Diethyl ether
View on Wikipediafrom Wikipedia
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| Names | |
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| Preferred IUPAC name
Ethoxyethane | |
Other names
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| Identifiers | |
3D model (JSmol)
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| 1696894 | |
| ChEBI | |
| ChEMBL | |
| ChemSpider | |
| ECHA InfoCard | 100.000.425 |
| EC Number |
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| 25444 | |
| KEGG | |
PubChem CID
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| RTECS number |
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| UNII | |
| UN number | 1155 |
CompTox Dashboard (EPA)
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| Properties | |
| C4H10O | |
| Molar mass | 74.123 g·mol−1 |
| Appearance | Colorless liquid |
| Odor | Dry, rum-like, sweetish odor[1] |
| Density | 0.7134 g/cm3, liquid |
| Melting point | −116.3 °C (−177.3 °F; 156.8 K) |
| Boiling point | 34.6 °C (94.3 °F; 307.8 K)[4] |
| 6.05 g/(100 mL)[2] | |
| log P | 0.98[3] |
| Vapor pressure | 440 mmHg (58.66 kPa) at 20 °C[1] |
| −55.1·10−6 cm3/mol | |
Refractive index (nD)
|
1.353 (20 °C) |
| Viscosity | 0.224 cP (25 °C) |
| Structure | |
| 1.15 D (gas) | |
| Thermochemistry | |
Heat capacity (C)
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172.5 J/(mol·K) |
Std molar
entropy (S⦵298) |
253.5 J/(mol·K) |
Std enthalpy of
formation (ΔfH⦵298) |
−271.2 ± 1.9 kJ/mol |
Std enthalpy of
combustion (ΔcH⦵298) |
−2732.1 ± 1.9 kJ/mol |
| Pharmacology | |
| N01AA01 (WHO) | |
| Hazards | |
| Occupational safety and health (OHS/OSH): | |
Main hazards
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Extremely flammable, harmful to skin, decomposes to explosive peroxides in air and light, may cause dizziness in a less ventilated place or if ingested.[1] |
| GHS labelling: | |
 
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| Danger | |
| H224, H302, H336 | |
| P210, P233, P240, P241, P242, P243, P261, P264, P270, P271, P280, P301+P312, P303+P361+P353, P304+P340, P312, P330, P370+P378, P403+P233, P403+P235, P405, P501 | |
| NFPA 704 (fire diamond) | |
| Flash point | −45 °C (−49 °F; 228 K)[7] |
| 160 °C (320 °F; 433 K)[7] | |
| Explosive limits | 1.85–48.0%[5] |
| Lethal dose or concentration (LD, LC): | |
LC50 (median concentration)
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73,000 ppm (rat, 2 hr) 6500 ppm (mouse, 1.65 hr)[6] |
LCLo (lowest published)
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106,000 ppm (rabbit) 76,000 ppm (dog)[6] |
| NIOSH (US health exposure limits): | |
PEL (Permissible)
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TWA 400 ppm (1200 mg/m3)[1] |
REL (Recommended)
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No established REL[1] |
IDLH (Immediate danger)
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1900 ppm[1] |
| Safety data sheet (SDS) | External MSDS |
| Related compounds | |
Related ethers
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Related compounds
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| Supplementary data page | |
| Diethyl ether (data page) | |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Diethyl ether, or simply ether (abbreviated as eth.[8] or Et2O)[a][8] is an organic compound with the chemical formula (CH3CH2)2O, belonging to the ether class. It is a colourless, highly volatile, sweet-smelling (termed "ethereal odour"), extremely flammable liquid. It is a common solvent and was formerly used as a general anesthetic.[9]
Production
[edit]Most diethyl ether is produced as a byproduct of the vapor-phase hydration of ethylene to make ethanol. This process uses solid-supported phosphoric acid catalysts and can be adjusted to make more ether if the need arises:[10] Vapor-phase dehydration of ethanol over some alumina catalysts can give diethyl ether yields of up to 95%.[11]
- 2 CH3CH2OH → (CH3CH2)2O + H2O
Diethyl ether can be prepared both in laboratories and on an industrial scale by the acid ether synthesis.[12]
Uses
[edit]The dominant use of diethyl ether is as a solvent. One particular application is in the production of cellulose plastics such as cellulose acetate.[10]
Laboratory solvent
[edit]It is a common solvent for the Grignard reaction in addition to other reactions involving organometallic reagents.[13] These uses exploit its basicity. Diethyl ether is a popular non-polar solvent in liquid-liquid extraction. As an extractant, it is immiscible with and less dense than water.
Although immiscible, it has significant solubility in water (6.05 g/(100 ml) at 25 °C[2]) and dissolves 1.5 g/(100 g) (1.0 g/(100 ml)) water at 25 °C.[14]
Fuel
[edit]Diethyl ether has a high cetane number of 85–96 and, in combination with petroleum distillates for gasoline and diesel engines,[15] is used as a starting fluid because of its high volatility and low flash point. Ether starting fluid is sold and used in countries with cold climates, as it can help with cold starting an engine at sub-zero temperatures. For the same reason it is also used as a component of the fuel mixture for carbureted compression ignition model engines.
