1,2-Dimethoxyethane, commonly abbreviated as DME and also known as ethylene glycol dimethyl ether or monoglyme, is an organic diether compound with the chemical formulaC₄H₁₀O₂ and a molecular weight of 90.12 g/mol.[1][2] It exists as a colorless, volatile liquid with a sharp, ether-like odor, exhibiting a density of 0.868 g/cm³ at 20°C, which makes it less dense than water.[1] The compound has a boiling point of 82–85°C, a melting point of -58°C, and a low flash point of -2°C, rendering it highly flammable with lower and upper explosive limits of 1.6% and 10.4% in air, respectively.[1] DME is fully miscible with water, as well as with organic solvents such as ethanol, chloroform, ether, acetone, and benzene, and it serves as a polar aprotic solvent capable of forming coordination complexes with metal ions.[1]In chemical applications, 1,2-dimethoxyethane is prized for its solvating properties in organometallic chemistry, where it stabilizes reactive intermediates and facilitates reactions such as the N-alkylation of indoles, palladium-catalyzed cross-couplings, and the synthesis of cyclic amines from amino alcohols.[3] It plays a critical role as an electrolyte solvent in lithium-ion and lithium-metal batteries, enabling high ionic conductivity, low interfacial resistance, and improved compatibility with lithium anodes due to its ether structure.[4][5] Additionally, DME is utilized as a medium for separating neutral sugars in analytical chemistry.[6]Regarding safety, 1,2-dimethoxyethane poses hazards as a highly flammable liquid that can form explosive peroxides when exposed to air over time, necessitating storage under inert atmospheres or with stabilizers.[1] It is mildly toxic upon ingestion or inhalation, with an oral LD50 in rats of 5,500 mg/kg, but it acts as a severe irritant to the skin, eyes, and respiratory tract.[1] Furthermore, DME is classified as a reproductive toxin, potentially interfering with fertility and embryonic development, which has led to regulatory restrictions in some industrial uses.[1] Proper handling involves the use of ventilation, protective gloves, and eye protection to mitigate exposure risks.[1]
Chemical Identity and Structure
Nomenclature and Isomers
The systematic IUPAC name for dimethoxyethane is 1,2-dimethoxyethane, reflecting its structure as a derivative of ethane with methoxy groups on adjacent carbons.[1]Common names include glyme, DME (an abbreviation for dimethoxyethane), monoglyme, ethylene glycol dimethyl ether, and dimethyl cellosolve, with "glyme" and "monoglyme" emphasizing its role as the simplest member of a solvent family.[1][7]As the first member (n=1) of the glyme series—polyethylene glycol dimethyl ethers with the general formula CH₃O(CH₂CH₂O)ₙCH₃—1,2-dimethoxyethane serves as monoglyme, distinguishing it from higher homologs like diglyme (n=2) and triglyme (n=3), which feature longer oligoether chains for enhanced solvating properties.[7]1,2-Dimethoxyethane has no significant structural isomers that share its utility as an aprotic solvent, though the positional isomer 1,1-dimethoxyethane (also known as acetaldehyde dimethyl acetal) exists with the formula CH₃CH(OCH₃)₂; this compound is chemically distinct, functioning as an acetal rather than a diether, and is less stable due to its tendency to form peroxides upon exposure to oxygen.[1][8]The nomenclature for 1,2-dimethoxyethane and the broader glyme series evolved in mid-20th-century chemical literature, with widespread adoption of terms like "glyme" beginning in the 1960s to describe these polyether solvents in organic synthesis and electrochemistry applications.[7]
Molecular Structure
