Functional Derivatives of Carboxylic Acids
O
R C
Cl
acid chloride
O
R C
O
R C
O
anhydride
O
R C
NH2
amide
O
R C
OR'
ester
R may be H or Ar
Nomenclature: the functional derivatives’ names are derived from the
common or IUPAC names of the corresponding carboxylic acids.
Acid chlorides: change –ic acid to –yl chloride
O
C
Cl
O
CH3CH2CH2C
Cl
butanoyl chloride
butyryl chloride
benzoyl chloride
Anhydrides: change acid to anhydride
O
H3C C
O
H3C C
O
ethanoic anhydride
acetic anhydride
O
O
O
phthalic anhydride
O
O
O
maleic anhydride
Amides: change –ic acid (common name) to –amide
-oic acid (IUPAC) to –amide
O
CH3CH2CH2C
NH2
butanamide
butyramide
O
C
NH2
benzamide
Esters: change –ic acid to –ate preceded by the name of the alcohol group
O
CH3CH2CH2C
O CH3
methyl butanoate
methyl butyrate
O
C
O CH2CH3
ethyl benzoate
Nucleophilic acyl substitution:
O
+ :Z
R C
W
O
R C
O
R C W
Z
-W = -OH, -Cl, -OOCR, -NH2, -OR'
= "acyl" group
O
R C + :W
Z
Mechanism: Nucleophilic Acyl Substitution
1)
O
+ :Z
R C
W
2)
O
R C W
Z
O
R C W
Z
O
R C + :W
Z
RDS
Mechanism: nucleophilic acyl substitution, acid catalyzed
O
1) R C + H+
W
OH
2) R C
+ :ZH
W
OH
3) R C W
ZH
OH
R C
W
OH
R C W
ZH
RDS
O
R C + HW + H+
Z
nucleophilic acyl substitution vs nucleophilic addition to carbonyl
aldehydes & ketones – nucleophilic addition
O
+ :Z
R C
R'
O
R C R'
Z
Y
OY
R C R'
Z
functional deriv. of carboxylic acids – nucleophilic acyl substitution
O
+ :Z
R C
W
O
R C W
Z
-W = -OH, -Cl, -OOCR, -NH2, -OR'
O
R C + :W
Z
Acid Chlorides
Syntheses:
RCOOH +
SOCl2
PCl3
PCl5
O
C
OH
 RCOCl
O
C
Cl
+ SOCl2
benzoic acid
benzoyl chloride
O
O
OH
3-methylbutanoic acid
isovaleric acid
+ PCl3
Cl
3-methylbutanoyl chloride
isovaleryl chloride
Acid chlorides, reactions:
1. Conversion into acids and derivatives:
a) hydrolysis
b) ammonolysis
c) alcoholysis
2. Friedel-Crafts acylation
3. Coupling with lithium dialkylcopper
4. Reduction
acid chlorides: conversion into acids and other
derivatives
Hydrolysis
O
O
H2O
Cl
OH
isovaleryl chloride
3-methylbutanoyl chloride
Ammonolysis
CH3CH2
O
C
Cl
NH3
CH3CH2
propionyl chloride
propanoyl chloride
Alcoholysis
O
C
Cl
benzoyl chloride
isovaleric acid
3-methylbutanoic acid
O
C
NH2
propionamide
propanamide
CH3CH2OH
O
C
OCH2CH3
ethyl benzoate
Schotten-Baumann technique – aromatic acid chlorides are
less reactive than aliphatic acid chlorides. In order to speed up
the reactions of aromatic acid chlorides, bases such as NaOH
or pyridine are often added to the reaction mixture.
