Microwave-assisted, rapid, solvent-free aza-michael reaction by perchloric acid impregnated on silica gel

Article abstract of DOI:10.1080/00397910902883579

Highly efficient solvent-free aza-Michael additions of a variety of amines to,-unsaturated carbonyl compounds under microwave-irradiation conditions catalyzed by perchloric acid impregnated on silica gel (HClO4/SiO2) is reported. The reactions are completed within 2-7min in a microwave oven to produce the corresponding adducts in excellent yields, and the catalyst can be recovered and reused.

Full text of DOI:10.1080/00397910902883579

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Microwave-Assisted, Rapid,
Solvent-Free Aza-Michael
Reaction by Perchloric Acid
Impregnated on Silica Gel
a
b
Surya Prakash Singh , T. Vijaya Kumar , M.
b
b
b
Chandrasekharam , L. Giribabu & P. Yella Reddy
a
Department of Applied Chemistry, Graduate School
of Engineering, Osaka University, Suita, Osaka,
Japan
b
Nano Materials Laboratory, Inorganic and Physical
Chemistry Division, Indian Institute of Chemical
Technology, Hyderabad, India
Version of record first published: 16 Oct 2009.
To cite this article: Surya Prakash Singh , T. Vijaya Kumar , M. Chandrasekharam ,
L. Giribabu & P. Yella Reddy (2009): Microwave-Assisted, Rapid, Solvent-Free
Aza-Michael Reaction by Perchloric Acid Impregnated on Silica Gel, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 39:22, 3982-3989
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1
Synthetic Communications , 39: 3982–3989, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910902883579
Microwave-Assisted, Rapid, Solvent-Free
Aza-Michael Reaction by Perchloric Acid
Impregnated on Silica Gel
1
Surya Prakash Singh, T. Vijaya Kumar, M. Chandrasekharam,
2
2
2
L. Giribabu, and P. Yella Reddy
2
1
Department of Applied Chemistry, Graduate School of Engineering,
Osaka University, Suita, Osaka, Japan
2
Nano Materials Laboratory, Inorganic and Physical Chemistry Division,
Indian Institute of Chemical Technology, Hyderabad, India
Abstract: Highly efficient solvent-free aza-Michael additions of a variety of
amines to a,b-unsaturated carbonyl compounds under microwave-irradiation
conditions catalyzed by perchloric acid impregnated on silica gel (HClO =SiO )
4 2
is reported. The reactions are completed within 2–7 min in a microwave oven
to produce the corresponding adducts in excellent yields, and the catalyst can
be recovered and reused.
Keywords: Aza-Michael reaction, HClO =SiO , hydroamination, microwave
4
2
irradiation, reusable catalyst, solvent-free
INTRODUCTION
The development of catalysts for the formation of carbon–nitrogen
bonds by hydroamination of olefins is a synthetically important
[
1,2]
problem.
synthetic intermediates for the synthesis of a variety of biologically
The resulting b-amino carbonyl compounds are versatile
important natural products, antibiotics, b-amino alcohols, chiral
Received September 3, 2008.
Address correspondence to Surya Prakash Singh, Department of Applied
Chemistry, Graduate School of Engineering, Osaka University, Suita, 2-1 Yama-
daoka, Osaka 565-887, Japan. E-mail: singhsp@chem.eng.osaka-u.ac.jp
3
982

