Nickel nanoparticles: A highly efficient catalyst for one pot synthesis of tetraketones and biscoumarins

Article abstract of DOI:10.1007/s12039-012-0275-8

A novel and practically useful protocol has been designed wherein, polyvinyl pyrrolidone (PVP) stabilized nickel nanoparticles have been used as a catalyst for promoting the synthesis of 2,2'-aryl-methylene bis(3-hydroxy-5,5- dimethyl-2-cyclohexene-1-one)

Full text of DOI:10.1007/s12039-012-0275-8

c
J. Chem. Sci. Vol. 124, No. 4, July 2012, pp. 907–912. ꢀ Indian Academy of Sciences.
Nickel nanoparticles: A highly efficient catalyst for one pot
synthesis of tetraketones and biscoumarins
JITENDER M KHURANA∗ and KANIKA VIJ
Department of Chemistry, University of Delhi, Delhi 110 007, India
e-mail: jmkhurana1@yahoo.co.in
MS received 18 March 2011; revised 17 November 2011; accepted 20 December 2011
Abstract. A novel and practically useful protocol has been designed wherein, polyvinyl pyrrolidone (PVP)
stabilized nickel nanoparticles have been used as a catalyst for promoting the synthesis of 2,2ꢁ-aryl-methylene
bis(3-hydroxy-5,5-dimethyl-2-cyclohexene-1-one), 2,2ꢁ-aryl-methylene bis(3-hydroxy-2-cyclohexene-1-one),
also known as tetraketones, and biscoumarins via Knoevenagel condensation followed by rapid Michael
addition.
Keywords. PVP-stabilized Ni nanoparticles; ethylene glycol; tetraketones; biscoumarins;
cyclo-condensation.
1. Introduction
Raney Ni catalyst. Ni nanoparticles have been used as
catalyst for functional group transformations like trans-
fer hydrogenation of carbonyl compounds,22–24 reduc-
tive amination of aldehydes,25 alkylation of ketones
and indirect aza-Wittig reaction with alcohols,26 oxida-
tive coupling of thiols27 and Hantzsch condensa-
tion for polyhydroquinoline derivatives.28 Recently,
we have reported the Knoevenagel condensation of
aldehydes with barbituric acids29 and with o-phenylene
diamine and 2-aminothiophenol30 catalyzed efficiently
by PVP-stabilized Ni(0) nanoparticles in ethylene gly-
col prepared by the polyol method.31 We have also
reported nickel nanoparticles catalyzed chemoselec-
tive Knoevenagel condensation of Meldrum’s acid and
tandem enol lactonizations via cascade cyclization
sequence.32 One of the prime steps in the synthesis of
tetraketones and biscoumarins is the Knoevenagel con-
densation of aldehydes with dimedone. Therefore, we
envisaged the possibility of applying nickel nanoparti-
cles for the synthesis of 3 and 4.
Tetraketones such as 2,2ꢁ-aryl-methylene bis(3-
hydroxy-5,5-dimethyl-2-cyclohexene-1-one) or tetra-
ketones (3), are important precursors extensively
used in the synthesis of acridinediones, as laser dyes
and for the synthesis of various heterocyclic com-
pounds.1 Tetraketones show significant lipoxygenase
inhibitor activity and strong anti-oxidant potential.2
They exhibit broad spectrum of therapeutic and
biological properties.3–5 3,3ꢁ-(4-aryl methylene) bis-(4-
hydroxycoumarin), commonly known as biscoumarins
(4), are of considerable interest due to their biological
activities, e.g., anticoagulant activity,6 prevention and
treatment of thrombosis,7 urease inhibitors.8 Various
methods have been reported for the synthesis of com-
pounds belonging to these classes: (3 and 4).9–18 Each
of these methods have their own advantages but also
suffer from certain disadvantages such as prolonged
reaction time, tedious work-up processes, low yield,
high temperature and hazardous reaction conditions.
Transition metal nanoparticles have gained tremen-
dous importance due to their interesting electrical,
optical, magnetic, chemical properties, and especially
catalytic properties, which cannot be achieved by their
bulk counterparts.19–21 Recently, there has been grow-
ing interest in using nickel nanoparticles in organic
synthesis owing to their easy preparation, potent
catalytic activity, possible processability, high stabi-
lity and ease of recyclability compared to traditional
2. Experimental
2.1 General
All the chemicals used were of research grade and
were used without further purification. The size and
morphology of nickel nanoparticles were character-
ized with the help of TEM (JEOL 2100-F operating at
200 kV) and QELS analysis (PHOTOCOR-FC-1135P).
1HNMR spectra were recorded on Brucker Spectro-
spin AVANCE (300 MHz). IR spectra were recorded on
∗For correspondence
907

