ethers differ from their saturated counterparts; furan serves as the retained preferred IUPAC name for the five-membered unsaturated ring with two double bonds, while its fully saturated analog is (retained name) or systematically oxolane. Epoxides, a subset of three-membered cyclic ethers, can be named as oxiranes (e.g., oxirane for the parent ) or using the "epoxy-" prefix in substitutive nomenclature, such as 1,2-epoxyethane. Special cases include diethers like , a six-membered heterocyclic ring with two oxygens at positions 1 and 4, named as a retained IUPAC term or systematically as 1,4-dioxacyclohexane. This highlights the positions of multiple heteroatoms in the ring.

Physical properties

Thermodynamic properties

Ethers exhibit lower boiling points compared to alcohols of similar molecular weight, primarily due to the absence of intermolecular bonding in ethers. For instance, (molecular weight 74 g/mol) has a of 34.6 °C, whereas (also 74 g/mol) boils at 117.7 °C. /Chapters/Chapter_09:_Alcohols_Ethers_and_Epoxides/9.04:_Physical_Properties) Boiling points of ethers generally increase with molecular weight and chain length, reflecting stronger dispersion forces in longer alkyl chains. Melting points of ethers are typically low, facilitating their use as liquids at . Diethyl ether, for example, melts at -116.3 °C. These values are influenced by molecular symmetry and branching; symmetric ethers often display higher melting points than their asymmetric isomers of comparable molecular weight due to more efficient crystal packing. (-116 °C) contrasts with methyl propyl ether (-139 °C), both C4H10O isomers. Low-molecular-weight ethers possess high vapor pressure and volatility, attributes that render them effective as volatile solvents. , for instance, has a vapor pressure of 58.6 kPa at 20 °C. The heat of vaporization for is approximately 26.7 kJ/mol at its , significantly lower than that of (40.65 kJ/mol), underscoring the weaker intermolecular forces in ethers. /02:_The_Chemical_Foundation_of_Life/2.13:Water-_Heat_of_Vaporization)

Solubility and miscibility

Ethers possess a moderate arising from the electronegative oxygen atom in the C-O-C linkage, which enables dipole-dipole interactions with other polar molecules. This polarity renders ethers highly soluble in a wide range of solvents, such as hydrocarbons, alcohols, and chlorinated solvents. In , however, their solubility is more limited compared to alcohols, primarily because the ether oxygen can act as a acceptor but cannot donate bonds. For instance, exhibits a of 6.9 g/100 mL in at 20°C. Miscibility with follows a clear trend based on molecular weight and alkyl chain length: lower-molecular-weight ethers are more and even , while diminishes as chain length increases due to the growing hydrophobic character of the alkyl groups. , for example, is highly soluble at 46 g/L (4.6 g/100 mL) at 25°C, whereas remains moderately soluble, and longer-chain analogs like dipropyl ether show much lower of 0.25 g/100 mL at 25°C. Liquid ethers typically have densities in the range of 0.7–0.9 g/cm³, which is lower than that of (1.0 g/cm³), causing them to float on aqueous layers during extractions or spills. , a common example, has a density of 0.713 g/cm³ at 20°C. The constant of , measured at approximately 4.3 at 20°C, further underscores its moderate , facilitating its use as a in moderately polar reactions. From an environmental perspective, some ethers like methyl tert-butyl ether (MTBE) demonstrate high aqueous solubility combined with persistence, resisting natural degradation and leading to significant contamination issues identified in the 1990s from leaking fuel storage tanks.

