Asam Karboksilat dan

Turunannya
Ayik Rosita P., M.Farm., Apt
Bagian Kimia Farmasi
Universitas Jember
Asam Karboksilat
Senyawa yang memiliki satu gugus karbonil
yang berikatan dengan 1 gugus hidroksil
R C
O
O H
Karbonil
Hidroksil
Karbonil + Hidroksil gugus Karboksil
O
OH
O
O
aspirin
3
The CO single bond of a carboxylic acid is shorter than the CO bond of an
alcohol.
This can be explained by looking at the hybridization of the respective carbon
atoms.
Structure and Bonding
Because oxygen is more electronegative than either carbon or hydrogen, the C
O and OH bonds are polar.
Tata Nama IUPAC
Mengganti akhiran a dari alkana induk
dengan imbuhan asam oat
Karbon karboksil diberi no. 1
Jika memiliki 2 gugus karboksilat, penamaan
diberi akhiran -dioat


C
O
OH
H C
O
OH
H
3
C
C
O
OH
H
C
H
2
C
C
O
OH
H
2
C C
Br
O
HO
Asam metanoat
Asam etanoat
Asam 2-bromobutanoat
H
3
C
Asam propanadioat
5
Compounds containing two carboxy groups are called diacids. Diacids are named
using the suffix dioic acid.
Metal salts of carboxylate anions are formed from carboxylic acids in many
reactions. To name the metal salt of a carboxylate anion, put three parts together:
H
3
C CO
2
H
CO
2
H
CO
2
H
CO
2
H
H
2
C CHCO
2
H
asam p-toluat
asam o-ftalat
asam sikloheksanakarboksilat
asam akrilat
Penamaan IUPAC, Struktur cincin mgd gugus karboksil
Asam (struktur cincin)karboksilat
IUPAC
Tata Nama Trivial
Tanpa sistematika
4 asam karboksilat pertama, sering dinamai
dengan nama trivial

Banyaknya
atom C Struktur Nama Trivial Penurunan nama
1 HCOOH Asam format semut
2 CH
3
CO
2
H Asam asetat cuka
3 CH
3
CH
2
CO
2
H Asam propionat susu, keju
4 CH
3
(CH
2
)
2
CO
2
H Asam butirat mentega
5 CH
3
(CH
2
)
3
CO
2
H Asam valerat akar valeria
6 CH
3
(CH
2
)
4
CO
2
H Asam kaproat kambing
7 CH
3
(CH
2
)
5
CO
2
H Asam enantat anggur
8 CH
3
(CH
2
)
6
CO
2
H Asam kaprilat kambing
Chapter 20 8
Common Names
Many aliphatic acids have historical names.
Positions of substituents on the chain are
labeled with Greek letters.
CH
3
CH
2
CHC
Cl
OH
O
o-chlorobutyric acid
CH
3
CH
2
CH
2
CHCH
2
COOH
Ph
|-phenylcaproic acid
=>
Chapter 20 9
Naming Cyclic Acids
Cycloalkanes bonded to -COOH are named
as cycloalkanecarboxylic acids.
Aromatic acids are named as benzoic acids.
COOH
CH(CH
3
)
2
2-isopropylcyclopentanecarboxylic acid
COOH
OH
o-hydroxybenzoic acid
(salicylic acid)
=>
10
Give the IUPAC and common names:
A. CH
3
COOH

CH
3

|
B. CH
3
CHCOOH


C.
Learning Check
COOH
Br


11
A. CH
3
COOH ethanoic acid (acetic acid)
CH
3

|
B. CH
3
CHCOOH 2-methylpropanoic acid
(o-methylpropionic acid)

C. 2-bromobenzoic acid
(o-bromobenzoic acid)

Solution
COOH
Br


Sifat Fisika Kimia
Asam karboksilat memiliki 3 ikatan kovalen
polar senyawa polar
H
3
C
C
O
O
H
o+
o
o+
o
Asam karboksilat mampu membentuk ikatan H dg
Sesamanya atau dengan air
dijumpai dlm bentuk dimer (bahkan dalam fase uap)

H
3
C C
O
O H
H O
C CH
3
O
H
3
C C
O
O H
H
O H
Sifat Fisika Kimia
Karena ikatan H asam karboksilat > alkohol
m.p & b.p lebih tinggi dari alkohol dg mw
ekivalen



Karena As. Karboksilat mampu membentuk ikatan
H dengan air mudah larut air

H
3
C
H
2
C C
OH
O
H
3
C
H
2
C
H
2
C OH
m.p -22
0
C
b.p 141
0
C
m.p -126
0
C
b.p 97,2
0
C
H
3
C
H
2
C C
OH
O
Gugus polar
Rantai C non polar
Physical Properties
Highest bp of compounds studied so far!
B
Alcohols
Alkyl halides
Alkanes
I
n
c
r
e
a
s
i
n
g

