Reactions of the Amides | 酰胺的反应

📚 Reactions of the Amides | 酰胺的反应

Amides are organic compounds containing the carbonyl group bonded to a nitrogen atom, written as RCONH₂ for primary amides. This article reviews the principal reactions of amides covered in Cambridge A Level Chemistry, including hydrolysis, reduction, dehydration and the Hofmann rearrangement, together with the conditions and products for each transformation.

酰胺是一类含有与氮原子相连的羰基的有机化合物，伯酰胺可写作 RCONH₂。本文梳理剑桥 A Level 化学中考到的酰胺主要反应，包括水解、还原、脱水以及霍夫曼重排，并给出各反应的条件和产物。

1. Structure and General Reactivity of Amides | 酰胺的结构与一般反应性

In an amide, the carbonyl carbon is bonded directly to a nitrogen atom, as in CH₃CONH₂ (ethanamide). The nitrogen lone pair can delocalise into the C=O π system, giving the C–N bond partial double-bond character. This resonance stabilises the amide and makes the carbonyl carbon much less electrophilic than in acyl chlorides, acid anhydrides or esters.

在酰胺中，羰基碳直接与氮原子相连，例如 CH₃CONH₂（乙酰胺）。氮上的孤对电子可以离域到 C=O 的 π 体系中，使 C–N 键具有部分双键性质。这种共振稳定了酰胺，使其羰基碳的亲电性远低于酰氯、酸酐或酯。

Because the amide group is planar and resonance-stabilised, amides require more vigorous conditions for nucleophilic addition–elimination reactions. The key reactions of amides are therefore acid-catalysed hydrolysis, base-catalysed hydrolysis, reduction using LiAlH₄, dehydration to nitriles and, for primary amides, the Hofmann degradation.

由于酰胺基团是平面结构并受共振稳定，酰胺的亲核加成–消除反应需要更剧烈的条件。因此，酰胺的关键反应包括酸催化水解、碱催化水解、用 LiAlH₄ 还原、脱水生成腈，以及伯酰胺的霍夫曼降解。

2. Acid-Catalysed Hydrolysis of Amides | 酰胺的酸催化水解

Primary amides are hydrolysed when heated under reflux with dilute aqueous acid, such as dilute hydrochloric acid or dilute sulfuric acid. The products are a carboxylic acid and an ammonium salt. For ethanamide, the equation is:

伯酰胺与稀酸（如稀盐酸或稀硫酸）在回流条件下加热会发生水解，生成羧酸和铵盐。以乙酰胺为例，方程式为：

CH₃CONH₂ + H₂O + H⁺ → CH₃COOH + NH₄⁺

The reaction is not a simple equilibrium because the ammonia produced is protonated to form NH₄⁺. Removing the amine as an ammonium ion drives the hydrolysis to completion. If the free amine is required, the reaction mixture can be treated with a base after hydrolysis.

该反应不是简单平衡，因为生成的氨被质子化形成 NH₄⁺。胺以铵离子的形式被移出体系，推动水解反应进行完全。如果需要游离胺，水解后可用碱处理反应混合物。

For N-substituted amides such as N-methylethanamide, acid hydrolysis produces the corresponding carboxylic acid and an alkylammonium salt. The concept is identical: water acts as the nucleophile and the amine is protonated under the acidic conditions.

对于 N-甲基乙酰胺等 N-取代酰胺，酸水解生成相应的羧酸和烷基铵盐。原理相同：水作为亲核试剂，胺在酸性条件下被质子化。

3. Base-Catalysed Hydrolysis of Amides | 酰胺的碱催化水解

When an amide is heated under reflux with aqueous sodium hydroxide or potassium hydroxide, it undergoes alkaline hydrolysis. A primary amide gives the sodium or potassium salt of the carboxylic acid and ammonia gas. For ethanamide:

酰胺与氢氧化钠或氢氧化钾水溶液在回流条件下加热时，发生碱催化水解。伯酰胺生成羧酸钠盐或钾盐和氨气。以乙酰胺为例：

CH₃CONH₂ + OH⁻ → CH₃COO⁻ + NH₃

Ammonia gas is evolved on heating and can be detected by its characteristic smell or by turning damp red litmus paper blue. The carboxylate salt remains in solution and the carboxylic acid can be liberated by adding a stronger acid afterwards.

