Crystallization sodium chloride, recrystallization

Alberger A process for crystallizing sodium chloride from brine. The brine is heated under pressure to 145°C to remove calcium sulfate. Flashing to atmospheric pressure produces fine cubic crystals of sodium chloride, and surface evaporation in circular vessels produces flakes of it. Developed by J.L. and L.R. Alberger in the 1880s. See also Recrystallizer. 

A solution of 0.25 g sodium borohydride in 140 ml of ethanol is added to a stirred solution of 0.56 g of calcium chloride in 60 ml of ethanol at —25°. The vigorously stirred mixture is treated dropwise at —25° over 5 min with 4.87 g of 1 la-hydroxy-5/S-pregnane-3,20-dione in 100 ml of ethanol. After a further 3 hr at —20°, 10 ml of 40% aqueous acetic acid is added and the mixture is evaporated to dryness under vacuum. The residue is dissolved in 150 ml of ether and the ethereal solution is washed with 30 ml of 2 A hydrochloric acid and twice with 30 ml of water and dried over Na2S04. Removal of the solvent gives 4.6 g of crystals, which are recrystallized from 20 ml of ether to yield 2.9 g (60%) of the dihydroxy ketone, mp 182-184° [aj 110° (ethanol). 

A total of 3 g (0.13 moles) of sodium hydride is added to a solution consisting of 10 g of 17 -hydroxy-5a-androstan-3-one (36 mmoles) in 200 ml of benzene and 10 ml of ethyl formate. The reaction mixture is allowed to stand under nitrogen for 3 days followed by dropwise addition of 10 ml of methanol to decompose the excess of sodium hydride. The solution is then diluted with 300 ml water and the layers are separated. The basic aqueous solution is extracted with ether to remove neutral material. The aqueous layer is acidified with 80 ml of 3 A hydrochloric acid and the hydroxymethylene steroid is extracted with benzene and ether. The combined organic extracts are washed with water and saturated sodium chloride solution and then dried over magnesium sulfate and concentrated. The residue, a reddish-yellow oil, crystallized from 10 ml of ether to yield 9.12 g (83%) of 17 -hydroxy-2-hydroxymethylene-5a-androstan-3-one mp 162-162.5°. Recrystallization from chloroform-ether gives an analytical sample mp 165-165.5° [a]o 53° (ethanol) 2 ° 252 mjj. (g 11,500), 307 m u (e 5,800). 

A mixture consisting of 0.69 g (10.5 mmoles) of zinc-copper couple, 12 ml of dry ether, and a small crystal of iodine, is stirred with a magnetic stirrer and 2.34 g (0.7 ml, 8.75 mmoles) of methylene iodide is added. The mixture is warmed with an infrared lamp to initiate the reaction which is allowed to proceed for 30 min in a water bath at 35°. A solution of 0.97 g (2.5 mmoles) of cholest-4-en-3/ -ol in 7 ml of dry ether is added over a period of 20 min, and the mixture is stirred for an additional hr at 40°. The reaction mixture is cooled with an ice bath and diluted with a saturated solution of magnesium chloride. The supernatant is decanted from the precipitate, and the precipitate is washed twice with ether. The combined ether extracts are washed with saturated sodium chloride solution and dried over anhydrous sodium sulfate. The solvent is removed under reduced pressure and the residue is chromatographed immediately on 50 g of alumina (activity III). Elution with benzene gives 0.62 g (62%) of crystalline 4/5,5/5-methylene-5 -cholestan-3/5-ol. Recrystallization from acetone gives material of mp 94-95° Hd -10°. 

The mixture is decanted into an Erlenmeyer flask, the residual green salts are washed with two 15-ml portions of acetone, and the washings are added to the main acetone solution. Cautiously, sodium bicarbonate (approx. 13 g) is added to the solution with swirling until the pH of the reaction mixture is neutral. The suspension is filtered, and the residue is washed with 10-15 ml of acetone. The filtrate is transferred to a round-bottom flask and concentrated on a rotary evaporator under an aspirator while the flask temperature is maintained at about 50°. The flask is cooled and the residue transferred to a separatory funnel, (If solidification occurs, the residue may be dissolved in ether to effect the transfer.) To the funnel is added 100 ml of saturated sodium chloride solution, and the mixture is extracted with two 50-ml portions of ether. The ether extracts are combined, washed with several 5-ml portions of water, dried over anhydrous magnesium sulfate, and filtered into a round-bottom flask. The ether may be distilled away at atmospheric pressure (steam bath) or evaporated on a rotary evaporator. On cooling, the residue should crystallize. If it does not, it may be treated with 5 ml of 30-60° petroleum ether, and crystallization may be induced by cooling and scratching. The crystalline product is collected by filtration and recrystallized from aqueous methanol. 4-r-Butylcyclohexanone has mp 48-49° (yield 60-90 %). 

