Williamson ether synthesis: sodium ethoxide + 1-bromobutane → ethyl butyl ether

Substitution SN2

Et–O⁻ Na⁺ + n-Bu–Br → Et–O–Bu + NaBr↓

Textbook SN2 ether-formation. Sodium ethoxide (typically generated in situ from NaH + EtOH or used as a solid) attacks the primary alkyl bromide via backside attack; the bromide leaves as NaBr, precipitating from DMF as the reaction advances. Primary substrates only — secondary alkyl halides give E2 elimination at these conditions because the alkoxide is sterically demanding.

Conditions: Generate the alkoxide: under N2, suspend NaH (60% in mineral oil, 1.05 equiv) in dry DMF (~3 mL per mmol substrate). Add ethanol (1.05 equiv) dropwise — vigorous H2 evolution; control addition rate. Once H2 stops, add 1-bromobutane (1.0 equiv) via syringe. Stir at 50–80 °C for 6–24 h until starting material is consumed (TLC). NaBr precipitates as a fine white solid. Workup — Quench with sat. NH4Cl; partition into Et2O / water; wash organic with water + brine; dry MgSO4; concentrate. Distil at atmospheric pressure (bp 92 °C) to isolate. Substrate-scope reminder: Williamson works ONLY for primary alkyl halides.

Expected yield: 70–88 %
Expected duration: 6–24 h at 50–80 °C after in-situ alkoxide generation

Reagents

Reagents involved in Williamson ether synthesis: sodium ethoxide + 1-bromobutane → ethyl butyl ether, grouped by role.
Reagent	Role	Equiv	MW	ρ
109-65-9 109-65-9 · C4H9Br 1-Bromobutane — limiting reagent; primary alkyl bromide is the textbook substrate. Distil before use to remove HBr and any 2-bromobutane impurity. Switching to the iodide (1-iodobutane) accelerates the SN2 ~10x but invites side reactions; the bromide is the safer bet.	reactant	1.0	137.02	1.270
Sodium Ethoxide 141-52-6 · C2H6NaO Sodium ethoxide — nucleophile. Often generated in-situ from NaH + EtOH (cleaner than the commercial solid which absorbs CO2 + moisture). Slight excess to drive the SN2 to completion.	reactant	1.05	69.06	0.870
68-12-2 68-12-2 · C3H7NO DMF — polar aprotic, stabilises the alkoxide free of H-bond donor that would protonate it. DMSO is an alternative; THF works if the alkoxide is generated in situ but slows the SN2.	solvent	—	73.10	0.940
628-81-9 628-81-9 · C6H14O Ethyl butyl ether — colourless liquid, bp 92 °C; ethereal smell; pungent at high concentrations. Dry over 4 Å sieves for use as an anhydrous solvent in subsequent steps.	product	1.0	102.18	—

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