B
P

Ethers/Aldehydes/Ketones
Carboxylic acids
Solubility of Organics
One electronegative group per four
carbons will make a compound dissolve in
water
Fatty Acids
Long un-branched carboxylic acids
Most have between 12 and 20 carbons
Derived from the hydrolysis of fats
Most have an even number of Cs
If unsaturated, the cis isomer predominates
Unsaturated have lower melt points than saturated


Melting Points
Saturated have higher melting points than
unsaturated fatty acids
Soap
Soap is made by adding NaOH to a fat
This reaction is called soponification
This cleaves each of the fatty acids
producing the solid fatty acid salt (soap)
The other product is glycerol
C
C
C
O C
O
O C
O
O C
O
H
H
H
H
H
+
NaOH 3
C
O
O Na
+
3
+ H
H OH
OH H
OH H
H
fat or oil
glycerol
soap
Soap
C
O
O
Na
+
soap
polar
non polar
Soap Micelles
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
Modern Detergents
Dodecylbenzene Sodium
4dodecylbenzenesulfonate
CH
2
(CH
2
)
10
CH
2
H
2
SO
4
NaOH
CH
2
(CH
2
)
10
CH
2
SO
3
-Na+
Keasaman Asam Karboksilat
Mrpk sifat kimia yang paling menonjol
Asam karboksilat terionisasi dalam air mbtk larutan
yang bersifat sedikit asam
Keasaman < dari asam anorganik. Karena bersifat
asam lemah
Dibanding alkohol, pKa as. Karboksilat lebih kecil
karena asam karboksilat dapat beresonansi
terstabilkan & meningkatkan Ka

H
3
C C
O
O
-
H
3
C C
O
-
O
Acidic Properties
It is the release of the hydrogen ion
(proton) to the water molecule
This forms the acid particles H
+
or H
3
O
+

Reactions due to the acidic nature
of carboxylic acids
This release of protons when in water
gives the solution a pH of less than 7.
The usual reactions of acids are present.
The conditions for all these reactions is
room temperature.
Acids as Proton Doners
The carboxylate anion helps in the understanding of the
carboxyl group to release a proton.




The extra negative charge can be on either oxygen. It is
partially delocalised and adds to the stability of the
anion
This extra stability increased the chances of it being
formed.

CH
3
C
O
O
-
CH
3
C
O
-
O
26
Carboxylic AcidsStrong Organic Brnsted-Lowry Acids
Carboxylic acids are strong organic acids, and as such, readily react with
Brnsted-Lowry bases to form carboxylate anions.
27
An acid can be deprotonated by a base that has a conjugate acid with
a higher pK
a
.
Because the pK
a
values of many carboxylic acids are ~5, bases that
have conjugate acids with pK
a
values higher than 5 are strong
enough to deprotonate them.
28
29
Carboxylic acids are relatively strong acids because
deprotonation forms a resonance-stabilized conjugate basea
carboxylate anion.
The acetate anion has two CO bonds of equal length (1.27 )
and intermediate between the length of a CO single bond
(1.36 ) and C=O (1.21 ).
30
Resonance stabilization accounts for why carboxylic acids are
more acidic than other compounds with OH bondsnamely
alcohols and phenols.
To understand the relative acidity of ethanol, phenol and acetic
acid, we must compare the stability of their conjugate bases
and use the following rule:
- Anything that stabilizes a conjugate base A: makes the starting
acid HA more acidic.
31
Ethoxide, the conjugate base of ethanol, bears a negative charge on
the O atom, but there are no additional factors to further stabilize the
anion. Because ethoxide is less stable than acetate, ethanol is a
weaker acid than acetic acid.
Phenoxide, the conjugate base of phenol, is more stable than
ethoxide, but less stable than acetate because acetate has two
electronegative O atoms upon which to delocalize the negative
charge, whereas phenoxide has only one.
32
Note that although resonance stabilization of the conjugate base is
important in determining acidity, the absolute number of resonance
structures alone is not what is important!
Figure 19.7
Summary: The relationship
between acidity and conjugate
base stability for acetic acid,
phenol, and ethanol
33
The Inductive Effect in Aliphatic Carboxylic Acids
34
35
Substituted Benzoic Acids
Recall that substituents on a benzene ring either donate or withdraw
electron density, depending on the balance of their inductive and
resonance effects. These same effects also determine the acidity of
substituted benzoic acids.
[1] Electron-donor groups destabilize a conjugate base, making an acid
less acidicThe conjugate base is destabilized because electron
density is being donated to a negatively charged carboxylate anion.
36
[2] Electron-withdrawing groups stabilize a conjugate base, making an
acid more acidic. The conjugate base is stabilized because electron
density is removed from the negatively charged carboxylate anion.
37
Figure 19.8
How common substituents
affect the reactivity of a
benzene ring towards
electrophiles and the acidity of
substituted benzoic acids
38
Sulfonic Acids
Sulfonic acids have the general structure RSO
3
H.
The most widely used sulfonic acid is p-toluenesulfonic acid.
Sulfonic acids are very strong acids because their conjugate bases
(sulfonate anions) are resonance stabilized, and all the resonance
structures delocalize negative charge on oxygen.
Pembuatan Asam Karboksilat
1. Hidrolisis derivat asam karboksilat
Derivat diserang air / OH
-
pada C karbonil
ex derivat : ester, amida, anhidrida, dll


