Download Carboxylic Acids - GCG-42

Carboxylic Acids
SANTOSH
CHEMISTRY DEPT
Carboxylic acids:
R-COOH, R-CO2H,
O
R C
OH
Common names:
HCO2H
formic acid
CH3CO2H
acetic acid
CH3CH2CO2H
propionic acid
CH3CH2CH2CO2H
butyric acid
CH3CH2CH2CH2CO2H
valeric acid
5 4 3 2 1
C—C—C—C—C=O
δ γ β α
Br
CH3CH2CH2CHCOOH
 bromovaleric acid
used in common names
CH3
CH3CHCH2COOH
 -methylbutyric acid
isovaleric acid
COOH
benzoic acid
COOH
CH3
COOH
COOH
CH3
CH3
o-toluic acid
m-toluic acid
p-toluic acid
IUPAC nomenclature for carboxylic acids:
parent chain = longest, continuous carbon chain that
contains the carboxyl group  alkane, drop –e, add –oic
acid
HCOOH
methanoic acid
CH3CO2H
ethanoic acid
CH3CH2CO2H
propanoic acid
CH3
CH3CHCOOH
2-methylpropanoic acid
Br
CH3CH2CHCO2H
2-bromobutanoic acid
Dicarboxylic acids
HOOC-COOH
oxalic acid
HO2C-CH2-CO2H
malonic acid
HO2C-CH2CH2-CO2H
succinic acid
HO2C-CH2CH2CH2-CO2H
glutaric acid
HOOC-(CH2)4-COOH
adipic acid
HOOC-(CH2)5-COOH
pimelic acid
CO2H
CO2H
CO2H
CO2H
CO2H
CO2H
phthalic acid
H
H
C
C
isophthalic acid
terephthalic acid
COOH
H
COOH
HOOC
maleic acid
C
C
COOH
H
fumaric acid
salts of carboxylic acids:
name of cation + name of acid: drop –ic acid, add –ate
CH3CO2Na
sodium acetate or sodium ethanoate
CH3CH2CH2CO2NH4
ammonium butyrate
ammonium butanoate
(CH3CH2COO)2Mg
magnesium propionate
magnesium propanoate
Physical Properties:
polar + hydrogen bond  relatively high mp/bp
water insoluble
exceptions: four carbons or less
acidic
turn blue litmus  red
soluble in 5% NaOH
RCO2H + NaOH  RCO2-Na+ + H2O
stronger
stronger
weaker
weaker
acid
base
base
acid
• Two molecules of a carboxylic acid can hydrogen bond together.
O
CH3
H O
C
C
O H
O
CH3
RCO2H
RCO2-
covalent
water insoluble
ionic
water soluble
Carboxylic acids are insoluble in water, but soluble in 5%
NaOH.
1. Identification.
2. Separation of carboxylic acids from basic/neutral organic
compounds.
The carboxylic acid can be extracted with aq. NaOH and
then regenerated by the addition of strong acid.
General Methods of preparation of Carboxylic Acids:
1. oxidation of 1o alcohols:
CH3CH2CH2CH2-OH + CrO3  CH3CH2CH2CO2H
n-butyl alcohol
butyric acid
1-butanol
butanoic acid
CH3
CH3
CH3CHCH2-OH + KMnO4  CH3CHCOOH
isobutyl alcohol
isobutyric
acid
2-methyl-1-propanol`
2-methylpropanoic
acid
2. Oxidation of alkylbenzenes:
CH3
KMnO4, heat
COOH
toluene
CH3
benzoic acid
COOH
KMnO4, heat
note: aromatic acids
only!
