Preparing Ethers

Name the following ethers and snlfides according to lUPAC rules  

Diethyl ether and other simple symmetrical ethers are prepared industrially by the sulfuric acid-catalyzed reaction of alcohols. The process occurs hy 5 2 displacement of water from a protonated ethanol molecule by the oxygen atom of a second ethanol. Unfortunately, the method is limited to use with primary alcohols because secondary and tertiary alcohols dehydrate by an El mechanism to yield alkenes. 

The most generally useful method of preparing ethers is by the Williamson ether synthesis, in which an alkoxide ion reacts with a primary alkyl hahde or tosylate in an Sn2 reaction. As we saw earlier in Section 13.2, the alkoxide ion is normally prepared hy reaction of an alcohol with a strong base such as sodium hydride, NaH. 

Because the Williamson synthesis is an 5 2 reaction, it is subject to all the usual constraints, as discussed in Section 12.7. Primary halides and tosylates work best because competitive E2 elimination can occur with more hindered substrates. Unsymmetrical ethers should therefore he synthesized by reaction 

CHAPTER 13 ALCOHOLS, PHENOLS, AND THIOLS ETHERS AND SULFIDES 

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Sections 16 5 The two major methods for preparing ethers are summarized m Table and 16 6 16 1... 

The most versatile method of preparing ethers is the Williamson ether synthesis, particularly in the preparation of unsymmetrical alkyl ethers (12,13). The reaction of sodium alcoholates with halogen derivatives of hydrocarbons gives the ethers ... 

Strategy Draw the target ether, identify the two groups attached to oxygen, and recall the limitations of the two methods for preparing ethers. The Williamson synthesis uses an Sn2 reaction and requires that one of the two groups attached to oxygen be either... 

The first reaction offers a general way of preparing ethers from alcohol. The second reaction is that of esterification, referred to earlier. 

To 2 mmol of freshly prepared ethereal LiCu(C.H3), are added 154 mg (1 mmol) of ( — )-m-5-melhyl-2-cyclo-hexenyl acetate (3a). [a]25 —2.7 (c = 3, CHC1,), in a centrifuge tube at 0°C. The mixture is kept at 0 °C for 8 h after which 1 mL of water is added. Methane is evolved and a reddish precipitate forms. After centrifuging, the supernatant liquid is decanted and concentrated, and the product trims-4 is isolated by preparative GC. Isolated yields range from 30% and 40%. However, it was reported in a similar reaction that the yields range from 90% and 95% 5. Analysis by capillary GC shows the product to be 99.5% trans-4 and 0.5% t -4. Capillary GC of the starting 3a shows the acetate 3a to be homogeneous except for a trace ( — 1.0%) of the trans-isomers. 

In preparing ethers of phenols, aqueous IN sodium hydroxide should be substituted for the sodium bicarbonate solution. 

Many borohydrides are highly unstable and have to be used as freshly prepared ethereal solutions. However there are instances where the polymer-supported versions are more stable e. g. an Amberlyst anion exchange resin supported borohydride and cyanoborohydride [61], polyvinylpyridine supported zinc borohydride [62] and the corresponding zirconium borohydride [63]. Such compounds, in their labeled forms, should turn out to be very useful. 

Fales, H. M., Jaouni, T. M., and Babashak, J. F. (1973). Simple device for preparing ethereal diazomethane without resorting to codistillation. Analytical Chemistry 45 2302-2303. 

However, this intramolecular cycloadditiou methodology has found more widespread use in the preparation of cis-fused heterobicychc rather than carbobicyclic products, by insertion of a heteroatom into the hydrocarbon tail of the alkenyl nitrone. Particular attention has been given to the synthesis of THF adducts (326, X = 0) (202,317,354,358-365), and to a lesser extent the N (82,361,366-368) S (202,203,369), or silyloxy analogues (54,55,370). Aurich and Biesemeier (359) prepared ether dipoles (327), which slowly cyclized at ambient temperature to afford the cis-fused bicyclic adducts 328 (Scheme 1.70). Reductive cleavage of the... 

WILLIAMSON SYNTHESIS. An organic method for preparing ethers by the interaction of an alkylhalide with a sodium alcoholate (or phenolate). 

