Heterogeneous silica-supported copper catalyst for the ultrasound-mediated rapid reaction between dimedone, formaldehyde, and amines at room temperature

Article abstract of DOI:10.1007/s00706-015-1457-0

A copper-incorporated mesoporous silica catalyst was synthesized and characterized by N₂ adsorption analysis, HRTEM, EDX-elemental analysis, and XRD studies. The silica material possesses mesopores of dimension 3-5 nm. Incorporation of copper within the silica network produces enhanced surface acidity in comparison to pure silica, which is reflected in the sonication-assisted rapid reaction between dimedone, formaldehyde, and amines. Sonication-mediated room temperature synthesis was proved to be more convenient and rapid than ordinary stirring. A standard leaching experiment proved that the reaction was heterogeneous with this recyclable catalyst. Graphical abstract: [Figure not available: see fulltext.]

Full text of DOI:10.1007/s00706-015-1457-0

Monatsh Chem
DOI 10.1007/s00706-015-1457-0
ORIGINAL PAPER
Heterogeneous silica-supported copper catalyst
for the ultrasound-mediated rapid reaction between dimedone,
formaldehyde, and amines at room temperature
Suman Ray1 Asim Bhaumik2 Biplab Banerjee2 Priyabrata Manna3
Chhanda Mukhopadhyay1
•
•
•
•
Received: 3 February 2015 / Accepted: 10 March 2015
ꢀ Springer-Verlag Wien 2015
Abstract A copper-incorporated mesoporous silica cata-
lyst was synthesized and characterized by N2 adsorption
analysis, HRTEM, EDX-elemental analysis, and XRD
studies. The silica material possesses mesopores of
dimension 3–5 nm. Incorporation of copper within the
silica network produces enhanced surface acidity in com-
parison to pure silica, which is reflected in the sonication-
assisted rapid reaction between dimedone, formaldehyde,
and amines. Sonication-mediated room temperature syn-
thesis was proved to be more convenient and rapid than
ordinary stirring. A standard leaching experiment proved
that the reaction was heterogeneous with this recyclable
catalyst.
Keywords Ultrasound-assisted synthesis Á
Heterogeneous catalyst Á
Mesoporous silica-supported copper catalyst Á
Multicomponent synthesis
Introduction
The collective accomplishment of making multiple bonds
in a one-pot synthesis operation is well known as multi-
component reaction (MCR), which promotes a sustainable
synthesis approach to molecule and drug discovery pro-
cesses [1]. An important reaction in the realm of
multicomponent syntheses is the three-component con-
densation of aromatic amines with dimedone and
formaldehyde in the presence of a catalyst leading to the
formation of 3,5-dispirosubstituted piperidines. Spiro-fused
piperidine compounds have attracted particular attention as
synthesis targets due to their miscellaneous important ac-
tivities as pharmacophores in several biologically active
compounds, mainly alkaloids, which are responsible for a
number of unique activities, including anti-hypertensive,
anticonvulsant, and anti-inflammatory activities [1–6].
Again in recent years, the concept of ‘‘green chemistry’’
has been well accepted to meet the fundamental scientific
challenges of protecting the environment while simulta-
neously achieving commercial feasibility [7]. One of the
thrust areas of sustainable synthesis is to explore alterna-
tive reaction conditions. The development in the last few
years of synthesis protocols employing ultrasound irra-
diation has led to an important change in organic reactions
and has permitted the activation of poorly reactive sub-
strates [8]. Ultrasonic (US) waves are propagated via
alternating compressions and rarefactions cycles, induced
in the transmitting liquid, with the expansion cycles
Graphical abstract
Electronic supplementary material The online version of this
article (doi:10.1007/s00706-015-1457-0) contains supplementary
material, which is available to authorized users.
& Chhanda Mukhopadhyay
cmukhop@yahoo.co.in
1
Department of Chemistry, University of Calcutta,
92 APC Road, Kolkata 700009, India
2
Department of Materials Science, Indian Association for the
Cultivation of Science, Jadavpur, Kolkata 700032, India
3
Department of Chemical Technology, University of Calcutta,
92 APC Road, Kolkata 700009, India
123

