123-91-1 Usage
Production
1,4-Dioxane can be prepared by dehydration of ethylene glycol orpolyglycol ether by the catalysis of sulfuric acid and can also be prepared by direct dimerization of Ethylene oxide. The dimerization process was carried out in the presence of acid catalysts such as sulfuric acid, Sodium bisulfate, boron trifluoride, etc. Powdered sodium hydroxide can be added to 1,4-Dioxane of industrial grade to remove the acid and water, by filtering the solid and distillation to get prurified product.
Mechanism of action
An inhalation study in four male volunteers exposed to 50 ppm of dioxane determined that the majority (99.3%) of dioxane is eliminated by metabolism to β-hydroxyethoxyacetic acid (HEAA) with the remaining 0.7% being excreted through the urine (Young et al., 1977). Further studies suggest that the metabolism of dioxane is mediated by cytochrome P450 (Woo et al., 1978). The concentrations of HEAA were found to be 118% higher than the concentration of dioxane, suggesting rapid and extensive metabolism with a calculated metabolic clearance rate of 75 m/min. This same study concluded that repeated daily exposures to 50 ppm of dioxane would not cause adverse effects because accumulated concentrations would never exceed those attained at 50 ppm or less. β-Hydroxyethoxyacetic acid also accounted for >99% of the total urinary excretion of inhaled dioxane in rats (Young et al., 1978). Conversely, when dioxane is intravenously injected in rats, the metabolic clearance decreased indicating metabolic saturation at high doses (1000 mg/kg). Saturation was found to occur at doses >10 mg/kg/bw resulting in accumulation of 1,4-dioxane (HSDB, 1995).
Air & Water Reactions
Highly flammable. When exposed to air 1,4-Dioxane undergoes autooxidation with formation of peroxides. In the distillation process peroxides will concentrate causing violent explosion. Water soluble.
Reactivity Profile
1,4-Dioxane is a flammable liquid; when exposed to air 1,4-Dioxane undergoes autooxidation with formation of peroxides. In the distillation process peroxides will concentrate causing violent explosion. The addition complex with sulfur trioxide (1:1) sometimes decomposes violently on storing at room temperature [Sisler, H. H. et al., Inorg. Synth., 1947, 2, p. 174]. Evaporation of boron trifluoride in aqueous 1,4-Dioxane with nitric acid led to an explosion upon addition of perchloric acid [MCA Guide, 1972, p. 312]. Explosive reaction with Raney nickel catalyst above 210° C {Mozingo R., Org. Synth., 1955, Coll. Vol. 3, p. 182].
Health Hazard
The toxicity of 1,4-dioxane is low in testanimals by all routes of exposure. However,in humans the toxicity of this compoundis severe. The target organs are theliver, kidneys, lungs, skin, and eyes. Exposureto its vapors as well as the absorptionthrough the skin or ingestion can cause poisoning,the symptoms of which include drowsiness,headache, respiratory distress, nausea,and vomiting. It causes depression of centralnervous system. There are reports of humandeaths from subacute and chronic exposures todioxane vapors at concentration levels rangingbetween 500 and 1000 ppm. Serious healthhazards may arise from its injurious effects onthe liver, kidneys, and brain. Rabbits died ofkidney injury resulting from repeated inhalationof 1,4-dioxane vapors for 30 days (Smyth1956). It is an irritant to the eyes, nose, skin,and lungs. In humans, a 1-minute exposure to5000-ppm vapors can cause lacrimation.LC50 value, inhalation (rats): 13,000 ppm/2 hLD50 value, oral (mice): 5700 mg/kg1,4-Dioxane is an animal carcinogen oflow potential. Ingestion of high concentrationsof this compound at a level of7000–18,000 ppm in drinking water for14–23 months caused nasal and liver tumorsin rats (ACGIH 1986). Guinea pigs developedlung tumors.
Flammability and Explosibility
Dioxane is a highly flammable liquid (NFPA rating = 3). Its vapor is heavier than air and may travel a considerable distance to a source of ignition and flash back. Dioxane vapor forms explosive mixtures with air at concentrations of 2 to 22% (by volume). Fires involving dioxane should be extinguished with carbon dioxide or dry powder extinguishers. Dioxane can form shock- and heat-sensitive peroxides that may explode on concentration by distillation or evaporation. Samples of this substance should always be tested for the presence of peroxides before distilling or allowing to evaporate. Dioxane should never be distilled to dryness.
