Caro's acid-silica gel-catalyzed one-pot synthesis of 12-aryl-8,9,10,12- tetrahydrobenzo[a] xanthen-11-ones

Article abstract of DOI:10.1080/00397910903537372

The synthesis of 12-aryl-8,9,10,12-tetrahydrobenzo[a] xanthen-11-ones from aldehyde, β-naphthol, AND dimedone in the presence of a catalytic amount of Caro's acid-silica gel in good yields under solvent-free conditions is reported. Copyright Taylor & Fran

Full text of DOI:10.1080/00397910903537372

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Caro's Acid–Silica Gel–Catalyzed One-
Pot Synthesis of 12-Aryl-8,9,10,12-
tetrahydrobenzo[a] Xanthen-11-ones
Narges Karimi a , Hossein Abdi Oskooie a , Majid M. Heravi a & Leila
Tahershamsi a
a Department of Chemistry, School of Science, Azzahra University,
Vanak, Tehran, Iran
Published online: 15 Dec 2010.
To cite this article: Narges Karimi , Hossein Abdi Oskooie , Majid M. Heravi & Leila Tahershamsi
(2010): Caro's Acid–Silica Gel–Catalyzed One-Pot Synthesis of 12-Aryl-8,9,10,12-tetrahydrobenzo[a]
Xanthen-11-ones, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 41:2, 307-312
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Synthetic Communications1, 41: 307–312, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903537372
CARO’S ACID–SILICA GEL–CATALYZED ONE-POT
SYNTHESIS OF 12-ARYL-8,9,10,12-
TETRAHYDROBENZO[a] XANTHEN-11-ONES
Narges Karimi, Hossein Abdi Oskooie, Majid M. Heravi, and
Leila Tahershamsi
Department of Chemistry, School of Science, Azzahra University,
Vanak, Tehran, Iran
The synthesis of 12-aryl-8,9,10,12-tetrahydrobenzo[a] xanthen-11-ones from aldehyde,
b-naphthol, AND dimedone in the presence of a catalytic amount of Caro’s acid–silica
gel in good yields under solvent-free conditions is reported.
Keywords: Aldehydes; dimedone; multicomponent reaction; b-naphthol; solvent-free; xanthen
INTRODUCTION
Multicomponent reactions (MCRs) have attracted considerable interest
because of their exceptional synthetic and practical efficiency.[1] MCRs involve three
or more starting materials reacting in a single flask to form a new product. One
example of an MCR is a three-component, one-pot synthesis of 12-aryl-8,9,10,12-
tetrahydrobenzo[a] xanthen-11-ones.
The preparation of xanthenes, especially benzoxanthenes, has received signifi-
cant attention in previous years because of the broad spectrum of their biological
and pharmaceutical properties, such as antiviral,[2] antibacterial,[3] and anti-
inflammatory[4] activities as well as efficacy in photodynamic therapy[5] technologies.
A number of xanthene-based compounds are also available from plant sources.[6]
Various methods have been reported for the synthesis of xanthenes and benzo-
xanthenes, including cyclocondensation of 2-hydroxyaromatic aldehydes with
2-tetralone,[7] trapping of benzynes by phenols,[8] and the reaction of 2-naphthol with
aldehydes and formamide.[9]
However, these methodologies suffer from one or more disadvantages such as
poor yield, lack of easy availability or preparation of the starting materials, pro-
longed reaction time, use of toxic organic solvents, and requirements for excess of
reagents=catalysts, special apparatus, and harsh reaction conditions.
There is an increasing interest in the use of environmentally feasible reagents,
particularly in solvent-free conditions. Avoiding organic solvents during reactions
Received August 30, 2009.
Address correspondence to Majid M. Heravi, Department of Chemistry, School of Science,
Azzahra University, Vanak, Tehran, Iran. E-mail: mmh1331@yahoo.com
307

