Chapter 11. Carboxylic acids 羧 酸 Ref: p. 900~939

Carboxyl group （羧基） Carbonyl group （羰基） Acyl group （酰基） R = alkyl, aliphatic acids; R = aryl, aromatic acids

Contents 1. Nomenclature 2. Structure, physical properties, and spectroscopy 3. Reactions acidity (convert to salts) acylation (convert to esters, anhydrides, acid chlorides, amides ) decarboxylation reduction (to primary alcohols, aldehydes) esterification using diazomethane (CH2N2) 4. Synthesis

11.1 Nomenclature of carboxylic acids Common name IUPAC name (Historical name) Alkanoic acid formic acid 蚁酸 methanoic acid甲酸 acetic acid 醋酸 ethanoic acid乙酸 propionic acid propanoic acid丙酸 butyric acid butanoic acid丁酸

γ-methylhexanoic acid （4-甲基己酸） 4-hexenoic acid （4-己烯酸） octadec-9-enoic acid 9-十八碳烯酸(油酸)

cyclohexanecarboxylic acid 环己烷羧酸 benzoic acid 苯甲酸 2-hydroxybenzoic acid 2-羟基苯甲酸 salicyclic acid (水扬酸) 1-naphthoic acid 1-萘酸

Dicarboxylic acids (二羧酸) Common name IUPAC name (Historical name) alkanedioic acid HOOC-COOH oxalic acid 草酸 ethanedioic acid 乙二酸 malonic acid 丙二酸 propanedioic acid 丙二酸 HOOCCH2COOH butanedioic acid 丁二酸 HOOC(CH2)2COOH succinic acid 琥珀酸

phthalic acid 邻苯二甲酸 1,2-benzenedicarboxylic acid isophthalic acid 间苯二甲酸 m-phthalic acid 1,3-benzenedicarboxylic acid terephthalic acid 对苯二甲酸 p-phthalic acid 1,4-benzenedicarboxylic acid

11.2 Structure, physical properties, and Spectroscopy of carboxylic acids major very minor minor Hydrogen bonded acid dimer (二聚体) bp, mp, s: higher than alcohols, ketones of similar molecular weight.

IR: (C=O) (OH) RCOOH 1700-1725 cm-1 3000~2500cm-1 ArCOOH 1680-1700 cm-1 1712 C=O 3500-2300 OH

1H NMR : COOH 10~13 ppm (unsplit) α-H 2.0~2.5 ppm 11.51, single 0.98, triplet 2.33, triplet 1.68, sextet

13C NMR COOH ~180 ppm α-C 30~40 ppm 180.7 36.2 18.4 13.6

MS 60 73 M+, 88

(1) McLafferty rearrangment (麦氏重排) (2) Forming a stable allylic system and two oxygen atoms. m/e: 73

11.3 Reactions of Carboxylic acids Reaction sites of carboxylic acids Nucleophilic acyl substitution Acidity Reduction to CH2 α-H reaction Decarboxylation 脱羧反应

Acidity: reaction with base to form salts(盐) (20-4) Most unsubstituted carboxylic acids have pKa values in the range of 4~5. sodium bicarbonate Application：separation and purification of carboxylic acids by extraction (萃取法分离和提纯羧酸)

Substituent effects on acidity(取代基效应对酸度的影响) Inductive effects(诱导效应): -NO2>N+(CH3)3>-CN>F>Cl>Br>I>-OH>-OCH3>-Ph>H>R FCH2CO2H  ClCH2CO2H  BrCH2CO2H  ICH2CO2H Cl3CCO2H  Cl2CHCO2H  ClCH2CO2H ClCH2CO2H  ClCH2CH2CO2H  ClCH2CH2CH2CO2H strong weak

2. Condensation of acids with alcohols: The Fischer esterification (酯化反应)

Mechanism of esterification Isotopic labeling 同位素标记法

Acid-Catalyzed esterification mechanism 1°, 2 °alcohols Nucleophilic acyl substitution(亲核酰基取代) addition-elimination mechanism(加成-消除机理)

Problem: rank the following compounds in order of increasing esterification rate. A. CH3COOH, B. (CH3)2CHCOOH, C. (CH3)3CCOOH Answer: A>B>C （位阻影响, hindrance）

3° alcohols

(1) Synthesis of acid chlorides(酰氯) 3. Acylation (酰化反应) (1) Synthesis of acid chlorides(酰氯) Acid chloride is important acylation reagent (酰化试剂)

(2) Synthesis of carboxylic acid anhydrides（酸酐） dehydrating agent 脱水剂 poor yield Acid anhydride is also important acylation reagent (酰化试剂)

Mixed anhydride混酐

(3) Direct synthesis of amides（酰胺） an ammonium carboxylate salt amide acid Amine 胺 Temperature: > 100 degree. An important industrial process to synthesize amides.

