Natural phosphate as an efficient and green catalyst for synthesis of tetraketone and xanthene derivatives

Article abstract of DOI:10.1007/s11164-016-2603-y

Abstract: Natural phosphate was applied as an efficient and ecofriendly catalyst for the synthesis of tetraketones (2–2.5?h, 90–100?%) and xanthenes (6.5–8.5?h, 84–95?%) via Knoevenagel–Michael cascade reaction of aromatic aldehydes with 1,3-cyclic diketones in water and ethanol, respectively. This protocol provides several advantages over the traditional chemical synthesis, such as simple work-up, easy handling procedure, non-toxicity and stability of catalyst, low cost and environmental friendliness. Graphical Abstract: [Figure not available: see fulltext.]

Full text of DOI:10.1007/s11164-016-2603-y

Res Chem Intermed
DOI 10.1007/s11164-016-2603-y
Natural phosphate as an efficient and green catalyst
for synthesis of tetraketone and xanthene derivatives
Azadeh Fallah1 Mahmood Tajbakhsh2
•
•
Hooshang Vahedi1 Ahmadreza Bekhradnia3
•
Received: 8 January 2016 / Accepted: 31 May 2016
Ó Springer Science+Business Media Dordrecht 2016
Abstract Natural phosphate was applied as an efficient and ecofriendly catalyst for the
synthesis of tetraketones (2–2.5 h, 90–100 %) and xanthenes (6.5–8.5 h, 84–95 %) via
Knoevenagel–Michael cascade reaction of aromatic aldehydes with 1,3-cyclic diketones
in water and ethanol, respectively. This protocol provides several advantages over the
traditional chemical synthesis, such as simple work-up, easy handling procedure, non-
toxicity and stability of catalyst, low cost and environmental friendliness.
Graphical Abstract
&
Mahmood Tajbakhsh
tajbaksh@umz.ac.ir
1
2
Department of Chemistry, Payame Noor University, P.O. Box 19395-4697, Tehran, Iran
Department of Organic Chemistry, Faculty of Chemistry, University of Mazandaran,
Babolsar 47416-95447, Iran
3
Department of Medicinal Chemistry, Pharmaceutical Sciences Research Center, Mazandaran
University of Medical Sciences, Sari, Iran
123

A. Fallah et al.
Keywords Heterogeneous catalyst
Tetraketone Á Xanthene
Á
Natural phosphate
Á
Fluorapatite
Á
Introduction
Solid catalysts are known as new alternatives to replace homogeneous catalysts due
to advantages including less corrosive action, being easier to handle and separate, as
well as being reusable and generating less amount of toxic wastes [1]. Natural
phosphate (NP) is readily available, cheap, nontoxic and a non-pollutant [2]. NP and
synthetic phosphates such as fluorapatite (FAP, Ca10(PO4)6F2) or hydroxyapatite
(HAP, Ca10(PO4)6(OH)2) [3] were used as efficient catalysts for various organic
transformations, e.g. Knoevenagel condensation [4], transesterification reaction [5],
Michael addition of mercaptans to a,b-unsaturated carbonyl compounds [6],
synthesis of 5-arylhydantoins [7], a-hydroxyphosphonates [8], and Suzuki coupling
reactions [9].
Tetraketone and xanthene derivatives are important classes of oxygen-containing
heterocyclic compounds that have gained much attention owing to their numerous
applications.
They have exhibited antibacterial, antiviral, anti-inflammatory [10, 11] and
biological [12, 13] properties, in addition to their applications in material science.
Apart from quantum dots, which are known as inorganic fluorophores [14–16],
xanthene-based compounds as organic fluorophores are commonly used in
applications due to their brightness, high quantum yields, and low-energy excitation.
Because of the extensive use of these chemicals, the search for efficient and facile
synthesis of these heterocyclic compounds continues to attract much attention. They
are commonly synthesized through the Knoevenagel condensation followed by
Michael addition of carbonyl compounds to 1,3-cyclic diketones employing natural
alumina [17], KF/Al2O3 [18], alumina-sulfuric acid [19], Fe3?-montmorillonite
[20], mesoporous silica nanoparticles (MSN) adsorbed HBF4 [21], silica boron–
sulfuric acid nanoparticles (SBSANs) [22], HY zeolite [23], SmCl3 [24],
tetrabutylammonium hydrogen sulfate (TBAHS) [25], nano Fe/NaY [26], anchored
MnO2 (P-MnO2) [27], and cerium-impregnated-MCM-41 [28] as catalysts.
Although each of these methods has its own benefits, some of them often endure
one or more disadvantages. Hazardous and harsh reaction conditions [17], low yield
and prolonged reaction time [22], expensive reagents, leaving harmful waste on
work-up [21], and tedious work-up procedure [25] are the most important
deficiencies associated with these methods. Therefore, there is still scope for
development of a green and sustainable process.
Herein, we report a convenient, simple, selective and eco-friendly method for the
preparation of tetraketones 3 and xanthenes 4, using clean solvents (water and
ethanol) in combination with NP as a heterogeneous, inexpensive, reusable,
nontoxic and non-corrosive catalyst (Scheme 1).
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Natural phosphate as an efficient and green catalyst for…
Scheme 1 Synthesis of tetraketones 3a–3o and xanthenes 4a–4o
Experimental
Reagents and materials
Chemicals were purchased from Merck and Sigma Chemical Companies. All
products are known compounds and their structures were identified by comparison
of their melting points and spectral data with authentic samples or literature data.
Instrumentation
The chemical composition of NP was determined using PANalytical’s XRF
spectrometer Venus 200. X-ray powder diffractions were performed at room
temperature on a vertical Philips PW1050/25 goniometer mounted in the Bragg–
˚
Brentano configuration (h, 2h) using Ni-filtered Cu–Ka radiation (k = 1.54 A), and
were analyzed by PANalytical X’Pert HighScore Plus software and the standard
data base ICDD-PDF 2004. Scanning electron microscopy (SEM) was obtained on
an EM-3200 instrument. Surface areas were determined at 77 K using a Coulter SA
31000 instrument with an automated gas volumetric method employing nitrogen as
the adsorbate. The pH measurements were performed by a microprocessor pH meter
(Metrohm, model 827 pH lab). Fourier Transform-Infrared (FT-IR) spectra were
1
recorded on a Bruker Tensor 27 spectrometer, using KBr pellets for solids. H and
13C nuclear magnetic resonance (NMR) spectra were recorded on 400 MHz
machine, Bruker Advance DRX spectrometer in DMSO-d6 and CDCl3, using
tetramethylsilane as an internal reference.
123

A. Fallah et al.
General procedure
Preparation of the catalyst
NP was collected from an extracted ore in Yazd, Iran. The phosphate particles were
refluxed and washed with water, calcined at 900 °C for 2.5 h, then was washed again
and recalcined at 900 °C for 0.5 h prior to use as catalyst [3, 29]. The chemical
composition was determined as: P2O5 (37.61 %), CaO (48.53 %), MgO (1.16 %),
SiO2 (4.26 %), Fe2O3 (5.26 %), Cl (0.13 %), TiO2 (0.25 %), Ce2O3 (0.86 %), La2O3
(0.4 %) Nd2O3 (0.42 %), Y2O3 (0.26 %), Al2O3 (0.19 %), MnO (0.08 %), Na2O
(0.28 %), K2O (0.06 %) SO3 (0.32 %) with the Ca/P molar ratio of 1.62.
pH measurement of the catalyst
A suspension of NP in deionized water was stirred at room temperature for 2 h and
kept in closed vessel for 24 h without stirring. The supernatant pH at room
temperature was measured to be 8.2–8.5 [30–32].
