Synthesis of Tetraketones Using ZnS Nanoparticles as an Efficient Catalyst

Article abstract of DOI:10.1002/jccs.201700250

An efficient pseudo-three-component synthesis of tetraketones is described by one-pot condensation of 5,5-dimethylcyclohexane-1,3-dione and aldehydes using ZnS nanoparticles at room temperature. This method provides several advantages such as mild reactio

Full text of DOI:10.1002/jccs.201700250

JOURNAL OF THE CHINESE
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Article
Synthesis of Tetraketones Using ZnS Nanoparticles as an Efficient Catalyst
*
Javad Safaei-Ghomi , Saeedeh Asadian, Seyed Hadi Nazemzadeh and
Hossein Shahbazi-Alavi
Department of Organic Chemistry, Faculty of Chemistry, University of Kashan, 51167 Kashan, Iran
(Received: July 15, 2017; Accepted: November 16, 2017; DOI: 10.1002/jccs.201700250)
An efficient pseudo-three-component synthesis of tetraketones is described by one-pot condensa-
tion of 5,5-dimethylcyclohexane-1,3-dione and aldehydes using ZnS nanoparticles at room temper-
ature. This method provides several advantages such as mild reaction conditions, applicability to a
wide range of substrates, reusability of the catalyst, and low catalyst loading.
Keywords: Pseudo-three-component; Tetraketones; ZnS nanoparticles; Nanocatalyst; One-pot.
INTRODUCTION
Tetraketones show significant biological activities
5,5-dimethylcyclohexane-1,3-dione
(Scheme 1).
and
aldehydes
including as tyrosinase inhibitors,1 lipoxygenase inhibi-
tors, and antioxidants.2 These attributes make tetrake-
tones noteworthy targets in organic synthesis for future
considerations. A number of improved procedures have
been reported for the synthesis of tetraketones in the
presence of catalysts including cetyltrimethyl ammo-
nium bromide (CTMAB),3 L-proline,4 Fe/NaY zeolite,5
urea,6 (NH4)2HPO4,7 BiOCl.8 nickel nanoparticles
(NPs),9 and ionic liquids.10 Each of these methods has
its own advantages but also suffers from certain disad-
vantages such as prolonged reaction time, tedious
work-up processes, low yield, high action temperature,
and hazardous reaction conditions. Despite the avail-
ability of these methods, there remains enough space
for a capable and reusable catalyst with high catalytic
activity for the preparation of tetraketones. The use of
environmentally friendly and green catalysts that can
be easily recycled at the end of reactions has attracted
great attention in recent years.11–14 ZnS NPs have
emerged as a suitable class of heterogeneous catalysts
owing to their numerous applications in synthesis and
catalysis.15–18 Since these NPs can often be recovered
simply by an easy work-up, which prevents contamina-
tion of the products, they may be considered as promis-
ing, safe, and reusable catalysts as well as greener
compared to traditional catalysts.19,20 Here we reported
the use of ZnS NPs as an efficient catalyst for the prep-
aration of tetraketones by a one-pot condensation of
RESULTS AND DISCUSSION
The morphology and particle size of ZnS NPs
were investigated by scanning electron microscopy
(SEM) as shown in Figure 1. The SEM images show
particles with diameters in the range of nanometers.
The crystalline nature of the synthesized ZnS NP sam-
ples was further verified by X-ray diffraction (XRD)
patterns. The crystallite diameter (D) of the ZnS NPs
was calculated by the Debye–Scherrer equation
(D = Kλ/β cos θ). The results show that the obtained
ZnS NPs had an average diameter of 25–30 nm
(Figure 2).
Initially, we explored and optimized different
reaction parameters for the synthesis of tetraketones
by one-pot condensation of 5,5-dimethylcyclohexane-
1,3-dione and 4-chlorobenzaldehydeas a model reac-
tion (Table 1). These reactions were carried out in the
presence of various catalysts, such as (NH4)2Ce
(NO3)6, FeCl3, nano-Fe3O4, nano-ZnO, and nano-
ZnS. The best results were obtained in water, and the
reaction gave satisfactory results in the presence
nano-ZnS. In order to optimize the reaction condi-
tions, we performed the reaction using different quan-
tities of the catalyst. There was no difference in yield
and reaction time when catalyst loading was
enhanced to 6 mol%.
*Corresponding author. Email: safaei@kashanu.ac.ir
J. Chin. Chem. Soc. 2017
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Article
Safaei-Ghomi et al.
R
R
H
O
O
O
O
O
O
2
O
R
nano-ZnS
H2O, rt
+
O
O
OH OH
3 a-l
2
1a-l
Scheme 1. Synthesis of tetraketones.
