Tetrahydrofuran, preparation

Tetrahydrofurans, preparation, from 1,4-diols, 839 from furans, 833... 

Dibromobutane and 1 5 dibromopentane are conveniently prepared from the readily available tetrahydrofuran (I) and tetrahydrop3uan (II) respectively ... 

Another method of aldehyde bromination, apart from Riehl s established method (432) from bromine at 20°C, is to use trimethylphenyl-ammonium bromide in tetrahydrofuran solution, prepared by Vorlander and Siebert s method (50). However, the yield of 5-phenylthiazole using this method with thioformamide dissolved in dioxane is only 8% (513). 

Grignard reagents (Section 14 4) Grignard reagents are prepared in a manner similar to that used for organolithium compounds Di ethyl ether and tetrahydrofuran are appro priate solvents... 

Therapeutics. Compounds containing the furan or tetrahydrofuran ring are biologically active and are present in a number of pharmaceutical products. Eurfurjdamine [617-89-0] is an intermediate in the diuretic, furosemide. Tetrahydrofurfurylamine [4795-29-3] may also have pharmaceutical applications. 5-(E)imethyiaininomethyi)furfuryi alcohol [15433-79-17 is an intermediate in the preparation of ranitidine, which is used for treating ulcers. 2-Acet5dfuran [1192-62-7] prepared from acetic anhydride and furan is an intermediate in the synthesis of cefuroxime, a penicillin derivative. 2-Euroic acid is prepared by the oxidation of furfural. Both furoic acid [88-14-2] and furoyl chloride [527-69-5] are used as pharmaceutical intermediates. 

Hexanitrostilbene may be prepared by a dding a solution of TNT ia tetrahydrofuran and methanol at 5°C to aqueous sodium hypochlorite. To this mixture a 20% solution of trimethyl amine hydrochloride is added at 5—15°C. Hexanitrostilbene precipitates, and is filtered and washed with methanol and... 

The products are Hquids, soluble in various solvents and stable over prolonged periods. Monochloroborane is an equiUbtium mixture containing small amounts of borane and dichloroborane complexes with dimethyl sulfide (81). Monobromoborane—dimethyl sulfide complex shows high purity (82,83). Solutions of monochloroborane in tetrahydrofuran and diethyl ether can also be prepared. Strong complexation renders hydroboration with monochloroborane in tetrahydrofuran sluggish and inconvenient. Monochloroborane solutions in less complexing diethyl ether, an equiUbtium with small amounts of borane and dichloroborane, show excellent reactivity (88,89). Monochloroborane—diethyl etherate [36594-41-9] (10) may be represented as H2BCI O... 

Dicyclohexylborane [1568-65-6], Chx2BH (12) is prepared in quantitative yield by the same method. It is a white soHd, sparingly soluble in ether or tetrahydrofuran. For most purposes isolation is not necessary and it can be used as a slurry in these solvents. Its stetic requirements are slightiy lower as compared to Sia2BH (57,106—109). Much better thermal stabiUty allows its use at higher temperatures. 

The most hindered of all presently known hydroborating agents is possibly dimesitylborane, an air-stable white soHd, slightly soluble in tetrahydrofuran, the best etheral solvent. It is commercially available or can be prepared according to the following reaction (117) ... 

Among chiral dialkylboranes, diisopinocampheylborane (8) is the most important and best-studied asymmetric hydroborating agent. It is obtained in both enantiomeric forms from naturally occurring a-pinene. Several procedures for its synthesis have been developed (151—153). The most convenient one, providing product of essentially 100% ee, involves the hydroboration of a-pinene with borane—dimethyl sulfide in tetrahydrofuran (154). Other chiral dialkylboranes derived from terpenes, eg, 2- and 3-carene (155), limonene (156), and longifolene (157,158), can also be prepared by controlled hydroboration. A more tedious approach to chiral dialkylboranes is based on the resolution of racemates. /n j -2,5-Dimethylborolane, which shows excellent enantioselectivity in the hydroboration of all principal classes of prochiral alkenes except 1,1-disubstituted terminal double bonds, has been... 

Mercuration. Mercury(II) salts react with alkyl-, alkenyl-, and arylboranes to yield organomercurials, which are usehil synthetic intermediates (263). For example, dialkyhnercury and alkyhnercury acetates can be prepared from primary trialkylboranes by treatment with mercury(II) chloride in the presence of sodium hydroxide or with mercury(II) acetate in tetrahydrofuran (3,264). Mercuration of 3 -alkylboranes is sluggish and requires prolonged heating. Alkenyl groups are transferred from boron to mercury with retention of configuration (243,265). 

