Reactions of ethers

Ethers are relatively unreactive compounds however, they will react under certain circumstances. In this section we describe situations where reactions occur. 

In addition to reacting under certain conditions, ethers will slowly air oxidize to produce explosive peroxides. 

Mechanism forthe cleavage of an ether by a hydrohalic acid. 

Reaction of ethers with cold concentrated sulfuric acid. 

Epoxides are more reactive than other ethers. This is due to ring strain inherent in any three-atom ring system. The most useful reactions are acidic cleavage and nucleophilic cleavage. 

Ethers are unreactive to many reagents used in organic chemistry, a property that accounts for their wide use as reaction solvents. Halogens, dilute acids, bases, and nucleophiles have no effect on most ethers. 

Ethers undergo only one reaction of truly general use—they are cleaved by strong acids. Aqueous HBr and HI both work well, but HCl does not cleave ethers. 

Acidic ether cleavages are typical nucleophilic substitution reactions and take place by either SnI or Sn2 mechanisms depending on the structure of the substrate. Ethers with only primary and secondary alkyl groups react by an Sn2 mechanism, in which 1 or Br attacks the protonated ether at the less hindered site. This usually results in a selective cleavage into a single alcohol and a single alkyl halide. For example, ethyl isopropyl ether yields exclusively isopropyl alcohol and iodoethane on cleavage by HI because nucleophilic attack by iodide ion occurs at the less hindered primary site rather than at the more hindered secondary site. 

Ethers with a tertiary, benzylic, or allylic gronp cleave by either an S l or El mechanism because these substrates can prodnce stable intermediate carbocations. These reactions are often fast and take place at moderate temperatures. tert-Butyl ethers, for example, react by an El mechanism on treatment with trifluoroacetic acid at 0 °C. We ll see in Section 19.7 that the reaction is often used in the laboratory synthesis of peptides. 

CHAPTER 13 ALCOHOLS, PHENOLS, AND THIOLS ETHERS AND SULFIDES 

Ethers are very stable compounds that react with few common reagents. They do not react with bases, but do react with strong acids whose conjugate bases are good nucleophiles. For example, ethers react with HI (or with HBr) with cleavage of the carbon—oxygen bond to produce alkyl iodides (or bromides). 

Based on the mechanism of ether cleavage, write the products of the reaction of HI with each of the following compounds. 

Allylic and benzylic ethers are not cleaved by an Sj 2 process. Suggest an alternate mechanism for the acid-catalyzed cleavage of benzyl ethyl ether. 

A benzyl carbon-oxygen bond of the conjugate acid of benzyl ethyl ether can cleave in an S l reaction. The leaving group is ethanol, and the resulting benzyl carbocation is resonance stabilized. 

Write mechanisms for the following two reactions, (a) 1,4-Butanediol -I- oxacyclopentane 

As we know, tertiary and secondary ethers may also form by the alcoholysis of the corresponding haloalkanes or alkyl sulfonates (Section 7-1). The starting material is simply dissolved in an alcohol until the SnI process is complete (see margin). 

You now know several ways of constructing an ether from an alcohol and a haloalkane. Which approach would you choose for the preparation of (a) 2-methyl-2-(l-methylethoxy)butane (b) l-methoxy-2,2-dimethylpropane [Hint The product for (a) is a tertiary ether, that for (b) is a neopentyl ether.] 

In Summary Ethers can be prepared by treatment of alcohols with acid through Sn2 and SnI pathways, with alkyloxonium ions or carbocations as intermediates, and by alcoholysis of secondary or tertiary haloalkanes or alkyl sulfonates. 

As mentioned earlier, ethers are normally rather inert. They do, however, react slowly with oxygen by radical mechanisms to form hydroperoxides and peroxides. Because peroxides can decompose explosively, extreme care should be taken with samples of ethers that have been exposed to air for several days. 

Dialkyl ethers react with very few reagents other than acids. The only reactive sites that molecules of a dialkyl ether present to another reactive substance are the C—H bonds of the alkyl groups and the —O—group of the ether linkage. Ethers resist attack by nucleophiles (why ) and by bases. This lack of reactivity coupled with the abihty of ethers to solvate cations (by donating an electron pair from their oxygen atom) makes ethers especially useful as solvents for many reactions. 

Ethers are like alkanes in that they undergo halogenation reactions (Chapter 10), but these reactions are of little synthetic importance. They also undergo slow autoxidation to form explosive peroxides (see Section 11.3D). 

