AMINES, AMIDES and ANILINE
Amines
• An amine is a base as well as a nucleophile
• Some amines are heterocyclic compounds
(or heterocycles)
• Most drugs, vitamins, and many other natural products
are heterocycles
• A natural product is a compound synthesized by a plant
or an animal
Organic bases are amines
Amines are derivatives of ammonia
H
N
H
R
N
H
H
H
A m m o n ia
P rim a ry (1 ) A m in e
R
N
o
R
H
N
R
R
R
o
S e c o n d a ry (2 ) A m in e
o
T e rtia ry (3 ) A m in e
N 1s2, 2s2 2p1 2p1 2p1----------- lone pair
occupies an sp3 orbital
Amines are bases because of the lone pair on the
nitrogen atom - red litmus paper to blue
H
H
Cl
NH 2
N
H
Cl
H
B ase
+
A c id
=
A m m o n iu m S a lt
O
H O
O
O H
O
o x a lic a c id
+
2 N( C H 2 C H 3 ) 3
trie th yla m in e
O
O
+
2 H N( C H 2 C H 3 ) 3
O
trie th yla m in iu m o x a la te
The lone-pair electrons on nitrogen allows an amine to
turn “inside out” rapidly at room temperature
Some Common Amines
1,4-butanediamine
NH 2
H 2N
P u tre s c in e
(fo u n d in d e c a yin g m e a t)
NH 2
Both upper amines are 1o
A m p h e ta m in e
(d a n g e ro u s s tim u la n t)
N
N
Is o p ro p yla m in e
H
T rie th yla m in e
P ip e rid in e
This amine is are
2o
This amine is 3o
NH 2
This amine is 1o
Aniline can be converted into useful diazonium salt
N H2
N a N O 2, H C l
N N + C l-
0 C
b e n z e n e d ia z o n iu m c h lo rid e
N N + Cl -
Nuc -
-
N N
Nuc
Relative Reactivity of Amine
most reactive
least reactive
RCH2F > RCH2OH ~ RCH2OCH3 > RCH2NH2
HF
H2O
RCH2OH
NH3
pKa = 3.2
pKa = 15.7
pKa = 15.5
pKa = 36
The leaving group of a protonated amine cannot
dissociate to form a carbocation or be replaced by a
halide ion
Reactions of Amines
nucleophilic substitution reactions
CH 3 C H 2 Br
CH 3 N H 2
+
CH 3 C H 2 NH CH 3
CH 3 C H 2 NH 2 CH 3
+
HBr
Br
nucleophilic acyl substitution reactions
O
O
C
CH 3 C H 2
+
Cl
2
C
CH 3 N H 2
CH 3 C H 2
+
NH C H 3
CH 3 N H 3 Cl
Oxidation of Amines
oxd
R
oxd
NH 2
R
NH
oxd
OH
R
O
O-
R
R
R
NH
+ H 2O 2
N+
R
H
+ OH
-
R
R
N
OH
R
R
R
+ H 2O 2
R
+
H 2O
N
OH
R
N+
R
a nitroso
compound
a hydroxylamine
R
N
O
N+
OH
R
+ OH
-
R
N
O_
+
H 2O
R
Nitrite Ion, Nitrous Acid, and Nitrosyl Cation
– ••
•• O
••
••
O ••
N
••
H
+
••
O
H
••
+
H
• O ••
•
H
O ••
N
H
H
••
••
+
••
N
+
+
•• O
••
O ••
H
••
N
••
O ••
Example
CH3NH2+HNO2
••
(CH3)2NH
CH3OH+N2+H2O
NaNO2, HCl
H2O
••
(CH3)2N
••
N
••
O ••
(88-90%)
Nitrosation of Secondary Alkylamines
+
N
••
••
O ••
N
•• N
H
H
O ••
N
+
H
N ••
••
••
+
••
N
+
••
O ••
+
nitrosation
of
secondary amines
gives an Nnitroso amine
Nitrosation of Primary Arylamines
gives
aryl diazonium ions
aryl
diazonium ions are much more stable than
alkyl diazonium ions
most
aryl diazonium ions are stable under the
conditions of their formation (0-10°C)
+
RN
+
ArN
N
N
fast
+
R
+ N2
slow
+
Ar
+ N2
Example:
(CH3)2CH
NH2
NaNO2, H2SO4
H2O, 0-5°C
(CH3)2CH
+
N
N HSO4–
Transformations of Aryl Diazonium Salts
Ar
Ar
Cl
Ar
CN
+
N
Ar
Ar
Ar
F
Ar
I
N
H
Ar
Br
OH
Azo Coupling
Diazonium
salts are weak electrophiles.
React with strongly activated aromatic
compounds by electrophilic aromatic
substitution.
Ar
+
N
N + Ar'
H
Ar
N
N
Ar'
an azo compound
Ar' must bear a strongly electron-releasing group
such as OH, OR, or NR2.
Example
OH
+
+ C6H5N
N
OH
N
NC6H5
Cl–
Amides
R'
------------- Not acids or bases
R'
N
C
R
O
N
C
R
O
Features of a Peptide Bond
1.
2.
3.
4.
Usually inert
Planar to allow delocalisation
Restricted Rotation about the amide bond
Rotation of Groups (R and R’) attached to the amide
bond is relatively free