Names | |||
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Preferred IUPAC name Oxolane [1] | |||
Systematic IUPAC name 1,4-Epoxybutane 1-Oxacyclopentane | |||
Other names Tetrahydrofuran THF 1,4-Butylene oxide Cyclotetramethylene oxide fraction Furanidin Tetra-methylene oxide, Oxolane | |||
Identifiers | |||
3D model (JSmol) | |||
Abbreviations | THF | ||
ChEBI | |||
ChEMBL | |||
ChemSpider | |||
ECHA InfoCard | 100.003.389 | ||
PubChem CID | |||
RTECS number |
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UNII | |||
CompTox Dashboard (EPA) | |||
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Properties | |||
C4H8O | |||
Molar mass | 72.107 g·mol−1 | ||
Appearance | Colorless liquid | ||
Odor | Ether-like [2] | ||
Density | 0.8876 g/cm3 at 20 °C, liquid [3] | ||
Melting point | −108.4 °C (−163.1 °F; 164.8 K) | ||
Boiling point | 66 °C (151 °F; 339 K) [4] [3] | ||
Miscible | |||
Vapor pressure | 132 mmHg (20 °C) [2] | ||
Refractive index (nD) | 1.4073 (20 °C) [3] | ||
Viscosity | 0.48 cP at 25 °C | ||
Structure | |||
Envelope | |||
1.63 D (gas) | |||
Hazards | |||
GHS labelling: | |||
[5] | |||
Danger | |||
H225, H302, H319, H335, H351 [5] | |||
P210, P280, P301+P312+P330, P305+P351+P338, P370+P378, P403+P235 [5] | |||
NFPA 704 (fire diamond) | |||
Flash point | −14 °C (7 °F; 259 K) | ||
Explosive limits | 2–11.8% [2] | ||
Lethal dose or concentration (LD, LC): | |||
LD50 (median dose) |
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LC50 (median concentration) | 21000 ppm (rat, 3 h) [6] | ||
NIOSH (US health exposure limits): | |||
PEL (Permissible) | TWA 200 ppm (590 mg/m3) [2] | ||
REL (Recommended) | TWA 200 ppm (590 mg/m3) ST 250 ppm (735 mg/m3) [2] | ||
IDLH (Immediate danger) | 2000 ppm [2] | ||
Related compounds | |||
Related heterocycles | Furan Pyrrolidine Dioxane | ||
Related compounds | Diethyl ether | ||
Supplementary data page | |||
Tetrahydrofuran (data page) | |||
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). |
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 mainly used as a precursor to polymers. [8] Being polar and having a wide liquid range, THF is a versatile solvent. It is an isomer of another solvent, butanone.
About 200,000 tonnes of tetrahydrofuran are produced annually. [9] The most widely used industrial process involves the acid-catalyzed dehydration of 1,4-butanediol. Ashland/ISP is one of the biggest producers of this chemical route. The method is similar to the production of diethyl ether from ethanol. The butanediol is derived from condensation of acetylene with formaldehyde followed by hydrogenation. [8] DuPont developed a process for producing THF by oxidizing n-butane to crude maleic anhydride, followed by catalytic hydrogenation. [10] A third major industrial route entails hydroformylation of allyl alcohol followed by hydrogenation to 1,4-butanediol.
THF can also be synthesized by catalytic hydrogenation of furan. [11] [12] This allows certain sugars to be converted to THF via acid-catalyzed digestion to furfural and decarbonylation to furan, [13] although this method is not widely practiced. THF is thus derivable from renewable resources.
In the presence of strong acids, THF converts to a linear polymer called poly(tetramethylene ether) glycol (PTMEG), also known as polytetramethylene oxide (PTMO):
This polymer is primarily used to make elastomeric polyurethane fibers like Spandex. [14]
The other main application of THF is as an industrial solvent for polyvinyl chloride (PVC) and in varnishes. [8] It is an aprotic solvent with a dielectric constant of 7.6. It is a moderately polar solvent and can dissolve a wide range of nonpolar and polar chemical compounds. [15] THF is water-miscible and can form solid clathrate hydrate structures with water at low temperatures. [16]
THF has been explored as a miscible co-solvent in aqueous solution to aid in the liquefaction and delignification of plant lignocellulosic biomass for production of renewable platform chemicals and sugars as potential precursors to biofuels. [17] Aqueous THF augments the hydrolysis of glycans from biomass and dissolves the majority of biomass lignin making it a suitable solvent for biomass pretreatment.
