双语化学辞典Chem Lexicon
反应 · 有机化学 · 羰基缩合 Organic chemistry · Carbonyl condensations

克莱森缩合Claisen condensation

拼音Pinyin kè lái sēn suō hé　别名Also 克莱森酯缩合； Claisen ester condensation

定义Definition

克莱森缩合是两分子酯（或酯与另一羰基化合物）在醇钠等强碱作用下缩合，生成 β-酮酸酯并失去一分子醇的反应。

The Claisen condensation joins two esters (or an ester and another carbonyl compound) under a strong base such as sodium ethoxide to form a β-keto ester with loss of an alcohol.

机理Mechanism

醇钠夺取酯 α-H 生成烯醇负离子；它进攻另一分子酯羰基，形成四面体中间体，消除烷氧负离子得 β-酮酸酯。产物两个羰基之间的 α-H 酸性强（pKa ≈ 11），被醇钠完全去质子化，这一步不可逆，推动平衡；最后酸化得产物。因此需要化学计量的碱，且酯至少要有两个 α-H。

Ethoxide forms the ester enolate, which attacks a second ester; the tetrahedral intermediate expels alkoxide to give the β-keto ester. Its doubly activated α-H (pKa ≈ 11) is removed irreversibly by ethoxide, driving the equilibrium; acidification gives the product. Hence a stoichiometric base is needed and the ester must have two α-H.

由来Origin

德国化学家路德维希·克莱森于 1887 年报道。分子内版本称迪克曼缩合；交叉克莱森缩合需一个组分无 α-H（如甲酸酯、苯甲酸酯、草酸酯、碳酸酯）。

Reported by the German chemist Ludwig Claisen in 1887. The intramolecular version is the Dieckmann condensation; crossed Claisen reactions need one partner without α-H (formates, benzoates, oxalates, carbonates).

应用Applications

乙酰乙酸乙酯（由乙酸乙酯自缩合得到）是乙酰乙酸乙酯合成法的原料，可经烷基化、水解脱羧制备甲基酮。生物体内脂肪酸合成与降解中的硫酯缩合也属于克莱森型反应。

Ethyl acetoacetate (from self-condensation of ethyl acetate) underpins the acetoacetic ester synthesis of methyl ketones via alkylation, hydrolysis and decarboxylation. Thioester condensations in fatty-acid biosynthesis and degradation are biological Claisen reactions.

反应Reactions

2 CH3CO2Et NaOEt; H3O+⟶ CH3COCH2CO2Et + EtOH

NaOEt/EtOH（碱与酯的烷氧基一致，避免酯交换），回流；酸化后处理

NaOEt in EtOH (matching alkoxide to avoid transesterification), reflux; acidic work-up

  1. 生成酯烯醇负离子。

    Ester enolate formation.

  2. 亲核加成到第二分子酯羰基。

    Addition to a second ester.

  3. 消除烷氧负离子得 β-酮酸酯。

    Loss of alkoxide gives the β-keto ester.

  4. 产物去质子化（驱动力），最后酸化。

    Deprotonation of the product drives the reaction; acidify at the end.

2 乙酸乙酯 ⟶ 乙酰乙酸乙酯2 Ethyl acetate ⟶ Ethyl acetoacetate

经典自缩合。

Classic self-condensation.

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.

1

乙醇钠夺取酯的 α-H，生成烯醇负离子

Ethoxide removes an α-H of the ester, giving the enolate

2

烯醇负离子进攻另一分子酯的羰基

The enolate attacks the carbonyl of a second ester

3

四面体中间体赶走乙氧负离子

The tetrahedral intermediate expels ethoxide

4

乙酰乙酸乙酯；它被去质子化，推动平衡，最后酸化

Ethyl acetoacetate; its deprotonation drives the equilibrium, then acid work-up

年表Timeline

  • 1887

    克莱森报道酯缩合

    Claisen reports the ester condensation

  • 1894

    迪克曼报道分子内版本

    Dieckmann reports the intramolecular version