308
N. KARIMI ET AL.
in organic synthesis leads to a clean, efficient, and economical technology, not only
with the increased safety, simplicity of workup, and reduction of cost, but also
increased amount of reactants can be achieved in the same equipment without huge
modifications. Reactivity and sometimes selectivity may be enhanced without
dilution.[10]
The syntheses of 12-aryl-8,9,10,12-tetrahydrobenzo[a] xanthen-11-one deriva-
tives involves the use of a number of catalysts such as p-toluenesulfonic acid
(PTSA),[11] Sr(OTf)2,[12] and I2.[13]
Recently, the use of Caro’s acid–silica gel (CA-SiO2) as catalyst or promoter in
organic synthesis has attracted great interest from many chemists. CA-SiO2 can
enhance the reactivity and selectivity of many types of reaction, such as oxidative
coupling of thiols to disulfides,[14] conversion of thioamides into amides,[15] and
carbonyl compounds from oximes.[16]
RESULTS AND DISCUSSION
In connection with our ongoing work on the synthesis of heterocyclic
compounds with CA-SiO2,[17] we report a facile procedure for preparation of
12-aryl-8,9,10,12-tetrahydrobenzo[a] xanthen-11-one derivatives with CA-SiO2 as a
nontoxic, inexpensive, and easily available reagent (Scheme 1).
To optimize the reaction temperature, the reactions were carried out at
different temperatures ranging from room temperature to 70 ꢀC. We found that
the yield of product 4 was improved and the reaction time was shortened as the
temperature was increased to 60 ꢀC. The yield plateaued when temperature was
further increased to 70 ꢀC (Table 1, entry 5). Therefore, the most suitable reaction
temperature is 60 ꢀC.
To find the optimum quantity of Caro’s acid–silica gel, the reaction of
aromatic aldehyde, b-naphthol, and dimedone was carried out under thermal
solvent-free conditions, using different quantities of Caro’s acid–silica gel (Table 2).
Under the optimized reaction condition, a series of derivatives were synthesized
(Table 3).
We found that with several aromatic aldehydes carrying either electron-
releasing or electron-withdrawing substituents in the meta and para positions, the
reaction proceeded very efficiently in all cases, but for electron-withdrawing substi-
tuents, shorter reaction times are needed to drive the reaction to completion.
1
All reaction products were known and characterized by H NMR, infrared
(IR), gas chromatography (GC)–mass, and melting points by comparing them with
those obtained from authentic samples.
Scheme 1. Synthesis of 12-aryl-8,9,10,12-tetrahydrobenzo[a] xanthen-11-one.

CARO’S ACID–SILICA GEL
309
Table 1. Optimization of temperature for the reaction of benzaldehyde,
b-naphthol, and dimedone
Entry
Temperature (ꢀC)
Time (min)
Yield (%)a
1
2
3
4
5
30
40
50
60
70
70
65
50
45
55
55
66
72
80
75
aYields refer to the pure isolated products.
Table 2. Optimization amount of CA-SiO2 for the reaction of benzaldehyde,
b-naphthol, and dimedone
Entry
Catalyst (g)
Time (min)
Yield (%)a
1
2
3
0.06
0.08
0.1
55
50
45
65
73
80
aYields refer to the pure isolated products.
Table 3. Synthesis of compound 4a–j by Caro’s acid
Entrya
Ar
Product
Time (min)
Yield (%)b of 4
Mp (ꢀC)
1
2
C6H5
4a
4b
4c
4d
4e
4f
45
40
50
55
35
40
45
30
35
35
80
75
80
80
90
85
80
90
87
89
149–152[18]
223–226[18]
175–177[18]
203–205[18]
175–176[18]
166–168[18]
224–226[18]
188–189[18]
179–182[18]
185–187[13]
4-HO-C6H4
4-Me-C6H4
4-OMe-C6H4
4-NO2-C6H4
3-NO2-C6H4
2-NO2-C6H4
4-Cl-C6H4
3
4
5
6
7
4 g
4 h
4i
8
9
10
2-Cl-C6H4
4-Br-C6H4
4j
aAll the products were characterized by comparison of spectroscopic data and melting points with those
reported in the literature.
bYield refers to the pure isolated products.
CONCLUSION
In conclusion, we have described a simple, one-pot, three-component reaction
involving aldehydes, b-naphthol, and dimedone for the synthesis of a series of
12-aryl-8,9,10,12-tetrahydrobenzo[a] xanthen-11-one derivatives under solvent-free
conditions. Particularly valuable features of this method include the greater yields
of the products, short times, an easy workup procedure, and the use of cheap,
nontoxic, and easily available CA-SiO2, which make it a useful and attractive process
for the synthesis of these important compounds.