908
Jitender M Khurana and Kanika Vij
Perkin-Elmer FT-IR SPECTRUM-2000. X-ray diffrac- product was filtered using a pump, washed with water,
tion pattern was obtained on BRUKER D8.
dried and recrystallised from hot ethanol. 2, 2ꢁ-(4-
bromophenyl)-methylene bis(3-hydroxy-5, 5-dimethyl-
2-cyclohexene-1-one) (3a, 93%) was obtained as
identified by m.p. 155◦C (lit 158–159◦C) and spectral
data.
2.2 Preparation of Ni nanoparticles
Nickel nanoparticles were prepared by the modi-
fied polyol process.31 2 × 10−4 molL−1 solution
of NiCl2.6H2O in ethylene glycol was reduced with
NaBH4 in the presence of PVP (Ni2+: PVP:: 1: 5 wt%)
at 140◦C. The sample for TEM was prepared by addi-
tion of acetone to the nickel nanoparticles dispersion in
ethylene glycol, followed by centrifugation (6000 rpm).
The particles, so obtained, were washed free of any
residual components using ethanol. Methanol disper-
sion of the nickel nanoparticles was placed on carbon
coated Cu grid (mesh size 300). The ethylene glycol
dispersion was used as such for QELS analysis. Sam-
ple for the X-ray diffraction was obtained by depositing
a thin-coating of the isolated nickel nanoparticles (dis-
persed in absolute ethanol) onto a glass plate followed
by vacuum drying.
3a: M.P. = 155◦C (lit.9 158–159◦C); IR (KBr, cm−1)
υmax = 3053, 2959, 2873, 1723, 1594. 1H NMR
(300 MHz, CDCl3) δ: 1.13 (s, 6H, 2Me), 1.23 (s, 6H,
2Me), 2.20–2.53 (m, 8H, 4CH2), 5.47 (s, 1H, CH), 6.96
(d, 2H, J = 6.6 Hz, H-Ar), 7.38 (d, 2H, J = 6.6 Hz),
11.93 (brs, 1H, OH).
2.4 General procedure for the synthesis of 3,3ꢁ-
(4-aryl methylene) bis-(4-hydroxycoumarins) (4a–f)
In
a
typical experiment, 4-chlorobenzaldehyde
(2 mmol) was added to a well-stirred dispersion of
nickel nanoparticles in ethylene glycol (2 mL/0.1 g
of 1) in a 25 mL reaction flask. 4-Hydroxycoumarin
(4 mmol) was added to the mixture and the stirring was
continued. The progress of the reaction was monitored
by TLC using petroleum ether: ethyl acetate (60:40,
v/v) as eluent. After completion of the reaction, the
solid product was filtered using a pump, washed with
water, dried and recrystallized from hot ethanol. 3, 3ꢁ-
(4-chlorophenylmethylene)-bis-(4-hydroxycoumarin)
(4a, 92%) was obtained as identified by m.p. 250◦C
(lit. 252–254◦C) and spectral data.
2.3 General procedure for the synthesis of
2,2ꢁ-aryl-methylene bis(3-hydroxy-5,5-dimethyl-2-
cyclohexene-1-one) and 2,2ꢁ-aryl-methylene
bis(3-hydroxy-2-cyclohexene-1-one) (3a–z)
In
a
typical experiment, 4-bromobenzaldehyde
(2 mmol) was added to a well stirred dispersion of
nickel nanoparticles in ethylene glycol (2 mL/0.1 g of
1) in a 25 mL reaction flask. Dimedone (2, 4 mmol)
was added to the mixture and the stirring was contin-
ued. The progress of the reaction was monitored by
TLC using petroleum ether: ethyl acetate (70:30, v/v)
as eluent. After completion of the reaction, the solid
4a: M.P. = 250◦C (lit.17 252–254◦C); IR (KBr cm−1):
1
υmax = 3075, 2919, 2733, 1663, 1612, 1567. HNMR
(300 MHz, CDCl3) δ: 6.03 (s, 1H, CH), 7.13–7.29 (m,
4H, H-Ar), 7.35–7.42 (m, 4H, H-Ar), 7.60–7.66 (m, 2H,
H-Ar), 7.97–8.07 (m, 2H, H-Ar), 11.31 (s, 1H, OH),
11.53 (s, 1H, OH).
Figure 1. (a) HRTEM image of Ni nanoparticles. The scale bar corresponds to
20 nm in the images; (b) QELS data of Ni nanoparticles: plot of population distri-
bution in percentile versus size distribution in nanometers (nm); (c) X-ray diffraction
pattern of PVP-Ni nanoparticles.