Synthesis

Dehydration of alcohols

The dehydration of alcohols represents a classical method for synthesizing symmetrical ethers through . In this process, two molecules of a react in the presence of a strong acid, such as (H₂SO₄), at elevated temperatures around 140°C, leading to the elimination of water and formation of the ether linkage. The mechanism proceeds via an SN2 pathway for primary alcohols. Initially, the hydroxyl group of one alcohol molecule is protonated by the acid catalyst, converting it into a good (water). A second alcohol molecule then acts as a , attacking the carbon atom of the protonated alcohol in an SN2 fashion, displacing and forming the protonated ether. yields the neutral symmetrical ether. The overall reaction can be represented as: $2 \ce{ROH} \xrightarrow{\ce{H2SO4, 140^\circ C}} \ce{ROR + H2O} This method is particularly effective for primary alcohols, producing symmetrical dialkyl ethers in good yields under controlled conditions. However, the reaction's selectivity depends on the alcohol's structure. Primary alcohols favor ether formation due to the SN2 mechanism, but secondary and alcohols tend to undergo E1 elimination instead, yielding alkenes as major products rather than ethers, especially at higher temperatures. This limitation arises because intermediates form readily in secondary and tertiary cases, promoting β-elimination over . Additionally, the method is unsuitable for aryl alcohols like , as their requires harsher conditions and different catalysts, often leading to alternative products. Side reactions, such as further dehydration to olefins even with primary alcohols if overheating occurs, can reduce ether yields. A representative example is the synthesis of from : $2 \ce{CH3CH2OH} \xrightarrow{\ce{H2SO4, 140^\circ C}} \ce{(CH3CH2)2O + H2O} This reaction was first reported by Valerius Cordus in 1540 through of with , marking an early milestone in . Historically, acid-catalyzed dehydration served as the primary industrial route for production until the mid-20th century, when processes based on became more economical, often generating ether as a .

Alkene addition and epoxide opening

Ethers can be synthesized through the acid-catalyzed of to , a process that follows where the hydroxyl group from the alcohol attaches to the more substituted carbon of the . In this reaction, the alkene is protonated by the acid catalyst, such as (H₂SO₄), forming a intermediate on the more stable (more substituted) carbon; the alcohol then acts as a to attack this , yielding an ether after . For example, the addition of (CH₃OH) to propene (CH₂=CHCH₃) produces 2-methoxypropane ((CH₃)₂CHOCH₃) under these conditions, though rearrangements can occur if secondary or tertiary form. A prominent application of this is the production of methyl tert-butyl ether (MTBE), a high-octane additive, via the reaction of with isobutene ((CH₃)₂C=CH₂) over an acidic catalyst at 40–60°C and moderate pressure. The process achieves high selectivity (>95%) for MTBE ((CH₃)₃COCH₃) due to the stable tertiary intermediate, with the equilibrium driven forward by excess and continuous removal of water. This synthesis has been widely adopted since the 1970s for its efficiency in utilizing refinery byproducts like isobutene from . Another key route to ethers involves the ring-opening of epoxides with alcohols, which can proceed under either acid or base catalysis to form hydroxy ethers, such as glycol ethers. In basic conditions, the alkoxide ion (RO⁻) attacks the less substituted carbon of the epoxide in an SN2-like manner, leading to anti addition and regioselectivity favoring the primary position; for instance, ethylene oxide reacts with methanol in the presence of a base to yield 2-methoxyethanol (CH₃OCH₂CH₂OH). Under acidic conditions, the epoxide oxygen is protonated, making the ring more electrophilic and promoting attack at the more substituted carbon via an SN1-like mechanism involving a partial carbocation character, which enhances reactivity for unsymmetrical epoxides. These addition methods are particularly advantageous for preparing branched or cyclic ethers that are challenging to access via other routes, as the strained ring facilitates regioselective opening without requiring harsh conditions, and the approach allows direct incorporation of unsaturation-derived structures. For the general epoxide reaction under basic catalysis: \ce{RO^- + CH2-CH2O -> RO-CH2-CH2-O^-} followed by protonation to \ce{RO-CH2-CH2-OH}, or inverted regiochemistry in acid.

