Tetrahydrofuran from diols

Chromium coordinates selectively with the 1,2-diol, forming a stable cyclic chromate ester that evolves producing the formation of a tetrahydrofuran. Observe that no formation of tetrahydrofuran from the alcohol on the left occurs, for this would involve the intermediacy of a less stable simple chromate ester (vide infra). The experimental conditions are so mild that no direct oxidation of the secondary alcohol to ketone is observed, either on the starting compound or in the product. 

The method is readily adapted for the preparation of dibromides from diols. Typical examples are provided in Expt 5.54. The cyclic ethers tetrahydrofuran and tetrahydropyran are readily cleaved by the hydrobromic acid-sulphuric acid medium, and this provides an alternative and convenient preparation of the corresponding a, co-dihalides. 

The authors opted to install the bromotetrahydropyran A-ring last due to its possible instability under radical, strongly basic, and/or acidic conditions. The D-ring was envisioned to arise from a stereoselective epoxidation followed by cyclization to afford the tetrahydrofuran framework. Key to achieving this plan was accessibility to structure 56 (Scheme 10). This fragment in turn was envisioned to be assembled by coupling the anion derived from 57 with epoxide 58. Compound 58 could presumably be accessed via stereoselective cyclizations from diol 59. 

Benzenesulfonyl chloride pyridine Cyclic ethers from diols s. 7, 355 stereospecific ring closure, tetrahydrofurans, C OH also with f. reagents, and from dimesylates preferably with NaOH, s. M. L. Mihailovid, S. Gojkovic, and 2. Cekovic, Soc. Perkin I 1972, 2460... 

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. 

The polyols used are of three types polyether, polyester, and polybutadiene. The polyether diols range from 400 to about 10,000 g/mol. The most common polyethers are based on ethylene oxide, propylene oxide, and tetrahydrofuran or their copolymers. The ether link provides low temperature flexibility and low viscosity. Ethylene oxide is the most hydrophilic and thus can increase the rate of ingress of water and consequently the cure rate. However, it will crystallize slowly above about 600 g/mol. Propylene oxide is hydrophobic due to hindered access to the ether link, but still provides high permeability to small molecules like water. Tetrahydrofuran is between these two in hydrophobicity, but somewhat more expensive. Propylene oxide based diols are the most common. 

A slow stream of purified and dried acetylene is passed for 3 hr through a solution containing 25 ml (75 mmoles) of a 3 TV solution of methyl magnesium bromide and 100 ml of anhydrous tetrahydrofuran. A solution consisting of 5 g (17 mmoles) of 3)5-hydroxyandrost-5-en-17-one and 50 ml of anhydrous tetrahydrofuran is then added and the mixture is boiled at reflux for 15 min, during which time a heavy precipitate forms. The reaction mixture is cooled and poured into 1 liter of water containing 20 ml of concentrated sulfuric acid. The crude product is obtained as a precipitate, which is filtered, washed with water and dried to yield 5.2 g of 17a-ethynylandrost-5-ene-3, 17 -diol mp 228-232°. One crystallization from chloroform-hexane yields 4.5 g (83%) mp 238-240° [[Pg.73]

Vinyllithium Reaction To a cooled solution of 80 g of 3y -hydroxy-5a-androstan-17-one in 1.5 liters of tetrahydrofuran is added 400 ml of 2 4/ vinyllithium in tetrahydrofuran. The solution is stirred at 0° for 0.5 hr, allowed to warm to room temperature, and stirred an additional hr. Cone ammonium chloride solution is added, and the mixture is concentrated under reduced pressure until a precipitate begins to form. The slurry is poured into water, and the precipitate is filtered and recrystallized twice from methanol, affording 52.2 g (60%) of 17a-vinyl-5a-androstane-3, 17i -diol mp 205-207.5°. 

Selective hydroxylation with osmium tetroxide (one equivalent in ether-pyridine at 0 ) converts (27) to a solid mixture of stereoisomeric diols (28a) which can be converted to the corresponding secondary monotoluene-sulfonate (28b) by treatment with /7-toluenesulfonyl chloride in methylene dichloride-pyridine and then by pinacol rearrangement in tetrahydrofuran-lithium perchlorate -calcium carbonate into the unconjugated cyclohepte-none (29) in 41-48 % over-all yield from (27). Mild acid-catalyzed hydrolysis of the ketal-ketone (29) removes the ketal more drastic conditions by heating at 100° in 2 hydrochloric acid for 24 hr gives the conjugated diketone (30). 

Preparation of cholesta-5,7-diene-ia,3/3-diol a solution of 500 mg of the 1,4-cyclized adduct of cholesta-5,7-dien-3/3-ol-ia,2a-epoxideand 4-phenyl-1,2,4-triazoline-3,5-dione in 40 ml of tetrahydrofuran is added dropwise under agitation to a solution of 600 mg of lithium aluminum hydride in 30 ml of THF. Then, the reaction mixture liquid Is gently refluxed and boiled for 1 hour and cooled, and a saturated aqueous solution of sodium sulfate is added to the reaction mixture to decompose excessive lithium aluminum hydride. The organic solvent layer is separated and dried, and the solvent Is distilled. The residue Is purified by chromatography using a column packed with silica gel. Fractions eluted with ether-hexane (7 3 v/v) are collected, and recrystallization from the methanol gives 400 mg of cholesta-5,7-diene-la, 3/3-diol. 

A solution of 1.0 g of 1,4 (11 )-pregnatriene-170 1 -diol-3 0-dione-21 -acetate and 5,0 g of lithium chloride in 40 ml of glacial acetic acid is treated with 0.410 g of Nchlorosuccinimide, followed by 0.104 g of anhydrous hydrogen chloride dissolved in 2.5 ml of tetrahydrofuran. The reaction mixture is stirred for 2 hours and poured into ice water. The crude product Is filtered and washed with water to give 1.12 g of solid material, which is recrystallized from acetone-hexane to give substantially pure 90 ,11 -dichloro-1,4-pregnadiene-170 ,21 -diol-3,20-dione-21 -acetate MP 246°C to 253°C (dec.). 

A solution of sodium borohydride (8 grams) in water (16 ml) was added to a stirred solution of 2(3,16(3-bis-piperidino-5a-androstan-3a-ol-17-one (17 grams) in tetrahydrofuran (70 ml) and methanol (30 ml) and the solution stirred at room temperature for 16 hours. The product was precipitated by the addition of water, filtered off, dried, and crystallized from acetone to give the diol (14.9 grams). 

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 synthesis of tetrahydrofuran derivatives from unsaturated alcohols via hydroformylation intermediates was developed many years ago. Moderate yields are obtained from but-2-en-l,4-diol (Scheme 54)94 but hydroformylation is not the major pathway when coniferyl alcohol is subjected to the oxo process (Scheme 55).9S A more complicated reaction is involved... 

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