Ether sulfates isolation

Tetrahydropyranylation The reaction of an alcohol (even tertiary) with dihydropyran is catalyzed efficiently by [(CH3)3Si0]2S02. The resulting ether is isolated in 90-100% yield by addition of pyridine and concentration of the solvent. The sulfate also catalyzes alcoholysis of the derivative at 25° (10-90 minutes). It is also useful in some transesterifications. 

Separate off the toluene layer and dry over sodium sulfate. Filter the solution, then remove most of the solvent by rotary evaporation. Add petroleum ether to promote crystallization and filter off the crystals. Concentrate supernatant and add more petroleum ether and isolate a second crop of crystals. 

Benzidine methods make use of the very low solubility of benzidine sulfate which can be isolated and titrated as an add as in the method of Rosenheim and Drummond (79), or determined by means of a color reaction such as that with hydrt en peroxide and ferric chloride (91), or sodium fi-naphthoquinone-4-sulfonate(59),orbydiazotizationandcoupling(33,55,72). The colorimetric methods are claimed to be very sensitive. The benzidine method provides a rapid method for estimating ethereal sulfate but since, like the Folin (43) method, it is a difference method it becomes less reliable as the inorganic. ethereal sulfate ratio increases. The precipitation of benzidine sulfate by the original method, especially from hydrolyzed urines, may occasionally be capricious, even to the extent that less benzidine sulfate is precipitated from hydrolyzed urine than from unhydrolyzed urine. This difficulty can be largely overcome by preliminary removal of phosphates and precipitation under conditions recommended by Fiske (42). Under experimental conditions dietary control may serve to ensure that the excretion of phosphate is so low as not to interfere with precipitation of benzidine sulfate (e. g.. Maw (63)). 

Both a- and 3-naphthols are converted to glucuronosides and ethereal sulfates in the body and also probably are oxidized to a slight extent (220). Both glucuronosides were isolated from urine. a-Naphthyl /3-glucuronoside is a crystalline solid (m.p. 202-3°, [a]i> —89.3°) and also was formed during metabolism of naphthalene. /3-Naphthyl )3-glucuronoside crystallizes as a hydrate (m.p. 100°, [a]o —90.65° in the anhydrous state, m.p. 151°, [a]o -100.85°) (24). 

Indole is oxidized in the animal body to indoxyl or /3-hydroxyindole. Indoxyl occurs normally in the urine as an ethereal sulfate but when dogs were fed indole (308) the glucuronoside of indoxyl was isolated from the urine as a barium double salt of indoxyl glucuronoside and indoxyl sulfuric acid (LXIII). The salt was levorotatory and its specific rotation changed in 24 hrs. from —64.9° to —34°. 

Endo-exo product mixtures were isolated using the following procedure. A solution of cyclopentadiene (concentration 2-10" M in water and 0.4 M in oiganic solvents) and the dienophile (concentration 1-5 mM) in the appropriate solvent, eventually containing a 0.01 M concentration of catalyst, was stirred at 25 C until the UV-absorption of the dienophile had disappeared. The reaction mixture (diluted with water in the case of the organic solvents) was extracted with ether. The ether layer was washed with water and dried over sodium sulfate. After the evaporation of the ether the... 

Hydroxy-B-homo-5a-cholestan-7-one acetate (54b) A solution of 3/3-hydroxy-5a-cholestan-7-one acetate (51b 5 g mp 146-148°) in dioxane-ethanol (100 ml, 1 1) is placed in a 250 ml three-necked flask equipped with a mechanical stirrer and thermometer and is cooled to 0° (iee-salt bath). Powdered potassium cyanide (7.3 g) is added portionwise with stirring. Acetic acid (8 ml) is then added dropwise with constant stirring over 30 min. The resultant mixture is stirred for 1 hr at 0° C and for an additional 2 hr at room temperature. It is then poured into ice water (200 g ice, 100 ml water) and after standing for 1 hr the precipitate is collected by filtration. The product is dissolved in ether (100 ml), the ether solution is washed with 5% sodium bicarbonate, water and dried over anhydrous sodium sulfate. The filtrate is evaporated at reduced pressure and the solid residue (5.1 g) is crystallized from ethyl acetate (30 ml) to yield 2.8 g of cyanohydrin (52b) mp 160-164° repeated crystallization from the same solvent gives a product mp 164-167°. An alternative method of isolation of the cyanohydrin is used when 100 g or larger quantities are worked up. The reaction mixture is poured directly into a mixture of ice water and sodium bicarbonate, the precipitate (mp 155-156°) is washed well with water, dried and used directly for the next step. 

