Recrystallization scratching

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 %). 

The N-[)3-(p-aminophenyl)ethyl]-4-phenyl-4-carboethoxypiperidine is dissolved in 50 cc of hot anhydrous ethanol, an excess (about 20 cc) of 20% alcoholic hydrochloric acid solution is added upon scratching the side of the container crystals form. One hundred cubic centimeters of ether are then added to the mixture, the ethereal mixture is cooled, and the crystalline material which precipitates is recovered by filtration, washed with ether, and dried to give 12.7 grams of N-[)3-(p-aminophenyl)ethyl]-4-phenyl-4-carboethoxypiperidine dihydrochloride which can be further purified by recrystallization from ethanol or methanol to give substantially pure material MP 275°-277°C. 

A mixture of 5.0 g of 3-chloro-5-(3-chloropropyl)-10,11 -dihydro-5H-dibenz(b,f)azepine, 5.0 g of 4-carbamoyl-4-piperidinopiperidine and 50 mi of dimethylformamide is heated at 100°C for 10 hours. The solvent is distilled off. After the addition of a 2% sodium carbonate solution to the flask, the content is scratched to yield a semisolid, which is dissolved in 50 ml of isopropanol. A solution of 5 g of maleic acid in 50 ml of isopropanol is added, and the precipitate is collected by filtration and recrystallized from isopropanol to give 5.6 g of crystalline 3-chloro-5-[3-(4-carbamoyl-4-piperidino-piperidino)propy I] -10,1 l-dihydro-SH-dibenz-Ib.fjazepine dilhydrogen maleate) with 1/2 molecule of water of crystallization melting at 181°C to 183°C. 

Turanose Phenylosotriazole. A solution of 15 g. of turanose phenylosazone in 300 cc. of hot water was placed on the steam-bath and a solution of 22 g. of copper siilfate pentahydrate in 150 cc. of hot water was added. The mixture turned a deep cherry-red at once and in a short time (fifteen min.) a red precipitate had formed and the solution had become green. After thirty minutes from the time of addition of the copper solution, the solution was cooled, filtered, and the copper removed as sulfide. The clear light yellow filtrate was neutralized with 45 g. of barium carbonate and the insoluble material removed by filtration. The filtrate was extracted with five 50-cc. portions of ether to remove the aniline, and the aqueous portion was concentrated in vacuo to a thick sirup. The sirup was dissolved in 60 cc. of warm alcohol, filtered to remove a slight turbidity and diluted with 65 cc. of ether. Upon cooling and scratching, the product crystallized as large prisms yield 8.9 g. (72%). The phenylosotriazole was recrystallized from 10 parts of alcohol and when pure showed the melting point 193-194° and rotated [a Jj" + 74.5° in aqueous solution (c, 0.90). 

B. 4-Phenyl-5-anilino-l,2,3-triazole. Six grams (0.025 mole) of 1,4-diphenyl-5-amino-l,2,3-triazole is dissolved in 20 g. of dry pyridine (distilled from solid sodium hydroxide) and heated under reflux for 24 hours (Note 6). The reaction mixture (Note 7) is poured into 11. of ice water. The product separates as a slightly yellowish milky oil which is converted to white needle-like crystals by stirring the mixture and scratching the beaker with a glass rod. The product is collected by suction filtration, washed with water, suction-dried, and recrystallized from aqueous ethanol (Note 8). The yield is 5.5-5.6 g. (92-93%) of fine white needle-like crystals, m.p. 167-169° (Note 9), soluble in hot water and ether, but difficultly soluble in benzene. 

Heat 85.5 g 3-carbethoxy-2-piperidone and 30 g KOH in 1 L water for twelve hours at 30°. Filter, cool to 0°, add 50 ml 6N HCI. Prepare a fresh solution by diazotizing at 0-5° a mixture of 85 g 3-amino-4-Cl-acetophenone, 250 ml concentrated HCI and 750 ml water with a solution of 36 g Na nitrite in 125 ml water. Add the piperidone solution at 0° to the diazonium salt solution and stir five hours at 10°. Filter, wash precipitate with water to get 80% yield of the hydrazone (1) (recrystallize-95% ethanol). Reflux 62 g (I) in 310 ml 88% formic acid to get 40 g of the carboline (II) (recrystallize-absolute ethanol) (test for activity). Reflux 40 g (II), 100 g KOH, 480 ml ethanol and 360 ml water for eighteen hours and evaporate in vacuum. Add 480 ml water to the residue, cool and adjust pH to 6 with glacial acetic acid. Scratch glass to precipitate filter, wash precipitate with cold water to get 41 g 4-acetyl-2-COOH-7-CI-tryptamine (recrystallize-50% ethanol) which can be alkylated to the active dialkyltryptamine as described elsewhere here. 

