Part of JOC-05 — Alcohols, Phenols & Ethers

Williamson Synthesis and Ether Preparation

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Williamson synthesis (RONa + R'X -> R-O-R') is the most important ether preparation method. The mechanism is SN2, which imposes a critical constraint: R'X must be primary (or methyl). Secondary halides give mixed results (some elimination). Tertiary halides give exclusively elimination — no ether formed.

Strategy for mixed ethers: always use the more hindered group as the alkoxide and the less hindered as the halide. To make (CH3)3C-O-CH3: use (CH3)3CONa + CH3I (correct). NOT CH3ONa + (CH3)3CBr (gives alkene).

Alternative: acid-catalysed dehydration of 1° alcohols (2ROH + H2SO4, 140°C -> R-O-R + H2O). Limitations: only symmetric ethers, only from primary alcohols, and the competing elimination at higher temperature.

For diaryl ethers, standard Williamson fails (aryl halides resist SN2). The Ullmann synthesis (ArX + ArONa, Cu catalyst) is used instead.

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