Safety Profile
Confirmed carcinogen
with experimental carcinogenic,
neoplastigenic, tumorigenic, and teratogenicdata. Poison by intraperitoneal route.
Moderately toxic by ingestion and
inhalation. Mildly toxic by skin contact.
Human systemic effects by inhalation:
lachrymation, conjunctiva irritation,
convulsions, hgh blood pressure,
unspecified respiratory and gastrointestinal
system effects. Mutation data reported. An
eye and slun irritant. The irritant effects
probably provide sufficient warning, in acute
exposures, to enable a worker to leave
exposure before being seriously affected.
Repeated exposure to low concentrations
has resulted in human fatahties, the organs
chefly affected being the liver and kidneys.
A very dangerous fire and explosion
hazard when exposed to heat or flame; can
react vigorously with oxidizing materials.
Violent reaction with (H2 + Raney Ni),
AgClO4. Can form dangerous peroxides
when exposed to air. Potentially explosive
reaction with nitric acid + perchloric acid,
Raney nickel catalyst (above 210°C). Forms
explosive mixtures with decaborane (impactsensitive), triethynylaluminum (sensitive to
heating or drying). Violent reaction with
sulfur trioxide. Incompatible with sulfur
trioxide. To fight fire, use alcohol foam,
CO2, dry chemical. When heated to
decomposition it emits acrid smoke and
irritating fumes. See also GLYCOL
ETHERS.
Carcinogenicity
1,4-Dioxane is reasonably anticipated to be a human carcinogen basedon sufficient evidence of carcinogenicity from studies in experimental animals.
Source
Improper disposal of products listed below may result in 1,4-dioxane leaching into
groundwater.
Environmental fate
Biological. Heukelekian and Rand (1955) reported a 10-d BOD value of 0.00 g/g which is 0.0%
of the ThOD value of 1.89 g/g.
Photolytic. Irradiation of pure 1,4-dioxane through quartz using a 450-W medium-pressure
mercury lamp gave meso and racemic forms of 1-hydroxyethyldioxane, a pair of diastereomeric
dioxane dimers (Mazzocchi and Bowen, 1975), dioxanone, dioxanol, hydroxymethyldioxane, and
hydroxyethylidenedioxane (Houser and Sibbio, 1977). When 1,4-dioxane is subjected to a
megawatt ruby laser, 4% was decomposed yielding ethylene, carbon monoxide, hydrogen, and a
trace of formaldehyde (Watson and Parrish, 1971).
Chemical/Physical. Anticipated products from the reaction of 1,4-dioxane with ozone or OH
radicals in the atmosphere are glyoxylic acid, oxygenated formates, and OHCOCH2CH2OCHO
(Cupitt, 1980). Storage of 1,4-dioxane in the presence of air resulted in the formation of 1,2-
ethanediol monoformate and 1,2-ethane diformate (Jewett and Lawless, 1980). Stefan and Bolton (1998) studied the degradation of 1,4-dioxane in dilute aqueous solution by OH radicals.
Degradation follows pseudo-first-order kinetics at a rate of 8.7 x 10-3/sec. Within 5 min of direct
photolysis of hydrogen peroxide to generate OH radicals, almost 90% of the 1,4-dioxane reacted.
Four primary intermediate formed were 1,2-ethanediol monoformate, 1,2-ethanediol diformate,
formic acid, and methoxyacetic acid. These compounds were attacked by OH radicals yielding
glycolic, glyoxylic, and acetic acids which led to oxalic acid as the last intermediate. Malonic acid
was also identified as a minor intermediate. Twelve minutes into the reaction, the pH decreased
rapidly to 3.25 from 5.0, then less rapidly to 3.25 after 23 min. After 1 h, the pH rose to 4.2 min.
