Acid cooling

Dibromobutane from 1 4 butanediol). In a 500 ml. threenecked flask fltted with a stirrer, reflux condenser and dropping funnel, place 154 g. (105 ml.) of 48 per cent, hydrobromic acid. Cool the flask in an ice bath. Add slowly, with stirring, 130 g. (71 ml.) of concentrated sulphuric acid. To the resulting ice-cold solution add 30 g. of redistilled 1 4-butanediol dropwise. Leave the reaction mixture to stand for 24 hours heat for 3 hours on a steam bath. The reaction mixture separates into two layers. Separate the lower layer, wash it successively with water, 10 per cent, sodium carbonate solution and water, and then dry with anhydrous magnesium sulphate. Distil and collect the 1 4-dibromo-butane at 83-84°/12 mm. The yield is 55 g. 

N-Nitrosodiethylamine. Add 36-5 g. (51-5 ml.) of diethylamine slowly to the calculated quantity of carefully standardised 5A-hydra chloric acid cooled in ice (1). Introduce the solution of the hydi ochloride into a solution of 39 g. of sodium nitrite (assumed to be of 90 per cent, purity) in 45 ml. of water contained in a 250 ml. distilling flask. Distil the mixture rapidly to dryness. Separate the yellow upper layer of the nitrosamine from the distillate saturate the aqueous layer with soUd potassium carbonate and remove the nitroso compound which separates and add it to the main product. Dry over anhydrous potassium carbonate and distil. Collect the diethylnitrosamine at 172-173-5°, The yield is 41 g. 

Hydrolysis of benzanilide. Place 5 g. of benzanilide and 50 ml. of 70 per cent, sulphuric acid in a small flask fitted with a reflux condenser, and boU gently for 30 minutes. Some of the benzoio acid will vapourise in the steam and solidify in the condenser. Pour 60 ml. of hot water down the condenser this will dislodge and partially dissolve the benzoic acid. Cool the flask in ice water filter off the benzoic acid (anifine sulphate does not separate at this dilution), wash well with water, drain, dry upon filter paper, and identify by m.p. (121°) and other tests. Render the filtrate alkaline by cautiously adding 10 per cent, sodium hydroxide solution, cool and isolate the aniline by ether extraction. Recover the ether and test the residue for anifine (Section IV,100). 

In a 1 or 1-5 htre round-bottomed flask prepare a solution of 53-5 g. of o-toluidine in 170 ml. of 48 per cent, hydrobromic acid, cool to 5° by immersion in a bath of ice and salt. Diazotise by the gradual addition of a solution of 36 -5 g. of sodium nitrite in 50 ml. of water stopper the flask after each addition and shake until all red fumes are absorbed. Keep the temperature between 5° and 10°. When the diazotisation is complete, add 2 g. of copper powder or copper bronze, attach a reflux condenser to the flask, and heat very cautiously on a water bath. Immediately evolution of gas occurs, cool the flask in crushed ice unless the... 

Dissolve 1 g. of the secondary amine in 3-5 ml. of dilute hydrochloric acid or of alcohol (in the latter case, add 1 ml. of concentrated hydrochloric acid). Cool to about 5° and add 4-5 ml. of 10 per cent, sodium nitrite solution, and allow to stand for 5 minutes. Add 10 ml. of water, transfer to a small separatory funnel and extract the oil with about 20 ml. of ether. Wash the ethereal extract successively with water, dilute sodium hydroxide solution and water. Remove the ether on a previously warmed water bath no flames should be present in the vicinity. Apply Liebermann s nitroso reaction to the residual oil or solid thus. Place 1 drop or 0 01-0 02 g. of the nitroso compovmd in a dry test-tube, add 0 05 g. of phenol and warm together for 20 seconds cool, and add 1 ml. of concentrated sulphuric acid. An intense green (or greenish-blue) colouration will be developed, which changes to pale red upon pouring into 30-50 ml. of cold water the colour becomes deep blue or green upon adding excess of sodium hydroxide solution. 

Cautiously add 250 g. (136 ml.) of concentrated sulphuric acid in a thin stream and with stirring to 400 ml. of water contained in a 1 litre bolt-head or three-necked flask, and then dissolve 150 g. of sodium nitrate in the diluted acid. Cool in a bath of ice or iced water. Melt 94 g. of phenol with 20 ml. of water, and add this from a separatory funnel to the stirred mixture in the flask at such a rate that the temperature does not rise above 20°. Continue the stirring for a further 2 hours after all the phenol has been added. Pour oflF the mother liquid from the resinous mixture of nitro compounds. Melt the residue with 500 ml. of water, shake and allow the contents of the flask to settle. Pour oflF the wash liquor and repeat the washing at least two or three times to ensure the complete removal of any residual acid. Steam distil the mixture (Fig. II, 40, 1 or Fig. II, 41, 1) until no more o-nitrophenol passes over if the latter tends to solidify in the condenser, turn oflF the cooling water temporarily. Collect the distillate in cold water, filter at the pump, and drain thoroughly. Dry upon filter paper in the air. The yield of o-nitrophenol, m.p. 46° (1), is 50 g. 

Benzoylpropionitrile. To a mixture of 21 4 g. of p dimethylamino propiophenone hydrochloride, 13 0 g. of potassium cyanide in a 500 ml. flask, add 260 ml. of boiling water heat the heterogeneous mixture under reflux for 30 minutes. Part of the dimethylamine, which is eliminated in the reaction, distils collect this in dilute hydrochloric acid. Cool the reaction mixture in ice the oil sohdifies and crystals form from the aqueous layer. Collect the solid (crude p benzoylpropiouitrile, 10-5 g.) by suction filtration and recrystallise it from benzene - light petroleum (b.p. 40-60°) it separates as almost colourless blades, m.p. 76°. 

Add 50 g. of the crude acetothiomorpholide to 400 ml. of 10 per cent, alcoholic sodium hydroxide solution and reflux the mixture for 10 hours. Distil off most of the alcohol, add 100 ml. of water to the residue, and strongly acidify the alkahne solution with hydrochloric acid. Cool, extract thrice with ether, dry the combined ether extracts, evaporate the solvent, and recrystallise the residue from water or dilute alcohol. The yield of p-methoxyphenylacetic acid, m.p. 85-86°, is 26 g. A further quantity of acid may be obtained by extracting the mother hquors with ether. 

Rinse the walls of the flask with a httle water and complete the reaction by heating the mixture (which consists of two layers and a precipitate of sodium chloride) on a boiling water bath for 15 minutes with vigorous mechanical stirring. Pour the hot reaction mixture into 1500 ml. of glacial acetic acid contained in a 4-htre round-bottomed flask rinse the flask with 250 ml. of acetic acid. Cool the solution in an ice bath to 5° (11), stir mechanically, and add a solution of 125 g. of sodium nitrite in 250 ml. 

The residue (5) in the distilhng flask may stUl contain a water-soluble, non-volatile acid. Cool the acid solution, neutralise it with dilute sodium hydroxide solution to Congo red, and evaporate to dryness on a water bath under reduced pressure (water pump). Heat a httle of the residual salt (G) upon the tip of a nickel spatula in a Bunsen flame and observe whether any charring takes place. If charring occurs, thus... 

The fatty acids that emerge from the top of the column contain entrained water, partially hydroly2ed fat, and the Zn—soap catalyst. This product stream is passed into a vacuum dryer stage where the water is removed through vapori2ation and the fatty acid cooled as a result of this vapori2ation process. The dried product stream is then passed to a distillation system. 

This is enough acid to turn Congo Red paper distinctly blue. If less acid is used, a troublesome emulsion is likely to form. If such an emulsion forms it can be broken by pouring into it a small amount of sulfuric acid cooled by the addition of ice. 

Although this material is suitable for most purposes, it may be purified further in the following manner. It is dissolved by heating in a solution of 2 g. of stannous chloride and 2 cc. of concentrated hydrochloric acid in i 1. of water, and the hot solution is clarified by filtration through a 5-mm. mat of decolorizing carbon (Note g). The yellow or red color which may develop disappears on reheating to the boiling point. After the addition of 100 cc. of concentrated hydrochloric acid the solution is allowed to cool in an ice bath, treated with a second roo cc. of acid, cooled to 0°, and collected and washed as befor The ciystalline product is colorless, ash-free, and of analytical purity. The loss in the crystallization of an 80-g. lot amounts to 5-10 g. (6-12 per cent). 

The reaction mixture is cooled in an ice bath and slowly poured into 1000 cc. of 10 per cent acetic acid cooled to 0° (ice< salt mixture). The toluene layer is separated, washed once with water, twice with cooled 7 per cent sodium carbonate solution, and again with water. The toluene is removed by distillation at ordinary pressure, and the residue is distilled under reduced... 

An additional 2-5 g. (4-10%) of product can be obtained by concentrating the filtrate to one-third its volume, adding 25 ml. of concentrated hydrochloric acid, cooling the mixture, separating crude acid by filtration, and recrystallizing the acid from water. 

To a solution of 112 (2.0 g, 43.0 mmol) in 50 mL of dry THF at -65°C was added a solution of 111 (4.45 g, 34.0 mmol) in 100 mL of absolute ethanol containing 5 mL of acetic acid cooled to - 65°C in one portion. After stirring for 15 min., dry triethylamine (4.8 g, 510 mmol) was added. The reaction continued for 24 h with slow warming to room temperature before reducing the volume to 10 mL. The crude 113 was brought to pH 10 with potassium carbonate. The aqueous solution was continuously extracted with chloroform, dried (K2CO3), evaporated onto neutral alumina, placed on a column of neutral alumina (50 g) and eluted with chloroform. The solvent was evaporated and the residue crystallized from ethanol to yield 113 (2.86 g 55%). The yellow solid had a mp = 72.5-73.8°C. 

Procedure The crude product from (A) is suspended in the hydrochloric acid, cooled in an ice-salt mixture, and chlorine is passed Into the mixture with stirring for A to 1 hour. Transient blue and green colors may be noticed in the mixture during this time. The temperature will probably rise to 3° to S C. The solid is collected by suction filtration and dried for an hour or so on the filter before use in (C). If at all possible, it should be used on the day of preparation. Yield is 71 grams (after Vh hours on the filter). 

Procedure. To 100 mL of distilled water, add 5mL of concentrated sulphuric acid, cool and then add 5 g of pure boric acid when this has dissolved cool the mixture in ice. Transfer gradually from a weighing bottle about 0.5 g (accurately weighed) of the sodium peroxide sample (handle with care) to the well-stirred, ice-cold solution. When the addition is complete, transfer the solution to a 250 mL graduated flask, make up to the mark, and then titrate 50 mL portions of the solution with standard 0.02 JVf permanganate solution. 

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