Chemistry Reference
In-Depth Information
HN
NH
2
Ph
Ph
Ph
Ph
1. acetylation
Ph
Ph
Ph
N
NH
O
O
2. H
+
O
2
DME, reflux
H
2
N
NH
2
Ph
isoamarine (
8
)
Scheme 3.6
Alkylation of phenylamidine by cyclic sulfate for the synthesis of amidine
Cyclic sulfate is transformed to cyclic amidine [isoamarine (8)] by reaction with
phenylamidine [17]. The cyclic amidine is hydrolyzed after acetylation to give chiral
1,2-diphenylethylenediamine, a useful chiral building block (Scheme 3.6).
3.2.2 Condensation of 1,2-Diamine
Cyclic amidines are prepared by the condensation of 1,2-diamines and
-ketoester
derivatives [18]. Reaction of N-monomethyl-1,2-diamine and formylacetate acetal in the
presence of an acid catalyst such as hydrochloric acid (HCl) or p-TsOH initially forms
amidines by cyclocondensation. Elimination of ethanol to ethoxyvinyl amidine, followed
by incorporation of a different 1,2-diamine, furnishes 1,3-dimethyl- and 1-butylimidazo-
lidines (Scheme 3.7). This reaction is applied to the preparation of several kinds of diamines
as a key step [19].
b
3.2.3 Coupling of Imines (Isoamarine Synthesis)
A sequence of hydrobenzamide-amarine-isoamarine (8) is one of the useful synthetic
routes for C
2
-symmetric 1,2-diamines through cyclic amidines (Scheme 3.8). The reaction
course is proposed as follows: (i) formation of hydrobenzamide from benzaldehyde and
ammonia, (ii) trimeric condensation to amarine, and (iii) isomerization to isoamarine (8)
under basic condition [20] (path A). Corey and Kuhnle [21] proposed an alternative path
for the reaction course (path B) based on characterization of each intermediate. This
amidine is found to be rather stable to acid-catalysed hydrolysis. Thus, reduction of
isoamarine (8) to imidazolidine with aluminum amalgam in wet tetrahydrofuran (THF)
followed by acid hydrolysis yields the corresponding 1,2-diamine.
H
N
N
NH
2
EtO
2
C
CH(OEt)
2
H
2
N
NHBu
N
OEt
R
1
N
N
N
Bu
H
c. HCl
N
77%
R
2
NHMe
N
Me
230 ˚C, 6 h
R
1
= H, R
2
= Bu
R
1
= R
2
= Me
Me
Scheme 3.7
Amidine formation from
b
,
b
-diethoxypropionate and N-methyl- and N-
butylethylenediamine
