Acid Hydrochloric Crude

Add 23 g. of powdered (or flake ) sodium hydroxide to a solution of 15 ml. (18 g.) of nitrobenzene in 120 ml. of methanol contained in a 250 ml. short-necked bolt-head flask. Fix a reflux water-condenser to the flask and boil the solution on a water-bath for 3 hours, shaking the product vigorously at intervals to ensure thorough mixing. Then fit a bent delivery-tube to the flask, and reverse the condenser for distillation, as in Fig. 59, p. 100, or Fig. 23(D), p. 45). Place the flask in the boiling water-bath (since methanol will not readily distil when heated on a water-bath) and distil off as much methanol as possible. Then pour the residual product with stirring into about 250 ml. of cold water wash out the flask with water, and then acidify the mixture with hydrochloric acid. The crude azoxybenzene separates as a heavy oil, which when thoroughly stirred soon solidifies, particularly if the mixture is cooled in ice-water. 

D) 1-p-Chlorobenzoyl-2-Methyl-S-Methoxy-3-lndolylacetic Acid A mixture of 1 g ester and 0.1 g powdered porous plate is heated in an oil bath at 210°C with magnetic stirring under a blanket of nitrogen for about 2 hours. No intensification of color (pale yellow) occurs during this period. After cooling under nitrogen, the product is dissolved in benzene and ether, filtered, and extracted with bicarbonate. The aqueous solution is filtered with suction to remove ether, neutralized with acetic acid, and then acidified weakly with dilute hydrochloric acid. The crude product (0.4 g, 47%) is recrystallized from aqueous ethanol and dried in vacuo at 65°C MP 151°C. 

Chloropropionaldehyde is a very unstable substance which polymerizes rapidly especially in the presence of traces of hydrochloric acid. The crude material must be oxidized without delay as standing before oxidation will cause a lowering of the yield. 

B. Coumarilic acid. In a 5-1. three-necked flask fitted with a mechanical stirrer and reflux condenser, 450 g. (8 moles) of solid potassium hydroxide is dissolved in 700 ml. of absolute alcohol. The solution is cooled to 15° by immersing the flask in an ice bath, and 215 g. (0.7 mole) of finely divided coumarin dibromide is added in 10- to 15-g. portions to the well-stirred basic solution. The rate of addition is controlled so that the temperature never rises above 20° the addition requires about 30 minutes. After all the dibromide has been added, the reaction mixture is refluxed, with stirring, for 30 minutes (Note 7). One and a half liters of water is added, and the resulting solution is steam-distilled until 2.5 1. of distillate has been collected (Note 8). The residue is cooled to room temperature by the addition of 1 kg. of cracked ice (Note 9) and is then acidified by the addition of 1.2 1. of 6 N hydrochloric acid. The crude coumarilic acid is collected on a filter and stirred with 600 ml. of cold water. The acid is separated from the water by filtration, sucked as dry as possible on the filter, and then crystallized from a mixture of 250 ml. of alcohol and 250 ml. of water (Note 10). The recrystallized coumarilic acid is colorless, weighs 93-100 g. (82-88%) (Note 11), and melts at 190-193°. 

The metal is not attacked by hydrochloric acid, nor does it react with dilute nitric and sulfuric acids. High purity selenium reacts slowly with concentrated nitric acid. The crude metal, however, dissolves in cold concentrated nitric acid. 

A rapidly stirred mixture of 10 gm (0.185 mole) of potassium borohydride and 250 ml of ethanol containing a small amount of potassium hydroxide is heated to the reflux temperature. Then a solution of 5.0 gm (0.033 mole) of m-nitrobenzaldehyde in a small amount of ethanol is added and heating is continued for 24 hr. After this period, half of the solvent is removed by distillation under reduced pressure. The residue is cooled and added, with stirring, to a mixture of ice and concentrated hydrochloric acid. The crude product is collected on a filter, washed free of excess acid with water, and dried. The product is ultimately recrystallized. Yield 4.3 gm (71 %), m.p. 82°-83°C. 

The product was precipitated by the addition of an excess of hydrochloric acid. The crude product was purified by reprecipitation from bicarbonate solution and recrystallization from dilute alcohol. The yield was 20.0 grams (64%) melting at 194°-196°C. 

In general, the active acid esters are set free from the salts merely by adding the salts, alone or dissolved in aoetone or ethanol, to warm water containing a moderate excess of hydrochloric acid. The crude active hydrogen phthalates separate sometimes as oils which solidify on cooling and standing. They are filtered, ground in a mortar with water, refiltered, and washed with dilute hydrochloric add and water to remove any entrapped base. 

Considering this information, another method was worked out as described in Chart 14. The lactone ring of compound (51) was cleaved by potassium hydroxide and careful neutralization gave the unsaturated hydroxy acid (54). Crude compound (54) was hydrogenated on Pd-C in EtOH and the reaction mixture was subsequently acidified with concentrated hydrochloric acid. After usual worked-up, the reaction mixture showed the existence of two products on thin layer chromatography. 

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