Carboxylic AcidsNitriles

Natural Products

Nomenclature

Acidity

Preparation

Reactions

Analgesics

ibuprofinHO2C

acetyl salicylic acid

CO2H

OCCH3

O

(S)(+)-

Fats and Fatty Acids

CO2H

palmitic acid (a fatty acid)

CH2

CH

CH2

OCR

OCR

O

O

O

OCR

a triglyceride

R = n-C15H31

Prostaglandins

a prostaglandin

O

HO

CO2H

OHarachadonic acid

CO2Hcyclo-

oxygenase

natural mediators of inflammation

Penicillins from moldPenicillium chrysogenum

R= NH2 ampicillin

N

S

CO2H

PhCHCNH

O

R

O

R = H penicillin G

From Ergot Fungus

(+) lysergic acid

N

NH

CH3HO2C

H

Common Nomenclature

HCO2H

CH3CO2H

CO2H

CO2H

CO2H

Prefix

form

acet

propion

butyr

valer

prefix + ic + _acid

CO2HCl

-chlorovaleric acid

CO2H

CO2H

CO2H

capro

enanth

capryl

CO2Hpelargon

CO2Hcapr

CO2H

Cl Cl

dichloro--phenylcaprylic acid

I.U.P.A.C. Nomenclature

O

OHheptanoic acid

drop e from alkane and add "oic acid"

CO2H(Z) 2-methyl-2-pentenoic acid

CO2H

cyclopentanecarboxylic acid

CH2CO2H

Brp-bromophenylethanoic acidp-bromophenylacetic acid

Dicarboxylic Acids

HO2CCO2H or ethanedioic acid

HO2CCH2CO2H

HO2CCH2CH2CO2H

HO2CCH2CH2CH2CO2H

HO2CCH2CH2CH2CH2CO2H

HO2CCH2CH2CH2CH2CH2CO2H

oxalic acid

malonic acid

succinic acid

glutaric acid

adipic acid

pimelic acid

'

A Diacid

OH

O

O

HO

Br Cl

-bromo-'-chloroadipic acid

2-bromo-4-chlorohexanedioic acid

Unusually High Melting and Boiling Points

Boiling Points

CH3COH

O

CH3CH2CH2OH

CH3CH2CH

O

b.p. Co

118

97

49

CH3CH2OCH3 8

Acidity is due to Delocalization of the Charge in the Conjugate Base

Alcohol vs. Acid

e- Withdrawing Groups Enhance Acidity

Benzoic acids

CO2H

NO2

CO2H

CHO

CO2H

H

CO2H

OCH3

pKa: 3.41 3.75 4.19 4.46

CO2H

Cl

4.0

most deactivated most activated

Deprotonation

COH

O

+ NaHCO3

CO

O

Na

+ H2CO3

pKa 4.2 pKa 6.5

Ester Formation

COH

O

1) NaOH

2) CH3CH2CH2CH2Brp.t.c.

COCH2CH2CH2CH3

O

Carboxylic Acid Preparations

• Oxidation of 1o alcohols and aldehydes with Na2Cr2O7/H2SO4

• KMnO4 oxidation of alkylbenzenes

• Grignard reaction with CO2 (Carboxylation)

• Hydrolysis of a carboxylic derivative:

e.g. acid chloride, acid anhydride, ester, amide, nitrile

Grignard Reaction with CO2

Br1) Mg, ether

2) CO2, -78oC3) H3O+

CO2H

Mechanism

CO2H

3) H3O+2) CO2, -78oC

1) Mg, etherBr

MgBr

C

O

O

C

O

O MgBr

H+Mg

Hydrolysis of a Nitrile

BrKCN

CNH3O+

or 1) NaOH2) H3O+

CO2HSN2

Reduction of Carboxylic Acids

Naming Nitriles

CH3CHCH2CH2CN

CH3

4-methylpentanenitrileCN

cyclohexanecarbonitrile

CN

5-hexynenitrile

CN

Clp-chlorobenzonitrile

Dehydration of an Amideuse strong dehydrating agent

or SOCl2+ H2O

Reduction of Nitriles

CN CH2NH2

1) LiAlH4

2) H2O

Grignard Addition to a Nitrile

CN1) CH3MgBr

2) H3O+, heat CH3

O

+ NH3heptanenitrile 2-octanone

Partial Mechanism

C N1) CH3MgBr

2) H3O+, heat CH3

O

+ NH3

CN

CH3

CN

CH3

H

an imine

H3O+

H

pH = 4-5

H3O+

imine hydrolysis

The Rest of the Mechanism

CH3

N H

H3O+

CH3

N H

H

H+

H2O

CH3

NH2OHH

NH3

CH3

OH

H+ transferintermolec.

CH3

OH

O

CH3

H2O