5. AMIDA (english)

Chemistry of Amides
 Amides are abundant in all living organisms…
proteins, nucleic acids, and other pharmaceut
icals have amid functional groups
1
Amides
 The
functional group of an amide is an acyl grou
p bonded to a nitrogen atom.
• drop -oic acid from the name of the parent acid and ad
d -amide. (For the common acid name, drop -ic of the a
cid name and add -amide.)
• an alkyl or aryl group bonded to the N: name the group
and show its location on nitrogen by N-.
O
C
H
C
N
H
3
2
OH
C
H
C
N
3
C
H
3
OC
H
3
H
C
N
C
H
3
A
c
e
t
a
m
id
e N
M
e
t
h
y
la
c
e
t
a
m
id
e N
,N
D
im
e
t
h
y
l(
a
1
°a
m
id
e
)
(
a
2
°a
m
id
e
)
f
o
r
m
a
m
id
e
(
D
M
F
)
(
a
3
°a
m
id
e
)
ethanamide
18-2
AMIDA
TATA NAMA


Suatu amida adalah suatu senyawa yang mempunyai suatu nitroge
n trivalen yang terikat pada suatu gugus karbonil.
Suatu amida diberi nama asam karboksilat induknya, dengan meng
ubah imbuhan asam....oat (atau –at) menjadi –amida.
O
O
H
C
3
N
H
2
H
C
3
H
2
C
C
H
2
I
U
P
A
C
:
E
ta
n
a
m
id
a
B
u
ta
n
a
m
id
a
T
r
iv
ia
l:
A
s
e
ta
m
id
a
B
u
tir
a
m
id
a
N
H
2

Amida dengan substituen alkil pada nitrogen diberi tambah
an N-alkil didepan namanya, dengan N merujuk pada atom
nitrogen.
O
H
C N C
H
3
O
H C N C
H
3
C
H
3
N
m
e
t
i
l
b
e
n
z
a
m
i
d
a
N
,
N
d
i
m
e
t
i
l
f
o
r
m
a
m
i
d
a
Amides; Lactams
 Lactams:
A cyclic amides are called lactams.
• Name the parent carboxylic acid, drop the suffix -ic aci
d and add -lactam.

2
3
H
3C
O
1
N
H



O
2
1
3
4
N
H
6
5


3-Butanolactam
6-Hexanolactam

-Butyrolactam)

-Caprolactam)
Indicates where the N is located.
18-5
Imides
 The
functional group of an imide is two acyl grou
ps bonded to nitrogen.
• Both succinimide and phthalimide are cyclic imides.
O
N
H
O
Succinim
ide
O
N
H
O
Phthalim
ide
18-6
AMIDA
 Ikatan
amida cukup stabil seperti yang terdapat pada ikatan antar asam a
mino dalam protein.
R
O
R
O
R
O R
O
H
N
C
C
N
C
C
N
C
C
H H
H H
H
H
N
C
C
O
H
2
H
a
s
a
m
a
m
i
n
o
s
u
a
t
u
p
r
o
t
e
i
n
(
p
o
l
i
a
m
i
d
a
)
Amida merupakan basa yang sangat lemah (bandingkan dengan amina).
C
H
N
H
3
2
H
C
l
m
e
t
ila
m
in
a
+C
H
N
H
l
3
3C
m
e
t
ila
m
o
n
iu
m
k
lo
r
id
a
O
C
H
C
N
H
3
2
t
id
a
k
t
e
r
ja
d
ip
e
n
g
g
a
r
a
m
a
n
H
C
l
Hal ini disebabkan adanya resonansi pada amida, sehingga atom N tidak ber
sifat basa dan tidak bersifat nukleofilik
O
C
R N
H
2
O
C
R N
H
2
k
u
r
a
n
g
b
a
s
a
d
i
b
a
n
d
i
n
g
k
a
n
N
i
t
r
o
g
e
n
a
m
i
n
a
Amides: resonance
18-8
Amides; Characteristics
18-9
Acidity of N-H bonds
 Amides
are comparable in acidity to alcohols.
• Water-insoluble amides do not react with NaOH or othe
r alkali metal hydroxides to form water-soluble salts.
 Sulfonamides
and imides are more acidic than a
mides.
O
C
H
C
N
H
3
2
O
S
N
H
2
O
N
H
O
N
H
O
O
O
A
c
e
t
a
m
id
eB
e
n
z
e
n
e
s
u
l
f
o
n
a
m
id
eS
u
c
c
in
im
id
eP
h
t
h
a
lim
id
e
p
K
1
5
1
7
p
K
1
0
p
K
9
.7
p
K
8
.3
a
a
a
a
18-10
Acidity of N-H bonds
 Effect
of neighboring carbonyl groups.
1.0
18-11
Acidity of N-H
• Imides such as phthalimide readily dissolve in aqueou
s NaOH as water-soluble salts.
O
N
H
+N
a
O
H
O
-
+
NN
a+H
O
2
O
O
pK
pK
a8 .3
a1 5.7
(s trong
(ser
trong er(weaker
(weaker
acid) bas e)
bas e)
acid)
18-12
Acidity of N-H bonds
 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. More resonance delocalization of the negative charge.
O
O
O
N
N
N
O
O
O
A
r
e
s
o
n
a
n
c
e
s
t
a
b
iliz
e
d
a
n
io
n
18-13
Preparation of Amides
 Prepared by reaction of an acid chloride with ammoni
a, monosubstituted amines, or disubstituted amines
14
PEMBUATAN AMIDA
Dari halida asam atau anhidrida asam dengan amonia, mono- atau dwi
substitusi amina (bagaimana dengan amina tersier ?)
O
O
SOCl2
C
R
Cl
klorida asam
C
R
OH
asamkarboksilat
NR'2
NH2R'
NH3
R
O
O
O
C
C
C
NH2
R
NHR'
R
NR'2
Pemanasan asam amino karboksilat akan membentuk laktam (amida
O
siklis)
O
N
H
2
C
O
H
C
H
C
H
C
H
C
H
2
2
2
2
a
s
a
m