Dimethoxyethane, also known as 1,2-dimethoxyethane, has the molecular formula C₄H₁₀O₂ and the structural formula CH₃OCH₂CH₂OCH₃.[1]The atomic arrangement consists of a central ethylene bridge flanked by two methoxy groups, forming a symmetric diether. Bond lengths are characteristic of aliphatic ethers, with C-O bonds measuring approximately 1.42 Å and the intervening C-C bond about 1.52 Å. Relevant bond angles include ~112° for the C-O-C at each ether oxygen and ~109.5° for the O-C-C angles, as determined from ab initiomolecular orbital calculations at the 6-31G* level.[9]In terms of conformation, the molecule adopts a preferred gauche arrangement for the O-C-C-O dihedral angle in the gas phase and solution, driven by the gauche effect arising from favorable interactions between the lone pairs on the adjacent oxygen atoms. Computational studies identify the TGG' rotamer (trans orientation of the methyl groups relative to the central C-C bond, with gauche for each O-C-C torsion) as the global energy minimum, with gauche-gauche forms being ~0.5-1.0 kcal/mol lower in energy than anti counterparts.[9][10]The electronic structure features a significant dipole moment of 1.71 D, attributable to the alignment of the polar C-O bonds in the favored gauche conformation. The ether oxygens exhibit modest basicity, with the pKa of the conjugate acid (protonated on oxygen) approximately -3.6, analogous to that of diethyl ether and reflecting the weak nucleophilicity of dialkyl ether lone pairs.[11][12]
Physical and Thermodynamic Properties
Appearance and Phase Behavior
Dimethoxyethane appears as a colorless, low-viscosityliquid at room temperature, with a viscosity of 1.1 mPa·s at 20 °C and a sharp etherealodor.[1][13]Under standard conditions, it exhibits a melting point of -58 °C and a boiling point of 85 °C at 1 atm, allowing it to remain in the liquid phase across a broad temperature range relevant to laboratory and industrial applications.[1] Its density is 0.868 g/cm³ at 20 °C, which is lower than that of water, contributing to its utility in solvent mixtures.[14]The vapor pressure of dimethoxyethane is approximately 48 mmHg at 20 °C, indicating moderate volatility that facilitates its handling as a solvent while requiring precautions against evaporation and flammability.[1] In terms of solubility, it is fully miscible with water, alcohols, and most organic solvents such as ethers and hydrocarbons, owing to its polar ether groups; its octanol-water partition coefficient (log P) is -0.21, underscoring its hydrophilic character.[1][15]
Spectroscopic Properties
Dimethoxyethane, also known as 1,2-dimethoxyethane, is characterized by nuclear magnetic resonance (NMR) spectroscopy, which provides detailed insights into its molecular structure and proton environments. In the ¹H NMR spectrum recorded in CDCl₃ at 400 MHz, two characteristic singlets are observed: one at approximately 3.39 ppm corresponding to the six equivalent methyl protons (OCH₃) and another at 3.55 ppm for the four methylene protons (OCH₂CH₂O).[16] The ¹³C NMR spectrum reveals two signals due to symmetry: around 59 ppm for the methyl carbons (O-CH₃) and 71 ppm for the methylene carbons (O-CH₂).[17] These shifts confirm the ether linkages and the absence of additional functional groups, with the methylene carbons deshielded relative to the methyls due to their position between two oxygen atoms.Infrared (IR) spectroscopy highlights the vibrational modes associated with dimethoxyethane's ether functionalities. The spectrum exhibits characteristic C-O stretching bands in the 1100-1150 cm⁻¹ region, typical for aliphatic ethers, and C-H stretching absorptions from the alkyl groups at 2800-3000 cm⁻¹.[18] These features are prominent in both gas and liquid phase measurements, aiding in purity assessment and structural confirmation without interference from other moieties.Mass spectrometry further supports the molecular identity, with the molecular ion peak at m/z 90 (M⁺, C₄H₁₀O₂) observed at low intensity (about 6%), and the base peak at m/z 45 attributed to the stable fragment CH₃OCH₂⁺ formed via alpha-cleavage.[19] This fragmentation pattern is consistent with ether compounds, where cleavage adjacent to oxygen yields prominent alkoxyalkyl ions.Ultraviolet-visible (UV-Vis) spectroscopy indicates that dimethoxyethane is largely transparent in the near-UV region, with no significant absorption bands above 220 nm, reflecting the absence of conjugated systems or chromophores.[20] The absorbance at 220 nm is approximately 1.00 (path length 1 cm), decreasing rapidly to 0.03 at 300 nm, making it suitable for applications requiring optical clarity.Thermodynamic properties relevant to spectroscopic studies include a heat of vaporization of approximately 32 kJ/mol near the boiling point and a liquid heat capacity of about 190 J/mol·K at 298 K, which influence sample preparation and phase-specific measurements.[2][21]