Williamson ether synthesis

The Williamson ether synthesis is a classic method for preparing ethers through an SN2 nucleophilic substitution reaction between an alkoxide ion and a primary alkyl halide. Developed by Alexander Williamson in 1850, this approach provided early evidence for the structural relationship between alcohols and ethers, demonstrating that ethers form via substitution of hydrogen in alcohols by alkyl groups. In his seminal work, Williamson reacted potassium ethoxide with ethyl iodide to yield diethyl ether, establishing the reaction as a foundational laboratory technique for ether synthesis. The mechanism involves the of an (ROH) with a strong base, such as or sodium metal, to generate the (RO⁻), which then attacks the carbon of a primary alkyl (R'X) in a backside , displacing the (X⁻) and forming the ether (ROR'). The general reaction is represented as: \text{RO}^- + \text{R'X} \rightarrow \text{ROR'} + \text{X}^- This process proceeds efficiently under SN2 conditions, favoring primary alkyl halides and unhindered alkoxides to minimize steric hindrance. For instance, sodium ethoxide reacts with methyl iodide to produce ethyl methyl ether and sodium iodide: \text{CH}_3\text{CH}_2\text{O}^- \text{Na}^+ + \text{CH}_3\text{I} \rightarrow \text{CH}_3\text{CH}_2\text{OCH}_3 + \text{NaI} The reaction is particularly suited for synthesizing unsymmetrical (mixed) ethers by selecting different alkyl groups for the alkoxide and halide components. Optimal conditions often employ the alcohol as solvent or polar aprotic solvents like dimethyl sulfoxide (DMSO) to enhance nucleophilicity and yields, with DMSO reported to increase ether formation to 95% in some cases compared to lower yields in protic media. Phase-transfer catalysis, using quaternary ammonium salts, facilitates the reaction in biphasic systems by transporting the alkoxide into the organic phase, improving efficiency for water-soluble alkoxides. For challenging substrates, such as those prone to elimination, silver oxide (Ag₂O) can assist by precipitating the halide, promoting the substitution under milder conditions. The scope of the Williamson synthesis is broad for primary alkyl halides, enabling the preparation of simple dialkyl ethers and some alkyl aryl ethers when the aryl component is activated, but it is limited with secondary or alkyl halides due to competing E2 elimination pathways that favor alkenes over substitution products. Aryl halides generally do not react without activation (e.g., nitro groups or to the ), as the C–X bond resists SN2 . These constraints make the method most reliable for unhindered primary systems, positioning it as a key tool in despite alternatives for more complex substrates.

Ullmann ether synthesis

The Ullmann ether synthesis is a classical method for preparing diaryl ethers through -catalyzed of with s. Developed by Ullmann and reported in 1905, it represents an early example of transition metal-mediated cross- in and has found industrial application, notably in the production of from and . The reaction proceeds under basic conditions, where the is deprotonated to form the phenoxide ion, which then reacts with the aryl halide in the presence of a . The mechanism of the Ullmann ether synthesis, often termed Ullmann condensation, begins with the formation of a phenoxide anion (ArO⁻) from the phenol (ArOH) and base. This nucleophile coordinates to a copper species, facilitating oxidative addition of the aryl halide (ArX) to generate a copper(III) intermediate, followed by reductive elimination to yield the diaryl ether (ArOAr). While this organometallic pathway is supported by computational and experimental studies, alternative radical mechanisms involving single-electron transfer have been proposed in some variants, though they remain debated. A simplified equation for the formation of diphenyl ether illustrates the overall transformation: \ce{ArO^- + Ar'X ->[Cu cat.] ArOAr' + X^-} Classical conditions for the Ullmann ether synthesis employ high temperatures, typically around 200°C, with copper powder or salts (e.g., CuI) as the catalyst and strong bases such as KOH or NaOH in polar solvents like nitrobenzene or pyridine. These harsh requirements stem from the need to activate the copper and promote the coupling, but they limit applicability to thermally stable substrates. The scope is centered on biaryl ethers, enabling the synthesis of symmetric and unsymmetric diaryl ethers from electron-deficient aryl halides and phenols, though yields can vary. Since the 1990s, the method has been refined through the introduction of ligands such as or , which stabilize species and allow catalytic turnover under milder conditions (80–110°C), expanding access to aryl alkyl ethers in some cases. Palladium-based variants, inspired by Buchwald-Hartwig protocols, further broaden the scope by accommodating electron-rich aryl halides and with high efficiency. These advancements have made the Ullmann ether synthesis a versatile tool in pharmaceutical and materials , contrasting with alkyl-focused methods like the . Despite improvements, the Ullmann ether synthesis retains limitations, including poor reactivity with alkyl halides due to competing elimination pathways and side reactions such as biaryl homocoupling or dehalogenation, which reduce selectivity. These challenges often necessitate excess reagents or optimized ligands to achieve practical yields.