a
m
in
o
b
u
tir
a
t
+
C
2
H
,p
a
n
a
s H
H
C
2
C
N
H
C
H
2

b
u
tir
o
la
k
ta
m
H
O
2
REAKSI AMIDA
1.
Hidrolisis ( RCONH2  RCOOH )
Amida mengalami hidrolisis menjadi asam karboksilat dan amina
bila dipanaskan dalam larutan asam maupun basa. Hidrolisis ami
da oleh asam atau basa berjalan searah (irreversible)
Mekanisme reaksinya mirip hidrolisis ester tetapi perlu kondisi re
aksi lebih kuat.
a. Hidrolisis oleh asam
O
O
C
N
H
2
C
O
H
H
S
O
2
4
+
N
H
H
S
O
4
4
H
O
2
a
s
a
m
b
e
n
z
o
a
t
b
e
n
z
a
m
i
d
a
a
m
o
n
i
u
m
h
i
d
r
o
g
e
n
s
u
l
f
a
t
b. Hidrolisis oleh basa
O
O
C
H
N
H
3
2
N
a
O
H
C
H
C
H
N
H
C
H
3
2
3
C
H
C
H
O
N
a
3
2
N
m
e
t
i
l
p
r
o
p
a
n
a
m
i
d
a
N
a
p
r
o
p
a
n
o
a
t
m
e
t
i
l
a
m
i
n
a
(1.a) Acidic Reaction with H2O - Amides
 Hydrolysis
of an amide in aqueous acid requires
one mole of acid per mole of amide.
• Reaction is driven to completion by the acid-base react
ion between the amine or ammonia and the acid.
O
O
H
O
2
++
H
O
+
H
C
l
+
N
H
l
O
H
N
H
4C
2 2
heat
P
h
P
h
2-Phenylbutanam
i
2-Phenyl
18-17
(1.b) Basic Reaction with H2O - Amides
 Hydrolysis
of an amide in aqueous base requires
one mole of base per mole of amide.
• Reaction is driven to completion by the irreversible for
mation of the carboxylate salt.
O
C
H
C
N
H
3
O
H
O
- ++
+
N
N
a
O
H2 C
H
C
O
a H
2
3 N
N
P
h
e
n
y
l
e
t
h
a
n
a
m
i
d
e
(
N
P
h
e
n
y
l
a
c
e
t
a
m
i
d
e
,
A
c
e
t
a
n
i
l
i
d
e
)
h
e
a
t
S
o
d
i
u
m
a
c
e
t
a
t
e
A
n
i
l
i
n
e
18-18
Mechanism: Acidic H2O - Amides
• Step1: Protonation of the carbonyl oxygen gives a reso
nance-stabilized cation intermediate.
O
+
RCN
H
2 +HOH
H
+
H
O
H
O
R
CN
H
2
RC N
H
2
+
H
O
+
+H
RCN
H
O
2
2
R
e
so
n
a
n
c
e
sta
b
iliz
e
dc
a
tio
n
in
te
r
m
e
d
ia
t
e
18-19
Acidic H2O - Amides
• Step 2: Addition of water (a nucleophile) to the carbonyl carbon (a
n electrophile) followed by proton transfer gives a TCAI.
O
H
+
R
C
N
H
+
O
H
2
H
proton
f
O
H transfer
O
H
O to N
+
R
C
N
H
R
C
N
H
3
2
+
O
H H
O
H
• Step 3: Collapse of the TCAI and proton transfer. (Elimination)
H
O
+
R
C
N
H
3
O
H
+H
O
N
H
R
C+
3
O
+
+
R
C
O
H
N
H
4
O
H
18-20
Reactions of Amides
(Acidic Hydrolysis)
 Heating in either aqueous acid or aqueous base prod
uces a carboxylic acid and amine
 Acidic hydrolysis by nucleophilic addition of water to t
he protonated amide, followed by loss of ammonia
21
Basic Hydrolysis of Amides
 Addition of hydroxide and loss of amide ion
22
Mechanism: Reaction with Basic H2O - Amides
Amide
hydroxide ion
Dianion!
18-23
2. REDUKSI ( RCONH2  RCH2NH2 )


