Ethers, test for

Respiratory Effects. Hexane was one of 16 industrial solvents (hydrocarbons, alcohols, ketones, esters, and ethyl ether) tested for irritation potential on an average of 10 volunteers of mixed sexes for 3-5 minutes in an inhalation chamber (Nelson et al. 1943). The purity and the isomer composition of the hexane was not specified. Hexane was the only one of the 16 solvents which caused no irritation to the eyes, nose, or throat at the highest concentration tested (500 ppm). No odor was reported. 

Like bromine, iodine is soluble in organic solvents, for example chloroform, which can be used to extract it from an aqueous solution. The iodine imparts a characteristic purple colour to the organic layer this is used as a test for iodine (p. 349). NB Brown solutions are formed when iodine dissolves in ether, alcohol, and acetone. In chloroform and benzene a purple solution is formed, whilst a violet solution is produced in carbon disulphide and some hydrocarbons. These colours arise due to charge transfer (p. 60) to and from the iodine and the solvent organic molecules. 

Ester formation. Heat under very efficient reflux 1 ml. of diethyl ether, 4 ml. of glacial acetic acid and i ml. of cone. H2SO4 for ro minutes. Distil off 2 ml. of liquid. Use a few drops of this liquid for the hydroxamic add test for esters (p. 334). Use the remainder for other tests for esters (p. 354). 

Di-n-butyl ether. Technical n-butyl ether does not usually contain appreciable quantities of peroxides, unless it has been stored for a prolonged period. It should, however, be tested for peroxides, and, if the test is positive, the ether should be shaken with an acidified solution of a ferrous salt or with a solution of sodium sulphite (see under Diethyl ether). The ether is dried with anhydrous calcium chloride, and distilled through a fractionating column the portion, b.p. 140-141°, is collected. If a fraction of low boiling point is obtained, the presence of n-butyl... 

Extract the acidified solution with ether, remove the ether and identify the phenol in the usual manner (see Section IV,114).f Add a few drops of bromine water or nitric acid to the aqueous layer and test for sulphate with barium chloride solution. 

It is convenient to consider the indiflferent or neutral oxygen derivatives of the hydrocarbons—(a) aldehydes and kelones, (b) esters and anhydrides, (c) alcohols and ethers—together. All of these, with the exception of the water-soluble members of low molecular weight, are soluble only in concentrated sulphuric acid, i.e., fall into Solubility Group V. The above classes of compounds must be tested for in the order in which they are listed, otherwise erroneous conclusions may be drawn from the reactions for functional groups about to be described. 

Low molecular weight ether hydroperoxides are similarly dangerous and therefore ethers should be tested for peroxides and any peroxidic products removed from them before ethers are distilled or evaporated to dryness. Many ethers autoxidize so readily that peroxidic compounds form at dangerous levels when stored in containers that are not airtight (133). Used ether containers should be handled cautiously and if they are found to contain hazardous soHd ether peroxides, bomb-squad assisted disposal may be required (134). ZeoHtes have been used for removal of peroxide impurities from ethers (135). 

Peroxide Formation. Except for the methyl alkyl ethers, most ethers tend to absorb and react with oxygen from the air to form unstable peroxides that may detonate with extreme violence when concentrated by evaporation or distillation, when combined with other compounds that give a detonable mixture, or when disturbed by heat, shock, or friction. Appreciable quantities of crystalline soHds have been observed as gross evidence for the formation of peroxides, and peroxides may form a viscous Hquid in the bottom of ether-fiHed containers. If viscous Hquids or crystalline soHds are observed in ethers, no further tests for the detection of peroxides are recommended. Several chemical and physical methods for detecting and estimating peroxide concentrations have been described. Most of the quaHtative tests for peroxides are readily performed and strongly recommended when any doubt is present (20). 

Chemical tests for particular types of impurities, e.g. for peroxides in aliphatic ethers (with acidified KI), or for water in solvents (quantitatively by the Karl Fischer method, see Fieser and Fieser, Reagents for Organic Synthesis J. Wiley Sons, NY, Vol 1 pp. 353, 528, 1967, Library of Congress Catalog Card No 66-27894). 