Chemical reactions
[edit]Triethyloxonium tetrafluoroborate is prepared from boron trifluoride, diethyl ether, and epichlorohydrin:[16]
- 4 Et2O·BF3 + 2 Et2O + 3 C2H3OCH2Cl → 3 [Et3O]+[BF4]− + B(OCH(CH2Cl)CH2OEt)3
Diethyl ether is a common laboratory aprotic solvent. It is susceptible to the formation of hydroperoxides.
Metabolism
[edit]A cytochrome P450 enzyme is proposed to metabolize diethyl ether.[17]
Diethyl ether inhibits alcohol dehydrogenase, and thus slows the metabolism of ethanol.[18] It also inhibits metabolism of other drugs requiring oxidative metabolism. For example, diazepam requires hepatic oxidization whereas its oxidized metabolite oxazepam does not.[19]
Safety, stability, regulations
[edit]Diethyl ether is extremely flammable and may form explosive vapour/air mixtures.[20]
Since ether is heavier than air it can collect low to the ground and the vapour may travel considerable distances to ignition sources. Ether will ignite if exposed to an open flame, though due to its high flammability, an open flame is not required for ignition. Other possible ignition sources include – but are not limited to – hot plates, steam pipes, heaters, and electrical arcs created by switches or outlets.[20] Vapour may also be ignited by the static electricity which can build up when ether is being poured from one vessel into another. The autoignition temperature of diethyl ether is 160 °C (320 °F). The diffusion of diethyl ether in air is 9.18 × 10−6 m2/s (298 K, 101.325 kPa).[citation needed]
Ether is sensitive to light and air, tending to form explosive peroxides.[20] Ether peroxides have a higher boiling point than ether and are contact explosives when dry.[20] Commercial diethyl ether is typically supplied with trace amounts of the antioxidant butylated hydroxytoluene (BHT), which reduces the formation of peroxides. Storage over sodium hydroxide precipitates the intermediate ether hydroperoxides. Water and peroxides can be removed by either distillation from sodium and benzophenone, or by passing through a column of activated alumina.[21]
Due to its application in the manufacturing of illicit substances, it is listed in the Table II precursor under the United Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances as well as substances such as acetone, toluene and sulfuric acid.[22]
History
[edit]The compound may have been synthesised by either Jābir ibn Hayyān in the 8th century[23] or Ramon Llull in 1275.[23][24] It was synthesised in 1540 by Valerius Cordus, who called it "sweet oil of vitriol" (oleum dulce vitrioli) – the name reflects the fact that it is obtained by distilling a mixture of ethanol and sulfuric acid (then known as oil of vitriol) – and noted some of its medicinal properties.[23] At about the same time, Paracelsus discovered the analgesic properties of the molecule in dogs.[23] The name ether was given to the substance in 1729 by August Sigmund Frobenius.[25]
It was considered to be a sulfur compound until the idea was disproved in about 1800.[26]
The synthesis of diethyl ether by a reaction between ethanol and sulfuric acid has been known since the 13th century.[26]
Anesthesia
[edit]
William T. G. Morton participated in a public demonstration of ether anesthesia on October 16, 1846, at the Ether Dome in Boston, Massachusetts. Morton had called his ether preparation, with aromatic oils to conceal its smell, "Letheon" after the Lethe River (Λήθη, meaning "forgetfulness, oblivion").[27] However, Crawford Williamson Long is now known to have demonstrated its use privately as a general anesthetic in surgery to officials in Georgia, as early as March 30, 1842, and Long publicly demonstrated ether's use as a surgical anesthetic on six occasions before the Boston demonstration.[28][29][30] British doctors were aware of the anesthetic properties of ether as early as 1840 where it was widely prescribed in conjunction with opium.[31] Diethyl ether was preferred by some practitioners over chloroform as a general anesthetic due to ether's more favorable therapeutic index, that is, a greater difference between an effective dose and a potentially toxic dose.[32]
Diethyl ether does not depress the myocardium but rather it stimulates the sympathetic nervous system leading to hypertension and tachycardia. It is safely used in patients with shock as it preserves the baroreceptor reflex.[33] Its minimal effect on myocardial depression and respiratory drive, as well as its low cost and high therapeutic index allows it to see continued use in developing countries.[34] Diethyl ether could also be mixed with other anesthetic agents such as chloroform to make C.E. mixture, or chloroform and alcohol to make A.C.E. mixture. In the 21st century, ether is rarely used. The use of flammable ether was displaced by nonflammable fluorinated hydrocarbon anesthetics. Halothane was the first such anesthetic developed and other currently used inhaled anesthetics, such as isoflurane, desflurane, and sevoflurane, are halogenated ethers.[35] Diethyl ether was found to have undesirable side effects, such as post-anesthetic nausea and vomiting. Modern anesthetic agents reduce these side effects.[28]
