The first catalytic application of copper aluminate nanoparticles in C–C and C–O coupling reaction: green synthesis of some new α‐lapachone derivatives

Article abstract of DOI:10.1007/s00706-016-1692-z

Abstract: This is the first use of copper aluminate nanoparticles (CuAl₂O₄ NPs) as efficient catalyst for the multicomponent organic synthesis. The CuAl₂O₄ NPs was prepared and characterized by XRD, SEM, and TEM

Full text of DOI:10.1007/s00706-016-1692-z

Monatsh Chem
DOI 10.1007/s00706-016-1692-z
ORIGINAL PAPER
The first catalytic application of copper aluminate nanoparticles
in C–C and C–O coupling reaction: green synthesis of some new
a-lapachone derivatives
Bahareh Abdolpour Mori1 Saeed Khodabakhshi2 Sanaz Tajik2
•
•
•
Mojtaba Baghernejad1 Amir Yadegari2
•
Received: 28 October 2015 / Accepted: 7 February 2016
Ó Springer-Verlag Wien 2016
Abstract This is the first use of copper aluminate
nanoparticles (CuAl2O4 NPs) as efficient catalyst for the
multicomponent organic synthesis. The CuAl2O4 NPs was
prepared and characterized by XRD, SEM, and TEM for
this purpose and applied in the green synthesis of pyra-
nonaphthoquinones (a-lapachone derivatives) under
solvent-free conditions. The nanocatalyst can be recycled
and reused for four times.
Introduction
Polyheterocyclic compounds containing quinonoids are
widely found in nature, and they possess a broad spectrum of
biological activities. Synthesis of pyranonaphthoquinones
such as a-lapachone [1] and pyranokunthone A and B [2, 3]
has gained much attention because of their interesting
pharmacological properties which result in manifestation of
the following: anti-bacterial, anti-fungal, anti-trypanosomal,
anti-malarial, and anti-tumor activities. (4S)-4-Hydroxy-a-
lapachone and rhinacanthin A have been known as anti-tu-
mor and mosquito cytochrome P450 enzyme inhibitor
compounds, respectively [4] (Fig. 1).
Graphical abstract
Multicomponent reactions (MCRs) are known as useful
methods to achieve a large number of heterocyclic scaffolds
and drug-like compounds. In fact, they have become
increasingly popular tools since they are economic, and
they minimize waste, labor, time, and cost [5, 6].
Until now, several methods have been described in the
literature for the synthesis of a-lapachone derivatives [7–
12]. To the best of our knowledge, there are only two reports
on the catalytic application of copper aluminate in organic
reactions including catalytic decomposition of benzyl alco-
hol using bulk copper aluminate [13] and oxidation of benzyl
alcohol using copper aluminate nanoparticles [14]. How-
ever, there is no report on the copper aluminate-catalyzed C–
C and C–O coupling reactions. In continuation, we describe a
three-component synthesis of a-lapachone derivatives in the
presence of CuAl2O4 nanoparticles.
Keywords CuAl2O4 NPs Á a-Lapachone Á Nanocatalyst Á
Multicomponent Á Solvent-free
Electronic supplementary material The online version of this
article (doi:10.1007/s00706-016-1692-z) contains supplementary
material, which is available to authorized users.
& Saeed Khodabakhshi
saeidkhm@yahoo.com
Result and discussion
1
Department of Chemistry, Gachsaran Branch, Islamic Azad
University, Gachsaran, Iran
As can be seen in Fig. 2a, the surface morphology of the
prepared CuAl2O4 NPs was investigated by scanning electron
microscopy (SEM). For further studies, the transmission
2
Department of Chemistry, Robatkarim Branch, Islamic Azad
University, Robatkarim, Iran
123

