KG-60-piperazine as a new heterogeneous catalyst for gewald three-component reaction

Article abstract of DOI:10.1080/00397911.2012.674607

Piperazine supported on amorphous silica (KG-60-piperazine) as a basic catalyst acts in the Gewald three-component reaction of some aldehydes and ketones with malononitrile as well as ethyl cyanoacetate. The catalyst shows general utility with a variety of starting carbonyl compounds. Moreover, the catalyst can be reused for four additional cycles without significant loss of the activity. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications to view the free supplemental file.

Full text of DOI:10.1080/00397911.2012.674607

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KG-60-Piperazine as a New
Heterogeneous Catalyst for Gewald
Three-Component Reaction
a
a
a
Esmail Rezaei-Seresht , Reza Tayebee & Mohammad Yasemi
a
Department of Chemistry, Faculty of Sciences, Hakim Sabzevari
University, Sabzevar, Iran
Accepted author version posted online: 02 Jan 2013.Version of
record first published: 04 Apr 2013.
To cite this article: Esmail Rezaei-Seresht , Reza Tayebee & Mohammad Yasemi (2013): KG-60-
Piperazine as a New Heterogeneous Catalyst for Gewald Three-Component Reaction, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
43:13, 1859-1864
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1
Synthetic Communications , 43: 1859–1864, 2013
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2012.674607
KG-60-PIPERAZINE AS A NEW HETEROGENEOUS
CATALYST FOR GEWALD THREE-COMPONENT
REACTION
Esmail Rezaei-Seresht, Reza Tayebee, and Mohammad Yasemi
Department of Chemistry, Faculty of Sciences, Hakim Sabzevari University,
Sabzevar, Iran
GRAPHICAL ABSTRACT
Abstract Piperazine supported on amorphous silica (KG-60-piperazine) as a basic catalyst
acts in the Gewald three-component reaction of some aldehydes and ketones with malononi-
trile as well as ethyl cyanoacetate. The catalyst shows general utility with a variety of
starting carbonyl compounds. Moreover, the catalyst can be reused for four additional
cycles without significant loss of the activity.
Supplemental materials are available for this article. Go to the publisher’s online edition
1
of Synthetic Communications to view the free supplemental file.
Keywords 2-Aminothiophenes; Gewald reaction; heterogeneous catalysis; multicompo-
nent reaction
INTRODUCTION
The most convergent and well-established classical approach for the prep-
[
1]
aration of 2-aminothiophenes is Gewald’s three-component reaction. Depending
on the starting substrates and the reaction conditions, four basic versions of the
[
1–4]
Gewald reaction have been developed.
cations to the Gewald reaction have been reported in the literature. For example,
Recently, efficient and convenient modifi-
[
5]
Sridhar et al. have carried out the reaction under microwave irradiation. The
microwave-assisted Gewald reaction on solid support was also employed in a
solid-phase thiophene synthesis. The reaction has been performed under microwave
irradiation and solvent-free conditions to yield substituted benzo[b]thiophenes in
[
good yields. Furthermore, a Gewald reaction induced by solar thermal energy
[6]
7]
Received December 15, 2011.
Address correspondence to Esmail Rezaei-Seresht, Department of Chemistry, Faculty of Sciences,
Hakim Sabzevari University, Sabzevar 96179-76487, Iran. E-mail: rezaei_seresht@yahoo.com
1
859

1860
E. REZAEI-SERESHT, R. TAYBEE, AND M. YASEMI
Scheme 1. Preparation of catalyst KG-60-piperazine (1).
[
8]
has been developed for synthesis of 2-aminothiophenes. Ionic liquids used as
solvents in combination with ethylenediammonium diacetate were shown to be
[
9]
very efficient in the case of the Gewald synthesis. Feroci et al. have developed
an electrochemically induced Gewald reaction for synthesis of substituted
[
10]
2
-aminothiophenes.
Immobilization of catalytically active species on inorganic solid materials
enables not only generation of recyclable catalysts but also greater catalytic activities
compared with their homogeneous precursors and analogs owing to unique environ-
[11]
ments of the surfaces. Catalysts and reagents immobilized upon a range of insolu-
12]
[
ble supports have been utilized and reported since the late 1960s.
Secondary
amines, immobilized on mesoporous FSM-16 silica, have been utilized to obtain sub-
stituted 5-ketoaldehydes by direct 1,4-conjugate addition of unmodified aldehydes to
[13]
vinyl ketones. Silica gel functionalized with a propylamino moiety [SiO -(CH ) -
2 3
2
NH ] was employed in the reaction of different methylene active compounds
2
[
14]
with aldehydes and ketones for the production of electron-poor olefins.
Diethylpropylamine supported on amorphous silica (KG-60-NEt ) has been utilized
N,N-
2
[
15]
as a solid and reusable catalyst in the Henry reaction of some nitroalkanes. Various
amines immobilized on acidic silica-alumina surfaces have showed excellent catalytic
Scheme 2. Gewald reaction catalyzed by catalyst 1.