To investigate the scope and limitation of this cat-
alytic process, aromatic aldehydes were chosen as sub-
strates (Table 2). Investigations of the reaction scope
revealed that various aromatic aldehydes (bearing
electron-withdrawing and electron-donating groups)
could be utilized in this protocol.
Fig. 2. X-ray diffraction pattern of the catalyst.
NPs were then washed 3–4 times with ethanol and dried
at 40ꢀC for 10 h.
We also investigated the reusability of the nano-
ZnS catalyst at room temperature in water for the syn-
thesis of product 3i, and it was found that product
yields decreased only slightly on each reuse (run
1, 97%; run 2, 97%; run 3, 96%; run 4, 96%; run
5, 95%). After completion of the reaction, CHCl3 was
added. The catalyst was insoluble in CHCl3 and it
could therefore be recovered by simple filtration. The
EXPERIMENTAL
The products were isolated and characterized by
physical methods and spectral data. H NMR and 13C
1
NMR spectra were recorded on a Bruker Avance-
400 MHz spectrometer with tetramethylsilane as inter-
nal standard. The IR spectra were recorded on an
FT-IR Magna 550 apparatus using KBr plates. Melting
points were determined on an Electro-Thermal 9200
instrument, and are not corrected. The elemental ana-
lyses (C, H, N) were carried out on a Carlo ERBA
Model EA 1108 analyzer. Powder XRD was carried
out on a Philips diffractometer (X’pert) with monochro-
matized Cu Kα radiation (λ = 1.5406 Å). Microscopic
morphology of the products was visualized by SEM
(MIRA3 TESCAN).
Preparation of ZnS nanoparticles
ZnS NPs were prepared by dropping simulta-
neously 50 mL of a 1 M solution of ZnSO4 and 50 mL
of a 1 M solution of Na2S into 200 mL of distilled
water containing 50 mL of 0.1 M solution of EDTA,
which was vigorously stirred using a magnetic stirrer
under Ar atmosphere. The high insolubility of ZnS
formed out of the chemical reaction resulted in the for-
mation of a number of new nuclei while preventing the
growth of the already existing ones, thus limiting the
particle size. The role of EDTA was to stabilize the par-
ticles against aggregation, which may lead to an
increase in the particle size. The precipitate was sepa-
rated from the reaction mixture and was dried at room
temperature. After sufficient drying, the precipitate was
Fig. 1. Scanning electron microscopy images of the
catalyst.
2
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ZnS NP-catalyzed Synthesis of Tetraketones
Table 1. Optimization of reaction conditions using different catalystsa
Entry
Solvent
Catalyst (mol%)
Time (min)
Yield (%)b
1
2
3
4
5
6
7
8
H2O
CH3CN
EtOH
EtOH
EtOH
H2O/EtOH (5:5)
CHCl3
CH3CN
EtOH
H2O
H2O
—
120
60
60
60
60
30
30
30
30
30
30
30
50
58
64
69
72
85
62
75
80
86
97
97
(NH4)2Ce(NO3)6 (6)
FeCl3 (7)
nano-Fe3O4 (6)
nano-ZnO (6)
nano-ZnS (4)
nano-ZnS (4)
nano-ZnS (4)
nano-ZnS (4)
nano-ZnS (2)
nano-ZnS (4)
nano-ZnS (6)
9
10
11
12
H2O
a 4-Chlorobenzaldehyde (1 mmol) and 5,5-dimethylcyclohexane-1,3-dione (2 mmol).
b Isolated yield.
crushed to fine powder with the help of a mortar and
Spectral data
pestle.18,19
2,20-(2,4-Dichlorophenyl)methylenebis(3-hydroxy-
5,5-dimethyl-2-cyclohexene-1-one) (3a). White powder;
m.p. 200–202ꢀC, IR (KBr) cm−1: 3352, 2958, 1722,
1611, 1468; 1H NMR (400 MHz, CDCl3): δ 1.10
(6H, s, 2 CH3), 1.12 (6H, s, 2 CH3), 2.21–2.46 (8H, m,
4 CH2), 5.57 (1H, s, CH), 7.19–7.30 (3H, m, Ar), 11.87
(2H, brs, OH) ppm; Anal. Calcd for C23H26Cl2O4: C,
63.16; H, 5.99; Found: C, 63.12; H, 5.90.
General procedure for the preparation of tetraketones
In a 20-mL flask was placed benzaldehydes
(1 mmol), 5,5-dimethylcyclohexane-1,3-dione (2 mmol),
and ZnS NPs (4 mol%) in water (5 mL). The resulting
yellow solution was stirred at room temperature for
30 min (TLC-monitored). A white precipitate formed,
which was filtered and CHCl3 was added to it. The cat-
alyst was insoluble in CHCl3, so it could be recovered
by a simple filtration. The solvent was evaporated and
the solid obtained was recrystallized from ethanol to
afford the tetraketones.