310
N. KARIMI ET AL.
EXPERIMENTAL
Chemicals and Apparatus
All the chemicals were purchased from Merck Company. Melting points were
measured using a Barnstead Electrothermal instrument. GC=mass analysis was per-
formed using Agilent 6890 GC system Hp-5 capillary 30 m ꢁ 530 mm ꢁ 1.5 mm nom-
inal. IR spectra were recorded as KBr discs on the Fourier transform (FT)-IR
Brucker Tensor 27 spectrometer. 1H NMR spectra were recorded on a Bruker
AQS-Avance spectrometer at 300 MHz, using TMS as an internal standard.
Representative Procedure for the Synthesis of 12-Aryl-
8,9,10,12-tetrahydrobenzo[a] Xanthen-11-ones Using CA-SiO2
A mixture of aromatic aldehyde (1 mmol), b-naphthol (1 mmol), dimedone
(1.2 mmol), and CA-SiO2 (0.1 gr) was magnetically stirred at 60 ꢀC for the appropri-
ate time as indicated in Table 3. The reaction was followed by thin-layer chromato-
graphy (TLC). After completion, the reaction mixture was washed with CHCl3. For
further purification, it was crystallized with ethanol to afford the pure product.
General Procedure for the Preparation of Catalyst
In small portions of potassium persulfate (4.5 g) were added to ice-cooled 98%
sulfuric acid (4.7 g) with stirring; to this, crushed ice (13 g) and water (4 g) were
added. The temperature was kept below 15 ꢀC. Silica gel (5 g, TLC grade, Kieselgel
60 G, particle size 15 mm) was added in portions to the mixture, and the mixture was
stirred for 4 h in an ice-water bath. The mixture was then filtered under suction and
dried in a desiccator to give a white free-flowing power.[14]
Selected Spectroscopic Data
9,9-Dimethyl-12-phenyl-8,9,10,12-tetrahydro-benzo[a] xanthen-11-one
(4a). White solid; mp 149–152 ꢀC; IR (KBr): 3060, 2890, 1654, 1380, 1240, 1185,
;
813 cmꢂ1 1H NMR (300 MHz, CDCl3) d: 0.96 (s, 3H), 1.11 (s, 3H), 2.26 (d,
J ¼ 16.2 Hz, 1H), 2.33 (d, J ¼ 16.2 Hz, 1H), 2.57 (s, 2H), 5.70 (s, 1H), 7.42–7.04
(m, 8H), 7.78–7.74 (m, 2H), 7.99 (d, J ¼ 8.1 Hz, 1H).[18]
12-(4-Hydroxyphenyl)-9,9-dimethyl-12-phenyl-8,9,10,12-tetrahydro-
benzo[a] xanthen-11-one (4b). White solid; mp 223–226 ꢀC; IR (KBr): 3309,
1
2963, 1645, 1578, 1384, 1230, 1183, 1030 cmꢂ1; H NMR (300 MHz, CDCl3) d:
0.97 (s, 3H), 1.12 (s, 3H), 2.27 (d, J ¼ 16.2 Hz, 1H), 2.34 (d, J ¼ 16.2 Hz, 1H), 2.56
(s, 2H), 5.49 (s, 1H), 5.63 (m, 1H), 6.61 (d, J ¼ 8.4 Hz, 2H), 7.45–7.15 (m, 5H),
7.78–7.73 (m, 2H), 7.98 (d, J ¼ 8.1 Hz, 1H).[18]
9,9-Dimethyl-12p-tolyl-8,9,10,12-tetrahydro-benzo[a] xanthen-11-one
(4c). White solid; mp 175–177 ꢀC; IR (KBr): 3070, 2951, 2863, 1645, 1597, 1373,
1
1228, 1070, 818 cmꢂ1; H NMR (300 MHz, CDCl3) d; 0.89 (s, 3H), 1.06 (s, 3H),
2.14 (s, 3H), 2.30 (d, J ¼ 16.2 Hz, 1H), 2.41 (d, J ¼ 16.2 Hz, 1H), 2.60 (d, J ¼ 17.4 Hz,

