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

Chapter 11. Carboxylic acids

羧 酸

Ref: p. 900~939

Carboxyl group（羧基）

Acyl group（酰基）

R C

O

OH

R C

O

OH

Carbonyl group（羰基）R C

O

OH

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 chl

orides, 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

HCOOH

CH3COOH

CH3CH2COOH

CH3(CH2)2COOH

formic acid 蚁酸 methanoic acid 甲酸ethanoic acid 乙酸

propanoic acid 丙酸

butanoic acid 丁酸

acetic acid 醋酸

propionic acid

butyric acid

CH3CH2CHCH2CH2COOH

CH3

CH3CH=CHCH2CH2COOH

4-methylhexanoic acidγ-methylhexanoic acid

（ 4- 甲基己酸）

4-hexenoic acid（ 4- 己烯酸）

CH3(CH2)7CH=CH(CH2)7COOH octadec-9-enoic acid9- 十八碳烯酸 ( 油酸 )

benzoic acid苯甲酸

1-naphthoic acid1- 萘酸

2-hydroxybenzoic acid2- 羟基苯甲酸salicyclic acid

( 水扬酸 )

COOH

COOH

COOH

OH

COOH

cyclohexanecarboxylic acid环己烷羧酸

Dicarboxylic acids ( 二羧酸 )

Common name IUPAC name(Historical name) alkanedioic acid

HOOC-COOH

HOOCCH2COOH

HOOC(CH2)2COOH

oxalic acid草酸

malonic acid丙二酸

succinic acid琥珀酸

ethanedioic acid乙二酸

propanedioic acid丙二酸

butanedioic acid丁二酸

COOH

COOHphthalic acid 邻苯二甲酸1,2-benzenedicarboxylic acid

COOHHOOC isophthalic acid 间苯二甲酸m-phthalic acid1,3-benzenedicarboxylic acid

HOOC

COOH

terephthalic acid 对苯二甲酸p-phthalic acid1,4-benzenedicarboxylic acid

11.2 Structure, physical properties, and Spectroscopy of carboxylic acids

CO

OR

HC

O

OHR

......

Hydrogen bonded acid dimer ( 二聚体 )

bp, mp, s: higher than alcohols, ketones of similar molecular weight.

CO

OR

HC

O

OR

HC

O

OR

H

sp2 major very minor minor

CH3CH2CH2COOH

1712C=O

3500-2300OH

RCOOH 1700-1725 cm-1

ArCOOH 1680-1700 cm-1

IR:

3000~2500cm-1

(OH)(C=O)

1H NMR COOH 10~13 ppm (unsplit)

RCOOH RCOO- H++

RCOOH + D2O RCOOD DOH+

α-H 2.0~2.5 ppm

:

CH3CH2CH2COOH

11.51, single 0.98, triplet

2.33, triplet 1.68, sextet

13C NMRCOOH ~180 ppmα-C 30~40 ppm

180.736.2

18.413.6

CH3CH2CH2COOH

CH3CH2CH2COOH

MS

60

73M+, 88

(2) Forming a stable allylic system and two oxygen atoms.

m/e: 60

m/e: 73

O

CHO C

H2

CH2

CH2

HOH

CHO CH2

CH2

CH2+

O

CHO CH2 CH2 CH3

O

CHO CH2 CH2+ CH3

(1) McLafferty rearrangment ( 麦氏重排 )

CC

C

OH

HO

CC

C

OH

HO

CC

C

OH

HO

CC

C

OH

HO

11.3 Reactions of Carboxylic acids

AcidityAcidityNucleophilicacyl substitution

Nucleophilicacyl substitution

Reaction sites of carboxylic acids

Reduction to CH2Reduction to CH2

Decarboxylation脱羧反应

Decarboxylation脱羧反应

α-H reactionα-H reaction

C

O

RC OH

H

1. Acidity: reaction with base to form salts( 盐 )(20-4)

Most unsubstituted carboxylic acids have pKa values in the range of 4~5.

NaOH + H2O

Benzoic acid Sodium benzoate

(water insoluble) (water soluble)

£¨±½¼×ËáÄÆ£©(pKa = 4.15)