Excess lithium is destroyed by the c irc/w/addition of 1-2 ml of ethanol, and hydrolysis of the reaction mixture is then effected by the addition of a mixture of ice (50 g) and water (100 ml). The solution is then acidified to pH 2 by the addition of 5 A hydrochloric acid, followed by rapid stirring for 1 or 2 minutes to hydrolize the HMPT. The aqueous solution is extracted with ether, the ether solution is dried with magnesium sulfate, then filtered, and the ether is evaporated. The product is isolated by distillation of the residue. 

This ester (70 g) and diethyl carbonate (250 mg) were stirred at 90°C to 100°C while a solution of sodium ethoxide [from sodium (7.8 g) and ethanol (1 54 ml)] was added over 1 hr. During addition, ethanol was allowed to distill and after addition distillation was continued until the column heat temperature reached 124°C. After cooling the solution to 90°C, dimethyl sulfate (33 ml) was followed by a further 85 ml of diethyl carbonate. This solution was stirred and refluxed for 1 hr and then, when Ice cool, was diluted with water and acetic acid (10 ml). The malonate was isolated in ether and fractionally distilled to yield a fraction boiling at 148°C to 153°C/0.075 mm, identified as the alpha-methyl malonate. This was hydrolyzed by refluxing for 1 hr at 2.5N sodium hydroxide (350 ml) and alcohol (175 ml), excess alcohol was distilled and the residual suspension of sodium salt was acidified with hydrochloric acid to give a precipitate of the alpha-methyl malonic acid. This was decarboxylated by heating at 180°C to 200°Cfor 30 minutes and recrystallized from petroleum ether (BP 80°C to 100°C) to give 2-(2-fluoro-4-biphenylyl)propionic acid, MP 110°C to 111°C. 

A solution of 3.1 g of (2-benzoyl-4-chlorophenyl-carbamoylmethyl)carbamic acid benzyl ester in 30 cc of 20% hydrobromic acid in glacial acetic acid was stirred for 45 minutes at room temperature. On addition of 175 cc of anhydrous ether, a gummy solid precipitated. After several minutes the ether solution was decanted. The resultant 5-chloro-2-gly-cylaminobenzophenone was not isolated, but about 155 cc of ether was added to the residue and after chilling in an ice bath, 10% sodium hydroxide was added until the mixture was alkaline. The ether layer was then separated, washed twice with water and dried over sodium sulfate. After filtration, the ether solution was concentrated to dryness in vacuo. The residue was crystallized from benzene to yield 7-chloro-5-phenyl-3H-1,4-benzodiazepin-2(1 H)-one. 

Ethyl Y-phenylbutyrate is prepared in 85-88 per cent yields by refluxing for three hours a mixture of 50 g. of 7-phenylbutyric acid (Org. Syn. 15, 64), 150 cc. of alcohol dried over lime, and 5 g. of concentrated sulfuric acid. The ester is isolated by distilling 100 cc. of the alcohol under reduced pressure from a steam bath, diluting with 200 cc. of water, separating, and extracting the aqueous layer twice with 50-cc. portions of ether. The combined ester and ether layers are dried with sodium sulfate, the ether removed, and the residue distilled under diminished pressure the portion boiling at 144-147° at 19 mm. is collected. 

The amount of residual sulfonate ester remaining after hydrolysis can be determined by a procedure proposed by Martinsson and Nilsson [129], similar to that used to determine total residual saponifiables in neutral oils. Neutrals, including alkanes, alkenes, secondary alcohols, and sultones, as well as the sulfonate esters in the AOS, are isolated by extraction from an aqueous alcoholic solution with petroleum ether. The sulfonate esters are separated from the sultones by chromatography on a silica gel column. Each eluent fraction is subjected to saponification and measured as active matter by MBAS determination measuring the extinction of the trichloromethane solution at 642 nra. (a) Sultones. Connor et al. [130] first reported, in 1975, a very small amount of skin sensitizer, l-unsaturated-l,3-sultone, and 2-chloroalkane-l,3-sultone in the anionic surfactant produced by the sulfation of ethoxylated fatty alcohol. These compounds can also be found in some AOS products consequently, methods of detection are essential. 

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