Ethyl ether, extraction with purification

According to the literature, the product obtained in this manner may contain ethyl adipate. To remove this, the product is cooled to 0° and run slowly into 600 cc. of 10 per cent potassium hydroxide solution maintained at 0° with ice-salt. Water is added until the salt which separates has dissolved, and the cold alkaline solution is extracted twice with 200-cc. portions of ether. The alkaline solution, kept at 0°, is run slowly into 900 cc. of 10 per cent acetic acid solution with stirring, the temperature remaining below 1° (ice-salt). The oil which separates is taken up in 400 cc. of ether, and the aqueous solution is extracted with four 250-cc. portions of ether. The ether extract is washed twice with cold 7 per cent sodium carbonate solution and dried over sodium sulfate. After removal of the ether the residue is distilled, b.p. 7g-8i°/3 mm. The recovery is only 80-85 per cent, and in a well-conducted preparation the ethyl adipate eliminated amounts to less than one per cent of the total product. Unless the preparation has proceeded poorly the tedious purification ordinarily is best omitted. 

A mixture of 125 g of o-(pethyl chlorocarbonate in 150 ml of ether. The mixture is kept at room temperature for 3 days, diluted with about 500 ml of water and extracted with 300 ml of ether. The ethereal extract Is washed with 300 ml of water, dried over calcium chloride, filtered and concentrated. The resulting ethyl o-(pnext step without further purification. 

Ethyl-a-Keto-y-dimethylaminobutyrate p-Acetylphenylhydrazone. (JMC, 7, 144 (1966)). 40 g of p-aminoacetophenone in 250 ml of water and 143 ml of coned hydrochloric acid is diazotized at 0-5° with 21 g of sodium nitrite in 200 ml of water. To the resulting solution is added 60.3 g of ethyl a-(2-dimethylaminoethyl)aceto-acetate followed by 63 g of sodium acetate. Raise the pH to 6.5 and maintain with the addition of 3 N NaOH (also use the 3 N for the initial raise to 6.5). Stir, with external cooling for 2 hours, make basic, and extract with three 400 ml portions of ehloroform. Combine the extracts and dry over sodium sulphate, eoneentrate in vacuo. Crystallize the residue with a mixture of benzene-petroleum ether, after purification with charcoal, to get 65 g. Crystallize two more times to get a melting point of 84-85°. 

Lyophilized, pulverized leaves (5.35 kg) of S. divinorum were extracted with ether. The nonpolar components were removed from the concentrated extract through partition between hexanes and 90% aqueous methanol. The dried methanolic fraction was crudely purified by silica gel flash column chromatography (hexanes-ethyl acetate 2/1). Further purification of the biologically active fractions by additional silica gel flash column chromatography (methylene chloride-methanol 20/1) followed by repeated recrystallization yielded pure divinorin A (1) (1.2 g) and B (3) 50mg. 

The impurities present in aromatic nitro compounds depend on the aromatic portion of the molecule. Thus, benzene, phenols or anilines are probable impurities in nitrobenzene, nitrophenols and nitroanilines, respectively. Purification should be carried out accordingly. Isomeric compounds are likely to remain as impurities after the preliminary purifications to remove basic and acidic contaminants. For example, o-nitrophenol may be found in samples of p-nitrophenol. Usually, the o-nitro compounds are more steam volatile than the p-nitro isomers, and can be separated in this way. Polynitro impurities in mononitro compounds can be readily removed because of their relatively lower solubilities in solvents. With acidic or basic nitro compounds which cannot be separated in the above manner, advantage may be taken of their differences in pKg values. The compounds can thus be purified by preliminary extractions with several sets of aqueous buffers of known pH (see for example Table 19, p. 43) from a solution of the substance in a suitable solvent such as ethyl ether. This method is more satisfactory and less laborious the larger the difference between the pK value of the impurity and the desired compound. Heterocyclic nitro compounds require similar treatment to the nitroanilines. Neutral nitro compounds can be steam distilled. 

Dimethylphenol [108-68-9] M 122.2, m 68 , b 219 . Heated with an equal weight of cone H2SO4 at 103-105° for 2-3h, then diluted with four volumes of water, refluxed for Ih, and either steam distd or extracted repeatedly with ethyl ether after cooling to room temperature. The steam distillate was also extracted and evaporated to dryness. (The purification process depends on the much slower sulphonation of 3,5-dimethylphenol than most of its likely contaminants.) [Kester lEC 24 770 1932]. It can also be crystd from water, hexane or pet ether, and vacuum sublimed. [Bemasconi and Paschalis JACS 108 1986]. 

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