Tetrahydrofurans continued

The synthesis of di- and tetrahydrofurans continues to be one of the most active areas in synthetic organic chemistry. In the construction of tetrahydrofurans, the Williamson cycloetherization has always been a practical approach. Lautens employed a three-step procedure to convert the alcohol shown below to a bis-tetrahydrofuran <02OL1879>. A similar cyclization route was also utilized in the total synthesis of muconin <02TL8661>. 

In ionic polymerizations termination by combination does not occur, since all of the polymer ions have the same charge. In addition, there are solvents such as dioxane and tetrahydrofuran in which chain transfer reactions are unimportant for anionic polymers. Therefore it is possible for these reactions to continue without transfer or termination until all monomer has reacted. Evidence for this comes from the fact that the polymerization can be reactivated if a second batch of monomer is added after the initial reaction has gone to completion. In this case the molecular weight of the polymer increases, since no new growth centers are initiated. Because of this absence of termination, such polymers are called living polymers. 

A suspension of lithium aluminum deuteride (80 mg) in dry tetrahydrofuran (6 ml) is stirred and cooled in an ice bath while f-butanol (0.4 ml) is added dropwise, followed by a tetrahydrofuran solution of crude cholest-5-en-3-one (200 mg, mixed with cholest-4-en-3-one). The stirring and cooling is continued for 0.5 hr at 0° and then at room temperature for 2 hr. The... 

A suspension of lithium aluminum deuteride (1.6 g) in dry tetrahydrofuran (60 ml) is added dropwise to a stirred and cooled (with ice-salt bath) solution of 5a-androst-l4-ene-3j3,17j3-diol (179, 1.6 g) and boron trifluoride-etherate (13.3 g) in dry tetrahydrofuran (60 ml). The addition is carried out in a dry nitrogen atmosphere, over a period of 30 min. After an additional 30 min of cooling the stirring is continued at room temperature for 2 hr. The cooling is resumed in a dry ice-acetone bath and the excess deuteriodiborane is destroyed by the cautious addition of propionic acid. The tetrahydrofuran is then evaporated and the residue is dissolved in propionic acid and heated under reflux in a nitrogen atmosphere for 8 hr. After cooling, water is added and the product extracted with ether. The ether... 

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... 

A solution of 50 g of 3 -acetoxy-16 -methyl-5a-pregnan-20-one in tetrahydrofuran (120 ml) is added over 5 to 10 min, the passage of oxygen being continued for a further 45 min while maintaining the temperature at... 

There are different reasons to discard a column a column can be damaged by irreversible adsorption of reactive polymer samples. Small amounts of styrene oligomers are known to permanently elute from styrene-divinylbenzene materials with tetrahydrofuran as the eluent, which means a continuous shear degradation of the separation material and consequently a decrease of the packing quality this observation is very important if fractions are collected and used for further analyses, e.g., for the determination of infrared (IR) spectra. One can presume that similar effects are present with other organic materials too. 

This thinking has carried through to the present day and is reflected in our choices of mobile-phase fluids in LC water, acetonitrile, methanol, tetrahydrofuran, hexane, etc., are still among our popular choices. However, these particular materials are completely dependent on the conditions of column temperature and outlet pressure. Tswett s original conditions at his column outlet, actually the earth-bound defaults we call ambient temperature and pressure, determined his solvent choices and continue to dominate our thinking today. 

A 1.5 to 2 M solution of methylsulfinyl carbanion in dimethyl sulfoxide is prepared under nitrogen as above from sodium hydride and dry dimethyl sulfoxide. An equal volume of dry tetrahydrofuran is added and the solution is cooled in an ice bath during the addition, with stirring, of the ester (0.5 equivalent for each 1 equivalent of carbanion neat if liquid, or dissolved in dry tetrahydrofuran if solid) over a period of several minutes. The ice bath is removed and stirring is continued for 30 minutes. The reaction mixture is then poured into three times its volume of water, acidified with aqueous hydrochloric acid to a pH of 3-4 (pH paper), and thoroughly extracted with chloroform. The combined extracts are washed three times with water, dried over anhydrous sodium sulfate, and evaporated to yield the jS-ketosulfoxide as a white or pale yellow crystalline solid. The crude product is triturated with cold ether or isopropyl ether and filtered to give the product in a good state of purity. 