O2N
CH3CH2CH2OH
O2N
O
C
OCH2CH2CH3
COCl
pyridine
O2N
3,5-dinitrobenzoyl chloride
O2N
n-propyl-3,5-dinitrobenzoate
acid chlorides: Friedel-Crafts acylation
O
R C
Cl
O
R C Ar
AlCl3
+ ArH
+ HCl
phenone
O
CH3CH2CH2C Cl
+
butyryl chloride
O
CH3CH2CH2C Cl
butyryl chloride
CH3
AlCl3
toluene
+
O
CH3CH2CH2C
CH3
p-methylbutyrophenone
NO2
AlCl3
No reacton
+ ortho-
acid chlorides: coupling with lithium dialkylcopper
O
R C
Cl
+ R'2CuLi
O
R C R'
ketone
O
C
Cl
O
C CH2CH2CH3
+ (CH3CH2CH2)2CuLi
lithium di-n-propylcopper
benzoyl chloride
O
C
Cl
isobutyryl chloride
butyrophenone
O
+
2CuLi
lithium diisopropylcopper
2,4-dimethyl-3-pentanone
acid chlorides: reduction to aldehydes
O
R C
Cl
LiAlH(t-BuO)3
O
LiAlH(t-BuO)3
C
Cl
O
R C
H
O
C
H
mechanism, nucleophilic acyl substitution by hydride :H-
1)
2)
O
R C
Cl
O
R C Cl
H
+ :H
O
R C Cl
H
O
R C
H
+ Cl
RDS
Anhydrides, syntheses:
Buy the ones you want!
Anhydrides, reactions:
1) Conversion into carboxylic acids and derivatives.
a) hydrolysis
b) ammonolysis
c) alcoholysis
2) Friedel-Crafts acylation
O
COOH
O
+ H2O
COOH
O
phthalic anhydride
(CH3CO)2O
+ NH3
acetic anhydride
O
O
+ CH3CH2OH
O
succinic anhydride
phthalic acid
O
+
CH3 C
NH2
acetamide
O
CH3 C
ONH4
ammonium acetate
O
CH2COCH2CH3
CH2COH
O
ethyl hydrogen succinate
2) anhydrides, Friedel-Crafts acylation.
(RCO)2O + ArH
(CH3CO)2O +
acetic anhydride
AlCl3
O
O
R C Ar + R C
OH
phenone
CH3
AlCl3
O
H3C C
CH3 + CH3CO2H
p-methylacetophenone
toluene
O
O
+
O
phthalic anhydride
AlCl3
O
C
C OH
O
o-benzoylbenzoic acid
Amides, synthesis:
Indirectly via acid chlorides.
O
R C
OH
SOCl2
O
R C
Cl
NH3
O
R C
NH2
[ carboxylic acids form ammonium salts when reacted directly with ammonia ]
CH3CH2CH2CO2H
PCl3
butyric acid
PCl5
COOH
benzoic acid
O
CH3CH2CH2C
Cl
butyryl chloride
O
C
Cl
NH3
NH3
benzoyl chloride
O
CH3CH2CH2C
NH2
butyramide
O
C
NH2
benzamide
Amides, reactions.
1) Hydrolysis.
O
R C
NH2
H2O, H+ or OHheat
CH3
O
+ H2O
CH3CHCH2C
NH2
isovaleramide
O
R C
OH
H+
heat
CH3
O
CH3CHCH2C
OH
isovaleric acid
O
O
O
O
O
O
H
H
H
H
H
HN CHC N CHC N CHC N CHC N CHC N CHC
R
R
R
R
R
R
proteins are polyaminoacids
"peptide bond"
hydrolysis
O
H2N CHC OH
R
aminoacids
Wool, hair, silk, spider web: fibrous proteins.
Silk is an extremely strong, thin, lightweight fiber, perfect for
making sheer stockings for women as well as parachutes. It is
made by the silkworm, a domesticated moth larva raised in
Japan and China. During World War II a substitute material
was needed and developed by DuPont – Nylon-66, a synthetic
polyamide of adipic acid and hexamethylenediamine:
O
O
Cl C(CH2)4C Cl +
adipoyl chloride
H2N (CH2)6 NH2
hexamethylenediamine
O
O
O
O
C(CH2)4C NH (CH2)6 NHC(CH2)4C NH (CH2)6 NH
Nylon-66
Esters, syntheses:
1) From acids
RCO2H + R’OH, H+
RCO2R’ + H2O
2) From acid chlorides and anhydrides
RCOCl + R’OH
RCO2R’ + HCl
3) From esters (transesterification)
RCO2R’ + R”OH, H+
RCO2R” + R’OH
RCO2R’ + R”ONa
RCO2R” + R’ONa
Esters often have “fruity” or “floral” odors:
isopentyl acetate
banana oil
n-pentyl butyrate
apricot
isopentyl isovalerate
apple
ethyl butyrate
peach
ethyl heptanoate
cognac
ethyl nonate
flower bouquet
ethyl laurate
tuberose
methyl butyrate
pineapple
octyl acetate
orange
“Direct” esterification is reversible and requires use of
LeChatelier’s principle to shift the equilibrium towards the
products. “Indirect” is non-reversible.
