Ether cleavage
Ether cleavage refers to chemical substitution reactions that lead to the cleavage of ethers. The most common reagents used in ether cleavage are hydrohalic acids and certain organolithium compounds.
Contents
General
In organic chemistry, ether cleavage is an acid catalyzed nucleophilic substitution reaction. Depending on the specific ether, cleavage can follow either SN1 or SN2 mechanisms. Distinguishing between both mechanisms requires consideration of inductive and mesomeric effects that could stabilize or destabilize a potential carbocation in the SN1 pathway.[1]
SN1 ether cleavage is generally faster than SN2 ether cleavage. However, reactions that would require the formation of unstable carbocations (methyl, vinyl, aryl or primary carbon) proceed via SN2 mechanism. The hydrohalic acid also plays an important role, as the rate of reaction is greater with hydroiodic acid than with hydrobromic acid. Hydrochloric acid only reacts under more rigorous conditions. The reason lies in the higher acidity of the heavier hydrohalic acids as well as the higher nucleophilicity of the respective conjugate base. Fluoride is not nucleophilic enough to allow for usage of hydrofluoric acid to cleave ethers in protic media. Usage of hydrohalic acids takes advantage of the fact that these agents are able to protonate the ether oxygen atom and also provide a halide anion as a suitable nucleophile. However, as ethers show similar basicity as alcohols (pKa of approximately 16), the equilibrium of protonation lies on the side of the unprotonated ether and cleavage is usually very slow at room temperature.
Ethers can also be cleaved by strongly basic agents, such as organolithium compounds. While acyclic ethers are cleaved by said reagents, cyclic ethers are especially susceptible to cleavage, though the process occurs faster at room temperature and it's very slow at very low temperatures.
Mechanism
SN1 ether cleavage
Example: Methyl tert-butyl ether and hydrobromic acid
The unimolecular SN1 mechanism proceeds via a carbocation (provided that the carbocation can be adequately stabilized). In the example shown below, the oxygen atom in methyl tert-butyl ether is reversibly protonated. The resulting oxonium ion then decomposes into methanol and a relatively stable tert-butyl cation. The latter is then attacked by a nucleophile halide (in this case, bromide), yielding tert-butyl bromide.
SN2 ether cleavage
Example: Methyl n-propyl ether and hydrobromic acid
If the potential carbocation can not be stabilized, ether cleavage follows a bimolecular, concerted SN2 mechanism. In the example, the ether oxygen is reversibly protonated. The halide ion (here bromide) then nucleophilically attacks the sterically less hindered carbon atom, thereby forming methyl bromide and 1-propanol.