B. A. Mori et al.
the best yield of the corresponding product was afforded
(Table 1). In another variation, the effect of catalyst
amount on the reaction rate and product yield was also
investigated (Table 1). Besides, the temperature played a
key role because there was no product formation at room
temperature under solvent-free conditions while the reac-
tion led to the desired product in 92 % yield at 110 °C. As
a matter of fact, increasing the temperature markedly
affects the reaction (Table 1).
After screening, it was found that the condensation
reaction can be efficiently performed by adding 0.07 mmol
of the catalyst at 110 °C under solvent-free conditions in a
short time span of 70 min. Encouraged by these results, as
shown in Table 2, we investigated the reaction scope for
the synthesis of compounds 4.
Fig. 1 Some biologically active pyranonaphthoquinones
electron microscopy (TEM) was also provided (Fig. 2b). The
TEM image clearly shows the nanometric particles of the
prepared CuAl2O4 with the diameters in the range of
10–30 nm. Figure 2c shows the XRD pattern of the as-syn-
thesized CuAl2O4 NPs calcinated at 800 °C. The XRD pattern
confirmstheformationofthe fullycrystallineandsinglephase
CuAl2O4. The six diffraction lines correspond to the CuAl2O4
phase having the perovskite crystal structure, and they are in
agreement with the JCPDS values [15, 16].
A variety of aldehydes 1 were reacted with 2 and 3
under standard conditions. Regardless of the electronic
nature and the substitution on the aromatic rings of 1 and 3,
the reaction afforded corresponding pyranonaphtho-
quinones 4 in good to excellent yields.
A mechanistic rationale for the formation of compounds
4 in the presence of metal oxides is proposed in Scheme 2.
It is conjectured that the reaction takes place in three steps.
The initial event involves the Knovenagel coupling of alde-
hyde with naphthol. Next, the Michael addition of
naphthoquinone to the intermediate and intramolecular
cyclization followed by dehydration leads to the final product.
Having in mind increasing pollution and decreasing
resources, one major goal of green chemistry is the
development of efficient routes to synthesize fine chemi-
cal under cost-effective and safe conditions. To make our
catalytic reaction in agreement with green chemistry cri-
teria, we concentrated on the catalyst recycling
experiment. As can be seen in Fig. 3, after recycling, the
CuAl2O4 NPs exhibited remarkable activity for the first
three consecutive runs while a little decrease was
observed during fourth run. However, the decrease in the
product yield for the fourth run is likely to be because of
handling loss of catalyst.
In continuation of the foregoing discussion and our
previous studies on the use of nanocatalysts in organic
reactions [17–19], the as-synthesized CuAl2O4 NPs was
used as a nanocatalyst in the synthesis of some pyranon-
aphthoquinones 4 (a-lapachone derivatives) through a
three-component reaction of aromatic aldehydes 1, 2-hy-
droxy-1,4-naphthoquinone (2), and b-naphthols 3 under
solvent-free conditions (Scheme 1).
What is widely known to make a sustainable green
process is synthesizing using no solvent. To explore and
ascertain the feasibility of the above-mentioned reaction,
the reaction of benzaldehyde (1a), 2, and b-naphthol (3a)
was initially chosen as a model. Firstly, solvent effect on
the reaction was explored and some solvents such as
MeOH, EtOH, H2O, and CH2Cl2 at 110 °C were tested. By
setting the reaction under solvent-free conditions, however,
Fig. 2 SEM image (a), TEM image (b), and XRD patterns (c) for CuAl2O4 NPs
123