CO2H + CO2Na

CO2H + NaHCO3 CO2Na + CO2 + H2O

Application ： separation and purification of carboxylic acids by extraction ( 萃取法分离和提纯羧酸 )

sodium bicarbonate

FCH2CO2H ClCH2CO2H BrCH2CO2H ICH2CO2H

Cl3CCO2H Cl2CHCO2H ClCH2CO2H

ClCH2CO2H ClCH2CH2CO2H ClCH2CH2CH2CO2H

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

COOH

CH3

COOH

NO2

COOH

Cl

COOH

H

COOH

OCH3

strong weak

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

R C

O

OH + HOR'H+

R C

O

OR' + H2OEster

+H+

H3C C

O

OCH2CH3

Ethyl acetateÒÒËáÒÒõ¥

CH3 C

O

OH + H2O

Acetic acidÒÒËá

Ethanol

HOCH2CH3

+H+

C

O

OCH2CH3

Esterification Methyl benzoate

±½¼×ËáÒÒõ¥

C6H5 C

O

OH + H2O

Benzoic acid

±½¼×Ëá

Ethanol

HOCH2CH3 C6H5

Mechanism of esterification

+H+

C

O

OCH2CH3 + H218OCH2CH3 C6H5OHC6H5 C

O18O H

+H+

C

O18OCH2CH3 + H2OC6H5CH2CH3OHC6H5 C

O18O H

Isotopic labeling 同位素标记法

Acid-Catalyzed esterification mechanism

C6H5 C

O18OH

H+

C6H5 C

O

18OH

H+HOCH2CH3

C6H5 C

OH18OH

OCH2CH3H+

C6H5 C

OH18OH

OCH2CH3

H

+

C

OH

OCH2CH3

+ H218O

C6H5C

O

OCH2CH3C6H5-H+

1°, 2 °alcohols

Nucleophilic acyl substitution( 亲核酰基取代 ) addition-elimination mechanism( 加成 - 消除机理 )

A. CH3COOH, B. (CH3)2CHCOOH, C. (CH3)3CCOOH

Problem: rank the following compounds in order of increasing esterification rate.

Answer: A>B>C （位阻影响 , hindrance ）

R'3C OH R'3C OH2+ R'3C

+H+.. -H2O

R CO

OH.. R'3C

+R C

OOCR'3H

+ H+-R C

OOCR'3

3° alcohols

3. Acylation ( 酰化反应 )

Acid chloride is important acylation reagent ( 酰化试剂 )

R C

O

OH

Acyl chlorideõ£ÂÈ

+ SOCl2 R C

O

Cl + SO2 + HCl

Thionyl chloride

ÑÇÁòõ£ÂÈ, ÂÈ» Ñ̄Çí¿

R C

O

OH

Acyl chloride

õ£ÂÈ

+ R C

O

Cl +

Phosphorus trichlorideÈýÂÈ» Á̄×

PCl3 H3PO3

R C

O

OH

Acyl chloride

õ£ÂÈ

+ R C

O

Cl +

Phosphorus pentachlorideÎå ÂÈ» Á̄×

PCl5 POCl3 + HCl

(1) Synthesis of acid chlorides( 酰氯 )

(2) Synthesis of carboxylic acid anhydrides （酸酐）

HOOCCH2(CH2)nCOOH O

O

On

heatn=1,2

COOH

COOHO

O

O

heat

poor yielddehydrating agent 脱水剂

2 RCOOH + RCOOCOR +P2O5 H3PO4

Acid anhydride is also important acylation reagent ( 酰化试剂 )

HO C

O

R'

Acyl chloride

õ£ÂÈ

R C

O

Cl +N

R C

O

O C

O

R' +N+H

Cl-

NaO C

O

R'

Acyl chloride

õ£ÂÈ

R C

O

Cl + R C

O

O C

O

R'(- NaCl)

Mixed anhydride 混酐

(3) Direct synthesis of amides （酰胺）

RCOOH NH2 RCOONH3R' RCONHR' H2O+heat

+R'

acid Amine胺

an ammonium carboxylate salt

amide

Temperature: > 100 degree.An important industrial process to synthesize amides.

RCOCl NH2 RCONHR' HCl+ +R'

RCOOH NH2 RCONHR' H2O+ +R'

DCC(dehydration reagent)

(RCO)2O NH2 RCONHR' RCOOH+ +R'

Strong electron-withdrawing group at -position can make the decarboxylation easier.

Koble reaction柯尔贝反应

4. Decarboxylation （脱羧反应）

CH3COONa CaO/NaOH CH4 CO2+heat

RCOOAg Br2 RBr AgBrCCl4

+heat

+ CO2 +

CH3COCH2COOH CH3COCH3 CO2

OCH2COOH

COOH

O

CH2COOHheat

+heat

CO2+

Hunsdiecher rea

ction

汉斯狄克反应

2RCOOK

electrolysis(电解)

CO2+R-R

5. Reduction （还原反应）

COOH1) LiAlH4/THF

2) H2O

CH2OH

COOH

1) B2H6/THF

2) H2O

CH2OH

NO2 NO2

COOH CH2OH

C OCH3

C OCH3

1) B2H6/THF

2) H2O

LiAlH4: strong-COOH, -CO, -CHO ， -COOR ， -CONHR

NaBH4: moderate-CO, -CHO

B2H6: siutable for acid-COOH

(1) Reduction to primary alcohols

(2) Reduction to aldehydes

RCOOHLi

CH3NH2RHC NCH3

H+

H2ORCHO

RCOOHSOCl2 RCOCl

LiAl[OC(CH3)3]3HRCHO

WAY 1

WAY 2

6. Alkylation of carboxylic acids to form ketones

R C

O

OH

carboxylic acidR C

O

R'

ketone

(1) 2 R'Li

(2) H2O

R C

O

OH

LiOH(or R'-Li)

