Cooling solution

Decolorisation by Animal Charcoal. It sometimes hap pens (particularly with aromatic and heterocyclic compounds) that a crude product may contain a coloured impurity, which on recrystallisation dissolves in the boiling solvent, but is then partly occluded by crystals as they form and grow in the cooling solution. Sometimes a very tenacious occlusion may thus occur, and repeated and very wasteful recrystallisation may be necessary to eliminate the impurity. Moreover, the amount of the impurity present may be so small that the melting-point and analytical values of the compound are not sensibly affected, yet the appearance of the sample is ruined. Such impurities can usually be readily removed by boiling the substance in solution with a small quantity of finely powdered animal charcoal for a short time, and then filtering the solution while hot. The animal charcoal adsorbs the coloured impurity, and the filtrate is usually almost free from extraneous colour and deposits therefore pure crystals. This decolorisation by animal charcoal occurs most readily in aqueous solution, but can be performed in almost any organic solvent. Care should be taken not to use an excessive quantity... 

Prepare the acetaldehyde solution by plunging a red hot oxidised copper coil (made by winding a copper wire round a glass tube and heating the resulting coil in a Bunsen dame) into 6 ml. of 60 per cent, alcohol in a Pyrex test-tube. Withdraw the coil, cool the test-tube under the tap, repeat the oxidation several times, and use the cooled solution for the test. 

Recovery of the wopropyl alcohol. It is not usually economical to recover the isopropyl alcohol because of its lo v cost. However, if the alcohol is to be recovered, great care must be exercised particularly if it has been allowed to stand for several days peroxides are readily formed in the impure acetone - isopropyl alcohol mixtures. Test first for peroxides by adding 0-6 ml. of the isopropyl alcohol to 1 ml. of 10 per cent, potassium iodide solution acidified with 0-6 ml. of dilute (1 5) hydrochloric acid and mixed with a few drops of starch solution if a blue (or blue-black) coloration appears in one minute, the test is positive. One convenient method of removing the peroxides is to reflux each one litre of recovered isopropyl alcohol with 10-15 g. of solid stannous chloride for half an hour. Test for peroxides with a portion of the cooled solution if iodine is liberated, add further 5 g. portions of stannous chloride followed by refluxing for half-hour periods until the test is negative. Then add about 200 g. of quicklime, reflux for 4 hours, and distil (Fig. II, 47, 2) discard the first portion of the distillate until the test for acetone is negative (Crotyl Alcohol, Note 1). Peroxides generally redevelop in tliis purified isopropyl alcohol in several days. 

Reduction of a nitro compound to a primary amine. In a 50 ml. round-bottomed or conical flask fitted with a reflux condenser, place 1 g. of the nitro compound and 2 g. of granulated tin. Measure out 10 ml. of concentrated hydrochloric acid and add it in three equal portions to the mixtiue shake thoroughly after each addition. When the vigorous reaction subsides, heat under reflux on a water bath until the nitro compound has completely reacted (20-30 minutes). Shake the reaction mixture from time to time if the nitro compound appears to be very insoluble, add 5 ml. of alcohol. Cool the reaction mixture, and add 20-40 per cent, sodium hydroxide solution imtil the precipitate of tin hydroxide dissolves. Extract the resulting amine from the cooled solution with ether, and remove the ether by distillation. Examine the residue with regard to its solubility in 5 per cent, hydrochloric acid and its reaction with acetyl chloride or benzene-sulphonyl chloride. 

Diethyl oxalate (29.2 g, 0.20mol) and 4-bromo-2-nitrotoluene (21.6 g, O.lOmol) were added to a cooled solution of sodium cthoxide prepared from sodium (4.6 g, 0.20 mol) and ethanol (90 ml). The mixture was stirred overnight and then refluxed for 10 min. Water (30 ml) was added and the solution refluxed for 2h to effect hydrolysis of the pyruvate ester. The solution was cooled and concentrated in vacuo. The precipitate was washed with ether and dried. The salt was dissolved in water (300 ml) and acidified with cone. HCl. The precipitate was collected, washed with water, dried and recrystallizcd from hexane-EtOAc to give 15.2 g of product. 

