Diethyl ether, peroxides, removal

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 ... 

The solvents used for the extraction and analysis of carotenoids should be carefully purified before use to remove impurities. In most cases this means redistillation of the solvent. In the case of diethyl ether, the removal of peroxides is also important. Petroleum ether used for the extraction and chromatography of carotenoids should be passed through silica gel to remove sulfur compounds and unsaturated hydrocarbons. The methodology used in the isolation and identification of carotenoids has been covered in a recent review (Davies, (1976). A brief introduction to these techniques is presented below. 

Absolute diethyl ether. The chief impurities in commercial ether (sp. gr. 0- 720) are water, ethyl alcohol, and, in samples which have been exposed to the air and light for some time, ethyl peroxide. The presence of peroxides may be detected either by the liberation of iodine (brown colouration or blue colouration with starch solution) when a small sample is shaken with an equal volume of 2 per cent, potassium iodide solution and a few drops of dilute hydrochloric acid, or by carrying out the perchromio acid test of inorganic analysis with potassium dichromate solution acidified with dilute sulphuric acid. The peroxides may be removed by shaking with a concentrated solution of a ferrous salt, say, 6-10 g. of ferrous salt (s 10-20 ml. of the prepared concentrated solution) to 1 litre of ether. The concentrated solution of ferrous salt is prepared either from 60 g. of crystallised ferrous sulphate, 6 ml. of concentrated sulphuric acid and 110 ml. of water or from 100 g. of crystallised ferrous chloride, 42 ml. of concentrated hydiochloric acid and 85 ml. of water. Peroxides may also be removed by shaking with an aqueous solution of sodium sulphite (for the removal with stannous chloride, see Section VI,12). 

Di-teo-propyl ether. The commercial product usually contains appreciable quantities of peroxides these should be removed by treatment with an acidified solution of a ferrous salt or with a solution of sodium sulphite (see under Diethyl ether). The ether is then dried with anhydrous calcium chloride and distilled. Pure di-iao-propyl ether has b.p. 68-5°/760 mm. 

CAUTION. Ethers that have been stored for long periods, particularly in partly-filled bottles, frequently contain small quantities of highly explosive peroxides. The presence of peroxides may be detected either by the per-chromic acid test of qualitative inorganic analysis (addition of an acidified solution of potassium dichromate) or by the liberation of iodine from acidified potassium iodide solution (compare Section 11,47,7). The peroxides are nonvolatile and may accumulate in the flask during the distillation of the ether the residue is explosive and may detonate, when distilled, with sufficient violence to shatter the apparatus and cause serious personal injury. If peroxides are found, they must first be removed by treatment with acidified ferrous sulphate solution (Section 11,47,7) or with sodium sulphite solution or with stannous chloride solution (Section VI, 12). The common extraction solvents diethyl ether and di-tso-propyl ether are particularly prone to the formation of peroxides. 

Peroxide-free ether should be employed for detection and removal of peroxides in diethyl ether, see Section 11,47,i. 

The purification of diethyl ether (see Chapter 4) is typical of liquid ethers. The most common contaminants are the alcohols or hydroxy compounds from which the ethers are prepared, their oxidation products (e.g. aldehydes), peroxides and water. 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 lithium aluminium hydride, redistilled and given a final fractional distillation. The drying process should be repeated if necessary. 

An amount of enzyme preparation equivalent to 900 mg of wet cells was made up to 25 ml with the above potassium phosphate buffer solution. 150 mg (1.15 mmol) of 5-fluorouracil and 1.0 gram of thymidine (4.12 mmol) were dissolved in 15 ml of the above potassium phosphate buffer solution. The mixture was incubated at 37°C for 18 hours. After this time, enzyme action was stopped by the addition of four volumes of acetone and one volume of peroxide-free diethyl ether. The precipitated solids were removed by filtration, and the filtrate was evaporated under nitrogen at reduced pressure until substantially all volatile organic solvent had been removed. About 20 ml of aqueous solution, essentially free of organic solvent, remained. This solution was diluted to 100 ml with distilled water. 

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. 

Apart from the conversion of peroxides to useful products, it is sometimes necessary to reduce peroxides, and especially hydroperoxides formed by auto-oxidation. Such compounds are formed especially in hydrocarbons containing branched chains, double bonds or aromatic rings, and in ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, etc. Since most peroxidic compounds decompose violently at higher temperatures and could cause explosion and fire it is necessary to remove them from liquids they contaminate. Water-immiscible liquids can be stripped of peroxides by shaking with an aqueous solution of sodium sulfite or ferrous sulfate. A simple and efficient way of removing peroxides is treatment of the contaminated compounds with 0.4 nm molecular sieves [669]. 

E. Ethers. Diethyl ether is available in very dry grades, which for most purposes can be used directly from the freshly opened can. Similarly, purified grades of tetrahydrofuran are available which are often sufficiently dry to be used directly (Fisher). When extremely sensitive materials are handled, diethyl ether and tetrahydrofuran are often distilled from LiAIHL,. However, great care must be taken first to remove all peroxides and never to let the still pot go dty (see the general discussion in Section 4.1). Sodium-benzophenone ketyl is also effective with ethers which are peroxide free, and it has the advantage of being safer than LiAlH4. A small amount of benzene is introduced into the solvent when sodium-benzophenone ketyl is used. 

Peroxides in ether solvents. This is one of the commonest causes of explosions in organic chemistry laboratories. Simple dialkyl ethers such as diethyl ether and di-isopropyl ether, and cyclic ethers such as 1,4-dioxane and tetrahydrofuran, form less volatile peroxides on exposure to air and light. If therefore one of these solvents is purified by distillation, the peroxide content in the residue is progressively increased and eventually a violent explosion may occur. In view of this (i) such solvents should not be stored for long periods or in half empty bottles containers should be of dark glass (ii) before the solvents are distilled a peroxide test should be carried out, and, if positive, the peroxide must be removed (Section 4.1.11, p. 402 and Section 4.1.75, p. 404) and (iii) since purified ethers in contact with air rapidly peroxidise again (10 minutes in the case of tetrahydrofuran) they should be retested for peroxides and purified if necessary immediately before use. 

The commercial grade of this solvent is obtainable in greater than 99.5 per cent purity, in which water and peroxides are the major impurities an inhibitor for peroxide formation may have been added by the manufacturers. Peroxide, if present, must be removed by passage through a column of alumina (see 1. Light petroleum for footnote on the disposal of used alumina), or by shaking with iron(n) sulphate solution as described under diethyl ether before drying and further purification is attempted. If the latter method is employed the solvent should then be dried initially over calcium sulphate or solid potassium... 

---