S. Ray et al.
exerting negative pressure on the liquid [9]. If this applied
negative pressure is strong enough to collapse the inter-
molecular van der Waals force of the liquid, small cavities
or gas-filled micro-bubbles are formed. These cavities ab-
sorb energy from US waves and grow to reach a stage
where it can no longer absorb energy efficiently and im-
plodes [10–14]. These rapid and violent implosions
generate short-lived regions with very high local tem-
perature and pressure. This cavitationally induced
phenomenon is known to activate reactant molecules en-
tering into cavity and consequently converts them into
reactive intermediates.
catalyst under ultrasound irradiation (Scheme 1). So far
only three reports on the synthesis of various 3,5-dispiro-
substituted piperidines are available [1, 7, 28]. Moreover,
at the outset of our studies, there was no literature prece-
dent for the direct application of a heterogeneous reusable
catalyst in combination with ultrasound for the synthesis of
3,5-dispirosubstituted piperidines.
The catalyst was prepared by co-condensation of te-
traethyl orthosilicate (TEOS) and Cu(OAc)2 in basic
medium followed by calcinations at 550 ꢁC. It was char-
acterized by N2 adsorption analysis, HRTEM, EDX-
elemental analysis, and XRD studies.
The use of heterogeneous catalysts has received
tremendous attention as alternatives in alleviating the
limitations of homogeneous catalysts [1]. Thus, the search
for an inexpensive, readily available, and convenient cat-
alyst is desirable. Solid catalysts provide numerous
opportunities for recovering and recycling catalysts from a
reaction mixture [1]. Among the various heterogeneous
catalysts, mesoporous silica-supported catalysts are of
particular advantage because of combination of interesting
properties, such as a high surface area with a robust yet
flexible structure and a wide range of compositional var-
iations [15, 16]. When such ultrasound-assisted synthesis is
coupled with heterogeneous catalysis, it fulfills most of the
criteria of sustainable synthesis.
Characterization of catalyst
Nitrogen adsorption analysis
The N2 adsorption/desorption isotherms and corresponding
pore size distribution of the silica-supported copper cata-
lyst is shown in Fig. 1. The isotherm is a typical type IV
isotherm with the presence of a hysteresis loop (H2 type),
which indicates the presence of mesopores in the material
(panel a). The BET surface area calculated from this iso-
therm is 4.78 9 104 cm2 g-1. The pore volume estimated
for this sample is 0.3819 cm3 g-1. Corresponding pore size
distribution was estimated by the non-local density func-
tional theory (NLDFT) model is shown in panel b (Fig. 1).
Estimated pore dimension for the sample is found to be ca.
5.7 nm.
Results and discussion
HRTEM images of Cu incorporated silica
It has been noticed that silica and some of the support
materials like alumina, zinc oxide, zirconia, etc. exhibit
significant surface acidity in copper-based catalysts [17–
24]. In recent past, the acidity of a mesoporous silica-
supported copper catalyst has been utilized in the Biginelli
reaction, Mannich reaction, different multicomponent re-
actions, and catalytic transformations of benzyl alcohol,
etc. [17, 25–27]. In the present context, we exploited the
surface acidity of Cu/SiO2 in the synthesis of 3,5-dispiro-
substituted piperidines using silica-supported copper as
Representative HRTEM images of material are shown in
Fig. 2 (panel a–c). From the representative TEM images, it
is clear that there are pores in the dimension of 3–5 nm
present throughout the specimen grid. These data match
well with the pore dimension obtained from N2 sorption
data.
Elemental analysis
The chemical characterization for the material was carried
out by EDX analysis. It revealed that three elements O, Si,
Scheme 1
123

