Suitable for HPLC, spectrophotometry, environmental testing
Tetrahydrofuran 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 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 [Chem. Eng. News 39(40):57. 1961]. THF forms explosive products with 2-aminophenol [Lewis 3227].
Tetrahydrofuran is a clear, colourless liquid with ether-like odour. 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.
Solvent for high polymers, especially polyvinyl chloride. As reaction medium for Grignard and metal hydride reactions. In the synthesis of butyrolactone, succinic acid, 1,4-butanediol diacetate. Solvent in histological techniques. May be used under Federal Food, Drug & Cosmetic Act for fabrication of articles for packaging, transporting, or storing of foods if residual amount does not exceed 1.5% of the film: Fed. Regist. 27, 3919 (Apr. 25, 1962).
Oral-rat; LD50: 1650 mg/kg; inhalation LC50: 21000 ppm/3H. Inhalation-mice LCLo: 24000 mg/m3/2H.
It has low toxicity. This product has irritation effect on the skin and mucous membranes. At high concentrations it has an anesthetic effect with the anesthetic concentration being similar as lethal concentrations. High dose also has certain liver toxicity.
Rats, when being inhaled of 590mg/m^ 3, after 3 hours, has their eyelids and nasal become redness; inhalation> 147750mg/m^ 3, corneal edema and opacity, salivation, runny nose and nasal bleeding can occur.
Rats, guinea pigs, rabbits and cats, when being placed in a concentration of 50mg/L concentration for 3 hours, some animals can get side down; deepened anesthesia can appear under a dose of 100mg/L; some animals can directly die after exposure of 1 to 4.5 hours; a dose of 200 mg/ L can cause anesthesia within 1 hour with long term action being able to cause death. Rats, when get the inhaled concentrations> 14000mg/m ^ 3, can sleep, get stiffness, enter into deep coma, get convulsions, and also have epileptic brain waves. For the anesthesia effect, the animals can development certain resistance after repeated inhalation. Animals, when exposed to high doses once or repeated exposure, can get liver fatty infiltration and cell lysis. The oral administration can cause stomach bleeding and ulcers.
Applying 20% aqueous solution directly to the skin of rabbits can cause moderate skin irritation while 50% aqueous solution can cause severe corrosive damage.
Applying 20% aqueous solution to the rabbit eyes can cause severe keratitis.
THF, when touched with air, can form explosive peroxides which can increase the stimulating effect of THF.
According the foreign report, the concentration for causing anesthesia of human is 73800mg/m ^ 3. The threshold of human olfactory is 88.5mg/m ^ 3.
The above information is edited by the Chemicalbook of Dai Xiongfeng.
flexographic inks for plastics
coating deposition for audio and video tapes
PVC and CPVC pipe cements
PVC film casting (food packaging)
Vapors cause nausea, dizziness, headache, and anesthesia. Liquid can de-fat the skin and cause irritation. Liquid also irritates eyes.
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.
1. It can be used as the solvent and the raw material of organic synthesis.
2. It can also be used as the chromatography analysis reagents, organic solvents and the intermediate of nylon 66.
3. Tetrahydrofuran is the intermediate for synthetic pesticides fenbutatin. In addition, it can be directly used for synthetic fibers, synthetic resins, synthetic rubber as well as the solvent of many polymeric materials, precision tape and electroplating industry. Moreover, it is also used for preparation of adiponitrile, adipic acid, hexamethylene diamine, succinic acid, butanediol, and γ-butyrolactone. In the pharmaceutical industry, it can be used for the production of carbetapentane, progesterone, rifamycin and pharmaceutical solvents.
