Functional Derivatives of Carboxylic Acids

O
O
R C
R C
O R may be H or Ar
Cl
R C
O
acid chloride
anhydride

O O
R C R C
NH2 OR'

amide ester
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 O
CH3CH2CH2C C
Cl Cl

butanoyl chloride benzoyl chloride

butyryl chloride

Anhydrides: change acid to anhydride

O O O
H3C C
O O O
H3C C
O O O

ethanoic anhydride phthalic anhydride maleic anhydride

acetic anhydride
Amides: change –ic acid (common name) to –amide
-oic acid (IUPAC) to –amide

O O
CH3CH2CH2C C
NH2 NH2

butanamide benzamide
butyramide

Esters: change –ic acid to –ate preceded by the name of the alcohol group

O O
CH3CH2CH2C C
O CH3 O CH2CH3
methyl butanoate ethyl benzoate
methyl butyrate
 O
Nucleophilic acyl substitution: R C = "acyl" group

O O O
R C + :Z R C W R C + :W
W Z Z

-W = -OH, -Cl, -OOCR, -NH2, -OR'

Mechanism: Nucleophilic Acyl Substitution

O O
1) R C + :Z R C W RDS
W Z

O O
2) R C W R C + :W
Z Z
Mechanism: nucleophilic acyl substitution, acid catalyzed

O OH
1) R C + H+ R C
W W

OH OH
2) R C + :ZH R C W RDS
W ZH

OH O
3) R C W R C + HW + H+
ZH Z
nucleophilic acyl substitution vs nucleophilic addition to carbonyl

aldehydes & ketones – nucleophilic addition

O O OY
Y
R C + :Z R C R' R C R'
R' Z Z

functional deriv. of carboxylic acids – nucleophilic acyl substitution

O O O
R C + :Z R C W R C + :W
W Z Z

-W = -OH, -Cl, -OOCR, -NH2, -OR'

Acid Chlorides
Syntheses:
SOCl2
RCOOH + PCl3  RCOCl
PCl5

O O
C + SOCl2 C
OH Cl
benzoic acid benzoyl chloride

O O
+ PCl3
OH Cl
3-methylbutanoic acid 3-methylbutanoyl chloride
isovaleric acid 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
O H2O O
Hydrolysis
Cl OH
isovaleryl chloride isovaleric acid
3-methylbutanoyl chloride 3-methylbutanoic acid

O NH3 O
Ammonolysis CH3CH2 C CH3CH2 C
Cl NH2
propionyl chloride propionamide
propanoyl chloride propanamide

Alcoholysis O CH3CH2OH O
C C
Cl OCH2CH3
benzoyl chloride 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 O2N
CH3CH2CH2OH O
COCl C
pyridine OCH2CH2CH3
O2N O2N

3,5-dinitrobenzoyl chloride n-propyl-3,5-dinitrobenzoate

 acid chlorides: Friedel-Crafts acylation

O AlCl3 O
R C + ArH R C Ar + HCl
Cl
phenone

O AlCl3 O
CH3CH2CH2C Cl + CH3 CH3CH2CH2C CH3 + ortho-

butyryl chloride toluene p-methylbutyrophenone

O AlCl3
CH3CH2CH2C Cl + NO2 No reacton

butyryl chloride
acid chlorides: coupling with lithium dialkylcopper

O O
R C + R'2CuLi R C R'
Cl
ketone

O O
C + (CH3CH2CH2)2CuLi C CH2CH2CH3
Cl

benzoyl chloride lithium di-n-propylcopper butyrophenone

O
O
C +
2CuLi
Cl
isobutyryl chloride lithium diisopropylcopper 2,4-dimethyl-3-pentanone
acid chlorides: reduction to aldehydes
O LiAlH(t-BuO)3 O
R C R C
Cl H

O LiAlH(t-BuO)3 O
C C
Cl H

mechanism, nucleophilic acyl substitution by hydride :H-

O O
1) R C + :H R C Cl RDS
Cl H

O O
2) R C Cl R C + Cl
H H
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 acid
phthalic anhydride

O O
(CH3CO)2O + NH3 CH3 C + CH3 C
NH2 ONH4
acetic anhydride acetamide ammonium acetate

O O
CH2COCH2CH3
O + CH3CH2OH CH2COH
O
O
succinic anhydride ethyl hydrogen succinate
2) anhydrides, Friedel-Crafts acylation.