The most generally useful methods of preparing ethers already have been discussed (Sections 8-7C, 8-7E, 15-4C, and 15-5C). These and some additional special procedures are summarized in Table 15-4. 

Oxymercuration may also be used to prepare ethers, acetates, amines, or amides (Markownikoff adducts). Several excellent procedures for these syntheses have been published by H. C. Brown and co-workers.4b... 

Of the numerous alkyl protecting groups known [8, 9], only those widely used in synthetic chemistry of carbohydrates will be discussed. Methyl ethers — with hundreds of selective methylations far exceeding the scope of the review — were excluded for their unimportant role as synthetic intermediates (great majority of partial methylations are carried out to complete the list of reference compounds for the methylation analysis of polysaccharides, or simply to prepare ethers widely occurring in biologically important molecules). 

Valerius Cordus (1515-1544), German physician, provides the first written description of how to prepare ether. 

In preparing ethers of o-carbomethoxyphenols it has been found that the slow dropwise addition of aqueous sodium hydroxide or potassium carbonate to a refluxing mixture of the proper phenol and halide in methyl ethyl ketone gives a smoother reaction with yields much better than those obtained when all the alkali is added before refluxing is begun.46 ... 

Silicon tetrachloride is a raw stock for preparing ethers of orthosilicon acid and is used in the production of silicone polymers used to obtain highly thermostable plastics and synthetic lubricants, as well as high-quality electroinsulation. Silicon tetrachloride is also used to prepare superfine silicon dioxide (Aerosil). A mixture of silicon tetrachloride and... 

Williamson ether synthesis (Section 9.6) A method for preparing ethers by reacting an alkoxide (RO ) with a methyl or primary alkyl halide. 

Preparation. Ethereal solutions of iodine thiocyanate are prepared essentially by the method of Raby. Bromine (0.025 mole) is added ail at once to a slurry of lead thiocyanate (0.025 mole, Eastman). The mixture is stirred at room temperature until the bromine fades (several minutes). A solution of iodine (0.025 mole) in dry ether is then added lo the solution of thioeyanogen, and the mixture is stirred for 15 min. at room temperature with protection from light. 

Esterification of 3 to give Dimethyl Ester 4 To a solution of 1.84 g of crude adduct 3 in dry Et20 is added dropwise a freshly prepared ethereal solution of diazomethanc until the yellow color of CH2N2 persists. The solvent is removed and the residue is purified by medium-pressure liquid chromatography with 30% EtOAc in petroleum ether (bp 30-60 CC) (Rf 0.38) to give a crystalline diester yield 1.19 g (55% based on starting enone) mp 107-108 °C (Et,0/petroleum ether). 

This method has the advantage over the use of ethereal solutions of magnesium and lithium alkyls in that the metal alkyls can be prepared ether-free. In certain cases, however, not all the alkyl groups of RSA1 are available. Thus in the preparation of gallium and indium alkyls the reaction proceeds according to the following equation (142) ... 

The reaction of the readily accessible trimethylsilyl enol ethers with methyllithium has been successfully applied to prepare ethereal solutions of lithium alkenolates RCH=CHOLi [3,5]. Good results can be obtained also with n-BuLi [4]. Both the trimethylsilyl enol ethers, which are prepared hy heating a mixture of the aldehyde, chlorotrimethylsilane, triethylamine and DMF, and the enolates are mixtures of the E- and Z-isomers. 

Many alkaloids may be only sparingly soluble in ether but, with the exception of pentane and hexane, their purification is more readily effected from this solvent than from any other. It is possible to prepare ether solutions of these bases of a concentration far in excess of their equilibrium value which then often yield a crystalline solid in reattaining a state of equilibrium. A supersaturated ethereal solution of these bases is readily prepared as follows The relatively dilute aqueous acid solution of the alkaloids, in a separatory funnel, is covered with a layer of ether, and a layer of water interposed between the two layers by the cautious addition of water down the side of the funnel. Aqueous ammonia is run in, in a like manner, the stopper inserted in the funnel, and the mixture shaken very vigorously. Often the more insoluble alkaloids will crystallize from the ether layer before it can be separated. In any case the wet turbid ethereal solution can be brought to brilliant clarity by treatment with charcoal. Removal of the ether leaves a residue which is now amenable to fractional crystallization from other solvents, to fractional distillation, or to salt formation. 

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