Separation ether extraction

If the organic compound which is being steam-distilled is freely soluble in water, an aqueous solution will ultimately collect in the receiver F, and the compound must then be isolated by ether extraction, etc. Alternatively, a water-insoluble compound, if liquid, will form a separate layer in F, or if solid, will probably ciystallise in the aqueous distillate. When steam-distilling a solid product, it is sometimes found that the distilled material crystallises in E, and may tend to choke up the condenser, in such cases, the water should be run out of the condenser for a few minutes until the solid material has melted and been carried by the steam down into the receiver. 

If only 100 ml. separating-funnels are available, the distillate must be divided into two portions and each extracted with ether as described, the final ether extracts being united for drying with potassium hydroxide. 

Place the distillate in a separating-funnel and extract the benzonitrile twice, using about 30 ml. of ether for each extraction. Return the united ethereal extracts to the funnel and shake with 10% sodium hydroxide solution to eliminate traces of phenol formed by decomposition of the benzenediazonium chloride. Then run off the lower aqueous layer, and shake the ethereal solution with about an equal volume of dilute sulphuric acid to remove traces of foul-smelling phenyl isocyanide (CaHjNC) which are always present. Finally separate the sulphuric acid as completely as possible, and shake the ether with water to ensure absence of acid. Run off the water and dry the benzonitrile solution over granular calcium chloride for about 20 minutes. 

Now transfer the cold distillate to a separating-funnel, and shake vigorously with about 50-60 ml. of ether run oflF the lower aqueous layer and then decantf the ethereal solution through the mouth of the funnel into a 200 ml. conical flask. Replace the aqueous layer in the funnel, and extract similarly twice more with ether, combining the ethereal extracts in the conical flask. Add 3-4 g. of dry powdered potassium carbonate to the ethereal solution, securely cork the flask and shake the contents gently. The ethereal solution of the phenol... 

If only sniall separating unnels are available, divide the distillate into portions, and extract each thoroughly with ether, uniting the ethereal extracts subsequently. 

Chill the concentrated solution of the amine hydrochloride in ice-water, and then cautiously with stirring add an excess of 20% aqueous sodium hydroxide solution to liberate the amine. Pour the mixture into a separating-funnel, and rinse out the flask or basin with ether into the funnel. Extract the mixture twice with ether (2 X25 ml.). Dry the united ether extracts over flake or powdered sodium hydroxide, preferably overnight. Distil the dry filtered extract from an apparatus similar to that used for the oxime when the ether has been removed, distil the amine slowly under water-pump pressure, using a capillary tube having a soda-lime guard - tube to ensure that only dry air free from carbon dioxide passes through the liquid. Collect the amine, b.p. 59-61°/12 mm. at atmospheric pressure it has b.p. 163-164°. Yield, 18 g. 

Cool the mixture and pour the liquid reaction product into a separating-funnel. Rinse out the flask (which may contain some unchanged zinc) with ether, pour the latter into the funnel, and extract the aqueous solution with the ether. Repeat the extrac tion with a second quantity of ether, unite the ether extracts, wash them by extracting once with water, and then dry the ethereal extract over sodium sulphate. 

Transfer the quinoline chlorozincate to a beaker, add a small quantity of water, and then add 10% sodium hydroxide solution until the initial precipitate of zinc hydroxide completely redissolves, and the free quinoline separates. Transfer the mixture to a separating-funnel, wash out the beaker with ether, adding the washings also to the solution in the funnel, and then extract the quinoline twice with ether. Dry the united ethereal extracts by adding an ample quantity of powdered potassium hydroxide and... 

Formation of nitrosaminey RgN NO. (a) From monomethylaniline. Dissolve I ml. of monomethylaniline in about 3 ml. of dil. HCl and add sodium nitrite solution gradually with shaking until the yellow oil separates out at the bottom of the solution. Transfer completely to a smdl separating-funnel, add about 20 ml. of ether and sh e. Run off the lower layer and wash the ethereal extract first with water, then with dil. NaOH solution, and finally with w ter to free it completely from nitrous acid. Evaporate the ether in a basin over a previously warmed water-bath, in a fume cupboard with no flames near. Apply Liebermann s reaction to the residual oil (p. 340). 

Into a 500 ml. three-necked flask, provided with a mechanical stirrer, a gas inlet tube and a reflux condenser, place 57 g. of anhydrous stannous chloride (Section 11,50,11) and 200 ml. of anhydrous ether. Pass in dry hydrogen chloride gas (Section 11,48,1) until the mixture is saturated and separates into two layers the lower viscous layer consists of stannous chloride dissolved in ethereal hydrogen chloride. Set the stirrer in motion and add 19 5 g. of n-amyl cyanide (Sections III,112 and III,113) through the separatory funnel. Separation of the crystalline aldimine hydrochloride commences after a few minutes continue the stirring for 15 minutes. Filter oflF the crystalline solid, suspend it in about 50 ml. of water and heat under reflux until it is completely hydrolysed. Allow to cool and extract with ether dry the ethereal extract with anhydrous magnesium or calcium sulphate and remove the ether slowly (Fig. II, 13, 4, but with the distilling flask replaced by a Claisen flask with fractionating side arm). Finally, distil the residue and collect the n-hexaldehyde at 127-129°. The yield is 19 g. 