Heterogeneous silica supported copper catalyst…
(a)
(b)
280
260
240
220
200
180
160
140
120
100
80
5.67 nm
0.030
0.025
0.020
0.015
0.010
0.005
0.000
Adsorption
Desorption
NLDFT Method
Surface area = 478.4 m2/g
Pore volume = 0.3819 cm3/g
0.0
0.2
0.4
0.6
0.8
1.0
0
100
200
300
400
Relative pressure (P/P0)
Pore width/Ǻ
Fig. 1 N2 adsorption isotherm and pore size distribution of Cu/SiO2. Adsorption points are marked by filled circle, whereas those for desorption
are marked by empty circles
Fig. 2 a–c HRTEM images of Cu/SiO2 catalyst, and d EDX spectrum of Cu/SiO2 catalyst
Powder XRD pattern
and Cu are present in the material (Fig. 2, panel d). EDX
chemical analysis confirmed that the expected copper-in-
corporated mesoporous silica has successfully developed in
this study.
The formation of copper oxide within the silica matrix was
confirmed from the wide-angle powder XRD pattern of Cu/
SiO2 sample (Fig. 3). Several diffraction peaks can be
123

S. Ray et al.
Synthesis application of the catalyst
Multicomponent reactions enable simultaneous cyclization
and functionalization making it possible to efficiently
prepare diverse derivatives bearing a variety of function-
alities. However, this type of multicomponent tandem
cyclization requires several reaction components having
multiple reaction sites; an unregulated reaction readily
forms a complex mixture of undesired products. The
challenge is to conduct an MCR in such a way that the
reaction yields only the main product and not the side-
products. In order to optimize the reaction condition
(Table 1), a series of experiments were conducted under
ultrasonic irradiation and ordinary stirring conditions,
taking the reaction of dimedone (2 mmol), 4-chloroaniline
(1 mmol), and formaldehyde (3 mmol) as a model reac-
tion. Different homogeneous acids like HCl, H2SO4,
HClO4, TfOH, PTS, HPF6, HBF4, and AcOH were tested
(Table 1). Ordinary to moderate conversions were
achieved with these homogeneous acids. However, they
Fig. 3 Powder XRD pattern of Cu/SiO2
ꢀ
indexed to the diffraction planes (110), (002), (111), (202),
ꢀ
ꢀ
(020), (202), (113), (311), and (113) for CuO in the
monoclinic phase [29].
Table 1 Optimization reaction conditions
Entry
Catalyst
Conventional heating
Time/min
Ultrasound irradiation
Yield/%a
Time/min
Yield/%a
1
HCl
60
60
60
60
60
60
60
60
60
60
600
33
30
30
35
36
34
37
39
36
43
81
60
60
60
60
60
60
60
60
60
60
600
39
36
35
41
43
41
78
81
77
91
91
2
H2SO4
HClO4
TfOH
PTS
3
4
5
6
AcOH
TiO2
7
8
SiO2
9
ZnTiO3
Cu/SiO2
Cu/SiO2
10
11
Reaction conditions: dimedone (2 mmol), 4-chloroaniline (1 mmol), formaldehyde (3 mmol), different catalysts (0.1 mmol for homogeneous
catalysts and 10 mg for heterogeneous catalysts), dichloromethane (4 cm3), different times, room temperature (25–30 ꢁC)
a
Isolated yields
123