Carbomethoxytropinone. A mixture of 1.35 g of sodium methoxide (this is sodium in a minimum amount of methanol), 3.5 g of tropinone, 4 ml of dimethylcarbonate and 10 ml of toluene is refluxed for 30 min. Cool to 0° and add 15 ml of water that contains 2.5 g of ammonium chloride. Extract the solution after shaking with four 50 ml portions of chloroform, dry, evaporate the chloroform in vacuo. Dissolve the oil residue in 100 ml of ether, wash twice with a mixture of 6 ml of saturated potassium carbonate and three ml of 3 N KOH. Dry and evaporate in vacuo to recover the unreacted tropinone. Take up the oil in a solution of aqueous ammonium chloride and extract with chloroform, dry, and evaporate in vacuo to get an oil. The oil is dissolved in hot acetone, cool, and scratch inside of flask with glass rod to precipitate 2-carbomethoxytropinone. Recrystallize 16 g of this product in 30 ml of hot methyl acetate and add 4 ml of cold water and 4 ml of acetone. Put in freezer for 2 /2 to 3 hours. Filter and wash the precipitate with cold methyl acetate to get pure product. 

The arsanilic acid can be obtained from the aqueous alkaline solution either as the free acid or as the sodium salt. To obtain the free acid the solution is acidified with concentrated hydrochloric acid until the purple color of tetrabromophenolsulfon-phthalein is changed to a faint yellow. Care should be taken, in the addition of the acid, not to overstep the end-point (Note 4). Crystallization is stimulated by scratching and the flask is allowed to stand over night to complete the precipitation. The crystals are filtered off and recrystallized once from water (about 2500 cc.) in order to obtain a white product. If the initial crystals obtained have an appreciable pink tinge, it is advisable to remove most of the color by digesting with a small volume of warm alcohol before crystallization from water is attempted (Note 5). 

To a rapidly stirred solution of bcnzimidazole-2-thiol (7 1.00 g, 6.66 mmol) in THF (10 mL) was added 2 M NaOH (3.4 mL, 6.8 mmol). After 4 min, pentafluorobenzyl bromide (1.74 g, 6.67 mmol) was added within (.5 inin. After 10 min, the solution was poured into H20 (50 mL). A solid readily formed upon scratching. After 5 min, filtration gave a solid, which was washed with H20 (10 mL) and dried under full vacuum to give 2-(pentafluorobenzylsulfanyl)benzimidazolc (8) as a colorless solid [yield 1.91 g (87%) mp 188.5-191.5 C], which can be further purified by recrystallization (EtOH). 

Z-K[Co(enta)] 2H20. The diastereoisomer (2.0 g.) is suspended in 15 ml. of water in a mortar. Four grams of potassium iodide is added and the mixture triturated for 4 to.5 minutes. The insoluble iodide d-[Co(en)2(N02)2]I precipitates and is filtered. Eighteen milliliters of ethanol is added slowly to the filtrate with scratching of the sides of the vessel, and the levo salt separates as sparkling violet plates. This is allowed to stand for 3 or 4 minutes. Then more ethanol is gradually added until a total volume of 40 ml. has been added. The crystals are collected and washed with cold ethanol. Recrystallization is usually not necessary, but may be effected by dissolution in 15 ml. of warm water followed by the addition of 40 ml. of ethanol. The crystals obtained are washed with ethanol and acetone and air-dried. The yield is 1.2 g., or, if the whole of the diastereoisomer is used (2.6 g.), 1.5 g., representing a 75% yield. 

A mixture of pyridin-2(l//)-one (1 48 g. 0.5 mol) and hexafluOrobut-2-ync (2 97 g. 0.6 mol) was placed in an autoclave blanketed with N, and heated -at 175 C for 12 h. The resulting mobile, black liquid was chromatographed (Florisil, hexanc/EtjO 9 1) 10 afford a pale yellow oil which crystallized on cooling and scratching yield 78.0 g (61%). Three recrystallizations (hcxanc/EijO) gave analytically pure 3 as long, white blades mp 55-56 C. 

To purify your product, recrystallize your collected solid from acetone. To accomplish this, transfer the solid to a 125-mL flask. Add a small amount (20 ruL to start) of acetone and a stir bar. Heat to fully dissolve the solid. Add small amounts of acetone, order 1 ruL at a time, as needed, to aid in the dissolution. When solid is dissolved, remove from heat. Cool with the aid of an ice bath. Crystals should form. If they do not, try scratching the inside of the flask with a glass rod. Or, boil off some solvent and recool. Remove these crystals by suction filtration just as you did to collect your impure product. Wash these crystals with a cold 5 ruL portion of acetone and allow them to dry on the filter paper. Transfer to a preweighed vial. Calculate yield of cholesteryl nonanoate from cholesterol and calculate the conversion of cholesterol to cholesteryl nonanoate. 

When the solution is cold (about 5 C), collect the solid by suction filtration (Box 5.2), using the filtrate, to transfer the solid completely from the collection flask. If crystals do not form, cither add a few crystals of the crude solid to seed the super saturated solution or scratch with a Pyrex" glass rod to induce recrystallization. 

The compound does not recrystallize. There are two reasons you have used too much solvent and you must evaporate off some solvent before cooling, or you have formed a supersaturated solution and you must seed or scratch the solution (see p. 98). 

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