4. THF is an important raw material for organic synthesis as well as a solvent with excellent performance, which is especially suitable for dissolution of PVC, polyvinylidene chloride and butyl aniline. It is widely used as surface coating, anti-corrosion coatings, printing inks, the solvent of tapes and films paint, and also being used as the reaction solvent. When being used as the electroplate aluminum solution, it can randomly control the thickness as well as brightness of aluminum layer. THF itself can be subject to condensation (caused by the ring-open reaction induced by cation and further polymerization) to generate poly-tetramethylene ether glycol (PTMEG). PTMEG, together with toluene diisocyanate (TDI) can generate special rubber of wear-resistant, oil resistance, excellent performance at low temperature as well as high strength; it can also generate block polyether/polyester elastic material with dimethyl terephthalate and 1, 4-butanediol. PTMGE of Molecular weight being 2000, together with methylene bis (4-phenyl) diisocyanate (MDI) can generate polyurethane elastic fiber (SPANDEX fiber), special rubber and the raw material of some kinds of coatings of special purpose. In the field of organic synthesis, it can be used for producing tetrahydrothiophene, 1, 4-dichloroethane, 2, 3-dichloro-tetrahydrofuran, valerolactone, butyrolactone and pyrrolidone. In the pharmaceutical industry, THF can be used for the synthesis of carbetapentane, rifamycin, progesterone, and some kinds of hormone drugs. THF, after being subject to hydrogen sulfide treatment, can generate tetrahydrothiophene. It can be used as the odor agent (identification additive) in fuel gas. THF can also be used as the surface treatment agent for synthetic leather.
5. It can also be applied to the paper chromatography of amino acids and peptides. It can be used as solvent; for organic synthesis as well as being applied to HPLC and UV spectrophotometry assay.
The earliest industrial production use uronic as raw material and put the mixture of uronic and steam into the reactor containing zinc-chromium-manganese metal oxide (or palladium) catalyst for stripping the carbonyl group at 400-420 ℃ to obtain furan; then take the raney nickel as the catalyst, perform furan hydrogenation reaction at 80-120 ℃ to obtain tetrahydrofuran. Applying this method for the production of one ton of tetrahydrofuran will cost about three tons of polysaccharide aldehyde. There are many kinds of production process developed later. Industrial methods include 1, 4-butanediol catalytic dehydration method; because butanediol is produced from acetylene and formaldehyde, this method is called as Reppe method; another method taking the byproduct of neoprene monomer chloroprene, 1, 4-dichloro-butene for production of tetrahydrofuran. This method is called dichloro butene method. In recent years, it was developed of the catalytic hydrogenation using maleic anhydride as the raw material.
There are mainly five kinds of approaches for production of tetrahydrofuran, as below:
1. Furfural method
It can be made through the decarbonylation of furfural can generate furan, and then have hydrogenation to obtain it.
This is one of the earliest ways of production of tetrahydrofuran on industrial process. Furfural is mainly produced through the hydrolysis of corn cob and other agricultural products. The pollution is serious and is not suitable for large-scale production and has been gradually eliminated.
2. Catalytic hydrogenation of maleic anhydride
Maleic anhydride and hydrogen gas were put into the reactor containing nickel catalyst inside of it from the bottom; the ratio between tetrahydrofuran and γ-butyrolactone in the product can be controlled by adjusting the operating parameters. The reaction product and the raw material hydrogen gas were cooled to about 50 ℃ and enter into the bottom of the scrubber to separate the unreacted hydrogen and gaseous product from liquid product; The unreacted hydrogen and the gaseous products were recycled to the reactor after washing while the liquid product was subject to distillation to obtain tetrahydrofuran.
This technology can randomly adjust the ratio of γ-butyrolactone and tetrahydrofuran at the range of 0 to (5:1) with the conversion rate of maleic anhydride in single round being 100%. The selectivity of tetrahydrofuran ranges from 85% to 95% with the product content being 99.97%. The process has good catalyst performance, simple process, and less investment.
3. 1, 4-butanediol dehydration cyclization
This process is that: ad 1087 kg of 22% aqueous sulfuric acid to the reactor, add 1,4-butanediol at 100 ℃ at a rate of 110kg/h with the overhead temperature being maintained at 80 °C. By doing this, we can obtain the 80% tetrahydrofuran anhydrous solution from the top of the tower at a speed of 110 kg/h speed. After adding 50 t of 1, 4-butanediol, you should further exclude approximately 70kg coke from the reactor. The coke was further filtered with the resulting aqueous sulfuric acid solution being able to be recycled. The tetrahydrofuran yield of this process can reach 99%.