Heterogeneous silica supported copper catalyst…
ordinary stirring condition, without the use of ultra-
sonication, moderate to good yields of spiro-piperidines 4
were only obtained after 10–12 h time (Table 1, entry 11).
In contrast, a much higher yield of 4 was obtained within
only 60 min at room temperature under ultrasound condi-
tion. Thus, the best yield, cleanest reaction, and most facile
work-up were achieved under ultrasonic irradiation at room
temperature, employing 10 mg of Cu/SiO2 as the right
choice of catalyst (entry 10).
H
O
H
O
H
O
H
O
δ+
δ+
O
O
O
O
Cu
Si
Cu
Si
Si
O
O
O
O
Cu/SiO2
The higher activity of the heterogeneous Cu/SiO2 cata-
lyst under sonochemical conditions can be explained on the
basis of higher adsorption and mass transfer of organic
molecules on the surface of catalyst, caused by shockwave
and microjets formed [30, 31]. Symmetrical cavitation and
collapse of bubbles in the liquid medium are very common;
however, if cavitation bubbles are formed at or near a solid
surface, the dynamics of cavity collapse change drastically.
Close to a solid boundary, cavity collapse is asymmetric
and creates high-speed jets of liquid. These jets hit the
surface with tremendous force. This process can produce
newly exposed highly reactive catalyst surfaces and in-
crease the mass transfer to the catalyst surface [32, 33].
Therefore, the shock waves and high-speed jets may
probably enhance the rate of the reaction under sonic
condition.
Fig. 4 Diagram explaining enhanced surface acidity of copper-
incorporated silica
required repeated work-up, neutralization of strong acids,
and extensive chromatographic purification. Ultimately,
the isolated yields were not satisfactory (Table 1, entries
1–6). Compared to these homogeneous catalysts, hetero-
geneous acid catalysts like TiO2, SiO2, and ZnTiO3
nanopowder afforded better isolated yields of 4 (Table 1,
entries 7–9). However, a maximum yield of 4 was obtained
with heterogeneous copper-incorporated silica catalyst
(Table 1, entry 10). This is because of the fact that intro-
duction of copper within the silica network produces
enhanced surface acidity in comparison to pure silica. The
significant surface acidity of Cu/SiO2 catalyst originates
from the combination of the Lewis acidic property of Cu2?
ion and Brønsted acidity of silica silanol. The silanol
oxygens coordinate with copper ion in the network and the
hydrogen of silanol becomes labile and easily comes out as
proton. In Fig. 4 the labile hydrogens are marked in red
color.
Plausible mechanism
A mechanism portraying the probable sequence of steps for
the synthesis of spiro-piperidine is shown in Scheme 2.
The spirocyclization may take place as a domino sequence
of Knoevenagel, Michael, and double Mannich reactions.
A literature survey [34, 35] revealed that dimedone is not
only a Knoevenagel reagent but it also adds easily to
Again, the yield of the spiro-piperidine 4 in the Cu/SiO2
catalyzed synthesis was always greater under ultrasound
irradiation than for ordinary stirring (Table 1). Under
Scheme 2
123

S. Ray et al.
Table 2 Cu/SiO2 catalyzed multicomponent synthesis of dispirosubstituted piperidines
Entry
Product
R1
Yield/%a
References
1
2
3
4
5
6
7
4a
4b
4c
4d
4e
4f
4-Cl
91
94
92
93
90
89
88
[1]
[1]
[2]
[2]
[28]
[2]
[2]
3,4-Me2
H
4-Me
3-Me
4-OMe
4-Br
4g
Reaction conditions: dimedone (2 mmol), amines (1 mmol), formaldehyde (3 mmol), Cu/SiO2 catalyst (10 mg), dichloromethane (4 cm3),
60 min ultrasound irradiation at room temperature (25–30 ꢁC)
a
Isolated yields
electron-poor alkenes in the Michael addition fashion
leading to the dimedone–formaldehyde adducts
variety of substitution patterns. It is pertinent to mention
that the product structure was unambiguously proved by
X-ray single crystal analysis of the two distinct compounds
4a (CCDC 1015248) and 4g (CCDC 1015247) (Fig. 5).
After successful formation of spiro-piperidines 4, to
delineate this approach, the scope and generality of this
catalyst were next extended in the reaction between
enaminoketones 8, formaldehyde, and dimedone to yield 9
(Table 3).
6
(Scheme 2). The well-known dimedone–formaldehyde
adducts then undergo two consecutive Mannich reactions
with aromatic amine and formaldehyde to produce the
dispirosubstituted piperidine. Again 6 was also formed by
the reaction of dimedone (2 mmol) and HCHO (1 mmol) at
room temperature in presence of Cu/SiO2 catalyst in
20 min. This compound 6 when reacted with aromatic
amine afforded the final product 4. Therefore, intermediacy
of 6 in this transformation is proved. Isolation of inter-
mediate 6 and its structure determination by NMR
spectroscopy proves the mechanism conclusively. Here,
Cu/SiO2 having enhanced surface acidity catalyzes all the
steps.
Moreover, the synthesis of compound 10 was also ex-
plored using this catalyst to further extend the generality of
this protocol (Table 4). The structure of 10 was unam-
biguously assigned by X-ray single crystal analysis
(Fig. 6).
Recycling and leaching experiment
Substrate scope
The reusability of the Cu/SiO2 catalyst in the spiro-piper-
idine 4 formation reaction was examined taking the
reaction forming 4a as model reaction. Nearly quantita-
tively catalyst (up to 98 %) could be recovered from each
run. In a test of six cycles, the catalyst could be reused
without significant loss of catalytic activity. The kinetics of
the fresh catalyst was evaluated as shown in Fig. 7. The
yield did not further increase substantially after 1 h. Also
we performed the kinetic study with the recycled catalyst
for the next consecutive five runs. The results of kinetic
plots suggested that the catalyst retained good efficiency
The attenuated acidity of the Cu/SiO2 was found to be
crucial for cyclization but insufficient to affect the acid-
sensitive moieties because methoxy-substituted aryl amines
as well as heteroaromatic amines reacted very efficiently
with no side reactions (Table 2). For precursors 3 bearing
either electron-donating or electron-withdrawing sub-
stituents on the aromatic ring, the reactions all proceeded
very smoothly to provide the corresponding spiro-
piperidines 4. Therefore, the present Cu/SiO2 catalyzed
protocol has a general applicability accommodating a
123