4. Decarboxylation（脱羧反应） Strong electron-withdrawing group at -position can make the decarboxylation easier. Koble reaction 柯尔贝反应 Hunsdiecher reaction 汉斯狄克反应

5. Reduction（还原反应） (1) Reduction to primary alcohols LiAlH4: strong -COOH, -CO, -CHO， -COOR， -CONHR NaBH4: moderate -CO, -CHO B2H6: siutable for acid -COOH

(2) Reduction to aldehydes WAY 1 WAY 2

6. Alkylation of carboxylic acids to form ketones

7. Esterification using diazomethane (重氮甲烷) CH2N2 High yield, usually used to protect carboxyl group.

Reactions of carboxylic acids Summary Reactions of carboxylic acids acidity —— salts; factors affecting acidity acylation —— esters, anhydrides, acid chlorides, amides decarboxylation —— loss CO2, reduction —— to primary alcohols, aldehydes alkylation—— ketones esterification using diazomethane (CH2N2) ——methyl ester Mechanism The Fischer esterification —— acid-catalyzed nucleophilic addition, then dehydration

11.4 Synthesis of carboxylic acids 1. By oxidation of aldehydes and primary alcohols.

2. By oxidation of alkenes and alkynes.

3. By oxidation of alkylbenzenes. Heat

4. By Cannizzaro reactions (坎尼查罗反应) + Be suitable for aldehydes without alpha-H

5. By haloform reaction (converts methyl ketones to acids and iodoform

6. By hydrolysis of cyanohydrins(氰醇) and other nitriles(腈） Hydroxy-acid 羟基酸 用于合成增加一个碳原子的羧酸。 仅适用于伯卤代烃。

Problem 1 Succinic acid 丁二酸

7. By carboxylation（羧化） of Grignard reagents. 用于合成增加一个碳原子的羧酸。 一般1，2和3级卤代烃均可以通过该法制备羧酸； 烯丙位和苄基位的卤代烃最好不要采用该法。可用氰化物法。

8. Commercial sources of carboxylic acids acetic acid 乙酸 糖和淀粉

benzoic acid 苯甲酸 Adipic acid (hexanedioic acid)己二酸 adipic acid

Long-chain aliphatic acid 长链脂肪酸 Fat or oil R, R’, R”: long-chain alkyl group

9. By malonic ester （丙二酸酯） synthesis (chapter 13)

11.5 Dicarboxylic acids 二元羧酸 (本节以中文教材为主) mp, s: higher than monocarboxylic acids of similar molecular weight. Acidity：stronger than monocarboxylic acids, and K1>K2. See Table 20-3, p 906

Problem：Explain the facts: Maleic acid 马来酸 Fumaric acid 富马酸 富马酸, trans- Maleic acid 马来酸 cis- Field effect 场效应 Problem：Explain the facts: Maleic acid 马来酸 Fumaric acid 富马酸 K1 1.0 ×10-2 > 9.6 ×10-4 K2 5.5 ×10-7 < 4.1 ×10-5

Decomposition 受热分解反应 可用于鉴别常见的二元羧酸

Reaction with diols to form cyclic esters (环状酯) or polyesters聚酯

11.6 Substituted carboxylic acids 取代羧酸 1. Hydroxyl acids 羟基酸 (本节以中文教材为主) Malic acid 2-hydroxysuccinic acid苹果酸 Tartaric acid 2,3-dihydroxysuccinic acid 酒石酸 Citric acid 2-hydroxypropane-1,2,3-tricarboxylic acid 柠檬酸 Salicyclic acid 水杨酸

Preparation of hydroxyl acids (1) Basic hydrolysis of halogenated acids 卤代酸的碱性水解 (2) Hydrolysis of cyanoalcohols 氰醇的水解

(3) Reformastky（雷福马斯基）反应

Organozinc 有机锌

Reactions of hydroxyl acids Dehydration 加热失水 -hydroxyl acids give cyclic diesters (lactide 交酯)

-hydroxyl acids give ,- unsaturated carboxylic acids (,-不饱和羧酸) Lactone 内酯 γ -butyrolactone 丁内酯 γ-hydroxyl acids give lactone (内酯)

2. Halogenated acids 卤代酸： -卤代酸 (1) Preparation (2) Reactions

Problem: Malonic acid 丙二酸

Darzen（达参）反应 ：-卤代酸在强碱作用下，与醛酮反应生成，-环氧酸酯。

Assignment Text 1: 20-1, 2, 3, 5, 11, 12(b), 29, 32, 35, 37, 39, 42,(40, 47) Text 2: 9, 10