Nanocrystalline TiO2-HClO4 catalyzed three-component preparation of derivatives of 1-amidoalkyl-2-naphthol, 1-carbamato-alkyl-2- naphthol, 1-(α-aminoalkyl)-2-naphthol, and 12-aryl-8,9,10,12- tetrahydrobenzo[a]-xanthen-11-one

Article abstract of DOI:10.1007/s11164-012-0938-6

1-Amidoalkyl-2-naphthols, 1-carbamatoalkyl-2-naphthols, and 1-(α-aminoalkyl)-2-naphthols have been prepared by three-component reaction of 2-naphthol, aromatic aldehydes, and NH compounds, i.e. amides, carbamates, and secondary amines, respectively, in th

Full text of DOI:10.1007/s11164-012-0938-6

Res Chem Intermed
DOI 10.1007/s11164-012-0938-6
Nanocrystalline TiO2–HClO4 catalyzed three-
component preparation of derivatives of 1-amidoalkyl-
2-naphthol, 1-carbamato-alkyl-2-naphthol, 1-(a-
aminoalkyl)-2-naphthol, and 12-aryl-8,9,10,12-
tetrahydrobenzo[a]-xanthen-11-one
•
Hamid Reza Shaterian Majid Mohammadnia
Received: 29 October 2012 / Accepted: 17 November 2012
Ó Springer Science+Business Media Dordrecht 2012
Abstract 1-Amidoalkyl-2-naphthols, 1-carbamatoalkyl-2-naphthols, and 1-(a-
aminoalkyl)-2-naphthols have been prepared by three-component reaction of
2-naphthol, aromatic aldehydes, and NH compounds, i.e. amides, carbamates, and
secondary amines, respectively, in the presence of a catalytic amount of nano-
crystalline TiO2–HClO4. In addition, 12-aryl-8,9,10,12-tetrahydrobenzo[a]-xan-
then-11-one derivatives have been synthesized by reaction of 2-naphthol, aromatic
aldehydes, and dimedone in the presence of the same nano catalyst. These reactions
were studied under solvent-free conditions. This white acidic heterogeneous catalyst
is very stable under the reaction conditions and was reused several times without
significant loss of activity.
Keywords Nanocrystalline Á TiO2–HClO4 Á Reusable catalyst Á
Three-component reactions
Introduction
Nano particles of TiO2 can catalyze reactions because of their low Lewis-acidic
properties [1–3]. Recently, perchloric acid-coated TiO2 nanoparticles have been
prepared [4]. This catalyst (nanoTiO2–HClO4) has been used for trimethylsilylation
of hydroxyl groups and cleavage of trimethylsilyl ethers [4]. The catalyst is easily
prepared from a suspension of HClO4 and nano TiO2 (particle size 30–40 nm and
BET specific area 34 m2 g-1) [4]. Transmission electron microscopic analysis of
H. R. Shaterian (&) Á M. Mohammadnia
Department of Chemistry, Faculty of Sciences, University of Sistan and Baluchestan,
PO Box 98135-674, Zahedan, Iran
e-mail: hrshaterian@chem.usb.ac.ir
123

H. R. Shaterian, M. Mohammadnia
OH
CHO
+
O
nano TiO2-HClO4 (Catalyst)
NH2 90 o
NH
X
+
X
H3C
C
,Solvent-free
O
OH
H3C
(4)
(1)
(3)
(2)
Scheme 1 Synthesis of 1-amidoalkyl-2-naphthols
TiO2–HClO4 showed that the nano catalyst aggregated after modification with
HClO4, with TiO2 particle size increasing to 150 nm.
Multi-component reactions have proved a valuable asset in organic and
medicinal chemistry; such procedures can be used for drug design and drug
discovery, because of their simplicity, efficiency, and high selectivity [5, 6].
Synthesis of bioactive and complex molecules by this methodology is facile, rapid,
and efficient, with minimum workup [5–7].
Compounds containing 1,3-amino oxygenated functional groups for example
1-amidoalkyl-2-naphthols, 1-carbamatoalkyl-2-naphthols, and 1-(a-aminoalkyl)-2-
naphthols are frequently found in biologically active natural products and potent
drugs, for example nucleoside antibiotics and HIV protease inhibitors [8–11].
12-Aryl-8,9,10,12-tetrahydrobenzo[a]-xanthen-11-one derivatives have attracted
much interest because of their varied biological activity for example anti-
inflammatory [12], antiviral [13], and antibacterial [14].
In continuation of our research on new synthetic methods in organic synthesis
using heterogeneous catalysts [15, 16], we developed the synthesis of 1-amidoalkyl-
2-naphthols (Scheme 1), 1-carbamato-alkyl-2-naphthols (Scheme 2), and 1-(a-
aminoalkyl)-2-naphthols (Scheme 3) under solvent-free conditions in the presence
of catalytic amounts of nanocrystalline titania coated with perchloric acid
(NanoTiO2–HClO4). In addition, preparation of 12-aryl-8,9,10,12-tetra-
hydrobenzo[a]-xanthen-11-one derivatives under thermal, solvent-free conditions
in the presence of the same catalyst is reported (Scheme 4).
Experimental
Chemicals and materials
All reagents were purchased from Merck and Aldrich and were used without further
purification. All yields refer to isolated products after purification. NMR spectra
were recorded on a Bruker Avance DPX 300 MHz instrument. Spectra were
measured in DMSO-d6 relative to TMS (0.00 ppm). IR spectra were recorded on a
Jasco FT-IR 460 plus spectrophotometer. Melting points were determined in open
capillaries with a Buchi 510 melting-point apparatus. TLC was performed on silica-
gel Poly Gram SIL G/UV 254 plates.
123

