定义Definition
羟醛缩合是含 α-氢的醛或酮在酸或碱催化下，一分子的烯醇（负离子）加成到另一分子的羰基上生成 β-羟基醛或 β-羟基酮（羟醛加成），加热后进一步脱水生成 α,β-不饱和羰基化合物（羟醛缩合）。
In the aldol reaction an enol or enolate of an aldehyde or ketone with α-hydrogens adds to another carbonyl under acid or base catalysis to give a β-hydroxy aldehyde or ketone (aldol addition); heating dehydrates it to an α,β-unsaturated carbonyl (aldol condensation).
机理Mechanism
碱催化：OH⁻ 夺取 α-H 生成烯醇负离子，进攻另一分子羰基碳得醇盐，质子化为 β-羟基羰基化合物；加热时经 E1cB 机理失水，生成共轭烯酮。酸催化经烯醇进攻质子化的羰基。
Base: hydroxide forms the enolate, which attacks another carbonyl; protonation gives the β-hydroxy carbonyl, which on heating loses water by E1cB to the conjugated enone. Acid: the enol attacks a protonated carbonyl.
交叉与定向羟醛Crossed and directed aldols
两种都有 α-H 的醛混合会得到四种产物；用无 α-H 的醛（苯甲醛、甲醛）作受体可得单一交叉产物（克莱森–施密特缩合，如查耳酮合成）。用 LDA 在 −78 °C 定量生成指定烯醇锂、或用硼烯醇（埃文斯）可实现区域与立体选择的定向羟醛反应；脯氨酸、醛缩酶催化不对称羟醛反应。
Two enolisable aldehydes give four products; using a non-enolisable acceptor (benzaldehyde, formaldehyde) gives one crossed product (Claisen–Schmidt, e.g. chalcones). Pre-forming a lithium enolate with LDA at −78 °C or using boron enolates (Evans) gives regio- and stereocontrolled directed aldols; proline and aldolases catalyse asymmetric versions.
由来与意义Origin and significance
1872 年武尔茨和作曲家兼化学家博罗金独立发现。羟醛反应是构建 C–C 键与多羟基天然产物（大环内酯、聚酮）的核心反应；糖酵解中醛缩酶催化的逆羟醛反应把果糖-1,6-二磷酸裂解为两个三碳糖。
Discovered independently in 1872 by Wurtz and by the composer-chemist Borodin. The aldol is central to C–C bond formation and polyketide natural products (macrolides); in glycolysis aldolase runs a retro-aldol that splits fructose-1,6-bisphosphate into two trioses.
反应Reactions
稀 NaOH 或 KOH，0–25 °C 得羟醛；加热得 α,β-不饱和产物
Dilute NaOH or KOH at 0–25 °C for the aldol; heat for the enone
生成烯醇负离子。
Enolate formation.
亲核加成到另一分子羰基。
Addition to a second carbonyl.
质子化得 β-羟基羰基化合物。
Protonation gives the β-hydroxy carbonyl.
加热经 E1cB 脱水得烯酮/烯醛。
Heating dehydrates via E1cB.
克莱森–施密特交叉缩合。
Claisen–Schmidt crossed 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.
OH⁻ 夺取 α-H，生成烯醇负离子
OH⁻ removes an α-H to give the enolate
烯醇负离子的 α-碳进攻另一分子醛
The enolate α-carbon attacks a second aldehyde
质子化得 β-羟基醛；加热脱水得 α,β-不饱和醛
Protonation gives the β-hydroxy aldehyde; heating dehydrates it
巴豆醛（2-丁烯醛）
Crotonaldehyde (but-2-enal)
年表Timeline
- 1872
武尔茨与博罗金发现
Discovered by Wurtz and Borodin
- 1881
克莱森–施密特缩合
Claisen–Schmidt condensation
- 1981
埃文斯手性噁唑烷酮羟醛反应
Evans oxazolidinone aldol
- 2000
脯氨酸催化不对称羟醛（李斯特等）
Proline-catalysed asymmetric aldol (List and co-workers)