Reactions

Cleavage reactions

Ethers are cleaved by strong acids such as hydrogen iodide (HI) or hydrogen bromide (HBr), which protonate the oxygen atom and facilitate nucleophilic attack by the halide ion, resulting in the formation of alkyl halides and alcohols. This reaction reverses ether synthesis by breaking the C-O bond, typically requiring concentrated acid and heating to 100–150°C for efficient progression. The mechanism begins with protonation of the ether oxygen, converting it into a good leaving group (an ). Subsequent halide attack occurs via an SN2 pathway for primary or methyl alkyl groups, where the less hindered carbon is targeted, or via SN1 for , allylic, or benzylic groups, involving formation at the more stable site. In the presence of excess , any initially formed is further converted to the corresponding alkyl . For symmetrical dialkyl ethers like , the reaction yields two equivalents of alkyl and water: (\ce{CH3CH2})_2\ce{O} + 2 \ce{HI} \rightarrow 2 \ce{CH3CH2I} + \ce{H2O} This outcome is observed under reflux conditions with concentrated HI. Cleavage selectivity depends on the ether structure: in unsymmetrical dialkyl ethers, the halide bonds to the less substituted alkyl group via SN2, leaving the more substituted as the alcohol. Aryl alkyl ethers, such as anisole (methoxybenzene), preferentially cleave at the alkyl-oxygen bond due to resonance stabilization of the aryl-oxygen linkage, producing phenols and alkyl halides (e.g., anisole + HI → phenol + CH₃I). Diaryl ethers resist cleavage under these conditions owing to the strength of both aryl-oxygen bonds. For selective demethylation of aryl methyl ethers without affecting other groups, (BBr₃) serves as an effective acid reagent. BBr₃ coordinates to the oxygen, promoting cleavage of the methyl-oxygen bond through a multi-step process involving charged intermediates and bromide ion transfer, ultimately yielding the free phenol and methyl bromide. A representative example is the conversion of to phenol using BBr₃ in at 0°C to . This method is particularly useful for removal in , as it operates under milder conditions than HI or HBr.

Peroxide formation and oxidation

Ethers, particularly dialkyl ethers such as , undergo in the presence of molecular oxygen to form through a free chain mechanism. The process begins with , where an alpha hydrogen atom adjacent to the oxygen is abstracted by a , generating an alpha-ether (RO-CH•-R'). This then reacts rapidly with O₂ to form a peroxy (RO-CH(O₂•)-R'), which propagates the chain by abstracting another alpha from a parent ether , yielding a hydroperoxy ether (RO-CH(OOH)-R') and regenerating the alpha-ether . Termination occurs via recombination, but the propagation steps lead to accumulation over time. This is promoted by exposure to air, light, and ions, often occurring slowly at during storage, with peroxides forming as low-concentration impurities that can become hazardous when the ether is concentrated, such as during or evaporation. Peroxides are unstable and can decompose explosively under heat, shock, friction, or light, posing severe risks in and settings; for instance, concentrated peroxides from have caused violent explosions, including historical laboratory incidents in the mid-20th century where old solvent bottles detonated during handling. In specifically, the primary product is 1-ethoxyethyl (CH₃CH₂OCH(OOH)CH₃), alongside minor cyclic peroxides like 3,6-diethyl-1,2,4,5-tetraoxacyclohexane formed via intramolecular reactions. To mitigate these risks, commercial ethers are typically supplied with stabilizers such as (BHT), an that interrupts the radical chain by scavenging peroxy radicals, thereby slowing formation without eliminating it entirely. Prevention strategies include storing ethers in airtight, glass containers in cool, dark places to minimize oxygen and light exposure, and discarding containers after 12 months or sooner if unopened stabilizers are absent; detection relies on commercial test strips that indicate levels via color change, with thresholds above 0.001 M warranting disposal or remediation. Beyond , ethers exhibit general inertness toward strong chemical oxidants like (KMnO₄), resisting oxidation under mild conditions due to the lack of easily abstractable hydrogens or reactive functional groups.