Nanocrystalline TiO2–HClO4 Catalyzed Three-Component Preparation
OH
NH
CHO
+
O
nano TiO2-HClO4 (Catalyst)
NH2 90 oC
X
+
X
H3CO
,Solvent-free
O
OH
H3CO
(8)
(5)
(6)
(7)
Scheme 2 Synthesis of 1-carbamato-alkyl-2-naphthols
OH
R1
R2
CHO
+
N
nano TiO2-HClO4 (Catalyst)
R1
R2
X
+
N
X
H
Room temperature, Solvent-free
OH
(12)
(9)
(10)
(11)
Scheme 3 Synthesis of 1-(a-aminoalkyl)-2-naphthols
O
O
CHO
+
nano TiO2-HClO4 (Catalyst)
90 o
X
+
C
,Solvent-free
O
OH
O
X
(13)
(14)
(15)
(16)
Scheme 4 Synthesis of 12-aryl-8,9,10,12-tetrahydrobenzo[a]-xanthen-11-ones
Preparation of titania-supported perchloric acid (TiO2–HClO4) [4]
A suspension of nano TiO2 (2 g) in Et2O (30 mL) was prepared. HClO4 (0.14 g,
1 mmol, as a 70 % aq. solution) was then added dropwise to the stirred suspension
at room temperature. The mixture was stirred for 24 h. The mixture was
concentrated and the residue was heated at 100 °C for 2 h under vacuum to furnish
TiO2–HClO4 (0.013 mmol g-1) as a white powder.
General procedure for preparation of 1-amidoalkyl-2-naphthols
Nano TiO2–HClO4 (5 mg) was added to a mixture of 2-naphthol (1 mmol),
aldehyde (1 mmol), and acetamide (1.2 mmol). The mixture was stirred at 90 °C in
an oil bath and the reaction was followed by TLC. After completion of the reaction,
it was cooled to room temperature. The mixture was then diluted with dichloro-
methane and the catalyst was separated by centrifugation and washed with CH2Cl2
(2 9 5 mL) to check the reusability. The decanted solution containing the product
123

