Eco-friendly and efficient one-pot synthesis of alkyl- or aryl-14H-dibenzo[a,j]xanthenes in water

Article abstract of DOI:10.1016/j.bmcl.2007.07.008

Alkyl- or aryl-14H-dibenzo[a,j]xanthene derivatives are synthesized efficiently by the reaction of β-naphthol and aliphatic and aromatic aldehydes in the presence of KAl(SO₄)₂·12H₂O (alum) under aqueous condition at 100 °C

Full text of DOI:10.1016/j.bmcl.2007.07.008

Bioorganic & Medicinal Chemistry Letters 18 (2008) 436–438
Eco-friendly and efficient one-pot synthesis of alkyl- or
aryl-14H-dibenzo[a,j]xanthenes in water
*
Minoo Dabiri, Mostafa Baghbanzadeh,
Maryam Shakouri Nikcheh and Elham Arzroomchilar
Department of Chemistry, Faculty of Science, Shahid Beheshti University, Postal Code 1983963113, Evin, Tehran, Iran
Received 12 April 2007; revised 5 June 2007; accepted 6 July 2007
Available online 13 July 2007
Abstract—Alkyl- or aryl-14H-dibenzo[a,j]xanthene derivatives are synthesized efficiently by the reaction of b-naphthol and aliphatic
4 2 2
and aromatic aldehydes in the presence of KAl(SO ) Æ12H O (alum) under aqueous condition at 100 °C. Different types of aromatic
and aliphatic aldehydes are used in the reaction and in all cases the products synthesized successfully. Several solvents were exam-
ined for this reaction; however, in terms of reaction yield and time, water was found to be the optimum solvent.
Ó 2007 Elsevier Ltd. All rights reserved.
Alkyl- or aryl-14H-dibenzo[a,j]xanthene functionality is
a key structural element of many biologically active
development of a new procedure for the synthesis of dib-
enzoxanthene derivatives would be highly desirable.
1
2
compounds such as antibacterials, antivirals, anti-
4
inflammatory agents and in photodynamic therapy.
3
The organic reactions in aqueous media have attracted
much attention in synthetic organic chemistry, not only
because water is one of the most abundant, cheapest and
environmentally friendly solvents but also because water
exhibits unique reactivity and selectivity, which is differ-
Xanthene-based compounds have also been investigated
for agricultural bactericide activity and some other ben-
zoxanthenes find application in industries such as dyes
5
in laser technology and fluorescent materials for visual-
6
16
ization of biomolecules. Xanthene dyes are extracted
naturally from soil and plants such as Indigofera longe-
ent from those in conventional organic solvents.
7
17
racemosa. Thus, the synthesis of benzoxanthene deriv-
atives currently is of great interest. Various methods
have been reported for the synthesis of benzoxanthenes,
Recently Sharpless and co-workers reported the obser-
vation that some organic molecules can react on the sur-
face of water and often a very strong enhancement of
reaction rates was noticed in this case, particularly when
at least one compound involved in these reactions bears
a polar group, enabling some degree of solubility
(carboxylic ether, amine, etc.,. . .) in water.
8
including the reaction of b-naphthol with formamide,
2
9
10
-naphthol-1-methanol and carbon monoxide. How-
ever, these methods have many disadvantages such as
low yields, the need for a prolonged reaction time, the
use of toxic organic solvents, excess reagents and harsh
reaction conditions. Because of these drawbacks, the
reaction has been improved by mixing b-naphthol with
aldehydes in the presence of a catalyst, such as amber-
As a continuation of our research devoted to the devel-
opment of green organic chemistry by performing
1
8
organic transformations under solvent-free conditions,
1
1
12
13
14
19
lyst, sulfamic acid, I , AcOH–H SO . These
2
or by using water as the reaction medium herein we
report an efficient and green procedure for the synthesis
of alkyl- or aryl-14H-dibenzo[a,j]xanthenes in water.
The results of the present work show the desired product
in excellent yield (Scheme 1).
2
4
methods also suffer from some disadvantages such as a
1
5
long reaction time, the use of toxic solvent, special
3
apparatus and the use of toxic catalysts. Thus, the
1
To study the reaction in water, we tested the reaction of
b-naphthol and 4-chlorobenzaldehyde as a simple
model substrate in different solvents in the presence
Keywords: Heterocycle; Water; Xanthene; Aldehyde; Green chemistry.
*
Corresponding author. Tel.: +98 21 22431661; fax: +98 21
2431663; e-mail: m-dabiri@sbu.ac.ir
2
0
960-894X/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.bmcl.2007.07.008