Solvent-Free Aza-Michael Reaction
3983
auxiliaries, and other nitrogen-containing compounds. Recently, much
attention has been paid to the development of efficient synthetic methods
leading to b-amino carbonyl compounds and derivatives. The conjugate
addition of nitrogen nucleophiles to a,b-unsaturated carbonyl com-
pounds (aza-Michael reaction) is one of the most simple and effective
methods for preparing these compounds. The aza-Michael reaction is
usually promoted by either acidic or basic catalysts. A variety of reagents
such as SnCl , TiCl , InCl , CeCl ꢀ7H O, Yb(OTf) , phosphine=TMSCl,
4
4
4
3
2
3
Cu(OTf) , LiClO , and KF=alumina have been reported to promote this
2
4
[
reaction. Recently, there were also reports of this reaction conducted in
3]
[
4]
[5]
ionic liquids, Cu(acac) =ionic liquid, ionic liquid=quaternary ammo-
nium salt in water, and boric acid in water. Solid-supported reagents
attracted interest in organic synthesis because of their reusability, stabi-
lity, and ease of handling. Among these, perchloric acid–impregnated
silica gel (HClO =SiO ) is a versatile catalyst that has been utilized for
[
acetylation of phenols, thiols, alcohols, and amines, peracetylation of
2
[6]
[7]
[8]
4
2
9]
[
10]
[11]
carbohydrates,
acetalization followed by acetylation,
glycosyla-
gem-diacylation of alde-
and more recently the Michael addition of thiols to
[
12]
[13]
tion,
Ferrier rearrangement of glycols,
[
14]
hydes,
electron-deficient alkenes
Microwave-assisted reactions are becoming popular because of their
[15]
[16]
and synthesis of acylals from aldehydes.
[
17]
simplicity in operation and milder reaction conditions.
The salient
features of the microwave approach are improved yields, enhanced reac-
tion rates, formation of pure products in good yields, and ease of isola-
tion. Green chemistry is becoming more important, in which harmful
organic solvents should be avoided and the catalyst can be recycled.
Recently, aza-Michael reactions promoted by various novel, safe,
[
5,7]
and recoverable catalysts have been reported.
for the application in microwave-induced organic reaction enhancement
MORE) chemistry to the synthesis of organic compounds involving
Exploring new catalysts
(
C–N bond formation expands chemistry. In this article, we report a
highly efficient, rapid, solvent-free aza-Michael reaction using a
solid-supported catalyst, perchloric acid–impregnated silica gel
(HClO =SiO ), under microwave irradiation conditions (Scheme 1).
4 2
The catalyst is highly efficient.
Scheme 1.

3984
S. P. Singh et al.
EXPERIMENTAL
Infrared (IR) spectra were recorded on Nicolet-740 Fourier transform
1
FT)–IR spectrometer. H NMR spectra were recorded on a Bruker
(
Avence 300 spectrometer at 300 MHz and Varian Gemini 200 spectro-
meter at 200 MHz. Chemical shifts are given in parts per million (ppm)
with respect to internal tetramethylsilane (TMS) for all recorded NMR
spectra, and J values are quoted in hertz (Hz). Mass spectra were
recorded on VG Micro mass-7070 H spectrometer at 70 eV. Reactions
were monitored on 0.25-mm Merck precoated silica-gel plates (60 F254).
Starting materials were used from commercial samples without purifica-
tion. All products were known and characterized by comparison of their
[
3f,18]
physical and spectroscopic data with those already reported.
Typical Experimental Procedure
A mixture of piperidine (85.1 mg, 1.0 mmol), methyl acrylate (103.3 mg,
.2 mmol), and a catalytic amount of HClO -SiO (20.0 mg, 0.1 mmol)
1
4
2
was charged in a sealed tube under nitrogen. The contents were irradiated
with microwaves (Ethos 1600 Advanced Microwave Labstation) for
2
.5 min at 540 W. After cooling the mixture to room temperature, the
contents were diluted with ethyl acetate and filtered, and the catalyst
was washed with ethyl acetate. The combined washings were concen-
trated under reduced pressure, and the residue was subjected to silica-gel
column chromatography using ethyl acetate–hexane (1:4) as eluent. The
pure product 1a (168 mg, 98%) was obtained as a light yellow oily liquid.
The structure of the compound was confirmed by the NMR, IR, and
mass spectra. The catalyst was washed thoroughly with ethyl acetate,
ꢁ
1
dried under vacuum for 4 h at 80 C, and used for the next run. H
NMR (200 MHz, CDCl ): d ¼ 1.30–1.42 (m, 2H), 1.48–1.57 (m, 4 H),
3
2
1
.33 (bt, 4H), 2.47 (t, J ¼ 7.30, 2H), 2.60 (t, J ¼ 6.90, 2H); IR (neat):
ꢂ1 þ
730 cm ; MS (EI): m=z ¼ 171 (M ).
RESULTS AND DISCUSSION
Initially, the reaction of piperidine on methyl acrylate was carried out
at room temperature in acetonitrile in the presence of 1.0 mol% of
HClO =SiO . HClO (1.25 g, 12.5 mmol, as a 70% aqueous solution) was
4
2
4
added to a suspension of silica gel (23.75 g, 230–400 mesh) in diethyl ether
(75 ml). The mixture was concentrated by rotary evaporator and subse-
quently dried under vacuum at 100 C for 72 h to afford HClO =SiO
ꢁ
4
2