Synthesis of tetraketones (3)
A mixture of aromatic aldehyde (1 mmol) and diketone (2 mmol) in water (5 mL)
was prepared. Afterwards, NP (0.5 g) was added and the reaction mixture was
stirred at room temperature. The progress of reaction was monitored by thin-layer
chromatography (TLC) (Silica gel, Hexane: EtOAc, 9:1). After completion of the
reaction, the residue (including crude product and catalyst) was filtered, washed
with water and dried. Then hot ethanol (5 mL) was added to the solid and filtered to
separate the catalyst. Evaporation of the ethanoic filtrate gave crude product
(Scheme 1a). The crude product was purified by recrystallization from ethanol. The
structure of the products was determined by FT-IR, 1H and 13C NMR spectral data,
and compared with data reported in the literatures.
Synthesis of xanthenes (4)
To a solution of aromatic aldehyde (1 mol) and diketone (2 mol) in ethanol
(3–5 mL), NP (1.5 g) was added and then refluxed for an appropriate time to afford
product 4. The reaction progress was monitored by TLC (Silica gel, Hexane:
EtOAc, 7:3). After completion of the reaction, the mixture was filtered and washed
with hot ethanol. Evaporation of the ethanoic filtrate gave xanthene 4 (Scheme 1b).
The obtained products were characterized by their melting point, FT-IR, 1H and 13
C
NMR spectra. Xanthenes 4 could be also prepared from tetraketones 3 (Scheme 1c).
Typically, tetraketone 3 (1 mmol) dissolved in ethanol (3–5 mL) and NP (1.5 g)
was added and refluxed for an appropriate time (Table 3). At the end of the reaction,
the mixture was filtered and washed with hot ethanol. Evaporation of the ethanoic
filtrate gave xanthene 4.
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Natural phosphate as an efficient and green catalyst for…
Selected spectral data
2,20-(4-Nitrophenyl) methylene bis (3-hydroxy-5,5-dimethyl-2-cyclohexene-1-one),
3
g (Table 2, entry 7) White solid; mp 188–190 °C [33]; IR (KBr, cm-1) t = 3426.1,
3069.9, 2958.4, 2871.0, 1592.2, 1513.4, 1375.8, 1345.7, 1248.6, 1159.3, 853.0, 586.6;
1H NMR (400 MHz, CDCl3) d = 11.82 (br, 1H, OH), 8.15 (d, J = 8.8 Hz, 2H, Ar–
H), 7.26 (d, J = 8.8 Hz, 2H, Ar–H), 5.56 (s, 1H, CH), 2.33–2.53 (m, 8H, 4CH2), 1.25
(s, 6H, 2CH3), 1.13 (s, 6H, 2CH3) ppm; 13C NMR (400 MHz, CDCl3) d = 191.0,
189.6, 146.5, 146.1, 127.6, 123.5, 114.9, 47.0, 46.4, 33.3, 31.5, 29.6, 27.4 ppm; Anal.
Calcd. for C23H27NO6: C, 66.81; H, 6.58; N, 3.39. Found: C, 66.79, H, 6.56; N, 3.35.
2,20-(2-Methoxyphenyl) methylene bis (3-hydroxy-5, 5-dimethyl-2-cyclohexene-1-
one), 3o (Table 2, entry 15) White solid; mp 184–186 °C [34]; IR (KBr, cm-1
)
t = 3385.8, 3036.7, 2954.9, 2362.8, 1721.6, 1609.3, 1466.4, 1385.4, 1290.6,
1
1249.2, 1140.4, 1067.0, 743.6; H NMR (400 MHz, CDCl3) d = 11.84 (br, 1H,
OH), 7.22 (d, J = 8 Hz, 2H, Ar–H), 6.91 (td, J = 7.6 Hz, J = 0.8 Hz, 1H, Ar–H),
6.81 (d, J = 8 Hz, 1H, Ar–H), 5.59 (s, 1H, CH), 3.73 (s, 3H, OCH3), 2.35 (s, 8H,
4CH2), 1.12 (s, 12H, 4CH3) ppm; 13C NMR (400 MHz, CDCl3) d = 189.3, 157.1,
128.5, 127.5, 126.8, 120.0, 116.5, 110.1, 55.3, 46.7, 31.2, 29.2 ppm. Anal. Calcd.
for C24H30O5: C, 72.34; H, 7.59. Found: C, 72.29, H, 7.58.
