Preparation ethers from alcohols

Both reactants m the Williamson ether synthesis usually originate m alcohol pre cursors Sodium and potassium alkoxides are prepared by reaction of an alcohol with the appropriate metal and alkyl halides are most commonly made from alcohols by reaction with a hydrogen halide (Section 4 7) thionyl chloride (Section 4 13) or phosphorus tri bromide (Section 4 13) Alternatively alkyl p toluenesulfonates may be used m place of alkyl halides alkyl p toluenesulfonates are also prepared from alcohols as their imme diate precursors (Section 8 14)... 

The p-cyanobenzyl ether, prepared from an alcohol and the benzyl bromide in the presence of sodium, hydride (74% yield), can be cleaved by electrolytic reduction (—2.1 V, 71% yield). It is stable to electrolytic removal ( — 1.4 V) of a tritylone ether [i.e., 9-(9-phenyl-10-oxo)anthiyl ether]. ... 

Protection of Alcohols. Trimethylsilyl ethers, readily prepared from alcohols by treatment with a variety of silylating agents have found considerable use for the protection of alcohols. They are thermally stable and reasonably stable to many organometallic reagents and they are easily cleaved by hydrolysis in acid or base or by treatment with fluoride ion. t, Butyl dimethylsilyl ethers have considerably greater hydrolytic stability and are easier to work with than trimethylsilyl ethers. They are prepared from alcohols by treatment with t. butyl dimethylsilyl chloride. 

Problem 14.14 (R)-2-Octanol and its ethyl ether are levorotatory. Predict the configuration and sign of rotation of the ethyl ether prepared from this alcohol by (a) reacting with Na and then CjHjBr (b) reacting in a solvent of low dielectric constant with concentrated HBr and then with CjHjO Na. ... 

Cleavage conditions for alkyl benzyl ethers prepared from acid-labile benzyl alcohols are similar to those for the corresponding benzyl esters (Table 3.30). Aryl benzyl ethers, however, are generally cleaved more easily by acidolysis than esters or alkyl ethers. Phenols etherified with hydroxymethyl polystyrene, for instance, can even be released by treatment with TFA (Entry 1, Table 3.31). It has also been shown that Wang resin derived phenyl ethers are less stable than Wang resin derived esters towards refluxing acetic acid [29]. Alternatively, boron tribromide may be used to cleave aryl ethers from hydroxymethyl polystyrene [573],... 

R)-(-)-2,2-Diphenylcyclopentanol (1) is a highly effective chiral auxiliary in asymmetric synthesis. Hydrogenation of chiral 0-acetamidocrotonates derived from this alcohol has afforded the corresponding 0-amido esters with high diastereoselectivity (96% de).6 In addition, (R)-1 has been used as a chiral auxiliary in Mn(lll)-based oxidative free-radical cyclizations to provide diastereomerically enriched cycloalkanones (60% de).7 Our interest in (R)-(-)-2,2-diphenylcyclopentanol is its utility as a chiral auxiliary in Lewis acid-promoted, asymmetric nitroalkene [4+2] cycloadditions. The 2-(acetoxy)vinyl ether derived from alcohol (R)-1 is useful for the asymmetric synthesis of 3-hydroxy-4-substituted pyrrolidines from nitroalkenes (96% ee).8 In a similar fashion, a number of enantiomerically enriched (71-97% ee) N-protected, 3-substituted pyrrolidines have been prepared in two steps from 2-substituted 1-nitroalkenes and (R)-2,2-diphenyl-1-ethenoxycyclopentane (2) (see Table).9... 

A hydroxide nucleophile is needed to synthesize an alcohol, and salts such as NaOH and KOH are inexpensive and commercially available. An alkoxide salt is needed to make an ether. Simple alkoxides such as sodium methoxide (NaOCH3) can be purchased, but others are prepared from alcohols by a Brpnsted-Lowry acid-base reaction. For example, sodium ethoxide (NaOCH2CH3) is prepared by treating ethanol with NaH. 

