Efficient synthesis of 2-indolyl-1-nitroalkanes catalyzed by tetramethyl-tetra-3,4-pyridinoporphyrazinato copper(II) methyl sulfate

Article abstract of DOI:10.1142/S1088424612004549

A new method for the synthesis of 2-indolyl-1-nitroalkanes from indoles and β-nitrostyrene via Michael addition catalyzed by [Cu(3,4-tmtppa)] (MeSO₄)₄ as a reusable catalyst under solvent-free conditions is described. This method has

Full text of DOI:10.1142/S1088424612004549

Journal of Porphyrins and Phthalocyanines
J. Porphyrins Phthalocyanines 2012; 16: 227–234
DOI: 10.1142/S1088424612004549
Published at http://www.worldscinet.com/jpp/
Efficient synthesis of 2-indolyl-1-nitroalkanes catalyzed
by tetramethyl-tetra-3,4-pyridinoporphyrazinato
copper(II) methyl sulfate
Elham Safaeia, Sara Sobhani*b and Nasrin Razavib
a Institute for Advanced Studies in Basic Sciences (IASBS), Zanjan 45195, Iran
b Department of Chemistry, College of Sciences, Birjand University, Birjand 414, Iran
Received 3 July 2011
Accepted 26 November 2011
ABSTRACT: Anewmethodforthesynthesisof2-indolyl-1-nitroalkanesfromindolesandb-nitrostyrene
via Michael addition catalyzed by [Cu(3,4-tmtppa)](MeSO4)4 as a reusable catalyst under solvent-free
conditions is described. This method has been also successfully applied for Michael addition of 3-methyl-
1-phenyl-5-pyrazolone with b-nitrostyrenes.
KEYWORDS: indole, b-nitrostyrene, pyrazole, Michael addition.
group is a powerful electron-withdrawing substituent and
INTRODUCTION
it may be transformedinto a legion of diversefunctionality
The indole nucleus is one of the most important
[6]. Michael addition of indoles to nitroalkenes can be
scaffolds found in natural products, pharmaceuticals,
catalyzed by either BrØnsted or Lewis acids. However,
functional materials, and agrochemicals [1]. Several
acid-catalyzed Michael addition of indole necessitates
indole derivatives that occur in nature possess
careful control over the acidity to avoid the undesirable
pharmacological activity. These include the hapalindole
side reactions such as dimerization, polymerization, and
alkaloids that exhibit significant antibacterial and
isomerization [7]. Incidentally, the polymerized products
antimycotic activity. Other indole alkaloids are
of indole derivatives involve troublesome isolation
uleine, aspidospermidine, the ibophyllidine alkaloids,
procedures to obtain the desired product. Many attempts
brivicolline and numerous tryptamine derivatives which
have been done by organic chemists to circumvent this
exhibit important biological activities [2]. Owing to the
problem such as using H2NSO3H [8a], ionic liquid-
great structural diversity and wide-ranging biological
coordinated Yb(III) sulfonate [8b], Zn(OAc)2 [8c, 8d],
activity of indole derivatives [3], construction and
Al(DS)3 [8e], I2 [8f], H3PW12O40 [8g], NBS [8h] and
functionalization of indole rings continue to attract the
microwave or ultrasound irradiation [8i, 8j]. However,
interest of both synthetic and pharmaceutical chemists.
most of the reported methods suffer from one or more
The conjugate addition of indoles to Michael acceptors
of the following drawbacks: using large amounts of
provides easy access to 3-substituted indole derivatives
solid supports or un-recyclable catalysts, which would
[4] that are important building blocks for the synthesis of
eventually result in the generation of a large amount
biologically important compounds. Among various types
of toxic waste, moderate yields of the products, long
of Michael acceptors, nitroalkenes are undoubtedly the
reaction time and difficult workup procedures. Although,
strongest and particularly versatile one [5], since the nitro
two catalyst-free methods were reported recently, the
yields of these reactions were somewhat low (63%–87%)
[8k, 8l]. Hence, the development of an effective method
SPP full member in good standing
for the synthesis of 2-indolyl-1-nitroalkanes via Michael
*Correspondence to: Sara Sobhani, email: ssobhani@birjand.
addition of indoles to nitroalkenes remains in great
demand.
ac.ir, sobhanisara@yahoo.com tel: +98 (561)-250-2008, fax:
+98 (561)-250-2009
Copyright © 2012 World Scientific Publishing Company

228
E. SAFAEI ET AL.
an effective catalyst for the synthesis of bis(indolyl)
methanes by the electrophilic substitution of indoles
with carbonyl compounds [12c]. These results prompted
us to apply [Cu(3,4-tmtppa)](MeSO4)4 as a catalyst for
the synthesis of 2-indolyl-1-nitroalkanes by Michael
addition of indoles with b-nitrostyrenes.
