Organocatalyst trityl chloride efficiently promoted the solvent-free synthesis of 12-aryl-8,9,10,12-tetrahydrobenzo[a]-xanthen-11-ones by in situ formation of carbocationic system in neutral media

Article abstract of DOI:10.1016/j.catcom.2012.01.001

A highly efficient and novel procedure for the preparation of 12-aryl-8,9,10,12-tetrahydrobenzo[a]-xanthen-11-one derivatives via the one-pot three-component condensation of 2-naphthol with arylaldehydes and dimedone in the presence of catalytic amount of

Full text of DOI:10.1016/j.catcom.2012.01.001

Catalysis Communications 20 (2012) 54–57
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Catalysis Communications
journal homepage: www.elsevier.com/locate/catcom
Short Communication
Organocatalyst trityl chloride efficiently promoted the solvent-free synthesis of
2-aryl-8,9,10,12-tetrahydrobenzo[a]-xanthen-11-ones by in situ formation of
carbocationic system in neutral media
1
a,
a,
a
b
Ardeshir Khazaei ⁎, Mohammad Ali Zolfigol ⁎, Ahmad Reza Moosavi-Zare , Abdolkarim Zare ,
c
a
a
d
Mahmoud Khojasteh , Zhila Asgari , Vahid Khakyzadeh , Ali Khalafi-Nezhad
Faculty of Chemistry, Bu-Ali Sina University, Hamedan, Iran. 6517838683
Department of chemistry, Payame Noor University, PO BOX 19395-4697 Tehran, Iran
IBM Corp., Hopewell Junction, New York, 12533, USA
a
b
c
d
Department of Chemistry, College of Science, Shiraz University, Shiraz 71454, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
A highly efficient and novel procedure for the preparation of 12-aryl-8,9,10,12-tetrahydrobenzo[a]-xanthen-
1-one derivatives via the one-pot three-component condensation of 2-naphthol with arylaldehydes and
dimedone in the presence of catalytic amount of trityl chloride (TrCl) as a homogeneous organocatalyst
under natural and solvent-free conditions is described. It is interesting that TrCl by in situ formation of trityl
carbocation with inherent instability catalyzes the reaction.
Received 14 November 2011
Received in revised form 23 December 2011
Accepted 3 January 2012
1
Available online 12 January 2012
©
2012 Elsevier B.V. All rights reserved.
Keywords:
Trityl chloride
Organocatalyst
Multi-component reaction
Solvent free
12-aryl-8,9,10,12-tetrahydrobenzo[a]-
xanthen-11-one
1
. Introduction
the one-pot multi-component condensation reaction between
-naphthol, arylaldehydes and dimedone. Some catalysts have been
employed to promote this reaction such as ceric ammonium nitrate
[11], proline triflate [12], NaHSO .SiO [13], strontium triflate [14],
Zr(HSO [15], dodecatungstophosphoric acid [16], iodine [17], InCl
[18] and p-toluenesulfonic acid/ionic liquid ([bmim]BF ) [19]
[20], bronsted ionic liquid [21], molecular iodine [22], trichloroa-
cetic acid [23]. However, most of them suffer from the drawbacks such
as the use of toxic metals, the use of volatile organic solvents, high cost
and low yields. Therefore, it is still needed to develop efficient and cost-
effective catalysts and methods with high novelty for the synthesis of
these valuable compounds.
Development of organocatalytic processes in which the reactions
are catalyzed by organic molecules has become an area of tremen-
dous importance in current organic synthesis particularly from the
green chemistry point of view [24]. Unlike the conventional catalysis,
these organocatalysts are advantageous in many ways like high sta-
bility, availability of the catalyst, metal free nature, reduced toxicity,
and simple reaction conditions and can promote a chemical reaction
through different activation modes [25].
2
Multi-component reactions (MCRs) play an important role in
combinatorial chemistry because of the ability to synthesize target
compounds with greater efficiency and atom economy by generating
structural complexity in a single step from three or more reactants.
Moreover, MCRs offer the advantage of simplicity and synthetic effi-
ciency over conventional chemical reactions [1–3].