Prior to 2005, it was on the World Health Organization's List of Essential Medicines for use as an anesthetic.[36][37]
Medicine
[edit]Ether was once used in pharmaceutical formulations. A mixture of alcohol and ether, one part of diethyl ether and three parts of ethanol, was known as "Spirit of ether", Hoffman's Anodyne or Hoffman's Drops. In the United States this concoction was removed from the Pharmacopeia at some point prior to June 1917,[38] as a study published by William Procter, Jr. in the American Journal of Pharmacy as early as 1852 showed that there were differences in formulation to be found between commercial manufacturers, between international pharmacopoeia, and from Hoffman's original recipe.[39] It is also used to treat hiccups through instillation into the nasal cavity.[40]
Recreational use
[edit]The recreational use of ether also took place at organised parties in the 19th century called ether frolics, where guests were encouraged to inhale therapeutic amounts of diethyl ether or nitrous oxide, producing a state of excitation. Long, as well as fellow dentists Horace Wells, William Edward Clarke, and William T. G. Morton, observed that during these gatherings, people would often experience minor injuries but appear to show no reaction to them, nor memory that it had happened, demonstrating ether's anaesthetic effects.[41]
In the 19th and early 20th centuries, ether drinking was popular among Polish peasants.[42] It is a traditional and still relatively popular recreational drug among Lemkos.[43] It is usually consumed in a small quantity (kropka, or "dot") poured over milk, sugar water, or orange juice in a shot glass. As a drug, it has been known to cause psychological dependence, sometimes referred to as etheromania.[44][medical citation needed]
Ether intoxication is referenced in Hunter S. Thompson's Fear and Loathing in Las Vegas, where in one of the book's most famous quotes, protagonist Raoul Duke declares that "There is nothing in the world more helpless and irresponsible and depraved than a man in the depths of an ether binge."[45]
See also
[edit]- The Great Moment – film about William T.G. Morton and ether
- Flurothyl – fluorinated derivative
Explanatory notes
[edit]- ^ "Et" stands for monovalent ethyl group CH3CH2 (see pseudoelement symbol)
References
[edit]- ^ a b c d e f NIOSH Pocket Guide to Chemical Hazards. "#0277". National Institute for Occupational Safety and Health (NIOSH).
- ^ a b Merck Index, 10th ed., Martha Windholz, editor, Merck & Co., Inc, Rahway, NJ, 1983, p. 551
- ^ "Diethyl ether_msds".
- ^ "Diethyl ether". ChemSpider. Retrieved 19 January 2017.
- ^ Carl L. Yaws, Chemical Properties Handbook, McGraw-Hill, New York, 1999, p. 567
- ^ a b "Ethyl ether". Immediately Dangerous to Life or Health Concentrations. National Institute for Occupational Safety and Health.
- ^ a b "Ethyl Ether MSDS". J.T. Baker. Archived from the original on 2012-03-28. Retrieved 2010-06-24.
- ^ a b Logan CM, Rice MK (1987). Logan's Medical and Scientific Abbreviations (Hardbound book). J. B. Lippincott. p. 182. ISBN 0-397-54589-4.
- ^ Sakuth, Michael; Mensing, Thomas; Schuler, Joachim; Heitmann, Wilhelm; Strehlke, Günther; Mayer, Dieter (2010). "Ethers, Aliphatic". Ullmann's Encyclopedia of Industrial Chemistry. doi:10.1002/14356007.a10_023.pub2. ISBN 978-3-527-30385-4.
- ^ a b "Ethers, by Lawrence Karas and W. J. Piel". Kirk‑Othmer Encyclopedia of Chemical Technology. John Wiley & Sons, Inc. 2004.
- ^ Ethyl Ether, Chem. Economics Handbook. Menlo Park, Calif: SRI International. 1991.
- ^ Cohen, Julius Berend (1920). A Class-book of Organic Chemistry, Volume 1. London: Macmillan and Co. p. 39.
the structure of ethyl alcohol cohen julius diethyl ether.
- ^ Moyer, W. W.; Marveltitle=Triethyl Carbinol, C. S. (1931). "Triethyl Carbinol". Organic Syntheses. 11: 98. doi:10.15227/orgsyn.011.0098.
- ^ H. H. Rowley; Wm. R. Reed (1951). "Solubility of Water in Diethyl Ether at 25 °". J. Am. Chem. Soc. 73 (6): 2960. Bibcode:1951JAChS..73.2960R. doi:10.1021/ja01150a531.
- ^ "Extra Strength Starting Fluid: How it Works". Valvovine. Archived from the original on 2007-09-27. Retrieved 2007-09-05.
- ^ H. Meerwein (1966). "Triethyloxonium fluoroborate". Organic Syntheses. 46: 113. doi:10.15227/orgsyn.046.0113.