H. R. Shaterian, M. Mohammadnia
was evaporated to give the crude solid product which was recrystallized from
aqueous EtOH (15 %).
Spectral details for two known products are given below.
N-[Phenyl-(2-hydroxynaphthalen-1-yl)methyl]acetamide (4a): mp 242–243 °C;
IR (KBr, cm-1): 3398, 3251, 3063, 1645, 1588, 1520, 1377, 1339, 1061, 818, 745,
1
699, 618; H NMR (300 MHz, DMSO-d6) d = 1.99 (s, 3H), 7.20–1.11 (m, 4H),
7.26–7.23 (m, 4H), 7.34 (t, J = 7.4 Hz, 1H), 7.77 (d, J = 9.1 Hz, 1H), 7.82 (d,
J = 8.1 Hz, 1H), 7.85 (s, 1H), 8.47 (d, J = 8.6 Hz, 1H), 10.03 (s, 1H) ppm; 13C
NMR (75 MHz, DMSO-d6): 23.1, 40.6, 119.4, 119.5, 122.8, 123.7, 126.6, 126.6,
128.4, 128.7, 128.9, 129.4, 129.5, 132.2, 143.2, 153.7, 169.2 ppm.
N-[(3-Nitrophenyl)-(2-hydroxynaphthalen-1-yl)methyl]acetamide
(4i):
mp
237–239 °C; IR (KBr, cm-1): 3377, 3090, 2595, 1644, 1530, 1351, 1233, 1152,
1063, 818, 707; 1H NMR (300 MHz, DMSO-d6) d = 2.02 (s, 3H), 7.15 (t,
J = 8.1 Hz, 1H), 7.18 (d, J = 8.5 Hz, 1H), 7.24 (t, J = 7.3 Hz, 1H), 7.35 (t,
J = 7.3 Hz, 1H), 7.52 (m, 2H), 7.74 (t, J = 8.5 Hz, 2H), 7.84 (br, 1H), 7.96–7.99
(m, 2H), 8.57 (d, J = 8.1 Hz, 1H), 10.15 (s, 1H) ppm; 13C NMR (75 MHz, DMSO-
d6): 23.2, 48.3, 118.4, 118.8, 120.8, 121.7, 123.2, 127.2, 123.3, 128.8, 129.1, 130.2,
130.4, 132.6, 133.5, 145.8, 148.1, 153.8, 170.4 ppm.
General procedure for preparation of 1-carbamatoalkyl-2-naphthol derivatives
Nano TiO2–HClO4 (5 mg) was added to a mixture of 2-naphthol (1 mmol),
aldehyde (1 mmol), and methyl carbamate (1.2 mmol). The mixture was stirred at
90 °C in an oil bath and the reaction was followed by TLC. After completion of the
reaction, it was cooled to room temperature. The mixture was then diluted with
dichloromethane and the catalyst was separated by centrifugation and washed with
CH2Cl2 (2 9 5 mL) to check the reusability. The decanted solution containing the
product was evaporated to give the crude solid product which was purified by
recrystallization from aqueous EtOH (20 %).
Spectral details for two known products are given below.
Methyl (2-hydroxynaphthalen-1-yl)(phenyl)methyl carbamate (8a): mp
220–221 °C; IR (KBr, cm-1): 3424, 3204, 1680, 1635, 1590, 1522, 1440, 1340,
1275, 1065, 1042, 938, 811, 743, 697; 1H NMR (300 MHz, DMSO-d6) d = 3.58 (s,
3H), 6.88 (d, J = 8.5 Hz, 1H), 7.19–7.29 (m, 7H), 7.37 (d, J = 7.3 Hz, 1H),
7.67–7.85 (m, 3H), 7.90 (d, J = 7.6 Hz, 1H), 10.13 (s, 1H, OH) ppm; 13C NMR
(75 MHz, DMSO-d6): d 50.6, 52.2, 118.7, 119.5, 123.1, 123.6, 126.6, 126.9, 127.1,
128.7, 128.9, 129.1, 129.9, 132.5, 142.7, 153.4, 157.2 ppm.
Methyl (2-hydroxynaphthalen-1-yl)(4-nitrophenyl)methyl carbamate (8e): mp
209–211 °C; IR (KBr, cm-1): 3425, 3267, 1687, 1627, 1605, 1514, 1433, 1342,
1271, 1249, 1069, 1047, 852, 824, 785, 741, 704; H NMR (300 MHz, DMSO-d6)
1
d = 3.62 (s, 3H), 6.97 (d, J = 8.2 Hz, 1H), 7.20 (d, J = 8.7 Hz, 1H), 7.27 (t,
J = 7.1 Hz, 1H), 7.38 (d, J = 7.8 Hz, 1H), 7.48 (d, J = 8.6 Hz, 2H), 7.78–7.88 (m,
4H), 8.15 (d, J = 8.5 Hz, 2H), 10.21 (s, 1H, OH) ppm; 13C NMR (75 MHz, DMSO-
d6): d = 50.7, 52.4, 118.5, 118.9, 123.2, 123.3, 123.9, 127.4, 127.7, 128.7, 129.2,
130.5, 132.5, 146.6, 151.4, 153.5, 157.1 ppm.
123

