Tetrahydrofuran, 3 -hydroxy

The polymerization of tetrahydrofuran was first studied ia the late 1930s (3,4). In 1960, this work was summarized (4), and the Hterature on tetrahydrofuran polymers and polymerization has been growing ever siace. Polytetrahydrofuran with hydroxy end groups has become a large-scale commercial product, used mainly as the flexible polyether segment ia elastomeric polyurethanes and polyesters. It is commercially available under the trade names Terathane (Du Pont), Polymeg (QO Chemicals), and PolyTHF (BASF). Comprehensive review articles and monographs have been pubUshed (2,5-8). 

The most important tetrahydrofuran polymers are the hydroxy-terrninated polymers, that is, the a,C0-poly(tetramethylene ether) glycols used commercially to manufacture polyurethanes and polyesters (see Urethane polymers Polyesters, thermoplastic). 

The hydroxy group can act as an intramolecular nucleophile. Solvolysis of 4-chlorobutanol in water gives as the product the cyclic ether tetrahydrofuran. The reaction is much faster than solvolysis of 3-chloropropanol under similar conditions. 

Hydrolysis of the above product (7 g in 40 ml tetrahydrofuran, 20 ml methanol and 0.3 ml concentrated hydrochloric acid for 1 hr at room temperature) affords an 84% yield of 3jS-hydroxy-17a-methylpregn-5-en-20-one after crystallization from acetone, mp 187-190°. reported mp 185-187°. ... 

While keeping the collected deuterioammonia at dry ice-isopropyl alcohol temperature, lithium wire (10 mg) is added, followed by a solution of 3/3-hydroxy-5a-cholest-7-en-6-one (161 50 mg) in anhydrous tetrahydrofuran (4 ml). The reaction mixture is stirred for 20 min, the cooling bath is then removed and the ammonia is allowed to boil under reflux for 40 min. A saturated solution of ammonium chloride in tetrahydrofuran is added dropwise until the deep blue color disappears and then the ammonia is allowed to evaporate. The residue is extracted with ether and the organic layer washed with dilute hydrochloric acid and sodium bicarbonate solution and then with water. Drying and evaporation of the solvent gives a semicrystalline residue which is dissolved in acetone and oxidized with 8 N chromic acid solution. After the usual workup the residue is dissolved in methanol containing sodium hydroxide (0.2 g) and heated under reflux for 1 hr to remove any deuterium introduced at C-5 or C-7. (For workup, see section II-B). 

A solution of 3jS-hydroxy-5a-androstan-17-one tosylate (193, 60 mg) in tetrahydrofuran (10 ml, freshly distilled from lithium aluminum hydride) is added dropwise to a boiling suspension of lithium aluminum deuteride (60 mg) in tetrahydrofuran (10 ml). The resulting suspension is heated under reflux for 30 min and after cooling the excess reagent is decomposed by the careful addition of a few drops of water. The heating is continued for a few minutes to coagulate the inorganic salts which are removed by filtration... 

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°. 

Preparation of 11 -Hydroxy-6a-Methylprogesterone A mixture of 2.68 g of 11-keto-6(3-methylprogesterone 3,20-bis-(ethylene ketal), 161 ml of tetrahydrofuran (previously distilled from lithium aluminum hydride), 1.34 g of lithium aluminum hydride and 14.5 ml of absolute ether was stirred and refluxed under nitrogen for 1.5 hours, then 27 ml of water was added cautiously, to decompose excess hydride. The resulting mixture was filtered and the filter cake was washed with 135 ml of ether. The combined filtrate and wash was shaken with 135 ml of water and separated. The aqueous layer was washed with four 55-ml portions of ether, then the organic layer and the washes were combined, washed once with water, and evaporated to dryness under diminished pressure leaving a tan residue. 

A solution of 1.5 g of dl-3-(1, r-dimethylheptyi)-6,6a,7,8-tetrahydro-1-hydroxy-6,6-di-methyl-9H-dibenzo(b,d] pyran-9-one in 50 mi of anhydrous tetrahydrofuran (THF) was added dropwise to a soiution of iithium metal in liquid ammonia at -80°C. Excess iithium metal was added in chunks to the solution as the biue color, indicating free dissolved lithium, disappeared. After the addition was complete, ammonium chloride was added to react with any excess lithium metal still present. 

To a stirred solution of 1.00 gram of 17/3-hydroxy-17o -methyl-4-androsteno[3,2-c] pyrazole in 200 ml of tetrahydrofuran and 400 ml of liquid ammonia was added 2.12 grams of iithium wire during 5 minutes. The dark biue mixture was stirred for 45 minutes. A solution of 40 ml of tertiary-butyl alcohol in 160 ml of diethyl ether was added with stirring. 

The outcomes of intramolecular cyclizations of hydroxy vinylepoxides in more complicated systems can be difficult to predict. In a study of the synthesis of the JKLM ring fragment of dguatoxin, epoxide 44 was prepared and subjected to acid-mediated cydization conditions (Scheme 9.24) [114]. Somewhat surprisingly, the expected oxepane 45 was not formed, but instead a mixture of tetrahydropyran 46 and tetrahydrofuran 47 was obtained, both compounds products of attack of the C6 and C5 benzyl ether oxygens, respectively, on the allylic oxirane position (C3). Repetition of the reaction with dimsylpotassium gave a low yield of the desired 45 along with considerable amounts of tetrahydropyran 48. 

Oxo-3-formyl-tetrahydrofuran/Dimethylamin und Natrium-cyano-trihydrido-borat 360 4-Hydroxy-3,3-dimcthyl- -lacton 360... 

Schatz, P. F. Ralph, J. Lu, F. Guzei, I. A. Bunzel, M. Synthesis and identification of 2,5-bis-(4-hydroxy-3-methoxyphenyl)-tetrahydrofuran-3,4-dicarboxylic acid, an unanticipated ferulate 8-8-coupling product acylating cereal plant cell walls. Org. Biomol. Chem. 2006, 4, 2801-2806. 

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