Chapter 19: Carboxylic

Acids

Carboxy group: -COOH, -CO2H,

Naming: Alkanoic Acids

IUPAC: Replace e of alkane name with oic acid
O
OH

4-Methylhexanoic acid

C1

Cyclic: Cycloalkanecarboxylic acids

O

OH

OH
C1, as in cyclic
aldehydes
Cyclohexanecarboxylic acid

1-Naphthalenecarboxylic acid

Common Names

Include as many functions as possible in stem

(Better than 4-acetylheptanoic acid)

Carboxylic acids take precedence over other groups:

Physical Properties

Planar
structure,
trigonal
carbonyl
carbon

The carboxy group is polar,

undergoes hydrogen bonding, and
forms dimers:

Dimerization causes relatively

high melting and boiling points

H NMR Chemical Shifts

O
HO
10-13 ppm

C
H

2-2.5 ppm
cf. aldehydes
and ketones

Aldehyde like
O

OH

C NMR Chemical
Shifts

13

Not quite
as low field
as aldehyde
or ketone

IR Spectroscopy

Two important bands:

O-H = 2500-3300 cm-1, C=O = 1710
-1

Resonance
~200 ppm

~180 ppm

Acidity

The carboxy group is relatively acidic:

Reasons: 1. Carbonyl carbon is inductively strongly electron

withdrawing, 2. Carboxylate ion is stabilized by resonance

Acetate

Compare

2-Propenyl (allyl)
H +

BH +

CH2 H2C
pKa ~ 40

Electron withdrawing groups

increase the acidity (decrease pKa):
CF3COOH pKa ~ 0.23

Distance affects acidity:

COOH

COOH

pKa 4.19

Cl

pKa 3.98

Basicity

Protonated on the carbonyl oxygen:

Allows for allylic resonance

Preparation
1. Oxidation of primary alcohols and aldehydes

With KMnO4; or CrO3, H2O; or HNO3; or H2O2; or Cu2+, or Ag+.

Recall Cr(VI) oxidation:

In H2O: Hydrate, which

oxidizes to acid

2. Carbonation: Organometallic
reagents and carbon dioxide

Example:

Synthetic strategy: RH RX RMgBr RCO2H

3. Nitrile hydrolysis

Mechanism:

Tautomerization

COOH

CN
1.NaOH, H2O
2. H+, H2O
90%

Cl

Cl

Cyanohydrin-hydrolysis: -Hydroxy acids

Reactions
Lead to carboxylic acid derivatives:

E+

General:
:Nu
Leaving
group

Nucleophilic substitution occurs

by addition-elimination

Nucleophilic Substitution
by Addition- Elimination
Acid or base catalyzed
:

Elimination

Addition

Tetrahedral
intermediate

Potential problem: Acidity

Base Catalyzed Mechanism

Must not compete with :Nu-

Acid Catalyzed Mechanism

Synthesis of Carboxylic
Acid Derivatives
A. Alkanoyl
Halides
:
O
R

X= Cl, Br

uphill

OH + -Cl

More
stable

Poor
Nu

O
R

+
OH
Cl

Less
stable

Bad leaving
group, strong
base, good
Nu

Therefore use other reagents: SOCl2, PCl5, PBr3

SOCl2:

Mechanism: First step is to convert the

bad leaving group OH into a good one

Good
leaving
group

Then it is addition-elimination:

Same as ROH RCl, except addition-elimination

and not SN2

PCl5:
O

O
OH

+ PCl5

PCl3
O

+ HCl

Cl

+
90%

PBr3:

PBr3 Mechanism:
1.

O
R

OH

Br

PBr2

OPBr2

+ HBr

2.

:O:
R

:OH

H+ + : Br: -

OPBr2

OPBr2
Br

HOPBr2 +

O
R

Br

B.
Anhydrides

Cyclic anhydrides: Just heat, or SOCl2

C.
Esters:
Alcohols + carboxylic acids, cat. mineral acid, reversible

Example:

H ~ 0, S ~ 0, G ~ 0

Reverse: Ester hydrolysis, driven by excess H2O. Can also be

effected by aqueous NaOH (Chapter 6: RX + Na+-O2CR).

EsterHydr
Gallag

Mechanism:
H+ mineral acid, e.g., H2SO4, HCl, proceeds initially like
acetalization of aldehydes and ketones

Note: Carbonyl oxygen is always more basic than

hydroxy oxygen, because of resonance in the
protonated product.

Ester

Intramolecular esterification: Lactones

Even without removing the water the equilibrium is

favorable because of entropy (positive). As always in
reversible reactions (thermodynamic control),
cyclization is best for five and six membered rings.

D. Amides

Note: M+ -NH2 are also

called amides.

Heat carboxylic acid with an amine:

This method is rarely used. Problem: Fast

(although reversible) salt formation (reverse is
slow, hence needed)

Mechanism:

Highly pH dependent profile. We shall see in

Chapter 20 that amide formation is better
accomplished by activation of the carboxy
group, as in alkanoyl halides or anhydrides or
even esters.

Cyclic amides: Imides from dioic

acids, or lactams fom amino acids
Imide formation:

Lactam formation:

Penicillins are lactams:

ROH stands for transpeptidase, the
enzyme necessary for all cell wall
construction. Osmotic pressure in a
cell is enormous, 10-20 atm. Penicillin
causes literally an explosion.

RHN H H
N

O
R'

OH

COOH

Other Reactions of
Carboxylic Acids
1. Reduction by LiAlH4

Mechanism complex,
not clear, possibly via:

O
R

Al

C O Li
H

:H

2. Hell-Volhard-Zelinsky Reaction:
Makes -bromocarboxylic acids

Carl Magnus von Hell

(1849-1926)

Nikolaj Zelinski
(1861-1953)

Jakob Volhard
(1834-1910)

P + Br2 PBr3

Important functionalization; can be exploited to access

-amino acids. Mechanism is reminiscent of acid
catalyzed halogenation of aldehydes and ketones.

Mechanism:
As in the acid catalyzed halogenation of aldehydes and ketones,
this needs enolization of RCH2COOH. However, the COOH group
is too stable to enolize sufficiently, hence it requires activation
to RCH2C(O)Br.

pKa ~ 16!

Detailed mechanisms of steps 2 and 3: