1,4-Dioxane () is a
heterocyclic
A heterocyclic compound or ring structure is a cyclic compound that has atoms of at least two different elements as members of its ring(s). Heterocyclic chemistry is the branch of organic chemistry dealing with the synthesis, properties, and ...
organic compound
In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. T ...
, classified as an
ether
In organic chemistry, ethers are a class of compounds that contain an ether group—an oxygen atom connected to two alkyl or aryl groups. They have the general formula , where R and R′ represent the alkyl or aryl groups. Ethers can again be ...
. It is a colorless liquid with a faint sweet
odor similar to that of
diethyl ether
Diethyl ether, or simply ether, is an organic compound in the ether class with the formula , sometimes abbreviated as (see Pseudoelement symbols). It is a colourless, highly volatile, sweet-smelling ("ethereal odour"), extremely flammable li ...
. The compound is often called simply dioxane because the other dioxane
isomers (
1,2- and
1,3-) are rarely encountered.
Dioxane is used as a solvent for a variety of practical applications as well as in the laboratory, and also as a stabilizer for the transport of
chlorinated hydrocarbons
An organochloride, organochlorine compound, chlorocarbon, or chlorinated hydrocarbon is an organic compound containing at least one covalently bonded atom of chlorine. The chloroalkane class ( alkanes with one or more hydrogens substituted by chlo ...
in aluminum containers.
[Wisconsin Department of Health Services (2013]
1,4-Dioxane Fact Sheet
Publication 00514. Accessed 2016-11-12.
Synthesis
Dioxane is produced by the acid-catalysed
dehydration
In physiology, dehydration is a lack of total body water, with an accompanying disruption of metabolic processes. It occurs when free water loss exceeds free water intake, usually due to exercise, disease, or high environmental temperature. Mil ...
of
diethylene glycol
Diethylene glycol (DEG) is an organic compound with the formula (HOCH2CH2)2O. It is a colorless, practically odorless, and hygroscopic liquid with a sweetish taste. It is a four carbon dimer of ethylene glycol. It is miscible in water, alcohol, ...
, which in turn is obtained from the
hydrolysis
Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution, elimination, and solvation reactions in which water is the nucleophile.
Biological hydrolys ...
of
ethylene oxide
Ethylene oxide is an organic compound with the formula . It is a cyclic ether and the simplest epoxide: a three-membered ring consisting of one oxygen atom and two carbon atoms. Ethylene oxide is a colorless and flammable gas with a faintly sw ...
.
In 1985, the global production capacity for dioxane was between 11,000 and 14,000 tons.
In 1990, the total U.S. production volume of dioxane was between 5,250 and 9,150 tons.
Structure
The dioxane molecule is centrosymmetric, meaning that it adopts a
chair conformation
In organic chemistry, cyclohexane conformations are any of several three-dimensional shapes adopted by molecules of cyclohexane. Because many compounds feature structurally similar six-membered rings, the structure and dynamics of cyclohexane are ...
, typical of relatives of
cyclohexane. However, the molecule is conformationally flexible, and the
boat conformation
In organic chemistry, cyclohexane conformations are any of several three-dimensional shapes adopted by molecules of cyclohexane. Because many compounds feature structurally similar six-membered rings, the structure and dynamics of cyclohexane are ...
is easily adopted, e.g. in the
chelation
Chelation is a type of bonding of ions and molecules to metal ions. It involves the formation or presence of two or more separate coordinate bonds between a polydentate (multiple bonded) ligand and a single central metal atom. These ligands are ...
of metal cations.
Dioxane resembles a smaller
crown ether
In organic chemistry, crown ethers are cyclic chemical compounds that consist of a ring containing several ether groups (). The most common crown ethers are cyclic oligomers of ethylene oxide, the repeating unit being ethyleneoxy, i.e., . Impo ...
with only two ethyleneoxyl units.
Uses
Trichloroethane transport
In the 1980s, most of the dioxane produced was used as a stabilizer for
1,1,1-trichloroethane
The organic compound 1,1,1-trichloroethane, also known as methyl chloroform, is a chloroalkane. This colorless, sweet-smelling liquid was once produced industrially in large quantities for use as a solvent. It is regulated by the Montreal Prot ...
for storage and transport in
aluminium
Aluminium (aluminum in American and Canadian English) is a chemical element with the symbol Al and atomic number 13. Aluminium has a density lower than those of other common metals, at approximately one third that of steel. I ...
containers. Normally aluminium is protected by a passivating oxide layer, but when these layers are disturbed, the metallic aluminium reacts with trichloroethane to give
aluminium trichloride
Aluminium chloride, also known as aluminium trichloride, is an inorganic compound with the formula . It forms hexahydrate with the formula , containing six water molecules of hydration. Both are colourless crystals, but samples are often conta ...