M. Dabiri et al. / Bioorg. Med. Chem. Lett. 18 (2008) 436–438
437
R
O
OH
2 mmol) +
Alum (0.5 mmol)
(
R
CHO (1 mmol)
o
Water, 100 C
Scheme 1.
of KAl(SO ) Æ12H O (alum) as an inexpensive and
Table 3. Effect of acidic catalyst on the reaction of 4-chlorobenzhyd-
razide and b-naphthol in water
4
2
2
available catalyst. The results are shown in Table 1.
It was found that water was a solvent of choice for
the reaction and the desired product obtained in high
yield in water. Entry 9 shows the effect of water in
the condensation of 4-chlorobenzaldehyde and
b-naphthol.
Entry
Catalyst
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
9
p-TsOH
6
12
12
12
12
6
60
30
NaHSO
NaHSO
4
3
20
H
2
SO
4
25
Montmorillonite K-10
Silica sulfuric acid
40
75
After optimizing the conditions, we next examined the
generality of this condition to other substrates using
b-naphthol and several aromatic and aliphatic aldehydes.
The results are summarized in Table 2. Aromatic alde-
hydes carrying different functional groups were subjected
to the reaction and in all cases the desired product synthe-
sized in high yields and short period of time. Another
advantage of this method is its efficiency for the high yield
synthesis of alkyl- or aryl-14H-dibenzo[a,j]xanthenes
from aliphatic aldehydes (Table 2, entries 11,12). Work-
up procedure is so simple and includes filtration of mix-
I
2
12
12
12
4
Trace
30
NH
(NH
Alum
4
Cl
4
)
2
HPO
4
Trace
90
1
0
2
0
ture to separate the product. The role of water as the
reaction medium and its mechanism is not clear. Despite
the low solubility of b-naphthol and aldehydes in water,
the reaction is accelerated in water and proceeds effi-
ciently in the presence of alum. This one-pot reaction with
1
7
regard to the sharpless observations might take place at
the interface of organic substrates with water in a hetero-
geneous system. It is worthy to note that vigorous stirring
is required for the success of this reaction.
Table 1. Solvent effects on the reaction of 4-chlorobenzaldehyde and
b-naphthol in the presence of 50 mol% of alum
b
Entry
Solvent
Yield (%)
Time (h)
1
2
3
4
5
6
7
8
9
EtOH
MeOH
35
40
24
24
24
24
24
24
24
4
To emphasize the effect of catalyst the model reaction
between 4-chlorobenzhydrazide and b-naphthol was
described and different acidic catalysts were subjected
to the reaction. All the reactions were run in the same
conditions and similar amounts of catalysts (50 mol%)
were used. As can be seen in Table 3 satisfactory results
were obtained only with alum (entry 10).
CH
CHCl
CH CN
PhCH
ClCH
2
Cl
2
Trace
Trace
20
3
3
3
Trace
20
2 2
CH Cl
H
2
a
O
90
—
60
12
a
The reaction was run under solvent-free condition at 100 °C.
Isolated yield.
b
In summary, we have reported a new and effective meth-
odology for the eco-compatible preparation of alkyl- or
aryl-14H-dibenzo[a,j]xanthene derivatives. The easy
purification of the products by simple filtration and
crystallization, short reaction times and the use of water
as the solvent suggest good prospects for the applicabil-
ity of this process. To the best of our knowledge this is
the first report on synthesis of alkyl- or aryl-14H-dib-
enzo[a,j]xanthene derivatives in water.
Table 2. Synthesis of alkyl- or aryl-14H-dibenzo[a,j]xanthenes by the
reaction of b-naphthol, and aromatic aldehydes in the presence of
alum in water
a
b
Entry
R
Time (h)
Yield (%)
Mp
1
1
1
1
1
1
1
1
4
4
4
5
4
4
4
5
1
2
3
4
5
6
7
8
9
C
6
H
5
3
90
90
89
91
90
88
91
90
88
90
80
82
185–186
289–290
296–298
238–240
308–310
227–229
203–205
260–261
4-ClC
4-BrC
4-FC
4-O NC
4-H CC
6
H
4
4
6
H
4
3
6
H
4
4
2
6
H
4
4
Acknowledgment
3
6
CH
4
3
4-CH
2-CH
3
OC
OC
6
H
4
3
The authors would like to acknowledge financial sup-
port from the Research Council of Shahid Beheshti
University.
3
6
H
4
4
1
3b
2-O
3-O
2
NC
NC
6
H
H
4
4
4
214–215
1
1
1
5
5
5
1
1
1
0
1
2
2
6
3.5
4
210–212
151–153
112–113
CH
(CH
3
CH
CHCH
2
3
)
2
2
4
References and notes
a
Isolated yield.
The products were characterized by comparison of their spectro-
scopic and physical data with those reported in the literature.
b
1
. Hideo, T. Chem. Abstr. 1981, 95, 80922b, Jpn. Tokkyo
Koho JP 56005480, 1981.