9-(4-Bromo-phenyl)-3,3,6,6-tetramethyl-3,4,5,6,7,9-hexahydro-2H-xanthene-1,8-
)
dione, 4c (Table 3, entry 3) White solid; mp 240–242 °C [35]; IR (KBr, cm-1
1
t = 2952.5, 2875.3, 1658.5, 1361.5, 1197.6, 1004.7; H NMR (400 MHz, CDCl3)
d = 1.00 (s, 6H, 2Me), 1.11 (s, 6H, 2Me), 2.21 (q, 4H, 2CH2), 2.47 (t, 4H, 2CH2),
4.71 (s, 1H, H-9), 7.18 (d, 2H, J = 7.8 Hz, H-Ar), 7.35 (d, 2H, J = 7.8 Hz, H-Ar)
ppm; 13C NMR (400 MHz, DMSO-d6) d = 196.3, 162.4, 143.2, 131.1, 130.2,
120.2, 115.2, 50.7, 40.8, 32.2, 31.6, 29.3, 27.3 ppm. Anal. Calcd. for C23H25BrO3:
C, 64.34; H, 5.87; Br, 18.16. Found: C, 64.32, H, 5.85; Br, 18.59.
4-(3,3,6,6-Tetramethyl-1,8-dioxo-2,3,4,5,6,7,8,9-octahydro-1H-xanthen-9-yl) ben-
zonitrile, 4e (Table 3, entry 5) White solid; mp 222–224 °C [36]; IR (KBr,
cm-1) t = 2952.5, 2875.3, 2260.5, 1660.4, 1471.4, 1361.5, 1197.6, 1151.3, 1004.7,
844.7; 1H NMR (400 MHz, CDCl3) d = 1.00 (s, 6H, 2Me), 1.13 (s, 6H, 2Me), (2.15
(d, 2H, J = 16 Hz, CH2), 2.25 (d, 2H, J = 16 Hz, CH2), 2.50 (brs, 4H, 2CH2)), 4.78
(s, 1H, H-9), 7.43 (d, 2H, J = 8.0 Hz, H-Ar), 7.53 (d, 2H, J = 8.0 Hz, H-Ar) ppm;
13C NMR (400 MHz, CDCl3) d = 196.4, 162.4, 142.7, 132.0, 129.8, 128.2, 115.2,
50.7, 40.8, 32.2, 31.5, 29.33, 27.3 ppm. Anal. Calcd. for C24H25NO3: C, 76.77; H,
6.71; N, 3.73. Found: C, 76.71, H, 6.69; N, 3.71.
Results and discussion
Catalyst characterization
There are several mineralogical classes of natural phosphate that generally belong to
the phosphocalcic apatite family, including (Ca10(PO4)6(OH)2) for hydroxyapatite
123

A. Fallah et al.
and (Ca10(PO4)6F2) for fluorapatite in its pure form [8, 37–39]. The phosphates in
sedimentary rocks are formed by partial isomorphic substitution of compounds
derived from apatite: Ca2? ions by Na?, Mg2?, Co2?, Fe3? or Al3?, PO43- ions by
VO43-, SO42-, CO32- or MnO4- and F- by HO- or Cl-. These substitutions possibly
cause distortions of the structure, depending on the nature and the radii of the ions [2].
The composition of natural phosphates in this study (‘‘Experimental’’ section)
consists of different oxides which phosphorus pentoxide and calcium oxide exist in
higher percent than other oxides [40].
