Cellulose-supported copper(0) catalyst for aza-Michael addition

Article abstract of DOI:10.1055/s-2006-949623

Cellulose-supported copper(0) efficiently catalyzes the aza-Michael reaction of N-nucleophiles, such as amines and imidazoles with α,β-unsaturated compounds to produce the corresponding β-amino compounds and N-substituted imidazoles in excellent yields. The reactions are facile and the recovered catalyst is used for several cycles with consistent activity. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-949623

LETTER
2246
Cellulose-Supported Copper(0) Catalyst for Aza-Michael Addition
C
K
ellulose-Supporte
.
d Copper(0)
R
Catalyst
f
or
A
za
a
-Michael
A
j
dditio ne nder Reddy,* Nadakudity S. Kumar
Inorganic and Physical Chemistry Division, Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500 007, India
Fax +91(40)27160921; E-mail: rajender@iict.res.in
Received 2 March 2006
In recent years the emphasis of science and technology is
shifting more towards environmentally friendly and sus-
tainable resources and processes, in this regard biopoly-
Abstract: Cellulose-supported copper(0) efficiently catalyzes the
aza-Michael reaction of N-nucleophiles, such as amines and imida-
zoles with a,b-unsaturated compounds to produce the correspond-
ing b-amino compounds and N-substituted imidazoles in excellent
mers are attractive candidates to explore for supported
yields. The reactions are facile and the recovered catalyst is used for catalysis.1 Several interesting features of the biopoly-
9,20
several cycles with consistent activity.
mers for example, high sorption capacity, stability of met-
Key words: cellulose, copper, aza-Michael, amines, imidazoles, al anions and physical and chemical versatility make them
a,b-unsaturated compounds, b-amino compounds, N-substituted attractive to use as supports. Moreover, the polymers can
imidazoles
be molded in different forms, flakes, gel beads, mem-
branes, fibers, hollow fibers, sponge or supported on inert
materials. Recently, several biopolymers, for example al-
2
1
22
23
24
The b-amino ketone functionality is an important segment ginate, gelatin, starch and chitosan derivatives have
for the synthesis of biologically active natural products been utilized as supports for catalytic applications.
and it also serves as an essential intermediate in the syn-
Cellulose is the most common biopolymer, which is wide-
1
–4
thesis of b-amino acids and b-lactam antibiotics. Con-
sequently, the development of novel synthetic methods
for their synthesis has attracted sustained interest in or-
ganic synthesis. The most common method for the prepa-5
ration of b-amino ketones is the Mannich reaction.
Classical Mannich-type reactions are certainly very pow-
erful but need quite severe reaction conditions and are
rather sluggish. Conjugate addition of amines to a,b-un-
saturated compounds which is also known as aza-Michael
is on the contrary, atom economic and quite easy to carry
out. However, these reactions require either basic
ly abundant in nature. Recently, we have prepared cellu-
lose supported Cu and Pd catalysts using biopolymer as a
support and applied these catalysts for C–C and C–N cou-
25
pling reactions. It is observed that cellulose fibers act as
a nanoreactor for the stabilization of metal nanoparti-
26
cles. Very recently, Verma and co-workers reported the
Cu-nanoparticles as a chemoselective catalyst for the aza-
Michael reactions of N-alkyl- and N-arylpiperazines with
27
acrylonitrile. These results prompted us to look the cat-
alytic activity of cellulose supported copper catalyst
[
CELL-Cu(0)], which is prepared from the reported
6
7
conditions or acidic catalysts, which can be detrimental
to the desired synthesis. Moreover, most Lewis acid cata-
lysts are likely to be poisoned by alkyl- and arylamine re-
25a
procedure for aza-Michael reactions (Scheme 1).
R''
R'
8
agents. In order to overcome some of the disadvantages,
R
R''
X
CELL-Cu(0)
MeOH, r.t.
+
X
a wide range of alternative procedures have been reported
over the past few years using stoichiometric or catalytic
Lewis acids such as Yb(OTf) , InCl , CeCl ·7H O,
NH
R'
N
R
3
3
3
2
1a–h
2
3
Bi(NO ) , Bi(OTf) , Cu(OTf) , FeCl ·7H O/Co(OAc) ,
2
3
3
2
3
2
2
9
–15
SmI and LiClO . However, many of these methods of-
2
4
X = COOMe, COMe,
CN, CONH2
ten involves the use homogeneous catalysts which have
difficulty in disposal and non-recyclability. In contrast,
there are only few reports on addition of amines to a,b-un-
saturated compounds activated by heterogeneous cata-
Scheme 1
1
6,17
lysts.
More recently, a green approach in ionic liquids The conjugate addition of amines with different Michael
has been developed for the conjugate addition of amines acceptors in presence of CELL-Cu(0) catalyst have been
1
8
to a,b-unsaturated compounds. Although the recent ad- studied and the results are summarized in Table 1. a,b-
vances made this route attractive, the development of sim- Unsaturated compounds such as methyl acrylate, acrylo-
ple, convenient and environmentally benign recyclable nitrile, methyl methacrylate, methyl vinyl ketone and
approaches are highly desirable.
acrylamide underwent conjugate addition with aliphatic
secondary amines to afford the corresponding product in
quantitative yields (Table 1, entries 1–11). However, the
reaction of morpholine with acrylamide required longer
reaction time compared to other Michael acceptors. Steri-
cally hindered amine, dibenzylamine was found to be
SYNLETT 2006, No. 14, pp 2246–2250
0
1
.0
9
.2
0
0
6
Advanced online publication: 24.08.2006
DOI: 10.1055/s-2006-949623; Art ID: D06806ST
©
Georg Thieme Verlag Stuttgart · New York