Synthesis and Production
Laboratory Synthesis
Dimethoxyethane is commonly prepared in laboratory settings via the Williamson ether synthesis, involving the reaction of ethylene glycol with methyl iodide in the presence of a strong base such as sodium hydride (NaH). This SN2 process deprotonates the diol to form the dialkoxide, which then displaces iodide from two equivalents of methyl iodide to form the diether. The reaction is typically conducted in an inert atmosphere to prevent side reactions, with the base added portionwise to control exothermicity.\ce{HO-CH2-CH2-OH + 2 NaH -> Na+ ^-O-CH2-CH2-O^- Na+ + 2 H2}\ce{Na+ ^-O-CH2-CH2-O^- Na+ + 2 CH3I -> CH3O-CH2-CH2-OCH3 + 2 NaI}Overall yields of approximately 80% can be obtained after workup, though optimization depends on reaction conditions like temperature and solvent choice (e.g., DMF or THF).[22]An alternative laboratory method, though less common, involves the catalytic hydrogenation of dimethoxymethane derivatives, such as methylglycol formal, using oxide-based catalysts under elevated pressure and temperature. This hydrogenolysis cleaves C-O bonds selectively to yield dimethoxyethane, offering a route from formaldehyde-derived precursors.[23]Following synthesis, dimethoxyethane is purified by fractional distillation under reduced pressure (boiling point ~85 °C at atmospheric pressure), which effectively separates it from lower-boiling impurities like methanol or unreacted methyl iodide. This step ensures high purity (>99%) suitable for use as a solvent in sensitive reactions.[24]
Industrial Production
Dimethoxyethane is produced industrially on a commercial scale primarily through the continuous reaction of ethylene glycol with methanol in the presence of an acid catalyst, such as a polyperfluorosulfonic acid resin, followed by purification via distillation.[25] The process operates under controlled temperature and pressure conditions to favor the etherification, yielding the desired product with high selectivity.[26]The key reaction is represented by the following equation:\ce{HO-CH2-CH2-OH + 2 CH3OH ->[H+] CH3O-CH2-CH2-OCH3 + 2 H2O}Water, the main byproduct, is efficiently removed through azeotropic distillation, often using entrainers like benzene or toluene, to shift the equilibrium toward product formation and minimize side reactions.[27]Global production of dimethoxyethane reaches thousands of tons annually, with the majority of capacity concentrated in Asia to meet demand in solvent and chemical intermediate markets.[28]Post-2020 developments have focused on bio-based routes incorporating renewable methanol, sourced from biomassgasification or CO2 hydrogenation with green hydrogen, to lower the overall carbon footprint of the manufacturing process.[29]
Chemical Reactivity
Stability and Reactivity
Dimethoxyethane, also known as 1,2-dimethoxyethane (DME), demonstrates good thermal stability under normal laboratory and industrial conditions, remaining intact up to temperatures near its boiling point of 85 °C. However, at elevated temperatures exceeding its autoignition point of approximately 202 °C, it undergoes pyrolysis, primarily through C–C bond fission and hydrogen abstraction mechanisms, yielding key intermediates such as methyl vinyl ether and methoxy acetaldehyde, which further decompose into C₂ oxygenated species like acetaldehyde and ethenol, as well as unsaturated hydrocarbons including ethylene and acetylene.[30][31][32]In terms of hydrolytic stability, DME is resistant to hydrolysis under mild acidic or basic conditions, making it suitable as a solvent in aqueous environments at neutral pH. It exhibits stability toward dilute acids and bases, but under strong acidic conditions, such as treatment with concentrated hydrogen iodide (HI), the ether linkages cleave via an SN2 mechanism on the methyl groups, ultimately producing ethylene glycol and methyl iodide.