FT-IR spectrum of NP (Fig. 1) shows strong peaks at: 1092, 1044, 600, 576 and
473 cm-1, which could be referred to vibrational modes of P–O, P–O–P bands in
3-
PO4 groups of the apatite structure [41, 42] similar to natural fluorapatite of
Morocco [9] and Tunisia [43].
XRD patterns of NP depicted in Fig. 2a, show relatively sharp reflections in
agreement with the standard patterns [44, 45]. All XRD peaks fit with standard
patterns of fluorapatite (JCPDS 15-876; Fig. 2b) except the diffraction peak around
2h = 28.54° which corresponds to Coesite, SiO2 (JCPDS 72-1601) [46] (Fig. 2c)
and also the diffraction peak around 2h = 32.99° was particularly stronger and
sharper than standard fluorapatite, which might be due to combination of two
diffraction peaks of (3 0 0) direction of fluorapatite and (1 0 4) direction of
Hematite, Fe2O3 (JCPDS 85-0987) [47, 48] (Fig. 2d).
The morphology and average particle size of the NP were characterized by SEM
(Fig. 3). SEM images of NP show that there are porosity and a heterogeneous
microstructure. The results are in good agreement with the earlier studies [3, 9]. The
average particle diameters were measured at around 10–14 and 20–22 lm. Higher
magnifications show that the microsphere shapes contain fine white particles with
the average diameter of 0.1–2 lm dispersed on the surface. However, some
aggregations of particles were observed.
Fig. 1 FT-IR spectrum of NP
123

Natural phosphate as an efficient and green catalyst for…
Fig. 2 XRD patterns of NP and standards
Fig. 3 SEM images of NP
The specific surface area and pore size distribution of NP were measured by the
nitrogen adsorption–desorption isotherms using the BET (Fig. 4a) and BJH
(Fig. 4b) methods. According to IUPAC classification, all the samples exhibit type
IV [49], and a hysteresis loop of type H3. Most particles of NP exhibit mesoporous
nature with a low surface area (BET, 2.081 m2 g-1 and BJH, 1.948 m2 g-1), as well
as a total pore volume (BJH, 7.22 cc g-1), pore volume of 0.007 cc g-1 and
average pore diameter of 0.127 nm.
Synthesis of tetraketones and xanthenes using NP as catalyst
In order to investigate the catalytic activity of NP, treatment of one equivalent of
4-chlorobenzaldehyde with two equivalents of dimedone, as a model reaction was
studied under different reaction conditions (Table 1). As is clear in Table 1, reaction
under solvent-free condition in the presence of NP at 70 °C afforded 3a in 100 % yield
after 12 h (Table 1, entry 1). Reaction was screened in different solvents including
protic and aprotic ones. In all aprotic solvents, a mixture of tetraketone 3a and
xanthene 4a was obtained (Table 1, entries 2–5). Screening temperature, reaction
period, solvent volume and catalyst loadings in protic solvents led to optimal
conditions for the synthesis of 3a (Table 1, entries 6–17) and 4a (Table 1, entries
123