Xanthenes and benzoxanthenes are important class of heterocycles
that are known to possess multiple biological activities. Although not
widely found in nature, xanthenes and compounds based on these
core templates exhibit a wide range of pharmaceutical activities such
as anti-bacterial [4], anti-inflammatory [5], andanti-viral [6]. Some
xanthene based compounds have found application as antagonists
for inhibiting the action of zoxalamine and in photodynamic therapy
4
2
)
4 4
3
/
P
2
O
5
4
RuCl
4
[
7]. In addition, their derivatives can be used as dyes [8], pH sensitive
fluorescent materials for the visualization of biomolecular assemblies
9] and in laser technologies [10]. The best synthetic route toward
2-aryl-8,9,10,12-tetrahydrobenzo[a]-xanthen-11-one derivatives is
[
1
Triarylmethyl chlorides are inexpensive and can be obtained com-
mercially or easily prepared by the known procedure [26]. These
compounds have been extensively studied as bulky protective groups
⁎
Corresponding authors. Fax: +98 8118257407.
E-mail addresses: Khazaei_1326@yahoo.com (A. Khazaei), mzolfigol@yahoo.com,
zolfi@basu.ac.ir (M.A. Zolfigol).
1566-7367/$ – see front matter © 2012 Elsevier B.V. All rights reserved.
doi:10.1016/j.catcom.2012.01.001

A. Khazaei et al. / Catalysis Communications 20 (2012) 54–57
55
for amino and primary hydroxyl functional groups in multi-step
organic synthesis [27]. Furthermore, triarylmethyl chlorides in com-
bination with metal salts particularly SnCl have been used in a few
2
organic transformations [28]. Nevertheless, the use of these com-
pounds in the absence of co-catalysts is really attractive. Along
this line, recently, we have introduced triarylmethyl chlorides
(
Ar
bis(indolyl)methanes [29], N-sulfonyl imines [30] and 1-amidoalkyl-
-naphtols [31] in which triarylmethyl cation has acted as catalyst.
3
CCl) as novel and efficient organocatalysts for the synthesis of
2
It should be mentioned that carbocations with their inherent instabil-
ity has precluded up to now their scarce use in catalysis with decent
turnover numbers [31].
Having the above facts in mind, in this paper, we wish to introduce
a high novelty in synthesis of 12-aryl-8,9,10,12-tetrahydrobenzo[a]-
xanthen-11-ones by the solvent-free one-pot three-component
condensation of 2-naphthol with aromatic aldehydes and dimedone,
and use trityl chloride as a highly efficient and homogeneous
and neutral organocatalyst for this transformation (Scheme 1). In-
terestingly, this method for the preparation of 12-aryl-8,9,10,12-
tetrahydrobenzo[a]-xanthen-11-ones has none of the above-
mentioned drawbacks at all.
2
. Experimental
All chemicals were purchased from Merck or Fluka Chemical Com-
panies. The known products were identified by comparison of their
melting points and spectral data with those in the authentic samples.
The 1H NMR (500 or 300 MHz) and C NMR (125 or 75 MHz) were
run on a Bruker Avance DPX-250 FT-NMR spectrometer (δ in ppm).
Melting points were recorded on a Büchi B-545 apparatus in open
capillary tubes.
13
2
.1. General procedure for the synthesis of 12-aryl-8,9,10,12-
tetrahydrobenzo[a]-xanthen-11-ones 1a-n
A mixture of β-naphthol (0.144 g, 1 mmol), dimedone (0.140 g,
mmol), aldehyde (1 mmol) and TrCl (0.019 g, 0.07 mmol) in a
Fig. 1. Catalytic activity of different triarylmethyl chlorides as well as triphenylmethyl
alcohol on the reaction of 2-naphthol, benzaldehyde and dimedone at 110 °C.
1
1
0 mL round-bottomed flask connected to a reflux condenser, was
stirred in an oil-bath (110 °C). After completion of the reaction, as
monitored with TLC, the reaction mixture was cooled to room tem-
perature, petroleum ether (5 mL) was added to the crude reaction
mixture and filtered to separate the catalyst which will be recycled
for other reactions. Subsequently, the crude product was recrystal-
lized from aqueous ethanol (90%) to afford the pure product which
required no further purification.
(TON) and turn over frequencies (TOF) states on the effectiveness
of these catalysts for the synthesis of 12-aryl-8,9,10,12-tetrahydro-
benzo[a]-xanthen-11-ones. The TON and TOF values showed that
TrCl is more effective than MMTCl, DMTCl and TrOH. Thus, TrCl
was chosen as catalyst for the synthesis of 12-aryl-8,9,10,12-tetra-
hydrobenzo[a]-xanthen-11-ones.
