Alkylation symmetrical ether

In general this method is limited to the preparation of symmetrical ethers m which both alkyl groups are primary Isopropyl alcohol however is readily available at low cost and gives high enough yields of diisopropyl ether to justify making (CH3)2CHOCH(CH3)2 by this method on an industrial scale... 

Ethers are compounds of the general formula Ar—O—Ar, Ar—O—R, and R—O—where Ar is an aryl group and R is an alkyl group. If the two R or Ar groups are identical, the compound is a symmetrical ether. Examples of symmetrical ethers are (di)methyl ether, CH OCH, and (di)phenyl ether,... 

This reaction, which is named after W. Williamson, is the most important method for the synthesis of unsymmetrical ethers 3. For this purpose an alkoxide or phenoxide 1 is reacted with an alkyl halide 2 (with R = alkyl, allyl or benzyl). Symmetrical ethers can of course also be prepared by this route, but are accessible by other routes as well. 

However, pMBCl 42 has a thermal stability issue and is expensive (Aldrich price 25 g for 69.90 the largest bottle). On the other hand, pMBOH 43 is stable and economically viable (Aldrich price 500 g for 84.90 the largest bottle). It was found that mono-N-alkylation of 36 proceeded well by slow addition (over 3 h) of 43 to a solution of 36 in acetonitrile in the presence of a catalytic amount of acid (p-TsOH) at 70 °C, as shown in Scheme 1.16. Slow addition of alcohol 43 minimized the self-condensation of 43 to form symmetrical ether 44, which was an equally effective alkylating agent. The product 41 was then directly crystallized from the reaction mixture by addition of water and was isolated in 90% yield and in >99% purity. A toluene solution of 41 can be used for the next reaction without isolation but the yield and optical purity of the asymmetric addition product were more robust if isolated 41 was used. In general, the more complex the reaction, the purer the starting materials the better. 

They offer the advantage that reductions can be effected under conditions that permit the conversion of substrates that may be adversely sensitive to the presence of strong Brpnsted acids. For example, in the presence of a 10% excess of triethylsilane, addition of one-half equivalent of boron trifluoride etherate to octanal results, within one hour, in the formation of a 66% yield of dioctyl ether after a basic hydrolytic workup. Benzaldehyde provides a 75% yield of dibenzyl ether under the same reaction conditions. The remainder of the mass is found as the respective alcohol.70 Zinc chloride is also capable of catalyzing this reaction. With its use, simple alkyl aldehydes are converted into the symmetrical ethers in about 50% yields.330... 

Symmetrical ethers are obtained from the dehydration of two molecules of alcohol with H2SO4 (see Section 5.5.3). Alcohols react with p-toluenesul-phonyl chloride (tosyl chloride, TsCl), also commonly known as sulphonyl chloride, in pyridine or EtsN to yield alkyl tosylates (see Section 5.5.3). Carboxylic acids, aldehydes and ketones are prepared by the oxidation of 1° and 2° alcohols (see Sections 5.7.9 and 5.7.10). Tertiary alcohols cannot undergo oxidation, because they have no hydrogen atoms attached to the oxygen bearing carbon atom. 

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). 

Alkyl halides can be converted to symmetrical ethers by treatment with oxide ion generated in situ by a reaction between an organotin oxide and fluoride ion in the presence of a quaternary ammonium iodide or a crown ether.715... 

The so-called Williamson synthesis of ethers is by far the most important ether synthesis because of its versatility it can be used to make unsymmetrical ethers as well as symmetrical ethers, and aryl alkyl ethers as well as dialkyl ethers. These reactions involve the nucleophilic substitution of alkoxide ion or phenoxide ion for halide (equation 70).26°... 

The resulting alkyl 3,5-dinitrobenzoate may be employed for the characterisation of the ether. The method is only applicable to symmetrical ethers a mixed aliphatic ether R OR2 would yield a mixture of solid esters. 

The two alkyl groups are the same in a symmetrical ether and different in an unsymmetrical ether. 

The least expensive method for synthesizing simple symmetrical ethers is the acid-catalyzed bimolecular condensation (joining of two molecules, often with loss of a small molecule like water), discussed in Section 11-10B. Unimolecular dehydration (to give an alkene) competes with bimolecular condensation. To form an ether, the alcohol must have an unhindered primary alkyl group, and the temperature must not be allowed to rise too high. If the alcohol is hindered or the temperature is too high, the delicate balance between substitution and elimination shifts in favor of elimination, and very little ether is formed. Bimolecular condensation is used in industry to make symmetrical ethers from primary alcohols. Because the condensation is so limited in its scope, it finds little use in the laboratory synthesis of ethers. 

Simple ethers are usually assigned common names. To do so, name both alkyl groups bonded to the oxygen, arrange these names alphabetically, and add the word ether. For symmetrical ethers, name the alkyl group and add the prefix di-. 

Symmetrical ether (Section 9.1) An ether with two identical alkyl groups bonded to the oxygen. 

The Williamson reaction, discovered in 1850, is still the best general method for the preparation of unsymmetrical or symmetrical ethers.The reaction can also be carried out with aromatic R, although C-alkylation is sometimes a side reaction (see p. 515). The normal method involves treatment of the halide with alkoxide or aroxide ion prepared from an alcohol or phenol, although methylation using dimethyl carbonate has been reported. It is also possible to mix the halide and alcohol or phenol directly with CS2CO3 in acetonitrile, or with solid KOH in Me2SO. The reaction can also be carried out in a dry medium,on zeolite-or neat or in solvents using microwave irradiation. Williamson ether synthesis in ionic liquids has also been reported. The reaction is not successful for tertiary R (because of elimination), and low yields are often obtained with secondary R. Mono-ethers can be formed from diols and alkyl halides. Many other... 

A number of symmetrical ethers containing the lower alkyl groups are prepared on a large scale, chiefly for use as solvents. The most important of these is... 

Name ethers that have two identical alkyl chains bonded to oxygen by first naming the alkyl group and then adding the word ether. Here are the names and structures of two of these symmetrical ethers. 

An equimolar mixture of methanol and ethanol would produce all three possible ethers. The difficulty in separating these compounds would preclude this method from being a practical route to any one of them. This method is practical only for symmetric ethers, that is, where both alkyl groups are identical. 

When an excess of the acid is applied, symmetrical alkyl ethers give the corresponding alkyl sulfonate as sole product, since the alcohol formed as intermediate is rapidly esterified this reaction is thus to be recommended for the preparation of alkyl sulfonates, though it should be noted that the water formed slows down the process the aryl-oxygen bond of alkyl aryl ethers is not broken, these compounds giving the alkyl sulfonate and the corresponding phenol. 

Ethers are compounds in which an oxygen is bonded to two alkyl substituents. If the alkyl substituents are identical, the ether is a symmetrical ether. If the substituents are different, the ether is an unsymmetrical ether. 

Some symmetrical ethers containing the lower alkyl groups may be prepared by reactions of the corresponding alcohols with sulfuric acid (H2SO1,). A water molecule is lost for every pair of alcohol molecules so that the reaction is termed dehydration. (Recall that alcohols Ccin be dehydrated also to alkenes. The conditions determine whether the alkene or ether results.) The dehydration to ethers is... 

Table 22.5 shows the structures and names of two of these symmetrical ethers, propyl ether and cyclohexyl ether. If the two alkyl groups are different, the groups are listed in alphabetical order and then followed by the word ether. Table 22.5 contains two examples of these asymmetrical ethers, butylethyl ether and ethylmethyl ether. 

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