Lewis basicity and coordination

Ethers exhibit Lewis basicity through the lone pairs of electrons on the oxygen atom, which can donate to Lewis acids to form coordinate complexes. For instance, coordinates to (BF₃), forming the Et₂O·BF₃, where the oxygen acts as a σ-donor to the electron-deficient center. This interaction is characterized by the formation enthalpies of such adducts, which quantify the basicity of ethers relative to other donors; 's binding energy with BF₃ in is approximately -14.5 kcal/, reflecting moderate Lewis basicity. In coordination chemistry, particularly with organometallic compounds, ethers serve as ligands or solvents that stabilize reactive species via oxygen-metal dative bonds. (THF), a cyclic ether, is widely used in Grignard reactions, where it coordinates to the magnesium center of the (RMgX), forming solvated complexes such as (THF)₂RMgX; this coordination enhances the reagent's solubility and reactivity by donating electron density to the electrophilic magnesium. Similarly, simple dialkyl ethers form etherate complexes with salts; for example, forms a tetrameric cubane-like structure Li₄Cl₄₄ with , where each ion is coordinated to oxygen atoms from the ether ligands, providing fourfold coordination. Crown ethers, such as 18-crown-6, demonstrate enhanced chelation for alkali metals; the oxygen atoms in 18-crown-6 form a pseudocavity that selectively binds K⁺ s through multiple dative bonds, with a stability constant in exceeding 10⁶ M⁻¹. The bonding in these ether-metal complexes involves a dative ( from the oxygen to the metal or , but ethers generally form weaker interactions compared to amines due to oxygen's higher , which reduces the availability of the ; for example, the Lewis basicity of (Gutmann donor number ~19) is significantly lower than that of (~46). These coordination properties find applications in stabilizing reactive intermediates, such as carbocations, where ether oxygen can solvate the positive charge to prevent aggregation or decomposition in synthetic media. Additionally, crown ethers enable selective liquid-liquid extraction of alkali metals; 18-crown-6 facilitates the transfer of K⁺ from aqueous to organic phases with high selectivity (separation factor >100 over Na⁺), useful in separation processes.

Alpha-carbon functionalization

Alpha-halogenation of ethers occurs under acid-catalyzed conditions using halogens such as or , targeting the hydrogens on the carbon adjacent to the oxygen atom. This reaction exploits the mild acidity of these alpha-hydrogens, facilitated by the electron-withdrawing effect of the oxygen. A representative example is the reaction of with at low temperatures, yielding alpha-chloro diethyl ether (CH3CHCl-O-CH2CH3) and, with excess halogen, the alpha,alpha'-dichloro derivative (CH3CHCl-O-CHClCH3). Similar behavior is observed with , producing alpha-bromo ethers like (1-bromoethyl) ethyl ether (CH3CH2OCHBrCH3) in the presence of acid, resembling formation in its . The proceeds via an enol-like formed upon of the ether oxygen, which increases the acidity of the alpha-hydrogen and allows to generate a resonance-stabilized species where the oxygen conjugates with the adjacent . This then reacts with the , delivering the halogen to the alpha-carbon while regenerating the proton. The process is typically limited to monosubstitution per alpha position because the introduced halogen deactivates the remaining hydrogens through inductive withdrawal, preventing polyhalogenation under mild conditions. Deprotonation of alpha-hydrogens in ethers requires strong bases due to their relatively high pKa values (approximately 43-45 in DMSO for simple dialkyl ethers). Alkyllithiums such as n-butyllithium (n-BuLi) are commonly employed for this purpose, generating alpha-lithiated ethers that serve as nucleophiles for subsequent alkylation or formation of enol ethers. For instance, treatment of alkyl benzyl ethers with n-BuLi leads to selective deprotonation at the benzylic alpha position, forming stable organolithium species that can be trapped with alkyl halides or carbonyl electrophiles to introduce new substituents. In cases where the alpha position is activated by additional groups, bases like lithium diisopropylamide (LDA) can also effect deprotonation, enabling analogous functionalizations. A notable application of alpha-carbon reactivity in functionalized ethers is the , particularly in allyl vinyl ethers, where the system undergoes a [3,3]-sigmatropic shift to functionalize the alpha-carbon with an , ultimately yielding γ,δ-unsaturated carbonyl compounds after tautomerization. This highlights the utility of enol ether precursors in carbon-carbon bond formation at the alpha position. The seminal work on this transformation established its scope for both aromatic and aliphatic systems, influencing modern synthetic strategies. Alpha-lithiation with n-BuLi extends to a broader range of ethers, including aryl alkyl ethers, allowing for directed at the alpha-carbon. These lithiated intermediates react efficiently with electrophiles like alkyl halides, aldehydes, or ketones, providing access to alpha-substituted ethers with high . This method is particularly valuable in , where the organolithium acts as a synthetic equivalent of an despite the absence of a .

