Tetrahydrofuran

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Tetrahydrofuran
Skeletal formula of tetrahydrofuran Structural formula of tetrahydrofuran.svg
Skeletal formula of tetrahydrofuran
Ball-and-stick model of the tetrahydrofuran molecule Tetrahydrofuran-3D-balls.png
Ball-and-stick model of the tetrahydrofuran molecule
Tetrahydrofuran sample.jpg
Names
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)
AbbreviationsTHF
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.003.389 OOjs UI icon edit-ltr-progressive.svg
PubChem CID
RTECS number
  • LU5950000
UNII
  • InChI=1S/C4H8O/c1-2-4-5-3-1/h1-4H2 Yes check.svgY
    Key: WYURNTSHIVDZCO-UHFFFAOYSA-N Yes check.svgY
  • InChI=1/C4H8O/c1-2-4-5-3-1/h1-4H2
    Key: WYURNTSHIVDZCO-UHFFFAOYAI
  • C1CCOC1
Properties
C4H8O
Molar mass 72.107 g·mol−1
AppearanceColorless 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 at 20 °C [2]
1.4073 at 20 °C [3]
Viscosity 0.48 cP at 25 °C
Structure
Envelope
1.63  D (gas)
Hazards
GHS labelling:
GHS-pictogram-flamme.svg GHS-pictogram-exclam.svg GHS-pictogram-silhouette.svg [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)
NFPA 704.svgHealth 2: Intense or continued but not chronic exposure could cause temporary incapacitation or possible residual injury. E.g. chloroformFlammability 3: Liquids and solids that can be ignited under almost all ambient temperature conditions. Flash point between 23 and 38 °C (73 and 100 °F). E.g. gasolineInstability 1: Normally stable, but can become unstable at elevated temperatures and pressures. E.g. calciumSpecial hazards (white): no code
2
3
1
Flash point −14 °C (7 °F; 259 K)
Explosive limits 2–11.8% [2]
Lethal dose or concentration (LD, LC):
  • 1650 mg/kg (rat, oral)
  • 2300 mg/kg (mouse, oral)
  • 2300 mg/kg (guinea pig, oral) [6]
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).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)

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.

Contents

Production

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.

Other methods

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.

Applications

Polymerization

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]

As a solvent

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, to remove extruder lines and add a shine to the finished product as well as to solvent weld printed parts.

Laboratory use

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]

Reaction with hydrogen sulfide

In the presence of a solid acid catalyst, THF reacts with hydrogen sulfide to give tetrahydrothiophene. [21]

Lewis basicity

Structure of VCl3(thf)3. CSD CIF CANZOG10.png
Structure of VCl3(thf)3.

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]

Precautions

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:

Tetrahydrofuran peroxide formation.svg

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.

Tetrahydrofurans

Chemical structure of annonacin, an acetogenin. Annonacin.svg
Chemical structure of annonacin, an acetogenin.
Eribulin (brand name: Halaven), a commercial THF-containing anticancer drug. Eribulin.svg
Eribulin (brand name: Halaven), a commercial THF-containing anticancer drug.

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]

Oxolanes

Tetrahydrofuran is one of the class of pentic cyclic ethers called oxolanes. There are seven possible structures, namely, [28]

See also

Related Research Articles

<span class="mw-page-title-main">Ether</span> Organic compounds made of alkyl/aryl groups bound to oxygen (R–O–R)

In organic chemistry, ethers are a class of compounds that contain an ether group—an oxygen atom bonded to two organyl groups. They have the general formula R−O−R′, where R and R′ represent the 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.

<span class="mw-page-title-main">Solvent</span> Substance dissolving a solute resulting in a solution

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.

<span class="mw-page-title-main">Formamide</span> Chemical compound

Formamide is an amide derived from formic acid. It is a colorless liquid which is miscible with water and has an ammonia-like odor. It is chemical feedstock for the manufacture of sulfa drugs and other pharmaceuticals, herbicides and pesticides, and in the manufacture of hydrocyanic acid. It has been used as a softener for paper and fiber. It is a solvent for many ionic compounds. It has also been used as a solvent for resins and plasticizers. Some astrobiologists suggest that it may be an alternative to water as the main solvent in other forms of life.

<span class="mw-page-title-main">Diisopropyl ether</span> Chemical compound

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.

<span class="mw-page-title-main">Dimethoxyethane</span> Chemical compound

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.

<span class="mw-page-title-main">2-Butanol</span> Secondary alcohol

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.

<i>n</i>-Butyllithium Chemical compound

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.

