定义Definition
霍夫曼重排是伯酰胺在溴（或次氯酸钠）和强碱作用下，经异氰酸酯中间体转化为少一个碳原子的伯胺并放出 CO₂ 的反应。
The Hofmann rearrangement converts a primary amide, with bromine (or hypochlorite) and strong base, into a primary amine with one carbon fewer via an isocyanate, releasing CO₂.
机理Mechanism
碱使酰胺 N–H 去质子化后被溴化得 N-溴酰胺；再去质子化得负离子，R 基带着电子对从羰基碳迁移到氮上，同时 Br⁻ 离去，生成异氰酸酯 R–N=C=O（迁移基团构型保持）；异氰酸酯水解得氨基甲酸，脱羧得伯胺。
Base and bromine give the N-bromoamide; its anion undergoes migration of R from carbon to nitrogen as Br⁻ leaves, forming the isocyanate R–N=C=O with retention of configuration; hydrolysis gives a carbamic acid that loses CO₂ to the amine.
由来Origin
德国化学家奥古斯特·威廉·冯·霍夫曼于 1881 年报道。同属“经异氰酸酯降解”的还有库尔提斯重排（酰基叠氮）、洛森重排（异羟肟酸）和施密特反应。
Reported by August Wilhelm von Hofmann in 1881. Related isocyanate-forming degradations are the Curtius (acyl azides), Lossen (hydroxamic acids) and Schmidt reactions.
应用Applications
用于由羧酸衍生物制备少一碳的胺，例如邻苯二甲酰亚胺 → 邻氨基苯甲酸（染料工业）、烟酰胺 → 3-氨基吡啶。在醇中进行时异氰酸酯被捕获为氨基甲酸酯。
Used to make amines one carbon shorter, e.g. phthalimide → anthranilic acid (dyes) and nicotinamide → 3-aminopyridine. In alcohols the isocyanate is trapped as a carbamate.
反应Reactions
Br₂/NaOH 水溶液或 NaOCl，0 °C 后加热至 70–80 °C
Br₂/NaOH(aq) or NaOCl, 0 °C then warm to 70–80 °C
N-溴化生成 N-溴酰胺。
N-Bromination.
去质子化后 R 迁移到 N 并失去 Br⁻，生成异氰酸酯。
Deprotonation, R migration to N and loss of Br⁻ give the isocyanate.
异氰酸酯水解、脱羧得伯胺。
Hydrolysis and decarboxylation give the amine.
苯甲酰胺转化为苯胺。
Benzamide to aniline.
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.
NaOBr 先把酰胺变成 N-溴酰胺，OH⁻ 再夺取 N–H
NaOBr makes the N-bromoamide; OH⁻ then removes the N–H
R 带着电子对迁移到 N 上，同时 Br⁻ 离去
R migrates to N with its electron pair as Br⁻ leaves
异氰酸酯被水（OH⁻）进攻
Water (OH⁻) attacks the isocyanate
氨基甲酸，不稳定
A carbamic acid, unstable
甲胺：比原料少一个碳
Methylamine — one carbon fewer
年表Timeline
- 1881
霍夫曼报道该重排
Hofmann reports the rearrangement
- 1890
库尔提斯报道酰基叠氮重排
Curtius reports the acyl azide rearrangement