Williamson s S3mthesis.—This reaction is known as Williamson s synthesis because, in 1851, he showed, by it, the true constitution of ether, and made possible the explanation of its preparation from alcohol and sulphuric acid as given a little later on. The reaction is similar to the Wurtz reaction between sodium and an alkyl halide by which a hydrocarbon is formed. 

The C27-C38 segment 208 was prepared from D-galactal 227 (O Scheme 26). The silyl ether, prepared from 227, was selectively benzylated, and the resulting C3-alcohol was desilylated and propanoylated to afford 228. After the Ireland-Claisen rearrangement of 228, carboxylic acid 229 was subjected to iodolactonization followed by reductive removal of iodine to give y-lactone 230. This was converted to the C27-C38 segment 208. 

Alcohols react with HX to form alkyl halides, but the reaction works well only for tertiary alcohols, R,COH. Primaiy and secondary alkyl halides are normally prepared from alcohols using either SOClj or PBr ). Alkyl halides react with magnesium in ether solution to form organomagnesium halides, or Grignard ret ents (RM O- Since Grignard reagents are both nucleophilic and basic, they react with acids to yield hydrocarbons. The overall result of Grignard formation and protonation is the conversion of an alkyl halide into an alkane (RX— RM RH). 

Esters can be prepared from alcohols and activated forms of carboxylic acids by a variety of meth-ods. Carboxylic acid esters are mainly base labile and, therefore, they complement the acid sensitive ether protecting groups. A variety of esters can be used for simpler and for more complex problems. Here, only the most practical groups will be treated. The application of esters as protected forms is frequently complicated by the possibility of acyl migration which may occur under basic, acidic and also neutral conditions. ... 

In contrast to the addition of water, the addition of alcohols to alkynes leads to stable enol ethers. Those of economic importance are almost exclusively the vinyl ethers prepared from acetylene. This preparation is carried out under base catalysis [41] (KOH, alcoholates, and the like). The noble metal-catalyzed alcohol addition does in fact likewise lead, in an intermediate stage, to vinyl ethers, but these react under the prevailing conditions, generally in a quantitative reaction, to give to corresponding acetaldehyde dialkyl acetals [42]. This is illustrated in (eq. (18)), which takes as its example the addition of n-butanol to acetylene in the presence of Na2PtCl6. 

Enol ethers. Enol ethers are prepared from alcohols by an exchange reaction with ethyl vinyl ether using the complex of Pd(OAc)2 with 1,10-phenanthroline. 

This ether is prepared by the Williamson ether synthesis from alcohols and phenols using a-bromomethylstyrene. It is cleaved by treating the ether in THF with f-BuLi at —78°C for 30 min (75-97% yield). The phenallyl ether can be cleaved in the presence of an allyl ether. Phenallyl amines and amides are cleaved similarly. Cleavage occurs by an addition of the alkyllithium to the olefin followed by elimination. 

Koreeda and Hamann have reported the use of silyl tethers in stereocontrolled syntheses of branched-chain 1,4-diols and 1,5-diols [61]. Exposure of (bromomethyl)silyl ethers prepared from the corresponding homoallylic alcohols with Bu SnH in the presence of AIBN allowed smooth conversion to the corresponding cyclic siloxanes, from which diol products were obtained using standard, oxidative cleavage protocols. While monosubstituted olefin 149 selectively underwent 1-endo cyclization, di- and trisubsti-tuted olefins 150 and 151 preferentially reacted through the 6-exo mode with complete stereocontrol, affording the diol products 152 and 153, respectively (Scheme 10-50). 

Ether can be prepared from alcohol by a method which has great historical interest, as it was through the discovery of this method that the structure of ethers and their relation to the alcohols were first made clear. When ethyl iodide is heated with sodium ethylate ether is formed —... 

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