[33][34]Oxidative stability of DME is limited due to its susceptibility to auto-oxidation in the presence of air and light, leading to the formation of peroxides over time, particularly when stored for extended periods or in contact with metals that can catalyze the process. These peroxides can accumulate and pose explosion risks during concentration or distillation, as evidenced by incidents involving aged samples.[1][35][36]DME has a low flash point of -2 °C, indicating high flammability, and an autoignition temperature of 202 °C, beyond which spontaneous combustion can occur in air.[1][37][32]As an aprotic solvent, DME is neutral with a pH of approximately 7 in aqueous solution, reflecting its lack of acidic or basic protons. It readily coordinates to Lewis acids through its oxygen lone pairs without undergoing protonation, serving as a bidentate ligand in coordination complexes, such as with transition metals like niobium or iron, enhancing solubility and stability in organometallic reactions.[34][38]
Reactions with Organometallics
Dimethoxyethane (DME), with its two ether oxygen atoms separated by an ethylene bridge, functions as a bidentate ligand in organometallic chemistry, coordinating to metal cations such as Li⁺ and Mg²⁺ to form stable five-membered chelate rings. This coordination mode involves both oxygen atoms binding to the metal center, creating a cyclic structure that enhances the solubility and stability of the resulting complexes. For instance, in gas-phase studies, the Mg⁺(DME) complex adopts a bidentate geometry where the metal ion bridges the O–C–C–O chain, forming a five-membered ring that is thermodynamically favored due to the optimal bite angle of approximately 85–90°. Similar bidentate chelation is observed with Li⁺ in solution, as evidenced by structural analyses of solvated lithium organometallics, where DME disrupts higher-order aggregates into lower-coordinate species.[39][40]A prominent example of DME's role in stabilizing organometallics is its interaction with Grignard reagents (RMgBr), where it solvates the magnesium center to form octahedral complexes such as [RMgBr(DME)₂]. This solvation occurs via the reaction RMgBr + 2 DME → [RMgBr(DME)₂], with the two DME ligands occupying equatorial positions around the Mg atom, providing steric protection and preventing Schlenk-type equilibria that could lead to precipitation. Such complexes, including those with thienyl or vinyl substituents, have been isolated as chiral cis-octahedral species, demonstrating DME's ability to maintain the integrity of the Grignard reagent in ethereal media.[41][42]In organolithium chemistry, DME solvates Li⁺ ions to break down oligomeric aggregates, thereby increasing the nucleophilicity and reactivity of the organolithium species. This effect is particularly pronounced in systems like lithium phenolates, where DME promotes the formation of monomeric or dimeric solvates over higher aggregates, as determined by concentration-dependent ⁶Li NMR studies showing symmetric solvation environments. By coordinating bidentately to Li⁺, DME reduces ion pairing and enhances the availability of the carbanionic center for reactions.[43][40]DME exhibits generally inert redox behavior toward most organometallics under typical conditions, maintaining its structural integrity during coordination. Spectroscopic evidence for complexation includes ¹H NMR shifts, where the CH₂ protons of DME are deshielded by 0.2–0.5 ppm upon binding to metal centers, reflecting the electron withdrawal from the oxygen atoms in the chelate ring; this is observed in lanthanide-shifted spectra and confirmed in Mg and Li complexes.[44][39]
Applications
Solvent Uses
