Chap 18. Carboxylic acids and their derivatives. Nucleophilic substitution at the acyl carbon 18.1 Introduction The carboxyl group, -COOH, -CO 2 H, is one of the most widely occurring functional groups in chemistry and biochemistry. Not only are carboxylic acids themselves important, but the carboxyl group is the parent group of a large family of related compounds.

All of these carboxylic acid derivatives contain the acyl group, RCO-. As a result, they are often called acyl compounds. They are called carboxylic acid derivatives.

18.2 Nomenclature and physical properties 18.2A Carboxylic acids

18.2C Acidity of carboxylic acids Most unsubtituted carboxylic acids have Ka values in the range of —10 -5 (pka = 4-5).

If carboxylic acids have electron- withdrawing groups, they are stronger than unsubstituted acids. 由于氯原子电负性比碳大，氯原子表现出拉电子 诱导效应 (Inductive effect) ，使羧酸容易电离出质子 (H + ) 。 羧酸的酸性增强。

氯原子的诱导效应随着距离的增长对羧 基的影响减弱，因而羧酸的酸性变弱。

18.2E Esters The names of esters are derived from the names of the alcohol (with the ending –yl) and the acid (with the ending –ate or –oate).

18.2F Carboxylic anhydrides （酸酐） Most anhydrides are named by dropping the word acid from the name of the carboxylic acid and then adding the word anhydride.

18.2G Acyl chlorides ( 酰氯） Acyl chlorides are also called acid chlorides. They are named by dropping –ic acid from the name of the acid and then adding –yl chloride. Examples are

18.2H Amides ( 酰胺）

18.2I Nitriles ( 腈）

18.2J Spectroscopic properties of acyl compounds

18.3 Preparation of carboxylic acids 1. By oxidation of alkenes. 2. By oxidation of aldehydes and primary alcohols.

3. By oxidation of alkylbenzenes. 4. By oxidation of methyl ketones. （甲基酮的氧化）

5. By hydrolysis of cyanohydrins and other nitriles.( 腈醇和腈的水解） 在合成上增加一个碳原子的羧酸。

6. By carbonation （羰基化） of Grignard reagents. Grigard reagents react with carbon dioxide to yield magnesium carbon dioxide to yield magnesium carboxylates. Acidification produces carboxylic acids.

18.4 Nucleophilic substitutions at the acyl carbon

2. The reaction of an acyl group with an alcohol.

The reaction mechanism is as follows

18.4A Relative reactivity of acyl compounds ( 酰基化合物相对反应活性） Acyl chlorides are the most reactive toward nucleophilic substitution and amides are the least reactive.

18.5 Acyl Chlorides 18.5A Synthesis of acyl chlorides

18.5B Reactions of acyl chlorides

18.6 Carboxylic acid anhydrides 18.6A Synthesis of carboxylic acid anhydrides （酸酐的合成）

Cyclic anhydrides can somethimes be prepared by simply heating the appropriate dicarboxylic acid.

The reactions of acid anhydride

18.7A Synthesis of esters: Esterification ( 酯化反应） Carboxylic acids react with alcohols to form esters through a condensation reaction known as esterification: General Reaction

Specific Examples;

用同位素 O 18 标记法来研究酯化反应机理 羧酸的酰氧键断裂 醇的烷氧键断裂 实验证明，羧酸的酯化是按照羧酸的酰氧键断裂方式进行。 即按 1 反应方式进行。

Acid-Catalyzed esterification mechanism

Acid-Catalyzed Ester Hydrolysis;

Esters from Acyl chlorides （由酰氯制备酯） 放出的氯化氢气体被吡啶吸收。

Esters from Carboxylic Acid Anhydrides ( 由酸酐制备酯）

18.7B Base-promoted hydrolysis of esters: Saponification ( 皂化反应） 酯的碱性条件下的水解 称为皂化反应。

Evidence for this mechanism comes from studies done with isotopically labeled esters. ( 同位素的标记来研究酯的水解机理） 实验证明；酯的水解一般按照酰氧键断裂方式进行。

18.7C Lactones ( 内酯）

Erythromycin A 红霉素 （抗生素的一种）

18.8 Amides ( 酰胺） 18.8A Synthesis of amides Amides can be prepared in a variety of ways starting with acyl chlorides, acid anhydrides, esters, carboxylic acids, and carboxylic salts. All of these methods involve nucleophilic substitution reactions by ammonia or an amine at an acyl carbon. As we might expect, acid chlorides are the most reactive and carboxylate ions are the least.

18.8B Amides from acyl chloride Primary amines, secondary amines, and ammonia all react rapidly with acid chlorides to from amides. 酰氯是非常活泼的，它很容易与氨，伯胺，仲胺反应生成酰胺

Reaction Mechanism

18.8C Amides from carboxylic anhydrides Acid anhydrides react with ammonia and with primary and secondary amines and form amides through ractions that are analogous to those of acyl chlorides.

18.8G Nitriles from the dehydration of amides ( 由酰胺制腈） Amides react with P 2 O 5 or with boiling acetic anhydride to form nitriles.

18.8H Hydrolysis of nitriles （腈的水解）

18.8I Lactams ( 内酰胺 ) Cyclic amides are called lactams.

Polyamides （聚酰胺） Nylon 6 or Nylon 6,6 can also be converted into fibers by melt spinning. ( 熔融纺丝 )

18.9 α- Halo Acids (α- 卤代酸） Aliphatic carboxylic acids react with bromine or chlorine in the presence of phosphorus (or a phosphorus halide) to give α- halo acids.

α- Halo acids are important synthetic intermediates because they are capable of reacting with a variety of nucleophiles; 1 ） Conversion to α- hydroxy acids (α- 卤代酸可以转换成 α- 羟基酸） 2 ） Conversion to α- amino acids (α- 卤代酸可以转换成 α- 氨基酸）

18.10 Derivatives of carbonic acid （碳酸的衍生物） Carboic acid H 2 CO 3 is an unstable compound that decomposes spontaneously (to produce carbon dioxide and water) and, therefore, can not be isolated. However, many acyl chlorides, esters, and amides that are derived from carbonic acid are stable compounds that have important applications.

Carbonyl dichloride (ClCOCl), a highly toxic compound that is also called phosgene, can be thought of as the diacyl chloride of carbonic acid.

18.11 Decarboxylation of carboxylic acids （羧酸的脱羧基 -COOH ） The reaction whereby a carboxylic acid loses CO 2 is called a decarboxylation.

P 807 Additional problems 18.19, 18.20, 18.21, 18.24, 18.27, 18.35, 18.44