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pter 13 Carboxylic acids Nomenclature Acidity of carboxylic acids Factors affecting the acidity carboxylic acids Dicarboxylic acids Preparation of carboxylic acids Preparation of carboxylic acids by carbonation of Grignard reagen Preparation of carboxylic acids by the preparation and hydrolysis nitriles

Chapter 13 Carboxylic acids 13.1 Nomenclature 13.2 Acidity of carboxylic acids Factors affecting the acidity of carboxylic acids Dicarboxylic acids 13.3

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Page 1: Chapter 13 Carboxylic acids 13.1 Nomenclature 13.2 Acidity of carboxylic acids Factors affecting the acidity of carboxylic acids Dicarboxylic acids 13.3

Chapter 13 Carboxylic acids13.1 Nomenclature13.2 Acidity of carboxylic acids Factors affecting the acidity of carboxylic acids Dicarboxylic acids13.3 Preparation of carboxylic acids13.3.1 Preparation of carboxylic acids by carbonation of Grignard reagents13.3.2 Preparation of carboxylic acids by the preparation and hydrolysis of nitriles

Page 2: Chapter 13 Carboxylic acids 13.1 Nomenclature 13.2 Acidity of carboxylic acids Factors affecting the acidity of carboxylic acids Dicarboxylic acids 13.3

13.4 Reactions of Carboxylic acids13.4.1 Esterification13.4.2 α-Halogenation of carboxylic acids: Hell-Volhard-Zelinsky reaction 13.4.3 Decarboxylation of malonic acid and related compounds13.5 Spectroscopic analysis of carboxylic acids

Page 3: Chapter 13 Carboxylic acids 13.1 Nomenclature 13.2 Acidity of carboxylic acids Factors affecting the acidity of carboxylic acids Dicarboxylic acids 13.3

C

OR OH

Carboxylic acid:Carboxyl group

(羧基)Acyl group

(酰基)

All of carboxylic acid derivativescontain the acyl group.

13.1 Nomenclature1. e oic acid

CH3CH2CHCH2CH2CCH3

OOH

CH3CH CHCH2CH2C

O

OH4-Hexenoic acid

( 4- 己烯酸)CHC

O

OH

OH

2-Hydroxy-2-phenylethanoic

acidMandelic acid

(扁桃酸)

4-Methylhexanoic acid( 4- 甲基己酸)2. For the compounds

with polyfunctional group carboxylic acids outrank all the common group.

Ch. P281Ch. P281

P308P308

Page 4: Chapter 13 Carboxylic acids 13.1 Nomenclature 13.2 Acidity of carboxylic acids Factors affecting the acidity of carboxylic acids Dicarboxylic acids 13.3

3-Bromocyclohexane-carboxylic acid(3- 溴环己烷甲酸 )

3-Bromocyclohexane-carboxylic acid(3- 溴环己烷甲酸 )

HY > RCOOH > H2CO3 >C6H5OH > H2O > RCH2OH >pka: 4 ~ 5 6.38 10 15.74 16 ~ 19

~ 25 ~ 34 ~50C CH > RNH2 > RH

13.2 Acidity of carboxylic acids

C

O

OHR C

O

OR + H+

R CO

O

¦Ä

¦Äsp2 hybridization, p - πconjugation

HOCCH2CHCH2CH2CHCH2COH

O OCH2CH3

CH33-Ethyl-6-methyloctanedioic acid(3- 甲基 -6- 乙基辛二酸 )

3-Ethyl-6-methyloctanedioic acid(3- 甲基 -6- 乙基辛二酸 )

COOH

Br

1-Cyclopentene-carboxylic acid(1- 环戊烯甲酸 )

1-Cyclopentene-carboxylic acid(1- 环戊烯甲酸 )

COOH1

2

345

Page 5: Chapter 13 Carboxylic acids 13.1 Nomenclature 13.2 Acidity of carboxylic acids Factors affecting the acidity of carboxylic acids Dicarboxylic acids 13.3

RCOOH + NaOH RCOO Na + H2OStronger

baseWeaker

baseWeaker

acidStronger

acidRCOOH + NaHCO3 RCOO Na + CO2 + H2O

Sodium bicarbonateRCOOH: Water insoluble; RCOO-M+(Carboxylic salt): Water solubleCarboxylic acids can be separated from alcohols and phenol.