HOOC
H3C
terephthalic acid
p-xylene
KMnO4, heat
CH2CH3
ethylbenzene
COOH + CO2
benzoic acid
3. Carbonation of Grignard Reagents:
O
R MgX +
CO2
R C O
ether
( R-Li )
H3O+
O
R C OH
+ MgX(OH)
+
MgX
CH3
CH3
Mg
CH3
CO2
Br
H+
MgBr
COOH
p-toluic acid
Br2, hv
CH3
Mg
CH2Br
CH2MgBr
CO2
H+
CH2 COOH
phenylacetic acid
Hydrolysis of Nitriles
R CH2 Cl
_
+ : C N:
SN2
DMSO
R CH2 C N
H2SO4
+ Cl
H 2O
heat
O
R CH2 C OH
+
+ NH4
CH3
Br2, hv
NaCN
CH2Br
toluene
CH2 CN
H2O, H+, heat
CH2 COOH
phenylacetic acid
KCN
CH3CH2CH2CH2CH2CH2-Br
CH3CH2CH2CH2CH2CH2-CN
1-bromohexane
H2O, H+, heat
CH3CH2CH2CH2CH2CH2-COOH
heptanoic acid
CH2OH
KMnO4
CH3
KMnO4, heat
CO2H
Br
Mg
MgBr
C N
H2O, H+, heat
CO2; then H+
SYNTHESIS OF CARBOXYLIC ACIDS
R C C R
R
R
H
KMnO4
H
DIBAL or
Rosenmund
O
KMnO4
CrO3
H2SO4
O
CrO3
H2SO4
R C OH
CO2
H2O
R C Cl
O
H2SO4
H2O
R C OR
R
Li
or
R Mg X
( benzene = R
sidechain = R’ )
R CH2 OH
KMnO4
O
R C H
R'
or KMnO4
H2O
H2SO4
R C N
NaCN
acetone
KMnO4
R X
Li or
Mg
SOCl2
R OH
R
R
H
H
OH OH
Carboxylate Ion Formation
O
O
R CH2 C OH + NaOH
carboxylic acid
pKa

5
R CH2 C O
carboxylate ion
+
Na
+ H2O
Protonation and Deprotonation
of a Carboxylic Acid
.. H
+ O
..
..
:O
:O
.. R C O
:
..
NaOH
..
R C O
H
..
H2SO4
..
:O
..
R C O
H
H
+
H2SO4
..
R C O
H
..
.. H
:O
+
R C O H
..
equivalent structures
due to resonance
O
X C C OH
O
X C C O
+ H
• Electron-withdrawing Groups:
– strengthen acids
– weaken bases
• Electron-releasing Groups:
– weaken acids
– strengthen bases
+
Substituents with Electron-Withdrawing
Resonance ( - R ) Effects
X
Y
O
C OH
carboxyl
NO2
nitro
alkoxycarbonyl
C N
cyano
acyl
SO3H
sulfo
O
C OR
O
C R
-R substituents strengthen acids and weaken bases
Substituents with Electron-Releasing
Resonance ( + R ) Effects
..
OH
..
hydroxy
..
OR
..
O
..
O C R
..
alkoxy
..
SH
..
mercapto
CH3
methyl
CR3
alkyl
amino
..
NR2
dialkylamino
..
NH2
..
F
.. :
fluoro
..
Br :
..
bromo
..
:
Cl
..
..
I:
..
acyloxy
chloro
iodo
+R substituents weaken acids and strengthen bases
..
Y
Substituents with Electron-Withdrawing
( - I ) Inductive Effects
O
C OH
carboxyl
O
C OR
alkoxycarbonyl
O
C R
OH
acyl
hydroxyl
SH
mercapto
NH2
amino
Cl
chloro
NO2
nitro
C N
cyano
SO3H
sulfonic acid
OR
alkoxy
NR2
dialkylamino
F
fluoro
Br
bromo
I
iodo
+
N(CH3)3
X
trimethylammonium
-I substituents strengthen acids and weaken bases
Substituents with Electron-Releasing
Inductive ( + I ) Effects
R
CH3
methyl
O
CR3
alkyl
O
oxide
C O
carboxylate
+I substituents weaken acids and strengthen bases
O
pKa = 4.75
CH3 C OH
increasing
acidity
3.83
2.34
Br CH2 C OH
2.86
Cl CH2 C OH
2.86
O
O
H O CH2 C OH
3.12
O
O
H2N CH2 C OH
I CH2 C OH
O
O
O2N CH2 C OH
O
1.68
F CH2 C OH
2.66
O
CH3 C OH
O
pKa = 4.75
H C OH
O
O
Cl CH2 C OH
2.86
CH3 C OH
4.75
O
O
Cl CH C OH
3.77
1.29
CH3 CH2 C OH
4.88
Cl
O
CH3 CH C OH
Cl O
Cl
C C OH
0.65
4.86
CH3
Cl
CH3 O
CH3 C
CH3
C OH
5.05
COOH
Cl
2.16
ortho
COOH
3.82
3.47
meta
meta
NO2
COOH
Cl
NO2
ortho
COOH
Cl
COOH
pKa = 2.92
COOH
3.98
para
O2N
Benzoic Acid: pKa = 4.19
para
3.41
COOH
COOH
4.08
4.06
OCH3
OH
COOH
COOH
CH3 O
4.46
4.48
HO
COOH
Benzoic Acid: pKa = 4.19
2.97
OH
Chemical Properties of Carboxylic Acids:
1. as acids
2. conversion into functional derivatives
a)  acid chlorides
b)  esters
c)  amides
3. reduction
4. alpha-halogenation
5. EAS
1) Salt formation:
a) with active metals
RCO2H + Na  RCO2-Na+ + H2(g)
b) with bases
RCO2H + NaOH  RCO2-Na+ + H2O
c) relative acid strength?