<span class="mw-page-title-main">2,2,2-Trifluoroethanol</span> Chemical compound

2,2,2-Trifluoroethanol is the organic compound with the formula CF3CH2OH. Also known as TFE or trifluoroethyl alcohol, this colourless, water-miscible liquid has a smell reminiscent of ethanol. Due to the electronegativity of the trifluoromethyl group, this alcohol exhibits a stronger acidic character compared to ethanol.

Tetrahydropyran (THP) is the organic compound consisting of a saturated six-membered ring containing five carbon atoms and one oxygen atom. It is named by reference to pyran, which contains two double bonds, and may be produced from it by adding four hydrogens. In 2013, its preferred IUPAC name was established as oxane. The compound is a colourless volatile liquid. Derivatives of tetrahydropyran are, however, more common. 2-Tetrahydropyranyl (THP-) ethers derived from the reaction of alcohols and 3,4-dihydropyran are commonly used as protecting groups in organic synthesis. Furthermore, a tetrahydropyran ring system, i.e., five carbon atoms and an oxygen, is the core of pyranose sugars, such as glucose.

<span class="mw-page-title-main">Hydrogen fluoride</span> Chemical compound

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.

<i>tert</i>-Butyllithium Chemical compound

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.

<span class="mw-page-title-main">Furfuryl alcohol</span> Chemical compound

Furfuryl alcohol is an organic compound containing a furan substituted with a hydroxymethyl group. It is a colorless liquid, but aged samples appear amber. It possesses a faint odor of burning and a bitter taste. It is miscible with but unstable in water. It is soluble in common organic solvents.

<span class="mw-page-title-main">Epichlorohydrin</span> Chemical compound

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.

<span class="mw-page-title-main">Nitroethane</span> Chemical compound

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.

<i>sec</i>-Butyllithium Chemical compound

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.

<span class="mw-page-title-main">Sodium aluminium hydride</span> Chemical compound

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.

<span class="mw-page-title-main">2-Methyltetrahydrofuran</span> Chemical compound

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.

<span class="mw-page-title-main">2,2,5,5-Tetramethyltetrahydrofuran</span> Chemical compound

2,2,5,5-tetramethyltetrahydrofuran (TMTHF) or 2,2,5,5-tetramethyloxolane (TMO) is a heterocyclic compound with the formula C
8H
16O, or (CH3)2(C(CH2)2OC)(CH3)2. It can be seen as derivative of tetrahydrofuran (oxolane) with four methyl groups replacing four hydrogen atoms on each of the carbon atoms in the ring that are adjacent to the oxygen. The absence of hydrogen atoms adjacent to the oxygen means that TMTHF (TMO) does not form peroxides, unlike other common ethers such as tetrahydrofuran, diethyl ether and CPME.

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.

<span class="mw-page-title-main">Transition metal ether complex</span>

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.