R C

O

OLi R'-Li

R C

OLi

OLi

R'carboxylic acid

H3O+

R C

OH

OH

R'

-H2OR C

O

R'

ketone

hydrate Ë®ºÏ Îï

7. Esterification using diazomethane ( 重氮甲烷 )

R C

O

OH

carboxylic acidR C

O

OCH3+ CH2N2

diazomethane methyl ester+ N2

R C

O

O

H2C N N

HC N NH R C

O

O H3C N N+

R C

O

OCH3 + N2

High yield, usually used to protect carboxyl group.

H2C N N HC N NCH2N2

Summary Reactions of carboxylic acids

acidity —— salts; factors affecting acidityacylation —— esters, anhydrides, acid chlorides, amides decarboxylation —— loss CO2, reduction —— to primary alcohols, aldehydesalkylation—— ketonesesterification 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.

RCH2OH RCOOH KMnO4

or H2CrO4

RCHO1) Ag2O, or Ag(NH3)3OH-

2) H3O+RCOOH + Ag

(Mirror reaction)

2. By oxidation of alkenes and alkynes.

RCH CR'R" RCOOH + R'COR''KMnO4

RC CR' RCOOH + R'COOHKMnO4

or O3; H2O

3. By oxidation of alkylbenzenes.

or Na2Cr2O7/H+CH3 C6H5COOH

COOH

COOH

KMnO4

KMnO4

or Na2Cr2O7/H+

Heat

H2N

CH3

H2N

COOH

Cl

CH3

Cl

COOH

4. By Cannizzaro reactions ( 坎尼查罗反应 )

HCHO + NaOH¡÷

HCOONa + CH3OH

CHO COONa CH2OH+

COOHH+

NaOH

Be suitable for aldehydes without alpha-H

5. By haloform reaction (converts methyl ketones to acids and iodoform.) 卤仿反应，将甲基酮转化为酸和碘仿。

R C

O

CH3 2) H3O+ RCOOH1) X2 / NaOH + CHX3

2) H3O+C C6H5COOH1) X2 / NaOH

O

CH3+ CHX3

6. By hydrolysis of cyanohydrins( 氰醇 ) and other nitriles( 腈）

用于合成增加一个碳原子的羧酸。仅适用于伯卤代烃。

RC

R'O + HCN

R

C

R'

OH

CN

H+

H2O

R

C

R'

OH

COOH

BrCH2CH2CH2CH2Br NaCN NC(CH2)4CNH3O+

HOOC(CH2)4COOH

cyanohydrin Hydroxy-acid羟基酸

RCH2X + NaCN RCH2COOHH+

H2ORCH2CN

Problem 1

C2H5OHH2SO4 Br2/CCl4 BrCH2CH2Br

NaCN NCCH2CH2CNH3O+

CH2=CH2

HOOCCH2CH2COOH

Succinic acid 丁二酸

HOOCCH2CH2COOHCH3CH2OH

CH3CH2OH CH3CH2COOH

CH3CH2BrCH3CH2OH CH3CH2CN

H3O+

HOOCCH2COOH

HBr NaCN

7. By carboxylation （羧化） of Grignard reagents.

R X + Mgdiethyl ether

RMgXC OO

R C OOMgX

H3O+R C O

OH

+ Mg OHX

R XMg, ether,

2. H3O+R C

O

OH1. CO2

R MgX

Mg, ether

2. H3O+

1. CO2Br C

O

OHMgBr

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。

Mgether

CH2=CHCH2X CH2=CHCH2MgX

CH2=CHCH2-CH2CH=CH2CH2=CHCH2X

CH2=CHCH2X CH2=CHCH2CN

CH2=CHCH2COOHH3O+

NaCN

8. Commercial sources of carboxylic acids

C CH

H H

H

O2

catalystH3C CH

O O2

catalystH3C C

O

OH

acetic acid 乙酸

Rh catalystH3C C

O

OHCH3OH + COheat, pressure

sugar and starch CH3CH2OH CH3COOH

糖和淀粉

benzoic acid 苯甲酸

or Na2Cr2O7/H+CH3 C6H5COOH

KMnO4

Adipic acid (hexanedioic acid) 己二酸

COOH

COOHH2, Ni

high pressureO2

catalyst

adipic acid

Long-chain aliphatic acid 长链脂肪酸

H2C

HC

H2C

O C R

O C R'

O C R''

O

O

O

H2C

HC

H2C

OH

OH

OH

+

RCOO-Na+

R'COO-Na+

R''COO-Na+

Glycerol ±ûÈý́¼

¸ÊÓÍ

Sodium carboxylates ôÈËáÄÆÑÎ

(soap)

H2O

NaOH

Fat or oilR, R’, R”: long-chain alkyl group

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

Acidity ： stronger than monocarboxylic acids, and K1>K2

.