RC OR' + H
2
O
O
RCO
2
H + R'OH
RC X + H
2
O
O
RCO
2
H + X
-
2. Reaksi Grignard
Reagen Grignard (1
o
, 2
o,
3
o
,vinil, aril) dan gas CO
2
kering

- Terjadi pemanjangan rantai (1 C lebih banyak)
RX RMgX RCO
2
H
Mg
Eter kering
1. CO
2
2. H
2
O, H
+
RX RCN RCO
2
H
CN
-
H
2
O, H
+
S
N2
MgBr
CO
2
H
fenilmagnesium bromida
asam benzoat (85%)
Ex:
3. Reaksi Oksidasi
Oksidasi alkohol primer dan aldehida
H
2
C OH + K
2
Cr
2
O
7
H
+
H
2
C H
3
C
C
H
2
C H
3
C
O
OH
H
2
C OH + KMnO
4
H
2
C
H
2
C H
3
C
H
+
C
H
2
C
H
2
C
O
OH
H
3
C
Oksidator kuat
C + Ag(NH
3
)
2
+
H
2
C H
3
C
O
H
NH
4
OH
C
H
2
C H
3
C
O
OH
Oksidator lemah
3. Reaksi Oksidasi
Oksidasi alkena
H
3
C
C
H
3
C
C
H
H
2
C CH
3
OKsidator
Kuat
H
3
C
C
H
3
C
O
C
H
2
C CH
3
O
H
+
OKsidator
Kuat
CO
2
H
CO
2
H
sikloheksena
asam adipat
Derivat Asam Karboksilat
Senyawa yang menghasilkan asam
karboksilat bila direx dg air
C
R X
O
Halida asam
(asil halida)
C
R O
O
Anhidrida asam
C
O
R'
C
R O
O
R'
Ester
C
R N
O
Amida
R C N
Nitril
Halida Asam
Acyl halides are compounds that have a
halogen atom in place of the OH group of a
carboxylic acid. The most common acyl halides
are acyl chlorides and acyl bromides.
C
R X
O
Halida asam
(asil halida)
F, Cl, Br, I
Tata Nama Klorida/Bromida Asam
Nama As. Karboksilat induk, dengan
mengubah imbuhan asam at menjadi
il klorida/bromida

C
H
3
C Cl
O
Etanoil klorida
asetil klorida
C
C
H
2
Br
O
C
H
CH
3
H
2
C H
3
C
3-metilpentanoil bromida
|-metilvaleril bromida
C
O
Cl
siklopentanakarbonil klorida
IUPAC
Trivial
46
Nomenclature of Acid Halides
IUPAC: alkanoic acid alkanoyl halide
Common: alkanic acid alkanyl halide
C
O
Cl
CH
2
NH
2
CH
2
C
O
Cl
I: 3-aminopropanoyl chloride
c: |-aminopropionyl chloride
I: benzenecarbonyl bromide
c: benzoyl bromide
Rings: (IUPAC only): ringcarbonyl halide
I: 3-cylcopentenecarbonyl chloride
CH
2
C
O
Cl C
O
Cl
4
I: hexanedioyl chloride
c: adipoyl chloride
C
O
Br
CH
NO
2
CH
2
CH
2
H
3
C C
O
Cl
I: 4-nitropentanoyl chloride
c: -nitrovaleryl chloride
R C
O
Cl
: :
:
..
..
Chapter 21 47
Reactivity
Reactivity decreases as leaving group
becomes more basic.
=>
Chapter 21 48
Interconversion of Derivatives
More reactive
derivatives can be
converted to less
reactive
derivatives.
=>
Chapter 21 49
Hydrolysis of Acid
Chlorides and Anhydrides
Hydrolysis occurs quickly, even in moist air
with no acid or base catalyst.
Reagents must be protected from moisture.
+
CH
3
C
O
Cl HOH
CH
3
C
O
OH + HCl
=>
Pembuatan Klorida Asam
Klorida asam didapat dari asam karboksilat
induk melalui reaksi dengan tionil klorida
(SOCl
2
) / zat penghalogen aktif lain (ex PCl
3
)

