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Carboxylic Acids
Carboxylic Acids
Carboxylic acids have one property that distinguishes them from most other
organic compounds – they’re acidic. Now not as acidic as fuming sulfuric acid,
but still pretty darned acidic. The acidity of these compounds arises from the
resonance stabilization of the conjugate base (bond lengths equalize):
Pr oto nat io n
OH OH OH
H H H
O R O R O R O
H3O+ favored
H
R O or
O
H
R O
H
- protonation at carbonyl is favored by resonance stabilization while
protonation at oxygen is disfavored by partial positive charge on carbon.
1
Pre par ation o f ca rb ox ylic a cids :
You’ve already seen a veritable plethora of methods for the preparation of
carboxylic acids. Let me run a few by you just to make sure everyone is up-to-
speed:
1) Oxidation of a PRIMARY alcohol with Na2Cr2O; e.g.
H O
Na2Cr2O7
CH3CH2 C OH CH3CH2 C OH
H2-SO4, H2O
H
2) Oxidation of aromatic side chains containing benzylic hydrogens with KMnO4
O
KMnO4 OH
KMnO4 oxidation of alkenes or alkynes is also possible although not common; e.g.
O
Ph
KMnO4
OH
Ph 18-crown-6, 25˚C
H OH
only the aldehyde is
oxidized, and not the 2˚
alcohol
There are a few other ways to get carboxylic acids out of various compounds.
For example, nitriles (formed by the reaction of an alkyl halide with KCN) can be
hydrolyzed under acidic (milder) or basic (very harsh) conditions to give the
corresponding acid. If the nitrile is hydrolyzed under basic conditions, the amide
is the compound more commonly isolated (rather high temperatures are required
to get the acid under basic conditions):
2
A somewhat more common method for the preparation of carboxylic acids is the
carboxylation of Grignard reagents. This is really a straightforward reaction – a
Grignard reagent is simply quenched with dry ice (solid CO2). The Grignard
attacks the carbonyl group to form the acid, which is relatively inert to further
attack. In fact, any of the R- M reagents we’ve talked about in the past will do
this carboxylation reaction:
see Fig ure 19 .7 – the more stable the conjugate base, the more acidic the
compound.
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- Electron donating groups destabilize a conjugate base, making a
carboxylic acid less acidic – pa ge 7 03- 704
Su bst it uted Benz o ic acid s
- electron donating groups activate benzene to electrophilic attack and
hence make the benzoic acid derivative less acidic
- electron withdrawing groups deactivate benzene to electrophilic attack
and hence make the benzoic acid derivative more acidic – see Figu re
19.8
Su lfo nic Acids –
- very strong acids (pKa values ~ -7) because their conjugate bases are
resonance stabilized and all resonance structures delocalize a negative charge on
oxygen; sulfonate ions are weak bases hence make good leaving groups in
nucleophilic substitution
O
OH
O S
R S OH e.g. O
O (TsOH)
O O O O
:B
R S OH R S O R S O R S O
- HB
O O O O
Am in o Acids
- most natural occurring amino acids have the amino group bonded to the α
carbon and hence are called α-amino acids
COOH
NH2 C H
R
!-amino acid
Glycine, the simplest amino acid has R = H. When R≠H, the α-carbon is a
stereogenic center and two enantiomers are possible:
NH2 H2N
R R
H H
COOH HOOC
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Exce pt fo r whe n R = CH 2 S H, the α carbon has the S configuration. The
natural occurring enantiomer of an amino acid is assigned as the L isomer and its
unnatural enantiomer is the D isomer.
Amino acids are never uncharged neutral compounds; they exist as zwitterionic
salts hence they have high melting points and are soluble in water
COOH COO
NH2 C H NH3 C H
R
!-amino acid R zwitterion
The isoelectric point (pI) is the pH at which the amino acid exists primarily in
its neutral form (as a zwitterion):
pI = [pKa (COOH) + pKa (NH3+)]/2