A. Fallah et al.
Fig. 4 a N2 adsorption–desorption isotherm (BET). b Pore size distribution curve (BJH) of NP
Table 1 The optimization of reaction conditionsa
Entry
Catalyst loading
Reaction conditiona (Temp. (°C)/solvent/time (h))
Yieldb 3a/4a (%)
1
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
0.5
–
70/solvent free/12
100/–
70/20
30/30
60/20 (90/10)
70/20 (80/20)
60/30 (80/20)
70/20
99/–
2
100/DMF/6.5
3
160/DMF/6
4
Reflux/CH3CN/4 (13)
Reflux/1,4-dioxane/4 (13)
Reflux/MeOH/3 (6.5)
Reflux/pure EtOH/4
Reflux/EtOH–H2O (1:1)/0.5
Reflux/H2O (3 mL)/0.5
Reflux/H2O (3 mL)/9
Reflux/H2O (3 mL)/0.5
rt/H2O (5 mL)/12
5
6
7
8
9
99/–
10
11
12
13
14
15c
16
17
18
19
20d
21
22e
23e
a
99/–
99/–
98/–
–
rt/EtOH (90 %)/30
96/–
0.25
0.5
–
rt/H2O (3 mL)/4
92/–
rt/H2O (5 mL)/2
98/–
Reflux/EtOH (90 %)/12
rt/EtOH (90 %)/18
62/10
87/–
0.5
0.5
1.0
1.5
2.5
3.5
10.5
Reflux/EtOH (90 %)/8
Reflux/EtOH (90 %)/9
Reflux/EtOH (90 %)/6.5
Reflux/EtOH (90 %)/6
rt/H2O (35 mL)/2
65/35
20/80
–/90
62/38
97/–
Reflux/EtOH (90 %) (21 mL)/8
–/85
Reaction conditions: 4-clorobezaldehyde (1 mmol), dimedone (2 mmol), NP, solvent (3–5 mL)
b
c
d
e
Yields refer to isolated product
Optimal reaction conditions for the synthesis of 3a
Optimal reaction conditions for the synthesis of 4a
Reaction conditions: 4-chlorobenzaldehyde (7mmol), dimedone (14mmol), NP, solvent
123

Natural phosphate as an efficient and green catalyst for…
Table 2 Synthesis of tetraketone 3 by using natural phosphate (NP) as catalyst
O
Ar
O
O
O
NP (0.5 g)
R
R
R
+
H
2
Ar
R
H2O (5 mL), rt
OH
HO
R
R
O
1
2: R= H, CH3
3a-3o
Entry
R
Ar
Product 3
Time (h)
Yielda 3 (%)
1
CH3
H
4-Cl–C6H4
3a
3b
3c
3d
3e
3f
2
98
92
97
96
96
95
100
98
99
98
90
92
90
91
93
2
4-Cl–C6H4
4-Br–C6H4
4-Br–C6H4
4-CN–C6H4
4-CN–C6H4
4-NO2–C6H4
4-NO2–C6H4
2,4-di-Cl–C6H3
2,4-di-Cl–C6H3
2-OH–C6H4
4-Me–C6H4
C6H5
2
3
CH3
H
2
4
2
5
CH3
H
2
6
2
7
CH3
H
3g
3h
3i
2
8
2
9
CH3
H
2
10
11
12
13
14
15
3j
2
CH3
CH3
CH3
H
3k
3l
2.5
2.5
2.5
2.5
2.5
3m
3n
3o
C6H5
CH3
2-OMe–C6H4
Reaction conditions: aldehyde (1 mmol), 1,3-diketone (2 mmol), NP (0.5 g), H2O (5 mL) at rt
a
Yields refer to isolated product
18–21). When one equivalent of 4-chlorobenzaldehyde reacted with two equivalents
of dimedone in H2O in the presence of NP (0.5 g) at room temperature, 3a was formed
as the sole product in 98 % yield after 2 h (Table 1, entry 15), while this reaction in
refluxing EtOH (90 %) in the presence of NP (1.5 g) afforded only 4a in 90 % yield
after 6.5 h (Table 1, entry 20). The model reaction in the absent of catalyst at room
temperature gave high yield of 3a in H2O after 12 h and in EtOH (90 %) after 30 h
(Table 1, entries 12 and 13). From the results in Table 1, it is concluded that in H2O, 3a
is not converted to 4a even at higher temperature and longer reaction time (Table 1,
entries 9–11). This could be due to ability of H2O to form hydrogen bonding with
diketone to prevent the formation of 4a. In refluxing ethanol, 3a is converted to 4a after
6.5 h, probably due to the lower tendency of ethanol to hydrogen bonding with
diketone compared with H2O (Table 1, comparing entry 15 with entry 20). The model
reactions in large scale (7 equivalents of 4-chlorobenzaldehyde and 14 equivalents of
dimedone) under the optimal reaction conditions went smoothly, to achieve the
expected products in high yields (Table 1, entries 22 and 23).