Nanocrystalline TiO2–HClO4 Catalyzed Three-Component Preparation
General procedure for preparation of 1-(a-aminoalkyl)-2-naphthol derivatives
A mixture of 2-naphthol (1.0 mmol), amine (1.0 mmol), and aldehyde (1.2 mmol)
was stirred at room temperature in the presence of nano TiO2–HClO4 (5 mg) as
catalyst for an appropriate time. After completion of the reaction (indicated by
TLC), the reaction mixture was dissolved in hot ethanol, the catalyst was recovered
by filtration, and the product was recrystallized from ethanol.
Spectral details for two known products are given below.
1-((3-Bromophenyl)(piperidin-1-yl)methyl)naphthalen-2-ol(12b):mp185–186 °C;
white solid; IR (KBr, cm-1): 3128, 3052, 2964, 2851, 1660, 1455, 1236, 755; 1H NMR
(300 MHz, DMSO-d6) d = 1.68 (br, s, 6H, –CH2), 2.78 (br, s, 4H, –NCH2), 5.04(s, 1H,
CH), 7.08–7.17 (m, 2H, ArH), 7.19-7.25 (m, 1H, ArH), 7.32–7.41(m, 2H, ArH),
7.48–7.51 (d, J = 5.55 Hz, 1H, ArH) 7.65 (t, J = 9.94 Hz, 3H, ArH), 7.77 (d,
J = 8.57 Hz, 1H, ArH), 13.72(s, 1H, OH).13CNMR(75 MHz, DMSO-d6)d = 24.02,
25.93, 71.45, 115.39, 120.01, 120.72, 122.41, 126.47, 127.64, 128.59, 128.90, 129.61,
130.37, 131.02, 132.15, 142.00, 155.
1-((4-Chlorophenyl)(dimethylamino)methyl)naphthalen-2-ol
(12g):
mp
130–132 °C; white solid; IR (KBr, cm-1): 3129, 3061, 2976, 2848, 1629,
1462, 1240, 758; 1H NMR (300 MHz, DMSO-d6) d = 2.34 (s, 6H, –NCH3), 4.95
(s, 1H, CH), 7.08–7.45 (m, 4H, ArH), 7.50–7.53 (m, 3H, ArH), 7.65–7.83 (m, 3H,
ArH), 9.98 (s, 1H, ArH). 13C NMR (75 MHz, DMSO-d6) d = 41.54, 72.76,
116.32, 119.85, 121.14, 122.38, 126.42, 127.70, 128.48, 128.67, 128.83, 128.89,
129.75, 131.21, 142.37, 155.20.
General procedure for preparation of 12-aryl-8,9,10,12-tetrahydrobenzo[a]-
xanthen-11-ones
A mixture of 2-naphthol (1 mmol), dimedone (1 mmol), aldehyde (1 mmol), and
nano TiO2–HClO4 (5 mg) was stirred in an oil-bath (90 °C). After completion of the
reaction, the mixture was cooled to room temperature. The mixture was then diluted
with dichloromethane, and the catalyst was separated by centrifugation and washed
with CH2Cl2 (2 9 5 mL) to checking the reusability. The decanted solution
containing the product was evaporated to give the crude solid product which was
purified by recrystallization from aqueous ethanol (90 %).
Spectral details for two known products are given below.
9,9-Dimethyl-12-(2-bromophenyl)-8,9,10,12-tetrahydrobenzo[a]xanthen-11-one
1
(16f): mp 171–172 °C; IR (KBr, cm-1): 2955, 1652, 1596, 1373, 1228, 1185. H
NMR (300 MHz, DMSO-d6) d = 0.97 (s, 3H), 1.11 (s, 3H), 2.25 (d, J = 16.3 Hz,
1H), 2.33 (d, J = 16.2 Hz, 1H), 2.58 (s, 2H), 5.68 (s, 1H), 7.21–7.24 (m, 2H),
7.27–7.35 (m,3H), 7.39–7.46 (m, 2H), 7.76–7.81 (m, 2H), 7.88 (d, J = 8.2 Hz,
1H), 13C NMR (75 MHz, DMSO-d6): d = 27.1, 29.2, 32.2, 34.1, 41.2, 50.7, 113.8,
116.9, 117.0, 120.1, 123.4, 125.1, 127.1, 128.6, 129.2, 130.2, 131.3, 131.2, 131.6,
143.8, 147.5, 164.1, 196.9.
9,9-Dimethyl-12-m-tolyl-8,9,10,12-tetrahydrobenzo[a]xanthen-11-one (16j): mp
179–181 °C; IR (KBr, cm-1): 2955, 1648, 1598, 1373, 1229, 1186. 1H NMR
(300 MHz, DMSO-d6) d = 0.98 (s, 3H), 1.11 (s, 3H), 2.18 (s, 3H), 2.24 (d,
123