RESULTS AND DISCUSSION
At first, a series of Michael reactions of indole with
b-nitrostyrene catalyzed by different molar ratio of
[Cu(3,4-tmtppa)](MeSO4)4 under solvent-free conditions
was investigated in order to find the best reaction
conditions. The best yield of the desired 2-indolyl-1-
nitroalkane was obtained in the presence of 0.6 mol.% of
the catalyst at 80 °C. The optimized reaction conditions
were then used for the synthesis of a variety of 2-indolyl-
1-nitroalkane from Michael addition of indole with
various b-nitrostyrenes (Scheme 1, Table 1).
Fig. 1. [Cu(3,4-tmtppa)](MeSO4)4 (1)
As Table 1 demonstrates, the reaction time varied
according to the nature of the substituent on indole. The
indole bearing Br group needed a longer reaction time
(Entry 2). In contrast, the indole bearing methyl group
at 2-position afforded the corresponding product in
short reaction time (Entry 3). The electronic density of
the aromatic ring in the b-nitrostyrenes also played an
importantroleinthisreaction.Forexample,b-nitrostyrene
possessing electron-releasing group (OMe and Me)
underwent slow reaction (7 h and 6 h, respectively)
to obtain their corresponding products (Entries 4 and
5). Whereas, the reaction of b-nitrostyrenes bearing
electron-withdrawing groups (Cl and NO2) proceeded
smoothly in 0.5 h and 1 h, respectively (Entries 6 and 7).
Short reaction time in the case of 4-hydroxy substituent
on the b-nitrostyrene was appeared unexpectedly, which
may be due to the interaction of the hydroxyl group
with the catalyst (Entry 8). Sterically hindered naphthyl
b-nitrostyrene reacted with indole to afford the desired
product in good yield (Entry 9). It is important to note
that the acid-sensitive moieties (furyl and thienyl) and
a less reactive aliphatic b-nitrostyrene also reacted
with equal ease to furnish the Michael addition reaction
(Entries 10–12).
Metallophthalocyanines (Mpc) that are structurally
similar to metal porphyrins are easily accessible;
more stable to degradation and cost effective than
porphyrins. They have been extensively used as
efficient catalysts in a variety of organic reactions [9].
Tetrapyridinoporphyrazines (tppa) are heterocyclic
phthalocyanine (pc) derivatives in which the benzene
rings are replaced with electron-withdrawing pyridine.
The presence of pyridine rings in these compounds not
only increases the reactivity of tppa compared with pc,
but also allows the facile quaternarization processes.
The N,N',N'',N'''-tetramethylated quaternized form
of tetrapyridinoporphyrazine can be prepared easily
by its reaction with dimethyl sulfate in dimethyl
formamide [10]. The resulting tetramethyl-tetra-3,4-
pyridinoporphyrazinato copper(II) methyl sulfate
[Cu(3,4-tmtppa)](MeSO4)4 (1) (Fig. 1) is a water soluble
compound,andhasconsiderablelowsolubilityincommon
organic solvents. Unlike for metallophthalocyanine,
the reports on catalytic activity of metallotetra-
pyridinoporphyrazine in organic reactions are rare in the
literature [11].