THF is often used in polymer science. For example, it can be used to dissolve polymers prior to determining their molecular mass using gel permeation chromatography. THF dissolves PVC as well, and thus it is the main ingredient in PVC adhesives. It can be used to liquefy old PVC cement and is often used industrially to degrease metal parts.
THF is used as a component in mobile phases for reversed-phase liquid chromatography. It has a greater elution strength than methanol or acetonitrile, but is less commonly used than these solvents.
THF is used as a solvent in 3D printing when printing with PLA, PETG and substantially similar filaments. It can be used to clean clogged 3D printer parts, as well as when finishing prints to remove extruder lines and add a shine to the finished product.
In the laboratory, THF is a popular solvent when its water miscibility is not an issue. It is more basic than diethyl ether [18] and forms stronger complexes with Li+, Mg2+, and boranes. It is a popular solvent for hydroboration reactions and for organometallic compounds such as organolithium and Grignard reagents. [19] Thus, while diethyl ether remains the solvent of choice for some reactions (e.g., Grignard reactions), THF fills that role in many others, where strong coordination is desirable and the precise properties of ethereal solvents such as these (alone and in mixtures and at various temperatures) allows fine-tuning modern chemical reactions.
Commercial THF contains substantial water that must be removed for sensitive operations, e.g. those involving organometallic compounds. Although THF is traditionally dried by distillation from an aggressive desiccant such as elemental sodium, molecular sieves have been shown to be superior water scavengers. [20]
In the presence of a solid acid catalyst, THF reacts with hydrogen sulfide to give tetrahydrothiophene. [21]
THF is a Lewis base that bonds to a variety of Lewis acids such as I2, phenols, triethylaluminum and bis(hexafluoroacetylacetonato)copper(II). THF has been classified in the ECW model and it has been shown that there is no one order of base strengths. [23] Many complexes are of the stoichiometry MCl3(THF)3. [24]
THF is a relatively acutely nontoxic solvent, with the median lethal dose (LD50) comparable to that for acetone. However, chronic exposure is suspected of causing cancer. [5] [25] Reflecting its remarkable solvent properties, it penetrates the skin, causing rapid dehydration. THF readily dissolves latex and thus should be handled with nitrile rubber gloves. It is highly flammable.
One danger posed by THF is its tendency to form the explosive compound 2-hydroperoxytetrahydrofuran upon reaction with air:
To minimize this problem, commercial supplies of THF are often stabilized with butylated hydroxytoluene (BHT). Distillation of THF to dryness is unsafe because the explosive peroxides can concentrate in the residue.
The tetrahydrofuran ring is found in diverse natural products including lignans, acetogenins, and polyketide natural products. [26] Diverse methodology has been developed for the synthesis of substituted THFs. [27]
Tetrahydrofuran is one of the class of pentic cyclic ethers called oxolanes. There are seven possible structures, namely, [28]
In organic chemistry, ethers are a class of compounds that contain an ether group—an oxygen atom connected to two organyl groups. They have the general formula R−O−R′, where R and R′ represent organyl groups. Ethers can again be classified into two varieties: if the organyl groups are the same on both sides of the oxygen atom, then it is a simple or symmetrical ether, whereas if they are different, the ethers are called mixed or unsymmetrical ethers. A typical example of the first group is the solvent and anaesthetic diethyl ether, commonly referred to simply as "ether". Ethers are common in organic chemistry and even more prevalent in biochemistry, as they are common linkages in carbohydrates and lignin.