Important ethers

Dialkyl ethers

Dialkyl ethers are organic compounds featuring an oxygen atom bonded to two alkyl groups, typically acyclic and without aromatic components, making them valuable for various industrial and practical applications due to their low reactivity, , and properties. These ethers, such as symmetric ones like and or asymmetric ones like methyl tert-butyl ether (MTBE), serve primarily as solvents, fuels, and additives, with their physical properties—such as boiling points and densities—influencing their utility in extractions, reaction media, and propellants. Diethyl ether, with the formula (CH_3CH_2)_2O, holds historical significance as the first widely used surgical , demonstrated publicly on October 16, 1846, by dentist during a procedure at , revolutionizing in . Today, it functions mainly as an organic solvent in laboratories and industry for extractions and as a reaction medium, prized for its ability to dissolve a broad range of non-polar substances. Its physical properties include a of 0.714 g/mL at 20°C and a of 34.6°C, contributing to its ease of handling and recovery in processes. Dimethyl ether, CH_3OCH_3, is a gaseous dialkyl ether at with a of -24°C, allowing it to be stored and transported as a under moderate pressure. It serves as an eco-friendly aerosol propellant in like hairsprays and deodorants, replacing more harmful chlorofluorocarbons due to its low environmental impact and high solvency for polymers. Additionally, it acts as a clean-burning , including in blends and as a substitute, offering reduced emissions of and nitrogen oxides compared to traditional fuels. Methyl tert-butyl ether (MTBE), (CH_3)_3COCH_3, exemplifies an asymmetric branched dialkyl ether introduced as a booster in 1979 to enhance engine performance and reduce emissions under the U.S. Clean Air Act. Its high in —4.2 g/100 mL at 20°C—enabled easy blending but also led to environmental concerns, as leaks from underground storage tanks caused widespread , prompting a nationwide phaseout in the U.S. starting in 2006. Despite this, it illustrates the role of dialkyl ethers in energy applications before regulatory shifts favored alternatives like . Branched dialkyl ethers like isopropyl methyl ether, also known as 2-methoxypropane (CH_3OCH(CH_3)_2), demonstrate structural variety and find niche uses, such as solvents in and processes, including in the of perfumes where their aids in blending oils. Overall, dialkyl ethers excel as solvents for separating compounds in extractions—such as in pharmaceutical purification—and as inert media for chemical reactions, leveraging their non-polar nature and stability.

