Silicon tetrachloride catalyzed aza-michael addition of amines to conjugated alkenes under solvent-free conditions

Article abstract of DOI:10.1055/s-0029-1219195

The efficient and very simple conjugate addition of aromatic and aliphatic amines to α,β-unsaturated carbonyl compounds under solvent-free conditions in the presence of catalytic amount of silicon tetrachloride is reported. The reaction of aryl and alkyl amines with different Michael acceptors gave the corresponding Michael adducts with simple catalyst and good to excellent yields. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0029-1219195

LETTER
379
Silicon Tetrachloride Catalyzed Aza-Michael Addition of Amines to
Conjugated Alkenes under Solvent-Free Conditions
Silicon
T
etrachlor
a
C
atalyz
j
edAz
a
m
A
ddition
o
e
f
A
mine
s
din Azizi,*a Roya Baghi,b Hossein Ghafuri,b Mohammad Bolourtchian,a Mohammad Hashemib
a
Chemistry and Chemical Engineering Research Center of Iran, P.O. Box 14335-186, Tehran, Iran
Fax +98(21)44580762; E-mail: azizi@ccerci.ac.ir
b
Department of Chemistry, Sharif University of Technology, P. O. Box 11365-9516, Tehran, Iran
Received 16 September 2009
As a part of our research aimed at developing green chem-
istry by using water as the reaction medium or by per-
forming organic transformations under solvent-free
conditions,8 we describe herein a simple, highly efficient,
Abstract: The efficient and very simple conjugate addition of aro-
matic and aliphatic amines to a,b-unsaturated carbonyl compounds
under solvent-free conditions in the presence of catalytic amount of
silicon tetrachloride is reported. The reaction of aryl and alkyl
amines with different Michael acceptors gave the corresponding and eco-friendly method for the synthesis of b-amino car-
Michael adducts with simple catalyst and good to excellent yields.
bonyl compounds from aromatic and aliphatic amines and
a,b-unsaturated Michael acceptors under solvent-free
conditions.
Key words: aromatic amine, conjugate addition, silicon tetrachlo-
ride, b-aminocarbonyl compounds
In order to find the best reaction conditions, we first stud-
ied the reaction of aniline and methyl acrylate with differ-
ent loadings of starting materials and catalyst. It was
found that the reaction of methyl acrylate (1.04 equiv) and
aniline (1 equiv) in the presence of commercially avail-
able silicon tetrachloride (2 mol%) under solvent-free
conditions proceeded smoothly within four hours to af-
ford the conjugate addition product exclusively and in
quantitative yield. Furthermore, in organic solvents, such
as CH2Cl2, MeCN, toluene, ethanol, water, and tetrahy-
drofuran the Michael addition reaction proceeded over
longer reaction times to give the desired product in lower
yields (Scheme 1).
The aza-Michael addition reaction is one of the most im-
portant methodologies in synthetic organic chemistry for
preparation of b-aminocarbonyl compounds, which not
only constitute components of biologically important nat-
ural products but also serve as key intermediates for the
synthesis of b-amino alcohols, antibiotics, b-amino acids,
chiral auxiliaries, and other nitrogen-containing com-
pounds.1,2
The Mannich reaction is a classical method for the synthe-
sis of b-amino carbonyl compounds. However, the reac-
tion has disadvantages such as harsh reaction conditions,
long reaction times, and a relatively narrow scope of sub-
strates.3 The aza-Michael addition of nitrogen nucleo-
philes including amides, carbamates, sulfonamides, and
amines to electron-deficient alkenes in the presence of
strong base or acid catalyst has attracted considerable at-
tention as an alternative route for the synthesis of b-amino
carbonyl compounds.4 Since some functional groups may
be susceptible to strong acid or base, a variety of catalysts5
and promoters for aliphatic amines6 have been introduced
over the past few years.
NH2
O
O
SiCl4 (2 mol%)
+
PhHN
OMe
OMe
solvent, 60 °C, 4 h
Solvent CH2Cl2 C6H12 MeCN THF toluene H2O EtOH SFC
Yield (%)
20
5
55
40
40
20
50
95
However, there are still some limitations with the existing
methods; for example, the range of amine nucleophiles
and Michael acceptors well suited to both catalytic and
stoichiometric methodologies is generally restricted to
simple aliphatic amines and Michael acceptors and there
have been few reports involving simple catalysts or re-
agents to effect these transformations.7 Thus, develop-
ment of an efficient catalytic protocol that could
overcome the above-mentioned disadvantages and facili-
tate the addition of both aromatic/aliphatic amines to a,b-
unsaturated compounds remains a challenge.
Scheme 1
To explore the scope of the protocol, a number of elec-
tron-deficient olefins and aromatic and aliphatic amines
was examined under the optimized conditions (Table 1).
Several primary and secondary amines underwent smooth
addition with a,b-unsaturated ketones, nitriles, and
amides under catalyst-free conditions. In all cases, reac-
tions proceeded smoothly and gave the corresponding
products in good to excellent yield. Both aliphatic and ar-
omatic amines react with a variety of conjugated alkenes
by this procedure to produce the corresponding adducts in
high yields. As evident from the results, anilines bearing
either electron-donating or electron-withdrawing groups
give the Michael addition products in good yields. Simi-
SYNLETT 2010, No. 3, pp 0379–0382
1
2.
0
2.
2
0
1
0
Advanced online publication: 14.01.2010
DOI: 10.1055/s-0029-1219195; Art ID: D18809ST
© Georg Thieme Verlag Stuttgart · New York