Solvent-Free Aza-Michael Reaction
3985
Table 1. Comparative study of the reaction of piperidine and methyl acrylate
under various conditions using HClO =SiO
4
2
Entry
Conditions
Time
Yield (%)
1
2
3
4
HClO
No catalyst, CH
4
=SiO
2
, neat, rt
CN, rt
60 min
7 h
30 min
2.5 min
85
50
92
98
3
HClO =SiO , CH CN, rt
4
2
3
HClO
4
=SiO
2
, Neat=MW
ꢂ1
(
0.5 mmol g ) as a free-flowing powder. After 30 min, the reaction gave
2% yield of the product (Table 1, entry 1). When the reaction was con-
ducted in the absence of solvent, the yield was 85% after 60 min (entry
). In the absence of any catalyst, the reaction gave only 50% of the
9
2
Michael addition product even after 7 h (entry 3). We envisaged that
microwave irradiation would enhance the reaction rate multifold even
in the absence of any solvent, which would contribute to green chemistry.
As expected, the reaction in the presence of a catalytic amount of
HClO =SiO proceeded rapidly in a microwave oven at 540 W in
4
2
2
.5 min (entry 4). The b-amino ester 1a was obtained in quantitative yield
after simple workup and purification through a silica column. A variety of
a,b-unsaturated compounds such as methyl acrylate, acrylonitrile, methyl
methacrylate, acrylamide, and cyclohexenone underwent conjugate addi-
tion with a wide range of aliphatic amines in the presence of 1.0 mol%
of perchloric acid catalyst in 2–7 min (Scheme 1). The results are summar-
ized in Table 2. The reaction of piperidine with methyl acrylate was
repeated three times with the catalyst recovered from the previous reac-
tion, and the yield of the product is not affected considerably, proving that
the catalyst can be recycled efficiently (Table 2, entry 1).
To prove the generality of the reaction, the 1,4-addition of piperidine
to different Michael acceptors such as acrylonitrile, methyl methacrylate,
and acrylamide was carried out, and the reaction proceeded smoothly in
2
–3 min to give the conjugate addition products 1b–d in excellent yields
(
entries 2–4). Cyclic a,b-unsaturated ketones, for example, cyclohexe-
none, underwent 1,4-addition with piperidine to afford the conjugate
addition product 1e in 80% yield (entry 5). Morpholine was allowed to
react under similar reaction conditions with different a,b-unsaturated
compounds to afford aza-Michael adducts 1f–i in excellent yields
(
91–98%, entries 6–9). Dibutylamine also worked as a good Michael
donor with activated olefins such as acrylonitrile to readily produce the
,4-addition products 1j in 92% yields under microwave irradiation con-
1
ditions within 3 min (entry 10). Primary amines gave less yields of the
product than secondary amines. Thus, n-butylamine and cyclohexylamine

3986
S. P. Singh et al.
a
4 2
Table 2. Aza-Michael reaction using HClO =SiO
b
Yield (%)
Entry
Amine
Acceptor
Time (min)
Product
c
1
3
4
5
6
7
8
2.5
3
1a
1c
1d
1e
1f
98,95
92
90
80
3
5
d
91
3
3
1g
1h
97
98
3
9
1i
1j
93
1
0
3
92
89
1
1
1
2
n-BuNH
n-BuNH
2
2
2
3
1k
1l
e
82
13
14
15
16
5
5
3
4
1m
1n
1o
1o
80
e
78
90
91
17
7
1p
85
a
b
c
Typical reaction procedure is given.
Isolated yield based on the amine after purification.
Isolated yield after fourth cycle.
d
The amine (5.0 mmol) is used.
Yield of the bis-adduct with 2.4 equiv of acceptor.
e

