109-99-9

A clear colorless liquid with an ethereal odor. Less dense than water. Flash point 6°F. Vapors are heavier than air.

TETRAHYDROFURAN(109-99-9) reacts violently with oxidizing agents leading to fires and explosions [Handling Chemicals Safely 1980. p. 891]. Subject to peroxidation in the air. Peroxides or their products react exothermically with lithium aluminum hydride [MCA Guide for Safety 1973]. Thus, use as a solvent for lithium aluminum hydride has led to fires. Using potassium hydroxide or sodium hydroxide to dry impure TETRAHYDROFURAN(109-99-9) that contains peroxides has resulted in explosions. A violent explosion occurred during the preparation of sodium aluminum hydride from sodium and aluminum in a medium of TETRAHYDROFURAN(109-99-9) [Chem. Eng. News 39(40):57. 1961]. THF forms explosive products with 2-aminophenol [Lewis 3227].

Highly flammable. Oxidizes readily in air to form unstable peroxides that may explode spontaneously [Bretherick, 1979 p.151-154, 164]. Soluble in water.

Vapors cause nausea, dizziness, headache, and anesthesia. Liquid can de-fat the skin and cause irritation. Liquid also irritates eyes.

The primary use of tetrahydrofuran is as a solvent to dissolve synthetic resins, particularly polyvinyl chloride and vinylidene chloride copolymers. It is also used to cast polyvinyl chloride films, to coat substrates with vinyl and vinylidene chloride; and to solubilize adhesives based on or containing polyvinyl chloride resins. A second large market for THF is as an electrolytic solvent in the Grignard reaction-based production of tetramethyl lead. THF is used as an intermediate in the production of polytetramethylene glycol.

If this chemical gets into the eyes, remove any contact lenses at once and irrigate immediately for at least 15 minutes, occasionally lifting upper and lower lids. Seek medical attention immediately. If this chemical contacts the skin, remove contaminated clothing and wash immediately with soap and water. Seek medical attention immediately. If this chemical has been inhaled, remove from exposure, begin rescue breathing (using universal precautions, including resuscitation mask) if breathing has stopped and CPR if heart action has stopped. Transfer promptly to a medical facility. When this chemical has been swallowed, get medical attention. Give large quantities of water and induce vomiting. Do not make an unconscious person vomit.

UN2056 Tetrahydrofuran, Hazard Class: 3; Labels: 3-Flammable liquid.

Forms thermally explosive peroxides in air on standing (in absence of inhibitors). Peroxides can be detonated by heating, friction, or impact. Reacts violently with strong oxidizers, strong bases and some metal halides. Attacks some forms of plastics, rubber and coatings.

Tetrahydrofuran (THF) is an industrial solvent widely recognized for its unique combination of useful properties. DuPont THF is better than 99.9% pure with a small (0.025-0.040 wt % ) amount of butylated hydroxytoluene (BHT, 4-methyl-2,6-di-tertbutyl phenol) added as an antioxidant. Tetrahydrofuran is a cycloaliphatic ether and is not "photochemically reactive" as defined in Section k of Los Angeles County's Rule 66 (equivalent to Rule 442 of the Southern California Air Pollution Control District). THF has an ethereal odor. The Odor Threshold is listed @ 3.8 (3M), 20-50ppm, and 31ppm. It is also a common laboratory reagent and an intermediate in chemical syntheses of consumer and industrial products such as nutritionals, pharmaceuticals, and insecticides (HSDB, 2011).

Consult with environmental regulatory agencies for guidance on acceptable disposal practices. Generators of waste containing this contaminant (≥100 kg/mo) must conform with EPA regulations governing storage, transportation, treatment, and waste disposal. Concentrated waste containing peroxides-perforation of a container of the waste from a safe distance followed by open burning.

Tetrahydrofuran is a clear, colourless liquid with a strong ether-like odour. Odor threshold concentration is 2 ppm (quoted, Amoore and Hautala, 1983). It is highly flammable. Contact of tetrahydrofuran with strong oxidising agents may cause explosions. Tetrahydrofuran may polymerise in the presence of cationic initiators. Contact with lithium–aluminium hydride, with other lithium–aluminium alloys, or with sodium or potassium hydroxide can be hazardous.

ChEBI: A cyclic ether that is butane in which one hydrogen from each methyl group is substituted by an oxygen.

THF is extremely flammable (NFPA rating = 3), and its vapor can travel a considerable distance to an ignition source and "flash back." A 5% solution of THF in water is flammable. THF vapor forms explosive mixtures with air at concentrations of 2 to 12% (by volume). Carbon dioxide or dry chemical extinguishers should be used for THF fires.
THF can form shock- and heat-sensitive peroxides, which may explode on concentration by distillation or evaporation. Always test samples of THF for the presence of peroxides before distilling or allowing to evaporate. THF should never be distilled to dryness.

Reactivity with Water No reaction; Reactivity with Common Materials: No data; Stability During Transport: Stable; Neutralizing Agents for Acids and Caustics: Not pertinent; Polymerization: May occur when the product is in contact with strong acids and bases; Inhibitor of Polymerization: No data.