To investigate the scope and generality of the application of NP as an efficient
catalyst for the synthesis of tetraketones 3 (Table 2) and xanthenes 4 (Table 3),
123

A. Fallah et al.
Table 3 Synthesis of xanthene 4 by using natural phosphate (NP) as catalyst
O
O
Ar
O
O
R
R
NP (1.5 g)
+
2
Ar
H
R
R
EtOH (90%) (3 mL), reflux
O
O
R
R
1
2: R= H, CH3
4a-4o
Entry
R
Ar
Product 4
Time (h)
Yielda 4 (%)
1
CH3
H
4-Cl–C6H4
4-Cl–C6H4
4-Br–C6H4
4-Br–C6H4
4-CN–C6H4
4-CN–C6H4
4-NO2–C6H4
4-NO2–C6H4
2,4-di-Cl–C6H3
2,4-di-Cl–C6H3
2-OH–C6H4
4-Me–C6H4
C6H5
4a
4b
4c
4d
4e
4f
6.5
6.5
7
90
92
93
91
91
93
95
94
91
90
85
84
86
84
85
2
3
CH3
H
4
6.5
7
5
CH3
H
6
7
7
CH3
H
4g
4h
4i
6.5
6.5
8
8
9
CH3
H
10
11
12
13
14
15
4j
8
CH3
CH3
CH3
H
4k
4l
8
8.5
8.5
8.5
8
4m
4n
4o
C6H5
CH3
2-OMe–C6H4
Reaction conditions: aldehyde 1 (1 mmol), 1,3-diketone 2 (2 mmol), NP (1.5 g) in refluxing EtOH
(90 %) (3–5 mL)
a
Yields refer to isolated product
Fig. 5 The recycling studies for the model reaction using NP under optimal reaction conditions
123

Natural phosphate as an efficient and green catalyst for…
Fig. 6 SEM images of the recycled NP
Table 4 Synthesis of tetraketone, 3a, and xanthene, 4a using different catalysts/methods
Entry
Catalyst
Reaction condition
(Temp./solvent/time (h))
Yield 3a/4a (%)
References
1
Fe3O4
60 °C/anhydrous EtOH/–
rt/H2O/1.5
62/–
95/–
81/
[14]
2
Fe3O4@SiO2–SO3H
Natural alumina
SiO2
[55]
3
MW/solvent free/0.16
rt/solvent free/2
Reflux/EtOH/4
[17]
4
42/–
–/83
–/97
–/95
–/75
–/98
–/88–98
–/88
98/–
97/–
–/90
[50]
5
Alumina-sulfuric acid
Fe?3-montmorillonite
SBSANa
PANI-PTSAb
SBSSAc
[19]
6
100 °C/EtOH/6
50 °C/solvent-free/2
Reflux/H2O/6
[20]
7
[22]
8
[53]
9
Reflux/EtOH/10
Reflux/EtOH/0.25
Reflux/EtOH/3
[54]
10
11
12
13
14
a
Nano ZnAl2O4
SBNPSAd
NP
[51]
[52]
rt/H2O/2
This work
This work
This work
NP
rt/H2O: EtOH (1:1)/2
80 °C/EtOH (90 %)/6.5
NP
Silica boron-sulfuric acid nano particles (SBSAN)
Poly aniline-p-toluenesulfonate salt (PANI-PTSA)
Silica bonded s-sulfonicacid (SBSSA)
b
c
d
Silica bonded N-pyropyl sulphamic acid (SBNPSA)
various aldehydes reacted with 1,3-diketones under the optimized conditions and
results are presented in Tables 2 and 3. As is clear in these tables, aldehydes bearing
both electron-withdrawing and electron-donating substituents readily participated in
these reactions and formed the desired products. The nature of substituents on the
1,3-diketone did not show significant influence.
