Recrystallization Tubes

Craig tubes are a particularly effective method for recrystallizing small quantities of reaction products. These tubes possess a nonuniform ground joint in the outer section. The substitution of Teflon for glass in the head makes these systems quite durable and much less susceptible to breakage during centrifugation (see Fig. 3.4). 

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Extrusion Resins. Extmsion of VDC—VC copolymers is the main fabrication technique for filaments, films, rods, and tubing or pipe, and involves the same concerns for thermal degradation, streamlined flow, and noncatalytic materials of constmction as described for injection-molding resins (84,122). The plastic leaves the extmsion die in a completely amorphous condition and is maintained in this state by quenching in a water bath to about 10°C, thereby inhibiting recrystallization. In this state, the plastic is soft, weak, and pHable. If it is allowed to remain at room temperature, it hardens gradually and recrystallizes partially at a slow rate with a random crystal arrangement. Heat treatment can be used to recrystallize at controlled rates. 

For further purification the material may be recrystallized from hot water, or dissolved in alkali and reprecipitated, or distilled under reduced pressure or sublimed. Each of these operations involves considerable loss of product, either through solubility or through decomposition by heat. The best-appearing product is obtained by distillation under reduced pressure. The crude acid is distilled from a Claisen flask with a delivery tube set low in order that the acid need not be heated much above the boiling j)oint. The product boiling at i4i-i44°/20 mm. is ])ure wliitc and melts at 125-132° (Note 8). The yield of distilled acid is about 75-85 per cent of the weight of the crude acid. 

The dry tosylhydrazone (20 g, 45.5 mmol) is dissolved in 750 ml of 1,2-dimethoxyethane (freshly distilled from lithium aluminum hydride) in a flame-dried 1 liter round bottom flask fitted with a 240 ml addition funnel, a drierite tube and a magnetic stirrer. A 2.05 M ether solution of methyllithium (130 ml, Alfa Inorganics, Inc.—Caution to avoid the mineral oil impurity the methyllithium solution is decanted from a cold solution which contains a precipitate) is placed in the dropping funnel and added over a 60 min period. The temperature of the reaction mixture increases to ca. 35° during the addition however, no cooling precautions are required. The highly colored reaction mixture is stirred for 7 hr and then poured into 1.5 liters of ice water. The flocculent precipitate is digested for 12 hr at room temperature to speed the filtration. After filtration the filter cake is washed with 500 ml water and dried under vacuum at 50° for several hr. The androsta-5,16-dien-3l5-ol is obtained in ca. 70% yield after recrystallization from methanol mp 138-139°. 

A mixture of the epoxide ca. 5 mmol), sodium azide (6 g, activated by the method of Smith) and 0.25 ml of concentrated sulfuric acid in 70 ml of dimethyl sulfoxide is heated in a flask fitted with a reflux condenser and a drierite tube on a steam bath for 30-40 hr. (Caution carry out reaction in a hood.) The dark reaction mixture is poured into 500 ml of ice water and the product may be filtered, if solid, and washed well with water or extracted with ether and washed with sodium bicarbonate and the water. The crude azido alcohols are usually recrystallized from methanol. 

A 500-ml rcund-bottom flask is equipped with a reflux condenser, a gas inlet tube, and a gas outlet leading to a bubbler. The flask is charged with a solution of rhodium (III) chloride trihydrate (2 g) in 70 ml of 95 % ethanol. A solution of triphenylphosphine (12 g, freshly recrystallized from ethanol to remove the oxide) in 350 ml of hot ethanol is added to the flask, and the system is flushed with nitrogen. The mixture is refluxed for 2 hours, following which the hot solution is filtered by suction to obtain the product. The crystalline residue is washed with several small portions of anhydrous ether (50 ml total) affording the deep red crystalline product in about 85% yield. 

A 250-mI round-bottom flask fitted with a condenser (drying tube) is charged with a mixture of 2-bromocholestanone (4.7 g, 0.01 mole), lithium carbonate (7.4 g, 0.10 mole), and 100 ml of dimethylformamide. The system is flushed with nitrogen and then refluxed (mantle) for 18-24 hours. After the reflux period, the solution is cooled and poured into 500 ml of water. The aqueous mixture is extracted with 50 ml of ether, the ether extract is dried (sodium sulfate), and the ether is removed (rotary evaporator). The residue may be recrystallized from ethanol or methanol. J -Cholestenone is a white solid, mp 98-100°. 

A mixture of 100 g (0.6 mole) of 1-morpholino-l-cyclohexene, 28.8 g (0,4 mole) of /3-propiolactone, and 100 ml of chlorobenzene is placed in a 500-ml round-bottom flask fitted with a condenser (drying tube). The mixture is refluxed for 4 hours. The solvent and excess enamine are removed by distillation at aspirator pressure. (The residue may be distilled to afford the pure morpholide, bp 187-18871 rnm, 1.5090.) Basic hydrolysis may be carried out on the undistilled morpholide. To the crude amide is added 400 ml of 10% sodium hydroxide solution. The mixture is cautiously brought to reflux, and refluxing is continued for 2 hours. The cooled reaction mixture is made acidic (pH 4) and is extracted three times with ether. The combined ether extracts are washed twice with 5 % hydrochloric acid solution and twice with water. The ethereal solution is dried (sodium sulfate), then filtered, and the solvent is removed (rotary evaporator). The residue may be recrystallized from petroleum ether-benzene, mp 64°. 