GEWALD REACTION CATALYZED BY KG-60-PIPERAZINE
1861
a
Table 1. Obtained Gewald products in the presence of catalyst 1
Starting compounds
b
ꢀ
Mp ( C)
Entry
1
Compound 2
Compound 3
Gewald product
Yield (%)
[19]
2a
3a
41
102 (104)
[
[
1]
1]
2
3
2b
2c
3b
3b
60
49
45 (46)
72 (73)
[1]
4
2d
3a
46
139 (142)
[
1]
5
6
7
8
9
2d
2e
2e
2f
3b
3a
3b
3a
3a
3b
43
66
43
37
47
42
91 (91)
[5]
140 (142)
[5]
97 (98)
[19]
153 (155)
150 (151)
[5]
2g
2g
[1]
1
0
89 (91)
(
Continued )

1862
E. REZAEI-SERESHT, R. TAYBEE, AND M. YASEMI
Table 1. Continued
Starting compounds
Compound 2 Compound 3
b
ꢀ
Mp ( C)
Entry
Gewald product
Yield (%)
89
[
20]
11
12
13
14
2h
3a
143 (144)
115 (115)
124 (126)
[
5]
2h
2i
2i
3b
3a
3b
86
45
56
[21]
[5]
88 (89)
a
ꢀ
Reaction conditions: time ¼ 4 h, temperature ¼ 80 C, catalyst ¼ 10 mol%, compound 2 ¼ 20 mmol,
compound 3 ¼ 20 mmol.
b
1
Isolated yields. All the products gave satisfactory H NMR and IR spectra.
[
16]
performance for the Michael reactions of nitrile compounds.
Here, we report a
silica-supported piperazine (KG-60-piperazine) as a new heterogeneous catalyst for
the Gewald three-component reaction.
RESULTS AND DISCUSSION
It has been already demonstrated that secondary amines such as morpholine
[
17]
and diethylamine excellently catalyze the Gewald reaction. Therefore, we searched
for a suitable amine and found piperazine (1), which was not only was structurally
similar to morpholine but also readily immobilized on solid support (silica gel).
Piperazine was then immobilized on silica according to a previously described
[
18]
procedure to yield catalyst KG-60-piperazine (1) (Scheme 1).
To investigate the catalytic activitiy of 1, the reaction of cyclohexanone with
malononitrile and sulfur was selected as a model reaction. At first, mixtures of cyclo-
hexanone (20 mmol), malononitrile (20 mmol), and sulfur (22 mmol) in the presence
ꢀ
of different quantities of catalyst 1 were reacted in ethanol at 80 C for up to 6 h.
An experiment was also conducted in the absence of the catalyst. In this case, only
very low amounts (<6%) of the Gewald product were formed after 6 h. The results
showed that the catalyst significantly improved the yield of the reaction, and the
optimum result was observed with 10 mol% of the catalyst after a 4-h reaction time.
The effect of the solvent was also investigated in the reaction. Thus, experiments
ꢀ
were run under the conditions previously mentioned (80 C, catalyst ¼ 10 mol%,

GEWALD REACTION CATALYZED BY KG-60-PIPERAZINE
1863
t ¼ 4 h). In all cases, solutions (20 mmol) of cyclohexanone in solvents hexane,
MeOH, dimethylformamide (DMF), dimethylsulfoxide (DMSO), and EtOH were
used, and the yields of the reaction were 17, 79, 82, 84, and 89% respectively.
To assess the generality of the method, a number of aldehydes and ketones
were reacted in the presence of catalyst 1 to afford the corresponding Gewald pro-
ducts in good to excellent yields (Scheme 2, Table 1). Spectral data for the Gewald
products 4 and 5 are available online in the Supplemental Material.
Finally, we faced the problem of catalyst recycling; at the end of the model
reaction between cyclohexanone and malononitrile, the catalyst was filtered on a
B u¨ chner funnel, washed thoroughly with absolute ethanol and acetone, dried under
vacuum for 12 h at room temperature, and reused. The catalyst could be utilized with
similar results for at least four additional cycles (reaction: First run 89%; fifth
run: 75%).
CONCLUSIONS
We have shown the utilization of KG-60-piperazine as a new heterogeneous
and reusable catalyst in the Gewald reaction. It is noteworthy that the catalyst shows
general applicability and good to excellent efficiency with all substrates utilized in the
reaction.
EXPERIMENTAL
Compounds 2 (20 mmol) and 3 (20 mmol) were dissolved in absolute ethanol
30 mL). Then, sulfur (22 mmol) and catalyst 1 (3.70 g) were added and the mixture
was refluxed at 80 C for 4 h. The reaction mixture was cooled to room temperature
and the solid catalyst was filtered off. The solution poured into an ice-water mixture
(
ꢀ
(
60 mL) and the precipitation was filtered off, washed with cold water, and dried in
vacuo to yield the Gewald products 4 and 5.
Compound 4 h: Yield, 3.17 g (89%); mp, 143 C (lit. 144 C); IR (KBr, cm
ꢀ
[20]
ꢀ
ꢁ1
)
1
3
2
1
420, 3320, 2950, 2205, 1631, 1120; H NMR (CDCl , 400 MHz) d 4.64 (s, 2H),
3
1
3
.49–2.42 (m, 4H), 1.78 (t, 4H); C NMR (100 MHz, CDCl ) d 160.1, 132.3,
3
20.6, 115.5, 88.6, 24.5, 24.1, 23.4, 22.1.
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