Dimethoxyethane (DME), with a dielectric constant of approximately 7.2 at 25°C, serves as a polar aprotic solvent capable of effectively solvating polar molecules and ions without donating protons, making it suitable for reactions requiring strong nucleophilic activity.[45] This property allows DME to stabilize cations while minimally coordinating anions, enhancing the reactivity of nucleophiles in polar environments.[45]In lithium-ion battery electrolytes, DME is valued for its low viscosity of 0.46 cP at 25°C, which facilitates high ionic conductivity and rapid lithium-ion transport, alongside a wide electrochemical stability window that supports stable operation in high-energy-density systems.[46] Its use as a co-solvent in ether-based electrolytes has enabled advancements in fast-charging capabilities and cycling stability for lithium-metal batteries, often in combinations with salts like LiTFSI.[47]As a solvent in organic synthesis, DME excels in facilitating SN2 reactions by dissolving ionic salts such as sodium iodide without proton donation, thereby promoting clean nucleophilic substitutions on alkyl halides.[45] Its aprotic nature prevents hydrogen bonding with nucleophiles, increasing their effective concentration and reaction rates compared to protic solvents. In pharmaceutical purification processes, DME acts as an extraction solvent, selectively dissolving organic compounds while adhering to regulatory limits as a Class 2 residual solvent, aiding in the isolation of active pharmaceutical ingredients.[48][3]Historically, since the 1970s, DME has been employed in polymerization reactions, supporting early developments in polymer processing and synthesis.[49] Its solvating power for oligo- and polysaccharides has also contributed to advancements in polymer chemistry applications.[1] DME is used in the production of polysiloxanes (silicones) and as a solvent for the separation of neutral sugars, such as in high-performance liquid chromatography of 2,4-dinitrophenyl derivatives.[1][6]
Ligand and Chelating Agent Roles
Dimethoxyethane (DME), with its two ether oxygen atoms, functions as a bidentate ligand capable of forming five-membered chelate rings with metal centers, thereby stabilizing organometallic complexes in synthetic and catalytic applications. This chelating property arises from the cooperative binding of both oxygen donors, which enhances complex stability compared to monodentate ethers through the chelate effect.[50]In organometallic chemistry, DME commonly coordinates to early transition metals such as titanium and zirconium, forming well-defined complexes like TiCl₄(DME) that serve as precursors for Ziegler-Natta-type polymerization catalysts. For instance, TiCl₄(DME) is employed in the synthesis of constrained-geometry titanium complexes, which exhibit activity in olefin polymerization by stabilizing the metal center during alkyl chain growth and insertion steps. Similar [Zr(DME)_n] species are utilized in the preparation of zirconocene-based catalysts for ethylene and propylene polymerization, where DME's chelation prevents premature decomposition and supports activator interactions like those with methylaluminoxane.[51]DME also plays a role in stabilizing transition metal precatalysts for cross-coupling reactions. In nickel-catalyzed processes, NiBr₂(DME) acts as a convenient source of the metal, where the labile DME ligands are displaced by chiral bis(oxazoline) ligands to form active species for enantioselective C-C bond formation. For example, in asymmetric Kumada cross-couplings of racemic α-bromoketones with aryl Grignard reagents, the DME-coordinated nickel precatalyst enables high enantioselectivities (up to 97% ee) by facilitating stereoconvergent mechanisms involving radical intermediates. This coordination stabilizes low-valent nickel species, promoting efficient transmetalation and reductive elimination while suppressing side reactions.[52]In palladium catalysis, DME similarly coordinates to Pd(II) centers, as seen in complexes like PdCl₂(DME), which are applied in cross-coupling protocols such as the Suzuki-Miyaura reaction; here, DME helps maintain solubility and prevents aggregation, contributing to consistent reaction outcomes. Recent developments in the 2020s have extended DME's utility to enantioselective nickel-catalyzed couplings, such as the reductive cross-coupling of acid chlorides with alkyl precursors, where NiBr₂(DME) with chiral ligands delivers ketones with excellent enantiocontrol (up to 99% ee).[53]Compared to tetrahydrofuran (THF), DME offers stronger chelation as a bidentate ligand versus THF's monodentate binding, leading to more robust stabilization of metal complexes, though DME's higher boiling point (85 °C versus 66 °C for THF) can restrict its application in thermally sensitive asymmetric syntheses requiring precise temperature control. In such chiral catalytic systems, DME's coordination to metal centers enhances enantioselectivity by enforcing a defined coordination sphere that favors one enantiotopic face during substrate approach.[50]