In another study, the multi-component reaction of 2-naphthol
(1 mmol) with benzaldehyde (1 mmol) and dimedone (1 mmol)
was examined at 110 °C in the absence of catalyst in order to establish
the real efficacy of the catalyst. It was found that the product was
obtained in only 12% yield after 2 hours. Then, to optimize amount
of the catalyst, the reaction was tested using 3 mol%, 5 mol%, 7 mol%
and 10 mol of TrCl at 110 °C. The results showed that 7 mol% loading
of TrCl was sufficient to push the reaction forward and higher
amounts of the catalyst did not increase the yield significantly. This
amount of catalyst was also examined at range of 50–120 °C. The
best results were obtained when the reaction was carried out with
at 110 °C. The results are summarized in Table 1.
3
. Results and discussion
First of all, to optimize the reaction conditions, the reaction of
-naphthol (1 mmol), benzaldehyde (1 mmol) and dimedone (1 mmol)
2
was selected as a model reaction, and its behavior was studied in
the presence of 7 mol% of trityl chloride (TrCl), monomethoxytrityl
chloride (Ph
Ph(p-MeOC
10 °C. The results are summarized in Fig. 1. As it is shown in
2
(p-MeOC
6 4
H )CCl or MMTCl), dimethoxytrityl chloride
(
1
6 4 2
H ) CCl or DMTCl) and trityl alcohol (TrOH) at
Fig. 1, higher yield and shorter reaction time were obtained using
trityl chloride. Furthermore, we calculated turn over numbers
R
O
OH
+
O
O
O
Trityl Chloride (7 mol%)
Solvent-free, 110 °C
H
R
O
4
0-70 min
1
a-n
Scheme 1. The reaction of 2-naphthol with aldehydes and dimedone catalyzed by trityl chloride.

56
A. Khazaei et al. / Catalysis Communications 20 (2012) 54–57
Table 1
Effect of amounts of the catalyst (TrCl) and temperature on the the condensation of
-naphthol (1 mmol) with benzaldehyde (1 mmol) and dimedone (1 mmol).
3
2
a
Entry
Catalyst amount (mol%)
Temp. (°C)
Time (min)
Yield (%)
3
3
1
2
3
4
5
6
7
8
9
–
3
5
7
10
7
7
7
7
7
110
110
110
110
110
50
70
90
100
120
120
90
90
50
50
120
120
120
90
12
53
78
89
86
–
14
53
72
87
3
10
50
a
Isolated yield.
To explore the generality and scope of the catalyst, we extended
our study using TrCl (7 mol %) in the absence of solvent with different
aromatic aldehydes to prepare a series of benzo[a]xanthene-11-one
derivatives (Table 2). Various aromatic aldehydes containing
electron-releasing substituents, electron-withdrawing substituents
and halogens on the aromatic ring of arylaldehydes showed equal
ease towards the corresponding products formation in good to high
yields.
3
3
According to the literature in a plausible reaction mechanism,
we purpose that aldehyde and trityl chloride produce complexes of
intermediates I and II in a reversible reaction (Scheme 2) [25–27].
To prove the formation of I and II, benzaldehyde was reacted with tri-
1
13
tyl chloride at room temperature, and then IR, H and C NMR spec-
tra of the aldehydic functional group in the benzaldehyde as follows
3
[31]:
−
1
IR ðnujolÞ : νmaxðcm Þ of C ¼ O in benzaldehyde ð1705Þ decreased to 1700
in the reaction mixture:
1
H NMR ð300MHz; CDCl Þ : δ ðppmÞ of the aldehydic hydrogen ð9:78Þ
3
increased to 10:04 in the reaction mixture:
1
3
CNMRð300MHz; CDCl Þ
3
:
δðppmÞ of the carbonyl carbon ð191:8Þ increased to 195:2 in the
2
reaction mixture:
These results confirm that intermediates I and II are present in the
reversible reaction media. Moreover, the cationic intermediates I and
II have been introduced by Oikawa et al. for the first time [32]. These
complexes act as activated carbonyl compound and then react with
3
3
Scheme 2. The plausible mechanism for the condensation reaction of 2-naphthol with
aldehydes and dimedone using trityl chloride.
Table 2
The solvent-free preparation of 12-Aryl-8,9,10,12- tetrahydrobenzo[a]-xanthen-
11-ones using trityl chloride.
a
Entry
R
Time (min)/Yield (%)
M.p. °C (Lit.)