- ^ 109. Aspergillus flavus mutant strain 241, blocked in aflatoxin biosynthesis, does not accumulate aflR transcript. Archived 2017-09-17 at the Wayback Machine Matthew P. Brown and Gary A. Payne, North Carolina State University, Raleigh, NC, fgsc.net
- ^ P. T. Normann; A. Ripel; J. Morland (1987). "Diethyl Ether Inhibits Ethanol Metabolism in Vivo by Interaction with Alcohol Dehydrogenase". Alcoholism: Clinical and Experimental Research. 11 (2): 163–166. doi:10.1111/j.1530-0277.1987.tb01282.x. PMID 3296835.
- ^ Larry K. Keefer; William A. Garland; Neil F. Oldfield; James E. Swagzdis; Bruce A. Mico (1985). "Inhibition of N-Nitrosodimethylamine Metabolism in Rats by Ether Anesthesia" (PDF). Cancer Research. 45 (11 Pt 1): 5457–5460. PMID 4053020.
- ^ a b c d "Archived copy" (PDF). Archived from the original (PDF) on 2014-11-13. Retrieved 2014-02-15.
{{cite web}}: CS1 maint: archived copy as title (link) - ^ W. L. F. Armarego; C. L. L. Chai (2003). Purification of laboratory chemicals. Boston: Butterworth-Heinemann. ISBN 978-0-7506-7571-0.
- ^ Microsoft Word – RedListE2007.doc Archived February 27, 2008, at the Wayback Machine
- ^ a b c d Toski, Judith A; Bacon, Douglas R; Calverley, Rod K (2001). The history of Anesthesiology. In: Barash, Paul G; Cullen, Bruce F; Stoelting, Robert K. Clinical Anesthesia (4th ed.). Lippincott Williams & Wilkins. p. 3. ISBN 978-0-7817-2268-1.
- ^ Hademenos, George J.; Murphree, Shaun; Zahler, Kathy; Warner, Jennifer M. (2008). McGraw-Hill's PCAT. McGraw-Hill. p. 39. ISBN 978-0-07-160045-3. Retrieved 2011-05-25.
- ^ "VIII. An account of a spiritus vini æthereus, together with several experiments tried therewith". Philosophical Transactions of the Royal Society of London. 36 (413): 283–289. 1730. doi:10.1098/rstl.1729.0045. S2CID 186207852.
- ^ a b Chisholm, Hugh, ed. (1911). . Encyclopædia Britannica. Vol. 9 (11th ed.). Cambridge University Press. p. 806.
- ^ Cavendish, Marshall (2008). Inventors and Inventions, Volume 4. Marshall Cavendish. p. 1129. ISBN 978-0-7614-7767-9.
- ^ a b Hill, John W. and Kolb, Doris K. Chemistry for Changing Times: 10th Edition. p. 257. Pearson: Prentice Hall. Upper Saddle River, New Jersey. 2004.
- ^ Madden, M. Leslie (May 14, 2004). "Crawford Long (1815–1878)". New Georgia Encyclopedia. University of Georgia Press. Retrieved February 13, 2015.
- ^ "Crawford W. Long". Doctors' Day. Southern Medical Association. Archived from the original on February 13, 2015. Retrieved February 13, 2015.
- ^ Gratian, N. (1840-11-07). "Dr. Grattan on the Treatment of Uterine Haemorrhage". BMJ. s1-1 (6): 107. doi:10.1136/bmj.s1-1.6.107. ISSN 0959-8138. PMC 2488546. PMID 21372908.
- ^ Calderone, F.A. (1935). "Studies on Ether Dosage After Pre-Anesthetic Medication with Narcotics (Barbiturates, Magnesium Sulphate and Morphine)" (PDF). Journal of Pharmacology and Experimental Therapeutics. 55 (1): 24–39.
- ^ "Ether effects". 31 October 2010.
- ^ "Ether and its effects in Anesthesia". Anesthesia General. 2010-10-31.
- ^ Morgan, G. Edward, Jr. et al. (2002). Clinical Anesthesiology 3rd Ed. New York: McGraw-Hill. p. 3.
- ^ "Essential Medicines WHO Model List (revised April 2003)" (PDF). apps.who.int (13th ed.). Geneva, Switzerland: World Health Organization. April 2003. Retrieved 6 September 2017.
- ^ "Essential Medicines WHO Model List (revised March 2005)" (PDF). apps.who.int (14th ed.). Geneva, Switzerland: World Health Organization. March 2005. Archived from the original (PDF) on 5 August 2005. Retrieved 6 September 2017.
- ^ The National Druggist, Volume 47, June 1917, pp. 220
- ^ Procter, William Jr. (1852). "On Hoffman's Anodyne Liquor". American Journal of Pharmacy. 28.
- ^ ncbi, Treatment of hiccups with instillation of ether into the nasal cavity.
- ^ "How Ether Went from a Recreational 'Frolic' Drug to the First Surgery Anesthetic". Smithsonian Magazine. Retrieved 2020-10-11.
- ^ Zandberg, Adrian (2010). "Short Article "Villages … Reek of Ether Vapours": Ether Drinking in Silesia before 1939". Medical History. 54 (3): 387–396. doi:10.1017/s002572730000466x. PMC 2890321. PMID 20592886.