Tetrahydrofuran (THF), the saturated derivative of furan, when used as a solvent for high molecular weight polyvinyl chloride (PVC), vinyl chloride copolymers, and polyvinylidene chloride copolymers at ambient temperatures yields solutions of high solids content. Blends of THF and methyl ethyl ketone are often used for increased solvency in certain polymer compositions. Applications for THF polymer solutions include PVC top coatings of automotive upholstery, audio tape coatings of polyurethane/metal oxides on polyester tape, polyurethane coatings for fabric finishes, water-vapor barrier film coatings of PVC, and polyvinylidene chloride copolymers onto cellophane film. Tetrahydrofuran is an excellent solvent for many inks used for printing on PVC film and on PVC plastic articles. Polyvinyl chloride pipe welding cements are made by dissolving the resin in THF solvent. Other adhesive applications include cements for leather, plastic sheeting, and for molded plastic assemblies. Other uses of THF are as a chemical intermediate and as a complexing solvent for various inorganic, organometallic, and organic compounds. These THF complexes are important as Grignard reagents, catalysts for organic reactions, and in stereo-specific polymerizations. Tetrahydrofuran is the solvent of choice in many pharmaceutical reactions and applications. The excellent solvency of THF makes this solvent ideal for solvent cleaning of polymer manufacturing and processing equipment.

THF showed little evidence of mutagenic activity in a variety of in vitro and in vivo assays.

Leaches from PVC cement used to join tubing (Wang and Bricker, 1979)

Photolytic. The rate constants for the reaction of tetrahydrofuran and OH radicals in the atmosphere are 1.67 x 10^-11 cm³/molecule?sec at 298 K (Moriarty et al., 2003) and 8.8 x 10^-12 cm³/molecule?sec at 300 K (Hendry and Kenley, 1979). Atkinson et al. (1988) reported a rate constant of 4.875 x 10^-15 cm³/molecule?sec for the reaction with NO3 radicals in air.

THF 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 THF should be dated when opened and tested periodically for the presence of peroxides.

It is obtained commercially by catalytic hydrogenation of furan from pentosan-containing agricultural residues. It was purified by refluxing with, and distilling from LiAlH4 which removes water, peroxides, inhibitors and other impurities [Jaeger et al. J Am Chem Soc 101 717 1979]. Peroxides can also be removed by passage through a column of activated alumina, or by treatment with aqueous ferrous sulfate and sodium bisulfate, followed by solid KOH. In both cases, the solvent is then dried and fractionally distilled from sodium. Lithium wire or vigorously stirred molten potassium have also been used for this purpose. CaH2 has also been used as a drying agent. Several methods are available for obtaining the solvent almost anhydrous. Ware [J Am Chem Soc 83 1296 1961] dried it vigorously with sodium-potassium alloy until a characteristic blue colour was evident in the solvent at Dry-ice/cellosolve temperatures. The solvent is kept in contact with the alloy until distilled for use. Worsfold and Bywater [J Chem Soc 5234 1960], after refluxing and distilling from P2O5 and KOH, in turn, refluxed the solvent with sodium-potassium alloy and fluorenone until the green colour of the disodium salt of fluorenone was well established. [Alternatively, instead of fluorenone, benzophenone, which forms a blue ketyl, can be used.] The tetrahydrofuran was then fractionally distilled, degassed and stored above CaH2. p-Cresol or hydroquinone inhibit peroxide formation. The method described by Coetzee and Chang [Pure Appl Chem 57 633 1985] for 1,4-dioxane also applies here. Distillations should always be done in the presence of a reducing agent, e.g. FeSO4. [Beilstein 17 H 10, 17 I 5, 17 II 15, 17 III/IV 24, 17/1 V 27.] It irritates the skin, eyes and mucous membranes, and the vapour should never be inhaled. It is HIGHLY FLAMMABLE, and the necessary precautions should be taken. Rapid purification: Purification as for diethyl ether.

The principal target organs in rodents receiving repeated exposures to THF are the central nervous system (CNS), kidney, and liver. The CNS effects caused by THF are thought to be mediated via the THF metabolites tetrahydro-2-furanone and 4-hydroxybutanoic acid. This is consistent with the CNS effects associated with these metabolites as well as the higher narcotic potency of THF in mice than in comparably exposed rats and the shorter half-life of THF in the presence of mouse versus rat hepatic microsomes. In contrast to the CNS effects, the male rat kidney tumors and female mouse liver tumors appear to be induced by the parent compound, not a metabolite. Lifetime exposures of rodents to tetrahydro-2-furanone, 4-hydroxybutanoic acid, and sodium succinate have not resulted in treatment-related carcinogenic effects, and a mechanistic study demonstrated that hepatocellular proliferation in female mice exposed to THF is actually enhanced by CYP450 inhibition, not decreased as one would predict if proliferation is mediated by a THF metabolite. The THF database has been reviewed against potential mode of action (MoA) candidates including direct DNA reactivity, cytotoxicity followed by regenerative cell proliferation, excessive accumulation of alpha 2u-globulin, exacerbation of rat chronic progressive nephropathy (CPN), and nuclear receptor (e.g., constitutive androstane receptor) activation leading to enzyme induction and enhanced cell proliferation. While the tumorigenic MoAs have not been identified, exacerbation of CPN (rat kidney) and nuclear receptor activation (mouse liver) are currently the more favored. BothMoAs are thought to involve nongenotoxic (i.e., threshold) events. CPN has no known counterpart in humans.