A solvent is a substance that dissolves a solute, resulting in a solution. A solvent is usually a liquid but can also be a solid, a gas, or a supercritical fluid. Water is a solvent for polar molecules, and the most common solvent used by living things; all the ions and proteins in a cell are dissolved in water within the cell.
In organometallic chemistry, organolithium reagents are chemical compounds that contain carbon–lithium (C–Li) bonds. These reagents are important in organic synthesis, and are frequently used to transfer the organic group or the lithium atom to the substrates in synthetic steps, through nucleophilic addition or simple deprotonation. Organolithium reagents are used in industry as an initiator for anionic polymerization, which leads to the production of various elastomers. They have also been applied in asymmetric synthesis in the pharmaceutical industry. Due to the large difference in electronegativity between the carbon atom and the lithium atom, the C−Li bond is highly ionic. Owing to the polar nature of the C−Li bond, organolithium reagents are good nucleophiles and strong bases. For laboratory organic synthesis, many organolithium reagents are commercially available in solution form. These reagents are highly reactive, and are sometimes pyrophoric.
Diisopropyl ether is a secondary ether that is used as a solvent. It is a colorless liquid that is slightly soluble in water, but miscible with organic solvents. It is used as an extractant and an oxygenate gasoline additive. It is obtained industrially as a byproduct in the production of isopropanol by hydration of propylene. Diisopropyl ether is sometimes represented by the abbreviation DIPE.
1,4-Dioxane is a heterocyclic organic compound, classified as an ether. It is a colorless liquid with a faint sweet odor similar to that of diethyl ether. The compound is often called simply dioxane because the other dioxane isomers are rarely encountered.
Dimethoxyethane, also known as glyme, monoglyme, dimethyl glycol, ethylene glycol dimethyl ether, dimethyl cellosolve, and DME, is a colorless, aprotic, and liquid ether that is used as a solvent, especially in batteries. Dimethoxyethane is miscible with water.
Butan-2-ol, or sec-butanol, is an organic compound with formula CH3CH(OH)CH2CH3. Its structural isomers are 1-butanol, isobutanol, and tert-butanol. 2-Butanol is chiral and thus can be obtained as either of two stereoisomers designated as (R)-(−)-butan-2-ol and (S)-(+)-butan-2-ol. It is normally encountered as a 1:1 mixture of the two stereoisomers — a racemic mixture.
The Mitsunobu reaction is an organic reaction that converts an alcohol into a variety of functional groups, such as an ester, using triphenylphosphine and an azodicarboxylate such as diethyl azodicarboxylate (DEAD) or diisopropyl azodicarboxylate (DIAD). Although DEAD and DIAD are most commonly used, there are a variety of other azodicarboxylates available which facilitate an easier workup and/or purification and in some cases, facilitate the use of more basic nucleophiles. It was discovered by Oyo Mitsunobu (1934–2003). In a typical protocol, one dissolves the alcohol, the carboxylic acid, and triphenylphosphine in tetrahydrofuran or other suitable solvent, cool to 0 °C using an ice-bath, slowly add the DEAD dissolved in THF, then stir at room temperature for several hours. The alcohol reacts with the phosphine to create a good leaving group then undergoes an inversion of stereochemistry in classic SN2 fashion as the nucleophile displaces it. A common side-product is produced when the azodicarboxylate displaces the leaving group instead of the desired nucleophile. This happens if the nucleophile is not acidic enough or is not nucleophilic enough due to steric or electronic constraints. A variation of this reaction utilizing a nitrogen nucleophile is known as a Fukuyama–Mitsunobu.
n-Butyllithium C4H9Li (abbreviated n-BuLi) is an organolithium reagent. It is widely used as a polymerization initiator in the production of elastomers such as polybutadiene or styrene-butadiene-styrene (SBS). Also, it is broadly employed as a strong base (superbase) in the synthesis of organic compounds as in the pharmaceutical industry.