[
18]
18]
16]
1
1
1
1
1
1
1
1
1
1
1
1
1
1
a
b
c
d
e
f
g
h
i
j
k
l
m
n
C
6
H
5
50/89
45/91
45/90
40/93
45/94
55/89
55/90
50/89
40/92
45/91
55/90
60/86
60/84
70/82
148–151 (151–153)
175–178 (−)
2-naphthol providing III, which converts to IV by proton transfer. IV
could be converted to V by removing Ph COH in the reversible reac-
3
tion. Afterward V reacts with dimedone to produce VI and then VII
is formed by ring closing via the reaction between hydroxyl group
and activated carbonyl. Subsequently by the elimination of one
[
19]
3-ClC
4-ClC
2,3-Cl
2,4-Cl
2-BrC
3-BrC
4-BrC
3- NO
4-NO
6
H
H
4
178–179 (180–182)[
223–225
6
4
2
C
C
6
H
H
3
[
2
6
3
179–181 (181–182)
[
[
19]
19]
6
H
6
H
6
H
4
170-172 (−)
161-164 (−)
4
4
6
molecule H
2
O from VII, VIII is formed. The reaction between VIII
CCl
185–187 (186–187)[
17]
18]
18]
18]
and Ph COH afford the main product and Ph3CCl. Therefore Ph
3
3
[
2
C
H
4
167–170 (168–170)
is formed again as reusable catalyst and catalyzes the reaction to com-
plete it.
In another study, to confirm that TrCl cannot convert to TrOH and
HCl by the water produced during the reaction, and consequently HCl
is not the real catalyst of the process, the reaction of 2-naphthol,
benzaldehyde and dimedone was examined in the absence of TrCl,
2
C
6
H
4
175–178 (178–180)[
[
3-OHC
2-MeC
3-MeC
6
6
6
H
H
H
4
4
237–239 (240–241)
[
33]
160–163 (−)
178–180
4
18]
4-OMeC
6
H
4
201–203 (204–205)[
a
Isolated yield.

A. Khazaei et al. / Catalysis Communications 20 (2012) 54–57
57
using a base (pyridine, 7 mol%) in which negligible progress in the
Appendix A. Supplementary data
reaction was observed. The reaction was also tested in the presence
of 7 mol% of TrCl and pyridine as acid scavenger wherein the reaction
was performed successfully and the product was obtained in 89%
yield within 50 min.
Supplementary data to this article can be found online at doi:10.
1016/j.catcom.2012.01.001.
It is clear that in this conditions, pyridine could be absorb one H+
from intermediate VI and produce pyridinium chloride. But pyridinium
chloride is reacted with TrOH (that produces in the conversion of inter-
mediate V to VI) and forms TrCl. To prove this, in a separate reaction,
pyridinium chloride was reacted with TrOH at room temperature in
which TrCl was obtained, and some starting materials remained. Finally,
the condensation of 2-naphthol with benzaldehyde and dimedone was
examined in the presence of only pyridinium chloride (7 mol%), but the
yield was 26% after 120 min. These evidences showed that HCl did not
produce from TrCl in this conditions, and TrCl really has catalyzed the
reaction.
References
[
[
1] J. Zhu, H. Bienayme, Multicomponent Reactions, Eds., Wiley, Weinheim, 2005.
2] A. Hasaninejad, A. Zare, M. Shekouhi, J. Ameri Rad, Journal of Combinatorial
Chemistry 12 (2010) 844.
[
3] M.A. Zolfigol, A. Khazaei, A.R. Moosavi-Zare, A. Zare, V. Khakyzadeh, Applied
Catalysis A: General 400 (2011) 70.
[
4] T. Hideo, J. Teruomi, (Sankyo Co.) Jpn. Patent 56005480, 1981.
[5] J.P. Poupelin, G. Saint-Ruf, O. Foussard-Blanpin, G. Marcisse, G. Uchida-Ernouf, R.
Lacroix, European Journal of Medicinal Chemistry 13 (1978) 67.
[
6] R. W. Lambert, J. A. Martin, J. H. Merrett, K. E.B. parkes, G. J. Thomas, PCT Int. Appl.
WO9706178, 1997.
[
7] R.M. Ion, Progress in Catalysis 2 (1997) 55.
[8] A. Banerjee, A.K. Mukherjee, Stain Technology 56 (1981) 83.
9] C.G. Knight, T. Stephens, The Biochemical Journal 258 (1989) 683.
[
In conclusion, we have introduced a highly efficient and homoge-
nous organiocatalyst for the one-pot three-component reaction of
[
10] P.V. Shinde, A.H. Kategaonkar, B.B. Shingate, M.S. Shingare, Beilstein Journal of Organic
Chemistry 7 (2011) 53.
2
-naphthol, various arylaldehydes and dimedone. The promising points
[11] A. Kumar, S. Sharma, R.A. Maurya, J. Sarkar, Journal of Combinatorial Chemistry 12
2010) 20.
