Part of JOC-05 — Alcohols, Phenols & Ethers

Ether Cleavage and Reactivity

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Ethers are relatively inert but can be cleaved by strong acids (HI > HBr >> HCl).

Mechanism of cleavage: (1) Protonation of ether oxygen (forms oxonium ion). (2) Nucleophilic attack by halide on one alkyl group. For simple ethers with limited HI: I- attacks the less hindered carbon (SN2). For ethers with a tertiary group: SN1 — the 3° carbocation forms and is captured by I-.

With excess HI, both alkyl groups become alkyl iodides: R-O-R' + 2HI -> RI + R'I + H2O.

Special case — anisole + HI: Only the CH3-O bond breaks (CH3I + C6H5OH). The aryl C-O bond has partial double-bond character and is too strong for HI to cleave.

Zeisel's method exploits this cleavage: ether + HI -> CH3I; then CH3I + AgNO3 -> AgI (yellow precipitate). This detects and quantifies methoxy groups in organic compounds. Ethers also form explosive peroxides with air (O2 + light), which is why they must be stored carefully and tested before distillation.

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