Ethanol steam distillation

Prepare a mixture of 30 ml, of aniline, 8 g. of o-chloro-benzoic acid, 8 g. of anhydrous potassium carbonate and 0 4 g. of copper oxide in a 500 ml. round-bottomed flask fitted with an air-condenser, and then boil the mixture under reflux for 1 5 hours the mixture tends to foam during the earlier part of the heating owing to the evolution of carbon dioxide, and hence the large flask is used. When the heating has been completed, fit the flask with a steam-distillation head, and stcam-distil the crude product until all the excess of aniline has been removed. The residual solution now contains the potassium. V-phenylanthrani-late add ca. 2 g. of animal charcoal to this solution, boil for about 5 minutes, and filter hot. Add dilute hydrochloric acid (1 1 by volume) to the filtrate until no further precipitation occurs, and then cool in ice-water with stirring. Filter otT the. V-phcnylanthranilic acid at the pump, wash with water, drain and dry. Yield, 9-9 5 g. I he acid may be recrystallised from aqueous ethanol, or methylated spirit, with addition of charcoal if necessary, and is obtained as colourless crystals, m.p. 185-186°. 

Difluorodiphenyl. Bis-diazotise a solution of 46 g. of benzidine (Section IV,88) in 150 ml. of concentrated hydrochloric acid and 150 ml. of water by means of a solution of 35 g. of sodium nitrite in 60 ml. of water add about 200 g. of crushed ice during the process (compare p-Fbtorotoluene above). Filter the solution and add it to a filtered solution of 85 g. of sodium borofluoride in 150 ml. of water. Stir for several minutes, collect the precipitated bis-diazonium borofluoride by suction filtration, wash with 5 ml. of ice-cold water, and dry at 90-100°. Place the dry salt in a flask fitted with an air condenser, immerse the flask in an oil bath, and slowly raise the temperature to 150° (Fume Cupboard ). When decomposition of the salt is complete, steam distil the mixture collect the 4 4 difluoro-diphenyl which passes over and recrystallise it from ethanol. The yield is 21 g., m.p. 92-93°. 

The amine (Imol) is added to a solution of anhydrous zinc chloride (Imol) in concentrated hydrochloric acid (42mL) in ethanol (200mL, or less depending on the solubility of the double salt). The solution is stirred for Ih and the precipitated salt is filtered off and recrystallised from ethanol. The free base is recovered by adding excess of 5-ION NaOH (to dissolve the zinc hydroxide that separates) and is steam distilled. Mercuric chloride in hot water can be used instead of zinc chloride and the salt is crystallised from 1% hydrochloric acid. Other double salts have been used, e.g. cuprous salts, but are not as convenient as the above salts. 

Purification as their N-acetyl derivatives is satisfactory for primary, and to a limited extent secondary, amines. The base is refluxed with slightly more than one equivalent of acetic anhydride for half to one hour, cooled and poured into ice-cold water. The insoluble derivative is filtered off, dried, and recrystallised from water, ethanol, aqueous ethanol or benzene (CAUTION toxic ). The derivative can be hydrolysed to the parent amine by refluxing with 70% sulfuric acid for a half to one hour. The solution is cooled, poured onto ice, and made alkaline. The amine is steam distilled or extracted as above. Alkaline hydrolysis is very slow. 

The phenol (Imol) in 5% aqueous NaOH is treated (while cooling) with benzoyl chloride (Imol) and the mixture is stirred in an ice bath until separation of the solid benzoyl derivative is complete. The derivative is filtered off, washed with alkali, then water, and dried (in a vacuum desiccator over NaOH). It is recrystalUsed from ethanol or dilute aqueous ethanol. The benzoylation can also be carried out in dry pyridine at low temperature ca 0°) instead of in NaOH solution, finally pouring the mixture into water and collecting the solid as above. The ester is hydrolysed by refluxing in an alcohol (for example, ethanol, n-butanol) containing two or three equivalents of the alkoxide of the corresponding alcohol (for example sodium ethoxide or sodium n-butoxide) and a few ca 5-10) millilitres of water, for half an hour to three hours. When hydrolysis is complete, an aliquot will remain clear on dilution with four to five times its volume of water. Most of the solvent is distilled off. The residue is diluted with cold water and acidified, and the phenol is steam distilled. The latter is collected from the distillate, dried and either fractionally distilled or recrystalUsed. 

These can be converted to their uranyl nitrate addition compounds. The crude or partially purified ester is saturated with uranyl nitrate solution and the adduct filtered off. It is recrystallised from -hexane, toluene or ethanol. For the more soluble members crystallisation from hexane using low temperatures (-40°) has been successful. The adduct is decomposed by shaking with sodium carbonate solution and water, the solvent is steam distilled (if hexane or toluene is used) and the ester is collected by filtration. Alternatively, after decomposition, the organic layer is separated, dried with CaCl or BaO, filtered, and fractionally distilled under high vacuum. 