O
C
H+
OH
isovaleric acid
+ CH3CH2OH
ethyl alcohol
O
C
O
+ H2O
ethyl isovalerate
SOCl2
O
C
Cl
+ CH3CH2OH
ethyl alcohol
isovaleryl chloride
O
C
O
ethyl isovalerate
+ HCl
In transesterification, an ester is made from another ester by
exchanging the alcohol function.
CH3
O
+ HO CHCH3
CH3CH2CH2C
OCH3
methyl butanoate
O
+
CH3CH2CH2C
OCH3
H+
isopropyl alcohol
CH2ONa
O
CH3
+ CH3OH
CH3CH2CH2C
O CHCH3
isopropyl butanoate
O
CH3CH2CH2C
O
benzyl alcohol
methyl butanoate
benzyl butanoate
+
CH2
CH3ONa
Esters, reactions:
1) Conversion into acids and derivatives
a) hydrolysis
b) ammonolysis
c) alcoholysis
2) Reaction with Grignard reagents
3) Reduction
a) catalytic
b) chemical
4) Claisen condensation
O
C
OH
O
H2O; H+ or OHC
OCH2CH3 heat
+ CH3CH2OH
ethyl benzoate
CH3 O
CH3CHC
O CH3
CH3 O
CH3CHC
NH2
NH3
+ CH3OH
methyl isobutyrate
H+
O
CH3C
OCH2CH3
ethyl acetate
+
OH
O
CH3C
O
cyclopentyl acetate
+ CH3CH2OH
Tracer studies confirm that the mechanism is nucleophilic acyl
substitution:
O
R C
18O R'
OH-
OR C 18O R
OH
OHH2O, heat
H+
O
R C + R'18OH
OH
H2C OOCR
HC OOCR'
H2C OOCR''
triglycerides, fats/oils
triesters of glycerol
RCOO-Na+
NaOH, H2O
heat
H2C OH
HC OH
H2C OH
glycerol
+ R'COO-Na+
R''COO-Na+
"SOAP"
Hydrolysis of a fat or oil is also called "saponification
Esters, reaction with Grignard reagents
O
R C
+ R'MgX
O R''
H2O
OH
R C R'
R'
3o alcohol
nucleophilic
acyl substitution
O
R C R'
ketone
nucleophilic
addition
+ R'MgX
+ R''OH
O
CH3CH2CH2C
+
MgBr
OCH3
methyl butanoate
phenyl magnesium bromide
H2O
OH
CH3CH2CH2C
1,1-diphenyl-1-butanol
Esters, reduction
a) catalytic
O
+ H2, Ni
R
NR
O R'
O
R
H2, CuO, CuCr2O4
O R'
150o, 5000 psi
O
LiAlH4
RCH2OH + R'OH
b) chemical
R
H+
RCH2OH + R'OH
O R'
O
O
H2, CuO, CuCr2O4
150o,
5000 psi
phenyl propanoate
+
OH
isobutyl alcohol isopropyl alcohol
isopropyl isobutyrate
O
CH3CH2C
O
OH
OH
1. LiAlH4
2. H+
CH3CH2CH2OH
n-propyl alcohol
+
phenol
Spectroscopy:
Infrared:
RCO2R 1740
strong absorbance ~ 1700 cm-1 for C=O
ArCO2R 1715-1730
RCO2Ar 1770
Esters also show a strong C—O stretch at 1050-1300
Amides show N—H stretch at 3050 –3550 and N—H bend in
the 1600-1640 region.
Nmr: NB in esters the protons on the alcohol side of the
functional group resonate at lower field than the ones on
the acid side.
RCOO—C—H
3.7 – 4.1 ppm
H—C—COOR
2 – 2.2 ppm
methyl propionate
C=O
C--O
butyramide
C=O
N—H
N—H bend
Ethyl acetate
CH3CO2CH2CH3
b
c a
Note which hydrogens
are upfield.
c
b a
Methyl propionate
CH3CH2CO2CH3
a b
c
Note which hydrogens
are upfield.
c
b
a