, which in turn catalyses the
dehydrohalogenation
In chemistry, dehydrohalogenation is an elimination reaction which removes a hydrogen halide from a substrate. The reaction is usually associated with the synthesis of alkenes, but it has wider applications.
Dehydrohalogenation from alkyl halid ...
of the remaining trichloroethane to
vinylidene chloride
1,1-Dichloroethene, commonly called 1,1-dichloroethylene or vinylidene chloride or 1,1-DCE, is an organochloride with the molecular formula CHCl. It is a colorless liquid with a sharp odor. Like most chlorocarbons, it is poorly soluble in water, ...
and
hydrogen chloride
The compound hydrogen chloride has the chemical formula and as such is a hydrogen halide. At room temperature, it is a colourless gas, which forms white fumes of hydrochloric acid upon contact with atmospheric water vapor. Hydrogen chloride ga ...
. Dioxane "poisons" this catalysis reaction by forming an
adduct
An adduct (from the Latin ''adductus'', "drawn toward" alternatively, a contraction of "addition product") is a product of a direct addition of two or more distinct molecules, resulting in a single reaction product containing all atoms of all co ...
with aluminum trichloride.
As a solvent
![Binary phase diagram dioxane-water](https://upload.wikimedia.org/wikipedia/commons/b/b4/Binary_phase_diagram_dioxane-water.svg)
Dioxane is used in a variety of applications as a versatile
aprotic solvent, e. g. for inks, adhesives, and cellulose esters. It is substituted for
tetrahydrofuran
Tetrahydrofuran (THF), or oxolane, is an organic compound with the formula (CH2)4O. The compound is classified as heterocyclic compound, specifically a cyclic ether. It is a colorless, water- miscible organic liquid with low viscosity. It is ...
(THF) in some processes, because of its lower toxicity and higher boiling point (101 °C, versus 66 °C for THF).
[Klaus Weissermel, Hans-Jürgen Arpe (2003) "Industrial Organic Chemistry". John Wiley & Sons, page 158. , 9783527305780.]
While diethyl ether is rather insoluble in water, dioxane is
miscible and in fact is
hygroscopic
Hygroscopy is the phenomenon of attracting and holding water molecules via either absorption or adsorption from the surrounding environment, which is usually at normal or room temperature. If water molecules become suspended among the substan ...
. At standard pressure, the mixture of water and dioxane in the ratio 17.9:82.1 by mass is a positive
azeotrope
An azeotrope () or a constant heating point mixture is a mixture of two or more liquids whose proportions cannot be altered or changed by simple distillation.Moore, Walter J. ''Physical Chemistry'', 3rd e Prentice-Hall 1962, pp. 140–142 This ...
that boils at 87.6 C.
The oxygen atoms are
Lewis-basic, and so dioxane is able to solvate many inorganic compounds and serves as a chelating diether ligand. It forms 1:1 adducts with a variety of Lewis acids such as I
2, phenols, alcohols, and bis(hexafloroacetylacetonato)copper(II). It is classified as a
hard base and its base parameters in the
ECW model are E
B =1.86 and C
B = 1.29. It reacts with
Grignard reagents
A Grignard reagent or Grignard compound is a chemical compound with the general formula , where X is a halogen and R is an organic group, normally an alkyl or aryl. Two typical examples are methylmagnesium chloride and phenylmagnesium bromide . ...
to precipitate the magnesium dihalide. In this way, dioxane is used to drive the
Schlenk equilibrium Schlenk can refer to:
People
* Wilhelm Schlenk (1879-1943), German chemist
In chemistry
* Schlenk flask
* Schlenk line
The Schlenk line (also vacuum gas manifold) is a commonly used chemistry apparatus developed by Wilhelm Schlenk. It consists ...
.
Dimethylmagnesium
Dimethylmagnesium is an organomagnesium compound. It is a white pyrophoric solid. Dimethylmagnesium is used in the synthesis of organometallic compounds.
Preparation
Like other dialkylmagnesium compounds, dimethylmagnesium is prepared by adding d ...
is prepared in this manner:
:2 CHMgBr + (CHO) → MgBr(CHO) + (CH)Mg
Spectroscopy
Dioxane is used as an internal standard for
nuclear magnetic resonance spectroscopy
Nuclear magnetic resonance spectroscopy, most commonly known as NMR spectroscopy or magnetic resonance spectroscopy (MRS), is a spectroscopic technique to observe local magnetic fields around atomic nuclei. The sample is placed in a magnetic fie ...
in
deuterium oxide.