RCOONa + HCl RCOOH + NaCl

OH

CH3

CH3

CH3

NaOHH2O

Water phase

Organic phase

COOH

CH3

CH3

COONa

ONa

CH3

CO2

Water phase

Organic phase

OH

CH3

COONa

H+

COOH

Page 6: Chapter 13 Carboxylic acids 13.1 Nomenclature 13.2 Acidity of carboxylic acids Factors affecting the acidity of carboxylic acids Dicarboxylic acids 13.3

Factors affecting the acidity of carboxylic acids:Inductive effects of the substituents

C COOHCl

Cl

Cl

> C COOHCl

Cl

H

> C COOHCl

H

H

> C COOHH

H

H

pKa 0.7 1.48 2.85 4.75

With more electron-withdrawing groups, acidity of the carboxylic acid is stronger. Inductive effects fall off rapidly as number ofσbond increases.

P313,10.3P313,10.3

Page 7: Chapter 13 Carboxylic acids 13.1 Nomenclature 13.2 Acidity of carboxylic acids Factors affecting the acidity of carboxylic acids Dicarboxylic acids 13.3

CH3 CH2 CH C

O

OH

Cl

> CH3 CH2CH C

O

OH

Cl

> CH2 CH2CH2 C

O

OH

Cl

pKa: 2.85 4.05 4.50

2-Chlorobutanoic 3-Chlorobutanoic 4-Chlorobutanoic acid acid acid

Carbon becomes more electron-withdrawing as its s character increases:

sp3 < sp2 < sp

CH3COOH CH2 CHCOOH COOH

pKa: 4.8 4.3 4.2

Page 8: Chapter 13 Carboxylic acids 13.1 Nomenclature 13.2 Acidity of carboxylic acids Factors affecting the acidity of carboxylic acids Dicarboxylic acids 13.3

Dicarboxylic acids:HOOCCH2COOH

pKa1 = 2.9HOOCCH2COO + H+

HOOCCH2COO pKa2 = 5.2 OOCCH2COO + H+

Oxalic acid(草酸或乙二酸)

Malonic acid(丙二酸)

Heptanedionic acid(庚二酸)

pKa1: 1.2 2.8 4.3

HOOC CH2 COOH

HO2CCO2H > HO2CCH2CO2H > HO2C(CH2)5CO2H

OOC CH2 COOH Carboxylate group with Electron-donating (+I)

Carboxylic group with electron-withdrawing (-I)

CH2

C

O

O

CO

O

HCH2

C

O

O

CO

O

HField effect(场效应) : electronic effects is transferred by space

Ch.P375Ch.P375

Page 9: Chapter 13 Carboxylic acids 13.1 Nomenclature 13.2 Acidity of carboxylic acids Factors affecting the acidity of carboxylic acids Dicarboxylic acids 13.3

13.3 Preparation of carboxylic acids13.3.1 Preparation of carboxylic acids by carboxylation (羧化作用) of Grignard reagentGrignard reagents react with carbon dioxide to yield Mg salt of carboxylic acids , acidification (酸化) produces RCOOH

BrMg

Et2O MgBr1) CO2

2) H3O+CO2H

2,2-Dimethylpropanoic acid

(80%)

Benzoic acid(85%)Carbonation = carboxylation

(CH3)3C MgCl + O C O O C O MgCl

C(CH3)3H3

+O(CH3)3CCOOH

P316, 10.4P316, 10.4

RX RCOOH1)2) Extension of C skeleton by 1 carbon atom.3) Limitation: OH, NH, SH or C=O

Page 10: Chapter 13 Carboxylic acids 13.1 Nomenclature 13.2 Acidity of carboxylic acids Factors affecting the acidity of carboxylic acids Dicarboxylic acids 13.3

13.3.2 Preparation of carboxylic acids by the preparation and hydrolysis of nitriles (腈) SN2 reaction of alkyl halide with sodium cyanide produce nitrile (alkyl cyanide)( 烷基氰 ),Hydrolysis of nitrile yields RCOOH.

