Primary alcohols ether preparation from

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 ... 

Picolyl ethers are prepared from their chlorides by a Williamson ether synthesis (68-83% yield). Some selectivity for primary versus secondary alcohols can be achieved (ratios = 4.3-4.6 1). They are cleaved electrolytically ( — 1.4 V, 0.5 M HBF4, MeOH, 70% yield). Since picolyl chlorides are unstable as the free base, they must be generated from the hydrochloride prior to use. These derivatives are relatively stable to acid (CF3CO2H, HF/anisole). Cleavage can also be effected by hydrogenolysis in acetic acid. ... 

As previously discussed, ethyl chlorocarbonate reacts rapidly and selectively with an equatorial 3-hydroxyl group to give the corresponding cathylate. Trityl ethers, usually employed as a selective protecting group for primary hydroxyls, can be prepared from A -3j3-ols by heating with triphenylmethyl chloride in pyridine, and from 5a-3 -alcohols by more prolonged heat-... 

Picolyl ethers are prepared from their chlorides by a Williamson ether synthesis (68-83% yield). Some selectivity for primary vs. secondary alcohols can be achieved (ratios = 4.3-4.6 1). Picolyl ethers are cleaved electrolytically ( —1.4 V,... 

Diethyl ether and other simple symmetrical ethers are prepared industrially by the sulfuric acid-catalyzed dehydration of alcohols. The reaction occurs by SN2 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 (Section 17.6). 

Ethers are prepared from alkyl halides by the treatment of metal alkoxide. This is known as Williamson ether synthesis (see Sections 4.3.6 and 5.5.2). Williamson ether synthesis is an important laboratory method for the preparation of both symmetrical and unsymmetrical ethers. Symmetrical ethers are prepared by dehydration of two molecules of primary alcohols and H2SO4 (see Sections 4.3.7 and 5.5.3). Ethers are also obtained from alkenes either by acid-catalysed addition of alcohols or alkoxymercuration-reduction (see Section 5.3.1). 

The preparation of 1 started with the addition of lithiated 4 to the enantiomcrically-pure epoxide 5, which was prepared from the racemate using the Jacobsen protocol. Reduction followed by selective protection of the primary alcohol gave the monosilyl ether, which was further protected with MOM chloride to give 7. Pd-mediated oxidation to the methyl ketone followed by condensation with the Horner-Emmons reagent gave the unsaturated ester 8 as an inconsequential mixture of geometric isomers. Oxidation then set the stage for the crucial cyclization. 

Protection of alcohols.1 Dimethylthexylsilyl ethers are prepared from primary or secondary alcohols by reaction with 1 and either imidazole or N(C2H5)3 in DMF. The ethers of tertiary alcohols are prepared by reaction with dimethylthexylsilyl trifluoromethanesulfonate in the presence of lutidine or N(C2H5)3. Silylation of amines, amides, mercaptans, and acids is conducted under similar conditions. 

Protection of primary alcohols p-Anisyl ethers are readily prepared from primary alcohols by the Mitsunobu reaction [P(C6H5)3 DEAD]. The ethers are stable to 3 N HC1 or 3 N NaOH at 100°, to Jones or PCC oxidation, and to LiAlH4. Deprotection is effected in 85-95% yield by oxidation with CAN in aqueous CH3CN. 

Reduction of halides.1 The reagent prepared from NaBH3CN and SnCl2 in a 2 1 ratio does not reduce primary or secondary alkyl halides or aryl halides in ether at 25°, but does reduce tertiary, allyl, and benzyl halides. It is thus comparable to NaBH3CN-ZnCl2 (12, 446). Aldehydes, ketones, and acid chlorides are reduced to alcohols, but esters and amides are inert. 

Reaction of COS with primary and secondary amines in alcoholic or ethereal media yields the unstable monothiocarbamic acid. A substantial excess of COS promotes the decomposition.74 The ligand is stabilized in alkaline medium, so either an excess of amine is maintained or the preparation is carried out in aqueous NaOH or KOH. Monothiocarbamato complexes, recently reviewed,75 are mostly prepared from a metal salt and (56). The ligand field strength of monothiocarbamate is somewhat less than that of the dithio analogue.76... 

Nonan-l-ol (primary alcohol from ethylene oxide). Prepare a Grignard reagent from 24.5 g (1 mol) of magnesium turnings, 179 g (157 ml, 1 mol) of 1-bromoheptane (Expt 5.55) and 300 ml of dibutyl ether as described above. Cool the solution to 0°C and, with vigorous stirring, add an excess of ethylene oxide. Maintain the temperature to 0 °C for 1 hour after the ethylene oxide has been introduced, then allow the temperature to rise to 40 °C and maintain the mixture at this temperature for 1 hour. Finally heat the mixture... 

Diethyl ether (Et20) can be prepared by heating ethanol with sulphuric acid at about 140 °C, and adding more alcohol as the ether distils out of the reaction medium. A similar continuous etherification process is used industrially. A more general procedure for the preparation of symmetrical ethers from primary alcohols (e.g. dibutyl ether, Expt 5.70) is to arrange for the water formed in the reaction to be removed azeotropically. 

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