The dried ethereal solution of adipyl azide is added to a 2-1. flask containing 400 ml. of absolute ethanol, and the ether and some of the ethanol are distilled on a steam bath through a short fractionating column. When the volume has reached about 200 ml., the solution may be poured into a 500-ml. Erlenmeyer flask, and the remainder of the solvents removed on a steam bath by means of an air stream. The residual, waxy, crystalline cake of N,N -dicarbethoxyputrescine weighs 84-91 g. (79-85%) and melts at 76-81°. It may be kept indefinitely. 

In a 1-1. round-bottomed flask equipped with a condenser are placed 78.0 g. (0.56 mole) of commercial anhydrous potassium arbonate, 45.0 g. (0.50 mole) of methallyl chloride (Note 1), 55.0 g. (0.55 mole) of 2,4-pentanedione (Note 1), and 300 ml. of anhydrous ethanol (Note 2). The mixture is refluxed on a steam bath for 16 hours. The condenser is replaced by a distilling head and condenser, and about 200 ml. of ethanol is distilled from the mixture (Note 3). Ice water (600 ml.) is added to dissolve the salts, and the mixture is extracted three times with ether. The... 

Benzyl phthalimide. Grind together 53 g. of finely-powdered, anhydrous potassium carbonate and 147 g. of phthalimide (Section IV,169) in a glass mortar, transfer the mixture to a 750 ml. round-bottomed flask, and treat it with 252 g. (230 ml.) of redistilled benzyl chloride. Heat in an oil bath at 190° under a reflux condenser for 3 hours. Whilst the mixture is still hot, remove the excess of benzyl chloride by steam distillation. The benzyl phthalimide commences to crystallise near the end of the steam distillation. At this point, cool the mixture rapidly with vigorous stirring so that the solid is obtained in a fine state of division. Filter the solid with suction on a Buchner funnel, wash well with water and drain as completely as possible then wash once with 200 ml. of 60 per cent, ethanol and drain again. The yield of crude product, m.p. 100-110°, is 180 g. Recrystallise from glacial acetic acid to obtain pure benzyl phthalimide, m.p. 116° the recovery is about 80 per cent. 

This is prepared from 2-nitrochlorobenzene and sodium disulfide in ethanol, and the reaction residue after recovery of the ethanol by steam distillation is known to be of limited thermal stability. On one occasion, a container (atypically with closed vents) of bulked residues totalling over 2 t exploded violently while awaiting collection for disposal. It seems remotely possible that an aci-nitro thioquinonimine species derived from 2-nitrobenzenethiol may have been involved. 

To 23 g Na in 350 ml ethanol add 146 g ethyl-oxalate and 171 g 2-nitro-6-CI-toluene and reflux forty minutes. Dilute the red solution with water and steam distill until no more starting material is distilled. The aqueous residue is filtered, acidified with HC1 and filtered to get 102 g 2-nitro-6-CI-phenylpyruvic acid (I) (recrystallize-benzene). Add 81 g (I) in dilute NH4OH to a solution of 560 g FeS04.7H20 and 230 ml concentrated NH4OH and 2 L water and boil five minutes. Filter, wash precipitate with dilute NH4OH, water and acidify filtrate with dilute HCI to get 60 g 4-CI-2-indole-COOH (11) (recrystallize-aqueous ethanol). 9.78 g (II) and 6.7 g CuCN in 35 g quinoline and reflux (about 237°) for twenty hours. Pour the hot solution into a mixture of 25 ml concentrated HCI and ice. Stir and filter wash precipitate with water and extract the filtrate and precipitate three times with ether. Wash the ether with HCI, water and dry, evaporate in vacuum to get 3.6 g 4-CN-indole (recrystallize-water). Or, heat (II) alone at 290° until fusion then heat at 250° for ten minutes until C02 evolution ceases to get 4-CN-indole. For conversion to 4-formyl-indole see HC A 51,1616(1968). 

After treatment with 0.5 M Na2C03, the resulting solution was steam distilled to remove the excess N-methylbenzyl amine. Water was removed and the crude residue was recrystallized from ethanol. 

Dibenzotellurophene Tellurium powder (6 g, 47 mmol) and dibenzothiophene S.S -diox-ide (8 g, 37 mmol) are mixed thoroughly, the mixture is carefully heated under an atmosphere of carbon dioxide until evolution of sulphur dioxide commences, and the temperature is then regulated to achieve a steady evolution of sulphur dioxide. From time to time the sublimed dibenzothiophene dioxide is melted and allowed to flow back into the reaction mixture. After 36 h, the mixture is cooled to 20°C and extracted with boiling acetone. The extract is evaporated to dryness, the solid residue is washed several times with cold ethanol, and the washings are collected and evaporated. The residue is steam distilled and the product is recrystallized from light petroleum ether. Yield 1.0 g (10%) m.p. 93°C. 