R
C
O
OH
+ SOCl
2
R
C
O
Cl
+ SO
2
+ HCl
R
C
O
OH
+ PCl
3
R
C
O
Cl
+ H
3
PO
3
H
3
C
C
O
OH
H
3
C
C
O
Cl
+ H
3
PO
3
+ PCl
3
contoh
Asam asetat
Asetil klorida
Anhidrida Asam
Loss of water from two molecules of a
carboxylic acid results in an acid
anhydride.
Anhydride means without water.

Tatanama Anhidrida asam
If the two carboxylic acid molecules forming the
acid anhydride are the same, the anhydride is a
symmetrical anhydride.
If the two carboxylic acid molecules are different,
the anhydride is a mixed anhydride.
Symmetrical anhydrides are named by using the
acid name and replacing acid with anhydride.
Mixed anhydrides are named by stating the
names of both acids in alphabetical order,
followed by anhydride.
tatanama indonesia Anhidrida ditempatkan di
awal

The word acid is replaced with anhydride.
For a mixed anhydride, name both acids.
Diacids may form anhydrides if a 5- or 6-membered ring
is the product.

O
O
O
1,2-benzenedicarboxylic anhydride
phthalic anhydride
54
Nomenclature of Acid Anhydrides
Acid anhydrides are prepared by dehydrating carboxylic acids
CH
3
C
O
OH H O C
O
CH
3
+
A
CH
3
C
O
O C
O
CH
3
- H
2
O
acetic acid
acetic anhydride
ethanoic anhydride
ethanoic acid
R
R
C
O
O C
O : : : :
..
..
CH
3
C
O
O C
O
H
C
O
O C
O
H
C
O
O C
O
C C
O
O O
I: benzenecarboxylic anhydride
c: benzoic andhydride
I: butanedioic acid
c: succinic acid
I: benzoic methanoic anhydride
c: benzoic formic anhydride
C C
O
OH
O
HO
C C
O
O O
A
-
H
2
O
I: butanedioic anhydride
c: succinic anhydride
I: cis-butenedioic anhydride
c: maleic anhydride
Some unsymmetrical anhydrides
I: ethanoic methanoic anhydride
c: acetic formic anhydride
Pembuatan Anhidrida
Umumnya, anhidrida asam tidak dapat
dibentuk langsung dari as. Karboksilat induk
harus dibuat bentuk derivat yang reaktif
(klorida asam)
R
C
O
Cl
+
R
C
O
O
OC
O
R'
klorida asam ion karboksilat
C
O
R'
anhidrida
56
Conversion of Carboxylic Acids to Acid Anhydrides
High temperature dehydration of carboxylic acids results in two molecules of the acid
combining and eliminating one molecule of water.

CH
3
C
O
OH H O C
O
CH
3
+
A
CH
3
C
O
O C
O
CH
3
- H
2
O
acetic acid
acetic anhydride
ethanoic anhydride
ethanoic acid
Cyclic anhydrides with 5 or 6-membered rings are prepared by dehydration of diacids.

2
HC
2
HC
C
OH
OH
C
O
O
A
2
HC
2
HC
C
O
C
O
O
H
2
O -
I: butanedioic acid
c: succinic acid
I: butanedioic anhydride
c: succinic anhydride
Draw a reaction showing the preparation of cyclohexanecarboxylic anhydride.

C
O
O C
O
H
2
O -
C
O
O H 2
A
Ester
An ester is a compound that has an OR
group in place of the OH group of a
carboxylic acid
Siklik ester lakton
C
R O
O
R'
Ester
Tatanama Ester
Nama suatu ester tdd 2 kata
Kata pertama gugus Alkil yang terikat
pada O karboksil
Kata kedua dari nama asam karboksilat
dengan membuatng kata asam
(inggris ic acid -ate)
Naming of Esters
Esters are named from the acid and
alcohol stem.
CH
3
C
O
O C
2
H
5
Alcohol Stem
Acid Stem
Naming of Esters
the alcohol stem comes at the start of the
ester name
the acid stem provides the second part of
the name
the name of the ester usually ends with
anoate.
The previous ester is ethyl ethanoate.
61
Nomenclature of Esters
CH
3
O C
O
CH
3
alkyl
I: alkanoate
c: alkanate
R C
O
OH
: :
..
..
R R C
O
O
..
..
: :
+
H
2
O -
carboxylic
acid
alcohol ester
H
+
H O R
..
..
O C
O
H
Esters occur when carboxylic
acids react with alcohols
I: methyl ethanoate
c: methyl acetate
C
O
O CH(CH
3
)
2
O C CH(CH
3
)
2
O
C O C(CH
3
)
3
O
CH
3
O C
O
C
O
O CH
3
I: phenyl methanoate
c: phenyl formate
I: t-butyl benzenecarboxylate
c: t-butyl benzoate
I: isobutyl cyclobutanecarboxylate
c: none
I: cyclobutyl 2-methylpropanoate
c: cyclobutyl o-methylpropionate
I: dimethyl ethanedioate
c: dimethyl oxalate
Uses of Esters
Esters can be used as
Adhesives
Perfumes
Flavourings
painkillers.
63
Ester Products
Aspirin
Is used to relieve pain and
reduce inflammation.
Is an ester of salicylic acid
and acetic acid.