H. R. Shaterian, M. Mohammadnia
Table 1 Optimization of conditions for preparation of N-[(4-chlorophenyl)-(2-hydroxynaphthalen-1-
yl)methyl]acetamide from 4-chlorobenzaldehyde, 2-naphthol, and acetamide in the presence of different
amounts of nano TiO2–HClO4 as catalyst and at different temperatures under solvent-free conditions
Entry
Catalyst (mg)
Temperature (°C)
Time (min)
Yield (%)a
1
2
3
4
5
6
a
15
10
7
25
60
60
90
90
90
60
50
45
13
10
10
Trace
35
50
2
83
5
94
8
95
Yields are for isolated pure product
J = 16.2 Hz, 1H), 2.31 (d, J = 16.2 Hz, 1H), 2.55 (s, 2H), 5.67 (s, 1H), 6.97 (d,
J = 8.0 Hz, 2H), 7.22–7.30 (m, 2H), 7.32–7.38 (m, 2H), 7.42–7.46 (m, 1H),
7.34–7.78 (m, 2H), 8.1 (d, J = 8.5 Hz, 1H). 13C NMR (75 MHz, DMSO-d6):
d = 20.9, 27.2, 29.2, 32.2, 34.2, 41.4, 50.9, 114.5, 117.0, 117.9, 123.6, 124.8, 126.7,
128.2, 128.3, 128.6, 128.9, 131.4, 131.5, 135.6, 141.8, 147.8, 163.8, 196.8,
Results and discussion
To study the effect of catalyst loading and temperature, the three component
condensation reaction used for synthesis of N-[(4-chlorophenyl)-(2-hydroxynaphth-
alen-1-yl)methyl]acetamide from 4-chlorobenzaldehyde, 2-naphthol, and acetam-
ide, in the presence of nano TiO2–HClO4 as catalyst, was selected as model reaction
under solvent-free conditions (Table 1). The reaction was performed with different
amounts of nano TiO2–HClO4 as catalyst (2, 5, 7, 8, 10, 15 mg) and at different
temperatures (25, 60, 90 °C). As is apparent from Table 1, 5 mg nano TiO2–HClO4
as a catalyst at 90 °C afforded the product in 10 min with 94 % yield.
Next, the three-component condensation reaction of aromatic aldehydes,
2-naphthol, and acetamide under the optimized conditions was investigated for
preparation of 1-amidoalkyl-2-naphthol derivatives. A wide range of substituted and
structurally diverse aldehydes, with nano TiO2–HClO4 as catalyst, enabled synthesis
of the corresponding products in high to excellent yields (Table 2).
Recycling of the nano TiO2–HClO4 was studied using reaction of 4-chlorobenz-
aldehyde, 2-naphthol, and acetamide as model reaction (Experimental section). The
recovered catalyst was reused six times without significant loss of its activity
(Fig. 1).
To show the merit of this work in comparison with results reported in the
literature, we compared the result obtained by use of nano TiO2–HClO4 with those
obtained by use of reported catalysts used for synthesis of N-[(4-chlorophenyl)-(2-
hydroxynaphthalen-1-yl)methyl]acetamide. As shown in Table 3, nano TiO2–
HClO4 acts as a suitable catalyst with regard to reaction times and product yield
(Table 3).
123

Nanocrystalline TiO2–HClO4 Catalyzed Three-Component Preparation
Table 2 Three-component synthesis of 1-amidoalkyl-2-naphthol derivatives by reaction of aldehydes,
2-naphthol, and acetamide in the presence of nano TiO2–HClO4 (5 mg) as catalyst
Entry
Aldehyde
Product
Time (min)
Yield (%)a
Melting point
m.p (°C)/L m.p (°C) [Ref.]
1
PhCHO
4a
4b
4c
4d
4e
4f
9
10
11
10
12
11
10
12
11
10
11
91
94
93
89
92
90
89
91
89
90
91
242–243/(241–243) [17]
223–225/(224–227) [17]
204–207/(203–205) [18]
196–198/(194–196) [18]
204–206/(203–205) [19]
201–202/(200–202) [20]
249–251/(248–250) [21]
234–236/(235–236) [19]
237–239/(236–237) [18]
228–229/(220–230) [21]
227–228/(228–230) [19]
2
4-ClC6H4CHO
4-FC6H4CHO
3
4
2-ClC6H4CHO
3-MeOC6H4CHO
2-MeC6H4CHO
4-NO2C6H4CHO
3,4-diMeOC6H3CHO
3-NO2C6H4CHO
4-MeC6H4CHO
4-BrC6H4CHO
5
6
7
4g
4h
4i
8
9
10
11
a
4j
4k
Yields are for isolated pure products
Known pure products were characterized by comparison of their physical data (melting points, IR, 1H and
13C NMR) with those of the known compounds
97
95
94
93
100
90
80
70
60
50
40
30
20
10
0
91
89
1
2
3
4
5
6
Reaction cycles
Fig. 1 Recycling of nano TiO2–HClO4 as catalyst in the preparation of N-[(4-chlorophenyl)-(2-
hydroxynaphthalen-1-yl)methyl]acetamide
We also used nano TiO2–HClO4 in the condensation reaction of 2-naphthol,
aldehyde, and methyl carbamate under solvent-free conditions for preparation of
1-carbamato-alkyl-2-naphthol derivatives (Scheme 2). Reaction of 4-chlorobenzal-
dehyde, 2-naphthol, and methyl carbamate was selected as model. The reaction was
performed in the presence of different amounts of catalyst, nano TiO2–HClO4 (2, 5,
7, 8, 10, 15 mg), and at different temperatures (25, 60, 90 °C) under solvent-free
conditions. The best results were obtained with 5 mg nano TiO2–HClO4 at 90 °C.
The three-component condensation reaction of aromatic aldehydes, 2-naphthol, and
methyl carbamate under optimized conditions for preparation of 1-carbamato-alkyl-
123