Toxicology
Safety
Dioxane has an of 5170 mg/kg in rats.
It is irritating to the eyes and respiratory tract. Exposure may cause damage to the central nervous system, liver and kidneys. In a 1978 mortality study conducted on workers exposed to 1,4-dioxane, the observed number deaths from cancer was not significantly different from the expected number. Dioxane is classified by the National Toxicology Program as "reasonably anticipated to be a human carcinogen". It is also classified by the
IARC IARC may refer to:
* International Aerial Robotics Competition
* International Age Rating Coalition
* International Agency for Research on Cancer
* International Arctic Research Center
* Israel Amateur Radio Club
The Israel Amateur Radio Club (IA ...
as a
Group 2B carcinogen: ''possibly carcinogenic to humans'' because it is a known carcinogen in other animals. The
United States Environmental Protection Agency
The Environmental Protection Agency (EPA) is an independent executive agency of the United States federal government tasked with environmental protection matters. President Richard Nixon proposed the establishment of EPA on July 9, 1970; it ...
classifies dioxane as a probable human
carcinogen
A carcinogen is any substance, radionuclide, or radiation that promotes carcinogenesis (the formation of cancer). This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes. Several radioactive subs ...
(having observed an increased incidence of cancer in controlled animal studies, but not in epidemiological studies of workers using the compound), and a known irritant (with a no-observed-adverse-effects level of 400 milligrams per cubic meter) at concentrations significantly higher than those found in commercial products.
[1,4-Dioxane (1,4-Diethyleneoxide). Hazard Summary. ''U.S. Environmental Protection Agency''. Created in April 1992; Revised in January 2000]
Fact Sheet
Under
California Proposition 65, dioxane is classified in the U.S. State of California to cause cancer.
Animal studies in rats suggest that the greatest health risk is associated with inhalation of vapors in the pure form. The State of New York has adopted a first-in-the-nation drinking water standard for 1,4-Dioxane and set the maximum contaminant level of 1 part per billion.
It tends to concentrate in the water and has little affinity for soil. It is resistant to abiotic degradation in the environment, and was formerly thought to also resist
biodegradation
Biodegradation is the breakdown of organic matter by microorganisms, such as bacteria and fungi. It is generally assumed to be a natural process, which differentiates it from composting. Composting is a human-driven process in which biodegrada ...
. However, more recent studies since the 2000s have found that it can be biodegraded through a number of pathways, suggesting that
bioremediation
Bioremediation broadly refers to any process wherein a biological system (typically bacteria, microalgae, fungi, and plants), living or dead, is employed for removing environmental pollutants from air, water, soil, flue gasses, industrial effluent ...
can be used to treat 1,4-dioxane contaminated water.
Explosion hazard
Like some other ethers, dioxane combines with atmospheric oxygen upon prolonged exposure to air to form potentially explosive
peroxide
In chemistry, peroxides are a group of compounds with the structure , where R = any element. The group in a peroxide is called the peroxide group or peroxo group. The nomenclature is somewhat variable.
The most common peroxide is hydrogen ...
s.
Distillation
Distillation, or classical distillation, is the process of separating the components or substances from a liquid mixture by using selective boiling and condensation, usually inside an apparatus known as a still. Dry distillation is the heat ...
of these mixtures is dangerous. Storage under metallic sodium could limit the risk of explosion.
Environment
Dioxane has affected groundwater supplies in several areas. Dioxane at the level of 1 μg/L (~1 ppb) has been detected in many locations in the US.
In the U.S. state of New Hampshire, it had been found at 67 sites in 2010, ranging in concentration from 2 ppb to over 11,000 ppb. Thirty of these sites are solid waste landfills, most of which have been closed for years. In 2019, the Southern Environmental Law Center successfully sued Greensboro, North Carolina's Wastewater treatment after 1,4-Dioxane was found at 20 times above EPA safe levels in the Haw River.
Cosmetics
As a byproduct of the
ethoxylation
Ethoxylation is a chemical reaction in which ethylene oxide adds to a substrate. It is the most widely practiced alkoxylation, which involves the addition of epoxides to substrates.