380
N. Azizi et al.
LETTER
larly, the corresponding products from the reaction of ali- nyl ketone, methyl methacrylate, methyl crotonate, and
phatic amines with a,b-unsaturated alkenes were also crotonitrile underwent 1,4-addition with a variety of
obtained with excellent yields. In general the reaction amines to furnish the corresponding addition products.
rates are faster with aliphatic amines compared to those of The reactive Michael acceptor methyl vinyl ketone
aromatic amines and very electron-withdrawn amines, (MVK) underwent Michael addition at room temperature
such as 4-nitroaniline, did not react. Addition to a,b-un- and short reaction time to give the mono-Michael adduct
saturated aldehydes was also unsuccessful. Primary when one equivalent of MVK was used (Table 1), but
amines give only monoaddition products in most cases when three equivalents of MVK were used, bisadduct was
and no bisaddition product was isolated. Similarly, vari- formed over a longer reaction time.
ous a,b-unsaturated compounds such as methyl acrylate,
acrylonitrile, acrylamide, benzylidenacetone, methyl vi-
Table 1 Michael Addition under Solvent-Free Conditions Catalyzed by Silicon Tetrachloride
R3
X
R1R2NH
SiCl4 (2 mol%)
60 °C, 1–4 h
R3
+
X
R1R2N
2
1
3
X = CN, COOMe, CONH2, COR
H
H
H
H
N
NH2
NH2
NH2
NH2
NH2
NH2
N
N
N
Me
Ph
NH2
1a
1b
1c
1d
1e
Cl
OMe
Br
1j
Me
1h
1i
1k
1l
1m
N
Ph
NHMe
H
1g
1f
Entry
Michael acceptor
Amine (R1R2NH)
Yields (%)a
1
2
3
4
5
6
7
8
9
10
11
12
13
1a
1b
1c
1d
1e
1f
1g
1h
1i
94
90
84
88
80
82
72
95
92
78
75
82
80
O
OMe
1j
1k
1l
1m
14
15
16
17
18
19
20
21
22
23
24
25
26
1a
1b
1c
1d
1e
1f
1g
1h
1i
1j
1k
1l
1m
94
90
84
88
80
82
72
95
92
78
75
82
80
CN
27
28
29
30
31
32
33
1a
1b
1c
1d
1f
80
72
74
60
64
50
56
O
OMe
1h
1l
Synlett 2010, No. 3, 379–382 © Thieme Stuttgart · New York

LETTER
Silicon Tetrachloride Catalyzed Aza-Michael Addition of Amines
381
Table 1 Michael Addition under Solvent-Free Conditions Catalyzed by Silicon Tetrachloride (continued)
R3
X
R1R2NH
SiCl4 (2 mol%)
60 °C, 1–4 h
R3
+
X
R1R2N
2
1
3
X = CN, COOMe, CONH2, COR
H
H
H
H
N
NH2
NH2
NH2
NH2
NH2
NH2
N
N
N
Me
Ph
NH2
1a
1b
1c
1d
1e
Cl
OMe
Br
1j
Me
1h
1i
1k
1l
1m
N
NHMe
Ph
H
1g
1f
Entry
Michael acceptor
Amine (R1R2NH)
Yields (%)a
34
35
36
37
38
39
40
41
1a
1b
1c
1f
1h
1i
90
90
84
76
82
80
60
68
O
OMe
1k
1m
42
43
44
45
1a
1b
1c
1d
82
78
70
75
O
NH2
46
47
1ab
1b
88
84
O
Ph
48
49
50
1a
1b
1c
88
90
80
CN
Ph
51
52
53
1a
1b
1c
82
80
85
CN
54
55
56
57
58
59
1ac
1b
1c
1f
1h
1l
90
90
84
78
94
88
O
a NMR and GC yields.
b Conditions: 5 mmol benzylidenacetone and 8 mmol amines were used.
c In the case of methyl vinyl ketone, bis-substitution products were observed with aromatic amines.
In summary, we have developed an efficient and very sim-
ple procedure for the aza-conjugate addition of a,b-unsat-
urated carbonyl compounds with aromatic and aliphatic
amines in the presence of a catalytic amount of silicone
tetrachloride that provides access to useful and syntheti-
cally challenging b-amino ketones. The use of inexpen-
sive and readily available reagents, chemical efficiency,
operational simplicity, and simple workup make this pro-
cess particularly attractive.9
Acknowledgment
Financial support of this work by Chemistry and Chemical Re-
search Center of Iran is gratefully appreciated.
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Synlett 2010, No. 3, 379–382 © Thieme Stuttgart · New York

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