Molecular iodine catalyzed synthesis of aryl-14H-dibenzo[a, j]xanthenes under solvent-free condition

Article abstract of DOI:10.1016/j.bmcl.2006.11.009

Molecular iodine efficiently catalyzes the reaction of β-naphthol and araldehydes on a preheated hot plate at 90-95 °C to give biologically active aryl-14H-dibenzo[a, j]xanthenes under solvent-free condition. The yields are excellent and the reactions go

Full text of DOI:10.1016/j.bmcl.2006.11.009

Bioorganic & Medicinal Chemistry Letters 17 (2007) 621–623
Molecular iodine catalyzed synthesis of aryl-14H-
dibenzo[a, j]xanthenes under solvent-free condition
Mohamed A. Pasha* and Vaderapura P. Jayashankara
Department of Studies in Chemistry, Central College Campus, Bangalore University, Bangalore-560 001, India
Received 19 July 2006; revised 1 November 2006; accepted 2 November 2006
Available online 7 November 2006
Abstract—Molecular iodine efficiently catalyzes the reaction of b-naphthol and araldehydes on a preheated hot plate at 90–95 °C to
give biologically active aryl-14H-dibenzo[a, j]xanthenes under solvent-free condition. The yields are excellent and the reactions go to
completion within 15–20 min.
Ó 2006 Elsevier Ltd. All rights reserved.
Aryl-14H-dibenzo[a, j]xanthene functionality is a key
structural element of many biologically active com-
pounds such as antibacterials,1 antivirals2 and anti-in-
flammatory agents3 and in photodynamic therapy.4
Xanthene-based compounds have also been investigated
for agricultural bactericide activity and some other ben-
zoxanthenes find application in industries such as dyes
in laser technology5 and fluorescent materials for visual-
ization of biomolecules.6 Xanthene dyes are extracted
naturally from soil and plants such as Indigofera longe-
racemosa.7 Chemical synthesis of xanthenes has been
documented by a variety of methods such as reactions
including palladium catalyzed cyclisation of polycyclic
aryltriflate esters,8 intermolecular trapping of benzenes
by phenols,9 reaction of aryloxymagnesium halides with
triethylorthoformate10 and using conc. HCl/CH3COOH
or H3PO4 from b-naphthol and araldehydes or ace-
tals.11a,1b Some of the methods involve tedious experi-
mental procedures such as heating the contents at
125 °C for 6–12 h,12a give a mixture of products12b and
the yields of some of the products are low.13
Khosropour et al.14 reported the synthesis of alkyl-14H
or aryl-14H-dibenzo[a,j]xanthenes from aldehydes,
b-naphthol and p-toluenesulfonic acid in 1,2-dichloro-
ethane as solvent and under solvent-free condition.
The yields of some of the products were not satisfactory;
the reactions require extended time as long as 2.5–24 h.
Therefore, practical methods of obtaining aryl-14H-di-
benzo[a,j]xanthenes are of great interest in the lead
optimization process of drug discovery. To avoid the
limitations, we started search for new catalysts, with
high catalytic activity, easy availability and short reac-
tion time involving simple work-up procedure, and
molecular iodine attracted our attention because molec-
ular iodine is known to catalyze a number of organic
transformations.15a Recently, we have reported the syn-
thesis of N,N0-disubstituted ureas/thioureas catalyzed by
molecular iodine15b and a-iodoacetates from alkenes/
ammonium acetate/I2.15c
Results and discussion: In continuation with the search
for simple non-hazardous methods for the transforma-
tions in organic synthesis using iodine, herein we re-
port a highly versatile and efficient synthesis of aryl-
14H-dibenzo[a, j]xanthenes 3 (Scheme 1) from aralde-
hydes 1, b-naphthol 2 and catalytic amounts of
iodine. In a typical reaction, a mixture of 1 and 2
(1:2) equivalents, respectively, and iodine (cat.) was
taken in a 50 mL flat-bottomed flask and heated for
15–20 min on a hot plate at 90–95 °C under solvent-
free condition to get 3 in excellent yield, the results
are summarized in Table 1. These conditions were
applied to a series of substituted araldehydes with
b-naphthol.16
Further, Rajitha et al.12a and Ahmad et al.13 carried out
the synthesis of aryl-14H-dibenzo[a, j]xanthenes from
araldehydes and b-naphthol in presence of sulfamic acid
and p-toluenesulfonic acid, respectively, under micro-
wave irradiation, where the chemistry community fails
to carryout reactions on a large-scale.
Keywords: b-Naphthol; Araldehydes; Aryl-14H-dibenzo[a,j]xanthenes;
Solvent-free condition.
*
Corresponding author. Tel.: +91 80 22961337; e-mail: m_af_pasha@
yahoo.co.in
0960-894X/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.bmcl.2006.11.009

