Cooling mixtures

Alternatively, the following procedure for isolating the glycol may be used. Dilute the partly cooled mixture with 250 ml. of water, transfer to a distilling flask, and distil from an oil bath until the temperature reaches 95°. Transfer the hot residue to an apparatus for continuous extraction with ether (e.g.. Fig. II, 44, 2). The extraction is a slow process (36-48 hours) as the glycol is not very soluble in ether. (Benzene may also be employed as the extraction solvent.) Distil off the ether and, after removal of the water and alcohol, distil the glycol under reduced pressure from a Claisen flask. 

SULPHONATION OF AROMATIC AMINES If aniline is treated with excess of concentrated sulphuric acid and the resulting mixture, which contains aniline sulphate, is heated at 180° until a test portion when mixed with sodium hydroxide solution no longer liberates aniline, p-aminobenzenesulphonic acid or sulphanilic acid is formed this separates as the dihydrate upon pouring the cooled mixture into water. The reaction prohahly proceeds as follows ... 

Sodium cyanide [143-33-9] NaCN, is a white cubic crystalline soHd commonly called white cyanide. It was first prepared in 1834 by heating Pmssian blue, a mixture of cyanogen compounds of iron, and sodium carbonate and extracting sodium cyanide from the cooled mixture using alcohol. Sodium cyanide remained a laboratory curiosity until 1887, when a process was patented for the extraction of gold and silver from ores by means of a dilute solution of cyanide (see Metallurgy, extractive). A mixture of sodium and potassium cyanides, produced by Edenmeyer s improvement of the Rodgers process, was marketed in 1890. 

A solution of 3 (1.35 g, 4 rrtmol) in 2N MeONa (50 mL) was refluxed under N2 for 2 h. The cooled mixture was neutralized with dilute HCI, the solid filtered and washed with water. RecrystalCzation from AcOH afforded 4, mp 278-280 0. 

Phenethylanillne 1 (hydrochloride) (23 3 g 01 mol) was heated in a sealed tube at 200 230 Clor6h The cooled mixture was extracted with 15% HCI and Et20 The Et20 layer was extracted with HCI The acid extract alter neutralization with S% NaOH, extraction with PhH and distillation gave 2 3 g of aniline and 4 2 g of 2 and 3 (24%), bp 165 170°C m a ratio of 3 7... 

Phenyl-4(4H)-ona-5,7-dlhydroxy-1-benzopyran (3) A mixture oi phioroglucino 1 (2 77 g 22 mnx)l) and ethyl benzoylacetate 2 (7 65 g 40 mmol) was heated lo 240 250°C l< I 5 h The cooled mixture was extracted with 5% NaOH and Ihe aqueous solution was extracted with EtaO Acidification afforded a brown product which after sublimation at 250 300°C/0 01 mm and recrystallizalion from EtOH gave 2 2 g of 3 (33 5%) mp 278°C... 

Quininone (2). Potassium melal (10 g, 0 2S at g) was dissolved In t-BuOH (200 mL). The excess o< t-BuOH was removed in vacuum until a dry mobile powder was obtained. A suspension oi t-BuOK and qumlne 1 (32.4 g, O.t mol), benzophenone (91.0 g, 0 5 moQ in PhH (500 mL) was refluxed for 15-18 h under Ng The cooled mixture was poured into ice and extracted with 10% HCI until the HCI was coiortess. The aad extract was washed with EIzO and dripped with stirring into NH4OH and ice Extraction with EI2O, washing of the extract with brme and evaporation of the extract afforded a total of 30-32 g of 2 (95-98%), mp 106-108 C. 

The cnjda 3 (10 g, 0.0325 mol) was heated In pyridine hydrochlonde for 30 min The cooled mixture was stirred with water, the product was filtered arxl purified via its sodium salt (NaOH then precipitation with HOAc). Recrystallizatlon from aqueous EtOH afforded 6 g of 4 (87%), mp 238 C. 

AcetyM-cyclohexene (2) and Cyclohexylldeneacetaldatiyde (3). A mixture of 1-ethynyt-1 -cycfohexanol 1 (6S.0 g, 0.5 mol) and 90% HCOOH (400 mL) was refluxed for 45 nmn Ttie cooled mixture was poured into water (2000 mL) and extracted with petroleum ether. The organic layer was washed with 10% NaOH, the solvent evaporated and the residue was carefully fractionated. One obtains 32 g of 2 (49%), bp 111°C (49 mm), n 1.5020, semicarbazone,... 

The ice bath is replaced, and 250 ml, of ethylene dichloride is added to the mixture. When the internal temperature has been lowered to 5°, a solution of 67 g. (1.0 mole) of freshly distilled pyrrole in 250 ml. of ethylene dichloride is added through a clean dropping funnel to the stirred, cooled mixture over a period of 1 hour. After the addition is complete, the ice bath is replaced with a heating mantle, and the mixture is stirred at the reflux temperature for 15 minutes, during which time there is copious evolution of hydrogen chloride. 