Olivetol. (5-Alkyl Resourcinol) BER 69, 1644 (1936). Mix 25 g of ethyl-3,4,5-trimethoxy benzoyl acetate and 2.0 g of clean sodium in 100 ml ethanol and warm to react. Add 2 g n-propyl iodide (this may be replaced with n-amyl iodide) and heat on a steam bath for 12 hours, then neutralize and remove the ethanol by distillation. Extract the residue with ether, dry, and evaporate in vacuo to get 30 g of the alkyl acetate. Heat 22 g of this acetate in 5% KOH ethanolic solution for 1 hour at 50° and let stand to precipitate 14 g of 3,4,5-trimethoxyvalerophenone. Mix 11 g of the above product with 60 g of sodium in 600 ml ethanol. Warm and after dissolving the sodium add 2 liters of water. M e acidic with HCl acid and remove the ethanol by distillation. Extract with ether, dry, and evaporate the ether in vacuo to get if. g olivetol dimethyl ether. To demethylate this ether add it to 70 ml of hydrogen iodide and heat to boiling and reflux for two hours. Distill and keep the fraction at 160°-170° with 3-4 mm of vacuum applied to the distillation set-up. Yield about 6 g. 

Methyl-2-aminobenzophenone can be prepared similarly by substituting toluene for benzene. The yield of crude material, m.p. 85-88°, is 70%. On recrystallization from 95% ethanol, using 5 ml. per g., there is obtained, in two crops, a 70% recovery of 4/-methyl-2-aminobenzophenone, m.p. 92-93°. Because of the higher temperature required in the steam distillation (cf. Note 5), the sulfonamide is obtained in a form difficult to purify. As a result the crude aminoketone usually contains 1-2 g. of aluminum oxide. 

B. o-Phthalaldehyde. The a,a,a, a -tetrabromo-0-xylene (344-370 g.) obtained as described above, part A, is placed in a 5-1. round-bottomed flask with 4 1. of 50% (by volume) ethanol and 275 g. of potassium oxalate. The mixture is heated under reflux for 50 hours (a clear yellow solution is formed after 25-30 hours). About 1750 ml. of the ethanol is then removed by distillation (which is stopped before the product begins to steam-distil), and 700 g. of disodium monohydrogen phosphate dodecahydrate (Na2HP04-12H20) is added to the aqueous residue. The mixture is steam-distilled rapidly (Note 4), using an efficient condenser, until 10-12 1. of distillate is collected and the distillate no longer gives a black color test for o-phthalaldehyde 8 when a portion is treated with concentrated ammonium hydroxide fol-... 

In a distillation apparatus fitted with mechanical stirrer, thermometer, and provisions for adding solids, to an agitated mixture of 26.7 gm (0.187 mole) erf 2-naphthylamine (CAUTION carcinogenic material) and 20 gm (0.163 mole) of nitrobenzene maintained at 180°C is added slowly 17 gm of powdered sodium hydroxide over a 20 min period. After completion of the addition, heating is continued for 10 min. After cooling, the reaction mixture is treated repeatedly with dilute hydrochloric acid. The excess nitrobenzene is then separated by steam distillation. The residue from the steam distillation is treated with ethanol at 70°C to precipitate insoluble impurities which are removed by filtration. On cooling the filtrate, product cyrstals separate which, after filtration, are taken up in petroleum ether, leaving petroleum ether-insoluble impurities behind. The petroleum ether extract is evaporated to dryness and the residue is recrystallized from ethanol at 75°C yield 17 gm (41 %), m.p. 84°C. 

To a stirred solution of 10 gm (0.040 mole) of m-iodonitrobenzene in 100 ml of ethanol is added 16 gm (0.30 mole) of potassium hydroxide. The mixture is then heated to reflux for 1 hr. After this, the reaction mixture is subjected to steam distillation. The distillation residue is then extracted with boiling benzene. After cooling, the benzene layer is separated and evaporated to dryness. Yield 5.9 gm (60 %), m.p. (after recrystallization from ethanol-benzene) 120°-121°C. 

The oxidation of A-acyl-A-arylhydroxylamines with lead tetraacetate is very rapid even at very low temperatures. The product obtained is the corresponding aromatic nitroso compound. The most favorable reaction conditions involve propionic acid or ethanol-acetic acid as a solvent and reaction times of less than 10 sec at temperatures of —20°C or lower [87]. The use of ethanol-acetic acid is particularly recommended for several reasons. First, since the product is best isolated by steam distillation, the solvent assists in steamdistilling rapidly. The ethanol in the distillate helps minimize clogging of the condenser and also solubilizes small quantities of impurities that may be entrained. 

In an apparatus set up for steam distillation and containing a rapidly stirred solution of 5.0 gm (0.023 mole) of jV-benzoylphenylhydroxylamine (N-phenylbenzohydroxamic acid) in 100 ml of a 1 1 solution of ethanol-acetic acid, cooled to —20°C, is added 11.5 gm (0.024 mole based on 94% purity) of lead tetraacetate in one portion. After approximately 10 sec (when the initial green color just begins to darken), 100 ml of water is added and the brown or black mixture is rapidly subjected to steam distillation. The distillate is collected in a receiver filled with chopped ice. The product is isolated by filtration of the distillate. Finally, it is dried by pressing dry between filter papers to yield 1.4-2.0 gm (56-80%), m.p. 66°-68°C. 

The ultraviolet spectrum in the 300-350 mp region showed that less than 1% of 1-indanone was present. If the 2-indanone darkens on standing, it can be repurified by steam distillation or by crystallization from ethanol. 

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