The oxygen of the ether linkage makes ethers basic. Ethers can react with proton donors to form oxonium salts  

Heating dialkyl ethers with very strong acids (HI, HBr, and H2SO4) causes them to undergo reactions in which the carbon-oxygen bond breaks. Diethyl ether, for example, reacts with hot concentrated hydrobromic acid to give two molecular equivalents of ethyl bromide  

The mechanism for this reaction begins with formation of an oxonium cation. Then, an Sn2 reaction with a bromide ion acting as the nucleophile produces ethanol and ethyl bromide. Excess HBr reacts with the ethanol produced to form the second molar equivalent of ethyl bromide. 

Recall from Section 9.5 that alcohols can be prepared from alkenes via a process called oxymercuration-demercuration. 

The net result is a Markovnikov addition of water (H and OH) across an alkene. That is, the hydroxyl group is ultimately placed at the more substituted position. The mechanism for this process was discussed in Section 9.3. 

If an alcohol (ROH) is used in place of water, then the result is a Markovnikov addition of the alcohol (RO and H) across the alkene. This process is called alkoxymercuration-demercuration, and it can be used as another way of preparing ethers. 

8 Show what reagents you would use to prepare each of the following ethers via an alkoxymercuration-demercuration. 

9 How would you use an alkoxymercuration-demercura-tion to prepare dicyclopentyl ether using cyclopentene as your only source of carbon  

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Section 16 8 The only important reaction of ethers is their cleavage by hydrogen halides... 

AIH3 is best prepared by the reaction of ethereal solutions of LiAlH4 and AICI3 under very carefully controlled conditions ° ... 

REACTION OF ETHERS AND CYCLIC ETHERS 5.5.1 Ethers and Cyclic Ethers... 

The polar media influences the reaction of peroxyl radicals with ether as on the reaction of two polar reagents [10] and on chain generation by the reaction of ether with dioxygen as reaction with the polar TS. 

A convenient procedure for catalytic carbonylation of bromooxazines (520) giving rise to previously unknown methoxycarbonylmethyl-substituted oxazines (525) in good yields (538) deserves note, all the more because this is the first example of catalytic C,C-coupling reactions of ethers of a-halo substituted oximes. 

A number of pentacovalent compounds of the type (47) have been isolated from reactions of ethers.57-69 The structures of the compounds were established by n.m.r. spectroscopy and Y-ray crystallography.58-69 The stability of these intermediates... 

The steric course at the Li-bearing center has been investigated nsing an enantiomer-ically enriched ethynylvinylmethanol-derived system. A reaction of ether 97 (78% ee) with n-BuLi gave [l,4]-prodnct ketone 98 only in the racemic form (equation 55 f. This lack of stereospecificity is partly due to racemization of the a-oxyafkyllithium and partly due to the [1,4]-rearrangement pathway. 

Ethers are compounds closely related to the alcohols. You probably think of anesthetics when you think of ethers, but these compounds are a lot more versatile than that. In this section, we look at the structures, properties, and reactions of ethers. 

Applying such mild conditions we further observed fission reactions of ether bonds (alkyl aryl ethers—e.g. ArOCH3) and —C—C—linkages by isolating fair amounts of methanol and carbon dioxide. 

The [1,2]-Wittig Rearrangement is the base-promoted reaction of ethers to yield secondary or tertiary alcohols. 

Li and coworkers published addition reactions of ethers, sulfides, or tertiary amines 40 to p-dicarbonyl compounds 39 (Fig. 8) [96]. Fe2(CO)9 proved to be the catalyst of choice and di-tert-butyl peroxide the optimal oxidant. a-Functionalized p-dicarbonyl compounds 41 were isolated in 52-98% yield. Although the details of the catalytic cycle remain unclear, it seems to be likely that the peroxide is reductively cleaved by the Fe(0) catalyst leading to an Fe(I) complex and a ferf-butoxyl radical, which abstracts the a-hydrogen atom of 40. Addition of the resulting radical to the free enol form of 39 or the corresponding iron enolate of 39 may subsequently occur. It remains unclear, however, whether the main catalytic reaction proceeds on an Fe(0)-Fe(I) oxidation stage or whether further oxidation of initially formed Fe(I) rather leads to an Fe(II) catalyst. This cannot be excluded,... 

Fig. 94 Radical addition reactions of ethers to a,(3-unsaturated carbonyl compounds...

The reaction of 5-chloro-6-nitroquinoxaline with />-methylbenzenethiolate ions, suggested to occur by the S l mechanism, has been reported to give disubstitution (both the nitro and chloro as leaving groups) without formation of any monosubstitution compound28215. On the other hand, the photostimulated reaction of ethers 229 derived from 5-chloro-7-iodo-8-hydroxy quinolines with different sulphanions has been studied and, in these cases, only monosubstitution products were obtained (equation 152)239. 

Summary Reactions of Ethers 641 14-10 Thioethers (Sulfides) and Silyl Ethers 642 14-11 Synthesis of Epoxides 646... 

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