(
for the presented methodology are efficiency, generality, high yield,
cleaner reaction profile and simplicity which makes it a useful and at-
tractive process for the synthesis of 12-aryl-8,9,10,12-tetrahydrobenzo
[
[
12] J. Li, L. Lu, W. Su, Tetrahedron Letters 51 (2010) 2434.
13] B. Das, K. Laxminarayana, M. Krishnaiah, Y. Srinivas, Synlett (2007) 3107.
[14] J. Li, W. Tang, L. Lu, W. Su, Tetrahedron Letters 49 (2008) 7117.
[
[
15] N. Foroughifar, A. Mobinikhaledi, H. Moghanian, International Journal of Green
Nanotechnology: Physics and Chemistry 1 (2009) 57.
16] H.-J. Wang, X.-Q. Ren, Y.-Y. Zhang, Z.-H. Zhang, Journal of the Brazilian Chemical
Society 20 (2009) 1939.
[a]-xanthen-11-ones as biologically interesting compounds.
4
. Conclusions
[
[
[
[
17] R.-Z. Wang, L.-F. Zhang, Z.-S. Cui, Synthetic Communications 39 (2009) 2101.
18] G.C. Nandi, S. Samai, R. Kumar, M.S. Singh, Tetrahedron 65 (2009) 7129.
19] J.M. Khurana, D. Magoo, Tetrahedron Letters 50 (2009) 4777.
20] K. Tabatabaeian, A. Khorshidi, M. Mamaghani, A. Dadashi, M.K. Jalali, Canadian
Journal of Chemistry 89 (2011) 623.
In conclusion, we have introduced a highly efficient and homoge-
nous organiocatalyst for the one-pot three-component reaction of
-naphthol, various arylaldehydes and dimedone. The promising
2
[21] M. Zakeri, M.M. Heravi, M. Saeedi, N. Karimi, H.A. Oskooie, N. Tavakoli-Hoseini,
Chinese Journal of Chemistry 29 (2011) 1441.
points for the presented methodology are efficiency, generality, high
yield, cleaner reaction profile and simplicity which makes it a useful
and attractive process for the synthesis of 12-aryl-8,9,10,12-tetrahy-
drobenzo[a]-xanthen-11-ones as biologically interesting compounds.
[
[
22] X.J. Sun, J.F. Zhou, P.S. Zhao, Journal of Heterocyclic Chemistry 48 (2011) 1347.
23] Z. Karimi-Jaberi, S.Z. Abbasi, B. Pooladian, M. Jokar, E-Journal of Chemistry.
8 (2011) 1895.
[24] A. Dondoni, A. Massi, Angewandte Chemie, International Edition 47 (2008) 4638.
[
[
[
25] S. Verma, L.S. Jain, B. Sain, Tetrahedron Letters 51 (2010) 6897.
26] W.E. Bachmann, Org. Synth. Coll. 3 (1955) 841.
27] T.W. Green, P.G.M. Wuts, Protective Group in Organic Synthesis, 3rd ed John
Wiley and Sons, New York, 1999.
Acknowledgements
[
28] T. Mukaiyama, S. Kobayashi, Journal of Organometallic Chemistry 382 (1990) 39.
The authors gratefully appreciate Dr. Abolfath Parhami, faculty
member of Payame Noor University, for his scientific help to this
work. Moreover, they acknowledge partial support of this work by
the Research Affairs Office of Bu-Ali Sina University (Grant number
[29] A. Khalafi-Nezhad, A. Parhami, A. Zare, A.R. Moosavi Zare, A. Hasaninejad, F.
Panahi, Synthesis (2008) 617.
[
30] A. Khalafi-Nezhad, A. Parhami, A. Zare, A. Nasrollahi Shirazi, A.R. Moosavi Zare, A.
Hasaninejad, Canadian Journal of Chemistry 86 (2008) 456.
[31] A. Khazaei, M.A. Zolfigol, A.R. Moosavi-Zare, A. Zare, A. Parhami, A. Khalafi-Nezhad,
Applied Catalysis A: General 386 (2010) 179.
3
2-1716 entitled development of chemical methods, reagents and
[
[
32] M. Oikawa, H. Yoshizaki, S. Kusumoto, Synlett (1998) 757.
33] M.M. Heravi, Molecular Diversity 14 (2010) 621.
molecules), and Center of Excellence in Development of Chemical
Method (CEDCM), Hamedan, I.R. Iran.