Acid-catalyzed cleavage of ethers

Just as the carbon-oxygen bond of alcohols is cleaved on reaction with hydrogen halides (Section 4.8), so too is an ether hnkage broken  

The cleavage of ethers is normally carried out under conditions (excess hydrogen halide, heat) that convert the alcohol formed as one of the original products to an alkyl halide. Thus, the reaction typically leads to two alkyl halide molecules  

PROBLEM 16.9 A series of dialkyl ethers was allowed to react with excess hydrogen bromide, with the following results. Identify the ether in each case. 

SAMPLE SOLUTION (a) In the reaction of dialkyl ethers with excess hydrogen bromide, each alkyl group of the ether function is cleaved and forms an alkyl bromide. Since bromocyclopentane and 1-bromobutane are the products, the starting ether must be butyl cyclopentyl ether. 

Step 1 Proton transfer to the oxygen of the ether to give a dialkyloxonium ion. CH3CH2 

The reaction follows a free-radical mechanism and gives a hydroperoxide, a compound of the type RCX)H. Hydroperoxides are unstable and shock-sensitive and form related peroxidic derivatives that are prone to violent decomposition. Air oxidation leads to peroxides within a few days if ethers are even briefly exposed to atmospheric oxygen. For this reason, one should never use old bottles of dialkyl ethers, and extreme care must be exercised in their disposal. 

The order of hydrogen halide reactivity is HI HBr HCl. Hydrogen fluoride is 

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The principal mechanism of polymer degradation during aging is the acid-catalyzed cleavage of the ether linkage in the backbone. The acid acceptor. 

Acid catalyzed cleavage of aromatic methyl or ethyl ethers Quantitative methoxy group determination Also ether cleavage with tnmethylsilyl Iodide ... 

Write the mechanism of the acid-catalyzed cleavage of tert-butyl cyclohexyl ether to yield cyclohexanol and 2-methylpropene. 

Notice that this reaction is the reverse of acid-catalyzed cleavage of a tertiary ether (Problem 18.8). 

In analogy to the preparation of iminium salts, thiocarbenium ions (115) can be created by treatment of carbonyl compounds (1) with thiols," by alkylating (or Lewis acid catalyzed) cleavage of dithioace-tals U14) or by protonation of vinyl sulfides (thio enol ethers) (116 Scheme 55)." ... 

The acid-catalyzed cleavage of acetals occurs much more readily than the acid-catalyzed cleavage of simple ethers (Sec. 8.6) because the intermediate carbocation is resonance stabilized. However, acetals, like ordinary ethers, are stable toward bases. 

Acid-Catalyzed Cleavage of a Dialkyl Ether (Section ii.sa)... 

Acid-Catalyzed Cleavage of Dialkyl Ethers (Section 11.5A) Cleavage of ethers requires both a strong acid and a good nucleophile, hence the use of concentrated HBr and HI. 

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. 

The reaction of monodeprotonated [ C2]acetylene with carbonyl compounds has been exploited as a means of extension of the carbon chain of various terpenes and steroids by two [ " C]carbon atoms. In the simplest case, reaction of potassium [ C2]acetylide with steroid ketone 1 and subsequent acid catalyzed cleavage of the enol ether protecting group gave 17a-[ C2]ethynyltestosterone (2). The sequential addition of deprotonated [ C2]acetylene to carbonyl compounds opens access to symmetrical or unsymmetrical [2,3- C2]alkyn-l,4-diols is exemplified in the synthesis of all-tran -/3-[15,15 - C2]-carotene ([ C2]provitamin A). Thus, treatment of lithium [ C2]acetylide with terpene aldehyde 2 followed by double deprotonation of the resultant alkynol 4 and reaction with a second equivalent of 3 provided alkyne-l,4-diol 5 the requisite key intermediate. Subsequent acid-catalyzed dehydration of 5 followed by Lindlar s catalyst-mediated partial hydrogenation and photoisomerization afforded the final product". ... 

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