Recently, we have focused on the discovery of new
applications of [Cu(3,4-tmtppa)](MeSO4)4 as a catalyst
in organic transformations [12]. In this regard, we have
found that [Cu(3,4-tmtppa)](MeSO4)4 can be used as
After performing Michael addition of indole
with b-nitrostyrene for the synthesis of 3-(2-nitro-1-
phenylethyl)-1H-indole under the conditions described
Scheme 1. Synthesis of 2-indolyl-1-nitroalkanes by Michael addition of indoles with b-nitrostyrenes catalyzed by [Cu(3,4-tmtppa)]-
(MeSO4)4
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EFFICIENT SYNTHESIS OF 2-INDOLYL-1-NITROALKANES CATALYZED
229
Table 1. Synthesis of 2-indolyl-1-nitroalkanes catalyzed by [Cu(3,4-tmtppa)](MeSO4)4 under solvent-free conditions at 80 °C
Entry [ref]
Indole
b-nitrostyrene
Time, h
Yielda, %
NO2
NO2
NO2
1 [8c]
5
95
N
H
Br
2 [8c]
3 [8c]
4 [8c]
5 [8c]
6 [8c]
6
0.25
7
90
90
80
80
80
N
H
N
H
NO2
N
H
MeO
NO2
6
N
H
NO2
0.5
N
H
Cl
NO2
7 [8c]
1
85
N
H
O2N
NO2
8 [8b]
9 [8c]
0.5
3
90
85
N
H
HO
NO2
N
H
NO2
10 [8c]
3
90
N
H
S
NO2
11 [8c]
12 [8i]
2
2
90
90
N
H
O
NO2
N
H
a Yields refer to isolated pure product characterized by spectroscopic methods and compared with the authentic samples. Reaction
conditions: indole (1 mmol), b-nitrostyrene (1 mmol), [Cu(3,4-tmtppa)](MeSO4)4 (0.006 mmol).
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230
E. SAFAEI ET AL.
conditions. It is worth noting that the recyclability test
was stopped after five runs.
A possible mechanism for the synthesis of 2-indolyl-
1-nitroalkanes in the presence of [Cu(3,4-tmtppa)]-
(MeSO4)4 is depicted in Scheme 2. In this mechanism,
indole is reacted with activated b-nitrostyrene by copper
of the catalyst 1 as a Lewis acid, and produced the desired
2-indolyl-1-nitroalkanes.
Showing the unique behavior of [Cu(3,4-tmtppa)]-
(MeSO4)4 for the synthesis of 2-indolyl-1-nitroalkanes,
we studied the reaction of indole with b-nitrostyrene
in the presence of a catalytic amount of [M(3,4-
tmtppa)](MeSO4)4 (M = Fe, Co) and Cu-phthalocyanine
tetrasulfate under solvent-free conditions (Table 2).
The results indicate well that the catalytic activity of
[Cu(3,4-tmtppa)](MeSO4)4 is superior than that of other
catalysts in terms of yield and the reaction time. We also
investigated the reusability of Cu-phthalocyanine for the
synthesis of 3-(2-nitro-1-phenylethyl)-1H-indole by the
present method. It was found that the reaction did not
work well in the presence of recycled catalyst, and the
starting material remained intact.
Fig. 2. Reusability of [Cu(3,4-tmtppa)](MeSO4)4 (1) as a
catalyst for the synthesis of 3-(2-nitro-1-phenylethyl)-1H-indole
in Table 1, EtOAc was added to the reaction mixture,
and the catalyst was filtered off and reused for the
similar reaction. This process was carried out for five
runs without noticeable reduction in the catalytic activity
of the catalyst. The average isolated yield for five
consecutive runs was 90%, which clearly demonstrates
the practical reusability of this catalyst (Fig. 2). This
reusability demonstrates the high stability and turnover
of [Cu(3,4-tmtppa)](MeSO4)4 under the employed
Pyrazoles are important classes of bio-active drug
targets in the pharmaceutical industry as they are the core
structure of numerous biologically active compounds
[13]. Among the pyrazole derivatives, the syntheses of
pyrazolone derivatives are paid much attention for their
Scheme 2. A plausible mechanism for the synthesis of 2-indolyl-1-nitroalkanes by Michael addition of indoles with b-nitrostyrenes
catalyzed by [Cu(3,4-tmtppa)](MeSO4)4 (1)
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EFFICIENT SYNTHESIS OF 2-INDOLYL-1-NITROALKANES CATALYZED
231
Table 2. Reaction of indole with b-nitrostyrene in the presence
on a Bruker Advance DPX-400. Mass spectra were
recorded on a Shimadzu GCMS-QP5050A. IR spectra
were run on a Perkin Elmer 780 instrument. The purity
of the products and the progress of the reactions were
accomplished by TLC on silica-gel polygram SILG/
UV254 plates. Elemental analysis for C, H and N were
obtained by using Elementar, Vario EL III.