- ^ Kaszycki, Nestor (2006-08-30). "Łemkowska Watra w Żdyni 2006 – pilnowanie ognia pamięci". Histmag.org – historia od podszewki (in Polish). Kraków, Poland: i-Press. Retrieved 2009-11-25.
Dawniej eteru używało się w lecznictwie do narkozy, ponieważ ma właściwości halucynogenne, a już kilka kropel inhalacji wystarczyło do silnego znieczulenia pacjenta. Jednak eter, jak każda ciecz, może teoretycznie być napojem. Łemkowie tę teorię praktykują. Mimo to, nazywanie skroplonego eteru – "kropki" – ich "napojem narodowym" byłoby przesadą. Chociaż stanowi to pewną część mitu "bycia Łemkiem".
- ^ Krenz, Sonia; Zimmermann, Grégoire; Kolly, Stéphane; Zullino, Daniele Fabio (August 2003). "Ether: a forgotten addiction". Addiction. 98 (8): 1167–1168. doi:10.1046/j.1360-0443.2003.00439.x. PMID 12873252.
- ^ "Hunter S. Thompson Quotes (Author of Fear and Loathing in las Vegas)".
External links
[edit]
Wikimedia Commons has media related to Diethyl ether.
- Michael Faraday's announcement of ether as an anesthetic in 1818 Archived 2011-05-22 at the Wayback Machine
- CDC – NIOSH Pocket Guide to Chemical Hazards
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Diethyl ether
View on Grokipediafrom Grokipedia
Molecular structure and properties
Chemical structure
Diethyl ether has the molecular formula C₄H₁₀O, commonly represented as (CH₃CH₂)₂O. Its IUPAC name is ethoxyethane, though it is more widely known by its common name, diethyl ether.[1] The molecular structure features a central oxygen atom bonded to two identical ethyl groups (–CH₂CH₃) via two sigma bonds, resulting in a bent C–O–C arrangement characteristic of ethers. This configuration classifies diethyl ether as a symmetrical dialkyl ether, where the alkyl substituents on either side of the oxygen are the same. The C–O–C bond angle is approximately 110°, influenced by the sp³ hybridization of the oxygen atom and lone pair repulsions./18%3A_Ethers_and_Epoxides_Thiols_and_Sulfides/18.01%3A_Names_and_Properties_of_Ethers)[5] For structural context, diethyl ether can be compared to related ethers such as dimethyl ether ((CH₃)₂O), which has shorter methyl groups and a slightly larger C–O–C angle of about 112°, or ethyl methyl ether (CH₃CH₂OCH₃), an unsymmetrical dialkyl ether with differing alkyl chains on each side of the oxygen./Ethers/Properties_of_Ethers/Physical_Properties_of_Ether) Spectroscopic techniques confirm this structure. In infrared (IR) spectroscopy, the C–O stretching vibration appears as a strong absorption band at approximately 1100 cm⁻¹. Proton nuclear magnetic resonance (¹H NMR) spectroscopy shows the methyl (CH₃) protons as a triplet at around 1.2 ppm and the methylene (CH₂) protons adjacent to oxygen as a quartet at about 3.5 ppm, reflecting their distinct chemical environments due to the ether linkage./18%3A_Ethers_and_Epoxides_Thiols_and_Sulfides/18.08%3A_Spectroscopy_of_Ethers)[1]Physical properties
Diethyl ether is a colorless, volatile liquid with a characteristic sweet, pungent odor.[1] The low boiling point of diethyl ether arises from weak intermolecular forces, as the ether oxygen cannot participate in hydrogen bonding to the same extent as in alcohols.[6] Key physical constants for diethyl ether under standard conditions are summarized in the following table:| Property | Value | Conditions |
|---|---|---|
| Molar mass | 74.12 g/mol | - |
| Melting point | -116.3 °C | - |
| Boiling point | 34.6 °C | 760 mmHg |
| Density | 0.7134 g/cm³ | 20 °C |
| Refractive index | 1.3526 | 20 °C (D line) |
Production
Industrial methods
The primary industrial method for producing diethyl ether involves the catalytic dehydration of ethanol, typically using sulfuric acid or supported phosphoric acid as catalysts at temperatures around 140°C. This process follows the reversible equilibrium reaction:
The reaction is carried out in a reactor where ethanol vapor is passed over the catalyst bed, with yields optimized by removing water to shift the equilibrium toward ether formation. Sulfuric acid acts as a strong proton donor to facilitate the formation of an oxonium ion intermediate, while phosphoric acid, often impregnated on carriers like alumina, provides a solid acid alternative that reduces corrosion and simplifies handling.[9][10][11]
A significant portion of diethyl ether is obtained as a side product, typically in yields of 5-10%, during the industrial production of ethanol via the vapor-phase hydration of ethylene. In this process, ethylene reacts with water over a solid phosphoric acid catalyst at high pressure (around 70 bar) and temperature (300°C), where minor side reactions lead to diethyl ether formation alongside the main ethanol product. The ether is then separated from the reaction mixture for recovery.[9][12]
Historically, diethyl ether production shifted from the Williamson ether synthesis, which involved reacting alkyl halides with sodium alkoxides and was more suited to laboratory-scale unsymmetrical ether preparation, to modern catalytic dehydration methods in the early 20th century for efficient large-scale output. This transition enabled cost-effective commercialization, with global annual production reaching approximately 300,000 metric tons as of 2020, driven by demand in solvents and pharmaceuticals.[13][14][15]
