Carboxylic Acids: common in nature

CH3COOH

COOH

COOH COOH

odor of sour butter

odor of goats, socks palmitic acid (precursor of fat)

vinegar

COOHCH3

CH3 H

HHO OH

OH

HCholic acid

(major component of human bile)

CH3COOHCH3CHOcobalt acetate

O2 80oCCH3OH

CORh catalyst

Industrial synthesis of acetic acid:

Ch.20 Carboxylic Acids and Nitriles

Carboxylic Acids: RCO2H

CO2H CO2H1 1

Propanoic acid 4-Methylpentanoic acid

- parent chain contains the -COOH group, - carboxyl carbon is numbered as 1

20.1 Nomenclature

alkane (-e) → -oic acid

HO2CCO2H

Et

1

3-Ethyl-6-methyloctanedioic acid

-carboxylic acid

COOH

3-Bromocyclohexanecarboxylic acid

Br 1

-COOH is attached to a ring

CO2H

1-Cyclopentenecarboxylic acid1

Common Names

HCOOH

H3C COOH

COOH

COOH

COOH

COOH

COOH

Formic acid

Acetic acid

Propionic acid

Butyric acid

Oxalic acid

Acrylic acid

Benzoic acid

HOOC

HOOC COOH Malonic acid

COOHHOOC Succinic acid

HCO-

H3C CO-

CO-

CO-

CO-

CO-

CO-

Formyl

Acetyl

Propionyl

Butyryl

Oxalyl

Acryloyl

-OC

-OC CO- Malonyl

CO--OC Succinyl

Acyl groups

Benzoyl

Nitrile: RCN

CN1

4

4-Methylpentanenitrile

- nitrile- CN carbon is numbered as 1

complex nitrile -(o)ic acid → onitrile-carboxylic acid → -carbonitrile

H3C C N

Acetonitrile

CN

Benzonitrile

CN

CH3CH3

1

2

2,2-Dimethylcyclohexanecarbonitrile

R OH

Osp2

120o

planar

R OH

O

ROH

O

dimer: H-bonding (high b.p.)

20.2 Structure and Physical Properties of Carboxylic Acids

Structure

- high b.p. and m.p.- b.p. of acetic acid: 118oC

20.3 Dissociation of Carboxylic Acids

R OH

O

water-insoluble

+ NaOHH2O R O

O

water-soluble

+ H2ONa+

Acidity: weak bases (NaOH, NaHCO3) generate carboxylate, RCO2

-Na+

H3C OH

O

CH3CH2OH HCl

pKa = 16 4.75 -7

Acetic acid: only 0.1% dissociate in 0.1M solutionHCl: 100% dissociate

Alkoxide / Carboxylate ion

localized charge

H3C

H2C

OH

H3C

H2C

O

H3C O

OH

H3C O

O

H3C O

O

delocalized chargeresonance-stabilized carboxylate ion

HC

O

ONa+

Sodium formate

127 pm

HC

O

O

Formic acid

120 pm

H

134 pm

purification of acid: dissolve salts in water, extract out organic impurities with organic solvent, acidify aqueous layer to obtaincarboxylic acids

Carboxylic acids with more than six carbons are insoluble in water

20.4 Substituent Effects on Acidity

Acid pKa

CH3CH2OHCH3CH2COOHCH3COOHH2C=CHCO2HPhCO2HHOCH2COOHHCO2HICH2CO2HBrCH2CO2HClCH2CO2HFCH2CO2HF3CCO2H

164.874.754.254.193.833.753.122.682.852.590.23

strongeracid

H3C OH

O

CH2 OH

O

Cl CH OH

O

C OH

OCl

ClCl

Cl

Cl

stronger acid

Acidity of chloroacetic acids: inductive effect

CH2 O-

O

Cl

electronegative Cl stabilizes anion

- inductive effect operates through σ-bond and depends on distance

COOH

Cl COOHCl COOHCl COOH

pKa = 2.86 4.05 4.52 4.82

20.5 Substituent Effects in Substituted Benzoic Acids

OH

O

stronger acid

OH

O

O2N

OH

O

MeO

pKa = 4.46 4.19 3.41

- acidity of substituted benzoic acid correlate reactivity of thesubstituted benzene