Heterogeneous catalysis by Ni nanoparticles
909
O
O
R1
O
PVP-Ni nps
R1CHO
R2
R2
R2
R2
R2
E.G., r.t.
1a-w
O
R2
2
OH
OH
R2 = CH3, H
3a-z
Scheme 1. PVP-Ni nanoparticles catalyzed synthesis of tetraketones (3a–z).
2.5 General procedure for the recyclability
of the catalyst
of 3a in ethyl acetate was observed. The two layers were
then separated. The ethylene glycol layer was sonicated
for 5–10 min and reused for the same experiment for
over five cycles.
Aldehyde (1a, 2 mmol) was added to nickel nanopar-
ticle dispersion in ethylene glycol (2 mL/0.1 g 1) in
25 mL reaction flask. Dimedone (2, 4 mmol) was added
to the reaction mixture and it was stirred. Upon com-
plete formation of 3a as monitored by TLC, 10.0 mL
3. Results and discussion
of ethyl acetate was added to the reaction mixture. The We report here a simple and highly efficient route for
reaction mixture was stirred until complete dissolution the synthesis of 2,2ꢁ-aryl-methylene bis(3-hydroxy-5,5-
Table 1. PVP stabilized Ni nanoparticles catalysed synthesis of 2,2ꢁ-aryl-methylene bis(3-hydroxy-5,5-
dimethyl-2-cyclohexene-1-one) and 2,2ꢁ-aryl-methylene bis(3-hydroxy-2-cyclohexene-1-one) (3a–z).
M.P. (◦C)
Entry
R1
R2
Product Time (min.) Yield (%) Obs.
Lit.
1.
2.
3.
4.
5.
6.
7.
8.
4-BrC6H4 (1a)
4-MeOC6H4 (1b)
3,4,5-(MeO)3C6H2 (1c)
C6H5 (1d)
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
3q
3r
3s
10
10
10
10
10
15
10
10
10
10
10
10
10
10
15
10
15
10
8
93
90
96
88
91
86
92
92
90
89
90
87
93
88
89
91
89
94
89
88
88
86
87
90
92
89
155
138
186
204
190
132
144
187
190
200
193
180
165
130
204
190
172
202
146
186
152
100
225
200
236
190
158–15911
142–1439
189–19115
194–1959
188–1909
126–1282
141–14311
194–19510
197–1989
203–20411
195–1969
187–1899
167–16814
134–1359
215–2179
19512
4-O2NC6H4 (1e)
4-MeC6H4 (1f)
4-ClC6H4 (1g)
2-BrC6H4 (1h)
3-O2NC6H4 (1i)
2,4-Cl2C6H3 (1j)
4-Me2NC6H4 (1k)
4-HOC6H4 (1l)
4-FC6H4 (1m)
CH3CH2CH2 (1n)
C6H5CH=CH (1o)
1-Naphthyl (1p)
2-Pyridinyl (1q)
2-HOC6H4 (1r)
2-Furanyl (1s)
CH3CH=CH (1t)
(CH3)2CH (1u)
n-C6H13 (1v)
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
175–17710
205–2069
152–1532
193–1949
153–1549
101–1039
229–23116
202–20313
240–24113
194–19613
3t
10
10
12
10
8
3u
3v
3w
3x
3y
3z
2-HO-3-MeO-C6H3 (1w) CH3
4-ClC6H4 (1g)
4-BrC6H4 (1a)
4-O2NC6H4 (1e)
H
H
H
10
7