O O
AlCl3
(RCO)2O + ArH R C Ar + R C
phenone OH

O
AlCl3
(CH3CO)2O + CH3 H3C C CH3 + CH3CO2H
acetic anhydride
toluene p-methylacetophenone

O
AlCl3 O
O + C

O C OH
phthalic anhydride O
o-benzoylbenzoic acid
Amides, synthesis:
Indirectly via acid chlorides.
O SOCl2 O NH3 O
R C R C R C
OH Cl NH2
[ carboxylic acids form ammonium salts when reacted directly with ammonia ]

PCl3 O NH3 O
CH3CH2CH2CO2H CH3CH2CH2C CH3CH2CH2C
Cl NH2
butyric acid butyryl chloride butyramide

PCl5 O NH3 O
COOH C C
Cl NH2
benzoic acid benzoyl chloride benzamide
Amides, reactions.
1) Hydrolysis.

O H2O, H+ or OH- O
R C R C
NH2 heat
OH

CH3 O H+ CH3 O
CH3CHCH2C + H2O CH3CHCH2C
NH2 heat OH
isovaleramide 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, China and India. 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 + H2N (CH2)6 NH2
adipoyl chloride 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 H+ O
C + CH3CH2OH C + H2O
OH O

isovaleric acid ethyl alcohol

ethyl isovalerate

SOCl2

O O
C + CH3CH2OH C + HCl
Cl O

ethyl alcohol
ethyl isovalerate
isovaleryl chloride
 In transesterification, an ester is made from another ester by
exchanging the alcohol function.

O CH3 H+ O
CH3CH2CH2C CH3 + CH3OH
CH3CH2CH2C + HO CHCH3
OCH3 O CHCH3
methyl butanoate isopropyl alcohol isopropyl butanoate

CH2ONa
O O
CH3CH2CH2C + CH3CH2CH2C + CH3ONa
OCH3 benzyl alcohol O
CH2
methyl butanoate
benzyl butanoate
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 H2O; H+ or OH- O
C + CH3CH2OH
C
OCH2CH3 heat OH

ethyl benzoate

CH3 O NH3 CH3 O

CH3CHC CH3CHC + CH3OH
O CH3 NH2

methyl isobutyrate

O H+ O
CH3C + OH CH3C + CH3CH2OH
OCH2CH3 O

ethyl acetate cyclopentyl acetate

Tracer studies confirm that the mechanism is nucleophilic acyl
substitution:

O OH- H+ O
R C R C + R'18OH
18O R' H2O, heat
OH

OH-

O-
R C 18O R
OH
H2C OOCR
triglycerides, fats/oils
HC OOCR' triesters of glycerol
H2C OOCR''
RCOO-Na+
NaOH, H2O H2C OH
HC OH + R'COO-Na+
heat
H2C OH
R''COO-Na+
glycerol
"SOAP"

Hydrolysis of a fat or oil is also called "saponification

Esters, reaction with Grignard reagents

O H2O OH
R C + R'MgX R C R' + R''OH
O R'' R'
3o alcohol
nucleophilic
acyl substitution
nucleophilic
O addition
R C R' + R'MgX

ketone
 O
CH3CH2CH2C + MgBr
OCH3
methyl butanoate phenyl magnesium bromide

H2O

OH
CH3CH2CH2C

1,1-diphenyl-1-butanol
Esters, reduction
a) catalytic
O
R + H2, Ni NR
O R'

O H2, CuO, CuCr2O4

R RCH2OH + R'OH
O R' 150o, 5000 psi

b) chemical

O LiAlH4 H+
R RCH2OH + R'OH
O R'
 O
H2, CuO, CuCr2O4 OH
O +
150o, 5000 psi
OH
isopropyl isobutyrate isobutyl alcohol isopropyl alcohol

OH
O
CH3CH2C 1. LiAlH4
O CH3CH2CH2OH +
2. H+
n-propyl alcohol phenol
phenyl propanoate
Spectroscopy:
Infrared: strong absorbance ~ 1700 cm-1 for C=O
RCO2R 1740 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