Solvent-Free Aza-Michael Reaction
3987
reacted with acrylonitrile to give the corresponding b-aminonitriles 1k and
m in 89% and 80% yields, respectively (entries 11 and 13), whereas the
1
reaction of n-butylamine with an excess of methyl acrylate and cyclohexy-
lamine with an excess of acrylonitrile yielded the respective bis-adducts 1l
and 1n as expected (entries 12 and 14). Acrylonitrile and methyl acrylate,
when reacted with benzylamine, produced the corresponding Michael
addition products 1o and p in 90 and 91%, respectively. Furthermore,
methyl acrylate underwent conjugate addition with diisopropylamine, a
hindered nitrogen nucleophile, to afford the product 1q in 85% yields.
In conclusion, we have shown that perchloric acid–impregnated silica gel
is a versatile catalyst for aza-Michael addition reactions of various secondary
and primary amines with different activated alkenes, including methyl
acrylate, acrylonitrile, methyl methacrylate, acrylamide, and cyclohexenone.
The solvent-free reaction is environmentally benign, and the catalyst can
be recovered and reused with negligible loss of activity. The reaction can be
carried out in a microwave oven and the yields are invariably very good.
ACKNOWLEDGMENTS
Financial assistance from Indian Institute of Chemical Technology–Aisin
Cosmos Collaborative Research Project is acknowledged. We thank P. S.
Sai Prasad for providing the microwave laboratory station facility.
REFERENCES
1
. Han, L. B.; Tanaka, M. Transition metal–catalysed addition reactions of
H-heteroatom and inter-heteroatom bonds to carbon–carbon unsatutared
linkage via oxidative additions. Chem. Commun. 1999, 5, 395–402.
2
. Arredondo, V. M.; Tian, S.; McDonald, F. E.; Marks, T. J. Organolanthanide-
catalyzed hydroamination=cyclization: Efficient allene-based transformations
for the syntheses of naturally occurring alkaloids. J. Am. Chem. Soc. 1999,
121, 3633–3639.
3
. (a) Teck-Peng, L.; Lin-Li, W. Indium trichloride–catalyzed conjugate
addition of amines to a,b-ethylenic compounds in water. Synlett 1998, 9,
975; (b) Bartoli, G.; Bosco, M.; Marcantoni, E.; Petrini, M.; Sambri, L.;
Torregiani, E. Conjugate addition of amines to a,b-enones promoted by
CeCl ꢀ7H O-NaI system supported in silica gel. J. Org. Chem. 2001, 66,
3
2
9052–9055; (c) Matsubara, S.; Yashiyoka, M.; Utimoto, K. Lanthanoid
triflate–catalyzed conjugate addition of amines to a,b-unsaturated esters: A
facile route to optically active b-lactam. Chem. Lett. 1994, 23, 827–830; (d)
Wabnitz, T. C.; Spencer, J. B. Convenient synthesis of Cbz-protected
b-amino ketones by
a copper-catalysed conjugate addition reaction.

3988
S. P. Singh et al.
Tetrahedron Lett. 2002, 43, 3891–3894; (e) Xu, L.-W.; Xia, C.-G. Highly
efficient phosphine-catalyzed aza-Michael reactions of a,b-unsaturated com-
pounds with carbamates in the presence of TMSCl. Tetrahedron Lett. 2004,
45, 4507–4510; (f) Jenner, G. Catalytic high pressure synthesis of hindered
b-aminoesters. Tetrahedron Lett. 1995, 36, 233–236; (g) Srivastava, N.; Banik,
B. K. Bismuth nitrate–catalyzed versatile Michael reactions. J. Org. Chem.
2003, 68, 2109–2114; (h) Varala, R.; Alam, M. M.; Adapa, S. R. Chemoselec-
tive Michael-type addition of aliphatic amines to a,b-ethylenic compounds
using bismuth triflate catalyst. Synlett 2003, 5, 720–722; (i) Azizi, N.; Saidi,
M. R. LiClO4 accelerated Michael addition of amines to a,b-unsaturated
olefins under solvent-free conditions. Tetrahedron 2004, 60, 383–387; (j)
2 3
Yang, L.; Xu, L.-W.; Xia, C.-G. Highly efficient KF=Al O -catalyzed versa-
tile hetero-Michael addition of nitrogen, oxygen, and sulfur nucleophiles to
a,b-ethylenic compounds. Tetrahedron Lett. 2005, 46, 3279–3282.
. Yadav, J. S.; Reddy, B. V. S.; Basak, A. K.; Narasaiah, A. V. Aza-Michael
reactions in ionic liquids: A facile synthesis of b-amino compounds. Chem.
Lett. 2003, 32, 988–989.
4
5
. (a) Kantam, M. L.; Neeraja, V.; Kavita, B.; Neelima, B.; Chaudhuri, M. K.;
Hussain, S. Cu(acac)
ble catalytic system for aza-Michael reactions. Adv. Synth. Catal. 2005, 347,
63–766; (b) Kantam, M. L.; Neelima, B.; Reddy, C. V. A recyclable protocol
2
immobilized in ionic liquids: A recoverable and reusa-
7
for aza-Michael addition of amines to a,b,-unsaturated compounds using
Cu-Al hydrotalcite. J. Mol. Catal. A: Chem. 2005, 241, 147–150.
6
7
8
. Xu, L.-W.; Li, J.-W.; Zhou, S.-L.; Xia, C.-G. A green, ionic liquid and qua-
ternary ammonium salt-catalyzed aza-Michael reaction of a,b-ethylenic com-
pounds with amines in water. New. J. Chem. 2004, 28, 183–184.
. Chaudhuri, M. K.; Hussain, S.; Kantam, M. L.; Neelima, B. Boric acid: A
novel and safe catalyst for aza-Michael reactions in water. Tetrahedron Lett.
2005, 46, 8329–8331.
. (a) Zhuang-Ping, Z.; Wen-Zhen, Y.; Rui-Feng, Y. Microwave-assisted addi-
tion of pyrroles to electron-deficient olefins: A rapid entry to C-alkyl pyr-
roles. Synlett 2005, 16, 2425–2428; (b) Hajipour, A. R.; Ruoho, A. E.
Nitric acid in the presence of P O supported on silica gel—A useful reagent
2
5
for nitration of aromatic compounds under solvent-free conditions. Tetrahe-
dron Lett. 2005, 46, 8307–8310; (c) Zhuang-Ping, Z.; Rui-Feng, Y.; Jun-Ping,
L. Microwave-assisted one-pot synthesis of a-amino phosphonates via three
component coupling on a silica gel support. Chem. Lett. 2005, 34, 1042–
1043; (d) Karimi, B.; Ma’Mani, L. A highly efficient and recyclable
silica-based scandium(III) interphase catalyst for cyanosilylation of carbonyl
compounds. Org. Lett. 2004, 6, 4813–4815.
9
. Chakraborti, A. K.; Gulhane, R. Perchloric acid adsorbed on silica gel as a
new, highly efficient, and versatile catalyst for acetylation of phenols, thiols,
alcohols, and amines. Chem. Commun. 2003, 15, 1896–1897.
1
0. Misra, A. K.; Tiwari, P.; Madhusudan, S. K. HClO
per-O-acetylation of carbohydrates. Carbohydr. Res. 2005, 340,
25–329.
4 2
=SiO catalyzed
3