CH4 < NH3 < HCCH < ROH < HOH < H2CO3 < RCO2H < HF
d) quantitative
HA + H2O  H3O+ + A-
Ka = [H3O+] [A-] / [HA]
ionization in water
2) Formation of acid chlorides:
O
R C
OH
SOCl2
O
R C
Cl
or PCl3
orPCl5
CO2H + SOCl2
O
CH3CH2CH2 C
OH
COCl
PCl3
O
CH3CH2CH2 C
Cl
3) Formation of esters:
“direct” esterification:
H+
RCOOH + R´OH  RCO2R´ + H2O
-reversible and often does not favor the ester
-use an excess of the alcohol or acid to shift equilibrium
-or remove the products to shift equilibrium to completion
“indirect” esterification:
RCOOH + PCl3  RCOCl + R´OH  RCO2R´
-convert the acid into the acid chloride first; not reversible
O
C
OH
H+
+
CH3OH
SOCl2
O
C
Cl
CH3OH
O
+ H2O
C
O CH3
4) Formation of amides:
“indirect” only.
RCOOH + SOCl2  RCOCl + NH3  RCONH2
amide
O
PCl3
OH
3-Methylbutanoic acid
O
NH3
Cl
O
NH2
Directly reacting ammonia with a carboxylic acid results in an
ammonium salt:
RCOOH + NH3  RCOO-NH4+
acid
base
O
C
OH
PCl3
O
C
Cl
NH3
O
C
NH2
amide
NH3
O
C
O
NH4
ammonium salt
5) Reduction:
RCO2H + LiAlH4; then H+  RCH2OH
1o alcohol
LiAlH4
H+
CH3CH2CH2CH2CH2CH2CH2COOH
Octanoic acid
(Caprylic acid)
CH3CH2CH2CH2CH2CH2CH2CH2OH
1-Octanol
Carboxylic acids resist catalytic reduction under normal
conditions.
RCOOH + H2, Ni  No Reaction (NR)
O
CH2 C
OH
H2, Pt
LiAlH4
H+
CH2CH2OH
NR
6) Halogenation of alkyl groups (Hell-Volhard-Zelinsky
reaction):
RCH2COOH + X2, P  RCHCOOH + HX
X
α-haloacid
X2 = Cl2, Br2
CH3CH2CH2CH2COOH
+
Br2,P
pentanoic acid
COOH
Br2,P
NR (no alpha H)
CH3CH2CH2CHCOOH
Br
2-bromopentanoic acid
RCH2COOH + Br2,P
RCHCOOH + HBr
+
H
n
he
t
;
H
O
Na
Br
NH3
RCHCOOH
RCHCOOH
NH2
OH
KOH(alc)
RCH2CHCOOH
Br
then H+
RCH=CHCOOH
aminoacid
5) Aromatic Substitution:
(-COOH is deactivating and meta- directing)
CO2H
HNO3,H2SO4
NO2
CO2H
CO2H
H2SO4,SO3
SO3H
CO2H
benzoic acid
Br2,Fe
Br
CH3Cl,AlCl3
NR