Tetrahydrofurans preparation from

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 ... 

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. 

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). 

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. 

Acetylene is passed for 1 hr through a mixture consisting of 0.5 g (72 mg-atoms) of lithium in 100 ml of ethylene-diamine. A solution prepared from 1 g (3.5 mmoles) of rac-3-methoxy-18-methylestra-l,3,5(10)-trien-I7-one and 30 ml of tetrahydrofuran is then added at room temperature with stirring over a period of 30 min. After an additional 2 hr during which time acetylene is passed through the solution the mixture is neutralized with 5 g of ammonium chloride, diluted with 50 ml water, and extracted with ether. The ether extracts are washed successively with 10% sulfuric acid, saturated sodium hydrogen carbonate and water. The extract is dried over sodium sulfate and concentrated to yield a solid crystalline material, which on recrystallization from methanol affords 0.95 g (87%) of rac-3-methoxy-18-methyl-17a-ethynyl-estra-l,3,5(10)-trien-17jB-ol as colorless needles mp 161°. 

A solution of the monosodium salt of diacetylene in 300 ml of liquid ammonia is prepared from 13.8 g (0.6 g-atoms) sodium and 24.6 g (0.2 moles) l,4-dichlorobut-2-yne. To this mixture is added a suspension of 5 g (17.6 mmoles) 3-methoxyestra-l,3,5(10)-trien-17-one in anhydrous tetrahydrofuran at —40° and the reaction mixture is stirred and maintained at this temperature for 2 hr. Ammonium chloride is then added and the ammonia is allowed to evaporate overnight. The residual solids are extracted with methylene dichloride and the extracts washed with water, dried over magnesium sulfate, and evaporated at 70°. The resultant dark gum is... 

A Grignard solution is prepared from 1.35 g (56 mg-atoms) magnesium, 3.7 ml (8.4 g, 59 mmoles) methyl iodide and 47 ml dry ether. After addition of 80 ml of dry tetrahydrofuran the solvent is removed by distillation until the boiling point reaches 62°. Additions of 0.27 g (2.7 mmoles) of cuprous... 

Mixtures of anhydrous hydrogen fluoride and tetrahydrofuran are successfully used as fluorinating agents to convert 1,1,2-trifluoro-l-allcen-3-ols, easily prepared from bromotrifluoroethene via lithiation followed by the reaction with aldehydes or ketones, to 1,1,1,2-tetrafluoro-2-alkenes The yields are optimal with a 5 1 ratio of hydrogen fluoride to tetrahydrofuran The fluorination reaction involves a fluonde lon-induced rearrangement (Sf,j2 mechanism) of allylic alcohols [65] (equation 40)... 

The residue was dissolved in 75 ml of tetrahydrofuran, treated with charcoal, and sodium sulfate and filtered. This solution was added to a solution in 250 ml of tetrahydrofuran of phenyl magnesium bromide prepared from 17.7 ml (0.17 mol) of bromobenzene. This mixture was stirred and heated under reflux for 1 hour. It was then cooled and diluted with 400 ml of ether and sufficient 3N hydrochloric acid to make it acidic. The aqueous phase was separated, adjusted to pH 8 with 3N sodium hydroxide and extracted 3 times with 200 ml of ether. The ether extracts were combined, washed with water and dried over sodium sulfate. The residue left on removal of the ether in vacuo was crystallized from petroleum ether to give 3.3 g of 7-chloro-2,3-dihvdro-1-methyl-5-phenvl-1 H-1,4-benzodiazepine, according to U.S. Patent 3,624,703. 

In addition to the boron trifluoride-diethyl ether complex, chlorotrimcthylsilanc also shows a rate accelerating effect on cuprate addition reactions this effect emerges only if tetrahydrofuran is used as the reaction solvent. No significant difference in rate and diastereoselectivity is observed in diethyl ether as reaction solvent when addition of the cuprate, prepared from butyllithium and copper(I) bromide-dimethylsulfide complex, is performed in the presence or absence of chlorotrimethylsilane17. If, however, the reaction is performed in tetrahydrofuran, the reaction rate is accelerated in the presence of chlorotrimethylsilane and the diastereofacial selectivity increases to a ratio of 88 12 17. In contrast to the reaction in diethyl ether, the O-silylated product is predominantly formed in tetrahydrofuran. The alcohol product is only formed to a low extent and showed a diastereomeric ratio of 55 45, which is similar to the result obtained in the absence of chlorotrimethylsilane. This discrepancy indicates that the selective pathway leading to the O-silylated product is totally different and several times faster than the unselective pathway" which leads to the unsilylated alcohol adduct. A slight further increase in the Cram selectivity was achieved when 18-crown-6 was used in order to increase the steric bulk of the reagent. 

The enantiomerically pure vinylic organolithium reagent 8 is prepared from (A )-ethyl lactate in four steps. Subsequent addition of A-mesitylsulfonylimines 7 (they provide better diastereo-selectivilies than the corresponding jV-Losylimines) at — 110°C in tetrahydrofuran affords the adducts 9a and 9b in moderate yields (20-63%) but high diaslereoselectivities (d.r. 96 4 — 98 2)l0. 