438
M. Dabiri et al. / Bioorg. Med. Chem. Lett. 18 (2008) 436–438
2
3
. Lambert, R. W.; Martin, J. A.; Merrett, J. H.; Parker, K. 17. Narayan, S.; Muldoon, J.; Finn, M. G.; Fokin, V. V.;
E. B.; Thomas, G. J. PCT Int. Appl. WO9706178, 1997.
. Poupelin, J. P.; Ruf, G. S.; Blanpin, O. F.; Narcisse, G.;
Ernouf, G. U.; Lacroix, R. Eur. J. Med. Chem. 1978, 13,
Kolb, H. C.; Sharpless, K. B. Angew. Chem., Int. Ed. 2005,
44, 3275.
18. (a) Salehi, P.; Dabiri, M.; Zolfigol, M. A.; Baghbanzadeh,
M. Tetrahdron Lett. 2005, 46, 7051; (b) Dabiri, M.; Salehi,
P.; Mohammadi, A. A.; Baghbanzadeh, M. Synth. Com-
mun. 2005, 35, 279; (c) Dabiri, M.; Salehi, P.; Moham-
madi, A. A.; Baghbanzadeh, M.; Kozehgiry, G. J. Chem.
Res., (S) 2004, 570; (d) Salehi, P.; Dabiri, M.; Zolfigol, M.
A.; Baghbanzadeh, M. Synlett 2005, 1155; (e) Salehi, P.;
Dabiri, M.; Baghbanzadeh, M.; Bahramnejad, M. Synth.
Commun. 2006, 36, 2287; (f) Salehi, P.; Dabiri, M.;
Zolfigol, M. A.; Baghbanzadeh, M. Heterocycles 2005,
62, 1417; (g) Dabiri, M.; Salehi, P.; Zolfigol, M. A.;
Baghbanzadeh, M. Heterocycles 2007, 71, 677; (h) Dabiri,
M.; Salehi, P.; Baghbanzadeh, M.; Zolfigol, M. A.;
Bahramnejad, M. Synth. Commun. 2007, 37, 1201; (i)
Dabiri, M.; Salehi, P.; Baghbanzadeh, M.; Vakilzadeh, Y.;
Kiani, S. Monatsh. Chem. 2007, 138, 595.
67.
4
5
. Ion, R. M.; Planner, A.; Wiktorowicz, K.; Frackowiak, D.
Acta Biochim. Pol. 1998, 45, 833.
. (a) Menchen, S. M.; Benson, S. C.; Lam, J. Y. L.; Zhen,
W.; Sun, D.; Rosenblum, B. B.; Khan, S. H.; Taing, M.
US Patent 6583168, 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) Buehler, C. A.; Cooper, D. E.;
Scrudder, E. O. J. Org. Chem. 1943, 8, 316.
. Licudine, P. J. A.; Kawate, M. K.; Li, Q. X. J. Agric. Food
Chem. 1997, 45, 766.
7
8
9
. Papini, P.; Cimmarusti, R. Gazz. Chim. Ital. 1947, 77, 142.
. Sen, R. N.; Sarkar, N. J. Am. Chem. Soc. 1925, 47, 1079.
1
1
1
0. Ota, K.; Kito, T. Bull. Chem. Soc. Jpn. 1976, 49, 1167.
1. Ko, S.; Yao, C.-F. Tetrahedron Lett. 2006, 47, 8827.
2. Rajitha, B.; Kumar, B. S.; Reddy, Y. T.; Reddy, P. N.;
Sreenivasulu, N. Tetrahedron Lett. 2005, 46, 8691.
3. (a) Das, B.; Ravikanth, B.; Ramu, R.; Laxminarayana, K.;
Rao, B. V. J. Mol. Catal. A: Chem. 2006, 255, 74; (b)
Pasha, M. A.; Jayashankara, V. P. Bioorag. Med. Chem.
Lett. 2007, 17, 621.
4. Sarma, R. J.; Baruah, J. B. Dyes Pigm. 2005, 64, 91.
5. Khosropour, A. R.; Khodaei, M. M.; Moghannian, H.
Synlett 2005, 955.
6. (a) Grieco, P. A. Organic Synthesis in Water; Blackie
Academic and Professional: London, 1998; (b) Demko, Z.
P.; Sharpless, K. B. J. Org. Chem. 2001, 66, 7945; (c) Li,
C.-J. Chem. Rev. 2005, 105, 3095.
19. (a) Dabiri, M.; Salehi, P.; Otokesh, S.; Baghbanzadeh, M.;
Kozehgary, Gh.; Mohammadi, A. A. Tetrahedron Lett.
2005, 46, 6123; (b) Baghbanzadeh, M.; Salehi, P.; Dabiri,
M.; Kozehgary, Gh. Synthesis 2006, 344; (c) Salehi, P.;
Dabiri, M.; Zolfigol, M. A.; Otokesh, S.; Baghbanzadeh,
M. Tetrahedron Lett. 2006, 47, 2557.
20. General procedure for the synthesis of alkyl- or aryl-14H-
dibenzo[a,j]xanthenes: A mixture of b-naphthol (2 mmol),
aldehyde (1 mmol) and alum (0.5 mmol) in water (3 mL)
was heated at 100 °C with stirring for appropriate time
(see Table 2). After completion of the reaction confirmed
by TLC (eluent: n-hexane/ethylacetate 2:1), mixture was
cooled to room temperature and the precipitated product
was filtered and recrystallized from ethanol.
1
1
1
1