2,20-(2-Chlorophenyl)methylene bis(3-hydroxy-5,5-
dimethyl-2-cyclohexene-1-one) (3b). White powder;
m.p. 202–204ꢀC, IR (KBr) cm−1: 3393, 2956, 1720,
1
1611, 1468; H NMR (400 MHz, CDCl3): δ 1.10 (6H,
s, 2 CH3), 1.14 (6H, s, 2 CH3), 2.21–2.47 (8H, m,
Table 2. Synthesis of tetraketones using ZnS nanoparticles
Entry
Aldehydes (R)
Product
Time (min)
Yield (%)a
m.p. (ꢀC)Ref
m.p. (ꢀC) (found)
1
2
3
4
5
6
7
8
2,4-Dichloro
2-Cl
2-NO2
3-OH
3-NO2
4-CH(CH3)2
4-Br
4-CH3
4-Cl
4-N(CH3)2
4-NO2
4-OH
3a
3b
3c
3d
3e
3f
3g
3h
3i
30
30
30
40
30
45
30
40
30
50
30
45
97
94
94
90
92
90
97
90
97
85
97
87
197–1997
199–2005
188–1896
243–24421
190–1916
—
154–1565
142–1436
143–1455
194–19522
188–1905
182–1845
200–202
202–204
194–196
245–246
194–196
167–169
170–172
140–142
144–146
196–198
185–187
189–191
9
10
11
12
3g
3k
3l
a Isolated yield.
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Article
Safaei-Ghomi et al.
4 CH2), 5.62 (1H, s, CH), 7.11–7.41 (4H, m, Ar), 11.87
(2H, brs, OH) ppm; Anal. Calcd for C23H27ClO4: C,
68.56; H, 6.75; Found: C, 68.48; H, 6.65.
s, 4CH3), 2.05 (3H, s, CH3), 2.30 (8H, s, 4CH2), 5.53
(1H, s, CH), 6.97–7.26 (4H, m, Ar), 11.92 (2H, brs,
OH) ppm; Anal. Calcd for C, 75.36; H, 7.91;
Found: C, 75.30; H, 7.87.
2,20-(2-Nitrophenyl)methylene bis(3-hydroxy-5,5-
dimethyl-2-cyclohexene-1-one) (3c). White powder;
m.p. 194–196ꢀC, IR (KBr) cm−1: 3421, 3390, 2956,
2,20-(4-chlorophenyl)methylene
bis(3-hydroxy-
5,5-dimethyl-2-cyclohexene-1-one) (3i). White pow-
der; m.p. 144–146ꢀC, IR (KBr) cm−1: 3397, 2930,
1703, 1644; 1H NMR (400 MHz, CDCl3): δ (ppm)
1.59 (12H, s, 4CH3), 2.35 (8H, s, 4CH2), 5.47 (1H, s,
CH), 7.0–7.38 (4H, m, Ar), 11.37 (2H,brs,OH) ppm;
Anal. Calcd for C, 68.56; H, 6.75; Found: C,
68.48; H, 6.63.
1
1722, 1615, 1467; H NMR (400 MHz, CDCl3): δ 1.16
(12 H, s, 4CH3), 2.29 (8H, s, 4CH2), 6.20 (1H, s, CH),
7.24–7.56 (4H, m, Ar), 11.89 (2H, brs, OH) ppm; Anal.
Calcd for C23H27NO6: C, 66.81; H, 6.58; N, 3.39;
Found: C, 66.79; H, 6.50; N, 3.27.
2,20-(3-Hydroxyphenyl)methylene bis(3-hydroxy-
5,5-dimethyl-2-cyclohexene-1-one) (3d). White powder;
m.p. 245–246ꢀC, IR (KBr) cm−1: 3419, 3387, 2947,
1718, 1609, 1456; 1H NMR (400 MHz, CDCl3): δ
(ppm) 1.09 (12H, s, 4CH3), 2.29 (8H, s, 4CH2), 5.43
(1H, s, CH), 6.58–7.27 (4H, m, Ar), 11.95 (3H, brs,
OH) ppm; Anal. Calcd for C23H28O5: C, 71.85; H,
7.34; Found: C, 71.78; H, 7.28.
2,20-(4-N,N-Dimethylaminophenyl)methylene bis(3-
hydroxy-5,5-dimethyl-2-cyclohexene-1-one) (3j). White
powder; m.p. 196–198ꢀC, IR (KBr) cm−1: 3129, 1628,
1
1611, 1506, 1311, 850; H NMR (400 MHz, CDCl3): δ
(ppm)1.12 (12H, s, 4CH3), 2.28 (8H,s,4CH3), 2.91 (6H, s,
N(CH3)2) 5.26 (1H, s, CH), 6.55–8.04 (4H, m, Ar), 11.88
(2H,s,OH) ppm; Anal. Calcd for C25H33NO4: C,
72.96; H, 8.08; N, 3.40; Found: C, 72.87; H,
7.78; N, 3.37.
