定义Definition
霍夫曼消除是胺经碘甲烷彻底甲基化为季铵盐，再与氧化银/水生成季铵碱，加热发生 E2 消除生成烯烃和三甲胺的反应。主要生成取代较少的烯烃（霍夫曼规则）。
In the Hofmann elimination an amine is exhaustively methylated with iodomethane to a quaternary ammonium salt, converted with silver oxide and water to the hydroxide, and heated to undergo E2 elimination to an alkene and trimethylamine. The less substituted alkene predominates (Hofmann rule).
霍夫曼规则Hofmann rule
体积大的 –NMe₃⁺ 离去基团使碱更易进攻位阻较小、酸性较强的 β-H，且过渡态偏“碳负离子”性质，所以生成取代较少的烯烃，与扎伊采夫规则相反。消除要求 H 与离去基团反式共平面。
The bulky –NMe₃⁺ leaving group steers the base to the less hindered, more acidic β-H, and the transition state has carbanion character, so the less substituted alkene forms — opposite to Zaitsev. Anti-periplanar geometry is required.
由来Origin
霍夫曼于 1851 年报道，19 世纪后期被广泛用于测定生物碱结构：反复甲基化–消除直到氮被除去，从而推断碳骨架。
Reported by Hofmann in 1851 and widely used in the late nineteenth century for alkaloid structure determination: repeated methylation–elimination removes nitrogen and reveals the carbon skeleton.
相关反应Related reactions
科普消除（胺氧化物的顺式热消除）同样得到取代较少的烯烃，条件更温和。
The Cope elimination (syn thermal elimination of amine oxides) also gives the less substituted alkene under milder conditions.
反应Reactions
过量 CH₃I；Ag₂O/H₂O 交换为氢氧化物；100–200 °C 加热
Excess CH₃I; Ag₂O/H₂O for the hydroxide; heat to 100–200 °C
彻底甲基化成季铵盐。
Exhaustive methylation to the quaternary salt.
Ag₂O 把 I⁻ 换成 OH⁻。
Ag₂O swaps iodide for hydroxide.
加热 E2 消除得霍夫曼烯烃。
Heating gives E2 elimination to the Hofmann alkene.
取代较少的烯烃为主。
The less substituted alkene dominates.
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.
OH⁻ 夺取 β-H，三甲胺离去（E2）
OH⁻ takes a β-H as trimethylamine leaves (E2)
大基团离去时，取代较少的烯烃为主（霍夫曼规则）
With a bulky leaving group the less substituted alkene dominates (Hofmann rule)
年表Timeline
- 1851
霍夫曼报道季铵碱热消除
Hofmann reports the thermal elimination of quaternary ammonium hydroxides