References

  1. ↑ "New IUPAC Organic Nomenclature - Chemical Information BULLETIN" (PDF).
  2. 1 2 3 4 5 6 NIOSH Pocket Guide to Chemical Hazards. "#0602". National Institute for Occupational Safety and Health (NIOSH).
  3. 1 2 3 Baird, Zachariah Steven; Uusi-Kyyny, Petri; Pokki, Juha-Pekka; Pedegert, Emilie; Alopaeus, Ville (6 Nov 2019). "Vapor Pressures, Densities, and PC-SAFT Parameters for 11 Bio-compounds". International Journal of Thermophysics. 40 (11): 102. Bibcode:2019IJT....40..102B. doi: 10.1007/s10765-019-2570-9 .
  4. ↑ NIST Chemistry WebBook. http://webbook.nist.gov
  5. 1 2 3 4 Record of Tetrahydrofuran in the GESTIS Substance Database of the Institute for Occupational Safety and Health, accessed on 2 June 2020.
  6. 1 2 "Tetrahydrofuran". Immediately Dangerous to Life or Health Concentrations (IDLH). National Institute for Occupational Safety and Health (NIOSH).
  7. "New Environment Inc. - NFPA Chemicals". Newenv.com. Retrieved 2016-07-16.
  8. 1 2 3 Müller, Herbert. "Tetrahydrofuran". Ullmann's Encyclopedia of Industrial Chemistry . Weinheim: Wiley-VCH. doi:10.1002/14356007.a26_221. ISBN   978-3527306732.
  9. ↑ Karas, Lawrence; Piel, W. J. (2004). "Ethers". Kirk‑Othmer Encyclopedia of Chemical Technology. John Wiley & Sons.
  10. ↑ Budavari, Susan, ed. (2001), The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals (13th ed.), Merck, ISBN   0911910131
  11. ↑ Morrison, Robert Thornton; Boyd, Robert Neilson (1972). Organic Chemistry (2nd ed.). Allyn and Bacon. p. 569.
  12. ↑ Starr, Donald; Hixon, R. M. (1943). "Tetrahydrofuran". Organic Syntheses ; Collected Volumes, vol. 2, p. 566.
  13. ↑ Hoydonckx, H. E.; Rhijn, W. M. Van; Rhijn, W. Van; Vos, D. E. De; Jacobs, P. A. (2007), "Furfural and Derivatives", Ullmann's Encyclopedia of Industrial Chemistry, American Cancer Society, doi:10.1002/14356007.a12_119.pub2, ISBN   978-3-527-30673-2
  14. ↑ Pruckmayr, Gerfried; Dreyfuss, P.; Dreyfuss, M. P. (1996). "Polyethers, Tetrahydrofuran and Oxetane Polymers". Kirk‑Othmer Encyclopedia of Chemical Technology. John Wiley & Sons.
  15. ↑ "Chemical Reactivity". Michigan State University. Archived from the original on 2010-03-16. Retrieved 2010-02-15.
  16. ↑ "NMR–MRI study of clathrate hydrate mechanisms" (PDF). Fileave.com. Archived from the original (PDF) on 2011-07-11. Retrieved 2010-02-15.
  17. ↑ Cai, Charles; Zhang, Taiying; Kumar, Rajeev; Wyman, Charles (13 August 2013). "THF co-solvent enhances hydrocarbon fuel precursor yields from lignocellulosic biomass". Green Chemistry. 15 (11): 3140–3145. doi:10.1039/C3GC41214H.
  18. ↑ Lucht, B. L.; Collum, D. B. (1999). "Lithium Hexamethyldisilazide: A View of Lithium Ion Solvation through a Glass-Bottom Boat". Accounts of Chemical Research. 32 (12): 1035–1042. doi:10.1021/ar960300e.
  19. ↑ Elschenbroich, C.; Salzer, A. (1992). Organometallics: A Concise Introduction (2nd ed.). Weinheim: Wiley-VCH. ISBN   3-527-28165-7.
  20. ↑ Williams, D. B. G.; Lawton, M. (2010). "Drying of Organic Solvents: Quantitative Evaluation of the Efficiency of Several Desiccants". Journal of Organic Chemistry. 75 (24): 8351–4. doi:10.1021/jo101589h. PMID   20945830. S2CID   17801540.
  21. ↑ Swanston, Jonathan. "Thiophene". Ullmann's Encyclopedia of Industrial Chemistry . Weinheim: Wiley-VCH. doi:10.1002/14356007.a26_793.pub2. ISBN   978-3527306732.
  22. ↑ F.A. Cotton; S.A. Duraj; G.L. Powell; W.J. Roth (1986). "Comparative Structural Studies of the First Row Early Transition Metal(III) Chloride Tetrahydrofuran Solvates". Inorg. Chim. Acta. 113: 81. doi:10.1016/S0020-1693(00)86863-2.
  23. ↑ Vogel G. C.; Drago, R. S. (1996). "The ECW Model". Journal of Chemical Education. 73 (8): 701–707. Bibcode:1996JChEd..73..701V. doi:10.1021/ed073p701.
  24. ↑ Manzer, L. E. "Tetrahydrofuran Complexes of Selected Early Transition Metals," Inorganic Synthesis. 21, 135–140, (1982).
  25. ↑ "Material Safety Data Sheet Tetrahydrofuran, 99.5+%, for spectroscopy". Fisher Scientific. Retrieved 2022-07-27.
  26. ↑ Lorente, Adriana; Lamariano-Merketegi, Janire; Albericio, Fernando; Álvarez, Mercedes (2013). "Tetrahydrofuran-Containing Macrolides: A Fascinating Gift from the Deep Sea". Chemical Reviews. 113 (7): 4567–4610. doi:10.1021/cr3004778. PMID   23506053.
  27. ↑ Wolfe, John P.; Hay, Michael B. (2007). "Recent advances in the stereoselective synthesis of tetrahydrofurans". Tetrahedron. 63 (2): 261–290. doi:10.1016/j.tet.2006.08.105. PMC   1826827 . PMID   18180807.
  28. ↑ Cremer, Dieter (1983). "Theoretical Determination of Molecular Structure and Conformation. XI. The Puckering of Oxolanes". Israel Journal of Chemistry. 23: 72–84. doi:10.1002/ijch.198300010.

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