Safety, Toxicity, and Environmental Considerations
Health Hazards
Dimethoxyethane exhibits low acute oral toxicity, with an LD50 value of approximately 5.4 g/kg in rats.[54] Direct contact with the skin or eyes can cause irritation, including redness, pain, and potential dermatitis with repeated exposure.Inhalation of dimethoxyethane vapors may lead to symptoms such as dizziness, nausea, headache, and central nervous system depression, akin to effects observed with other ethers. The American Conference of Governmental Industrial Hygienists (ACGIH) recommends a threshold limit value (TLV) of 0.5 ppm (skin) as an 8-hour time-weighted average to minimize these risks, based on concerns for hematologic and reproductive effects.[34]Chronic exposure to dimethoxyethane is associated with potential reproductive toxicity, including damage to fertility and the unborn child, leading to its classification as Repr. 1B under the EU REACH regulation.[28] It shows no evidence of mutagenicity in standard in vitro and in vivo assays.In vivo, dimethoxyethane is primarily metabolized via oxidation to 2-methoxyacetic acid, a toxic metabolite responsible for its reproductive effects, which can contribute to metabolic acidosis similar to that seen with related glycol ethers. The Occupational Safety and Health Administration (OSHA) does not establish a specific permissible exposure limit (PEL) for dimethoxyethane, though state regulations such as California's PEL of 1 ppm (with skin notation) provide guidance for workplace controls.[55]
Handling and Environmental Impact
Dimethoxyethane should be stored in airtight containers under an inert atmosphere, such as nitrogen, to prevent the formation of explosive peroxides upon exposure to air.[56] It is compatible with glass and polytetrafluoroethylene (PTFE) materials for containment, and storage in a cool, dry, well-ventilated area away from ignition sources is recommended to maintain stability.[57]In the event of a spill, evacuate personnel to a safe area, ensure adequate ventilation, and eliminate all ignition sources before absorbing the liquid with an inert material such as vermiculite, sand, or earth.[58] The absorbed material should then be placed in suitable closed containers for disposal, avoiding direct release into drains, surface water, or soil.[59]For disposal, dimethoxyethane is typically incinerated in a chemical incinerator equipped with an afterburner and scrubber to control emissions, in compliance with local regulations.[60] It is not readily biodegradable in standard tests, showing resistance in soil and water under pure culture conditions, though limited data suggest potential degradation in aerobic environments with an estimated volatilization half-life of approximately 240 days in a model lake scenario.[61] As a volatile organic compound (VOC), its emissions from industrial processes or evaporation can contribute to atmospheric pollution.[28]In terms of environmental fate, dimethoxyethane exhibits low bioaccumulation potential, with an estimated bioconcentration factor (BCF) of 0.4, indicating minimal uptake in aquatic organisms.[61] It demonstrates low aquatic toxicity, with an LC50 value greater than 5,000 mg/L for fish such as Danio rerio over 96 hours.[34] The compound is highly mobile in soil (estimated Koc of 18) and may volatilize from water surfaces, with an atmospheric degradation half-life of about 25 hours due to reaction with hydroxyl radicals.[61]Regulatory oversight includes listing under the U.S. Toxic Substances Control Act (TSCA) inventory.[34] In the European Union, it is registered under REACH at volumes between 1,000 and 10,000 tonnes per year and is designated as a substance of very high concern (SVHC) on the Candidate List due to its reproductive toxicity, subjecting it to restrictions and authorization requirements under the REACH Regulation.[28]