The decrease of pH during the initial stages of reaction is consistent with the formation of organic
acids. Oxidation of organic acid by OH radicals led to an increase of pH. The investigators
reported that the lower pH at the end of the experiment was due to carbonic acid formed during the
mineralization process.
storage
dioxane should be used only in areas free of ignition sources, and quantities greater than 1 liter should be stored in tightly sealed metal containers in areas separate from oxidizers. Containers of dioxane should be dated when opened and tested periodically for the presence of peroxides.
Purification Methods
It is prepared commercially either by dehydration of ethylene glycol with H2SO4 and heating ethylene oxide or bis(.-chloroethyl)ether with NaOH. The usual impurities are acetaldehyde, ethylene acetal, acetic acid, water and peroxides. Peroxides can be removed (and the aldehyde content decreased) by percolation through a column of activated alumina (80g per 100-200mL solvent), by refluxing with NaBH4 or anhydrous stannous chloride and distilling, or by acidification with conc HCl, shaking with ferrous sulfate and leaving in contact with it for 24hours before filtering and purifying further. Hess and Frahm [Chem Ber 71 2627 1938] refluxed 2L of dioxane with 27mL conc HCl and 200mL water for 12hours with slow passage of nitrogen to remove acetaldehyde. After cooling the solution, KOH pellets were added slowly and with shaking until no more would dissolve and a second layer had separated. The dioxane was decanted, treated with fresh KOH pellets to remove any aqueous phase, then transferred to a clean flask where it was refluxed for 6-12hours with sodium, then distilled from it. Alternatively, Kraus and Vingee [J Am Chem Soc 56 511 1934] heated it on a steam bath with solid KOH until fresh addition of KOH gave no more resin (due to acetaldehyde). After filtering through paper, the dioxane was refluxed over sodium until the surface of the metal was not further discoloured during several hours. It was then distilled from sodium. The acetal (b 82.5o) is removed during fractional distillation. Traces of *benzene, if present, can be removed as the *benzene/MeOH azeotrope by distillation in the presence of MeOH. Distillation from LiAlH4 removes aldehydes, peroxides and water. Dioxane can be dried using Linde type 4X molecular sieves. Other purification procedures include distillation from excess C2H5MgBr, refluxing with PbO2 to remove peroxides, fractional crystallisation by partial freezing and the addition of KI to dioxane acidified with aqueous HCl. Dioxane should be stored out of contact with air, preferably under N2. A detailed purification procedure is as follows: Dioxane is stood over ferrous sulfate for at least 2 days, under nitrogen. Then water (100mL) and conc HCl (14mL)/ litre of dioxane are added (giving a pale yellow colour). After refluxing for 8-12hours with vigorous N2 bubbling, pellets of KOH are added to the warm solution to form two layers and to discharge the colour. The solution is cooled rapidly with more KOH pellets being added (magnetic stirring) until no more dissolved in the cooled solution. After 4-12hours, if the lower phase is not black, the upper phase is decanted rapidly into a clean flask containing sodium, and refluxed over sodium (until freshly added sodium remained bright) for 1hour. The middle fraction is collected (and checked for minimum absorbency below 250nm). The distillate is fractionally frozen three times by cooling in a refrigerator, with occasional shaking or stirring. This material is stored in a refrigerator. Before use it is thawed, refluxed over sodium for 48hours, and distilled into a container. All joints are clad with Teflon tape. Coetzee and Chang [Pure Appl Chem 57 633 1985] dried the solvent by passing it slowly through a column (20g/L) of 3A molecular sieves activated by heating at 250o for 24hours. Impurities (including peroxides) are removed by passing the effluent slowly through a column packed with type NaX zeolite (pellets ground to 0.1mm size) activated by heating at 400o for 24hours or chromatographic grade basic Al2O3 activated by heating at 250o for 24hours. After removal of peroxides the effluent is refluxed for several hours over sodium wire, excluding moisture, distilled under nitrogen or argon and stored in the dark. One of the best tests of purity of dioxane is the formation of the purple disodium benzophenone complex during reflux and its persistence on cooling. (Benzophenone is better than fluorenone for this purpose and for the storing of the solvent.) [Carter et al. Trans Faraday Soc 56 343 1960, Beilstein 19 V 16.] TOXIC. Rapid purification: Check for peroxides (see Chapter 1 and Chapter 2 for test under ethers). Pre-dry with CaCl2 or better over Na wire. Then reflux the pre-dried solvent over Na (1% w/v) and benzophenone (0.2% w/v) under an inert atmosphere until the blue colour of the benzophenone ketyl radical anion persists. Distil, and store it over 4A molecular sieves in the dark.