Aryl ethers

Aryl ethers are compounds featuring an oxygen atom bonded to at least one aromatic (aryl) group, conferring greater thermal and chemical stability compared to their dialkyl counterparts due to the resonance stabilization of the aromatic ring. These ethers find applications in solvents, fragrances, preservatives, polymers, and agrochemicals, leveraging their moderate volatility, solubility properties, and resistance to oxidation. A representative aryl alkyl ether is anisole (C₆H₅OCH₃), a colorless liquid with a boiling point of 154 °C and an aromatic odor, which is insoluble in water but miscible with organic solvents. It serves as a solvent in organic synthesis and a key ingredient in perfumes and flavorings owing to its pleasant scent and stability. Anisole is commonly prepared via the Williamson ether synthesis from phenol and methyl halide under basic conditions. Diphenyl ether ((C₆H₅)₂O), a diaryl ether, exhibits a high of 259 °C, making it suitable for applications requiring thermal resilience, such as fluids and components in formulations. Its derivatives, including polybrominated variants, are incorporated as flame retardants in plastics and textiles to enhance . Industrial of diphenyl ether typically employs the Ullmann ether synthesis involving and sodium phenoxide. Phenoxyethanol (C₆H₅OCH₂CH₂OH), another aryl alkyl ether, is a with a rose-like , valued for its broad-spectrum properties. Introduced as a cosmetic in the , it prevents microbial growth in like lotions and shampoos at concentrations of 0.5–1%, ensuring product stability without significant irritation at approved levels. In , polyphenylene oxide (), featuring repeating aryl ether linkages, represents a high-performance with excellent dimensional stability, low moisture absorption, and heat resistance up to 150 °C. Commercialized in the 1960s by as , a blend of PPO and , it is used in automotive parts, electrical housings, and plumbing components for its mechanical strength and flame-retardant characteristics. Aryl ethers also play a critical role in agrochemicals, exemplified by phenoxy herbicides such as (2,4-D), which contains an aryl ether moiety linking a chlorinated phenyl ring to an acetic acid chain. Discovered and commercialized in the , 2,4-D revolutionized in by selectively targeting broadleaf through hormonal disruption, enabling efficient crop management worldwide.

Cyclic and polyethers

Cyclic ethers are characterized by their ring structures, which confer unique stability and reactivity compared to acyclic counterparts, enabling specialized applications in solvents, intermediates, and host-guest chemistry. (THF), a five-membered cyclic ether with the formula (CH₂)₄O, boils at 66 °C and serves as a ubiquitous , particularly for organometallic reactions such as Grignard and reagent manipulations due to its ability to solvate cations while remaining inert under conditions. Global annual production of THF reaches approximately 200,000 tonnes, primarily via dehydration of , supporting its role in precursor synthesis and pharmaceutical processing. Epoxides, three-membered cyclic ethers exemplified by (C₂H₄O), exhibit high that renders them highly reactive toward nucleophilic ring-opening, making them key intermediates in the production of polyesters, ethylene glycols for , and . 's global production exceeded 25 million tons annually in the early , derived mainly from silver-catalyzed oxidation of , underscoring its industrial scale despite handling hazards from its flammability and toxicity. 1,4-Dioxane, a six-membered cyclic diether (C₄H₈O₂), functions as a versatile for resins, dyes, and extractions owing to its high of 101 °C and with water and organics, though its use has declined due to classification as a probable by the U.S. Agency in the 1980s based on animal studies showing liver and nasal tumors. Crown ethers represent a class of larger macrocyclic polyethers designed for selective , with 12-crown-4 (a 12-membered ring with four oxygen atoms) exemplifying their utility in coordinating small cations like or sodium through cavity encapsulation. Discovered by Charles J. Pedersen in 1967, who received the in 1987 for this work, crown ethers facilitate phase-transfer by solubilizing inorganic salts in organic media and enable ion sensing in analytical devices via colorimetric or fluorescent responses to metal ion complexation. Polyethers extend the cyclic motif into linear or branched polymers, with (PEG) being a prominent example of water-soluble chains (HO(CH₂CH₂O)ₙH) typically spanning molecular weights of 200 to 20,000 Da, used in pharmaceuticals as excipients for , lubricants in ointments, and osmotic laxatives like MiraLAX to relieve by drawing into the intestines. (PPG), the analogous polymer from (HO(CH₂CH(CH₃)O)ₙH), finds application in flexible foams for cushioning in furniture and automotive seating, leveraging its low viscosity and hydrophobicity to enhance foam elasticity and durability during curing.