Chapter 24: Amines
Nomenclature:
Shape:
Nomenclature:
Basicity:
Notice that if we reverse this equation:
A
H
A
N
H +
N
or
H2O + RNH3
H3O + RNH2
it now resembles a normal acid/base reaction
1
1° amines
2° amines
3° amines
aromatic
this is a critical factor which we can
utilize in synthesis:
-- amides are neutral, and do not
form complexes with acids
-- they thus stay as o/p directors
under conditions where the amine
changes to a m-directing deactivator
synthesis of amines
synthesis of amines
by reduction of amides:
by reduction of nitriles:
Me
CN
LiAlH4
Et2O
∆
Me
H2O
NH2
88%
NH2
87%
H2
CN
synthesis of amines
RaNi
NH3 ∆
synthesis of amines
by reduction of nitro compounds:
by reduction of azides:
O
Cl
NaN3
acetone
H2O ∆
O
O
N3
O
H2
Pd/C
EtOH
O
H2N
O
82%
azide is:
N N N
2
synthesis of amines
the Gabriel synthesis – more examples:
by reduction of imides – the Gabriel synthesis:
O
O
Br
DMF
+
N K
N
90°
Br
Br
O
83%
NH2
NH2NH2
MeOH
∆
Br
O
83%
O
Br
N K
H2SO4
N
DMF
100°
O
synthesis of amines
O
HO
NH2
H2O, ∆
73%
O
93%
synthesis of amines
by reduction of imines and related compounds:
by reduction of imines and related compounds:
O
phenylpropanone
+
H2
OH
H2N
Pt
EtOH
O2N
CO2Et
OH
N
H
N
H2
+ CH2O
(excess)
95%
Pd/C
EtOH
CO2Et
77%
Ph
Ph
NOH
H2O
LiAlH4
Et2O
∆
Ph
Ph
61%
NH2
amphetamine
synthesis of amines
by rearrangement:
mechanism of the Hofmann rearrangement
O
R
N
R
H
O
R
N
O
H
N
Br
OH
Br
O
H
R
Br
H OH
O
C
N
R
N
OH
H
Br
O
H
O
N
H
-CO2
RNH2
R
OH
(same as the text, figure 24.5)
3
two examples:
mechanism of the Curtius rearrangement
O
R
O
N3
Cl
N N N
R
O
C
as
N
before
R
RNH2
83%
Acylation and Alkylation of amines
Acylation and Alkylation of amines
straightforward – no complications
O
O
NH4OAc
Cl
NH2
acetone
O
aq
Cl
+
83%
NH2
NH4OH
NH2
92%
O
O
O
aq
NaOH
Cl
N
H
O
Cl
+
HN
aq
NaOH
O
N
81%
complete alkylation to the quaternary ammonium salt is
followed by an elimination
The Hofmann elimination
which yields the least substituted alkene predominantly
91%
We will now skip over to section 24.8 – Diazonium salt reactions
Nitrous acid
4
H
HO NO
H2O NO
+ NO
Ar
NH2
Ar
H
N NO
Ar
N N OH
H
H2O + NO
Ar
H
Ar
H
H2
N NO
-H+
H
N N OH
ArN2
+
Ar
H
N N OH
H
H2O
the Sandmeyer reaction
peudohalogens include CN, NO2, SCN, CNO, etc. – monovalent
anions which act like halide ions
-- generally requires Cu I
-- reaction thought to be a radical mechanism
-- works with halogens (not F) and pseudohalogens
-- iodine does not need Cu I
OH
N2
Fluorine is a little different:
a mild way to introduce OH
F
N2
NO2
the Schiemann reaction
O 2N
Br
H2N
Br
NaNO2
HPF6
H2SO4
0-5°
heat in
70%
OMe
H2N
H2 N
Me
NO2
NaNO2
H2O
MeOH
H2SO4
0-5°
warm
H2N
85%
Br
F
mineral
oil
NO2
Na2S
HO
80%
Br
NaNO2
H2O
H2SO4
0-5°
warm
HO
Me
95%
OMe
NaNO2
H2SO4
0-5°
HPF6
heat in
mineral
oil
F
60%
use of Cu I can
aid in the reaction
5
and finally, one can replace the NH2 by H
-- this leads to the possibility of using NH2 for its directing and activating
powers, then eliminating it.
COOH
Br
Br2
H2 N
HCl
H2 N
COOH
Br
NaNO2
H3PO2
Br
H2SO4
0-5°
Br
COOH
Br
Br
70%
and lastly, there is a reaction in which the nitrogens are retained:
formation of azo compounds
N2
+
NMe2
N N
-
NMe2
O3S
N N
Butter yellow
HO
-
-
O3S
N N
Methyl Orange
O3S
NMe2
pH 3.2
λmax 520 nm
SO3-
-
N N
H
NMe2
pH 4.4
λmax 460 nm
Para-Red
O3S
N
-
N
O3S
N
NH2 OH
SO3-
N
OH NH2
Direct Blue 2B
6
Strategy in Synthesis
Strategy in Synthesis -2
Starting with MeO
Starting with
O2 N
NH2
H2N
Make:
Make:
NH2
Br
Br
NO2
Cl
NHAc
F
Cl
Cl
MeO
X
where X = OH, CN, COCH3
OH
7