The first catalytic application of copper aluminate nanoparticles in C–C and C–O coupling…
Scheme 1
Table 1 Optimization of the
Entry
Solvent (10 cm3)
Catalyst amount/ %
Temperature/ °C
Yield/ %
reaction conditions in the
synthesis of 4a at 110 °C.
Reaction time: 70 min
1
MeOH
EtOH
H2O
10 %
10 %
10 %
10 %
10 %
–
65
78
40
2
45
3
100
40
15
4
CH2Cl2
Free
–
5
110
110
110
110
110
80
91
6
Free
25
7
Free
3 %
7 %
15 %
7 %
7 %
7 %
55
8
Free
92
9
Free
90
10
11
12
Free
35
Free
50
Trace
Trace
Free
25
Table 2 Synthesis of a-
lapachone derivatives using
CuAl2O4 NPs under solvent-
free conditions (Scheme 1)
Entry
X
H
Ar
Ph
Time/ min
Yielda/ %
M.p./ °C (reported)
4a
4b
4c
4d
4e
4f
4g
4h
4i
70
75
60
90
65
75
92
85
88
82
95
90
82
90
85
88
318–320 ([300 [8])
310–312
OH
H
3-OH-Ph
4-CN-Ph
318–320
H
1-Naphthyl
2-MeO-Ph
4-Benzyloxy-Ph
270–272
H
390–392
OH
OH
H
295–297
(1,4-Phenylene)bis
2-Naphthyl
3-NO2-Ph
110
85
247–249
282–284 ([300 [8])
300–302 ([300 [8])
305–306 ([300 [8])
H
80
4j
a
H
4-Cl-Ph
80
Isolated yield
Table 3 demonstrates the merits of the present method for
the synthesis of pyranonaphthoquinones compared to some
previously ones. As can be seen, we believe that these
reactions can be efficiently carried out under our suggested
conditions in terms of the reaction time and product yield.
In conclusion, CuAl2O4 NPs has been prepared and
successfully used for the first time in the one-pot, three-
component synthesis of a-lapachone derivatives. The pre-
sent method possesses several advantages such as high
atom economy and product yields, using a stable, envi-
ronmentally benign, and renewable nanocatalyst,
simplicity of the procedure, and avoidance of solvent. It is
hoped this strategy to be used by the synthetic organic
community for the scale-up synthesis.
123

B. A. Mori et al.
Scheme 2
MO NPs
O
HO
O
Ar
H
Ar
H
Y
MO NPs
MO NPs
Ar
OH
Y
O
O
-H2O
O
O
Ar
Y
OH
MO NPs
Ar
Y
Y
O
Ar
O
OH
MO NPs
O
MO NPs
O
H
Ar
O
O
OH
Y
O
MO NPs
-H2O
Y
Ar
O
O
O
JFM-1200 EX transmission electron microscopy (TEM).
IR spectra were recorded on a FT-IR JASCO-680. 1H (400
and 500 MHz) and 13C NMR (100 and 125 MHz) spectra
were recorded on a Bruker Avance II model. The varioEl
CHNS was also used for elemental analysis. The com-
pounds 4a and 4 h–4j have been previously reported in the
literature [8].
Experimental
Chemicals were purchased from Merck and Aldrich and
used without further purification. Powder X-ray diffraction
measurements were made on a Philips X’pertdiffractome-
ter, using filtered Cuka radiation. A Philips XL30
instrument was used to record SEM micrographs. The
images of CuAl2O4 nanocrystals were obtained with JEDL-
123