H. R. Shaterian, M. Mohammadnia
Table 3 Comparison the results of nano TiO2–HClO4 with catalysts reported for synthesis of N-[(4-
chlorophenyl)-(2-hydroxynaphthalen-1-yl)methyl]acetamide under solvent-free conditions
Entry Catalyst
Conditions
Time Yield (%)a
(min) [Ref.]
1
2
Ferric hydrogen sulfate (5 mol %)
Solvent-free, 85 °C
25
88 [19]
85 [22]
N-(4-Sulfonic acid) butyl triethyl ammonium Solvent-free, 120 °C 10
hydrogen sulfate (5 mol %)
3
4
5
6
a
Bi(NO3)3.5H2O (20 mol %)
Nano-sulfated zirconia (0.2 g)
[Bmim]Br (1 g)
Solvent-free, 80 °C
Solvent-free, 120 °C 35
Solvent-free, 130 °C 30
90
92 [23]
92 [24]
90 [25]
Nano TiO2–HClO4(5 mg)
Solvent-free, 90 °C
10
94 (this work)
Yields are for isolated pure products and are based on reaction of 4-chlorobenzaldehyde, 2-naphthol,
and acetamide
Table 4 Three-component synthesis of 1-carbamato-alkyl-2-naphthol derivatives by reaction of alde-
hydes, 2-naphthol, and methyl carbamate in the presence of nano TiO2–HClO4 (5 mg) as catalyst under
solvent-free conditions at 90 °C
Entry
Aldehyde
Product
Time (min)
Yield (%)a
Melting point
m.p (°C)/L m.p (°C) [Ref.]
1
2
3
4
5
6
7
8
9
a
PhCHO
8a
8b
8c
8d
8e
8f
3
3
90
94
89
91
90
92
90
–
220–221/(217–218) [26]
202–203/(198–200) [26]
199–201/(196–198) [26]
195 dec/(192 dec) [26]
209–211/(205–207) [26]
223 dec/(215 dec) [26]
251 dec/(252 dec) [26]
–
4-ClC6H4CHO
3-ClC6H4CHO
2,4-diClC6H4CHO
4-NO2C6H4CHO
2,5-diMeOC6H3CHO
3-NO2C6H4CHO
Propanal
4
3
5
3
8g
8h
8i
4
50
50
n-Heptanal
–
–
Yields are for isolated pure products
Known pure products were characterized by comparison of their physical data (melting points, IR, 1H and
13C NMR) with those of the known compounds
2-naphthol derivatives was then investigated (Table 4). A wide range of substituted
and structurally diverse aldehydes were used and the corresponding products were
synthesized in high to excellent yields, which demonstrated that this method
tolerates both electron-withdrawing and electron-donating constituents (Table 4).
We then examined aliphatic aldehydes, for example propanal and n-heptanal,
instead of benzaldehyde in the reaction. Then, all the starting materials in the
reaction remained intact without formation of any side products (for example the
aldol condensation product) after 50 min (Table 4, Entries 8, 9).
Recycling of the nano TiO2–HClO4 was studied for this reaction also. The
recovered catalyst was reused in six runs without significant loss of its activity
(Fig. 2).
123

Nanocrystalline TiO2–HClO4 Catalyzed Three-Component Preparation
96
95
93
100
90
80
70
60
50
40
30
20
10
0
92
90
89
1
2
3
4
5
6
Reaction cycles
Fig. 2 Recycling of nano TiO2–HClO4 as catalyst in the preparation of methyl (4-chlorophenyl)(2-
hydroxynaphthalen-1-yl)methyl carbamate
To show the applicability of this work in comparison with results reported in the
literature, for example for use of silica-supported sodium hydrogen sulfate (0.05 g)
at 100 °C [26] and 4-(1-imidazolium)butane sulfonate (10 mol %) at 80 °C [27], we
summarized some of the results for preparation of methyl (4-chlorophenyl)(2-
hydroxynaphthalen-1-yl)methyl carbamate in Table 5. The results show that nano
TiO2–HClO4 (5 mg under ambient and solvent-free conditions) is the most efficient
catalyst with regard to reaction time; the yields obtained are also indicative of its
wide applicability.
In continuation of our research on new applications of the catalyst, preparation of
1-(a-aminoalkyl)-2-naphthol derivatives was studied (Scheme 3). To study the
effect of catalyst loading and temperature on three-component condensation
reactions for synthesis of 1-((4-chlorophenyl)(piperidin-1-yl)methyl)naphthalen-2-
ol the solvent-free reaction of 4-chlorobenzaldehyde, 2-naphthol, and piperidine in
the presence of nano TiO2–HClO4 as catalyst was selected as model reaction
(Table 6). The reaction was performed with different amounts of nano TiO2–HClO4
as catalyst (2, 5, 7 mg) under ambient conditions (Table 6). We found that 5 mg
nano TiO2–HClO4 was the most effective in catalyzing preparation of 1-((4-
chlorophenyl)(piperidin-1-yl)methyl)naphthalen-2-ol.
Next, three-component condensation of aromatic aldehydes, 2-naphthol, and
amines, under the optimized conditions, for preparation of 1-(a-aminoalkyl)-2-
naphthol derivatives was investigated. A wide range of substituted and structurally
diverse aldehydes and amines, with nano TiO2–HClO4 as catalyst, were used to
synthesize the corresponding products in high to excellent yields (Table 7).
Recycling of the nano TiO2–HClO4 was studied by using reaction of
4-chlorobenzaldehyde, 2-naphthol, and piperidin as model reaction (Experimental
section). The recovered catalyst was reused in six runs without any significant of its
activity (Fig. 3).
To show the merit of this work in comparison with results reported in the
literature, we compared results obtained by use of nano TiO2–HClO4 with results
123