加热时会放出氨气，可通过其特殊气味或使湿润的红色石蕊试纸变蓝来检验。羧酸盐留在溶液中，之后加入更强的酸即可游离出羧酸。

Alkaline hydrolysis is often preferred over acid hydrolysis in preparative work because the carboxylate salt is easily separated from the volatile amine. The reaction is driven to completion because the carboxylic acid is immediately deprotonated to the carboxylate anion.

在制备实验中，碱水解通常比酸水解更受欢迎，因为羧酸盐很容易与挥发性胺分离。由于生成的羧酸立即去质子化形成羧酸根离子，反应也能进行完全。

4. Nucleophilic Acyl Substitution Mechanism | 亲核酰基取代机理

Both acidic and alkaline amide hydrolysis proceed by a nucleophilic acyl substitution mechanism. In acid-catalysed hydrolysis, the carbonyl oxygen is protonated first, which increases the positive character of the carbonyl carbon. Water then attacks this carbon, forming a tetrahedral intermediate.

酸性和碱性酰胺水解都遵循亲核酰基取代机理。在酸催化水解中，羰基氧首先被质子化，从而增强羰基碳的正电性。随后水进攻该碳，形成四面体中间体。

In the tetrahedral intermediate, the original C=O double bond has become a single bond. Proton transfer steps then allow the C–N bond to break, expelling the amine as NH₃, which is immediately protonated to NH₄⁺. The protonated carbonyl group is finally deprotonated to regenerate the carboxylic acid.

在四面体中间体中，原来的 C=O 双键变为单键。经过质子转移步骤，C–N 键断裂，胺以 NH₃ 形式离去，并立即质子化为 NH₄⁺。质子化的羰基最后去质子化，重新生成羧酸。

In alkaline hydrolysis, the hydroxide ion attacks the carbonyl carbon directly. The same tetrahedral intermediate forms, then the C–N bond breaks and the amine leaves. Finally, the carboxylic acid transfers a proton to the amine or to hydroxide, producing the carboxylate ion. This deprotonation makes the overall reaction irreversible.

在碱水解中，氢氧根离子直接进攻羰基碳。形成相同的四面体中间体后，C–N 键断裂，胺离去。最后羧酸将质子转移给胺或氢氧根离子，生成羧酸根离子。这一去质子化步骤使整个反应不可逆。

5. Reduction of Amides with LiAlH₄ | 酰胺用 LiAlH₄ 还原

Amides can be reduced to amines using the powerful reducing agent lithium aluminium hydride, LiAlH₄, in dry ether. A primary amide is reduced to a primary amine with the same number of carbon atoms. The general equation is:

酰胺可用强还原剂氢化铝锂 LiAlH₄ 在干燥乙醚中还原为胺。伯酰胺被还原为碳原子数相同的伯胺。一般方程式为：

RCONH₂ + 4[H] → RCH₂NH₂ + H₂O

For example, propanamide gives propylamine. The reaction is typically written using [H] to represent the hydride provided by LiAlH₄. After reduction, the reaction mixture is treated with dilute acid to protonate the alkoxide intermediates and liberate the amine salt, which can then be neutralised.

例如，丙酰胺生成丙胺。反应通常用 [H] 表示 LiAlH₄ 提供的氢负离子。还原后，反应混合物用稀酸处理，使醇盐中间体质子化并释放出胺盐，再经中和得到胺。

Sodium borohydride, NaBH₄, is not strong enough to reduce amides because the carbonyl carbon of an amide is much less electrophilic than that of an aldehyde or ketone. LiAlH₄ is therefore the standard reducing agent for converting amides to amines.

硼氢化钠 NaBH₄ 不足以还原酰胺，因为酰胺羰基碳的亲电性远低于醛或酮。因此 LiAlH₄ 是将酰胺转化为胺的标准还原剂。

6. Dehydration of Amides to Nitriles | 酰胺脱水生成腈

Primary amides can be dehydrated to nitriles by heating with a strong dehydrating agent such as phosphorus(V) oxide, P₄O₁₀. Water is removed from the amide group. For ethanamide:

伯酰胺与强脱水剂如五氧化二磷 P₄O₁₀ 一起加热，可脱水生成腈。水从酰胺基团中脱去。以乙酰胺为例：

CH₃CONH₂ → CH₃CN + H₂O

The product is ethanenitrile. This reaction is useful in synthesis because nitriles can be hydrolysed or reduced further. It also illustrates the close relationship between amides and nitriles: hydrolysis of a nitrile gives an amide, and dehydration of an amide returns the nitrile.