Toxicity evaluation
Eye and respiratory irritation occurs from direct contact of
1,4-dioxane with mucous membranes. Pharmacokinetic and
toxicological data indicate that liver and kidney toxicity
induced by 1,4-dioxane occurs only after doses large enough to
saturate processes for detoxification and elimination.
1,4-Dioxane is one of many carcinogens that have not been
demonstrated to react significantly with DNA. Its cancer mode
of action is not sufficiently well understood to permit assignment
to a specific class of epigenetic agents. However, the data
suggest a tumor promotion mechanism associated with tissue
injury and subsequent regeneration.
Incompatibilities
Dioxane can form potentially explosive peroxides upon long exposure to air. Dioxane may react violently with Raney nickel catalyst, nitric and perchloric acids, sulfur trioxide, and strong oxidizing reagents.
Waste Disposal
Excess dioxane and waste material containing this substance should be placed in an appropriate container, clearly labeled, and handled according to your institution's waste disposal guidelines.
Precautions
Workers Should be careful during handling of 1,4-Dioxane and avoid open flames, sparks
and smoking. Workers should wear proper protectives since 1,4-Dioxane in known as hazardous,
cause damage to eyes, respiratory tract, liver and kidney.
Check Digit Verification of cas no
The CAS Registry Mumber 123-91-1 includes 6 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 3 digits, 1,2 and 3 respectively; the second part has 2 digits, 9 and 1 respectively.
Calculate Digit Verification of CAS Registry Number 123-91:
(5*1)+(4*2)+(3*3)+(2*9)+(1*1)=41
41 % 10 = 1
So 123-91-1 is a valid CAS Registry Number.
InChI:InChI=1/C4H8O2/c1-3-5-4-2;2*1-2/h3-4H2,1-2H3;2*1-2H2
123-91-1Relevant articles and documents
Synthesis of cyclic ethers from diols in the presence of copper catalysts
Bayguzina,Gimaletdinova,Khusnutdinov
, p. 1840 - 1843 (2017)
A number of cyclic ethers, namely tetrahydrofuran, 2,5-dimethyltetrahydrofuran, tetrahydropyran, 1,4-dioxane, oxepane, oxocane, and 1,4-oxathiane, have been synthesized in high yields by intramolecular dehydration of diols in the presence of copper-based catalysts.
Reaction of butyltin hydroxide oxide with p-toluenesulfonic acid: Synthesis, X-ray crystal analysis, and multinuclear NMR characterization of {(BuSn)12O14(OH)6}(4-CH3C 6H4SO3)2
Eychenne-Baron, Christophe,Ribot, Fran?ois,Steunou, Nathalie,Sanchez, Clément,Fayon, Franck,Biesemans, Monique,Martins, José C.,Willem, Rudolph
, p. 1940 - 1949 (2000)
The reaction of butyltin hydroxide oxide, BuSnO(OH), with p-toluenesulfonic acid, 4-CH3C6H4SO3H, yields the butyltin oxo cluster {(BuSn)12(μ3-O)14(μ2-OH) 6}2+ mixed with a soluble ill-defined butyltin oxo polymer, the presence of which was established by solid-state and quantitative solution 119Sn NMR. The reaction conditions were varied in order to optimize the yield of oxo cluster, which can be quantitatively isolated by crystallization as {(BuSn)12O14(OH)6}(4-CH3C 6H4SO3)2·C4H 8O2 (1·diox). The structure of the latter compound was determined by X-ray diffraction. 1·diox and {(BuSn)12O14(OH)6}-(4-CH3C 6H4SO3)2 (1) were also characterized by solid-state 119Sn MAS NMR and solution 119Sn, 1H, and 13C NMR. In 1·diox, the existence of weak Lewis interactions, taking place in the crystal between five-coordinate tin atoms and dioxane molecules, was evidenced by solid-state 119Sn NMR. 2D 1H-1H NOESY and ROESY experiments, along with ionic conductivity measurements, have proved that the ionic dissociation between {(BuSn)12O14(OH)6}2+ and 4-CH3C6H4SO3- (PTS-) does not take place in dichloromethane, while it does in the more polar and dissociating dimethyl sulfoxide. Using the 1H-119Sn J-HMQC NMR technique, the weak 2J(1H-O-119Sn) coupling constant between the μ2-OH and the six-coordinate tin nuclei was determined and shown to depend on the solvent.