of [M(3,4-tmtppa)](MeSO4)4 (M = Cu, Fe and Co) and
Cu-phthalocyanine tetrasulfate under solvent-free conditions at
80 °C
Entry
1
Catalyst
Time, h Yielda, %
[Cu(3,4-tmtppa)](MeSO4)4
5
5
5
5
95
45
32
63
2
3
4
[Fe(3,4-tmtppa)](MeSO4)4
[Co(3,4-tmtppa)](MeSO4)4
Cu-phthalocyanine tetrasulfate
General
General procedure for the synthesis of 2-indolyl-
1-nitroalkanes. [Cu(3,4-tmtppa)](MeSO4)4 (0.03 mmol)
was added to the stirring mixture of indole (5 mmol)
and b-nitrostyrene (5 mmol). The resulting mixture
was heated in an oil bath at 80 °C and stirred for an
appropriate time (Table 1). EtOAc (10 mL) was added to
the cooled reaction mixture. The catalyst was filtered off
and reused for a similar reaction. The organic solvent was
removed under reduced pressure, and the resulting crude
product was purified by column chromatography eluted
with n-hexane: EtOAc (1:1-3:1).
General procedure for the synthesis of 2-pyrazolyl-
1-nitroalkanes. [Cu(3,4-tmtppa)](MeSO4)4 (0.03 mmol)
was added to the stirring mixture of 3-methyl-1-phenyl-
5-pyrazolone (5 mmol) and b-nitrostyrene (5 mmol). The
resulting mixture was heated in an oil bath at 80 °C and
stirred for an appropriate time (Table 3). EtOAc (10 mL)
was added to the cooled reaction mixture. The catalyst
was filtered off and reused for a similar reaction. The
organic solvent was removed under reduced pressure,
and the resulting crude product was purified by column
chromatography eluted with n-hexane: EtOAc (1:1-3:1).
3-methyl-4-[2-nitro-1-(4-chlorophenyl)ethyl]-1-
phenyl-5-pyrazolone (Table 3, entry 2). Yield 1.61 g
(90%), mp 155 °C. Anal. calcd. for C18H16ClN3O3: C,
60.42; H, 4.51; N, 11.74%. Found: C, 60.51; H, 4.55; N,
11.81. 1H NMR (400 MHz; CDCl3; Me4Si): dH, ppm 1.91
(3H, s, CH3), 4.39 (1H, t, CH), 4.78 (1H, dd, CH2), 5.12
(1H, dd, CH2), 7.12 (1H, d, Ar), 7.15 (3H, t, Ar), 7.17–
7.28 (5H, m, Ar), 11.10 (1H, bs, OH). 13C NMR (CDCl3;
Me4Si): dC, ppm 10.5, 14.2, 39.0, 76.5, 120.9, 126.3,
128.9, 129.0, 129.1, 129.3, 133.3, 136.9, 137.7, 146.7. IR
(KBr): n, cm-1 2900 (O–H). MS (70 eV): m/z 358 ([M]+,
3.3), 360 ([M+ + 2], 1.1), 139 (3.3), 141 (1.1), 42 (100).
a Isolated yield.
various biological activities, such as antitumor [14] and
selective COX-2 inhibitory [15]. Besides, they can be
used as cytokine inhibitors [16], potent catalytic activity
inhibitor of human telomerase [17], therapeutics for
kinase mediated inflammatory disorders [18], and dyes
[19]. Reaction of pyrazolone with carbonyl compounds or
Michael acceptors provides easy access to 4-substituted
pyrazolone derivatives. Recently, different methods
have been described for the synthesis of 4-substituted
pyrazolone. A literature survey indicates that these
methods focused mainly on the condensation reaction
of 3-methyl-1-phenyl-5-pyrazolone with aldehydes [20],
whereas Michael addition of pyrazolone and different
Michael acceptors was less explored [21].
Successful application of [Cu(3,4-tmtppa)](MeSO4)4
as a re-usable catalyst for Michael reaction of indoles
withb-nitrostyreneencouragedustostudytheapplicability
of this method for the synthesis of 2-pyrazolyl-1-
nitroalkanes by the reaction of 3-methyl-1-phenyl-5-
pyrazolone with b-nitrostyrene (Scheme 3, Table 3).
As Table 3 indicates, Michael addition of 3-methyl-1-
phenyl-5-pyrazolone as a more reactive nucleophile than
indolewithb-nitrostyrenesbearingelectron-withdrawing,
electron-releasing or thienyl groups proceeded well, and
different types of 2-pyrazolyl-1-nitroalkanes obtained in
85%–95% yields in very short reaction times.