910
Jitender M Khurana and Kanika Vij
R'
O
CHO
O
O
OH
R'
PVP-Ni nps
E.G., r.t.
O
O
2
OH
1r:R'=H
1w:R'=OMe
3r: R'= H
3w: R'= OMe
Scheme 2. PVP-Ni nanoparticles catalyzed reaction of ortho-hydroxy benzaldehydes and dimedone.
dimethyl-2-cyclohexene-1-one) and 2,2ꢁ-aryl-methy- reactions of 4-bromobenzaldehyde (1a) and dimedone
lene bis(3-hydroxy-2-cyclohexene-1-one) (3) starting with varying amounts of nickel nanoparticulate dis-
from aldehydes and dimedone, and also the syn- persion in ethylene glycol were monitored by TLC.
thesis of biscoumarins (4) from aldehydes and 4- The reaction was complete using 1:2 molar ratio of
hydroxycoumarin, using highly monodispersed nickel aldehyde to dimedone in 10 min and 93% of 2,2ꢁ-(4-
nanoparticles as catalyst in ethylene glycol. The nickel bromophenyl)-methylene bis(3-hydroxy-5, 5-dimethyl-
nanoparticles were obtained as air-stable nanoparticu- 2-cyclohexene-1-one) (3a) was obtained as identified
late monodispersion by modified polyol method31 in by mp and spectral data. The reaction of 1a and dime-
ethylene glycol from nickel chloride hexahydrate and done in equimolar ratio gave a mixture of 3a and unre-
sodium borohydride using polyvinylpyrrolidone (PVP) acted aldehyde. Subsequent reactions of dimedone with
as the stabilizing agent (equation 1).
several aldehydes containing electron-donating as well
as electron-withdrawing groups underwent smooth and
effective one-pot Knoevenagel condensation followed
by Michael addition in the presence of PVP-coated Ni
nanoparticles to give tetraketones (3b–w). The alde-
hydes also underwent efficient Knoevenagel condensa-
tion and Michael addition with cyclohexane-1,3-dione
to give the corresponding 2,2ꢁ-aryl-methylene bis(3-
hydroxy-2-cyclohexene-1-one) (3x–z) (scheme 1, table
1). The condensation could be achieved with aryl, alkyl,
α, β-unsaturated (1o and 1t) as well as heteroaryl
aldehydes (1q and 1s). The products (3r and 3w)
2Ni2+ (eg) + BH−4 (s) + 2H2O (eg) + 2n PVP (eg)
→ 2Ni (PVP)n (s) + 2H2 (g) + 4H+ (eg) + BO2− (eg) .
(1)
The metal dispersion so obtained was characterized
by TEM analysis which revealed the formation of
coated Ni nanoparticles with average diameter 11 nm
(figure 1a) which was further supported by QELS anal-
ysis that showed a maximum population distribution
centred around 11 nm (figure 1b). XRD analysis further
supported the results (figure 1c).
The versatility of the catalyst was investigated for
the condensation of dimedone with aldehydes. The
Reusability of Nickel nanoparticles
100
80
60
40
20
0
Table 2. Reactions to confirm involvement of Ni nanopar-
ticles during synthesis of 3.
S. No.
Reaction condition
Time Yield (3a, %)
0
2
4
6
8
Number of cycles
1.
2.
3.
4.
5.
Ethylene glycol alone
Ni powder (size < 150 micron)
NiCl2.6H2O alone in EG
NaBH4 alone in EG
6 ha
40
45
42
–
a
–
8 ha
5 hb
(a)
(b)
Figure 2. (a) Recyclability data of PVP-Ni nanoparticles;
(b) QELS data of recycled Ni nanoparticles after 4th cycle:
Plot of population distribution in percentile versus size dis-
tribution in nanometers (nm).
Isolated Ni nanoparticles
redispersed in EG
15 min
90
aincomplete reaction; bmixture of products

