定义Definition
威廉姆森醚合成是醇钠（醇盐）或酚钠作为亲核试剂，与伯卤代烷（或磺酸酯）发生 SN2 取代生成醚的反应，可制备对称和不对称醚。
The Williamson ether synthesis forms an ether by SN2 reaction of an alkoxide or phenoxide with a primary alkyl halide (or sulfonate); it gives both symmetrical and unsymmetrical ethers.
选择底物Choosing partners
因为是 SN2，烷基化试剂应为甲基或伯卤代烷；醇盐既是亲核试剂也是强碱，与仲、叔卤代烷主要发生 E2 消除。所以制叔丁基甲基醚应用叔丁醇钠 + 碘甲烷，而不是甲醇钠 + 叔丁基氯。芳基醚须由酚盐与卤代烷制得（芳基卤不发生 SN2）。
Being SN2, the electrophile should be methyl or primary; alkoxides are strong bases and mainly cause E2 with secondary or tertiary halides. So make tert-butyl methyl ether from sodium tert-butoxide + iodomethane, not methoxide + tert-butyl chloride. Aryl ethers must come from phenoxides plus alkyl halides.
由来与意义Origin and significance
英国化学家亚历山大·威廉姆森于 1850 年报道。他用乙醇钾与碘乙烷制得乙醚，并证明乙醚分子含两个乙基，有力支持了“醚是水的类型”的结构理论和正确的原子量体系。
Reported by the British chemist Alexander Williamson in 1850. Making diethyl ether from potassium ethoxide and iodoethane showed that ether contains two ethyl groups, supporting the ‘water type’ theory and correct atomic weights.
现代条件Modern conditions
常用 NaH 在 THF 或 DMF 中生成醇盐；相转移催化（季铵盐）适合酚类；分子内反应可合成环醚（如环氧化物、四氢呋喃）。
NaH in THF or DMF is commonly used to make the alkoxide; phase-transfer catalysts suit phenols; intramolecular versions make cyclic ethers such as epoxides and THF rings.
反应Reactions
醇 + Na 或 NaH 生成醇钠，再加伯卤代烷，THF/DMF，室温至回流
Alcohol + Na or NaH to form the alkoxide, then a primary halide in THF/DMF, room temperature to reflux
醇被强碱去质子化。
The alcohol is deprotonated.
醇氧负离子背面进攻卤代烷碳（SN2）。
The alkoxide attacks the halide carbon from the back (SN2).
卤离子离去，生成醚。
Halide departs to give the ether.
制备苯甲醚。
Preparation of anisole.
反应机理图Mechanism
红色弯箭头表示一对电子的移动方向：从电子来源（孤对电子或化学键）指向电子去向。Red curly arrows show where an electron pair moves: from its source (lone pair or bond) to its destination.
醇钠的氧负离子按 SN2 进攻伯卤代烃
The alkoxide attacks a primary halide by SN2
甲乙醚
Ethyl methyl ether
年表Timeline
- 1850
威廉姆森报道醚合成
Williamson reports the ether synthesis