LETTER
Cellulose-Supported Copper(0) Catalyst for Aza-Michael Addition
2247
equally efficient for this reaction (Table 1, entries 12 and To explore further the activity of the present catalyst, we
3). Primary amines such as benzylamine, n-butylamine, have tested imidazole as a Michael donor for aza-Michael
1
and cyclohexylamine gave bis-adducts in the presence of reactions (Scheme 2) and the results are summarized in
excess amount of a,b-unsaturated compound (Table 1, en- Table 2.
tries 14–21). Similarly, piperazine also afforded the corre-
sponding bis-adduct in excellent yield (Table 1, entries
2
2–24).
28
Table 1 Aza-Michael Addition of Various Amines with a,b-Unsaturated Compounds
Entry
1
Amine 1
Acceptor 2
Time (h)
0.3
Product 3
Yield (%)a
98, 97b
CN
CN
NH
N
1a
2
3
4
1a
1a
1a
COOMe
0.3
0.3
1.0
COOMe
COMe
96
94
98
N
N
COMe
COOMe
COOMe
CN
N
5
6
7
8
9
CN
0.3
0.3
0.5
5.0
1.0
90
98
96
95
98
O
NH
O
O
O
N
N
N
N
1b
COOMe
COOMe
COMe
CONH2
CN
1b
1b
COMe
CONH2
CN
O
n-C H9
4
n-C H
4
9
NH
N
n-C4H9
n-C4H9
n-C4H9
1c
1
1
1
0
1
2
1c
COOMe
COMe
1.0
2.0
0.3
COOMe
COMe
98
N
N
n-C4H9
n-C4H9
1c
93
n-C4H9
98, 96b
Ph
Ph
COOMe
COOMe
COMe
Ph
NH
N
N
Ph
1d
1
3
1d
COMe
0.3
98
Ph
Ph
Ph
1
1
4
5
COOMe
COOMe
0.3
0.3
COOMe
COOMe
98
Ph
NH2
N
H
1e
1e
90c,d
Ph
Ph
N
N
COOMe
CN
1
6
1e
CN
0.3
90c
CN
Synlett 2006, No. 14, 2246–2250 © Thieme Stuttgart · New York