Hydrogen fluoride (fluorane) is an inorganic compound with chemical formula HF. It is a very poisonous, colorless gas or liquid that dissolves in water to yield an aqueous solution termed hydrofluoric acid. It is the principal industrial source of fluorine, often in the form of hydrofluoric acid, and is an important feedstock in the preparation of many important compounds including pharmaceuticals and polymers, e.g. polytetrafluoroethylene (PTFE). HF is also widely used in the petrochemical industry as a component of superacids. Due to strong and extensive hydrogen bonding, it boils at near room temperature, much higher than other hydrogen halides.
tert-Butyllithium is a chemical compound with the formula (CH3)3CLi. As an organolithium compound, it has applications in organic synthesis since it is a strong base, capable of deprotonating many carbon molecules, including benzene. tert-Butyllithium is available commercially as solutions in hydrocarbons (such as pentane); it is not usually prepared in the laboratory.
Grignard reagents or Grignard compounds are chemical compounds with the general formula R−Mg−X, where X is a halogen and R is an organic group, normally an alkyl or aryl. Two typical examples are methylmagnesium chloride Cl−Mg−CH3 and phenylmagnesium bromide (C6H5)−Mg−Br. They are a subclass of the organomagnesium compounds.
Epichlorohydrin is an organochlorine compound and an epoxide. Despite its name, it is not a halohydrin. It is a colorless liquid with a pungent, garlic-like odor, moderately soluble in water, but miscible with most polar organic solvents. It is a chiral molecule generally existing as a racemic mixture of right-handed and left-handed enantiomers. Epichlorohydrin is a highly reactive electrophilic compound and is used in the production of glycerol, plastics, epoxy glues and resins, epoxy diluents and elastomers.
Nitroethane is an organic compound having the chemical formula C2H5NO2. Similar in many regards to nitromethane, nitroethane is an oily liquid at standard temperature and pressure. Pure nitroethane is colorless and has a fruity odor.
sec-Butyllithium is an organometallic compound with the formula CH3CHLiCH2CH3, abbreviated sec-BuLi or s-BuLi. This chiral organolithium reagent is used as a source of sec-butyl carbanion in organic synthesis.
Sodium aluminium hydride or sodium alumanuide is an inorganic compound with the chemical formula NaAlH4. It is a white pyrophoric solid that dissolves in tetrahydrofuran (THF), but not in diethyl ether or hydrocarbons. It has been evaluated as an agent for the reversible storage of hydrogen and it is used as a reagent for the chemical synthesis of organic compounds. Similar to lithium aluminium hydride, it is a salt consisting of separated sodium cations and tetrahedral AlH−
4 anions.
2-Methyltetrahydrofuran (2-MeTHF) is an organic compound with the molecular formula C5H10O. It is a highly flammable, mobile liquid. It is mainly used as a replacement for Tetrahydrofuran (THF) in specialized applications for its better performance, such as to obtain higher reaction temperatures, or easier separations (as, unlike THF, it is not miscible with water). It is derived from sugars via furfural and is occasionally touted as a biofuel.
Cyclopentyl methyl ether (CPME), also known as methoxycyclopentane, is hydrophobic ether solvent. A high boiling point of 106 °C (223 °F) and preferable characteristics such as low formation of peroxides, relative stability under acidic and basic conditions, formation of azeotropes with water coupled with a narrow explosion range render CPME an attractive alternative to other ethereal solvents such as tetrahydrofuran (THF), 2-methyltetrahydrofuran (2-MeTHF), dioxane, and 1,2-dimethoxyethane (DME).
1,2,6-Hexanetriol is a trivalent alcohol with two primary and one secondary hydroxy group. It is similar to glycerol in many respects and is used as a substitute for glycerol in many applications due to its more advantageous properties, such as higher thermal stability and lower hygroscopicity.
In chemistry, a transition metal ether complex is a coordination complex consisting of a transition metal bonded to one or more ether ligand. The inventory of complexes is extensive. Common ether ligands are diethyl ether and tetrahydrofuran. Common chelating ether ligands include the glymes, dimethoxyethane (dme) and diglyme, and the crown ethers. Being lipophilic, metal-ether complexes often exhibit solubility in organic solvents, a property of interest in synthetic chemistry. In contrast, the di-ether 1,4-dioxane is generally a bridging ligand.