产物是乙腈。该反应在合成中很有用，因为腈可以进一步水解或还原。它也体现了酰胺与腈之间的密切关系：腈水解可得到酰胺，而酰胺脱水又可回到腈。

Other dehydrating agents such as thionyl chloride, SOCl₂, or phosphorus pentoxide can also be used, but P₄O₁₀ is commonly quoted in A Level specifications. The reaction requires heating and should be carried out in dry conditions to prevent the amide from hydrolysing instead.

其他脱水剂如亚硫酰氯 SOCl₂ 或五氧化二磷也可使用，但 A Level 考试大纲中常提到 P₄O₁₀。反应需要加热，并应在干燥条件下进行，以防止酰胺发生水解。

7. Hofmann Rearrangement of Primary Amides | 伯酰胺的霍夫曼重排

Primary amides undergo the Hofmann rearrangement when treated with bromine in aqueous sodium hydroxide. The product is a primary amine containing one fewer carbon atom than the original amide. For ethanamide, methylamine is formed:

伯酰胺与溴和氢氧化钠水溶液反应时会发生霍夫曼重排。产物是比原酰胺少一个碳原子的伯胺。以乙酰胺为例，生成甲胺：

CH₃CONH₂ + Br₂ + 4NaOH → CH₃NH₂ + Na₂CO₃ + 2NaBr + 2H₂O

The reaction involves loss of the carbonyl carbon as carbonate, CO₃²⁻. The nitrogen atom remains bonded to the R group and becomes the amine nitrogen. This provides a useful route for shortening a carbon chain by one atom while introducing an amine group.

该反应中，羰基碳以碳酸根 CO₃²⁻ 的形式离去。氮原子仍与 R 基团相连，并成为胺的氮原子。这提供了一条使碳链缩短一个碳原子并引入胺基的实用路线。

The Hofmann rearrangement is sometimes included as an extension topic in Cambridge A Level Chemistry. It is particularly important in synthesis problems where a primary amine needs to be prepared from a carboxylic acid derivative without increasing the chain length.

霍夫曼重排有时作为剑桥 A Level 化学的拓展内容出现。在需要从羧酸衍生物制备伯胺且不增加碳链长度的合成问题中，该反应尤为重要。

8. Reactions of N-Substituted Amides | N-取代酰胺的反应

N-substituted amides, such as N-methylethanamide CH₃CONHCH₃, undergo the same general reactions as primary amides. Acid hydrolysis gives the carboxylic acid and an alkylammonium salt, while alkaline hydrolysis gives the carboxylate salt and a free secondary amine.

N-取代酰胺（如 N-甲基乙酰胺 CH₃CONHCH₃）经历与伯酰胺相同的基本反应。酸水解生成羧酸和烷基铵盐，碱水解生成羧酸盐和游离仲胺。

Reduction of an N-substituted amide with LiAlH₄ produces a secondary or tertiary amine, depending on the substitution pattern. For example, N-methylethanamide is reduced to ethylmethylamine. This shows that the amide reduction is a general method for preparing different classes of amines.

N-取代酰胺用 LiAlH₄ 还原可生成仲胺或叔胺，具体取决于取代方式。例如 N-甲基乙酰胺被还原为乙基甲胺。这说明酰胺还原是制备多种胺类化合物的通用方法。

The key difference is the nature of the amine product: primary amides give ammonia or primary amines, whereas substituted amides give substituted amines. In each case, the carbonyl group is converted to a CH₂ group during reduction, or is removed entirely during hydrolysis or the Hofmann rearrangement.

关键区别在于胺产物的类型：伯酰胺生成氨或伯胺，而取代酰胺生成取代胺。在每种情况下，羰基在还原时转化为 CH₂ 基团，在水解或霍夫曼重排中则被完全移除。

9. Relative Reactivity of Carboxylic Acid Derivatives | 羧酸衍生物的相对反应性

Carboxylic acid derivatives can be arranged in order of decreasing reactivity toward nucleophilic substitution: acyl chlorides > acid anhydrides > esters > amides. Amides are the least reactive because the nitrogen lone pair donates strongly into the carbonyl π system, reducing the positive charge on the carbonyl carbon.

