Ethers, aliphatic

Saturated ethers may have symmetrical (ROR) or unsymmetrical (R O-R2) structures. Illustrative representations are given below for methyl propyl ether (1) CH3-CH2 CH2 OCH3, and for methyl isopropyl ether (2) 

Benzylic ethers (Ph CH2 OR), allylic ethers (R CH=CH CH2-OR) and vinylic ethers [R CH=CH(OR)] together with the most commonly encountered tetrahydropyranyl ethers [THP-ethers, (5)] and /J-methoxyethoxymethyl ethers [MEM-ethers, R0CH2 0(CH2)2 0CH3] play an important role in the protection of a hydroxyl group (p. 550). Macrocyclic ethers (the crown ethers) are important phase transfer catalysts [e.g. 18-Crown-6 (6)]. 

The synthesis of ethers is exemplified by two main general procedures. 

The formation of ethers from alcohols under acidic conditions (Expts 5.70 and 5.71). 

The interaction of an alcohol with a halogen compound under basic conditions (Expts 5.72 and 5.73). 

The spectra of a number of simple aliphatic ethers have been given Barnes et al. [3]. The exact positions of the C—O—C bands are not given, but from the spectra it can be seen that they all absorb in the approximate range 1150—1060 cm . They have also given the spectra of allyl ethyl ether and of diallyl ether, in both of which the C—O—C band is in approximately the same position as in the saturated materials. This last observation would appear to indicate that the structure C= C—C—O—C does not have any marked effect on the C—O frequency, and this agrees with Lecomte s [ 1 ] observation that the C—O stretching frequencies of vinyl alcohols are essentially normal. 

Studies on alkyl ethers which include successive deuteration in methyl ethyl ether [59], have already established that the antisymmetric C—O—C band is at 1120 cm for the trans configuration, and at 1068 cm for the gauche form. Weisner et al. [60] have made similar studies on diethyl ether and also find the antisymmetric stretch of the trans form at 1120 cm.  

A useful aid to the identification of the C—O stretching bands, apart from their intensities, is the movement to lower frequencies which takes place on complex formation with aluminium trichloride or boron trifluoride [61, 62]. In diethyl ether for example the band shifts to 1070 cm Derovault [62] has also obtained useful data by this method. The results, together with those of Synder and Zerbi [63] and by Mashiko et al. [39] fully confirm that the main C—O band of alkyl ethers in the infra-red is to be expected in the 1120 cm region with some variations on either side due to structural and conformational effects. 

Hydroperoxides are the primary products of the oxidation of aliphatic ethers [186—203,283,284]. Under mild conditions (30—70°C), the yield of hydroperoxides is close to 100%. The a-C—H bond of ether is most reactive and the hydroperoxides formed are a-alcoxyhydroperoxides, as found by the synthesis of such hydroperoxides and analysis of their decomposition products [194,284—286]. 

Dihydroperoxides are formed in the oxidation of diethyl and diisopropyl ethers, together with the hydroperoxides [203,283,285]. Their production can be explained by isomerization of peroxy radicals. 

The products of autoxidation and photo-oxidation of ethers are the same [187,287,288]. Aldehydes, alcohols, acids, and esters are the main products of hydroperoxide decomposition [186,187,202,283—285,289,290]. For example, ethanol, acetaldehyde, acetic acid, ethyl acetate, and ethyl formate were found in the products of diethyl ether oxidation [186,188, 202,203]. Their formation may be explained by the scheme 

Diethyl ether may be prepared from ethyl alcohol by the sulphuric acid process. A mixture of alcohol and sulphuric acid in equimolecular proportions is heated to about 140° and alcohol is run in at the rate at which the ether produced distils from the reaction mixture. Ethyl hydrogen sulphate (or ethyl sulphuric acid) is first formed and this yields ether either by reacting directly with a molecule of alcohol or by the formation and alcoholysis of diethyl sulphate (I)  

C2H5OSO2OH -f HjO C2H5OC2H5 + HOSOjOH C-sHjiOSOjOCjHs (I) -f HjO C HjjOCaHs + CaHjOSOjOH 

If the temperature is allowed to rise to 170°, much of the ethyl hydrogen sulphate decomposes into ethylene  

The sulphuric acid and ethyl hydrogen sulphate required in reactions 1 and 3 respectively are regenerated in reactions 2 and 4, but the water formed is retted in the acid mixture and ultimately results in such a dilution that the caiversion into ether is no longer efficient. Furthermore, some ethylene is always formed this partly polymerises to give materials capable of reacting with sulphuric acid and reducing it to sulphur dioxide. In industrial practice, me part of sulphuric acid is sufficient for the production of about 200 parts of ether. 

The above simple process cannot be applied to the preparation of the homo-logues a higher temperature is requir (di-n-amyl ether, for example, boils at 169°) and, under these conditions, alkene formation predominates, leading ultimately to carbonisation and the production of sulphur dioxide. If, however, the water is largely removed by means of a special device (see Fig. Ill, 57,1) as soon as it is formed, good 300 of ethers may be obtained from primary alcohols, for example  

Yuan et al. studied two types of condition for this reaction - use of either the alcohols or the corresponding halides as starting materials [16, 17]. In the presence of quaternary ammonium salts the reaction shown in Eq. (7) is complete within a few minutes. Typical results are given in Tab. 5.5. 

More recently, this method has been extensively applied to a wide range of Williamson syntheses in dry media with K2C03 and KOH as bases, TBAB as phase-transfer agent, and a variety of aliphatic alcohols (e. g. n-octanol and n-decanol, yields 75-92%) [18], 

Mixed ethers may be prepared by the interaction of an, alkyl halide and a sodium alkoxide (Williamson s synthesis), for example  

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Consequently traces of these unstable peroxides are present in samples of all the lower aliphatic ethers unless the samples have been freshly distilled. If these ethers when being distilled are heated on, for example, an electric heater, the final residue of peroxide may become sufficiently hot to explode violently. The use of a water-bath for heating, as described above, decreases considerably both the risk of the ether catching fire and of the peroxide exploding. 