Pour the reaction mixture into a 1-litre round-bottomed flaak, add 250 ml. of water, fit a still head and a condenser for downward distillation (Fig. II, 13, 3, but without the thermometer). Distil the mixture until about 125 ml. of distillate (two layers) have been collected. Saturate with salt (about 30 g. are required), and separate the upper layer of cj/cZohexanone extract the aqueous layer with 25-30 ml. of ether and combine the ether extract with the cycZohexanone layer. Dry with about 6 g. of anhydrous sodium or magnesium sulphate, filter the solution into a distilling flask of suitable size to which a condenser has previously been attached. Distil oflF the ether from a water bath—a beaker containing warm water is satisfactory. Distil the residual liquid from an air bath or a wire gauze, and collect the cyclohexanone at 153-156°. The yield is 16 g. 

Mix together in a 250 ml. flask carrying a reflux condenser and a calcium chloride drying tube 25 g. (32 ml.) of freshly-distilled acetaldehyde with a solution of 59-5 g. of dry, powdered malonic acid (Section 111,157) in 67 g. (68-5 ml.) of dry pyridine to which 0-5 ml. of piperidine has been added. Leave in an ice chest or refrigerator for 24 hours. Warm the mixture on a steam bath until the evolution of carbon dioxide ceases. Cool in ice, add 60 ml. of 1 1 sulphuric acid (by volume) and leave in the ice bath for 3-4 hours. Collect the crude crotonic acid (ca. 27 g.) which has separated by suction filtration. Extract the mother liquor with three 25 ml. portions of ether, dry the ethereal extract, and evaporate the ether the residual crude acid weighs 6 g. Recrystallise from light petroleum, b.p. 60-80° the yield of erude crotonic acid, m.p. 72°, is 20 g. 

Vinylacetic acid. Place 134 g. (161 ml.) of allyl cyanide (3) and 200 ml. of concentrated hydrochloric acid in a 1-htre round-bottomed flask attached to a reflux condenser. Warm the mixture cautiously with a small flame and shake from time to time. After 7-10 minutes, a vigorous reaction sets in and the mixture refluxes remove the flame and cool the flask, if necessary, in cold water. Ammonium chloride crystallises out. When the reaction subsides, reflux the mixture for 15 minutes. Then add 200 ml. of water, cool and separate the upper layer of acid. Extract the aqueous layer with three 100 ml. portions of ether. Combine the acid and the ether extracts, and remove the ether under atmospheric pressure in a 250 ml. Claisen flask with fractionating side arm (compare Fig. II, 13, 4) continue the heating on a water bath until the temperature of the vapour reaches 70°. Allow the apparatus to cool and distil under diminished pressure (compare Fig. II, 20, 1) , collect the fraction (a) distilling up to 71°/14 mm. and (6) at 72-74°/14 mm. (chiefly at 72 5°/ 14 mm.). A dark residue (about 10 ml.) and some white sohd ( crotonio acid) remains in the flask. Fraction (6) weighs 100 g. and is analytically pure vinylacetic acid. Fraction (a) weighs about 50 g. and separates into two layers remove the water layer, dry with anhydrous sodium sulphate and distil from a 50 ml. Claisen flask with fractionating side arm a further 15 g. of reasonably pure acid, b.p. 69-70°/12 mm., is obtained. 

Pimelic acid. Heat a mixture of 18 g. of pentamethylene dicyanide and 250 g. of 50 per cent, sulphuric acid by weight in a 750 ml. round-bottomed flask under reflux for 9 hours. INIost of the pimehc acid separates from the cold reaction mixture. Filter oflF the crystaUine acid upon a sintered glass funnel. Saturate the filtrate with ammonium sulphate and extract it with three 50 ml. portions of ether. Dissolve the residue on the filter (which is shghtly discoloured, but is fairly pure pimehc acid) in the combined ethereal extracts, dry with anhydrous sodium or magnesium sulphate, and remove the ether by distiUation. Recrystallise the residual sohd acid from benzene containing 5 per cent, of ether. The yield of pure pimehc acid, m.p, 105-106°, is 22 g. 

An alternative method of separation consists in treating the dry residue several times with a warm mixture of benzene and ether. The residual solid (about 20 g.) is moderately pure succinic acid, m.p. 183-184°. Upon evaporating the benzene - ether extract, and recrystallising the residue from chloroform or from benzene, about 70 g. of glutaric acid, m.p. 95-96°, are obtained. 