羧酸衍生物按亲核取代反应活性降低的顺序可排列为：酰氯 > 酸酐 > 酯 > 酰胺。酰胺的反应活性最低，因为氮的孤对电子强烈地给予到羰基 π 体系中，降低了羰基碳上的正电荷。

This low reactivity explains why amide hydrolysis requires heat under reflux with acid or alkali, whereas acyl chlorides react rapidly with water at room temperature. It also explains why amides require LiAlH₄ rather than NaBH₄ for reduction.

这种低反应性解释了为什么酰胺水解需要酸或碱回流加热，而酰氯在室温下就能与水迅速反应。它也解释了为什么酰胺还原需要 LiAlH₄ 而不是 NaBH₄。

In synthesis, amides are often chosen as stable protecting groups for carboxylic acids because they resist many mild reagents. However, they can be converted selectively under the vigorous conditions described above.

在合成中，酰胺常被选作羧酸的稳定保护基，因为它们能耐受许多温和试剂。但在上述剧烈条件下，它们仍可被选择性地转化。

10. Summary Table of Amide Reactions | 酰胺反应总结表

The table summarises the key reactions of primary amides, including reagents, conditions and products.

下表总结了伯酰胺的关键反应，包括试剂、条件和产物。

Reaction \| 反应	Reagents and conditions \| 试剂与条件	Products \| 产物
Acid hydrolysis \| 酸水解	Dilute HCl/H₂SO₄, heat under reflux	Carboxylic acid + ammonium salt
Alkaline hydrolysis \| 碱水解	Aqueous NaOH, heat under reflux	Carboxylate salt + ammonia/amine
Reduction \| 还原	LiAlH₄ in dry ether, then dilute acid	Primary amine
Dehydration \| 脱水	P₄O₁₀, heat	Nitrile + water
Hofmann rearrangement \| 霍夫曼重排	Br₂, excess NaOH	Primary amine (one C less) + carbonate

A common exam error is to write NaBH₄ for amide reduction or to forget that alkaline hydrolysis produces the carboxylate salt, not the free carboxylic acid. Always check the number of carbon atoms in the amine product after the Hofmann rearrangement.

常见的考试错误是在酰胺还原中写成 NaBH₄，或忘记碱水解生成的是羧酸盐而不是游离羧酸。在霍夫曼重排后，务必检查胺产物中的碳原子数。

11. Experimental Observations and Test Reactions | 实验现象与检验反应

When a primary amide is heated with sodium hydroxide solution, ammonia gas is evolved. It can be identified by its pungent smell and by the colour change of damp red litmus paper to blue. A white mist of ammonium chloride forms when a glass rod dipped in concentrated hydrochloric acid is held near the mouth of the test tube.

伯酰胺与氢氧化钠溶液加热时会放出氨气。氨气可通过其刺激性气味以及使湿润的红色石蕊试纸变蓝来确认。将蘸有浓盐酸的玻璃棒靠近试管口，会观察到氯化铵白烟。

In acid hydrolysis, no ammonia gas is evolved because the ammonia remains in solution as the ammonium ion. Instead, the product can be tested by adding sodium hydroxide to the reaction mixture after hydrolysis; heating this mixture will then release ammonia gas from NH₄⁺.

在酸水解中不会放出氨气，因为氨以铵离子的形式留在溶液中。要检验产物，可在水解后向反应混合物中加入氢氧化钠并加热，此时 NH₄⁺ 会释放出氨气。

Reduction of an amide is confirmed by the disappearance of the characteristic carbonyl absorption band in the infrared spectrum. The product amine shows N–H stretching absorptions and can be detected by its basicity towards indicators.

酰胺还原可通过红外光谱中特征羰基吸收带的消失来确认。产物胺显示 N–H 伸缩振动吸收，并可通过其对指示剂的碱性来检测。

12. Exam Tips and Common Misconceptions | 考试提示与常见误区

Students often confuse acid and alkaline hydrolysis products. In acid hydrolysis, the nitrogen-containing product is an ammonium ion; in alkaline hydrolysis, it is ammonia gas or a free amine. The organic product in alkaline hydrolysis is a carboxylate ion, not a carboxylic acid.

学生常将酸水解和碱水解的产物混淆。酸水解中，含氮产物是铵离子；碱水解中，含氮产物是氨气或游离胺。碱水解中的有机产物是羧酸根离子，而不是羧酸。

Another common error is to use NaBH₄ to reduce an

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Reactions of the Amides | 酰胺的反应