Following synthesis, diethyl ether is purified primarily through fractional distillation to achieve greater than 99% purity, effectively removing residual ethanol and water azeotropes. The crude product is fed into a distillation column where lower-boiling ether (boiling point 34.6°C) is collected as overhead, while ethanol (78.4°C) and water (100°C) are separated in subsequent stages or side streams; additional treatments like caustic washing may address trace acids.[16][17]
Economically, diethyl ether production benefits from the abundance and low cost of ethanol feedstock, particularly from bioethanol sources, keeping raw material expenses below 50% of total costs in many facilities. However, the process is energy-intensive due to the high-temperature dehydration step and requires periodic catalyst regeneration—such as reconcentration of diluted sulfuric acid—to maintain efficiency and minimize downtime.[18][19][20]
Laboratory synthesis
Diethyl ether was first synthesized in the laboratory by the German botanist and pharmacist Valerius Cordus in 1540 through the distillation of a mixture of ethanol and sulfuric acid, a method he termed the preparation of "sweet oil of vitriol."[21] This historical procedure laid the foundation for subsequent laboratory preparations and involved heating the reactants in an alembic still to collect the volatile ether distillate.[13] In contemporary laboratory settings, the preferred method for preparing diethyl ether on a small scale is the sulfuric acid-catalyzed dehydration of ethanol, conducted at temperatures of 130–140 °C to favor ether formation over elimination to ethene, which predominates above 150 °C.[13] The reaction proceeds via protonation of one ethanol molecule, followed by nucleophilic attack from a second ethanol molecule in an SN2 manner, displacing water to yield the protonated ether, which is then deprotonated.[22] Typically, concentrated sulfuric acid is added to excess anhydrous ethanol in a round-bottom flask equipped with a reflux condenser and a distillation setup; the mixture is heated gently while the low-boiling ether (b.p. 34.6 °C) is continuously distilled and collected in a receiver cooled with ice.[13] The crude product is then dried over anhydrous calcium chloride and redistilled to purify it, achieving typical yields of 50–70% based on the ethanol consumed.[10] An alternative classic approach is the Williamson ether synthesis, involving the reaction of sodium ethoxide (prepared from ethanol and sodium metal or a strong base like NaH) with an ethyl halide such as ethyl bromide or iodide in an SN2 displacement.[22] This method, while effective for symmetrical ethers like diethyl ether, is rarely employed in laboratories due to the toxicity and handling hazards of ethyl halides, which can cause severe irritation and systemic poisoning upon inhalation or skin contact.[23] Regardless of the synthesis route, freshly prepared diethyl ether must be stored under an inert atmosphere, such as nitrogen, to prevent autoxidation and the formation of explosive peroxides during prolonged exposure to air and light.[24]Applications
Solvent applications
Diethyl ether serves as a primary non-polar aprotic solvent in organic synthesis, particularly for reactions involving highly reactive organometallic reagents such as Grignard (RMgX) and organolithium compounds, where its ability to dissolve non-polar substances without donating protons prevents unwanted side reactions.[25][26] Its Lewis basic oxygen atom coordinates with magnesium or lithium centers, stabilizing these reagents in solution.[27] In liquid-liquid extractions, diethyl ether facilitates the separation of organic compounds from aqueous phases due to its low density of 0.71 g/cm³ and immiscibility with water, allowing the organic layer to form on top for easy isolation.[28] This property makes it ideal for partitioning non-polar solutes, enhancing recovery yields in purification workflows.[29] Within the pharmaceutical industry, diethyl ether is employed for extracting natural products like alkaloids from plant materials, as seen in the isolation of ephedrine from aqueous solutions, and as a reaction medium in the synthesis of active pharmaceutical ingredients.[30][31] Its solvating power supports scalable processes while minimizing interference with drug precursors.[32] Historically, diethyl ether has been a staple in laboratory settings for recrystallization of organic solids and as a mobile phase in chromatography techniques like thin-layer and column methods, where it effectively elutes non-polar compounds.[33] Compared to alternatives like tetrahydrofuran (THF), it offers advantages in moisture-sensitive applications due to lower hygroscopicity, requiring less rigorous drying.[34] In modern applications, diethyl ether finds niche use in the extraction of perfumes and essential oils, where it dissolves aromatic lipids and waxes from plant matter without altering volatile profiles.[35] A significant portion of global diethyl ether production supports solvent demands across these chemical and extraction processes.[1] Due to its high flammability, careful handling is essential in all solvent applications.[36]Fuel and industrial uses
