Ether cleavage refers to chemical substitution reactions that lead to the cleavage ofethers. Due to the high chemical stability of ethers, the cleavage of the C-O bond is uncommon in the absence of specialized reagents or under extreme conditions.[1][2]
Inorganic chemistry, ether cleavage is an acid catalyzednucleophilic substitution reaction. Depending on the specific ether, cleavage can follow eitherSN1 orSN2 mechanisms. Distinguishing between both mechanisms requires consideration ofinductive andmesomeric effects that could stabilize or destabilize a potentialcarbocation in theSN1 pathway. Usage ofhydrohalic 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 suitablenucleophile. However, as ethers show similar basicity asalcohols (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 be cleaved by strongly basic agents, e.g. organolithium compounds. Cyclic ethers are especially susceptible to cleavage, but acyclic ethers can be cleaved as well.
Ethers cleave in polar, acidic solutions. Provided that acarbocation intermediate can be adequately stabilized, the cleavage occurs via theunimolecular SN1 mechanism. Otherwise (methyl,vinyl,aryl orprimary carbocations), it follows abimolecular,concerted SN2 mechanism.
The hydrohalic acid plays an important role in the reaction, as the rate of reaction increasesdown the period. The cause is both higher acidity and the highernucleophilicity of the respectiveconjugate base.Fluoride is not nucleophilic enough to cleave ethers in protic media,hydrochloric acid only reacts under rigorous conditions, andhydrobromic acid cleaves slower thanhydroiodic acid.
Regardless of which hydrohalic acid is used, the reaction is slow and requires heat.
In the example, the oxygen atom inmethyltert-butyl ether is reversibly protonated. The resultingoxonium ion then decomposes intomethanol and a relatively stabletert-butyl cation. The latter is attacked by a halide nucleophile (here bromide), yieldingtert-butyl bromide.
In the example, the ether oxygen is reversibly protonated. The halide ion (here bromide) then nucleophilically attacks the sterically less hindered carbon atom, thereby formingmethyl bromide and1-propanol.
Basic ether cleavage begins with deprotonation at the α position.[3] The ether then decomposes into analkene and analkoxide. Cyclic ethers allow for an especially quickconcerted cleavage, as seen forTHF:
Deprotonated, acyclic etherseliminate hydride at the β position, forming anolefinic ether. The resulting hydride then attacks the olefin at a position α to the ether oxygen, releasing the alkoxide.
Organometallic agents are often handled in ethereal solvents, which coordinate to the metallic centers and enhance the reactivity of the organic groups. Here, the ether cleavage poses a problem, as it decomposes the solvent and consumes the organometallic agent. Reactions with organometallic agents are therefore typically performed at low temperatures (-78 °C). At these temperatures, deprotonation occurs more slowly than the intended reactions.
