Williamson ether synthesis: sodium ethoxide + 1-bromobutane → ethyl butyl ether
Ready to scaleSubstitutionSN2
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.
| Compound | Role | Equiv | MW (g/mol) | ρ (g/mL) | Safety |
|---|---|---|---|---|---|
| 1-Bromobutane109-65-9 · C4H9Br1-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 | DangerSDS |
| Sodium ethoxide141-52-6 · C2H5NaOSodium 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 | 68.05 | — | — |
| Dimethylformamide68-12-2 · C3H7NODMF — 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 | — | 73.09 | 0.940 | DangerSDS |
| Butyl ethyl ether628-81-9 · C6H14OEthyl 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 | — | 102.18 | — | Danger |