11.5 Dicarboxylic acids 二元羧酸

mp, s: higher than monocarboxylic acids of similar molecular weight.

See Table 20-3, p 906

( 本节以中文教材为主 )

Field effect 场效应

Fumaric acid 富马酸 , trans-

Maleic acid 马来酸 cis-

C

C

H

H

HOOC

COOH

C

C

H

H

COOH

COOH

C

C

H

H

-OOC

COO-

C

C

H

H

COO-

COO-

K2

K2

C

C

-OOC

COOH

H

H

C

C

C

O

O-

C

O

O

H

H

H

...

K1

K1

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

HOOCCOOH heat HCOOH CO2+

HOOCCH2COOH CH3COOHheat CO2+

O

O

O

heat

heatO

O

O

+ H2O

+ H2O

HOOC(CH2)2COOH

HOOC(CH2)3COOH

heat

heat

HOOC(CH2)4COOH

HOOC(CH2)5COOH

O

O

CO2+

CO2+

+ H2O

+ H2O

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

OH

OH

HO

HO

O

O

+

O

O O

O

H+

COOH

COOH

nHOCH2CH2OH C COO

OCH2CH2Onn +

H+

cyclic esters 环状酯

Polyesters 聚酯

1. Hydroxyl acids 羟基酸

11.6 Substituted carboxylic acids 取代羧酸

Tartaric acid2,3-dihydroxysuccinic acid酒石酸

Malic acid2-hydroxysuccinic acid苹果酸

Citric acid2-hydroxypropane-1,2,3-tricarboxylic acid柠檬酸

Salicyclic acid水杨酸

HOOC CH

OH

CH

OH

COOH HOOC CH2 CH

OH

COOH

HOOC CH2 C

OH

CH2COOH

COOH

OHCOOH

( 本节以中文教材为主 )

(2) Hydrolysis of cyanoalcohols 氰醇的水解

(1) Basic hydrolysis of halogenated acids 卤代酸的碱性水解

Preparation of hydroxyl acids

R CH

X

COOH + OH- R CH

OH

COOH

C OR

R'C

CN

R

R'

OH H3O+C

COOH

R

R'

OHHCN

(3) Reformastky （雷福马斯基）反应

C OR

R'XCH2COOEt

1)Zn

2)H3O+C

CH2COOEt

R

R'

OH

+

O HO CH2CO2EtBrCH2COOEt+

1)Zn

2)H3O+

CH3O COCH3 CH3O CH

OH

CH2CO2EtBrCH2COOEt+1)Zn

2)H3O+

BrZnCH2ZnBrCH2COOEt-+

+

CO2Et

C OR

R'C

CH2COOEt

R

R'

OZnX

CCH2COOEt

R

R'

OHH3O+

Organozinc 有机锌

Reactions of hydroxyl acids

Dehydration 加热失水

-hydroxyl acids give cyclic diesters (lactide 交酯 )

OHR

O OH

HO O

HO RO

OR

R

O

O

+加热

O

OPh

Ph

O

O

加热C O

Ph

H H3O+C

COOH

Ph

H

OH1)HCN

2)

-hydroxyl acids give ,- unsaturated carboxylic acids (,- 不饱和羧酸 )

Lactone 内酯

R CH

OH

CH2COOHheat

RCH=CHCOOH

HOCH2CH2CH2COOH O

Oheat

γ-hydroxyl acids give lactone ( 内酯 )

γ -butyrolactone 丁内酯

(2) Reactions

2. Halogenated acids 卤代酸： - 卤代酸

(1) Preparation

RCH2COOH Br2P(红) RCHCOOH

BrHBr+ +

R CH

X

COOH + OH- R CH

OH

COOH

CH3CH2OH HOOCCH2COOH

CH3COOHCH3CH2OHP(红 )Br2

BrCH2COOH

NaOHBrCH2COONa NaCN NCCH2COONa

H3O+

HOOCCH2COOH

K2Cr2O7

Malonic acid 丙二酸

Problem:

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。

C OR

R'XCH2COOEt C CHCOOEt

R

R'

O+

strong baseÇ¿¼î

C OPh

HXCH2COOEt C CHCOOEt

Ph

H

O+

EtONa

BrCH2COOEt + EtONa BrCH_

CO2Et

C OR

R' CCHCOOEt

R

R'

O-

Br

C CHCOOEtR

R'

O

Assignment

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

• Text 2: 9, 10