Oil of wintergreen
Is used to soothe sore
muscles.
Is an ester of salicylic acid
and methanol.

CH
3
O
C O
OH
O
C
OH
CH
3
O
O
C
64
Esters in Plants
Esters give
flowers and
fruits their
pleasant
fragrances and
flavors.



TABLE 16.4

Copyright 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings
Some Esters and uses
Ethyl 2-methylbutanoate CH
3
CH
2
CH(CH
3
)COOCH
2
CH
3
Apple flavour
3-Methylbutyl ethanoate CH
3
COOCH
2
CH
2
CH(CH
3
)
2
Pear flavour
1-Methylpropyl ethanoate CH
3
COOCH(CH
3
)CH
2
CH
3
Banana flavour
Ethyl methanoate HCOOCH
2
CH
3
Raspberry flavour
Butyl butanoate CH
3
CH
2
CH
2
COOCH
2
CH
2
CH
2
CH
3
Pineapple flavour
Phenylmethyl ethanoate CH
3
COOCH
2
C
6
H
5
Oil of Jasmine
2-Ethanoyloxybenzoic acid
(acetylsalicylic acid)
OCOCH
3
COOH

Aspirin
Methyl 2-hydroxybenzoate
(methyl salicylate)
OH
COOCH
3

Muscle rub
Ethyl ethanoate CH
3
COOCH
2
CH
3
Glue solvent
Methyl 2-cyanopropenoate CH
2
=C(CN)COOCH
3
Superglue
Ethenyl ethanoate CH
3
COOCH=CH
2
PVA glue

Pembuatan Ester
Dari asam karboksilat dan alkohol
CH
2
CH
2
CH
2
COH
O
asam 4-fenilbutanoat
+ CH
3
CH
2
OH
CH
2
CH
2
CH
2
COCH
2
CH
3
O
etanol etil 4-fenilbutanoat (85%)
Dari suatu karboksilat dan alkil halida yang reaktif
CH
2
Cl
benzil klorida
CH
2
OCCH
3
O
Benzil asetat (93 %)
+
OC
O
R'
ion karboksilat
Cyclic esters are called lactones. In systematic
nomenclature, they are named as 2-
oxacycloalkanones.
four-membered ring lactones are -lactones (the
carboxyl oxygen is on the -carbon),
five-membered ring lactones are -lactones and
six-membered ring lactones are -lactones