Synthesis of 1,4-dioxene from diethylene glycol in the presence of bifunctional copper-containing catalysts. Effect of support on the selectivity of dioxene formation
Gitis,Neumoeva,Isagulyants
, p. 23 - 29 (1996)
In the synthesis of 1,4-dioxene from diethylene glycol in the presence of a bifunctional copper-containing catalyst, the composition of the by-products has been studied and the effect of the support on the overall direction of the reactions has been investigated. It has been established that on Cu/SiO2, 1,4-dioxanone is formed together with dioxene, the yield of the former increasing with an increase in the content of copper in the catalyst. This is due to an increase in the dehydrogenating function of the latter. On the more acidic Cu/Al2O3, 1,4-dioxane is mainly obtained together with, to a lesser degree, methyl-1,3-dioxolane. This is due to the predominance of dehydration reactions followed by isomerization. Dioxene, dioxane, and methyldioxolane are formed on Cu/HNaY, and the yield of the latter increases with an increase in the degree of acidity (degree of decationization) of the zeolite. It is possible to increase the selectivity of dioxene formation substantially with the use of a catalyst with a moderately acidic zeolite, by varying its copper content and by dilution with water vapor. 1996 Plenum Publishing Corporation.
Catalysis, kinetic and mechanistical studies for the transformation of ethylene glycol by alumina and silica gel under autogenous pressure and solvent-free conditions
Rohand, Taoufik,Tanemura, Kiyoshi
, p. 387 - 394 (2021/06/25)
A kinetic and mechanistical studies of the new pathway for competitive transformation of ethylene glycol by alumina and silica gel have been described. Commercial alumina (Al com), synthetic alumina (Al syn), commercial silica gel (Si com) and synthetic silica gel (Si syn) were used for the transformation of ethylene glycol to a mixture of diethylene glycol, 1,4-dioxane and 2-methyl-1,3-dioxolane via acetaldehyde by heating at 150 °C under autogenous pressure without solvent. The results show that the yield of these three products strongly depends on the nature of the used catalyst and the reaction time.
Synthesis of dioxolanes and oxazolidines by silica gel catalysis
Rohand, Taoufik,Savary, Jér?me,Markó, István E.
, p. 1429 - 1436 (2018/06/25)
Abstract: Ethylene glycol condensed with carbonyl compounds in the presence of silica gel or alumina, without solvent and under pressure, affords 1,3-dioxolanes. 2-Amino-2-methylpropanol also condensed with carbonyl compounds in the presence of silica gel or an acid-activated clay, without solvent and under pressure, produces oxazolidines. To explain these results, we propose that the glycol and the aminopropanol react with Br?nsted (H+) and Lewis acid sites (Si and Al) located on the surface of the catalysts, leading to the products via various ionic intermediates.
Transition metal triflate catalyzed conversion of alcohols, ethers and esters to olefins
Keskiv?li,Parviainen,Lagerblom,Repo
, p. 15111 - 15118 (2018/05/04)
Herein, we report an efficient transition metal triflate catalyzed approach to convert biomass-based compounds, such as monoterpene alcohols, sugar alcohols, octyl acetate and tea tree oil, to their corresponding olefins in high yields. The reaction proceeds through C-O bond cleavage under solvent-free conditions, where the catalytic activity is determined by the oxophilicity and the Lewis acidity of the metal catalyst. In addition, we demonstrate how the oxygen containing functionality affects the formation of the olefins. Furthermore, the robustness of the used metal triflate catalysts, Fe(OTf)3 and Hf(OTf)4, is highlighted by their ability to convert an over 2400-fold excess of 2-octanol to octenes in high isolated yields.