EXPERIMENTAL
Chemicals were purchased from Merck and Fluka
Chemical Companies. NMR spectra were recorded
Scheme 3. Synthesis of 2-pyrazolyl-1-nitroalkanes by Michael addition of 3-methyl-1-phenyl-5-pyrazolone with b-nitrostyrenes
catalyzed by [Cu(3,4-tmtppa)](MeSO4)4
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232
E. SAFAEI ET AL.
Table 3. Synthesis of 2-pyrazolyl-1-nitroalkanes catalyzed by [Cu(3,4-tmtppa)]-
(MeSO4)4 under solvent-free conditions at 80 °C
Entry [ref]
1 [22]
b-nitrostyrene
Time, min
5
Yielda, %
85
NO2
NO2
2
3
2
3
90
92
Cl
NO2
Br
NO2
4
2
5
5
95
90
95
O2N
NO2
5
NO2
6 [21]
MeO
NO2
7
10
5
85
92
OMe
NO2
8
S
a
Yields refer to isolated pure product characterized by spectroscopic methods
and compared with the authentic samples. Reaction conditions: 3-methyl-1-
phenyl-5-pyrazolone (1 mmol), b-nitrostyrene (1 mmol), [Cu(3,4-tmtppa)]-
(MeSO4)4 (0.006 mmol).
3-methyl-4-[2-nitro-1-(4-Bromophenyl)ethyl]-1-
phenyl-5-pyrazolone (Table 3, entry 3). Yield 1.85 g
(92%), mp 169–170 °C.Anal. calcd. for C18H16BrN3O3: C,
53.75; H, 4.01; N, 10.45%. Found: C, 53.85; H, 4.21; N,
10.38. 1H NMR (400 MHz; DMSO; Me4Si): dH, ppm 2.18
(3H, s, CH3), 4.62 (1H, dd, CH), 5.36 (2H, dd, CH2), 7.22
(2H, d, Ar), 7.45 (3H, t, Ar), 7.53 (2H, d, Ar), 7.70 (2H, d,
Ar), 11.33 (1H, bs, OH). 13C NMR (DMSO; Me4Si): dC,
ppm 11.4, 38.6, 76.8, 103.2, 119.2, 120.7, 125.3, 129.4,
130.4, 131.9, 137.4, 139.9, 148.1. IR (KBr): n, cm-1 2703
(O–H). MS (70 eV): m/z 401 ([M]+, 2.0), 403 ([M+ + 2],
1.6), 226 (2.1), 228 (2.3), 173 (77.6), 76 (100).
15.11. 1H NMR (400 MHz; CDCl3; Me4Si): dH, ppm 2.24
(3H, s, CH3), 4.65 (1H, t, CH), 5.08 (1H, dd, CH2), 5.41
(1H, dd, CH2), 7.22 (1H, t, Ar), 7.38 (2H, t, Ar), 7.55 (2H,
d, Ar), 7.7 (2H, d, Ar), 8.2 (2H, d, Ar). 13C NMR (CDCl3;
Me4Si): dC, ppm 11.3, 39.7, 75.9, 120.0, 124.2, 124.4,
126.2, 128.8, 129.0, 129.3, 136.0, 146.2, 147.3, 148.4. IR
(KBr): n, cm-1 2832 (O–H). MS (70 eV): m/z 368 ([M]+,
1.2), 149 (2.9), 42 (100).
3-methyl-4-[2-nitro-1-(4-methylphenyl)ethyl]-1-
phenyl-5-pyrazolone (Table 3, entry 5). Yield 1.52 g
(90%), mp 80 °C, Anal. calcd. for C19H19N3O3: C,
67.64; H, 5.68; N, 12.46%. Found: C, 67.54; H, 5.71;
1
3-methyl-4-[2-nitro-1-(4-nitrophenyl)ethyl]-1-
phenyl-5-pyrazolone (Table 3, entry 4). Yield 1.75 g
(95%) mp 176–180 °C. Anal. calcd. for C18H16N4O5: C,
58.69; H, 4.38; N, 15.21%. Found: C, 58.71; H, 4.44; N,
N, 12.39. H NMR (400 MHz;CDCl3; Me4Si): dH, ppm
1.93 (3H, s, CH3 ), 2.31 (3H, s, CH3 ), 4.42 (1H, t, CH),
4.81 (1H, dd, CH2), 5.20 (1H, dd, CH2), 7.06 (3H, d,
Ar), 7.13 (2H, t, Ar), 7.20 (2H, d, Ar), 7.30 (2H, d, Ar),
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EFFICIENT SYNTHESIS OF 2-INDOLYL-1-NITROALKANES CATALYZED
233
10.9 (1H, bs, OH). 13C NMR (CDCl3; Me4Si): dC, ppm
1302–1307. b) Sundberg RJ. Indols, Academic
Press: London, UK, 1996. c) Faulkner DJ. Nat.