622
M. A. Pasha, V. P. Jayashankara / Bioorg. Med. Chem. Lett. 17 (2007) 621–623
R
CHO
OH
Iodine (0.25 mmole)
90 -95 0C
+
2
R
O
R = H, CH3, NO2, OCH3, Cl, Br, F
( 3a - j )
1
2
Scheme 1.
Table 1. Iodine catalyzed synthesis of aryl-14H-dibenzo[a, j]xanthenes
Entry
R (1)
Time (min)
Producta (3)
Yieldb (%)
Melting points (°C)
Found Reported
1
2
3
4
5
6
7
8
9
10
H
20
15
20
20
20
20
15
15
15
15
a
b
c
d
e
f
90
92
95
94
93
93
94
93
90
94
182–3
205–7
310
183
205
312
213
228
197–8
296
287
215
238
4-OCH3
4-NO2
2-NO2
4-CH3
3-CH3
4-Br
214
230
198
296
g
h
i
4-Cl
2-Cl
290
215–16
236
4-F
j
cMelting points of compounds are consistent with reported values (Refs. 12a,b,13,14).
a All the products are known, characterized by IR, NMR spectral analysis and compared with the authentic samples.
b Isolated yields.
2. Lambert, R. W.; Martin, J. A.; Merrett, J. H.; Parker, K.
E. B.; Thomas, G. J. PCT Int. Appl. WO9706178, 1997.
3. Poupelin, J. P.; Ruf, G. S.; Blanpin, O. F.; Narcisse, G.;
Ernouf, G. U.; Lacroix, R. Eur. J. Med. Chem. 1978, 13,
67.
4. Ion, R. M.; Albulescu, C.; Sirkecioglu, O.; Talinli, N.
Intenet. Photochem. Photobiol. 2000.
5. (a) Menchen, S. M.; Benson, S. C.; Lam, J. Y. L.; Zhen,
W.; Sun, D.; Rosenblum, B. B.; Khan, S. H.; Taing, M.
U.S. Patent 6,583, 168, 2003; (b) Banerjee, A.; Mukherjee,
A. K. Stain Technol. 1981, 56, 83.
6. (a) Bekaert, A.; Andrieux, J.; Plat, M. Tetrahedron Lett.
1992, 33, 2805; (b) Sarma, R. J.; Baruah, J. B. Dyes
Pigments 2005, 64, 91; (c) Buehler, C. A.; Cooper, D. E.;
Scrudder, E. O. J. Org. Chem. 1943, 8, 316.
7. Licudine, P. J. A.; Kawate, M. K.; Li, Q. X. J. Agric. Food
Chem. 1997, 45, 766.
8. Wang, J. Q.; Harvey, R. G. Tetrahedron 2002, 58, 5927.
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Trans. 1 2001, 14, 1771; (b) Knignt, D. W.; Little, P. B.
Synlett 1998, 1141.
10. Casiraghi, G.; Casnati, G.; Catellani, M.; Cornia, M.
Tetrahedron Lett. 1973, 14, 679.
To demonstrate the protocol, we selected p-anisaldehyde
as the model substrate and treated with b-naphthol in the
presence of catalytic iodine at 90–95 °C for 15 min to get
14-(40-methoxyphenyl)-14H-dibenzo[a, j]xanthene in 92%
yield (Table 1, entry 2). The interesting feature of the
present method of synthesis of aryl-14H-dibenzo[a, j]-
xanthenes is that, the substituents OCH3, Cl, Br, F and
NO2 are unaffected under the reaction condition.
Acknowledgements
One of the authors Jayashankara V. P. thanks Sri Sri Sri
Balagangadharanatha Swamyji of Adichunchanagiri
Mutt for the blessings and Mr. Mohamed Ghouse and
family, Nagamangala, Mandya District, Karnataka,
India, for the encouragement. Acknowledgements are
also due to SIF and Department of Organic Chemistry,
Indian Institute of Science, Bangalore, for recording
NMR spectra.
11. (a) Buu-Hoi, N. P.; Xuong, N. D. J. Org. Chem. 1951, 16,
1633; (b) Zad, A. K.; Kazemi, Z.; Rudbari, H. A.
J. Korean Chem. Soc. 2002, 46, 541.
Supplementary data
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.bmcl.
2006.11.009.
12. (a) Rajitha, B.; Sunil Kumar, B.; Reddy, Y. T.; Reddy, P.
N.; Sreenivasulu, N. Tetrahedron Lett. 2005, 46, 8691,
Sulfamic acid catalysed synthesis of aryl-14H-dibenzo[a,
j]xanthenes under conventional heating and under micro-
wave irradiation is reported, the reactions take 6–12 h for
completion under conventional heating at 125 °C; (b)
Woodroofe, C. C.; Lim, M. H.; Bu, W.; Lippard, S. J.
Tetrahedron. Lett. 2005, 61, 3097, Synthesis of carboxylate-
and sulfonate-substituted xanthene fluorophores in the
References and notes
1. Hideo, T. Chem. Abstr. 1981, 95, 80922b, Jpn. Tokkyo
Koho JP 56005480, 1981.