The first catalytic application of copper aluminate nanoparticles in C–C and C–O coupling…
(400 MHz, DMSO-d6): d = 10.00 (s, 1H), 9.29 (s, 1H),
8.21 (1H, d, J = 7.6 Hz), 7.99 (d, 1H, J = 7.6 Hz), 7.90 (t,
2H, J = 7.6 Hz), 7.81 (d, 1H, J = 7.6 Hz), 7.69 (t, 1H,
J = 7.6 Hz), 7.50 (d, 1H, J = 8.4 Hz), 7.26 (s, 1H),
7.05–7.0 (m, 2H), 6.81 (s, 1H), 6.70 (s, 1H), 6.50 (dd, 1H,
J = 7.6, 2.4 Hz) ppm; 13C NMR (100 MHz, DMSO-d6):
d = 177.7, 177.5, 157.3, 156.6, 156.3, 147.3, 144.74,
135.0, 132.2, 131.3, 130.3, 130.1, 129.1, 128.4, 125.83,
124.3, 119.2, 117.6, 115.2, 114.8, 113.67, 113.62, 105.3,
34.6 ppm.
14-(4-Cyanophenyl)-13H-dibenzo[a,i]xanthene-
Fig. 3 Recyclability study of CuAl2O4 NPs catalyst (10 mol %) for
the synthesis of 4a. Reaction conditions: 110 °C, solvent-free, 70 min
8,13(14H)-dione (4c, C28H15NO3)
ꢀ
M.p.: 318–320 °C; IR (KBr): m = 3073, 2227, 1703, 1664,
1
1635, 1590, 1369, 1238, 1214 cm-1; H NMR (400 MHz,
Table 3 Comparison of the present method with some previously
reported ones
DMSO-d6): d = 8.27 (d, 1H, J = 8.8 Hz), 8.09 (t, 2H,
J = 7.6 Hz), 7.99 (t, 2H, J = 7.6 Hz), 7.92 (t, 1H,
J = 8.8 Hz), 7.80 (d, 1H, J = 8.8 Hz), 7.23 (d, 1H,
J = 7.2 Hz), 7.69 (d, 2H, J = 8.4 Hz), 7.62 (d, 2H,
J = 8.4 Hz), 7.57–7.48 (m, 2H), 5.93 (s, 1H) ppm; 13C
NMR (100 MHz, DMSO-d6): d = 177.6, 177.3, 156.5,
148.9, 146.8, 144.4, 135.0, 132.3, 131.6, 131.4, 130.5,
130.1, 129.7, 128.7, 128.4, 127.6, 125.6, 124.5, 123.4,
118.5, 117.7, 117.4, 115.6, 114.5, 109.4, 35.0 ppm.
Entry Catalyst
Time/ min/ yield/ % References
1
2
3
4
Silica chloride
45/88
[7]
AcOH
300/93
600/88
[8]
p-TSA
[9]
Polystyrene-supported 89/120
GaCl3
[10]
5
6
7
[bmim]HSO4
HClO4-SiO2
CuAl2O4 NPs
30/91
–/92
[11]
[12]
14-(1-Naphthyl)-13H-dibenzo[a,i]xanthene-8,13(14H)-
70/92
Present work
dione (4d, C31H18O3)
ꢀ
M.p.: 270–272 °C; IR (KBr): m = 3055, 2932, 1700, 1635,
1
1590, 1368, 1288, 1237, 1215 cm-1; H NMR (400 MHz,
Preparation of nanocatalyst
DMSO-d6): d = 9.96 (s, 1H), 8.25 (d, 1H, J = 7.6 Hz),
7.96 (d, 1H, J = 7.6 Hz), 7.91–7.89 (m, 3H), 7.84–7.75
(m, 4H), 7.68 (t, 1H, J = 7.6 Hz), 7.54 (d, 1H,
J = 8.8 Hz), 7.48–7.39 (m, 3H), 7.34 (d, 1H, J = 2 Hz),
6.99 (dd, 1H, J = 8.8, 2 Hz), 5.73 (s, 1H) ppm; 13C NMR
(100 MHz, DMSO-d6): d = 177.7, 177.4, 156.6, 156.2,
147.3, 140.8, 135.0, 132.6, 131.7, 131.3, 130.3, 130.2,
130.1, 129.3, 128.4, 127.9, 127.6, 127.2, 127.0, 126.6,
126.1, 125.8, 124.4, 117.5, 115.4, 114.5, 113.7, 105.3,
35.2 ppm.
Typically, a solution of Al2(SO4)3 (10 mmol), Cu2SO4
(5 mmol), and Mg(OH)2 (35 mmol) in 100 cm3 deionized
water was stirred and heated at 80 °C for 24 h. The
resulting suspension was filtered and dried at 100 °C for
2 h followed by heating at 900 °C for 5 h to acquire the
nanosized CuAl2O4 particles.
Synthesis of pyranonaphthoquinones 4
A mixture of b-naphtol or 2,7-dihydroxynaphthalene
(1 mmol; 2 mmol for 4 g), aromatic aldehyde (1 mmol),
lawsone (1 mmol; 2 mmol for 4 g), and CuAl2O4 (7 mol %)
was stirred and heated at 110 °C in a preheated oil bath for an
appropriate time. After completion of the reaction as moni-
tored by TLC (AcOEt/hexane), the reaction mixture was
dissolved in hot EtOH. Then, the catalyst was separated by
simple filtration, washed with hot EtOH, and dried at 90 °C
to reuse. The solvent was removed and the corresponding
product purified by recrystallization from EtOH.
14-(3-Methoxyphenyl)-13H-dibenzo[a,i]xanthene-
8,13(14H)-dione (4e, C28H18O4)
ꢀ
M.p.: 390–392 °C; IR (KBr): m = 2920, 1668, 1637, 1590,
1575, 1365, 1290, 1246, 1235, 1215 cm-1 1H NMR
;
(400 MHz, DMSO-d6): d = 8.26 (d, 1H, J = 7.6 Hz), 8.10
(d, 1H, J = 7.6 Hz), 7.97–7.85 (m, 3H), 7.78 (d, 1H,
J = 7.6 Hz), 7.68–7.64 (m, 2H), 7.54 (t, 1H, J = 8.0 Hz),
7.40–7.38 (m, 2H), 7.18 (d, 1H, J = 8.0 Hz), 7.07 (t, 1H,
J = 7.6 Hz), 6.90 (t, 1H, J = 7.6 Hz), 5.80 (s, 1H), 3.69 (s,
3H) ppm; 13C NMR (100 MHz, DMSO-d6): d = 178.5,
178.2, 155.1, 147.1, 144.3, 141.7, 138.1, 137.0, 135.3,
134.9, 133.6, 130.3, 127.2, 127.0, 126.8, 125.3, 124.9,
124.4, 123.9, 123.4, 121.0, 118.9, 118.2, 113.6, 112.4,
111.7, 52.2, 35.7 ppm.
2-Hydroxy-14-(3-hydroxyphenyl)-13H-dibenzo[a,i]xan-
thene-8,13(14H)-dione (4b, C27H16O5)
ꢀ
M.p.: 310–312 °C; IR (KBr): m = 3410, 2925, 1690, 1634,
1593, 1518, 1452, 1378, 1290, 1245, 1215 cm-1; 1H NMR
123