Heterogeneous silica supported copper catalyst…
Fig. 5 X-ray single crystal structures of 4a (CCDC 1015248) and 4g (CCDC 1015247)
Table 3 Cu/SiO2 catalyzed multicomponent synthesis of compound 9
Entry
Product
R1
Yield/%a
References
1
2
3
9a
9b
9c
4-Me
4-OMe
4-Br
90
92
91
[35]
[35]
–
Reaction conditions: dimedone (1 mmol), formaldehyde (1 mmol), enaminoketones (1 mmol), Cu/SiO2 catalysts (10 mg), dichloromethane
(4 cm3), 60 min ultrasound irradiation at room temperature (25–30 ꢁC)
a
Isolated yields
after recycling. The recovered catalyst after six runs had no
obvious change in the structure referring to the HRTEM
images in comparison with the fresh one (figure given in
Supplementary material). These results revealed that the
catalyst was very stable.
corresponding product was observed, indicating that no
homogeneous catalyst was involved. XPS analysis of the
filtrate showed that copper was not leached in the solution.
To confirm the heterogeneous nature of catalyst and
catalytic activity bound to the solid phase, a standard
leaching experiment was conducted [36]. A mixture of
dimedone, 4-chloroaniline, and HCHO in DCM was al-
lowed to react for 30 min under sonication in the presence
of Cu/SiO2 to afford the corresponding spiro-piperidine 4a.
After this 30 min period, the reaction mixture was filtered.
The filtered reaction mixture was then sonicated without a
catalyst for the next 1 h; no further formation of the
Conclusion
In conclusion, as part of the continuing exploration of
combined use of ultrasound/heterogeneous catalyst for the
green organic reactions, this method has great prospects of
applications in organic syntheses, pharmacy, and industrial
processes. Simplicity of the procedure, rapid reaction, and
reusability of the catalyst makes it convenient for parallel
synthesis.
123

