Nucleophilic Addition with HCN | 氢氰酸的亲核加成反应

📚 Nucleophilic Addition with HCN | 氢氰酸的亲核加成反应

Nucleophilic addition is a fundamental reaction type in organic chemistry, particularly for carbonyl compounds. This article explores the addition of hydrogen cyanide (HCN) to aldehydes and ketones to form hydroxynitriles (cyanohydrins). A clear grasp of this mechanism, its conditions, and the resulting stereochemistry is essential for Cambridge A-Level Chemistry students.

亲核加成是有机化学中一个基本的反应类型，对羰基化合物尤为重要。本文将探讨氢氰酸（HCN）与醛和酮的加成反应，生成羟腈（氰醇）。清晰掌握该反应的机理、条件以及由此产生的立体化学，对Cambridge A-Level化学学生至关重要。

1. Introduction to Nucleophilic Addition Reactions | 亲核加成反应简介

Nucleophilic addition involves the attack of a nucleophile on an electron-deficient carbon atom of a polar multiple bond, leading to a new sigma bond and breaking of a pi bond. The carbonyl group (C=O) is the classic electrophile in this context.

亲核加成是指亲核试剂进攻极性多重键中缺电子的碳原子，形成新的σ键并断裂π键。羰基（C=O）是这类反应中经典的亲电体。

In aldehydes and ketones, the nucleophile donates an electron pair to the electrophilic carbonyl carbon, generating a tetrahedral intermediate. This mechanism differs fundamentally from electrophilic addition observed in alkenes.

在醛和酮中，亲核试剂向亲电的羰基碳提供一对电子，生成四面体中间体。该机理与烯烃中观察到的亲电加成有着本质区别。

Typical nucleophiles include cyanide ions, hydride ions, and Grignard reagents. The addition of HCN serves as a model reaction for building carbon–carbon bonds and extending molecular frameworks.

常见的亲核试剂包括氰根离子、氢负离子和格氏试剂。HCN的加成反应是构建碳–碳键、扩展分子骨架的一个模型反应。

---

2. The Carbonyl Group: A Dipolar Bond | 羰基：偶极键

The carbonyl functionality consists of a carbon atom doubly bonded to an oxygen atom. Oxygen is more electronegative than carbon, pulling the π-electron cloud toward itself and creating a pronounced dipole: carbon bears a partial positive charge (δ+), oxygen a partial negative charge (δ-).

羰基由一个碳原子与一个氧原子以双键连接而成。氧的电负性大于碳，将π电子云拉向自身，产生显著的偶极：碳带有部分正电荷（δ+），氧带有部分负电荷（δ-）。

This polarisation renders the carbonyl carbon highly electrophilic and therefore susceptible to nucleophilic attack. The π bond is weaker than a typical σ bond and readily breaks under reaction conditions.

这种极化使得羰基碳具有高度亲电性，容易受到亲核进攻。π键比典型的σ键弱，在反应条件下容易断裂。

In aldehydes, the carbonyl carbon is attached to at least one hydrogen atom; in ketones, it is linked to two alkyl or aryl groups. This structural difference has direct consequences for reactivity, as discussed later.

在醛中，羰基碳至少连接一个氢原子；而在酮中，它连接两个烷基或芳基。这一结构差异对反应活性有直接影响，后文将予以说明。

---

3. Hydrogen Cyanide as a Nucleophile | 作为亲核试剂的氢氰酸

Hydrogen cyanide, HCN, is a weak acid (pKₐ ~9.2) that partially ionises in water to give H⁺ and the cyanide ion, CN⁻. The cyanide ion is the actual nucleophile: its carbon atom possesses a negative charge and a lone pair of electrons capable of forming new bonds.

氢氰酸（HCN）是一种弱酸（pKₐ ≈ 9.2），在水中部分电离生成H⁺和氰根离子（CN⁻）。氰根离子是真正的亲核试剂：其碳原子带有一个负电荷和一对能够形成新键的孤对电子。

The nucleophilic character of CN⁻ enables the direct formation of a carbon–carbon bond, making this addition a valuable strategy for lengthening a carbon chain. Because free HCN is an extremely poisonous gas (b.p. 26 °C), it is never handled in its pure form in school laboratories.

CN⁻的亲核特性使得它能够直接形成碳–碳键，使该加成成为延长碳链的一种重要策略。由于游离的HCN是毒性极强的气体（沸点26 °C），学校实验室从不直接使用其纯品。

Instead, HCN is generated in situ by adding a mineral acid (usually dilute H₂SO₄) to a sodium or potassium cyanide solution. This method maintains a low but steady concentration of HCN while keeping the cyanide ion concentration sufficiently high for the reaction.

取而代之的是，通过向氰化钠或氰化钾溶液中加入无机酸（通常为稀H₂SO₄）来现场制备HCN。该方法可维持低但稳定的HCN浓度，同时使氰根离子浓度足够高以驱动反应。

---

4. Generating HCN Safely in the Lab | 实验室安全制备HCN

The standard procedure involves dissolving the aldehyde or ketone and NaCN (or KCN) in a small volume of water or aqueous ethanol. Dilute sulfuric acid is then added dropwise while cooling the flask in an ice bath to control the exothermicity and minimise gaseous HCN release.

标准操作是将醛或酮与NaCN（或KCN）溶于少量水或乙醇水溶液中，然后在冰浴冷却下逐滴加入稀硫酸，以控制放热并尽量抑制HCN气体逸出。

The equilibrium H⁺ + CN⁻ ⇌ HCN is shifted to the right as acid is introduced, liberating HCN molecules. These molecules immediately react with the carbonyl compound, so the free HCN concentration remains very low. The pH is carefully maintained around 8–9 during the addition to prevent rapid evolution of toxic gas.