Prod. Rep. 2001; 18: 1–49.
10.6, 21.0, 39.3, 76.8, 103.4, 120.7, 125.6, 127.4, 128.8,
129.5, 135.6, 136.2, 136.5, 137.1, 146.9. IR (KBr): n,
cm-1 2994 (O–H). MS (70 eV): m/z 337 ([M]+, 3.6), 118
(100), 42 (30.0).
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3-methyl-4-[2-nitro-1-(2-methoxyphenyl)ethyl]-1-
phenyl-5-pyrazolone (Table 3, entry 7). Yield 1.50 g
(85%), mp 147–149 °C. Anal. calcd. for C19H19N3O4: C,
64.58; H, 5.42; N, 11.89%. Found: C, 64.64; H, 5.48; N,
11.91. 1H NMR (400 MHz; DMSO; Me4Si): dH, ppm 2.16
(3H, s, CH3), 3.85 (3H, s, CH3), 4.95 (1H, dd, CH), 5.15
(1H, dd, CH2), 5.36 (1H, dd, CH2), 6.91 (1H, t, Ar), 7.01
(1H, d, Ar), 7.19 (1H, t, Ar), 7.24 (1H, t, Ar), 7.43 (2H, t,
Ar), 7.51 (1H, d, Ar), 7.70 (2H, d, Ar). 13C NMR (DMSO;
Me4Si): dC, ppm 11.7, 32.1, 56.0, 57.9, 76.1, 102.4, 111.3,
119.1, 120.7, 124.9, 127.5, 128.5, 128.6, 129.3, 137.8,
148.3, 156.5. IR (KBr): n, cm-1 2955 (O–H). MS (70 eV):
m/z 353 ([M]+, 3.9), 173 (30.8), 77 (100), 91 (64.8).
3-methyl-4-[2-nitro-1-(thiophen-2-yl)ethyl]-1-
phenyl-5-pyrazolone (Table 3, entry 8). Yield 1.51
g (92%), mp 124–125 °C. Anal. calcd. for C16H15N3O3
S: C, 58.34; H, 4.59; N, 12.76%. Found: C, 58.25; H,
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4.50; N, 12.69. H NMR (400 MHz; DMSO; Me4Si):
dH, ppm 2.13 (3H, s, CH3), 4.91 (1H, t, CH), 5.32
(2H, dd, CH), 6.97 (1H, dd, Ar), 7.11 (1H, d, Ar), 7.22
(1H, t, Ar), 7.39 (1H, d, Ar), 7.45 (2H, t, Ar), 7.71 (2H,
d, Ar), 11.35 (1H, bs, OH). 13C NMR (DMSO; Me4Si):
dC, ppm 11.1, 34.3, 77.3, 103.8, 119.0, 121.2, 125.4,
127.4, 129.4, 137.3, 143.0, 148.2, 162.4. IR (KBr): n,
cm-1 2802 (O–H).
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CONCLUSION
In conclusion, it has been found that [Cu(3,4-tmtppa)]
(MeSO4)4 can be used as a new, re-usable and efficient
catalyst for Michael addition of indoles with different
types of b-nitrostyrenes under solvent-free conditions.
Ease of recovery and catalyst reusability makes this
method an economic, benign and waste-free chemical
process for the synthesis of 2-indolyl-1-nitroalkanes.
Simple reaction setup, not requiring specialized
equipment, good to high yields of the products, no
by-product formation are the other advantages of the
present protocol. This method has also been successfully
applied for Michael addition of 3-methyl-1-phenyl-5-
pyrazolone with b-nitrostyrenes.
Aknowledgements
We are thankful to Birjand University Research
Council and Institute of Advanced Studies in Basic
Sciences (IASBS) for their support of this work.
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