Sulfuric acid is the earliest catalyst applied in the industrial production of tetrahydrofuran, and it also has a lot of applications in current production. This technology is mature with simple process, lower reaction temperatures, and high yield of tetrahydrofuran. However, the sulfuric acid is corrosive to equipment and can cause environmental pollution.
4. dichloro-butene method
This method takes 1, 4-dichloro-butene as raw material to produce butylene glycol through hydrolysis and further go through catalytic hydrogenation to obtain it.
1, 4-dichloro-butene can be hydrolyzed in sodium hydroxide solution with generating butylene glycol at 110°C. Centrifuge to remove the sodium chloride; the filtrate was concentrated in an evaporator crystallizer and the alkali metal carboxylate slat can be separated out; then remove the high-boiling matter in distillation column. Put the refined butenediol into the reactor; tae nickel as catalyst and have butenediol undergone hydrogenation reaction to generate butanediol at 80~120 ℃ and certain pressure. After distillation, the resulting product further entered into cyclization reactor to generate crude tetrahydrofuran in acidic medium at atmospheric pressure and at 120~140 ℃; Further conduct distillation and dehydration and remove high-boiling substance; finally distill again to obtain highly pure tetrahydrofuran.
This method is simple with mild conditions, high yield and less catalyst which can be used continuously.
5. Oxidation of butadiene
Use butadiene as raw material; it generate furan after oxidation; furan further generate the tetrahydrofuran through hydrogenation. This method has been industrialized in foreign countries.
It is colorless, transparent liquid with ether odor. It is miscible with water, alcohols, ketones, benzene, esters, ethers, and hydrocarbons.
Purification of tetrahydrofuran
Tetrahydrofuran is miscible with water and often contains a small amount of water and peroxide. For making dry tetrahydrofuran, you can make it through flux with lithium aluminium hydride insulting the moisture (typically 1000 mL takes about 2~4 lithium aluminum hydride for removing the water and peroxide inside it, then further go through distillation; when collect the distilling fraction at 66 ℃, don’t totally dry it without the remaining small amount of residue being poured). Add the sodium wire to the refined liquid and further store it in a nitrogen atmosphere. Upon processing of tetrahydrofuran, we should first apply a small amount of it for being subject to testing to make sure that it only contains a small amount of water and peroxide with a relative mild reaction before we can purify it. The peroxide contained in tetrahydrofuran can be determined by the acidified potassium iodide solution. If the peroxides are in relative large amount, it is recommended that it is processed separately.
Grignard Reagent formation processes
preparation of organometallic reagents
Air & Water Reactions
Highly flammable. Oxidizes readily in air to form unstable peroxides that may explode spontaneously [Bretherick, 1979 p.151-154, 164]. Soluble in water.
Tetrahydrofuran, the abbreviation of THF, is a heterocyclic organic compound. It belongs to ethers and is the fully hydrogenated product of the aromatic compound furan.
It can be used as an aprotic solvent with moderate polarity in chemical reaction and solvent extraction. Tetrahydrofuran is a colorless, low viscosity liquid with a similar smell as ether. At room temperature, tetrahydrofuran is partially miscible with water. This is exploited by some of the illegal businessmen for mixing water with tetrahydrofuran reagent to earn huge profits. Upon storage, tetrahydrofuran can easily become peroxide, and therefore, the commercialized tetrahydrofuran often used BHT, i.e., 2,6-tert butyl p-cresol for preventing oxidation. Tetrahydrofuran can be placed into sealed bottle through sodium hydroxide for being stored in a dark place.
A clear colorless liquid with an ethereal odor. Less dense than water. Flash point 6°F. Vapors are heavier than air.
ChEBI: A cyclic ether that is butane in which one hydrogen from each methyl group is substituted by an oxygen.