B. A. Mori et al.
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14-(4-Benzyloxyphenyl)-13H-dibenzo[a,i]xanthene-
8,13(14H)-dione (4f, C34H22O5)
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M.p.: 295–297 °C; 1H NMR (500 MHz, CDCl3): d = 9.20
(s, 1H), 7.96 (d, 1H, J = 8.0 Hz), 7.87 (d, 1H,
J = 7.6 Hz), 7.60 (t, 1H, J = 7.2 Hz), 7.55 (d, 1H,
J = 8.8 Hz), 7.48 (d, 1H, J = 8.8 Hz), 7.39 (t, 1H,
J = 7.6 Hz), 7.17–7.10 (m, 9 H), 6.85 (dd, 1H, J = 8.4,
2.4 Hz), 6.58 (d, 2H, J = 8.4 Hz), 5.49 (s, 1H), 4.73 (s,
2H) ppm; 13C NMR (125 MHz, CDCl3): d = 180.6, 165.3,
160.6, 157.7, 151.0, 150.1, 150.0, 140.1, 138.1, 135.4,
135.3, 133.9, 133.7, 133.5, 133.4, 123.4, 120.4, 120.0,
119.4, 116.6, 115.4, 111.5, 110.4, 104.4, 89.2, 58.5,
33.2 ppm.
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14,140-(1,4-Phenylene)bis(2-hydroxy-13H-
dibenzo[a,i]xanthene-8,13(14H)-dione) (4g, C48H26O8)
ꢀ
M.p.: 247–249 °C; IR (KBr): m = 3438, 2933, 1698, 1579,
1
1633, 1457, 1381, 1289, 1215 cm-1; H NMR (400 MHz,
DMSO-d6): d = 9.88 (s, 2H), 7.93–7.88 (m, 10 H),
7.81–7.88 (m, 6H), 7.59 (d, 4H, J = 8.0 Hz), 7.25 (s,
2H), 5.67 (s, 2H) ppm; 13C NMR (100 MHz, DMSO-d6):
d = 192.2, 192.4, 156.5, 149.8, 147.2, 135.0, 134.7, 132.1,
131.5, 130.4, 130.3, 129.9, 129.6, 129.3, 128.4, 125.8,
124.4, 117.6, 114.7, 113.9, 113.7, 105.18, 105.12,
35.30 ppm.
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Acknowledgments Partial support for this work by Islamic Azad
University is gratefully acknowledged.
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