Separate the upper hydrocarbon layer from the distillate and extract the aqueous layer twice with 20 ml. portions of ether dry the combined upper layer and ethereal extracts with anhydrous magnesium sulphate, remove the ether on a water bath, and distil the residue from a 50 ml. Claisen flask. Collect the ethylbenzene at 135-136° the yield is 20 g. By extracting the s3Tupy liquid in the reaction flask with three 30 ml. portions of ether, a further 2 g. of ethylbenzene, b.p. 136°, may be obtained. Note,... 

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). 

To a mixture of 10 g. of the compound and 3-5 ml. of 33 per cent, sodium hydroxide solution in a test-tube, add 2-5 ml. of 50 per cent, chloroacetic acid solution. If necessary, add a little water to dissolve the sodium salt of the phenol. Stopper the test-tube loosely and heat on agently-boiling water bath for an hour. After cooling, dilute with 10 ml. of water, acidify to Congo red with dilute hydrochloric acid, and extract with 30 ml. of ether. Wash the ethereal extract with 10 ml, of water, and extract the aryloxyacetic acid b shaking with 25 ml. of 5 per cent, sodium carbonate solution. Acidify the sodium carbonate extract (to Congo red) with dilute hydrochloric acid, collect the aryloxyacetic acid which separates, and recrystallise it from hot water. 

Y-Phenylbutyric acid. Prepare amalgamated zinc from 120 g. of zinc wool contained in a 1-litre rovmd-bottomed flask (Section 111,50, IS), decant the liquid as completely as possible, and add in the following order 75 ml. of water, 180 ml. of concentrated hydrochloric acid, 100 ml. of pure toluene (1) and 50 g. of p benzoylpropionic acid. Fit the flask with a reflux condenser connected to a gas absorption device (Fig. II, 8, l,c), and boil the reaction mixture vigorously for 30 hours add three or four 50 ml. portions of concentrated hydrochloric acid at approximately six hour intervals during the refluxing period in order to maintain the concentration of the acid. Allow to cool to room temperature and separate the two layers. Dilute the aqueous portion with about 200 ml. of water and extract with three 75 ml. portions of ether. Combine the toluene layer with the ether extracts, wash with water, and dry over anhydrous magnesium or calcium sulphate. Remove the solvents by distillation under diminished pressure on a water bath (compare Fig. II, 37, 1), transfer the residue to a Claisen flask, and distil imder reduced pressure (Fig. II, 19, 1). Collect the y-phenylbutyric acid at 178-181°/19 mm. this solidifies on coohng to a colourless sohd (40 g.) and melts at 47-48°. 

Place 200 g. (172 -5 ml.) of redistilled furfural (1) in a 1 litre beaker, provided with a mechanical stirrer and surrounded by an ice bath. Start the stirrer and, when the temperature has fallen to 5-8°, add a solution of 50 g. of sodium hydroxide in 100 ml. of water from a separatory funnel at such a rate that the temperature of the reaction mixture does not rise above 20° (20-25 minutes) continue the stirring for a further 1 hour. Much sodium furoate separates during the reaction. Allow to cool to room temperature, and add just enough water to dissolve the precipitate (about 65 ml.). Extract the solution at least five times with 60 ml. portions of ether in order to remove the furfuryl alcohol the best results are obtained by the use of the continuous extraction apparatus (charged with 350 ml. of ether) depicted in Fig. //, 44, 2. Keep the aqueous layer. Dry the ethereal extract with a httle anhydrous... 

Amino-5-methylthiazole. Suspend 76 g. of thiourea in 200 ml. of water in a 500 ml. three-necked flask equipped as in the preceding pre paration. Stir and add 92 -5 g. (80 ml.) of monochloroacetone (1) over a period of 30 minutes. The thiourea dissolves as the reaction proceeds and the temperature rises. Reflux the yellow solution for 2 hours. To the cold solution immersed in an ice bath add, with stirring, 200 g. of solid sodium hydroxide. Transfer to a separatory funnel, add a little ice water, separate the upper oil layer and extract the aqueous layer with three 100 ml. portions of ether. Dry the combined oil and ether extracts with anhydrous magnesium sulphate, remove the ether by distillation from a steam bath, and distil the residual oil under diminished pressure. Collect the 2-amino-5-methylthiazole at 130-133°/18 mm. it solidifies on coohng in ice to a solid, m.p. 44-45°. The yield is 84 g. 

Method 1. Reflux a mixture of pure nicotinic acid (Section V,22), 84 g. (105 ml.) of absolute ethanol and 90 g. (50 ml.) of concentrated sulphuric acid in a flask for 4 hours on a steam bath. Cool the solution and pour it slowly and with stirring on to 200 g. of crushed ice. Add sufficient ammonia solution to render the resulting solution strongly alkaline generally, some ester separates as an oil but most of it remains dissolved in the alkaline solution. Extract the solution with five 25 ml. portions of ether, dry the combined ethereal extracts with anhydrous magnesium sulphate, remove the ether and distil under reduced pressure. The ethyl nicotinate passes over at 117-118°/ 6 mm. the yield is 34 g. The b.p. under normal pressure is 222-224°. 

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