2
248
K. R. Reddy, N. S. Kumar
LETTER
28
Table 1 Aza-Michael Addition of Various Amines with a,b-Unsaturated Compounds (continued)
Entry
Amine 1
Acceptor 2
Time (h)
0.3
Product 3
Yield (%)a
1
7
n-C H NH
CN
CN
98c
4
9
2
n-C4H9
HN
1f
1
8
1f
1f
1f
CN
0.3
0.3
0.3
3.0
CN
95c
n-C4H9
n-C4H9
n-C4H9
N
CN
1
2
2
9
0
1
COOMe
COOMe
COOMe
COMe
95c
95c
95c
N
N
COMe
COMe
COMe
CH COMe
2
NH2
N
CH2COMe
1g
2
2
COOMe
0.3
COOMe
95c
HN
NH
N
N
MeOOC
1h
2
2
3
4
1h
CN
0.3
0.3
CN
95c
95c
N
N
NC
1h
COMe
COMe
N
N
MeOC
a
b
c
d
Isolated yields.
Yield after 4 cycle.
th
Reaction performed with 2 equiv of acceptor.
0% of monoadduct was observed.
1
CELL-Cu(0)
(Table 2, entries 1–4). However, the reaction of imidazole
with tert-butyl acrylate afforded the product in moderate
yield (Table 2, entry 5), whereas methyl methacrylate
gave trace amount of the addition product (Table 2, entry
+
X
N
NH
N
N
toluene, reflux
X
1i
2
4
X = COOMe, CN, etc.
6
). Among the cyclic a,b-unsaturated compounds, cyclo-
Scheme 2
hexenone was found to be more reactive than cyclopen-
tenone (Table 2, entries 7 and 8).
Under the above conditions with 1.2 mol% of CELL-
Cu(0) in methanolic solution, no addition product was ob-
served for the reaction of imidazole with acrylonitrile at
room temperature. Even an increase in catalyst loading
and temperature did not yield the product. After screening
various solvents, optimum product conversion (98%) was
observed with toluene as the solvent under reflux condi-
tions (Table 2, entry 1). It is observed that the temperature
is very crucial for the imidazole addition to the a,b-unsat-
urated compounds. There are only few examples reported
in literature for the imidazole addition to the a,b-unsatur-
ated compounds in which either an enzyme catalyst or ba-
sic clay catalyst under sonochemical conditions has been
The CELL-Cu(0) was recovered after the reaction by sim-
ple filtration, washed with methanol–toluene and dried.
The recovered catalyst is reused for aza-Michael addition
of amines (Table 1, entries 1 and 12) and imidazole
(
Table 2, entry 1). The leaching of the metal after the
fourth cycle was determined by ICP-AES and is negligi-
ble (0.01%).
In conclusion, a facile and clean aza-Michael reaction of
amines and imidazole with a,b-unsaturated carbonyl com-
pounds using cellulose supported Cu(0) catalyst has been
developed. This simple protocol works well for amines
and imidazoles with low catalyst loading and with easy re-
cycling of the catalyst.
2
9,30
utilized.
With this effective catalyst, the aza-Michael addition of
imidazole with a variety of a,b-unsaturated compounds
Acknowledgment
was studied and N-substituted imidazoles were obtained We wish to thank the CSIR for financial support under the Task
in moderate to good yields (Table 2). Simple as well as Force Project CMM-0006 and N.S.K thank the CSIR, India, for the
award of research fellowship.
long chain acrylates were equally reactive with imidazole
Synlett 2006, No. 14, 2246–2250 © Thieme Stuttgart · New York

LETTER
Cellulose-Supported Copper(0) Catalyst for Aza-Michael Addition
2249
3
1
Table 2 Aza-Michael Addition of Imidazole with a,b-Unsaturated Compounds
Entry
1
Donor 1i
Acceptor 2
Product 4
Yield (%)a
98, 97b
CN
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
NH
CN
1
i
2
3
4
5
6
7
1i
O
O
98
O
O
1i
1i
1i
1i
1i
O
O
98
O
O
O
O
O
O
O
O
O
O
98
80
O
O
trace
77
O
O
O
O
8
1i
56
O
N
N
O
a
Yields based on NMR.
Yield after 4th cycle.
b
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K. R. Reddy, N. S. Kumar
LETTER
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,11,15,17b,c
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(31) Typical Experimental Procedure for the Conjugate
Addition of Imidazole to a,b-Unsaturated Compounds:
In a typical procedure, a,b-unsaturated compound (1.0
mmol), imidazole (1.0 mmol) and catalyst (3.6 mol%) were
taken in toluene (5 mL) and stirred at reflux temperature for
12 h. The resulting reaction mixture was filtered and washed
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pressure. The crude product was purified by column
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2a,29
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5): H NMR (200 MHz, CDCl ): d = 7.44 (s, 1 H), 6.97 (s, 1
3
H), 6.87 (s, 1 H), 4.21 (t, J = 6.80 Hz, 2 H), 2.66 (t, J = 6.80
+
Hz, 2 H), 1.41 (s, 9 H). MS (70 eV): m/z = 196 [M ].
Synlett 2006, No. 14, 2246–2250 © Thieme Stuttgart · New York