R-CH2X + CN R-CH2CNH+ or OH

H2O R-CH2COOH

+ NH4+ ( or NH3)

HOCH2CH2ClNaCN

80%HOCH2CH2CN

(1) NaOH

(2) H3+O

HOCH2CH2COOH(75% ~ 80%)

3-Hydroxy-propanenitrile

3-Hydroxy-propanoic acid

Ch.P368, (2)Ch.P368, (2)

Page 11: Chapter 13 Carboxylic acids 13.1 Nomenclature 13.2 Acidity of carboxylic acids Factors affecting the acidity of carboxylic acids Dicarboxylic acids 13.3

BrCH2CH2CH2Br NaCN

H2ONCCH2CH2CH2CN

1,5-Pentanedioic acid(83-85%)

H2O, HCl

¡÷CCH2CH2CH2HO

OC OH

O1,3-Dibromopropane 1,5-Pentanedinitrile

(77-86%)

Preparation of α- hydroxy carboxylic acids

CH3CCH2CH2CH3

OH

COOHCH3CCH2CH2CH3

O

CH3CCH2CH2CH3

OCH3CCH2CH2CH3

OH

COOH

1. NaCN

2. H+ CH3CCH2CH2CH3

OH

CN

H2O, HCl

¡÷

2-Pentanone 2-Pentanonecyanohydrin

2-Hydroxy-pentanoic acid

(60%)

Preparation of dicarboxylic acids

Page 12: Chapter 13 Carboxylic acids 13.1 Nomenclature 13.2 Acidity of carboxylic acids Factors affecting the acidity of carboxylic acids Dicarboxylic acids 13.3

13.4 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

Page 13: Chapter 13 Carboxylic acids 13.1 Nomenclature 13.2 Acidity of carboxylic acids Factors affecting the acidity of carboxylic acids Dicarboxylic acids 13.3

13.4.1 Esterification (酯化反应)

C

O

OHC6H5 + CH318O H C

O

C6H518OCH3 + H2O

Carboxylic acid Alcohol Ester Water

Which C—O bond was broken?Mechanism of acid-catalyzed esterification: Step 1 Protonation on the carbonyl group of the carboxylic acid

C

O

OHRH+

C

OH

OHR C

OH

OHR

P322P322

Page 14: Chapter 13 Carboxylic acids 13.1 Nomenclature 13.2 Acidity of carboxylic acids Factors affecting the acidity of carboxylic acids Dicarboxylic acids 13.3

Step 2 Nucleophilic attack of a molecule of alcohol to the protonated carbonyl group

R'OH OHR

O HR'

C

OH

C

OH

OHR

Tetrahedral intermediate

OH2R

OR'

-H2OC

OH

R O R'C

OHOHR

O HR'

C

OHStep 3 The proton transfers and dehydration

Step 4 Deprotonation to form the ester

-H+

C

O

O R'RC

OH

R O R'

Page 15: Chapter 13 Carboxylic acids 13.1 Nomenclature 13.2 Acidity of carboxylic acids Factors affecting the acidity of carboxylic acids Dicarboxylic acids 13.3

The fundamental mechanistic patterns(基本机理模式) of nucleophilic reaction of a carboxylic acid and its derivatives

1. Activation of the carbonyl group - protonation of carbonyl group2. Nucleophilic addition to the protonated carbonyl to form a tetrahedral intermediate3. Elimination from the tetrahedral intermediate to restore the carbonyl group