H. R. Shaterian, M. Mohammadnia
Table 5 Comparison of results obtained by use of nano TiO2–HClO4 with results reported for other
catalysts used for synthesis of methyl (4-chlorophenyl)(2-hydroxynaphthalen-1-yl)methyl carbamate
under solvent-free conditions
Entry
Catalyst (mg)
Conditions
Time
(min)
Yield (%)a
[Ref.]
1
2
Silica-supported sodium hydrogen
sulfate (50 mg)
Solvent-free, 100 °C
Solvent-free, 80 °C
Solvent-free, 90 °C
6
92 [26]
4-(1-Imidazolium)butane sulfonate
(10 mol %)
120
3
82 [27]
3
Nano TiO2–HClO4 (5 mg)
94 (this work)
a
Yields are for isolated pure products and are based on the reaction of 4-chlorobenzaldehyde, 2-naph-
thol, methyl carbamate
Table 6 Optimization of conditions for preparation of 1-((4-chlorophenyl)(piperidin-1-
yl)methyl)naphthalen-2-ol from 4-chlorobenzaldehyde, 2-naphthol, and piperidine in the presence of
different amounts of nano TiO2–HClO4 as a catalyst under ambient conditions
Entry
Catalyst (mg)
Time (min)
Yield (%)a
1
2
3
a
2
5
7
42
25
25
81
93
94
Yields are for isolated pure products
reported for other catalysts in the synthesis of 1-((4-chlorophenyl)(piperidin-1-
yl)methyl)naphthalen-2-ol. As shown in Table 8, nano TiO2–HClO4 is a suitable
catalyst with regard to reaction times and yields of the products.
In addition, we used nano TiO2–HClO4 in condensation reaction of 2-naphthol,
aldehyde, and dimedone under solvent-free conditions for preparation of 12-aryl-
8,9,10,12-tetrahydrobenzo[a]-xanthen-11-one derivatives (Scheme 4). For optimi-
zation, reaction of 4-chlorobenzaldehyde, 2-naphthol, and dimedone was selected as
model. The reaction was conducted in the presence of different amounts of catalyst,
nano TiO2–HClO4 (2, 5, 7, 8, 10, 15 mg) and at different temperatures (25, 60,
90 °C) under solvent-free conditions. The best results were obtained with 5 mg
catalyst nano TiO2–HClO4 at 90 °C. The three-component condensation reaction of
aromatic aldehydes, 2-naphthol, and dimedone under the optimized conditions was
then investigated for preparation of 12-aryl-8,9,10,12-tetrahydrobenzo[a]-xanthen-
11-one derivatives. A wide range of substituted and structurally diverse aldehydes
were used and the corresponding products were synthesized in high to excellent
yields, which demonstrated this method tolerates both electron-withdrawing and
electron-donating constituents (Table 9).
Recycling of the nano TiO2–HClO4 was studied using reaction of 4-chlorobenz-
aldehyde, 2-naphthol, and dimedone as model reaction (Experimental section). The
recovered catalyst was reused in several runs without significant loss of its activity
(Fig. 4).
123