S. Ray et al.
Table 4 Cu/SiO2 catalyzed multicomponent synthesis of compound 10
Entry
Product
R1
Yield/%a
1
2
10a
10b
4-Me
4-Br
84
85
Reaction conditions: formaldehyde (1 mmol), enaminoketones (2 mmol), Cu/SiO2 catalysts (10 mg), dichloromethane (4 cm3), 60 min ultra-
sound irradiation at room temperature (25–30 ꢁC)
a
Isolated yields
100
80
60
40
20
0
1st run
2nd run
3rd run
4th run
5th run
6th run
10
20
30
40
50
60
Cycles
Fig. 7 Kinetic plot demonstrating the recycling efficiency of the
catalyst
Fig. 6 X-ray single crystal structure of 10a (CCDC 1035549)
samples were degassed for 2 h at 353 K. XPS analysis was
performed on the Omicron-Nanotech operated at 15 kV
and 20 mA using a monochromatic AlKa as X-ray source.
X-ray diffraction patterns of the powder sample were ob-
tained with a Seifert P3000 diffractometer using Cu Ka
(k = 0.15406 nm) radiation. Transmission electron mi-
croscopic images were recorded on a JEOL 2010 TEM
operated at 200 kV in the Indian Association for the Cul-
tivation of Science, Jadavpur, Kolkata-700032, India. All
known compounds were characterized by IR, NMR, CHN.
Experimental
1
The H and 13C NMR spectra were carried out on Bruker-
Avance Digital 300 MHz instrument in CDCl3 with TMS
as internal reference. CHN analysis was performed using a
Perkin-Elmer 2400 Series II CHN analyzer, their results
were found to be in good agreement ( 0.3 %) with the
calculated values. Melting points were determined on an
electrical melting point apparatus with an open capillary.
Sonication was carried out in TAKASHI ultrasonic clean-
ing bath (Model no. UD200SH). Nitrogen adsorption/
desorption isotherms were obtained using a Quantachrome
Autosorb 1C at 77 K. Prior to gas adsorption, all the
1
Spectral data and copy of H and 13C NMR spectra of
representative compounds are given in supporting
information.
123

