11.5:
Ethers to Alkyl Halides: Acidic Cleavage
Ethers are generally unreactive towards direct nucleophilic substitutions, as the resulting alkoxide ion is a strong base, and thus, a poor leaving group.
However, when heated with strong acids, such as hydrobromic or hydriodic acids, ethers get converted into alkyl halides.
Acidic cleavage of ethers is a typical nucleophilic substitution reaction. The type of nucleophilic substitution and the conditions required for the reaction depend on the nature of the alkyl groups bonded to oxygen.
Ethers with primary alkyl groups undergo acidic cleavage in the presence of excess hot concentrated acids by an SN2 mechanism.
The reaction mechanism begins with a proton transfer from the acid catalyst to the ether oxygen, forming an oxonium ion, a better leaving group.
Next, the halide ion acts as a nucleophile and attacks the less substituted carbon of the oxonium ion in an SN2 reaction, displacing alcohol and forming the first molecule of alkyl halide.
Excess hydriodic acid subjects the alcohol molecule to another round of SN2 reaction, forming a second molecule of alkyl halide.
Ethers with tertiary, allylic, or benzylic alkyl groups undergo acidic cleavage under mild conditions, such as moderate temperatures and dilute acids, by an SN1 mechanism.
For example, when ethyl tert-butyl ether reacts with dilute hydriodic acid, protonation of ether forms a stable tertiary carbocation with the loss of primary alcohol.
Finally, the tertiary carbocation reacts with the iodide ion by an SN1 mechanism, forming a tert-butyl iodide.
The reactivity of the halogen acids towards ether cleavage increases with the nucleophilicity of the halide ions.
Therefore, both hydriodic and hydrobromic acids readily cleave ethers. Hydrochloric acid is less efficient, and hydrofluoric acid does not cleave ethers.
11.5:
Ethers to Alkyl Halides: Acidic Cleavage
Ethers are generally unreactive and unsuitable for direct nucleophilic substitution reactions since the alkoxy groups are strong bases and, therefore, poor leaving groups. However, ethers readily undergo acidic-cleavage reactions. Ethers can be converted to alkyl halides when heated with strong acids such as HBr and HI in a sequence of two substitution reactions.
In the first step, the ether is converted into an alkyl halide and alcohol.
In the second step, the alcohol reacts with the excess HX acid to form another equivalent of an alkyl halide.
Acidic cleavage of ethers can occur either by the SN1 mechanism or SN2 mechanism, depending on the substrate. Ethers with primary and secondary alkyl groups as substrates react with the SN2 mechanism in which the nucleophile attacks the protonated ether at the less hindered site. Ethers with a tertiary, benzylic, or allylic group undergo the SN1 mechanism because the substrates can produce more stable intermediate carbocations. Reactivity of the halogen acids with ethers increases relative to the nucleophilicity of the halide ions. HI and HBr are more reactive, HCl is less efficient, and HF is unsuitable.