M. A. Pasha, V. P. Jayashankara / Bioorg. Med. Chem. Lett. 17 (2007) 621–623
623
presence of ZnCl2 on heating at 190 °C requires more than
4 h for completion, and gives a mixture of products..
13. Ahmad, K. Z.; Akbari, S. A.; Azam, S.; Hojat, V.
J. Chem. Res. (S) 2005, 277, 14H-Dibenzo[a, j]xanthene
derivatives are prepared under microwave irradiation in
the presence of p-toluenesulfonic acid and the yields are
low in a few cases..
14. Khosropour, A. R.; Khodaei, M. M.; Moghannian, H.
Synlett 2005, 955.
15. (a) Zhang, Z.; Liu, Q. Prog. Chem. 2006, 18, 270; (b)
Pasha, M. A.; Jayashankara, V. P. Synth. Commun. 2006,
36, 1787; (c) Myint, Y. Y.; Pasha, M. A. Synth. Commun.
2004, 34, 4477.
0.25 mmol) were ground well and transferred to a 50 mL
flat-bottomed flask and heated on a hot plate at 90–95 °C
for 15 min. After complete conversion (monitored on
TLC), the system was cooled to room temperature, the
mixture was washed with 10% Na2S2O3 solution and the
separated precipitate was purified by recrystallization
from aqueous ethanol to afford 14-(40-methoxyphenyl)-
14H-dibenzo[a,j]xanthene 3b [(3.68 g, 92%); mp: 205–
07 °C; IR (KBr) : 3042, 2924, 1620, 1591,1253, 841,
1
800 cmꢀ1; H NMR (200 MHz, CDCl3): d = 3.64 (s, 3H),
6.56 (s, 1H), 6.75 (d, J = 9.3 Hz, 2H), 7.38–7.95 (m, 14H),
8.40 (d, J = 9.5 Hz, 2H); 13C NMR (200 MHz, CDCl3):
d = 37.7, 54.0, 114.5, 118.2, 118.6, 124.0, 124.8, 127.3,
130.1, 131.5, 1334.0, 137.9, 149.3, 158.5; Anal. Calcd for
C28H20O2: C, 86.57; H, 5.20; Found: C, 86.60; H, 5.19;
MS: m/z = 403 (M+)].
16. Typical procedure for the synthesis of aryl-14H-dib-
enzo[a,j]xanthenes: p-anisaldehyde (1.36 g, 10 mmol),
b-naphthol (2.88 g, 20 mmol) and iodine (0.063 g,