随着酸的加入，平衡H⁺ + CN⁻ ⇌ HCN向右移动，释放出HCN分子。这些分子立即与羰基化合物反应，因此游离HCN浓度保持在极低水平。加酸过程中需将pH小心维持在8–9左右，以防有毒气体急剧逸出。

The entire experiment must be conducted in a well-functioning fume hood. Cyanide salts are also highly toxic, and any waste must be treated with an oxidising agent (such as bleach) before disposal. Good laboratory practice includes wearing appropriate personal protective equipment at all times.

整个实验必须在功能良好的通风橱中进行。氰化物盐同样有剧毒，所有废料在处置前必须用氧化剂（如漂白剂）处理。良好的实验规范包括始终穿戴适当的个人防护装备。

---

5. Step 1: Nucleophilic Attack by Cyanide Ion | 第一步：氰离子的亲核进攻

The mechanism occurs in two distinct steps. In the first, rate-determining step, the lone pair on the carbon atom of CN⁻ attacks the electrophilic carbonyl carbon. As the new C–C bond begins to form, the π electrons of the C=O bond move completely onto the oxygen, converting the oxygen into a negatively charged alkoxide ion.

该机理分为两个明确的步骤。第一步为速率决定步骤，CN⁻碳上的孤对电子进攻亲电的羰基碳。随着新C–C键开始形成，C=O键的π电子完全转移到氧上，使氧转变为带负电的氧负离子。

The carbonyl carbon undergoes rehybridisation from sp² to sp³, yielding a tetrahedral intermediate in which the cyanide group, the original oxygen (now O⁻), and the other substituents are all attached to a central carbon atom.

羰基碳从sp²杂化变为sp³杂化，生成一个四面体中间体，其中氰基、原氧原子（现为O⁻）以及其他取代基均连接在中心碳原子上。

This step is reversible in principle, but the reaction is driven forward by the excess of cyanide ions present and by the rapid protonation that follows. The tetrahedral alkoxide is a strong base and will quickly accept a proton in the second step.

此步原则上可逆，但反应被过量的氰根离子与后续快速的质子化所推动。四面体氧负离子是一种强碱，将在第二步中迅速接受一个质子。

---

6. Step 2: Protonation to Form the Hydroxynitrile | 第二步：质子化生成羟腈

The alkoxide intermediate, structure R₂C(O⁻)CN, is protonated by a proton source present in the mixture. Protons may be supplied by undissociated HCN, hydronium ions from the added acid, or water. The negatively charged oxygen picks up a proton, becoming a neutral –OH group.

氧负离子中间体（R₂C(O⁻)CN）被反应混合物中的质子源所质子化。质子可由未电离的HCN、所加酸产生的水合氢离子或水提供。带负电的氧结合一个质子，转变为中性的–OH基团。

This gives the final product, a hydroxynitrile, commonly referred to as a cyanohydrin. The overall transformation converts a planar carbonyl into a tetrahedral carbon bearing both a hydroxyl and a cyano group.

这样就得到了最终产物——羟腈，通常称为氰醇。总体转化将平面的羰基转变为带有一个羟基和一个氰基的四面体碳。

If the carbonyl starting material is unsymmetrical (for example, ethanal or an asymmetrical ketone), the product contains a chiral centre. Since the nucleophilic attack can occur from either face of the planar carbonyl with equal probability, the product is formed as a racemic mixture of two enantiomers.

如果起始羰基化合物是不对称的（例如乙醛或不对称酮），产物将含有一个手性中心。由于亲核进攻可以从平面羰基的任何一面以相同概率发生，产物会以两种对映体的外消旋混合物形式生成。

---

7. The Overall Reaction Equation | 总反应方程式

The general reaction for an aldehyde is: RCHO + HCN → RCH(OH)CN. For a ketone: RR′CO + HCN → RR′C(OH)CN, where R and R′ represent alkyl or aryl groups. The product is named as a hydroxynitrile, with the carbon chain numbered to give the –OH and –CN substituents the lowest possible locants.

醛的总反应式为：RCHO + HCN → RCH(OH)CN。酮的总反应式为：RR′CO + HCN → RR′C(OH)CN，其中R和R′代表烷基或芳基。产物以羟腈命名，编号碳链以使–OH和–CN取代基获得尽可能小的位号。

For a concrete example, propanal (CH₃CH₂CHO) reacts with HCN to yield 2-hydroxybutanenitrile, CH₃CH₂CH(OH)CN. Similarly, propanone (CH₃COCH₃) yields 2-hydroxy-2-methylpropanenitrile, (CH₃)₂C(OH)CN.

举个具体例子，丙醛（CH₃CH₂CHO）与HCN反应生成2-羟基丁腈，CH₃CH₂CH(OH)CN。同样，丙酮（CH₃COCH₃）生成2-羟基-2-甲基丙腈，(CH₃)₂C(OH)CN。

No additional catalyst is required beyond the base inherently present from the cyanide salt. The reaction proceeds smoothly at room temperature and typically reaches completion within minutes for most aldehydes.

除氰化物盐本身固有的碱性外，无须额外催化剂。该反应在室温下平稳进行，对大多数醛通常在数分钟内即可完成。

Published by TutorHao | A-Level Chemistry Revision Series | aleveler.com

更多咨询请联系16621398022（同微信）