68
CH
2
CH
2
CH
2
O
H
C
O
OH
H
+
H
2
O -
CH
2
CH
2
CH
2
O
C
O
O
C
O
O
O
I: 4-hydroxybutanoic acid
c: -hydroxybutyric acid
I: 4-hydroxybutanoic acid lactone
c: -butyrolactone
O
O
O
H
3
C
O
O
CH
3
O
Nomenclature of Cyclic Esters, Lactones
Cyclic esters, lactones, form
when an open chain hydroxyacid
reacts intramolecularly. 5 to 7-
membered rings are most stable.
lactone is added to the end of the IUPAC acid name.
olactone replaces the ic acid of the common name and hydroxy is dropped but its
locant must be included.
I: 4-hydroxypentanoic acid lactone
c: -valerolactone
I: 6-hydroxy-3-methylhexanoic acid lactone
c: |-methyl-c-caprolactone
I: 5-hydroxypentanoic acid lactone
c: o-valerolactone
I: 3-hydroxypentanoic acid lactone
c: |-valerolactone
Chapter 21 69
Lactones
Formation favored for five- and six-
membered rings.
O
O
COOH
OH
H
+
H
2
O +
For larger rings, remove water to
shift equilibrium toward products
H
+
H
2
O +
O
O
OH
COOH
=>
70
Esters react like acid halides and anhydrides but are less reactive toward nucleophiles
because the carbonyl C is less electrophilic. Both acyclic esters and cyclic esters
(lactones) react similarly. Esters are hydrolyzed by HOH to carboxylic acids, react with
amines to amides, are reduced by hydrides to aldehydes, then to 1alcohols, and react
with Grignards to 3 alcohols.
Reactions of Esters
R C
O
OH
: :
..
H
2
O
R C
O
NH
2
: :
..
NH
3
R
C
O
H
: :
[H]
RCH
2
OH
[H]
R':
-
MgBr
+
R C
O
R'
R C
OH
R'
R'
R':
-
MgBr
+
3 alcohol
1 alcohols
amide
acid
ketone
aldehyde
R
C
O
O
: :
..
R'
..
+
R'OH
H
+
71
Esters are hydrolyzed (broken down by water) to carboxylic acids or carboxylates by
heating in acidic or basic media, respectively.
Base-promoted ester hydrolysis is called saponification (Latin soap-making). Boiling
animal fat (which contains ester groups) in an aqueous solution of a strong base (NaOH,
KOH, etc.) makes soap. A soap is long hydrocarbon chain with an ionic end group.
Base Hydrolysis of Esters
The mechanism of base hydrolysis is nucleophilic acyl substitution in which OH
-
adds to
the ester carbonyl group producing a tetrahedral intermediate. The carbonyl group
reforms as the alkoxide ion leaves, yielding a carboxylate.
CH
3
(CH
2
)
10
C
O
O CH
3
K
+
OH
-
CH
3
(CH
2
)
10
C
O
O H
OCH
3
-
-
c: potassium laurate
CH
3
(CH
2
)
10
C
O
O
-
K
+
+ CH
3
OH
liquid soap
The leaving group, methoxide (OCH
3
-
), like all alkoxides, is a strong base (pKb = -2).
It will deprotonate the carboxylic acid intermediate converting it to a carboxylate. The
alkoxide, when neutralized, becomes an alcohol.
c: sodium laurate
I: sodium dodecanoate
C
O
O
-
Na
+
bar soap
Hydrolysis of Esters
Hydrolysis means the break-up of a
molecule using water.
Esters can be hydrolysed by both acids and
alkalis.
CH
3
C
O
O C
2
H
5
+ H
2
O
reflux
CH
3
C
O
O H
+ C
2
H
5
OH
Hydrolysis of Esters
Alkali hydrolysis gives the carboxylate salt.
Acid hydrolysis leads to equilibrium, the yield
of products is never 100%
Alkaline hydrolysis breaks up the ester
completely.

CH
3
C
O
O C
2
H
5
+ H
2
O
CH
3
C
O
O
-
+ C
2
H
5
OH
alkali
74
Base hydrolysis (also called saponification)
Is the reaction of an ester with a strong base.
Produces the salt of the carboxylic acid and an alcohol.
O
||
CH
3
COCH
2
CH
3
+

NaOH
O
,,
CH
3
CO

Na
+
+ HOCH
2
CH
3

salt of carboxylic acid alcohol
Base Hydrolysis (Saponification)
R O
CH
3
O
R
O
CH
3
O
HO
addition elimination
R O
O
Ester
O-H Na
+
Na
+
O-CH
3
H
Na
+
R O
O
O-CH
3
Na
+
H
sodium salt
of carboxylic
acid
75
Cleaning Action of Soap
A soap
Contains a nonpolar end
that dissolves in
nonpolar fats and oils,
and a polar end that
dissolves in water.
Forms groups of soap
molecules called
micelles that dissolve in
water and are washed
away.

Copyright 2007 by Pearson Education, Inc.
Publishing as Benjamin Cummings
76
C
O
OCH
3
H
O
H
H
+
Acidic hydrolysis of an ester yields a carboxylic acid (and an alcohol). The mechanism
of acidic ester hydrolysis is the reverse of Fischer esterification. The ester is protonated
by acid then attacked by the nucleophile HOH. Transfer of a proton and elimination of
ROH yields the carboxylic acid. The reaction is not favorable. It requires at least 30
minutes of refluxing.
Draw the complete mechanism of acid hydrolysis of methyl cyclopentanecarboxylate.
Acid Hydrolysis of Esters
C
O
OCH
3
H
+
H
2
O
H
2
O
C
O
OCH
3
H
+
..
C
O
OCH
3
H
O
H
H
+
..
C
O
OH
+ + H
3
O
+
CH
3
OH
Acid hydrolysis of an ester can be reversed by adding excess alcohol. The reverse
reaction is called Fischer Esterification. Explain why base hydrolysis of an ester is not
reversible.
77
In acid hydrolysis
An ester reacts with water to produce a carboxylic acid and an alcohol.
An acid catalyst is required.
O O
,, H
+
,,
HCOCH
2
CH
3
+