Nanocrystalline TiO2–HClO4 Catalyzed Three-Component Preparation
123

H. R. Shaterian, M. Mohammadnia
123

Nanocrystalline TiO2–HClO4 Catalyzed Three-Component Preparation
96
95
94
100
90
80
70
60
50
40
30
20
10
0
92
88
87
1
2
3
4
5
6
Reaction cycles
Fig. 3 Recycling of nano TiO2–HClO4 as catalyst in the preparation of 1-((4-chlorophenyl)(piperidin-1-
yl)methyl)naphthalen-2-ol
Table 8 Comparison of results obtained by use of nano TiO2–HClO4 with results reported for other
catalysts used for synthesis of 1-((4-chlorophenyl)(piperidin-1-yl)methyl)naphthalen-2-ol under solvent-
free conditions
Entry Catalyst
Conditions
Time (min) Yield (%)a [Ref.]
1
Non-ionic surfactant
Water (2 mL)
120
86 [28]
Triton X-100 (5 mol %)
LiClO4 (5 M)
Room temperature
Ether, room temperature
2
3
4
60
65 [29]
95 [30]
70 [31]
Cu(OTf)2ÁSiO2 (10 mol %) Solvent-free, 40 °C
Fe–Fe–PEG (0.5 mmol)
60
15 mL water
240
Room temperature
5
Nano TiO2–HClO4 (5 mg) Solvent-free, room temperature
3
94 (this work)
a
Yields are for isolated pure products and are based on reaction of 4-chlorobenzaldehyde, 2-naphthol,
and piperidine
To show the merit of this work in comparison with results reported in the
literature, we compared results for nano TiO2–HClO4 with results reported for
other catalysts used in the synthesis of 9,9-dimethyl-12-(4-chlorophenyl)-
8,9,10,12-tetrahydrobenzo[a]xanthen-11-one. As shown in Table 10, nano TiO2–
HClO4 can act as a suitable catalyst with regard to reaction times and yields of the
products.
Conclusion
New applications of nanocrystalline TiO2–HClO4 as an efficient catalyst for three
component preparation of 1-amidoalkyl-2-naphthols, 1-carbamato-alkyl-2-naphthols,
1-(a-aminoalkyl)-2-naphthols, and 12-aryl-8,9,10,12-tetrahydrobenzo[a]-xanthen-11-
123

H. R. Shaterian, M. Mohammadnia
Table 9 Three-component synthesis of 12-aryl-8,9,10,12-tetrahydrobenzo[a]-xanthen-11-one deriva-
tives by reaction of aldehydes, 2-naphthol, and dimedone in the presence of nano TiO2–HClO4 (5 mg) as
a catalyst at 90 °C
Entry
Aldehyde
Product
Time
(min)
Yield
(%)a
Melting Point
m.p (°C)/Lit. m.p (°C)
[Ref.]
1
2
16a
22
20
92
92
151–152/(151–153) [32]
CHO
16b
203–204/(204–205) [32]
CHO
MeO
Cl
3
4
16c
16d
18
25
93
90
180–181/(180–182) [32]
162–163/(161–164) [33]
CHO
CHO
Br
5
6
16e
16f
23
27
93
89
181–182/(181–182) [34]
171–172/(170–172) [33]
CHO
Cl
Cl
CHO
Br
7
16g
23
88
170–171/(168–170) [32]
CHO
NO2
8
9
16h
16i
25
28
90
91
177–178/(178–180) [32]
161–163/(160–163) [33]
CHO
O2N
CHO
Me
123

Nanocrystalline TiO2–HClO4 Catalyzed Three-Component Preparation
Table 9 continued
Entry
Aldehyde
Product
Time
(min)
Yield
(%)a
Melting Point
m.p (°C)/Lit. m.p (°C)
[Ref.]
10
16j
29
29
31
87
92
90
179–181/(178–180) [33]
239–240/(240–241) [32]
225–227/(223–225) [33]
CHO
CHO
Me
11
12
a
16k
16l
OH
CHO
Cl
Cl
Yields are for isolated pure products
Known pure products were characterized by comparison of their physical data (melting points, IR, 1H and
13C NMR) with those of the known compounds
98
95
93
100
90
80
70
60
50
40
30
20
10
0
90
88
86
1
2
3
4
5
6
Reaction cycles
Fig. 4 Recycling of nano TiO2–HClO4 as catalyst in the preparation of 9,9-dimethyl-12-(4-
chlorophenyl)-8,9,10,12-tetrahydrobenzo[a]xanthen-11-one
ones were described. The catalyst was reused several times without significant loss of
its activity in the reactions. Simple reaction, easy work-up, and solvent-free conditions
are advantages of these procedures.
123

H. R. Shaterian, M. Mohammadnia
Table 10 Comparison of results obtained by use of nano TiO2–HClO4 with results reported for other
catalysts used for synthesis of 9,9-dimethyl-12-(4-chlorophenyl)-8,9,10,12-tetrahydrobenzo[a]xanthen-
11-one under thermal solvent-free conditions
Entry
1
Catalyst
Conditions
Time (min)
120
Yield (%)a [Ref.]
p-TSA (10 mol %)
[bmim]BF4 (5 mL)
Room temperature
Solvent-free, 120 °C
Solvent-free, 110 °C
Solvent-free, 90 °C
85 [35]
2
3
4
a
p-TSA (2 mol %)
35
45
18
86 [35]
Trityl chloride (7 mol %)
Nano TiO2–HClO4 (5 mg)
90 [33]
93 (this work)
Yields are for isolated pure products and are based on the reaction of 4-chlorobenzaldehyde, 2-naph-
thol, and dimedone
Acknowledgments We are grateful to the University of Sistan and Baluchestan Research Council for
partial support of this research.
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