Indium triflate-catalyzed one-pot synthesis of 14-alkyl or aryl-14h-dibenzo[a,j]xanthenes in water

Article abstract of DOI:10.1002/hc.20539

A mild, efficient, and environment friendly method has been developed for the synthesis of 14-alkyl or aryl-14H-dibenzo[a, j]xanthenes by condensation of 2-naphthol and aldehydes in the presence of a catalytic amount ofindium(III) triflate (2 mol%) in wat

Full text of DOI:10.1002/hc.20539

Heteroatom Chemistry
Volume 20, Number 4, 2009
Indium Triflate-Catalyzed One-Pot Synthesis of
14-Alkyl or Aryl-14H-dibenzo[a,j ]xanthenes
in Water
Sharmistha Urinda, Dhiman Kundu, Adinath Majee,
and Alakananda Hajra
Department of Chemistry, Visva-Bharati University, Santiniketan731 235, West Bengal, India
Received 19 January 2009; revised 11 May 2009
ent advantages over reactions in conventional or-
ABSTRACT: A mild, efficient, and environment
ganic solvents. Generally, typical Lewis acids such
friendly method has been developed for the synthesis of
as BF3, AlCl3, TiCl4, and SnCl4 are immediately hy-
14-alkyl or aryl-14H-dibenzo[a, j]xanthenes by con-
drolyzed by atmospheric moisture, and therefore
densation of 2-naphthol and aldehydes in the presence
they should be treated strictly in dry conditions
of a catalytic amount of indium(III) triflate (2 mol%)
to prevent the loss of their catalytic activities. Be-
in water at 100◦C. Different types of aromatic and
cause of the increasing awareness of environmental
aliphatic aldehydes are used in the reaction, and in all
problems in chemical research and industry, water-
cases the products synthesized in moderate to excellent
accessible Lewis acid catalysts have attracted much
ꢀ
C
yields. 2009 Wiley Periodicals, Inc. Heteroatom Chem
attention [3]. In the course of our studies to develop
a new synthetic methodology based on green synthe-
sis, we have become interested in a Lewis acid cata-
20:232–234, 2009; Published online in Wiley InterScience
(www.interscience.wiley.com). DOI 10.1002/hc.20539
lyst that can be used in pure water, not in aqueous
media [4].
INTRODUCTION
Indium(III) compounds have evolved as mild
and water-tolerant Lewis acids, imparting high
regio-, stereo-, and chemoselectivity in various or-
ganic transformations [5]. In contrast to classical
Lewis acids, which often are required in stoichiomet-
ric quantities, indium(III) compounds readily pro-
mote a wide variety of organic reactions in catalytic
quantities soluble both in organic solvents and in
aqueous media. Particularly, in accordance with the
recent surge of interest in moisture-stable metal tri-
flates, In(OTf)3 has emerged as a promising catalyst
for various types of organic reactions [6].
The synthesis of xanthenes, especially benzoxan-
thenes, has been of great interest to chemists because
of their wide range of biological and pharmaceutical
properties such as antiviral, antibacterial, and anti-
inflammatory activities as well as efficiency in photo-
dynamic therapy and antagonists for the paralyzing
Lewis acids promoted organic reactions in water or
aqueous media have recently attracted great inter-
est [1]. Water has aroused considerable attention in
synthetic community and proved to be a promising
solvent in organic synthesis due to its economic, en-
vironment friendly, and polar nature [2]. In relation
to this, significant efforts have been dedicated to de-
velop organic reactions in water with many inher-
Correspondence to: Adinath Majee; e-mail: adinath.majee@
visva-bharati.ac.in; Alakananda Hajra; alakananda.hajra@visva-
bharati.ac.in.
Contract grant sponsor: Department of Science and Technol-
ogy, Government of India, New Delhi, India.
Contract grant number: SR/FTP/CS-107/2006.
Contract grant sponsor: DST-FIST.
Contract grant sponsor: UGC-SAP.
2009 Wiley Periodicals, Inc.
c
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232