The above product (24 g, 0.067 mol) was dissolved in 90 10 dioxane-water (300 ml) and sodium borohydride (92.5 g, 0.067 mol) was added. The mixture was refluxed for 4h. The cooled solution was poured into 0.1 N HCl (1.11). A solid precipitated and was collected by filtration, dried and recrystallized from ether hexane to give 6,7-dibromo-4-methoxyindole (18.5 g, 90%). 

To a stirred ice-cooled solution of 2-(dimethylamino)-l-nitroethene (1.67 g, 14.4mmol) in TFA (7.2ml) was added 6-benzyloxy-l-methylindole (3.42g, 14.4 mmol). The solution was allowed to warm to room temperature and poured into ice water. The product was extracted using EtOAc to give 6-benzyloxy-l-methyl-3-(2-nitroethenyl)indoIe (4.2 g, 95%). 

GaUic acid is heated with about half its weight of water in a copper autoclave until the pressure reaches 1.2 MPa (12 atm) and the temperature is 175°C. Steam and carbon dioxide are released but sufficient water is retained to maintain the pyrogaHol as a Hquid. The cooled solution is decolorized with animal charcoal and is then evaporated until the volatile pyrogaHol distills into iron receivers. The sohdified material is purified by repeated distillation, sublimation, or vacuum distillation at 200°C in the presence of diaLkyl phthalates (8). 

Methyl-2-naphthylamlne (2) A mixture ol 1 methyl 2 naphthol 1 (7 8 g, 50 mmol), NaHSOs (10 g 0 1 mol) 28% NH4OH (40 mL) and water (10 mL) was healed to 200 205°C lor 48 (1 The cooled solution was made alkaline with NaOH solution and extracted with EI2O The dned ether solution was treated with HCI gas to allord 2 hydrochlonde which was littered treated with alkali and extracted with El20 Evaporation ol the solvent gave 7 2 g ol 2 (S3%), mp 46 SQ C Recrysiallized from petroleum ether (bp 60 70°C) mp 49 50°C... 

Perhydrodlpyrldlno(l,2-a][l, 2 -c]-pyrlmldlne (2). (a) To an ice-cooled solution of 2-(2-(pipendyl)ethyll pipendine 1 (3.2 g, 10 2 mmol) in EtaO (200 mL) was added N-chlorosuccinimlde (NCS) (1.7 g, 12 7 mmol) Under stirring, the reaction mixture was inadated with a 300 W high pressure mercury lamp under N2 for 5 h. The precipitate was filtered, dryed and extracted with n-pentane Evaporation of the solvent and distillation gave 1.0 g of 2 (50%). bp 140 C (20 torr)... 

Methoxyurldlne-2,3,S-trl-0 benzoate (4).3 To 5-methoxy-2,4-bis(tnmethylsiiyloxy)uracil 1(11 mmol, 34 mL of 0 356 N solution In 1,2-dichioroethane) and 1-0-acetyl-2,3,5-lrl-0-benzoyl-p 0-ribofuranose 2 (5 04 g, 10 mmol) in dichioroethane (75 mL) was added trimethyisllyl inflate 3(12 mmol, 22 8 mL of 0 522 N solution in dichioroethane) and the mixture was stirred lor 4 h at 2S C The clear yellow solution was diluted with CH2CI2 (50 mL) extracted with an ice cooled solution of NaHCOa (50 mL) and after washing with water (2x20 mL), the organic phase was dned (Na2S04), the solvent evaporated and the residue recrystallized from EtOAc-hexane to afford 5 24 g of 4 (89%), mp 205-207°C... 

Spray solution Ilb Dissolve 1 g 7V-(l-naphthyl)ethylenediamine dihydrochloride in 50 ml dimethylformamide and 50 ml hydrochloric acid (< Hci = 4 mol/1) with warming. If the cooled solution is not clear it should be filtered. A pale violet coloration does not interfere with the reaction [4]. 

Methoxypregna-3,5-dien-20-oned A solution of progesterone (0.3 g) dissolved in 5 ml of 2,2-dimethoxypropane-dimethylformamide (1 1) is treated with p-toluenesulfonic acid monohydrate (8 mg) and 0.1 ml of methanol and then heated under reflux for 3.5 hr. The cooled solution is neutralized with 45 mg of sodium bicarbonate, dissolved in 200 ml of ice water, stirred for 0.5 hr and filtered. The enol ether thus obtained (0.29 g, 92%) is purified by crystallization from acetone-methanol containing a trace of pyridine mp 135-160° [a]o —61° (CHCI3). 

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