2,20-(4-Nitrophenyl)methylene bis(3-hydroxy-5,5-
dimethyl-2-cyclohexene-1-one) (3k). White powder;
m.p. 185–187ꢀC, IR (KBr) cm−1: 3123, 1674, 1622,
1510, 1363, 1340, 1463, 845 cm−1; 1H NMR (400 MHz,
CDCl3): δ 1.24 (12H, s,4CH3), 2.36 (8H, s, 4CH2), 5.55
(1H, s, CH), 7.24–8.15 (4H, m, Ar), 11.81 (2H, brs,
2OH) ppm; Anal. Calcd for C, 66.81; H, 6.58; N, 3.39;
Found: C, 66.75; H, 6.46; N, 3.28.
2,20-(4-Hydroxyphenyl)methylene bis(3-hydroxy-
5,5-dimethyl-2-cyclohexene-1-one) (3l). White powder;
m.p. 189–191ꢀC, IR (KBr) cm−1: 3120, 1673, 1621,
1514, 1360, 1342; 1H NMR (400 MHz, CDCl3): δ
(ppm) 1.16 (12H, s, 4CH3), 2.29 (8H, s, 4CH2), 5.47
(1H, s, CH), 6.69–7.26 (4H, m, Ar), 11.89 (3H, brs,
OH) ppm; Anal. Calcd for C, 71.85; H, 7.34;
Found: C, 71.75; H, 7.28.
2,20-(3-Nitrophenyl)methylene bis(3-hydroxy-5,5-
dimethyl-2-cyclohexene-1-one) (3e). White powder;
m.p. 194–196ꢀC, IR (KBr) cm−1: 3414, 3385, 2943,
1
1715, 1605; H NMR (400 MHz, CDCl3): δ (ppm) 1.12
(12H, s, 4CH3), 2.36 (8H, s, 4CH2), 5.54 (1H, s, CH)
7.26–8.05 (4H, m, Ar), 11.87 (2H, brs, OH) ppm; Anal.
Calcd for C, 66.81; H, 6.58; N, 3.39; Found: C,
66.75; H, 6.48; N, 3.28.
2,20-(4-isopropylphenyl)methylene bis(3-hydroxy-
5,5-dimethyl-2-cyclohexene-1-one) (3f). White powder;
m.p. 167–169ꢀC, IR (KBr) cm−1: 3399, 2942, 1710,
1608; 1H NMR (400 MHz, CDCl3): δ 1.17 (12H, s,
4CH3), 1.23 (6H, s, 2CH3), 2.34 (8H, s, 4CH2), 2.86
(1H, s, CH), 5.51 (1H, s, CH), 7.00–7.26 (4H, m, Ar),
11.91 (2H, brs, OH) ppm; Anal. Calcd for C, 76.06; H,
8.35; Found: C, 75.95; H, 8.29.
2,20-(4-Bromophenyl)methylene
bis(3-hydroxy-
5,5-dimethyl-2-cyclohexene-1-one) (3g). White pow-
der; m.p. 170–172ꢀC, IR (KBr) cm−1: 3398, 2939,
1703, 1647; 1H NMR (400 MHz, CDCl3): δ 1.14
(12H, s, 4 CH3), 2.40 (8H, s, 4CH2), 5.45 (1H, s,
CH), 6.95–7.63 (4H, m, Ar), 11.90 (2H, brs, OH)
ppm; Anal. Calcd for C, 61.75; H, 6.08; Found: C,
61.70; H, 6.15.
CONCLUSIONS
In conclusion, we have developed a simple and
highly efficient protocol for the synthesis of tetraketones
by a one-pot condensation of 5,5-dimethylcyclohexane-
1,3-dione and aldehydes using ZnS NPs at room tem-
perature. The salient features of this protocol are short
reaction times, high yields, and the absence of any haz-
ardous organic solvent.
2,20-(4-Methylphenyl)methylene
bis(3-hydroxy-
5,5-dimethyl-2-cyclohexene-1-one) (3h). White powder;
m.p. 140–142ꢀC, IR (KBr) cm−1: 3390, 2934, 1705,
1645; 1H NMR (400 MHz, CDCl3): δ (ppm) 1.27 (12H,
4
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ZnS NP-catalyzed Synthesis of Tetraketones
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14, 22.
11. A. R. Moosavi-Zare, H. Goudarziafshar, S. Dastbaz,
J. Chin. Chem. Soc. 2017, 64, 727.
ACKNOWLEDGMENTS
We are grateful to the University of Kashan for
supporting this work (Grant no: 159196/XXII).
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Supporting information
1H NMR spectra of tetraketones are available in
the online version of this article.
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