Solvent-Free Aza-Michael Reaction
3989
1
1
1
1
1. Mukhopadhyay, B.; Russel, D. A.; Field, R. A. one-pot acetalation–
acetylation of sugar derivatives employing perchloric acid immobilised on
silica. Carbohydr. Res. 2005, 340, 1075–1080.
2. Agarwal, A.; Rani, S.; Vankar, Y. D. Protic acid (HClO supported on silica
4
gel)–mediated synthesis of 2,3-unsaturated-O-glucosides and a chiral furan
diol from 2,3-glycals. J. Org. Chem. 2004, 69, 6137–6140.
3. Mukhopadhyay, B.; Collet, B.; Field, R. A. Glycosylation reactions with
‘
‘disarmed’’ thioglycoside donors promoted by N-iodosuccinimide and
HClO =silica. Tetrahedron Lett. 2005, 46, 5923–5925.
4. Khan, A. T.; Choudhury, L. H.; Ghosh, S. Silica-supported perchloric acid
HClO -SiO ): A highly efficient and reusable catalyst for geminal diacylation
of aldehydes under solvent-free conditions. J. Mol. Catal. A: Chem. 2006,
55, 230–235.
5. Khan, A. T.; Ghosh, S.; Choudhury, L. H. Perchloric acid impregnated on
silica gel (HClO =SiO ): A versatile catalyst for Michael addition of thiols
4
(
4
2
2
1
1
4
2
to the electron-deficient alkenes. Eur. J. Org. Chem. 2006, 9, 2226–2231.
6. Vinod, T. K.; Vasant, S. J.; Neeta, S. J.; Ankush, V. B.; Rameshchandra, Y. D.
An efficient method for the synthesis of acylals from aldehydes using
4 2
silica-supported perchloric acid (HClO =SiO ). Tetrahedron Lett. 2006, 47,
5573–5576.
1
1
7. For example, see Microwaves in Organic Synthesis; A. Loupy (Ed.);
Wiley-VCH: Weinheim, 2002.
8. Shaikh, N. S.; Deshpande, V. H.; Bedekar, A. V. Clay-catalyzed chemoselec-
tive Michael-type addition of aliphatic amines to a,b-ethylenic compounds.
Tetrahedron 2001, 57, 9045–9048.