定义Definition
柯尔贝-施密特反应是酚钠在加热加压下与二氧化碳反应，在羟基邻位引入羧基，酸化后得到水杨酸的反应；用酚钾时主要得到对羟基苯甲酸。
The Kolbe–Schmitt reaction carboxylates sodium phenoxide with carbon dioxide under heat and pressure, placing a carboxyl group ortho to the hydroxyl; acidification gives salicylic acid. With potassium phenoxide the para isomer predominates.
机理Mechanism
酚氧负离子使苯环高度富电子，弱亲电试剂 CO₂ 进攻邻位。钠离子同时与酚氧和 CO₂ 配位，形成有利于邻位进攻的螯合过渡态；随后芳构化（质子转移）得到水杨酸盐。较大的 K⁺ 螯合作用弱，热力学更稳定的对位产物增多。
The phenoxide makes the ring very electron-rich, so the weak electrophile CO₂ attacks the ortho position. Na⁺ coordinates both the phenoxide oxygen and CO₂, giving a chelated transition state that favours ortho attack; rearomatisation by proton transfer gives the salicylate. The larger K⁺ chelates less, so the thermodynamically favoured para product increases.
由来Origin
赫尔曼·柯尔贝于 1860 年用酚钠与 CO₂ 制得水杨酸；1885 年鲁道夫·施密特改为在压力下反应，大幅提高了产率，奠定了工业化基础。
Hermann Kolbe made salicylic acid from sodium phenoxide and CO₂ in 1860; in 1885 Rudolf Schmitt ran it under pressure, greatly raising the yield and making it industrial.
工业意义Industrial importance
该反应是工业生产水杨酸的方法，水杨酸再乙酰化即得阿司匹林。对羟基苯甲酸则用于生产对羟基苯甲酸酯类防腐剂和液晶聚合物。
It is the industrial route to salicylic acid, which is acetylated to aspirin. p-Hydroxybenzoic acid is used for paraben preservatives and liquid-crystal polymers.
反应Reactions
约 125 °C，约 100 atm CO₂，干燥酚钠；最后用硫酸酸化
About 125 °C and 100 atm CO₂ with dry sodium phenoxide, then acidification with sulfuric acid
苯酚与 NaOH 生成酚钠并彻底干燥。
Phenol and NaOH give sodium phenoxide, which is dried thoroughly.
CO₂ 在 Na⁺ 螯合辅助下进攻邻位碳。
CO₂ attacks the ortho carbon assisted by Na⁺ chelation.
质子转移恢复芳香性，生成水杨酸钠。
Proton transfer restores aromaticity to give sodium salicylate.
酸化析出水杨酸。
Acidification precipitates salicylic acid.
钾盐主要得对位产物。
The potassium salt gives mainly the para product.
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.
酚氧负离子的邻位进攻 CO₂（Na⁺ 螯合使邻位优先）
The phenoxide attacks CO₂ at the ortho carbon (Na⁺ chelation favours ortho)
非芳香中间体
Non-aromatic intermediate
水杨酸根
Salicylate
水杨酸
Salicylic acid
年表Timeline
- 1860
柯尔贝首次合成水杨酸
Kolbe first synthesises salicylic acid this way
- 1885
施密特改进为加压反应
Schmitt introduces the pressurised process
- 1897
拜耳公司由水杨酸制得阿司匹林
Bayer makes aspirin from salicylic acid