Iron-Catalyzed Ring-Closing C?O/C?O Metathesis of Aliphatic Ethers
Biberger, Tobias,Makai, Szabolcs,Lian, Zhong,Morandi, Bill
supporting information, p. 6940 - 6944 (2018/05/14)
Among all metathesis reactions known to date in organic chemistry, the metathesis of multiple bonds such as alkenes and alkynes has evolved into one of the most powerful methods to construct molecular complexity. In contrast, metathesis reactions involving single bonds are scarce and far less developed, particularly in the context of synthetically valuable ring-closing reactions. Herein, we report an iron-catalyzed ring-closing metathesis of aliphatic ethers for the synthesis of substituted tetrahydropyrans and tetrahydrofurans, as well as morpholines and polycyclic ethers. This transformation is enabled by a simple iron catalyst and likely proceeds via cyclic oxonium intermediates.
Thermal and hydrolytic decomposition mechanisms of organosilicon electrolytes with enhanced thermal stability for lithium-ion batteries
Guillot, Sarah L.,Pe?a-Hueso, Adrian,Usrey, Monica L.,Hamers, Robert J.
, p. A1907 - A1917 (2018/02/28)
The high flammability and thermal instability of conventional carbonate electrolytes limit the safety and performance of lithiumion batteries (LIBs) and other electrochemical energy storage devices. Organosilicon solvents have shown promise due to their reduced flammability and greater chemical stability at high temperatures. A series of organosilicon electrolytes with different functional substituents were studied to understand the structural origins of this enhanced stability. The thermal and hydrolytic stability of organosilicon and carbonate solvents with LiPF6 was probed by storage at high temperatures and with added water. Quantitative monitoring of organosilicon and carbonate electrolyte decomposition products over time using NMR spectroscopy revealed mechanisms of degradation and led to the discovery of a key PF5-complex that forms in organosilicon electrolytes to inhibit further salt breakdown. Increased knowledge of specific structural contributions to electrolyte stability informs the development of future electrolyte solvents to enable the safer operation of high-performing lithium-ion batteries.
Selective synthesis of dimethoxyethane via directly catalytic etherification of crude ethylene glycol
Yu, Weiqiang,Lu, Fang,Huang, Qianqian,Lu, Rui,Chen, Shuai,Xu, Jie
supporting information, p. 3327 - 3333 (2017/07/28)
Etherification of ethylene glycol with methanol provides a sustainable route for the production of widely used dimethoxyethane; dimethoxyethane is a green solvent and reagent that is applied in batteries and used as a potential diesel fuel additive. SAPO-34 zeolite was found to be an efficient and highly selective catalyst for this etherification via a continuous flow experiment. It achieved up to 79.4% selectivity for dimethoxyethane with around 96.7% of conversion. The relationship of the catalyst's structure and the dimethoxyethane selectivity was established via control experiments. The results indicated that the pore structure of SAPO-34 effectively limited the formation of 1,4-dioxane from activated ethylene glycol, enhanced the reaction of the activated methanol with ethylene glycol in priority, and thus resulted in high selectivity for the desired products. The continuous flow technology used in the study could efficiently promote the complete etherification of EG with methanol to maintain high selectivity for dimethoxyethane.
METHOD FOR PREPARING DOUBLE-SEALED-END GLYCOL ETHER
-
Paragraph 0042; 0044; 0046, (2017/12/27)
Disclosed is a method for preparing a double end capped glycol ether, the method comprising: introducing into a reactor a raw material comprising a glycol monoether and a monohydric alcohol ether, and enabling the raw material to contact and react with an acidic molecular sieve catalyst to generate a double end capped glycol ether, a reaction temperature being 50-300° C., a reaction pressure being 0.1-15 MPa, a WHSV of the glycol monoether in the raw material being 0.01-15.0 h?1, and a mole ratio of the monohydric alcohol ether to the glycol monoether in the raw material being 1-100:1. The method of the present invention enables a long single-pass lifespan of the catalyst and repeated regeneration, has a high yield and selectivity of a target product, low energy consumption during separation of the product, a high economic value of a by-product, and is flexible in production scale and application.