To 10 g of cyclohexane-1,4-oxide is added 48% aqueous hydrobromic acid (60 g). The phases are mixed thoroughly and allowed to stand at room temperature until the solution separates into two layers (usually 5 days). The mixture is saturated with sodium chloride and extracted twice with 25-ml portions of ether. The ether layer is washed with an equal volume of saturated sodium bicarbonate solution, then with the same amount of water. Finally, the ether solution is dried over anhydrous sodium sulfate, the ether is evaporated, and the residue is allowed to cool, whereupon crystallization should follow. The crude product may be recrystallized from petroleum ether giving material of mp 81-82° (yield, 11 g). 

The solvent was evaporated to yield a colorless solid residue, which was taken up In ethyl acetate-ice water. The two layers were separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with water, saturated sodium chloride solution and filtered through anhydrous sodium sulfate. The solvent was evaporated to yield 1.20 grams of light tan crystals, MP 151° to 155°C, ultraviolet maximum at 224 mp (E = 4,095). Two recrystallizations from ethanol afforded 1st crop, 0.619 grams (62%) of colorless crystals (dried at 120°C in vacuo for 17 hours), (VIP 232.8° to 238.0°C, ultraviolet maximum at 224 mp (E = 4,840) 2nd crop, 0.142 gram (14%) of colorless crystals, MP 234° to 242°C. 

The organic fractions are combined and washed successively with N,N-dimethyl-1,3-propane-diamine, dilute hydrochloric acid, saturated sodium bicarbonate solution and saturated sodium chloride solution. The organic fraction is dried over anhydrous magnesium sulfate. The solvent is then evaporated off. Upon trituration of the residue with methanol, a solid crystallizes, 5-(p-toluovl)-1 -methvlpvrrole-2-acetonitrile, which is removed by filtration and purified by recrystallization from benzene. 

B. 2,2-(Trimethylenedithio)cyclohexanone. A solution of 3.02 g. (0.02 mole) of freshly distilled 1-pyrrolidinocyclohexene, 8.32 g. (0.02 mole) of trimethylene dithiotosylate4 (Note 2), and 5 ml. of triethylamine (Note 3) in 40 ml. of anhydrous acetonitrile (Note 4), is refluxed for 12 hours in a 100-ml., round-bottom flask under a nitrogen atmosphere. The solvent is removed under reduced pressure on a rotary evaporator, and the residue is treated with 100 ml. of aqueous 0.1 N hydrochloric acid for 30 minutes at 50° (Note 5). The mixture is cooled to ambient temperature and extracted with three 50-ml. portions of ether. The combined ether extracts are washed with aqueous 10% potassium bicarbonate solution (Note 6) until the aqueous layer remains basic to litmus, and then with saturated sodium chloride solution. The ethereal solution is dried over anhydrous sodium sulfate, filtered, and concentrated on a rotary evaporator. The resulting oily residue is diluted with 1 ml. of benzene and then with 3 ml. of cyclohexane. The solution is poured into a chromatographic column (13 x 2.5 cm.), prepared with 50 g. of alumina (Note 7) and a 3 1 mixture of cyclohexane and benzene. With this solvent system, the desired product moves with the solvent front, and the first 250 ml. of eluent contains 95% of the total product. Elution with a further 175 ml. of solvent removes the remainder. The combined fractions are evaporated, and the pale yellow, oily residue crystallizes readily on standing. Recrystallization of this material from pentane gives 1.82 g. of white crystalline 2,2-(trimethylenedithio)cyclo-hexanone, m.p. 52-55° (45% yield) (Note 8). 

The flask contents are transferred to a separatory funnel, washed with 100 mL of water, 100 mL of saturated sodium chloride solution, and dried over anhydrous magnesium sulfate. The solvent is removed by rotary evaporator and the solid residue is triturated with three portions of cold (0-5°C) methanol (50 mL, then 20 mL twice). The insoluble product is filtered, air dried, and recrystallized from acetone to give as the first crop 3.0-3.4 g of the pure anti isomer (Notes 6, 7) mp (dec) > 250°C (Note 8). Additional crystallizations bring the yield to 4.6 g (22%). 

The reaction mixture is poured slowly into a vigorously stirred solution of 28 ml. (0.28 mole) of concentrated hydrochloric acid and 350 ml. of ice water placed in a 1-1. threenecked round-bottomed flask fitted with an efficient stirrer and immersed in an ice bath (Note 7, Note 8). The mixture is stirred for 20 minutes with ice cooling and extracted three times with 200-ml. portions of a 3 1 (vjv) mixture of ether and methylene chloride. The extracts are washed with three 200-ml. portions of aqueous 2M sodium hydroxide, two 200-ml. portions of water, and one 200-ml. portion of saturated aqueous sodium chloride, and then dried over anhydrous sodium sulfate, and evaporated under reduced pressure (Notes 9 and 10). The crystalline residue, weighing 2.70 g., is recrystallized by dissolving it in 7.5-8 ml. of hot (almost boiling) benzene and adding 25 ml. of n-pentane (distilled) to the hot solution (Note 11). 3j3-Acetoxy-5a-cyanocholestan-7-one is obtained as white crystals, m.p. 192.5-193.5° the yield is 2.27-2.41 g. (86—91%). A second crop can be obtained in 50—170 mg. yield, m.p. 188.5-190° (Note 12) the total yield is 92-93% (Notes 13 and 14). 

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