H
2
O HCOH + HOCH
2
CH
3




Acid Hydrolysis of Esters
78
+
H
+
R R C
O
O
..
..
: :
ester
alcohol
H O R'
..
..
R R' C
O
O
..
..
: :
ester
+
alcohol
H O R
..
..
Nucleophilic acyl substitution of an ester with an alcohol produces a different ester. The
mechanism is the same as acid hydrolysis of esters except that that the nucleophile is an
alcohol rather than water. A dry acid catalyst must be used, e.g., HCl(g) or H
2
SO
4
. If
water is present, it will compete with the alcohol as the nucleophile producing some
carboxylic acid in place of the ester product.
The process is also called Ester Exchange or Transesterification
Alcoholysis of Esters
CH
3
CH
2
OH 2
H
2
SO
4
C
O
O C
O
O
C
O
OCH
2
CH
3
C
O
CH
3
CH
2
O +
OH 2
dicyclobutyl terephthalate
dicyclobutyl 1,4-benzenedicarboxylate
diethyl terephthalate
diethyl 1,4-benzenedicarboxylate
cyclobutanol
79
CH C
O
OCH
3
H
3
C
H
3
C
NH
3
A
Amines can react with esters via nucleophilic acyl substitution yielding amides but the
reaction is difficult, requiring a long reflux period. Aminolysis of acid chlorides is
preferred.
Draw the mechanism aminolysis of methyl isobutyroxide with ammonia.
Aminolysis of Esters
CH C
O
N
H
3
C
H
3
C
H
H
H
-
OCH
3
-
+
CH C
O
N
H
3
C
H
3
C
H
H
+ CH
3
OH
c: o-methylpropionamide
I: 2-methylpropanamide
Write an equation showing how the following amide can be prepared from an ester.
C
O
N(CH
3
)
2
C
O
(CH
3
)
2
N
C
O
OCH
3
C
O
CH
3
O + 2
NH(CH
3
)
2
Note that the amide intermediate must deprotonate to form a stable, neutral amide.
Thus the amine must have at least one H. NH
3
, 1 and 2 amines will work but not 3.
80
Esters are easily reduced with LiAlH
4
to yield 1 alcohols. The mechanism is similar to
that of acid chloride reduction. A hydride ion first adds to the carbonyl carbon
temporarily forming a tetrahedral alkoxide intermediate. Loss of the OR group reforms
the carbonyl creating an aldehyde and an OR
-
ion. Further addition of H:
-
to aldehyde
gives the 1 alcohol. Draw the mechanism and show all products.
Hydride Reduction of Esters
The hydride intermediate can be isolated if DIBAH is used as a reducing agent instead of
LiAlH
4
. 1 equivalent of DIBAH is used at very low temp. (-78 C).
1.
2. H
3
O
+
excess
LiAlH
4
O
O Draw and name the products.
1 equiv.
1.
2. H
3
O
+
78C
-
DIBAH
O
O
CH
3
O
CH
3
H
OH
CH
2
OH
OH
c: -butyrolactone
I: 4-hydroxybutanoic acid lactone
c: none
I: 1,4-butanediol
c: -valerolactone
I: 4-hydroxypentanoic acid lactone
I: 4-hydroxypentanal
c: -hydroxyvaleraldehyde
R C
O
O R'
LiAlH
4
R C
O
H
-
OR'
-
LiAlH
4
R C
O
H
H
-
R C
O
H
H
H
+
R'OH
H
3
O
+
81
Esters and lactones react with 2 equivalents of Grignard reagent to yield 3 alcohols in
which the 2 substituents are identical. The reaction occurs by the usual nucleophilic
substitution mechanism to give an intermediate ketone, which reacts further with the
Grignard to yield a 3 alcohol.
Grignard Reduction of Esters
C
O
OCH
3
MgBr
C
O
-
OCH
3
-
MgBr
C
O
-
C
O
H
+
CH
3
OH
H
3
O
+
O
-
O
CH
3
CH
3
MgBr
O
-
CH
3
CH
3
O
-
H
3
O
+
OH
CH
3
CH
3
OH
I: 4-hydroxybutanoic acid lactone
methyl benzoate
benzophenone
triphenylmethanol
triphenylmethoxide
c: -butyrolactone
4-methyl-1,4-pentanediol
CH
3
MgBr
O
O
Amida
Senyawa yang mempunyai satu Nitrogen
trivalen yang terikat pada suatu gugus karbonil
An amide has an NH
2
,NHR, NR
2
or group in
place of the OH group of a carboxylic acid.

