Ether, purification peroxides

Oglialoro modification of, 708 Perkin triangle, 108, 218f Kon modification of, 109 Peroxides, detection of, in ether, 163 removal from diethyl ether, 163 removal from isopropyl alcohol, 886 Petroleum ether, purification of, 174 Phenacetin, 996, 997 1 10-Phenanthroline, 991, 992 p-Phenetidine, 997, 998 Phenetole, 665,670 Phenobarbitone, 1003,1004,1005 Phenol, 595, 613 Phenol aldehyde polymers, 1016 formation of, 1022 Phenolphthalein, 984, 985 action as indicator, 984 ... 

NPGDA), trimethylol propane triacrylate (TMPTA), Trigonal 14 (Noury Chem. Corp. mixture of benzoin butyl ethers), benzoyl peroxide, and t-butyl perbenzoate were used as obtained from commercial suppliers without further purification. 

The purification of diethyl ether (see Chapter 4) is typical of liquid ethers. The most common contaminants are the alcohols or hydroxy compoimds from which the ethers are prepared, their oxidation products (e g. aldehydes), peroxides and water. Dialkyl ethers form peroxides much more readily than other ethers, e.g. ethyl phenyl ethers, on standing in air. Peroxides, aldehydes and alcohols can be removed by shaking with alkaline potassium permanganate solution for several hours, followed by washing with water, concentrated sulfuric acid [CARE], then water. After drying with calcium chloride, the ether is distilled. It is then dried with sodium or with li um aluminium hydride, redistilled and given a final fractional distillation. The drying process is repeated if necessary. 

Greater selectivity in purification can often be achieved by making use of differences in chemical properties between the substance to be purified and the contaminants. Unwanted metal ions may be removed by precipitation in the presence of a collector (see p. 54). Sodium borohydride and other metal hydrides transform organic peroxides and carbonyl-containing impurities such as aldehydes and ketones in alcohols and ethers. Many classes of organic chemicals can be purified by conversion into suitable derivatives, followed by regeneration. This chapter describes relevant procedures. 

Rapid purification Check for peroxides (see Chapter 1 and Chapter 2 for test under ethers). Pre-dry with CaCl2 or better over Na wire. Then reflux the pre-dried solvent over Na (1 % w/v) and benzophenone (0.2% w/v) under an inert atmosphere until the blue colour of the benzophenone ketyl radical anion persists. Distil, and store over 4A molecular sieves in the dark. 

A solution of 1 equivalent of the oxazolidinone in diethyl ether is cooled to —78 C. To the resultant suspension are added 1.4 equivalents of triethylamine. followed by 1.1 equivalents of dibutylboryl triflate. The cooling bath is removed and the reaction mixture is stirred at 25 °C for 1.5 h. The resultant two-phase mixture is cooled to — 78 "C with vigorous stirring. After 1 equivalent of aldehyde is added, the reaction is stirred at —78 °C Tor 0.5 h, and 0 "C for 1 to 2 h. The solution is diluted with diethyl ether, washed with 1 N aq sodium bisulfate, and concentrated. Following oxidation with 30% aq hydrogen peroxide (10 equivalents, 1 1 methanol/water, 0 C. 1 h), extractive workup and chromatographic purification, the aldol adduct is obtained with >99% diastcrcomeric purity. 

In 1972, Chinese researchers isolated, by extraction at low temperature from a plant, a crystalline compound that they named qinghaosu [the name artemisinin (la) is preferred by Chemical Abstracts, RN 63968-64-9]. The plant source of artemisinin is a herb, Artemisia annua (Sweet wormwood), and the fact that artemisinin is a stable, easily crystallizable compound renders the extraction and purification processes reasonably straightforward. The key pharmacophore of this natural product is the 1,2,4-trioxane unit (2) and, in particular, the endoperoxide bridge. Reduction of the peroxide bridge to an ether provides an analogue, deoxyartemisinin 3, that is devoid of antimalarial activity. ... 

Procedures. Chromatographic Purification of Ozonization Products. Ozonization products from ethyl 10-undecenoate and 1-octene were chromatographed on silica gel columns (Baker) and eluted with 15 or 25% ether in petroleum ether (b.p., 30°-60°). Fractions were examined by thin-layer chromatography (TLC) on silica gel G Chroma-gram sheet eluted with 40% ether in petroleum ether. For development of ozonide and peroxide spots, 3% KI in 1% aqueous acetic acid spray was better than iodine. The spots (of iodine) faded, but a permanent record was made by Xerox copying. Color of die spots varied from light brown (ozonide) to purple-brown (hydroperoxide), and the rate of development of this color was related to structure (diperoxide > hydroperoxide > ozonide). 2,4-Dinitrophenylhydrazine spray revealed aldehyde spots and also reacted with ozonides and hydroperoxides. Fractions were evaporated at room temperature or below in a rotary evaporator. 

As a safety precaution against EXPLOSION (in case the purification has been insufficiently thorough) at least a quarter of the total volume of ether should remain in the distilling flask when the distillation is discontinued. To minimize peroxide formation, ethers should be stored in dark bottles and, if they are liquids, they should be left in contact with type 4A Linde molecular sieves, in a cold place, over sodium amalgam. The rate of formation of peroxides depends on storage conditions and is accelerated by heat, light, air and moisture. The formation of peroxides is inhibited in the presence of diphenylamine, di-tert-butylphenol, or other antioxidant as stabilizer. 

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