Peroxides. These are formed by aerial oxidation or by autoxidation of a wide range of organic compounds, including diethyl ether, allyl ethyl ether, allyl phenyl ether, dibenzyl ether, benzyl butyl ether, n-butyl ether, iso-butyl ether, r-butyl ether, dioxane, tetrahydrofuran, olefins, and aromatic and saturated aliphatic hydrocarbons. They accumulate during distillation and can detonate violently on evaporation or distillation when their concentration becomes high. If peroxides are likely to be present materials should be tested for peroxides before distillation (for tests see entry under "Ethers", in Chapter 2). Also, distillation should be discontinued when at least one quarter of the residue is left in the distilling flask. 

A simple test for ether peroxides is to add lOmL of the ether to a stoppered cylinder containing ImL of freshly prepared 10% solution of potassium iodide containing a drop of starch indicator. No colour should develop during one minute if free from peroxides. Alternatively, a 1% solution of ferrous ammonium sulfate, O.IM in sulfuric acid and O.OIM in potassium thiocyanate should not increase appreciably in red colour when shaken with two volumes of the ether. 

An isopropyl ether was developed as a phenol protective group that would be more stable to Lewis acids than would be an aryl benzyl ether. The isopropyl group has been tested for use in the protection of the phenolic oxygen of tyrosine during peptide synthesis."... 

Arsine, AsHs, is formed when many As-containing compounds are reduced with nascent hydrogen and its decomposition on a heated glass surface to form a metallic mirror formed the basis of Marsh s test for the element. The low-temperature reduction of AsCls with LiAlH4 in diethyl ether solution gives good yields of the gas as does the dilute acid hydrolysis of many arsenides of electropositive elements (Na, Mg, Zn, etc.). Similar reactions yield stibine, e.g. ... 

The reactions of nitrones constitute the absolute majority of metal-catalyzed asymmetric 1,3-dipolar cycloaddition reactions. Boron, aluminum, titanium, copper and palladium catalysts have been tested for the inverse electron-demand 1,3-dipolar cycloaddition reaction of nitrones with electron-rich alkenes. Fair enantioselectivities of up to 79% ee were obtained with oxazaborolidinone catalysts. However, the AlMe-3,3 -Ar-BINOL complexes proved to be superior for reactions of both acyclic and cyclic nitrones and more than >99% ee was obtained in some reactions. The Cu(OTf)2-BOX catalyst was efficient for reactions of the glyoxylate-derived nitrones with vinyl ethers and enantioselectivities of up to 93% ee were obtained. 

Tests for Caramel.—Valuable indications of the nature of an extract are obtained in the process of determination of vanillin and coumarin. Pure extracts of vanilla beans give, with lead acetate, a bulky, more or less glutinous, brown-grey precipitate, and a yellow or straw-coloured filtrate, whereas purely artificial extracts coloured with caramel give a slight dark brown precipitate and a dark brown filtrate. If both vanilla bean extract and caramel are present the precipitate is more or less bulky and dark coloured, and the filtrate is more or less brown. The soluticm remaining after extraction of the vanillin and coumarin with ether, if dark coloured, should be tested for caramel. 

This solution is extracted several times with 5% acetic acid, until the silico-tungstate test (an identification test for alkaloids) yields a negative result, and the acetic solutions are washed with 10 ml ether. 

From the detailed studies performed either using individual alcohol sulfates and alcohol ether sulfates or formulated products by oral administration and skin contact, no evidence of carcinogen risk was found. Similar conclusions were obtained when these sulfates or formulated products were tested for mutagenic and teratogenic properties. 

In 1973 it was published that in contrast to lauryl ether sulfate the lauryl ether carboxylic acid sodium salt with 3 mol EO did not disturb the skin s water loss and did not decrease the skin s resistance [74], Formulation tests for the use as emulsifier in creams were described in 1976 [75]. 

Results. Various solvent mixtures were tested for extraction efficiency. The test sample was a bone-dry sediment reference material containing 24.6 ppm of Arochlor 1242. This reference material is a real sediment from New Bedford Harbor which was homogenized and carefully assayed for PCB s by the Cincinnati EPA facility. Figure 3 shows recovery of 1242 using (1) hexane alone, (2) hexane and water (1 1), (3) hexane, water, and ethyl ether, (4) ethyl ether and water, (5) ethyl ether, water, and methanol, (6) methanol and hexane (1 1), and (7) water, methanol, and hexane (1 4 5). This last combination appears to give the best recovery. When added in this order to a dry sample, the effect of the water is to wet the sample, thus permitting extraction by methanol. The extracted PCB is partitioned almost exclusively into the hexane from the aqueous methanol. Final recovery is calculated from initial weight and hexane volume. 

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