Heterogeneous catalysis by Ni nanoparticles
911
OH
R
OH
OH
PVP-Ni nps
E.G., r.t.
O
RCHO
1a-f
O
O
O
O
O
4a-f
Scheme 3. PVP-Ni nanoparticles catalyzed synthesis of biscoumarins (4a–f).
obtained from the reaction of salicylaldehyde (1r) and was observed along with a increase in the particle size
2-hydroxy-3-methoxy benzaldehyde (1w) with dime- as is evident from the QELS data (figure 2).
done has been assigned a pyran structure (scheme 2).
The applicability of the catalyst was further extended
The role of nickel nanoparticles in catalyzing the to the reaction of 4-chlorobenzaldehyde with 4-
formation of tetraketones (3a–z) was confirmed by a hyroxycoumarin under otherwise identical conditions.
blank reaction of 1a with dimedone in ethylene gly- The reaction was complete in 15 min and 92% of 3,3ꢁ-
col in the absence of catalyst. The reaction was incom- (4-chlorophenyl methylene)-bis (4-hydroxycoumarin)
plete even after 6 h of stirring though formation of a (4a) was obtained after work up. Subsequently, reac-
small amount of 3a was observed. The reaction of 1a tions of other aldehydes with 4-hydroxycoumarin also
with dimedone was also attempted with Ni powder (size gave the corresponding biscoumarins in high yields
< 150 micron). The reaction was only 45% complete (scheme 3, table 3).
even after stirring for 24 h. One of the most crucial
Scheme 4 represents a plausible mechanism for the
result came from the reaction of 1a with dimedone formation of tetraketones in the presence of PVP-
in the presence of isolated Ni nanoparticles (obtained stabilized Ni nanoparticles. It is believed that Ni nano-
from the dispersion by the polyol method) which were particles promote enolization in dimedone and facili-
washed repeated by with absolute ethanol followed by tate domino Knoevenagel condensation Michael addi-
dispersal in ethylene glycol. The reaction was found to tion reaction leading to tetraketones. Also, it is a well
be complete in 15 min and 90% of 3a was isolated. All known fact that polymer capped nanoparticles repre-
these results have been summarized in table 2.
sent semi-heterogeneous catalytic system, as presence
Reusability of nickel nanoparticles was examined by of polymer increases the interaction in the organic
the reaction of p-bromobenzaldehyde (1a) with dime- phase. So, in addition to promoting enolization, PVP-
done in the presence of PVP-Ni nanoparticles. Upon stabilized Ni nanoparticles act as semi-heterogeneous
completion, the product (3a, 93%) was extracted in high surface area catalyst and promote rapid tetraketone
ethyl acetate followed by isolation of ethylene glycol or biscoumarin formation.
layer which was then used for subsequent cycles. The
Ethylene glycol, besides being a green solvent,
catalyst retained optimum activity up to four cycles proved advantageous for this transformation based on
after which a drop in yield (74%) of the product (3a) the solubility difference of the starting materials and the
Table 3. PVP stabilized Ni nanoparticles catalyzed synthesis of biscoumarins (4a–f) in
ethylene glycol from aldehyde and 4-hydroxycoumarin.
M.P. (◦C)
Entry
R
Product Time (min) Yield (%)
Obs.
Lit.
1.
2.
3.
4.
5.
6.
4-ClC6H4 (1a)
4a
4b
4c
4d
4e
4f
15
15
20
15
20
15
92
93
87
94
90
89
250
252–25417
232–23418
222–22418
247–24818
4-O2NC6H4 (1b)
4-HOC6H4 (1c)
2-HOC6H4 (1d)
3,4-(CH3O)2C6H3 (1e)
Piperonyl (1f)
230
198
244
270–272 273–27517
244–246 247–24818

912
Jitender M Khurana and Kanika Vij
PVP
O
O
R
O
R
O
PVP
Ni
O
(-H2O)
OH
R
Ni
O
O
OH
O
O
R
PVP
Ni
O
H
O
O
R
O
O
PVP
Ni
OH
O
O
OH
3
Scheme 4. Plausible mechanism for the formation of tetraketones in the presence of Ni nanoparticles.
final product. Hence, during the course of the reaction,
the product precipitated out and was isolated simply by
filtration and washing.
9. Horning E C and Horning M G 1946 J. Org. Chem. 11
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5056
4. Conclusion
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Med. Chem. 41 882
We have developed a practically efficient and novel
protocol for the synthesis of tetraketones (3) and bis-
coumarins (4) using air stable PVP coated nickel
nanoparticles as the catalyst in ethylene glycol at room
temperature. The yields and the reaction time com-
pletely highlight the practical synthetic efficiency of
this novel protocol.
18. Kidwai M, Bansal V, Mothsra P, Saxena S, Somvanshi
R K, Dey S and Singh TP 2007 J. Mol. Catal. A: Chem.
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Acknowledgement
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1847
KV is thankful to the Council of Scientific and Indus-
trial Research (CSIR), New Delhi, India for the award
of Junior and Senior Research Fellowships.
23. Alonso F, Riente P and Yus M 2008 Tetrahedron Lett. 49
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