Indium Triflate-Catalyzed One-Pot Synthesis of 14-Alkyl- or Aryl-14H-dibenzo[a,j]xanthenes in Water 233
TABLE
1
Synthesis
of
Alkyl
or
Aryl-14H-
R
O
OH
dibenzo[a, j ]xanthenes by the Reaction of 2-Naphthol,
In(OTf)3, 2 mol%
and Aldehydes in the Presence of 2 mol% ln(OTf)3 in Water
+ R CHO
(1 mmol)
°
Water, 100 C
Yield (%)a
( 2 mmol)
R = alkyl or aryl
Entry
R
Time (h)
1
2
3
C6H5
4-Me-C6H4
4-OMe-C6H4
8
8
8
82
82
85
SCHEME 1
O
4
9
90
O
action of zoxazolamine [7]. Thus, the synthesis
of benzoxanthene derivatives currently is of great
interest.
5
6
7
4-OH-C6H4
3-OH-4-OMe-C6H3
4-Cl-C6H4
13
11
7
9
12
5
70
93
80
80
80
88
For the synthesis of benzoxanthenes, various
methods have been reported including the reac-
tion of β-naphthol with formamide, 2-naphthol-1-
methanol, and carbon monoxide [8]. Furthermore,
14H-dibenzo[a, j]xanthenes and its analogues are
prepared by using the condensation reaction of the
mixture of 2-naphthol with aldehydes in the pres-
ence of a catalyst, such as silica sulfuric acid [9],
Dowex-50W [10], NH4H2PO4 [11], I2 [12], sulfamic
acid [13], HClO4–SiO2 [14], PW acid [15], cyanuric
chloride [16], Yb(OTf)3 [17], alum [18], and BF3.SiO2
[19]. However, the above-mentioned catalysts have
several disadvantages because they are corrosive,
toxic, or volatile and generate large amounts of waste
material. Thus, search for eco-friendly catalyst as
well as green solvent is highly desirable.
8
9
10
4-Br-C6H4
3-NO2-C6H4
4-NO2-C6H4
11
13
54
N
12
13
(CH3)2CH
CH3CH2CH2
12
15
59
56
14
15
76
aYields refer to those of pure isolated products fully characterized by
spectral and physical data.
The aromatic aldehydes containing electron-
donating as well as electron-withdrawing groups un-
derwent the conversion equally. Acid-sensitive sub-
strate such as 2-pyridinecarboxaldehyde produced
the desired condensation product in good yield
(entry 11, Table 1). Another advantage of this
method is its efficiency for the synthesis of alkyl-
14H-dibenzo[a,j]xanthenes from aliphatic aldehy-
des (entries 12–14, Table 1). However, the reaction
conducted with phenol and 1-naphthol instead of 2-
naphthol could not afford any product. The work-up
procedure is so simple and includes filtration of the
mixture to separate the product. After isolation of
the product from the water mixture, the water layer
containing indium triflate was washed with ether
and was reused. The effectiveness of the catalyst was
decreased after each run. In comparison with other
reported methods of dibenzoxanthene synthesis, the
use of In(OTf)3 as a catalyst and water as a solvent
is very much versatile and efficient catalyst for ob-
taining 14-aryl or alkyl-14H-dibenzo[a, j]xanthenes
from different types of aldehydes.
In continuation of our work to apply indium(III)
compound as catalyst to organic reactions [20],
herein, we report an efficient and environment
friendly method for the synthesis of 14-aryl or alkyl-
14H-dibenzo[a, j]xanthene derivatives catalyzed by
indium triflate in water (Scheme 1).
RESULTS AND DISCUSSION
To study the reaction in water, we tested the reaction
of β-naphthol and 4-chlorobenzaldehyde as a simple
model substrate in water in the presence of indium
triflate (2 mol%) as a nonhazardous and available
catalyst. It was found that the condensation reaction
was proceeded very well in water, and the desired
product obtained in high yield. The structure of the
product was settled from the spectral data. Use of
just 2 mol% of In(OTf)3 in water is sufficient to push
the reaction forward. Higher amount of In(OTf)3 did
not improve the result to a great extent. Presumably,
the reaction proceeds by the usual mechanism pro-
posed using Lewis acids [17].
In conclusion, In(OTf)3 is an efficient and versa-
tile catalyst for the preparation of aryl or alkyl 14H-
dibenzo[a,j] xanthene derivatives. The significant ad-
vantages offered by this method are the following:
(i) water as solvent, (ii) high yields, (iii) no waste pro-
duction, (iv) nontoxic metal catalyst, and (v) simple
After optimizing the reaction conditions, we next
examined the generality of this condition to other
substrates using several aromatic and aliphatic alde-
hydes. The results are summarized in Table 1.
Heteroatom Chemistry DOI 10.1002/hc

234 Urinda et al.
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ficiency for the synthesis of xanthenes from aliphatic
aldehydes. Further studies on the application of the
present methodology to the synthesis of biologically
active compounds are under investigation.
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Typical Procedure for the Synthesis of
14-Cyclohexyl-14H-dibenzo[a,j]xanthene
(entry 14)
A mixture of β-naphthol (577 mg, 4 mmol) and cyclo-
hexanecarboxaldehyde (225 mg, 2 mmol) was stirred
in presence of indium triflate (22 mg, 2 mol%) in
water (4 mL) at 100◦C for 15 h (TLC). After comple-
tion of the reaction confirmed by TLC, the mixture
was cooled to room temperature and the precipi-
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ethanol to afford the pure product as white crystals
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1
1622, 1585, 1452, 1234 cm−1; H NMR (300 MHz,
CDCl3) δ: 8.29 (d, J = 8.4 Hz, 2H), 7.85 (d, J = 8.1
Hz, 2H), 7.75 (d, J = 8.7 Hz, 2H), 7.61–7.55 (m, 2H),
7.45–7.23 (m, 4H), 5.39 (d, J = 3.6 Hz, 1H), 1.89–
1.38 (m, 6H), 1.04–0.76 (m, 5H); 13C NMR (75 MHz,
CDCl3) δ: 150.9, 132.2, 131.0, 128.6, 127.9, 126.2,
123.9, 123.9, 123.0, 47.1, 36.3, 30.7, 26.5, 25.9; Anal.
Calcd for C27H24O: C, 88.97; H, 6.64. Found: C, 88.78;
H, 6.47.
ACKNOWLEDGMENTS
Dhiman Kundu thanks to CSIR for the fellowship.
We also express our sincere thanks to Prof. B. C.
Ranu, Department of Chemistry, Indian Association
for the Cultivation of Science, Kolkata, India, for his
advice and constant encouragement.
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Heteroatom Chemistry DOI 10.1002/hc