In the usual application, alcohols and phenols are converted in ...
process, a route to some ingredients found in cleansing and moisturizing products, dioxane can contaminate cosmetics and personal care products such as deodorants, perfumes, shampoos, toothpastes and mouthwashes. The ethoxylation process makes the cleansing agents, such as
sodium laureth sulfate
Sodium laureth sulfate (SLES), an accepted contraction of sodium lauryl ether sulfate (SLES), also called sodium alkylethersulfate, is an anionic detergent and surfactant found in many personal care products (soaps, shampoos, toothpaste, etc.) an ...
and ammonium laureth sulfate, less abrasive and offers enhanced foaming characteristics. 1,4-Dioxane is found in small amounts in some cosmetics, a yet unregulated substance used in cosmetics in both China and the U.S. Research has found the chemical in ethoxylated raw ingredients and in off-the-shelf cosmetic products. The
Environmental Working Group
The Environmental Working Group (EWG) is an American activist group that specializes in research and advocacy in the areas of agricultural subsidies, toxic chemicals, drinking water pollutants, and corporate accountability. EWG is a nonprofit ...
(EWG) found that 97% of hair relaxers, 57% of baby soaps and 22 percent of all products in Skin Deep, their database for cosmetic products, are contaminated with 1,4-dioxane.
Since 1979 the
U.S. Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...
(FDA) have conducted tests on cosmetic raw materials and finished products for the levels of 1,4-dioxane.
1,4-Dioxane was present in ethoxylated raw ingredients at levels up to 1410 ppm (~0.14%wt), and at levels up to 279 ppm (~0.03%wt) in off the shelf cosmetic products.
Levels of 1,4-dioxane exceeding 85 ppm (~0.01%wt) in children's shampoos indicate that close monitoring of raw materials and finished products is warranted.
While the FDA encourages manufacturers to remove 1,4-dioxane, it is not required by federal law.
[FDA/CFSAN--Cosmetics Handbook Part 3: Cosmetic Product-Related Regulatory Requirements and Health Hazard Issues]
Prohibited Ingredients and other Hazardous Substances: 9. Dioxane
Web.archive.org
On 9 December 2019, New York passed a bill to ban the sale of cosmetics with more than 10 ppm of 1,4-dioxane as of the end of 2022. The law will also prevent the sale of household cleaning and personal care products containing more than 2 ppm of 1,4-dioxane at the end of 2022.
See also
![Dioxane isomers named](https://upload.wikimedia.org/wikipedia/commons/b/ba/Dioxane_isomers_named.PNG)
*
1,2-Dioxane
1,2-Dioxane or ''o''-dioxane is an organic compound with the molecular formula (CH)O, classified as a cyclic peroxide. Its synthesis was reported in 1956 by Criegee and Müller, who prepared it by reacting butane-1,4-diol bis(methanesulfonate) wi ...
*
1,3-Dioxane
1,3-Dioxane or ''m''-dioxane is a chemical compound with the molecular formula C4H8O2. It is a saturated six-membered heterocycle with two oxygen atoms in place of carbon atoms at the 1- and 3- positions. The corresponding five-membered rings are ...
*
Dioxolane
Dioxolane is a heterocyclic acetal with the chemical formula (CH2)2O2CH2. It is related to tetrahydrofuran by interchange of one oxygen for a CH2 group. The corresponding saturated 6-membered C4O2 rings are called dioxanes. The isomeric 1,2-diox ...
*
9-crown-3
*
Crown ether
In organic chemistry, crown ethers are cyclic chemical compounds that consist of a ring containing several ether groups (). The most common crown ethers are cyclic oligomers of ethylene oxide, the repeating unit being ethyleneoxy, i.e., . Impo ...
*
Dioxane tetraketone
Dioxane tetraketone (or 1,4-dioxane-2,3,5,6-tetrone) is an organic compound with the formula C4O6. It is an oxide of carbon (an oxocarbon), which can be viewed as the fourfold ketone of dioxane. It can also be viewed as the cyclic dimer of oxi ...
*
Oxalic anhydride
Oxalic anhydride or ethanedioic anhydride, also called oxiranedione, is a hypothetical organic compound, one of several isomers having the formula C2O3 that have been studied computationally. It can be viewed as the anhydride of oxalic acid or ...
*
Sodium laureth sulfate
Sodium laureth sulfate (SLES), an accepted contraction of sodium lauryl ether sulfate (SLES), also called sodium alkylethersulfate, is an anionic detergent and surfactant found in many personal care products (soaps, shampoos, toothpaste, etc.) an ...
*
Dioxanone
References
{{DEFAULTSORT:Dioxane, 1, 4-
Dioxanes
Ether solvents
IARC Group 2B carcinogens
Crown ethers
Sweet-smelling chemicals