Reactions of Ethers Acidic Cleavage

Ethers are unreactive to many reagents used in organic chemistry, a prop erty that accounts for their wide use as reaction solvents. Halogens, dilub 

Alexander M. Butlerov (1828-1886) was born in Tschistopol, Russia, and received his Ph.D. in 1854 I the University of scow. His mother died ortly after giving birth, he was raised by his itcrna) grandfather, 

1854 to 1867, he i professor of chemistry the University of Kazan, Ifrom 1867 to 1880 f taught at the Univer- of St. Petersburg. His ny and varied interests I from bee-keeping to a llief in spiritualism. 

The first example of acid-induced ether cleavage was observed in 1861 by Alexander Butlerov, who found that 2-ethoxypropanoic acid reacts with aqueous HI at 100 C to yield iodoethane and lactic acid  

In addition to HI, aqueous HBr also works well, but HCl does not cleave ethers. 

How would you prepare the following ethers Use whichever method you think is more appropriate, the Williamson synthesis or the alkoxymercuration reaction. 

Rank the following halides in order of their reactivity in the Williamson synthesis  

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. In fact, ethers undergo only one truly general reaction—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 S l or Sn2 mechanisms depending on the stmcture 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 

Ethers with a tertiary, benzylic, or allylic group cleave by either an SnI or El mechanism because these substrates can produce stable intermediate carbo-cations. These reactions are often fast and take place at moderate temperatures. fert-Butyl ethers, for example, react by an El mechanism on treatment with trifluoroacetic acid at 0 °C. We ll see in Section 26.7 that the reaction is often used in the laboratory synthesis of peptides. 

Primary carbon compatible with Williamson method 

Alkene derived compatible with alkoxymercuration method 

1 Rank the following halides in order of their reactivity in the Williamson synthesis (a) Bromoethane, 2-bromopropanc, bromobenzene 1 (b) Chloroethane, bromoethane, 1-iodopropene 

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A commonly used and important reaction of sulfonic acids, or sulfonates, is their conversion to sulfonyl chlorides by treatment with phosphorus halides, or sometimes with thionyl chloride. Although it is easy to postulate mechanisms for this conversion, the exact path followed has never been determined. Similarly, although mechanisms can be suggested for other known reactions involving sulfonic acids, such as the cleavage of dialkyl ethers by anhydrous sulfonic acids (Klamann and Weyerstahl, 1965), or the formation of sulfones by treatment of an aromatic hydrocarbon with a mixture of sulfonic acid plus polyphosphoric acid (Graybill, 1967), nothing truly definitive is known about the details of the actual mechanisms of these reactions. 

Carboxylic acid anhydrides generally react with sulfur tetrafluoride in the same manner as carboxylic acids to give acid fluorides, then trifluoromethyl derivatives. Various cyclic anhydrides, which are particularly stable under acidic conditions, react without cleavage to give, in a stepwise fashion, difluoro lactones and a,a,a, a -tetrafluoro ethers. Conversely, the corresponding diacids are readily dehydrated by sulfur tetrafluoride to give anhydrides in the first step of the reaction. Therefore, in this section reactions of carboxylic acids and carboxylic acid anhydrides are discussed together. 

Acetyl chloride/methanol has often been employed by Hove for cleaving the silyl protecting group. Mechanistically one can postulate that reaction of the acid chloride with methanol leads to an ether solution of anhydrous hydrogen chloride, which then effects the cleavage. 

Alkyl esters are efficiently dealkylated to trimethylsilyl esters with high concentrations of iodotrimethylsilane either in chloroform or sulfolane solutions at 25-80° or without solvent at 100-110°.Hydrolysis of the trimethylsilyl esters serves to release the carboxylic acid. Amines may be recovered from O-methyl, O-ethyl, and O-benzyl carbamates after reaction with iodotrimethylsilane in chloroform or sulfolane at 50—60° and subsequent methanolysis. The conversion of dimethyl, diethyl, and ethylene acetals and ketals to the parent aldehydes and ketones under aprotic conditions has been accomplished with this reagent. The reactions of alcohols (or the corresponding trimethylsilyl ethers) and aldehydes with iodotrimethylsilane give alkyl iodides and a-iodosilyl ethers,respectively. lodomethyl methyl ether is obtained from cleavage of dimethoxymethane with iodotrimethylsilane. 

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