Carboxyl Derivatives pps

An acid
chloride An es ter
An acid
anhydride
O
O
RCCl RCOR'RCOCR'
O
RC- OH H- Cl
O
RC- OH H- OCR'
O
RC- OH H- OR'
O
O
O
An amide A nitrile
O
RC NRCNH
2
O
RC- OH H- NH
2
RC= N
HO H
The enol of
an amide

RC-
O
RCCl
O
CH
3
CCl
O
CCl
O
ClC(CH
2
)
4
CCl
OO
Benzoyl
chloride
Ethanoyl chloride
(Acetyl chlorid e)
An acyl ch loride
(An acid chloride)
An acyl
group
Hexanedioyl chloride
(Adipoyl ch loride)

replacement of -OH in a sulfonic acid by -Cl gives
a sulfonyl chloride
SOHH

3
C
O
O
CH
3
SOH
O
O
SClH
3
C
O
O
CH
3
SCl
O
O
Methanes ulfon ic
acid
p-Toluenesulfon ic
acid
Methanes ulfonyl chloride
(Mesyl chloride, MsCl)
p-Toluenesulfon yl chloride
(Tosyl chloride, TsCl)

The functional group of an acid anhydride is two
acyl groups bonded to an oxygen atom


the anhydride may be symmetrical (two identical
acyl groups) or mixed (two different acyl groups)

to name, replace
acid
acid of the parent acid by
anhydride
anhydride
Acetic benz oic
anhydride
Benz oic anhydride
Acetic anhydride
COC
CH
3
COCCH
3
CH
3
COC
OO
O
O
O
O

Cyclic anhydrides are named from the
dicarboxylic acids from which they are derived
Maleic

anhydride
O
O
O
Phthalic
anhydride
Succinic
anhydride
O
O
O
O
O
O

The functional group of an ester is an acyl
group bonded to -OR or -OAr

name the alkyl or aryl group bonded to oxygen
followed by the name of the acid

change the suffix
-ic acid
-ic acid to
-ate
-ate
Ethyl ethanoate
(Ethyl acetate)
Diethyl butanedioate
(Diethyl succinate)

O
O
O
O
O
O
O
O
Is opropyl
benz oate

Cyclic esters are called lactones

name the parent carboxylic acid, drop the suffix
-ic
-ic
acid
acid, and add
-olactone
-olactone
5-Hexanolacton e
(δ-Caprolacton e)
4-Bu tanolactone
(γ-Bu tyrolacton e)
3-Bu tanolactone
(β-Butyrolactone)
δ
β
α
γβ

α
β
α
γ
O
O
O
O
O
O
H
3
C
CH
3
2
3
1
2
2
1
3
1
3 4
4
5

The functional group of an amide is an acyl
group bonded to a nitrogen atom


IUPAC: drop -
oic acid
oic acid from the name of the parent
acid and add
-amide
-amide

if the amide nitrogen is bonded to an alkyl or aryl
group, name the group and show its location on
nitrogen by
N-
N-
N-Methylacetamide
(a 2° amide)
Acetamide
(a 1° amide)
CH
3
CNH
2
CH
3
CNHCH
3
HCN( CH
3
)
2
N,N-Dimethyl-
formamide (DMF)

(a 3° amide)
O O O

Cyclic amides are called lactams

Name the parent carboxylic acid, drop the
suffix
-ic acid
-ic acid and add
-lactam
-lactam
α
β
γ
δ
ε
6-Hexanolactam
(ε-Caprolactam)
α
β
H
3
C
O
NH
O
NH
1
2
1

2
3
4
5
6
3
3-Butanolactam
(β-Butyrolactam)

The functional group of a nitrile is a cyano
group

IUPAC: name as an
alkanenitrile
alkanenitrile

Common: drop the
-ic acid
-ic acid and add
-onitrile
-onitrile
CH
3
C N C N
CH
2
C N
Ethanenitrile
(A cetonitrile)
Benzonitrile Phenylethanenitrile