Anisole is a colourless and almost odourless liquid, having b.p. 154°, and dy 0-99. Like the aliphatic ethers, it is chemically inert, although of course the phenyl group shows the normal aromatic reactions. 

Physical Properties. All th e ethers are insoluble in water. The aliphatic ethers have strong characteristic odours, have anaesthetic properties and are extremely inflammable. 

Aliphatic ethers are broken down by heating with ZnClj. 

Formation of, -dinitrobenzoates. Aliphatic ethers are broken up by heating with ZnClg, and a 3,5--dinitrobenzoate of the residue can then be prepared. This is suitable only for symmetrical ethers. 

A), -Dinitrohenzoates. Only suitable for symmetrical aliphatic ethers. Preparation, see above. The yields are usually very low. 

The low reactivity of aliphatic ethers renders the problem of the preparation of suitable crystalline derivatives a somewhat difficult one. Increased importance is therefore attached to the physical properties (boding point, density and refractive index) as a means for providing preliminary information. There are, however, two reactions based upon the cleavage of the ethers which are useful for characterisation. 

The resulting alkyl 3 5-dinitrobenzoate may be employed for the characterisation of the ether. The method is only applicable to symmetrical or simple ethers a mixed aliphatic ether ROR would yield a mixture of inseparable solid esters. 

Cleavage of ethers with hydriodic acid. Aliphatic ethers suflFer fission when boiled with constant boiling point hydriodic acid ... 

If the ether is a simple one (R — R ), the identification of the resulting alkyl iodide presents no difficulties. If, however, it is a mixed aliphatic ether, the separation of the two alkyl iodides by fractional distillation is generally difficult unless R and R differ considerably in molecular weight and sufficient material is available. 

The physical properties of a number of aliphatic ethers are collected in Table 111,60. Some related heterocyclic compounds are included in the Table. 

Experimental details can easily be adapted from those given under Aliphatic Ethers, Section 111,60, 2. 

Fission of ethers with hydriodic acid. Reflux 1 ml. of the compound with 5 ml. of freshly distilled constant b.p. hydriodic acid (b.p. 126-128°) for 2-3 hours in a small flask fitted with a double surface condenser. Add 10 ml. of water, distil and collect about 7 ml. of liquid. Decolourise the distillate by the addition of a little sodium bisulphite and separate the two layers by means of a dropper pipette. If the original compound is suspected to be an aliphatic ether, determine the b.p. of the iodide by the Siwoloboff method (Section 11,12) if the amount of product is insufficient, repeat the original experiment. 

Aliphatic Halogen Compounds, Table III, 42 Aromatic Halogen Compounds, Table IV, 28. Aliphatic Ethers, Table III, 60. 

The tendency of aliphatic ethers toward oxidation requires the use of antioxidants such as hindered phenoHcs (eg, BHT), secondary aromatic amines, and phosphites. This is especially tme in polyether polyols used in making polyurethanes (PUR) because they may become discolored and the increase in acid number affects PUR production. The antioxidants also reduce oxidation during PUR production where the temperature could reach 230°C. A number of new antioxidant products and combinations have become available (115,120,124—139) (see Antioxidants). 

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). 

Ethers — (R-O-R) are low on the scale of chemical reactivity. Aliphatic ethers are generally volatile, flammable liquids with low boiling points and low flashpoints. Well known hazardous ethers include diethyl ether, dimethyl ether, tetrahydrofuran. Beyond their flammability, ethers present an additional hazard they react with atmospheric oxygen in the presence of light to form organic peroxides. 

Fluorination of aliphatic ethers at gentle conditions with cobalt trifluoride or potassium tetrafluorocobaltate do not give perfluorinated products and cause only negligible cleavage of the ether bond. Complex mixtures are formed from ethyl methyl ether and from diethyl ether [9] (equations 16 and 17)... 

From simple ethers of the thiophene series, such as (230), aliphatic ethers such as (231) have been obtained by desulfurization in ether. ... 

Carboxylic acids, particularly aromatic acids with a methyl group ortho to the carboxyl group Aliphatic ethers with one alkyl group containing more than eight carbons... 

The silica gel surface is extremely polar and, as a result, must often be deactivated with a polar solvent such as ethyl acetate, propanol or even methanol. The bulk solvent is usually an n-alkane such as n-heptane and the moderators (the name given to the deactivating agents) are usually added at concentrations ranging from 0.5 to 5% v/v. Silica gel is very effective for separating polarizable materials such as the aromatic hydrocarbons, nitro hydrocarbons (aliphatic and aromatic), aliphatic ethers, aromatic esters, etc. When separating polarizable substances as opposed to substances with permanent dipoles, mixtures of an aliphatic hydrocarbon with a chlorinated hydrocarbon such as chlorobutane or methylene dichloride are often used as the mobile... 

Note There appear to be no recent examples of this reaction with simple alkoxy substrates (perhaps because normal aliphatic ethers need quite vigorous treatment, such as boiling hydriodic acid), but so-called isopropylidenedioxy derivatives (that undergo facile hydrolysis) have been used in this way. l-[2,3-(Isopropylidenedioxy)propyl]-3-methyl-2(17/)-quinoxalinone (165) gave l-(2,3-dihydroxypropyl)-3-methyl-2(l//)-quinoxahnone (70% AcOH, reflux, 2 h 35% homologs likewise). ... 

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