Although it is unlikely that the tetrahydrofuran ring would open under these conditions of polymerization, the polymer was hydrolyzed in 0.2 M sodium hydroxide solution, in order to confirm its structure. Clear colorless liquid was obtained after acidification followed by esterification with diazomethane. Its IR and NMR data compares exactly to that obtained from 59 which was prepared from the neutral hydrolysis of 57 and esterification of the resultant acid with diazomethane. Since the apparent sole product obtained from hydrolysis of the polymer was 59, they conclude that 58 represents the correct structure for this polymer. 

Ketones can also be prepared from acyl chlorides by reaction at low temperature using an excess of acyl chloride. Tetrahydrofuran is the preferred solvent.91 The reaction conditions must be carefully controlled to prevent formation of tertiary alcohol by addition of a Grignard reagent to the ketone as it is formed. 

For the preparation of sterically crowded amides amino magnesium salts have been recommended for the reaction with imidazolides in order to increase the nucleophilicity of the amine moiety. Amino magnesium salts are prepared from the appropriate amines and ethyl magnesium bromide in tetrahydrofuran [90]... 

The iron(II) chloride7 is prepared from 1.5 g. (0.0268 mol) of iron powder (hydrogen-reduced, 100-mesh), 6.0 g. (0.370 mol) of anhydrous sublimed iron(III) chloride (Matheson, Coleman and Bell, reagent-grade), and 150 ml. of tetrahydrofuran (THF) freshly distilled under nitrogen from lithium tetrahydroaluminate or preferably calcium hydride. 

This procedure illustrates a fundamentally new method for constructing substituted tetrahydrofurans.5-10 This practical method assembles the tetrahydrofuran ring from allylic diol and carbonyl components and in the process forms three ring bonds C(2)-C(3), C(4)-C(5) and 0-C(5). Both aldehydes (eq 1) and ketones (illustrated in the present procedure) can be employed as the carbonyl component. Although it is often convenient to isolate the acetal intermediate, conversion to the 3-acyltstrahydrofuran can also be accomplished in many cases by the direct reaction of the diol and carbonyl components.8 High ds stereoselectivity (at least 20 1) is observed in the preparation of tetrahydrofurans that contain single side chains at carbons 2 and 5 (eq 1). The kinetically controlled product also has the cis relationship of these side chains and the 3-acyl substituent. 

The reactions with ruthenium carbonyl catalysts were carried out in pressurized stainless steel reactors glass liners had little effect on the activity. When trimethylamine is used as base, Ru3(CO) 2> H Ru4(CO) 2 an< H2Ru4(CO)i3 lead to nearly identical activities if the rate is normalized to the solution concentration of ruthenium. These results suggest that the same active species is formed under operating conditions from each of these catalyst precursors. The ambient pressure infrared spectrum of a typical catalyst solution (prepared from Ru3(CO)i2> trimethylamine, water, and tetrahydrofuran and sampled from the reactor) is relatively simple (vq q 2080(w), 2020(s), 1997(s), 1965(sh) and 1958(m) cm ). However, the spectrum depends on the concentration of ruthenium in solution. The use of Na2C(>3 as base leads to comparable spectra. 

Hydroxy- 1-butanesulfonic acid sultone has been made through the chlorosulfonation of 1-chlorobutane,3 from 4-chlorobutyl acetate 2 4 which is prepared through the reaction of tetrahydrofuran and acetyl chloride,2 from 4-chlorobutanol,4 and from bis-4-chlorobutyl ether.2 Both 4-chlorobutanol and bis-4-chlorobutyl ether can be prepared from tetrahydrofuran.6... 

Asymmetric hydrogenation of nitrones in an iridium catalyst system, prepared from [IrCl(cod)]2, (S)-BINAP, NBu 4 BH4, gives with high enantioselectivity the corresponding A-hydroxylamines which are important biologically active compounds and precursors of amines (480). Further reduction of hydroxylamines to secondary amines or imines can be realized upon treatment with Fe/AcOH (479), or anhydrous titanium trichloride in tetrahydrofuran (THF) at room temperature (481). 

The retention indices, measured on the alkyl aryl ketone scale, of a set of column test compounds (toluene, nitrobenzene, p-cresol, 2-phenyl ethanol, and IV-methylaniline) were used to determine the changes in selectivity of a series of ternary eluents prepared from methanol/0.02M phosphate buffer pH 7 (60 40), acetonitrile/0.02 M phosphate buffer pH 7 (50 50) and tetrahydrofuran/0.02 M phosphate buffer pH 7 (25 65). The analyses were carried out on a Spherisorb ODS reversed-phase column. The selectivity changes were often nonlinear between the binary composition [83]. 

The isomeric propargylic stannylated aldehyde intermediate, on the other hand, could be prepared from the alcohol precursor without competing cyclization to an seven-membered enol ether product (Eq. 9.105). Treatment of this stannane with SnCl4 afforded the cis-disubstituted tetrahydrofuran stereoselectively. Presumably, this reaction proceeds through an allenyl trichlorostannane intermediate. 

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