(Phenylacetonitrile)

Amides are comparable in acidity to alcohols

water-insoluble amides do not react with NaOH or
other alkali metal hydroxides to form water soluble
salts

Sulfonamides and imides are more acidic than
amides
CH
3
CNH
2
O
NH
O
O
NH
O
O
O
SNH
2
O
pK
a
8.3
pK
a

9.7pK
a
10
PhthalimideSuccinimideBenzen esulfonamide
Acetamide
p K
a
15-17

Imides are more acidic than amides because
1. the electron-withdrawing inductive of the two
adjacent C=O groups weakens the N-H bond, and
2. the imide anion is stabilized by resonance
delocalization of the negative charge
Phthalimide A resonance-stabiliz ed anion
+
N-H
O
O O
O
N
-
N
O
-
O
H
3
O
+

+
H
2
O

imides such as phthalimide readily dissolve in
aqueous NaOH as water-soluble salts
(stronger
acid)
(weaker
acid)
(weaker
base)
(stronger
bas e)
pK
a
15.7pK
a
8.3
+
+
O
O
NH N
-
Na
+
O
O

NaOH H
2
O
Additional
Stretchings (cm
-1
)
O-H at 2400-3400
C-O at 1210-1320
(2° have one N-H peak)
(1° have two N-H peaks)
N-H at 3200 and 3400
C-O at 900-1300
C-O at 1000-1100
and 1200-1250
(cm
-1
)
C=O Stretch
1740-1760
and
1800-1850
1630-1680
1735-1800
1700-1725
O
O
O
O
RCOH

RCOCR
RCOR
RCNH
2
Cmpd
O

1
H-NMR

H on the α-carbon to a C=O group are slightly
deshielded and come into resonance at δ 2.1-2.6

H on the carbon of the ester oxygen are more
strongly deshielded and come into resonance at δ
3.7-4.7

13
C-NMR

the carbonyl carbons of esters show characteristic
resonance at δ 160-180
Methyl propanoate
δ 3.68(s)
δ 2.33(q)
O
CH
3
-CH
2

-C-O-CH
3

Nucleophilic acyl substitution:
Nucleophilic acyl substitution: an addition-
elimination sequence resulting in substitution
of one nucleophile for another
Tetrahedral carbonyl
addition intermediate
-
-
++
C
NuR
C
Y
R
Y
O
O
-
Nu Y
Subs titution
product
:
:
:
R
C
Nu

O

in this general reaction, we have shown the leaving
group as an anion to illustrate an important point
about them: the weaker the base, the better the
leaving group
Increasing basicity
Increasing leaving ability
X
-
RO
-
R
2
N
-
RCO
-
O

halide ion is the weakest base and the best leaving
group; acid halides are the most reactive toward
nucleophilic acyl substitution

amide ion is the strongest base and the poorest
leaving group; amides are the least reactive toward
nucleophilic acyl substitution
O
RCX
RCOCR'RCOR'RCNH

2
Increasing reactivity toward nucleophilic acyl substitution
Amide Ester
Anhydride
Acid halide
O
O O
O

low-molecular-weight acid chlorides react rapidly
with water

higher molecular-weight acid chlorides are less
soluble in water and react less readily
+
+
O
O
CH
3
CCl H
2
O
CH
3
COH HCl

low-molecular-weight acid anhydrides react readily
with water to give two molecules of carboxylic acid


higher-molecular-weight acid anhydrides also react
with water, but less readily
CH
3
COCCH
3
O O
H
2
O
CH
3
COH
O
O
HOCCH
3
++

Esters are hydrolyzed only slowly, even in
boiling water

Hydrolysis becomes more rapid if they are
heated with either aqueous acid or base

Hydrolysis in aqueous acid is the reverse of
Fischer esterification

the role of the acid catalyst is to protonate the
carbonyl oxygen and increase its electrophilic

character toward attack by water to form a
tetrahedral carbonyl addition intermediate

collapse of this intermediate gives the carboxylic
acid and alcohol