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

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

3. 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

4. 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

5. 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)

6. 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

7. 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

8. 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

9. 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.

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

11. 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

12. 13C NMR
COOH ~180 ppm
α-C 30~40 ppm
180.7
36.2
18.4
13.6

13. MS 60 73
M+, 88

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

15. 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

16. 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)

17. 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

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

19. Mechanism of esterification
Isotopic labeling 同位素标记法

20. 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)

21. 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）

22. 3° alcohols

23. (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)

24. (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)

25. Mixed anhydride混酐

26. (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.

27. 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

28. 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

29. (2) Reduction to aldehydes
WAY 1
WAY 2

30. 6. Alkylation of carboxylic acids to form ketones

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

32. 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

33. 11.4 Synthesis of carboxylic acids
1. By oxidation of aldehydes and primary alcohols.

34. 2. By oxidation of alkenes and alkynes.

35. 3. By oxidation of alkylbenzenes.
Heat

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

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

38. 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。

39. Problem 1
Succinic acid 丁二酸

40. 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。

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

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

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

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

46. 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

47. 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
K × > ×10-4
K × < ×10-5

48. Decomposition 受热分解反应
可用于鉴别常见的二元羧酸

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

50. 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

51. 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

52. (3) Reformastky（雷福马斯基）反应

53. Organozinc 有机锌

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

55. -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)

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

57. Problem:
Malonic acid 丙二酸

58. 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。

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