The cooled mixture is transferred to a 3-1. separatory funnel, and the ethylene dichloride layer is removed. The aqueous phase is extracted three times with a total of about 500 ml. of ether. The ether and ethylene chloride solutions are combined and washed with three 100-ml. portions of saturated aqueous sodium carbonate solution, which is added cautiously at first to avoid too rapid evolution of carbon dioxide. The non-aqueous solution is then dried over anhydrous sodium carbonate, the solvents are distilled, and the remaining liquid is transferred to a Claisen flask and distilled from an oil bath under reduced pressure (Note 5). The aldehyde boils at 78° at 2 mm. there is very little fore-run and very little residue. The yield of crude 2-pyrrolealdehyde is 85-90 g. (89-95%), as an almost water-white liquid which soon crystallizes. A sample dried on a clay plate melts at 35 0°. The crude product is purified by dissolving in boiling petroleum ether (b.p. 40-60°), in the ratio of 1 g. of crude 2-pyrrolealdehyde to 25 ml. of solvent, and cooling the solution slowly to room temperature, followed by refrigeration for a few hours. The pure aldehyde is obtained from the crude in approximately 85% recovery. The over-all yield from pyrrole is 78-79% of pure 2-pyrrolealdehyde, m.p. 44 5°. 

Bisethylenedioxypregn-5-ene. Method A. A mixture of progesterone (10 g), freshly distilled ethylene glycol (80 ml) and benzene (350 ml) is slowly distilled for 15 min to remove traces of water. p-Toluenesulfonic acid monohydrate (0.3 g) is added and the mixture is heated under reflux with stirring for 5 hr with a water separator. Saturated sodium bicarbonate solution is added to the cooled mixture and the benzene layer is separated. The organic layer is washed twice with water, dried and evaporated in vacuo. The residue is crystallized twice from acetone-methanol to give 4.15 g (32%) of bisketal, mp 178-181°. 

Acetic anhydride (75 ml) and pulverized calcium carbide (15 g) are refluxed for 60 minutes in an apparatus as described above. Sufficient benzene is then added to reduce the boiling temperature to 110-112°. After cooling, 14.4 g of pinacol is introduced, and the mixture is refluxed with stirring for 30 hours. The cooled mixture is then stirred into ice, extracted into ether and washed with sodium carbonate solution. The solution is dried, then filtered, and theether is evaporated. The residue is clarified with Norit and recrystallized from benzene-petroleum ether or methanol, mp 67-68°. 

A 250-ml flask is charged with 28 g (0.20 mole) of 2-acetyIcyclohexanone and 25 g (0.22 mole) of 30% hydrogen peroxide in 100 ml of /-butyl alcohol. The solution is refluxed for 3 hours, cooled, and a pinch of palladium on charcoal (10%) is cautiously added. The mixture is refluxed for an additional hour to decompose excess peroxide. The cooled mixture is then filtered through celite, and the volume is reduced by removal of /-butyl alcohol and water at reduced pressure. Distillation of the residue affords about 85% of cyclopentanecarboxylic acid, bp 59-6271 rnm, 123727 mm, 215-21671 atm. 

The vinyl ether may be further purified by dissolving it in 15 ml of dry ether and adding a solution of 0.25 g of lithium aluminum hydride in 10 ml of dry ether. The mixture is refluxed for 30 minutes, and excess hydride is destroyed by addition of ethyl acetate (1 ml). Ice-cold dilute (0.5 N) sulfuric acid (25 ml) is gradually added to the cooled mixture, the ethereal layer is rapidly separated, the aqueous layer is extracted once with 10 ml of ether, and the combined ethereal solution is washed once with water and dried over potassium carbonate. Removal of the solvent, followed by distillation of the residue affords about 85% recovery of the pure vinyl ether, bp 102-10376 mm, 1.5045. 

A 100-ml flask is charged with 25 ml of bromine and 10 g of adamantane and heated under reflux for 3 hours. The cooled mixture is dissolved in 100 ml of carbon tetrachloride, and the carbon tetrachloride solution is washed with 100-ml portions of saturated bisulfite solution until the color of bromine is discharged. The solution is then washed twice with water and dried (magnesium sulfate). The solvent is removed (rotary evaporator) and the product is recrystallized from methanol. (For best recovery of the recrystallized material, the methanol solution should be cooled in a Dry Ice cooling bath.) The product has mp 108°. 

Another piece of glassware used in synthetic procedures is the cold finger condenser (Fig. A3.7). Used in the case where the reaction is carried out in a low-boiling solvent (for example, liquid ammonia), the condenser is filled with a suitable cooling mixture and fitted with a drying tube. 

A mixture of 6.65 g of 3-chloro-6-nitroacetanilide, 3.2 ml of propylmercaptan, 5.6 g of 50% sodium hydroxide and 100 mi of water Is heated at reflux overnight. The cooled mixture is filtered to give the desired 2-nitro-5-propyithioaniline, MP 69.5°-71.5°C after recrystailiza-tion from ethanoi then hexane-ether. NMR (CDCi3) 40%. 

A suspension of 37.3 g (0.1 mol) of 7/3-amino-3-methoxy-3-cephem-4-carboxylic acid hydrochloride dioxanate in 500 ml methylene chloride is stirred for 15 minutes at room temperature under an argon atmosphere and treated with 57.2 ml (0.23 mol) of bis-(trimethylsilyl)-acetamide. After 45 minutes the faintly yellow slightly turbid solution is cooled to 0°C and treated within 10 minutes with 31.2 g (0.15 mol) of D-Ct-amino-Ct-d, 4-cyclohexadienyl (acetyl chloride hydrochloride. Thirty minutes thereafter 15 ml (about 0.21 mol) of propylene oxide is added and the mixture is further stirred for 1 hour at 0°C. A cooled mixture of 20 ml of absolute methanol in 200 ml of methylene chloride is added within 30 minutes, after another 30 minutes the precipitate is filtered off under exclusion of moisture, washed with methylene chloride and dried under reduced pressure at room temperature. The obtained hygroscopic crystals of the hydrochloride of 7j3-[D-a-(1,4-cyclohexadienyl)acetylamino] -... 

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