One of the most pivotal advantages of NP catalyst in organic synthesis is their
ease of separation by filtration. After the completion of the reaction, NP was
separated from the reaction mixture by simple filtration, washed with acetone or
ethanol, calcined at 900 °C for 0.5 h and the recycling studies were then performed
123

A. Fallah et al.
Natural phosphate
Natural phosphate
O
P
O
O
O
O
O
O
O
O
O
Ca
O
Ca
O
O
O
O
O
P
P
P
O
O
H
O
OH
O
O
H
O
O
O
O
H
Ar
Ar
2
R
R
Knovenagle
condensation
R
R
[I]
1
Natural phosphate
O
P
O
O
O
O
-H2O
Ca
O
O
O
P
O
H
Ar
O
O
O
H
O
H
Micheal addition
Ar
R
R
R
O
O
O
O
R
R
R
[II]
1
Ar
O
O
Ar
O
Ar
O
O
O
R
R
EtOH
R
O
HO
R
R
R
R
R
O
OH
HO
H
R
R
R
R
4
3
O
Ca
O
O
O
O
O
P
P
O
O
O
Natural phosphate
Scheme 2 Suggested mechanism for synthesis of tetraketone and xanthene derivatives catalyzed by
natural phosphate (NP)
thorough the utilization of separated catalyst in subsequent reactions (for the
synthesis of 3a and 4a) at least four times without significant loss in its catalytic
activity (Fig. 5). A slight reduction in catalyst activity observed for the recycled NP
could be due to catalyst pollution with reagents.
Surface morphology of sixth recycled NP was investigated by using SEM
(Fig. 6). As depict in Fig. 5, the recycled NP shows no change in shape. It contains
particles with an average diameter of 0.28–0.59 lm due to the agglomeration of NP
and surface growth of NP particles.
In order to attain a deeper insight into NP as efficient catalyst for the synthesis of
tetraketone and xanthene derivatives, an evaluation was performed with the other
comparable catalysts/methods (Table 4). According to the data reported in the
literature for the synthesis of compounds 3a and 4a, NP is considered as a good
catalyst compared with those in Table 4. The present procedures not only afford the
products in excellent yield in short reaction times, but also avoid problems
123

Natural phosphate as an efficient and green catalyst for…
associated with catalyst cost, difficult preparation and handling, tedious work-up,
safety and pollution (Table 4, entries 12–14).
A possible mechanism for this transformation is proposed in Scheme 2.
Relatively natural phosphate has been extensively used as a basic [30, 56–58]
catalyst in synthetic applications. First, the basic sites (oxygens of phosphate group
and calcium oxide on NP surface) absorbed the proton from the active methylene
compounds and catalyzed Knoevenagle condensation [57], to form the intermediate
I. Subsequently, dehydration took place to generate the intermediate II [58, 59],
which was attacked by another activated 1, 3-cyclic diketone (Michael addition) [6]
to give the tetraketon 3. Dehydration and aromatization of 3 afforded the xanthene 4
in EtOH (90 %) as solvent [40].
Conclusion
In summary, we have developed a new, convenient, environmental friendly and
green synthesis of tetraketone and xanthene derivatives in good to excellent yields
via Knoevenagel–Michael cascade reactions of aryl aldehydes with 1,3-diketones by
using NP as heterogeneous catalyst. These methodologies are applicable to
demonstrate their potential for commercial purposes. In contrast to earlier ones, this
synthesis does not employ any harmful and expensive catalysts. The NP can be used
as catalyst due to its special properties such as easy handling, non-toxicity, and
stability in air, inexpensiveness and reusability. These results open the way for the
use of this inexpensive and eco-friendly solid as basic catalyst for other
applications.
Acknowledgments We are grateful to the Payame Noor University (PNU) for their partial support and
the Mazandaran University of Medical Sciences for providing laboratory facilities to carry out this
research.
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