Amida direduksi oleh LiAlH4 menghasilkan amina
Reduksi terhadap laktam menghasilkan amina siklis
O
1
.L
iA
lH
,e
te
r
4
C
H
(C
H
)10 C N
H
C
H
3
2
3
2
.H
O
2
N
-m
e
tild
o
d
e
k
a
n
a
m
id
a
O
N
H
C
H
3
N
-m
e
til-
-v
a
le
ro
la
k
ta
m
C
H
(C
H
)10
3
2
C
H
H
C
H
2 N
3
N
-m
e
tild
o
d
e
s
ila
m
in
a
1
.L
iA
lH
,e
te
r
4
2
.H
O
2
N
H
C
H
3
N
-m
e
tilp
ip
e
rid
in
(2) Reduction: Conversion of Amid
es into Amines
 Reduced by LiAlH4 to an amine rather than an alcoh
ol
 Converts C=O  CH2
25
Mechanism of Reduction
 Addition of hydride to carbonyl group
 Loss of the oxygen as an aluminate anion to give an i
minium ion intermediate which is reduced to the amin
e
26
Uses of Reduction of Amides
 Works with cyclic and acyclic
 Good route to cyclic amines
27
PENISILIN DAN SEFALOSPORIN
Adalah antibiotika yang mengandung cincin β-laktam.
Penisilin ditemukan oleh Alexander Fleming (1928); diisolasi dari jamur Penic
illium notatum. Dapat menghambat pertumbuhan bakteri Staphylococcus au
reus.
Cincin β-laktam (dari Penisilin maupun Sefalosporin) berinteraksi dengan enzi
m transpeptidase sehingga enzim tersebut tidak aktif. Bakteri akan mati kar
ena kekurangan enzim transpeptidase yang diperlukan untuk pembentukan
dinding sel bakteri.
H
2
C
H
N
C
HH
S
H
2
C
C
H
3
H
N
HH
C
C
O
C N
O
O
C
H
3
- +
C
O
O
N
a
C N
O
C
H
3
C
O
O
H
c
in
c
in
-la
k
ta
m
B
e
n
z
y
lp
e
n
ic
illin
=
P
e
n
ic
illinG
S
e
fa
le
k
s
in
(s
e
n
y
a
w
ag
o
lo
n
g
a
ns
e
fa
lo
s
p
o
rin
)
a
k
tiv
ita
sa
n
tib
a
k
te
rile
b
ih
p
o
te
n
d
ib
a
n
d
in
g
p
e
n
is
ilin
SENYAWA TERKAIT DENGAN AMI
DA
Kelebihan Nitrogen pada metabolisme protein oleh hewan tingkat tinggi d
iekskresi sebagai urea. Pada hewan tingkat rendah ekskresi berupa amo
nia, sedangkan pada reptil dan burung mengekskresi guanidin.
O
O
H
N
C
N
H
2
2
R
N
C
N
R
2
2
u
r
e
a
u
r
e
a
t
e
r
s
u
b
s
t
i
t
u
s
i
N
H
H
N
C
N
H
2
2
g
u
a
n
i
d
i
n
Urea dipakai untuk sintesis golongan obat barbiturat (untuk obat penenang
) dengan cara mereaksikan dengan dietil malonat
O
N
H
2
O
C
N
H
2
u
r
e
a
C
H
C
H
O
C
3
2
O
C
H
N
C
H
C
H
O
3
2
H
O
C C
C
H
2
2
C
H
C
H
O
C
3
2
O
d
i
e
t
i
lm
a
l
o
n
a
t
C
H
N
O
a
s
a
m
b
a
r
b
i
t
u
r
a
t
2
C
H
C
H
O
H
3
2
SENYAWA YANG TERKAIT DENGAN AMIDA
Struktur parsial
golongan
contoh
O
O
amida
CN
H 3 C C NH 2
O
O
laktam
NH
CN
O
O
C
N C
imida
O
O
N C N
urea
H 2N
O
C
NH 2
O
karbamat
= uretan
O
S N
O
O
O
N C O
H
N
H 2N
C
OCH 3
O
sulfonamida
S
O
NH 2