Heterogeneous silica supported copper catalyst…
Preparation of copper-incorporated mesoporous
silica
2-[[2-(4-Bromophenylamino)-4,4-dimethyl-6-oxocyclohex-
1-enyl]methyl]-3-hydroxy-5,5-dimethylcyclohex-2-enone
(9c, C23H28BrNO3)
In a 1 dm3 open beaker fitted with a magnetic stirrer,
390 cm3 water and 400 cm3 MeOH were mixed. Then
3.52 g CTAB was added at 30–35 ꢁC and stirred for
30 min. After a clear solution was obtained, tetraethy-
lorthosilicate (TEOS) was added drop wise from a
dropping funnel under stirring. Next, 71.3 mg Cu(OAc)2
was added and the stirring was continued for another
5 min. Then 10 cm3 0.4 N NaOH solution was added drop
wise for 1 h. The stirring was continued for the next 8 h at
room temperature and then aged overnight (12–14 h) at
room temperature. It was filtered and washed thoroughly
with deionized water and dried at 35–40 ꢁC for 5 days. The
dry powder was calcined at 550 ꢁC for 6–8 h under static
air.
White solid, m.p.: 196–198 ꢁC (EtOAc); IR (KBr):
m = 2956, 2924, 1634, 1584, 1511, 1488, 1444, 1401,
1
1391, 1363, 1324, 1282, 1211, 1154, 1082, 944 cm-1; H
NMR (300 MHz, CDCl3): d = 12.79 (1H, s, OH), 10.53
(1H, s, NH), 7.48 (2H, d, J = 8.7 Hz, ArH), 7.03 (2H, d,
J = 8.7 Hz, ArH), 3.34–3.29 (2H, m, CH2), 2.53–2.19 (8H,
m, 4 9 CH2), 1.05 (9H, br s, 3 9 CH3), 0.98 (3H, s, CH3)
ppm; 13C NMR (75 MHz, CDCl3): d = 200.9, 197.7,
189.5, 177.2, 162.1, 138.1, 132.3, 125.6, 118.4, 113.3,
111.0, 50.1, 49.0, 46.0, 43.5, 40.4, 33.0, 31.8, 29.1, 28.7,
27.3, 17.4, 15.9 ppm.
General synthesis of the compounds 10
A mixture of 0.03 g formaldehyde (2, 1 mmol) and
enaminoketones 8 in 5 cm3 dichloromethane was heated
under reflux for a few minutes just to dissolve the starting
materials. Then 10 mg of the silica-supported copper cat-
alyst was added and the mixture was subjected to
ultrasound irradiation for 60 min at room temperature
(25–30 ꢁC). The progress of the reaction was monitored by
TLC. After the completion of the reaction, the reaction
mixture was diluted with dichloromethane and filtered. The
solvent was removed in a rotary evaporator and the product
was purified by silica gel column chromatography using
EtOAc/petroleum ether as eluent.
General synthesis of the dispirosubstituted
piperidines derivatives 4
A mixture of 0.14 g dimedone (1, 1 mmol), 0.09 g
formaldehyde (2, 3 mmol), and 1 mmol amine 3 in
dichloromethane was heated under reflux for a few minutes
just to dissolve the starting materials. Then 10 mg of the
silica-supported copper catalyst was added and the mixture
was subjected to ultrasound irradiation for 60 min at room
temperature (25–30 ꢁC). The progress of the reaction was
monitored by TLC (10 % EtOAc/90 % petroleum ether).
After the completion of the reaction, the reaction mixture
was diluted with dichloromethane and filtered to separate
the product as filtrate from the catalyst (as residue). The
solvent was dried in a rotary evaporator and the product
was purified by silica gel column chromatography using
EtOAc/petroleum ether as eluent.
2-[[2-(p-Tolylamino)-4,4-dimethyl-6-oxocyclohex-1-enyl]-
methyl]-3-(p-tolylamino)-5,5-dimethylcyclohex-2-enone
(10a, C31H38N2O2)
White solid, m.p.: 192–194 ꢁC (EtOAc); IR (KBr):
m = 2922, 1638, 1581, 1512, 1481, 1442, 1392, 1361,
1322, 1281, 1154, 1082 cm-1
;
1H NMR (300 MHz,
CDCl3): d = 10.68 (2H, s, NH), 7.15 (4H, d, J = 8.1 Hz,
ArH), 7.03 (4H, d, J = 8.1 Hz, ArH), 3.54 (2H, s, CH2),
2.35–2.28 (14H, m, 4 9 CH2 and 2 9 CH3), 0.98 (12H, s,
4 9 CH3) ppm; 13C NMR (75 MHz, CDCl3): d = 195.8,
162.1, 136.9, 134.7, 129.6, 124.6, 109.7, 50.0, 40.9, 32.6,
28.1, 20.9, 17.8 ppm.
General synthesis of the compounds 9
A mixture of 0.14 g dimedone (1, 1 mmol), 0.06 g
formaldehyde (2, 1 mmol), and enaminoketones 8 in
5 cm3 dichloromethane was heated under reflux for a few
minutes just to dissolve the starting materials. Then
10 mg of the silica-supported copper catalyst was added
and the mixture was subjected to ultrasound irradiation
for 60 min at room temperature (25–30 ꢁC). The progress
of the reaction was monitored by TLC. After the com-
pletion of the reaction, the reaction mixture was diluted
with dichloromethane and filtered. The solvent was
evaporated in a rotary evaporator and the product was
purified by silica gel column chromatography using
EtOAc/petroleum ether as eluent.
2-[[2-(4-Bromophenylamino)-4,4-dimethyl-6-oxocyclohex-
1-enyl]methyl]-3-(4-bromophenylamino)-5,5-dimethylcy-
clohex-2-enone (10b, C29H32Br2N2O2)
White solid, m.p.: 222–224 ꢁC (EtOAc); IR (KBr):
m = 2926, 1634, 1582, 1510, 1481, 1452, 1382, 1361,
1281, 1152, 1088 cm-1 1H NMR (300 MHz, CDCl3):
;
d = 10.60 (2H, s, NH), 7.36 (4H, d, J = 8.7 Hz, ArH),
6.99 (4H, d, J = 8.7 Hz, ArH), 3.59 (2H, s, CH2), 2.40
(4H, s, 2 9 CH2), 2.30 (4H, s, 2 9 CH2), 1.00 (12H, s,
123

S. Ray et al.
4 9 CH3) ppm; 13C NMR (75 MHz, CDCl3): d = 196.0,
162.4, 150.1, 132.0, 120.2, 113.7, 110.0, 50.1, 41.0, 32.8,
28.4, 21.0 ppm.
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Acknowledgments We thank the Council of Scientific and Indus-
trial Research, New Delhi for fellowship (SRF to SR and SPM to BB).
We also acknowledge TEQIP for instrumental facility.
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