Much more important is the hydrogenation product of butynediol, 1,4-butanediol [110-63-4]. The intermediate 2-butene-l,4-diol is also commercially available but has found few uses. 1,4-Butanediol, however, is used widely in polyurethanes and is of increasing interest for the preparation of thermoplastic polyesters, especially the terephthalate. Butanediol is also used as the starting material for a further series of chemicals including tetrahydrofuran, y-butyrolactone, 2-pyrrohdinone, A/-methylpyrrohdinone, and A/-vinylpyrrohdinone (see Acetylene-DERIVED chemicals). The 1,4-butanediol market essentially represents the only growing demand for acetylene as a feedstock. This demand is reported (34) as growing from 54,000 metric tons of acetylene in 1989 to a projected level of 88,000 metric tons in 1994. 

These reactions are usehil for the preparation of homogeneous difunctional initiators from a-methylstyrene in polar solvents such as tetrahydrofuran. Because of the low ceiling temperature of a-methylstyrene (T = 61° C) (26), dimers or tetramers can be formed depending on the alkaU metal system, temperature, and concentration. Thus the reduction of a-methylstyrene by sodium potassium alloy produces the dimeric dianionic initiators in THF (27), while the reduction with sodium metal forms the tetrameric dianions as the main products (28). The stmctures of the dimer and tetramer correspond to initial tail-to-tail addition to form the most stable dianion as shown in equations 6 and 7 (28). 

Iron(III) iodide [15600-49-4], Fefy, is prepared by the oxidative photodecarbonylation of diiodotetracarbonylkon(II) ki the presence of dkodine (7). The black soHd obtained is extremely hygroscopic, spariagly soluble only ki dichloromethane, and decomposes to kon(II) iodide and dkodine when exposed to donor solvents such as tetrahydrofuran, acetonitrile, water, or pyridine. It also decomposes when exposed to light. 

Many organic syntheses requHe the use of stericaHy hindered and less nucleophilic bases than //-butyUithium. Lithium diisopropylamide (LDA) and lithium hexamethyldisilazide (LHS) are often used (140—142). Both compounds are soluble in a wide variety of aprotic solvents. Presence of a Lewis base, most commonly tetrahydrofuran, is requHed for LDA solubdity in hydrocarbons. A 30% solution of LHS can be prepared in hexane. Although these compounds may be prepared by reaction of the amine with //-butyUithium in the approprite medium just prior to use, they are also available commercially in hydrocarbon or mixed hydrocarbon—THF solvents as 1.0—2.0 M solutions. 

Solubility and Solvent Resistance. The majority of polycarbonates are prepared in methylene chloride solution. Chloroform, i7j -l,2-dichloroethylene, yy -tetrachloroethane, and methylene chloride are the preferred solvents for polycarbonates. The polymer is soluble in chlorobenzene or o-dichlorobenzene when warm, but crystallization may occur at lower temperatures. Methylene chloride is most commonly used because of the high solubiUty of the polymer (350 g/L at 25°C), and because this solvent has low flammabiUty and toxicity. Nonhalogenated solvents include tetrahydrofuran, dioxane, pyridine, and cresols. Hydrocarbons (qv) and aUphatic alcohols, esters (see Esters, organic), or ketones (qv) do not dissolve polycarbonates. Acetone (qv) promotes rapid crystallization of the normally amorphous polymer, and causes catastrophic failure of stressed polycarbonate parts. 

A variant of the Wurtz reaction is the preparation of tetrabutyltin from activated magnesium chips, butyl chloride, and stannic chloride in a hydrocarbon mixture. Only a small amount of tetrahydrofuran is required for the reaction to proceed in high yield (86). 

Lithium metal in tetrahydrofuran can also be used as the coupling reagent, and unsymmetrical ditins can be prepared when the reaction is conducted in stages (162,163). 

Acetone, methyl ethyl ketone, methyl isobutyl ketone, dimethylformamide, ethyl acetate, and tetrahydrofuran are solvents for vinyhdene chloride polymers used in lacquer coatings methyl ethyl ketone and tetrahydrofuran are most extensively employed. Toluene is used as a diluent for either. Lacquers prepared at 10—20 wt % polymer sohds in a solvent blend of two parts ketone and one part toluene have a viscosity of 20—1000 mPa-s (=cP). Lacquers can be prepared from polymers of very high vinyhdene chloride content in tetrahydrofuran—toluene mixtures and stored at room temperature. Methyl ethyl ketone lacquers must be prepared and maintained at 60—70°C or the lacquer forms a sohd gel. It is critical in the manufacture of polymers for a lacquer apphcation to maintain a fairly narrow compositional distribution in the polymer to achieve good dissolution properties. 

Synthesis. An efficient, convenient synthesis for the preparation of ammonia borane [13774-81 -7] the inorganic analogue of ethane, is shown in equation 1 where THF is tetrahydrofuran (6). 

Organometallic Chemistry. Only a few organocalcium compounds have been reported. Alkyl calcium haUdes have been prepared by reaction of the hahdes and calcium ia tetrahydrofuran (17). 

Most attempts to differentiate these hydroxyl groups with conventional derivatives resulted in the formation of a tetrahydrofuran. The dithiocarbonate can also be prepared by phase-transfer catalysis (Bu4N HS04T, 50% NaOH/H20, CS2, Mel, rt,. 5h) ... 

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