Download Carboxylic Acids

Car b ox ylic 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):
Carboxylic acids undergo hydrogen bonding much like alcohols. However, in a
carboxylic acid you have both a hydrogen bond donor and acceptor in the same
molecule. These acids thus form highly stable dimers (as shown below). For small
acids (e.g. acetic acid) this dimer cannot even be broken down by distillation –
which explains why the boiling point for these acids is so high (the molecular
weight is essentially doubled.
The acidity of these compounds can be modified by changing the substituents
on the alkyl portion of the acid. Electron withdrawing groups make the molecule
more acidic (by stabilizing the negative charge on the conjugate base), while
electron-donating groups make it less acidic, by destabilizing that same charge.
You should know this relationship already! It’s the same one that determines
good leaving groups and electrophiles, the stability of carbocations and
carbanions, it is a major force in organic chemistry.
Again:
Electron withdrawing groups stabilize negative charges
Electron donating groups destabilize negative charges.
Pr oto nat io n
OH
OH
O
R
H3O+
O
R
O
H
OH
H
R
O
favored
R
O
H
H
or
O
R
-
O
H
H
protonation at carbonyl is favored by resonance stabilization while
protonation at oxygen is disfavored by partial positive charge on carbon.
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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-tospeed:
1) Oxidation of a PRIMARY alcohol with Na2Cr2O; e.g.
O
H
Na2Cr2O7
CH3CH2
C
CH3CH2
OH
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
18-crown-6, 25˚C
Ph
18-crown-6 is used to make KMnO4 soluble in benzene
3) Oxidative cleavage of internal and terminal alkynes with O3.
O3
H
H2O
O
OH
4) Oxidation of aldehydes with silver.
O
HO
H
Ag2O, NH4OH
(Tollens reagent)
O
HO
+ Ag (mirror)
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):
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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:
Ge nera l feat ur es of ca r box ylic acid s
- strong acids protonate the carbonyl group of carboxylic acids – see above
discussion
- carboxylic acids react as Bronsted-Lowry acids, i.e. proton donors. They
are strong organic acids; even a weak base such as NaHCO3 is strong
enough to deprotonate carboxylic acids – see Tab le 1 9.3
Again, acidity of these compounds arises from the resonance stabilization of the
conjugate base (bond lengths equalize):
see Fig ure 19 .7 – the more stable the conjugate base, the more acidic the
compound.
-
Electron withdrawing groups stabilize a conjugate base, making a
carboxylic acid more acidic
3
-
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
O
R
S
OH
e.g.
O
(TsOH)
O
O
R
S
O
O
O
OH
:B
OH
S
R
S
R
O
O
S
O
R
S
O
- HB
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
R
H
!-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
H
L amino
R
COOH
acid
H
HOOC
D amino
acid
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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
NH2
C
R
COO
H
!-amino acid
NH3
C
R
H
zwitterion
An amino acid can exist in three different forms depending on pH of the
solution:
- at low pH, the amino acid has a net positive charge due to protonation of
the carboxylate anion
- at pH = ~7, the amino acid exists as the zwitterion (no net charge)
- at high pH, the ammonium cation is deprotonated and the amino acid has a
net negative charge
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
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