Diethyl ether serves as an oxygenate additive in diesel fuels, typically blended at concentrations up to 30% to enhance combustion properties. Its high cetane number, ranging from 85 to 96, significantly shortens ignition delay compared to conventional diesel, facilitating smoother starts and reducing unburned hydrocarbon emissions during operation.[37] This additive effect is particularly beneficial for cold starts in low-temperature environments, where diethyl ether's low autoignition temperature and oxygen content promote premixed combustion, improving fuel evaporation and overall engine performance without requiring engine modifications.[38] In rocketry, diethyl ether has historical applications as a liquid propellant in early experimental engines, notably tested by Harry W. Bull at Syracuse University in 1932 with gaseous oxygen to evaluate its viability alongside other hydrocarbons like gasoline and kerosene. Its role extended to ignition enhancement in liquid oxygen (LOX)-based systems, where it functioned as a starting slug to initiate combustion in hydrocarbon-fueled motors, such as those developed by Eugen Sänger. The compound's high vapor pressure contributes to effective atomization during injection, aiding propellant mixing and thrust generation in these hybrid or bipropellant setups, though it was largely supplanted by more reliable hypergolic alternatives in subsequent designs.[39] Industrially, diethyl ether is a key component in engine starting fluids, comprising 30-50% of formulations used to aid ignition in diesel and gasoline engines during cold weather. Its volatility and low ignition temperature provide rapid vaporization in the intake manifold, compensating for poor fuel atomization in sub-zero conditions and preventing battery drain from prolonged cranking. Additionally, diethyl ether finds minor application in polymer manufacturing processes, where it influences chain growth in free-radical polymerizations, though its use remains limited compared to dedicated transfer agents.[40] As a biofuel, diethyl ether holds potential for renewable production through the dehydration of bioethanol over heteropolyacid catalysts like tungstophosphoric acid, yielding up to 75% selectivity at 140-180°C and offering a sustainable pathway from biomass-derived feedstocks. This process aligns with environmental goals by reducing reliance on fossil oxygenates, providing lower lifecycle greenhouse gas emissions and compatibility with existing diesel infrastructure. Bio-based diethyl ether variants may support EU renewable fuel targets by enhancing diesel blend oxygen content without increasing particulate matter.[41][42] Global production of diethyl ether allocates a notable portion to fuel applications, including diesel additives and starting fluids, though its incorporation into gasoline blends has been discontinued in regions like the United States due to regulatory restrictions on volatile oxygenates aimed at curbing evaporative emissions. As of 2024, market analyses project steady growth in fuel-related demand through 2030, driven by biofuel integration, but constrained by safety handling requirements.[15][43]Chemical reactivity
Acid-base reactions
Diethyl ether exhibits Lewis base character due to the lone pairs on its oxygen atom, which can coordinate to Lewis acids to form stable complexes. For instance, it readily forms a 1:1 adduct with boron trifluoride, known as boron trifluoride diethyl etherate ((CH₃CH₂)₂O·BF₃), where the oxygen donates electron density to the electron-deficient boron center.[44][45] This complex is widely used as a convenient source of BF₃ in synthetic applications, highlighting the moderate basicity of diethyl ether compared to stronger donors like amines.[46] In coordination chemistry, diethyl ether can further react with strong alkylating agents to generate trialkyloxonium salts, such as triethyloxonium tetrafluoroborate (Et₃O⁺ BF₄⁻), typically prepared by treating diethyl ether with ethyl fluoroborate or via Meerwein's method involving BF₃ etherate and epichlorohydrin.[47] These oxonium ions are highly reactive electrophiles employed in the ethylation of nucleophiles, including the synthesis of other ethers through alkylation of alcohols or phenols under mild conditions.[47] Diethyl ether undergoes acid-catalyzed cleavage with strong acids like HBr, proceeding via protonation of the oxygen to form an oxonium intermediate, followed by nucleophilic attack by bromide on one of the ethyl groups. The reaction yields ethyl bromide and ethanol:
This cleavage requires forcing conditions, such as concentrated aqueous HBr at elevated temperatures (typically above 100°C), as the reaction is rare at room temperature due to the high stability of the C-O bond and the need for protonation to activate the ether.[48]
Diethyl ether is generally inert toward dilute acids and bases at ambient conditions, reflecting its low reactivity as a neutral molecule, but it protonates readily in concentrated sulfuric acid to form a dialkyloxonium ion. At high temperatures (around 140-160°C), this leads to decomposition via cleavage, producing ethanol and potentially further dehydration products under pressure.[48][9]
In inorganic chemistry, diethyl etherates serve analytical purposes, such as forming soluble complexes with gases like hydrogen chloride (HCl·OEt₂) to facilitate drying and purification by distillation, or as solvents for metal salts where the ether coordinates to cations like Li⁺ or Mg²⁺, enhancing solubility in non-aqueous media.[49]
Oxidation and peroxide formation
Diethyl ether is highly susceptible to auto-oxidation in the presence of atmospheric oxygen, a radical chain process that generates hazardous peroxides. The mechanism begins with initiation via abstraction of an alpha hydrogen atom, forming an alkyl radical that reacts with O₂ to produce a peroxy radical (e.g., DEEOO•). Propagation involves hydrogen abstraction by the peroxy radical, leading to hydroperoxides such as 1-ethoxyethyl hydroperoxide (CH₃CH(OOH)OCH₂CH₃) as primary products, with possible secondary formation of dialkyl peroxides, alongside other oxygenated species.[50][51] This autoxidation proceeds slowly at room temperature under ambient pressure, often exhibiting a long induction period of several months, but is significantly accelerated by exposure to light, heat, or trace metals.[50][51] The resulting peroxides are unstable and potentially explosive at concentrations above 100 ppm (0.01%) by weight, capable of violent decomposition triggered by shock, friction, or heat, especially when concentrated by distillation or evaporation; notably, they are odorless and thus undetectable by smell alone, unlike diethyl ether itself. To mitigate this risk, commercial diethyl ether is typically stabilized with antioxidants such as butylated hydroxytoluene (BHT), which interrupts the radical chain by scavenging reactive species. Peroxide accumulation enhances the overall flammability of ether, contributing to severe fire hazards if ignited.[52][53][54] Detection of peroxides relies on sensitive colorimetric assays, such as the potassium iodide/starch test, where a blue-black color develops upon reaction with hydroperoxides in an acidic medium. Prevention involves inert storage under nitrogen gas or in contact with copper wire, which acts as a radical scavenger, along with regular testing and avoidance of prolonged air exposure; ether should not be stored for more than 6-12 months without verification. Distillation of peroxide-contaminated ether is particularly dangerous, as evaporation concentrates the peroxides in the residue or distillate, potentially leading to detonation. Safe handling thresholds are set below 100 ppm peroxide content to prevent instability.[52] Historical laboratory incidents underscore these risks, including a 2006 explosion at UC Berkeley that injured a researcher when peroxides in aged THF (mixed with diethyl ether) detonated during manipulation, highlighting the consequences of inadequate testing on old stock.[55] Similar accidents have been reported in academic settings due to overlooked peroxide buildup in stored ether. Compared to tetrahydrofuran (THF), diethyl ether forms peroxides more slowly owing to steric hindrance at the alpha positions, despite sharing weak C-H bonds vulnerable to radical abstraction; however, both require vigilant management.[50]Biological interactions
Metabolism
Diethyl ether undergoes hepatic metabolism primarily through the cytochrome P450 2E1 (CYP2E1) enzyme, which catalyzes oxidative dealkylation to produce acetaldehyde and ethanol. This pathway is supported by in vitro studies using rat liver microsomes, where CYP2E1 demonstrates high activity toward diethyl ether as a substrate, with kinetic parameters indicating efficient turnover (Km ≈ 13.4 µM, Vmax ≈ 8.2 nmol/min/nmol P-450 in acetone-induced preparations).[56] The metabolic reaction can be represented as:
Isolated rat hepatocytes exposed to anesthetic concentrations of diethyl ether exhibit dose-dependent production of these metabolites, with enhanced rates in cells from phenobarbital-pretreated animals, confirming involvement of an inducible microsomal system akin to CYP2E1.[57] In humans, diethyl ether anesthesia similarly results in detectable blood acetaldehyde levels (average ≈ 21 µM), comparable to those observed after moderate ethanol consumption, though ethanol production is less emphasized in clinical contexts.[58]
Approximately 90% of absorbed diethyl ether is eliminated unchanged via exhalation through the lungs, reflecting its high volatility and low solubility in aqueous media, which limits extensive tissue retention.[1] [59] Blood concentrations decline rapidly, with a half-life of approximately 10–15 minutes, facilitating quick recovery from exposure. Only 1–2% is excreted in urine, primarily as unchanged compound or minor metabolites.[59]
Diethyl ether interacts with alcohol-metabolizing enzymes by inhibiting alcohol dehydrogenase (ADH) in a mixed noncompetitive/uncompetitive manner, as demonstrated in kinetic assays with equine liver ADH (Ki ≈ 20 mM). This inhibition reduces ethanol oxidation to acetaldehyde, potentially causing acetaldehyde accumulation and disulfiram-like effects if diethyl ether is co-ingested with ethanol.[60]
Metabolic rates differ across species; in rats, diethyl ether induces CYP2E1 activity (1.5–2-fold increase), accelerating clearance compared to humans, where baseline CYP2E1 expression yields slower metabolism without significant induction under typical exposure.[56] No substantial conjugation of diethyl ether with glutathione occurs, distinguishing it from many xenobiotics that undergo phase II detoxification via this pathway.
Toxicokinetics of diethyl ether involve rapid absorption primarily through inhalation (alveolar uptake proportional to inspired concentration) or ingestion (gastrointestinal tract), followed by distribution favoring lipid-rich tissues such as the brain and liver due to its high blood-gas partition coefficient (≈12).