A 250-ml three-necked flask is fitted with a condenser (drying tube). The system is flushed with dry nitrogen, and a dry nitrogen atmosphere is maintained. In the flask is placed a solution of potassium /-butoxide (2.8 g, 0.025 mole) in dry /-butyl alcohol (100 ml). 4-Benzoyloxycyclohexanone (5 g, 0.022 mole, Chapter 7, Section X) is added to the solution, the transfer being assisted by the use of 10-15 ml of dry /-butyl alcohol. The mixture is cautiously brought to reflux, and refluxing is continued for 45 minutes. The mixture is then cooled rapidly to room temperature and carefully acidified by the addition of 10 ml of 6 A hydrochloric acid (potassium chloride will precipitate). The mixture is placed on a rotary evaporator and the bulk of the solvent is removed. The residue is diluted with sufficient water to dissolve the potassium chloride and extracted three times with 50-ml portions of ether. The ether extracts are combined and extracted four times with 100-ml portions of aqueous 5% sodium bicarbonate solution. The bicarbonate extracts are combined and the solution is acidified by the addition of concentrated hydrochloric acid to pH 4. The mixture is now extracted three times with 100-ml portions of ether, the combined ethereal extracts are washed with water, then dried, and the solvent is removed. The residual product may be recrystallized from benzene-hexane. The acid has mp 65-68°. 

A mixture of 3 gof 8-(2-hydroxy-3-chloropropoxy)-5-methyl coumarin,4.3 g of t-butylamine and 60 ml of ethenol Is heated et 100°C in a sealed tube for 15 hours. The reaction mixture is concentrated under reduced pressure to dryness. The residue Is recrystallized from a mixture of ethanoi and ether to give 2.1 g of the desired product melting at 226° to 228 C (with decomposition). 

A solution or dispersion consisting of 20.1 g (0.1 mol) of 7-chloro-p-fluorobutyrophenone, 19.8 g (0.2 mol) of 4-methylpiperidine end 0.1 g of potassium iodide in 150 ml toluene is heated in a seeled gless tube for 15 hours at 100°C to 110°C. The potassium iodide and the 4-methylpiperidine hydrochloride formed in the reaction are separated by filtration and the solvent removed from the filtrate by evaporation In vacuum on a steam bath. The residue is distilled and the fraction obtained at 120°C to 125 0 and at a pressure lower than 0.1 mm Hg is collected. The basa Is dissolved in ether and the 4-fluoro-7-(4-methylpiperidino)-butyro-phenone precipitated as the hydrochloride. The reaction product is purified by recrystallization in ethanol/ether. 

Chloro-lO-13-(di-N-2-chloroethvl)aminopropvl)lphenthiazine hydrochloride (1.8 g) is heated in a sealed tube for 4 hours at 140°C with a 290 g/l aqueous solution (9 cc) of monomethylpiperazine. The contents of the tube are treated with chloroform (40 cc). The aqueous layer is decanted and the chloroform layer is shaken with N hydrochloric acid (15 cc followed by 2 cc). The aqueous solution is treated with sodium hydroxide (d = 1.33, 10 cc) and chloroform (20 cc). After evaporation of the solvent, the base (1.5 g) is obtained. A solution of maleic acid (1 g) in ethanol (5 cc) is added and after recrystallization from water, 3-chloro-10-13-(4 -methyl-1 -piperazinvDpropyll phenothiazine dimaleate is obtained, melting point 228°C (inst.). 

The following description is taken from U.S. Patent 2,712,012 2.3 parts of clean sodium metal is dissolved in 50 parts of anhydrous methyl alcohol. 11.4 parts of 3-sulfanilamido-6-chloropyridazine is added and the mixture heated in a sealed tube 13 hours at 130° to 140°C. After the tube has cooled it is opened and the reaction mixture filtered, acidified with dilute acetic acid, then evaporated to dryness on the steam bath. The residue is dissolved in 80 parts of 5% sodium hydroxide, chilled and acidified with dilute acetic acid. The crude product is filtered and then recrystallized from water to give 3-sulfanilamido-6-methoxypyridazine of melting point 182° to 183°C. 

Aero Hydrolysis. A solution of kasugamycin hydrochloride (1.5 grams, 3.46 mmoles) dissolved in 15 ml. of 6N hydrochloric acid was heated at 105°C. for five hours in a sealed tube. The solution was condensed to 5 ml. under a reduced pressure and the addition of 50 ml. of ethyl alcohol afforded a crude solid overnight. It was recrystallized from aqueous ethyl alcohol, showing m.p. 246°-247°C. (dec.). It showed no depression in the mixed-melting point and completely identical infrared spectrum with d-inositol which was supplied by L. Anderson of the University of Wisconsin. The yield was 81% (503 mg., 2.79 mmoles). Anal Calcd. for CgH12Og C, 40.00 H, 6.71 O, 53.29 mol. wt., 180.16. Found C, 40.11 H, 6.67 O, 53.33 mol. wt., 180 (vapor pressure osmometer). 

Method A 169 A mixture of biphenyl-2,2 -diamine and an ortho ester (4 mol equiv) was heated in an oil bath in a flask fitted with a reflux condenser and a CaCl2 guard tube for the specified time. EtOH and the excess ortho ester were removed under reduced pressure and the residue was cither recrystallized (benzene) or converted into a salt by adding an appropriate acid. 

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