C
R N
O
Amida
Tatanama Amida
Amides are named by using the acid
name, replacing oic acid or ic acid
withamide.
For acids ending with carboxylic acid,
ylic acid is replaced with amide.

84
R C
O
N
H
H
R C
O
N
H
R
R C
O
N
R
R
CH
3
CH
2
CH
2
C
O
N
H
H
C
O
N
H
H
Cl
CH
3
CH
CH
3
C
O
N
CH
3
H
C
O
N
H
H
3
C
C
O
N
CH
3
CH
2
CH
3
Nomenclature of Amides
1 amide
2 amide
N-substituted amide
3 amide
N,N-disubstituted amide
1 amides: alkanoic acid + amide alkanamide
a ring is named ringcarboxamide
I: butanamide
c: butyramide
I: 3-chlorocyclopentanecarboxamide
c: none
I: p-nitrobenzenecarboxamide
c: p-nitrobenzamide
C
O
N
H
H
NO
2
2 and 3 amides are N-substituted amides
I: N,2-dimethylpropanamide
c: N,o-dimethylpropionamide
I: N-phenylethanamide
c: N-phenylacetamide
I: N-ethyl-N-methylcyclobutanecarboxamide
c: none
c: acetanilide
N O
H
2
N
nicotinamide
O
N
N
N
N
O
caffeine
Cyclic amides are called lactams.
Their nomenclature is similar to that of lactones.
They are named as 2-azacycloalkanones in systematic nomenclature
(aza is used to designate the nitrogen atom).
86
Nomenclature of Cyclic Amides, Lactams
CH
2
CH
2
CH
2
N
H
C
O
OH
H
H
2
O -
CH
2
CH
2
CH
2
NH
C
O
NH
O
NH
O Br
Cyclic amides, lactams, form
when an open chain aminoacid
reacts intramolecularly. 5 to 7-
membered rings are most stable.
I: 4-aminobutanoic acid
c: -aminobutyric acid
I: 4-aminobutanoic acid lactam
c: -butyrolactam
lactam is added to the end of the IUPAC acid name.
olactam replaces the ic acid of the common name and amino is dropped but its
locant must be included.
I: 5-aminohexanoic acid lactam
c: o-caprolactam
I: 3-amino-2-bromopropanoic acid lactam
c: o-bromo-|-propionolactam
I: 4-amino-3-methylbutanoic acid lactam
c: |-methyl--butyrolactam
NH
O
H
3
C
NH
O
CH
3
A
Pembuatan Amida
Disintesis dari derivat asam karboksilat dan
amonia atau amina yang sesuai
C
R
O
Cl
C
R
O
O
C
R
O
O
C
R'
O
R'
R'
2
NH
R'
2
NH
R'
2
NH
C
R
O
NR'
2
89
CH
3
C N
C N CH
2
CH
2
CH
2
I
CH
3
O CN
CN HS
R C
O
N
H
H
H
2
O
-
POCl
3
R C N
Nomenclature of Nitriles
Nitriles are produced when 1 amides are
dehydrated with reagents like POCl
3

IUPAC: alkane + nitrile alkanenitrile
IUPAC rings: ringcarbonitrile
Common: alkanic acid + onitrile alkanonitrile
I: ethanenitrile
c: acetonitrile
I: 4-iodobutanenitrile
c: -iodobutyronitrile
I: 3-methoxycyclohexanecarbonitrile
c: none
I: p-thiobenzenecarbonitrile
c: p-mercaptobenzonitrile
COOH
CN
I: 2-cyanocyclopentanecarboxylic acid
c: none
Chapter 21 90
Thioesters
More reactive than esters because:

-
S-R is a better leaving group than
-
O-R
Resonance overlap is not as effective.
=>
Chapter 21 91
Carbonic Acid Esters
CO
2
in water contains some H
2
CO
3
.
Diesters are stable.
Synthesized from phosgene.
+ C
O
Cl Cl
CH
3
CH
2
OCOCH
2
CH
3
O
2 CH
3
CH
2
OH
diethyl carbonate
=>
Chapter 21 92
Urea and Urethanes
Urea is the diamide of carbonic acid.
Urethanes are esters of a monoamide
of carbonic acid.
+ C
O
Cl Cl
C
O
NH
2
H
2
N
2 NH
3
urea
N C O
H
2
O
NH C OH
O
a carbamic acid
ROH
NH C OR
O
a urethane
=>
Chapter 21 93
Polymers
Polycarbonates are long-chain esters of
carbonic acid.
Polyurethanes are formed when a diol
reacts with a diisocyanate.
N C O N C O
CH
3
HOCH
2
CH
2
OH
NH C HN
CH
3
C
O
O CH
2
CH
2
O
O
n
=>