Alternatively, as described in U.S. Patent 3,341,557, 6-dehydro-17-methyltestosterone may be used as the starting material. A mixture of 0.4 g of cuprous chloride, 20 ml of 4 M methylmagnesium bromide in ether and 60 ml of redistilled tetrahydrofuran was stirred and cooled in an ice bath during the addition of a mixture of 2.0 g of 6-dehydro-l 7-methyl-testosterone, 60 ml of redistilled tetrahydrofuran and 0.2 g of cuprous chloride. The ice bath was removed and stirring was continued for four hours. Ice and water were then carefully added, the solution acidified with 3N hydrochloric acid and extracted several times with ether. The combined ether extracts were washed with a brine-sodium carbonate solution, brine and then dried over anhydrous magnesium sulfate, filtered and then poured over a 75-g column of magnesium silicate (Florisil) packed wet with hexanes (Skellysolve B). The column was eluted with 250 ml of hexanes, 0.5 liter of 2% acetone, two liters of 4% acetone and 3.5 liters of 6% acetone in hexanes. 

After this reaction-time, the evolution of hydrogen is ceased. Then there are added successively 60 parts dimethylformamide and 8 parts of p-chlorobenzylchloride and stirring and refluxing is continued for another two hours. The tetrahydrofuran is removed at atmospheric pressure. The dimethylformamide solution is poured onto water. The product, 1-[2,4-dichloro-/3-(p-chlorobenzyloxy)phenethyl] imidazole, is extracted with benzene. The extract is washed with water, dried, filtered and evaporated in vacuo. From the residual oily free base, the nitrate salt is prepared in the usual manner in 2-propanol by treatment with concentrated nitric acid, yielding, after recrystallization of the crude solid salt from a mixture of 2-propanol, methanol and diisopropylether, 1-[2,4-dichloro-/3-(p-chlorobenzyl-oxylphenethyl] imidazole nitrate MP 162°C. 

To a suspension of 73.9 g of 1 -methyl-5-nitro-3-phenylindole-2-carbonitrile in 1.5 liters of dry tetrahydrofuran Is added dropwise a solution of 126 g of boron trifluoride etherate in 220 ml of dry tetrahydrofuran with stirring for 2 hours. After addition, stirring is continued for an additional 3 hours. To the reaction mixture Is added dropwise 370 ml of water and then 370 ml of concentrated hydrochloric acid with stirring under ice-cooling. 

Cooling is continued. A solution of 8.31 g. (0.05 mole) of methyl anisate (methyl 4-methoxybenzoate) (Notes 7 and 8) in 100 ml. of anhydrous tetrahydrofuran is added to the stirred mixture during a 6-10-minute period, and the resulting mixture is then stirred for an additional 30 minutes (Note 9). At the end of this period, 300 ml. of aqueous 3N hydrochloric acid is added. The nitrogen-inlet tube is removed and replaced by a reflux condenser, and the dropping funnel is replaced by a ground-glass stopper. The ice bath is removed, and the mixture is heated under reflux for 1 hour. The flask is then cooled, and its contents are poured into a 2-1. Erlenmeyer flask, and solid sodium bicarbonate is added to the mixture until neutralization is complete (Note 10). 

Copper(I) iodide, purchased from Fisher Scientific Company, was purified by continuous extraction with anhydrous tetrahydrofuran in a Soxhlet extractor for approximately 12 hours in order to remove colored impurities. The residual copper(I) iodide was then dried under reduced pressure at 25° and stored under nitrogen in a desiccator. 

On the assumption that = 2, the theoretical values of the ion solvation energy were shown to agree well with the experimental values for univalent cations and anions in various solvents (e.g., 1,1- and 1,2-dichloroethane, tetrahydrofuran, 1,2-dimethoxyethane, ammonia, acetone, acetonitrile, nitromethane, 1-propanol, ethanol, methanol, and water). Abraham et al. [16,17] proposed an extended model in which the local solvent layer was further divided into two layers of different dielectric constants. The nonlocal electrostatic theory [9,11,12] was also presented, in which the permittivity of a medium was assumed to change continuously with the electric field around an ion. Combined with the above-mentioned Uhlig formula, it was successfully employed to elucidate the ion transfer energy at the nitrobenzene-water and 1,2-dichloroethane-water interfaces. 

The product workup consisted of continuously extracting the filter cake with tetrahydrofuran (THF) and combining the THF and filtrate to make up a sample for distillation. In some experiments the THF extracted filter cake was extracted with pyridine and the pyridine extract was included in the liquid products. Extraction with pyridine increased coal conversion to soluble products by an average of 1.6 weight percent. The hot filtrate-THF-pyridine extract was distilled. Distillation cuts were made to give the following fractions, THF (b.p. <100 C), light oil (b.p. 100-232 C), solvent (b.p. 232-482), and SRC (distillation residue, b.p. >482 C). 

THF Conversion. Tetrahydrofuran (THF) conversion was calculated from the difference between the initial and the final solubilities of the total coal-solvent slurry in THF. It was assumed that all of the solvent and none of the starting coal was soluble in THF. THF conversions were calculated on an MAF coal basis and adjusted for the coal not recovered from the autoclaves. The filter cake resulting from filtration of the product at 250 C was continuously extracted with THF for up to 3 days. 

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