CARO’S ACID–SILICA GEL
311
1H), 2.72 (d, J ¼ 17.4 Hz, 1H), 5.52 (s, 1H), 6.98 (d, J ¼ 7.2 Hz, 2H), 7.17–7.15
(m, 2H), 7.46–7.42 (m, 3H), 8.04–7.88 (m, 3H).[18]
12-(4-Methoxyphenyl)-9,9-dimethyl-12-phenyl-8,9,10,12-tetrahydro-
benzo[a] xanthen-11-one (4d). White solid; mp 203–205 ꢀC; IR (KBr): 3062,
1
2955, 1648, 1232, 1175, 1029 cmꢂ1; H NMR (300 MHz, CDCl3) d: 0.97 (s, 3H),
1.11 (s, 3H), 2.26 (d, J ¼ 16.2 Hz, 1H), 2.33 (d, J ¼ 16.2 Hz, 1H), 2.55 (s, 2H), 3.68
(s, 3H), 5.65 (s, 1H), 6.70 (d, J ¼ 8.4 Hz, 2H), 7.44–7.22 (m, 5H), 7.77–7.72 (m,
2H), 7.99 (d, J ¼ 8.1 Hz, 1H).[18]
9,9-Dimethyl-12-(4-nitrophenyl)-8,9,10,12-tetrahydro-benzo[a] xanthen-
11-one (4e). White solid; mp 175–176 ꢀC; IR (KBr): 3069, 2958, 1593, 1516,
1
1374, 1225, 1167, 1064, 828 cmꢂ1; H NMR (300 MHz, CDCl3) d: 0.94 (s, 3H),
1.13 (s, 3H), 2.26 (d, J ¼ 16.2 Hz, 1H), 2.36 (d, J ¼ 16.2 Hz, 1H), 2.59 (s, 2H), 5.81
(s, 1H), 7.52–7.33 (m, 5H), 7.82–7.79 (m, 3H), 8.04 (d, J ¼ 8.4 Hz, 2H).[18]
9,9-Dimethyl-12-(3-nitrophenyl)-8,9,10,12-tetrahydro-benzo[a] xanthen-
11-one (4f). White solid; mp 166–168 ꢀC; IR (KBr): 3071, 2955, 1528, 1374, 1225,
1
1169, 1025, 810 cmꢂ1; H NMR (300 MHz, CDCl3) d: 0.95 (s, 3H), 1.13 (s, 3H),
2.26 (d, J ¼ 16.2 Hz, 1H), 2.36 (d, J ¼ 16.2 Hz, 1H), 2.61 (s, 2H), 5.81 (s, 1H),
7.47–7.35 (m, 4H), 7.95–7.80 (m, 5H), 8.10 (s, 1H).[18]
9,9-Dimethyl-12-(2-nitrophenyl)-8,9,10,12-tetrahydro-benzo[a] xanthen-
11-one (4g). White solid; mp 224–226 ꢀC, IR (KBr): 3069, 2957, 1526, 1369,
1
1225, 1172, 1026, 821 cmꢂ1; H NMR (300 MHz, CDCl3) d: 0.86 (s, 3H), 1.11 (s,
3H), 2.19 (d, J ¼ 16.2 Hz, 1H), 2.29 (d, J ¼ 16.2 Hz, 1H), 2.52 (d, J ¼ 17.4 Hz, 1H),
2.60 (d, J ¼ 17.4 Hz, 1H), 6.58 (s, 1H), 7.46–7.03 (m, 6H), 7.86–7.77 (m, 3H), 8.56
(d, J ¼ 8.1 Hz, 1H)[18]
.
12-(4-Chlorophenyl)-9,9-dimethyl-12-(2-nitrophenyl)-8,9,10,12-tetrahydro-
benzo[a] xanthen-11-one (4h). White solid; mp 188–189 ꢀC; IR (KBr): 3070,
1
2925, 1645, 1374, 1225, 1172, 1086 cmꢂ1; H NMR (300 MHz, CDCl3) d: 0.96 (s,
3H), 1.12 (s, 3H), 2.26 (d, J ¼ 16.2 Hz, 1H), 2.34 (d, J ¼ 16.2 Hz, 1H), 2.56 (s, 2H),
5.67 (s, 1H), 7.45–7.11 (m, 7H), 7.79–7.75 (m, 2H), 7.90 (d, J ¼ 8.1 Hz, 1H).[18]
12-(2-Chlorophenyl)-9,9-dimethyl-12-(2-nitrophenyl)-8,9,10,12-tetrahydro-
benzo[a] xanthen-11-one (4i). White solid; mp 179–182 ꢀC; IR (KBr): 3075, 2930,
1645, 1373, 1227, 1175, 1028 cmꢂ1; 1H NMR (300 MHz, CDCl3) d: 0.99 (s, 3H), 1.13
(s, 3H), 2.24 (d, J ¼ 16.2 Hz, 1H), 2.34 (d, J ¼ 16.2 Hz, 1H), 5.98 (s, 1H), 7.07–6.96
(m, 2H), 7.49–7.26 (m, 5H), 7.76–7.72 (m, 2H), 8.23 (d, J ¼ 8.4 Hz, 1H).[18]
12-(4-Bromophenyl)-9,9-dimethyl-12-(2-nitrophenyl)-8,9,10,12-tetrahydro-
benzo[a] xanthen-11-one (4j). White solid; mp 185–187 ꢀC; IR (KBr): 2962, 2868,
1643, 1593, 1483, 1375, 1145, 1006, 835 cmꢂ1; 1H NMR (300 MHz, CDCl3) d: 0.97 (s,
3H), 1.12 (s, 3H), 2.25 (d, J ¼ 16.2 Hz, 1H), 2.30 (d, J ¼ 16.2 Hz, 1H), 2.57 (s, 2H),
5.67 (s, 1H), 7.20–7.46 (m, 7H), 7.78 (t, J ¼ 7.6 Hz, 2H), 7.89 (d, J ¼ 8.4 Hz, 1H).

312
N. KARIMI ET AL.
ACKNOWLEDGMENT
We are grateful to Azzahra University Research Council for partial support of
this work.
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