Ether cleavage with HBr

It was synthesized from p-iodoanisole (65) by copper-catalyzed coupling with p-trifluoromethyliodobenzene (66) to give the expected statistical mixture from which unsymmetrical product 67 could be separated. Ether cleavage with HBr and HOAc gave 68 this was then alkylated with the aziridinium ion derived from N-(2-chloroethyl)pyrrolidine, using NaH as base, to complete the synthesis of boxidine (69). 

Esterification, crotonic acid, 149 levulinic acid, 157 thiophene-2-carboxylic acid, 182 o-toluic acid, 162 Ester interchange, 152 Ethanolysis of ethyl iminoacetate, 159 Ether cleavage with HBr, 271... 

Hydride Reduction of a Carbonyl Group 454 Reaction of a Tertiary Alcohol with HBr(S[ 1) 480 Reaction of a Primary Alcohol with HBr (SN2) 480 Reaction of Alcohols with PBr3 485 (Review) Acid-Catalyzed Dehydration of an Alcohol 487 The Pinacol Rearrangement 495 Cleavage of an Ether by HBr or HI 639 Acid-Catalyzed Opening of Epoxides in Water 649 Acid-Catalyzed Opening of an Epoxide in an Alcohol Solution 650... 

HX first protonates the oxygen atom, and halide then effects a nucleophilic displacement to form an alcohol and an organic halide. The better the nucleophile, the more effective the displacement. Since I- and Br- are better nucleophiles than Cl-, ether cleavage proceeds more smoothly with HI or HBr than with HC1. 

The cleavage of ethers by HI or HBr occurs more rapidly if the reaction can take place by an S l pathway. If the instability of the carbocation requires the reaction to follow an Sn2 pathway, cleavage will be more rapid with HI than with HBr because F... 

Iodide and bromide ions are good nucleophiles but weak bases, so they are more likely to substitute by the Sn2 mechanism than to eliminate by the E2 mechanism. Mechanism 14-1 shows how bromide ion cleaves the protonated ether by displacing an alcohol. In most cases, the alcohol reacts further with HBr to give the alkyl bromide (see Section 11-7). The reaction of cyclohexyl ethyl ether with HBr is an example of this displacement. The cyclohexanol produced by the cleavage reacts further with HBr, and the final products are ethyl bromide and bromocyclohexane. 

CH3OH) across the carbon-carbon double bond of crotonic acid [( )-2-butenoic acid] followed by potassium bromide treatment of the initial adduct to yield the corresponding mercuric bromide and then the formation of 2-bromo-3-methoxybutanoic acid by the addition of bromine (Br2) to the latter. Acidification to the free acid, followed by amination (NH3), formylation with the equivalent of acetic-formic anhydride, hydrogen bromide (HBr) ether cleavage, and a final pH adjustment with ammonium hydroxide produced the desired amino acid. 

Ether cleavage forms only a substitution product because any alkene that would be formed in an elimination reaction would undergo electrophilic addition with HBr or HI to form the same alkyl halide that is obtained from the substitution reaction. 

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). 

The order of reactivity of hydrogen halides is as follows HI > HBr > HCl. The cleavage of ethers takes place with concentrated HI or HBr at high temperature. 

Cleavage of ethers with HI or HBr 0-70 Cleavage of carboxylic esters with Lil... 

Entry 9 in Table 3.13 is an example of a safety-catch linker, which requires activation by TFA-mediated cleavage of a tert-butyl ether. The unactivated 2-(tm-butoxyj-phenyl esters are cleaved by amines 700 times more slowly than the corresponding 2-hydroxyphenyl esters [289]. A similar linker has been described [290], in which a benzyl ether is used instead of a ferf-butyl ether. Activation of this linker by debenzy-lation was achieved by treatment with HF or HBr/TFA [290]. 

When perfluoro-2-methylpent-2-ene reacts with glycidol, the initially formed product is vinyl ether 38, whose epoxide ring opens under the action of mineral acids (8% HBr, 33% HC1). Alcohol 39 formed in the course of ring cleavage is readily cyclized into 1,3-dioxolane 40 in the presence of catalytic amounts of NEt3. 

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