P318, 10.5P318, 10.5R C

O

Y R C

OH

YH+ :Nu

R C

OH

Y

Nu

R C

OH

NuR C

O

Nu-H+

Page 16: Chapter 13 Carboxylic acids 13.1 Nomenclature 13.2 Acidity of carboxylic acids Factors affecting the acidity of carboxylic acids Dicarboxylic acids 13.3

RCH2COOH + Br2(1) P

(2) H2ORCHCOOH + HBr

Br

13.4.2α-Halogenation of carboxylic acids: Hell-Volhard-Zelinsky reactionAliphatic carboxylic acids react with Br2 or Cl2 in the presence of P or PX3 to give α- halo acids

α- Halo acid

CH3CH2CH2CO

OH+ Br2

P CH3CH2CHCO

BrBr

H2O CH3CH2CHCO

BrOH Ch.P379,(5)Ch.P379,(5)

Page 17: Chapter 13 Carboxylic acids 13.1 Nomenclature 13.2 Acidity of carboxylic acids Factors affecting the acidity of carboxylic acids Dicarboxylic acids 13.3

α- Halo acids are important synthetic intermediates:

CH3CH2CHCOOH

Br

(1) K2CO3,H2O

100¡æ

(2) H+

CH3CH2CHCOOH

OH2-Hydroxybutanoic acid

(69%)A standard method for the preparation of α- amino acid:

(CH3)2CHCH2COOHBr2

PCl3(CH3)2CHCHCOOH

BrNH3

H2O(CH3)2CHCHCOOH

NH2

2-Amino-3-methylbutanoic acid (48%)

Page 18: Chapter 13 Carboxylic acids 13.1 Nomenclature 13.2 Acidity of carboxylic acids Factors affecting the acidity of carboxylic acids Dicarboxylic acids 13.3

C

O

HO CH2C

O

O

Hslowly

HOC

CH2

OH

O C O

13. 4. 3 Decarboxylation (脱羧反应) of Malonic acid and related compounds

R C

O

OHdecarboxylation R H + CO2

HO C

O

C

O

CH3OH 150 ¡æC

O

CH2HO + CO2

Malonic acid Acetic acidCarbondioxide

Mechanism

HOC

O

CH3

Thermaldecarboxylation

Thermaldecarboxylation

C

O

HO CH2C

OH

O

Transitionstate

Malonic acid decarboxylates readily:

Page 19: Chapter 13 Carboxylic acids 13.1 Nomenclature 13.2 Acidity of carboxylic acids Factors affecting the acidity of carboxylic acids Dicarboxylic acids 13.3

100 ~ 150 ¡æ-CO2

When α- H was replaced, decarboxylation also occurs readily.

2-(2-Cyclopentenyl)malonic acid

(2-Cyclopentenyl)acetic acid(96~99%)

Decarboxylation of β- keto acids leads to ketones

R C

O

C

O

CH3OH 100 ~ 150 ¡æC

O

CH2R-CO2

Page 20: Chapter 13 Carboxylic acids 13.1 Nomenclature 13.2 Acidity of carboxylic acids Factors affecting the acidity of carboxylic acids Dicarboxylic acids 13.3

13.5 Spectroscopic analysis of carboxylic acids

IR: O - H Stretching 3500~2500 cm-1

C = O Stretching 1700 cm-1

NMR: COOH: 10-12 ppm

Page 21: Chapter 13 Carboxylic acids 13.1 Nomenclature 13.2 Acidity of carboxylic acids Factors affecting the acidity of carboxylic acids Dicarboxylic acids 13.3
Page 22: Chapter 13 Carboxylic acids 13.1 Nomenclature 13.2 Acidity of carboxylic acids Factors affecting the acidity of carboxylic acids Dicarboxylic acids 13.3

Ar - H

CH2

COOH