OH

O

Y Y

pKapredict reactivity ofelectrophilic attack

"inverse relationship"

20.6 Preparation of Carboxylic Acids

Oxidation of benzylic C-H

COOHCH3 KMnO4

H2O95oC

KMnO4

H3O+O

HO+ CO2

H

HH

Oxidation of alcohol/aldehyde

R CH2OHCrO3

R COOHH2SO4, H2O

R CHOAgNO3

R COOHNH4OH

Hydrolysis of nitrile

R CN1. H2O, OH-

R COOH2. H3O+

OBr

1. KCN

3. H3O+O

COOH2. H2O, OH-

- a typical way to introduce one carbon fragment from alkyl halides

R COH-

H3O+

NN

R OH

NH

R OH

H3O+ O

R OH

Carboxylation of Grignard reagents

R CH2MgXCO2

R CH2R CH2 CO

O MgXH3O+

COOHC OO

2. H3O+

BrMg

ether

MgBr1. CO2

COOH

20.7 Reactions of Carboxylic Acids: An Overview

General reactions of carboxylic acids

CC

O

OH

CC

OH

HH

H

CC

Y

OHC

COH

OR

Deprotonation Reduction

Alpha-substitution Nucleophilic acyl substitution

CC

OH

OH

20.8 Reduction of Carboxylic Acids

LiAlH4: alkenes are not reduced

OH

O 1. LiAlH4

2. H3O+ OH

BH3: alkenes can be hydroborated, esters are not reduced

OH

O 1. BH3, THF

2. H3O+

O2N

OH

O2N

- LiAlH4 reduces both nitro and acid

20.9 Chemistry of Nitriles

RC

OH

OC NR

same oxidation level

Preparation

BrCH2R C NCH2RNaCN

SN2 substitution by -CN

C NCH2RR NH2

O SOCl2

benzene80oC

+ + 2 HClSO2

From amide: SOCl2, POCl3

R NH2

O ClS

Cl

O

R NH2

OS

Cl

O

R N

OS

Cl

O

H

R C N+SO2 + HCl

Reactions of Nitriles

R R

O

Nu-

O-

RNu

R

C NRNu-

N

NuR

products

products

alkoxide ion

imine ion

R R'

O

R NH2

H2O1. R'MgX

R OH

O

1. [H-]

R C N

2. H3O+

2. H3O+

1. [H-]

2. H3O+

R H

O

Hydrolysis: acidic or basic conditions

R CNH2O, OH-

R COOHor H3O+

C NRN

OHR

imine anion

-OH

H2O NH

OHRO

NH2R

O

OHR

Reduction: LiAlH4, DIBAL

R R NH21. LiAlH4

2. H3O+C N

to primary amine:

1. DIBAL

2. H2OC N CHO

to aldehyde:

C NRN

HR

imine anion

R H

NH2

H-H2. H3O+

LiAlH41. LiAlH4

DIBALtoluene N

HR

imine anion

H2O O

HR

Grignard addition: ketone formation

C NRN

R'R

imine anion

R R'

O

R'MgX

+MgXH3O+

+ NH3

CN 1. EtMgBr

2. H3O+

O

20.9 Spectroscopy of Carboxylic Acids and Nitriles

IR Spectroscopy

associated carboxyl (usual case)1710 cm-1

1760 cm-1

very broad2500-3300 cm-1O-H

free carboxyl (uncommon)C=O

R OH

O

R OH

O

ROH

O

1760 cm-1 1710 cm-1

2250 cm-1RCN

IR Spectrum of n-Butanoic acid

NMR Spectroscopy

165-185 ppm~ 12 ppm,

C=O13C NMRCOO-H1H NMR

CH3CH2CN

12110 11

1H NMR Spectrum

Vitamin CChemistry @ Work

Vitamin C: ascorbic acid

H

OH

OH

HO O

HO OH

Vitamin C(Ascorbic acid)

OHOHO

OHOH

OH

Glucose

Industrial synthesis of ascorbic acid from glucose

Chemistry @ Work

Chapter 20

Problem Sets

20, 26, 35, 39, 45