Mild and highly efficient method for synthesis of 14-Aryl(alkyl)-14H- dibenzo[a,j]xanthenes and 1,8-dioxooctahydroxanthene derivatives using pentafluorophenyl ammonium triflate as a novel organocatalyst

Article abstract of DOI:10.1016/S1872-2067(11)60393-8

A simple and facile synthesis of 14-aryl and alkyl-14H-dibenzo[a,j] xanthenes and 1,8-dioxooctahydroxanthene derivatives has been successfully developed by treatment of β-naphthol or dimedone with aldehydes under mild conditions in the presence of a penta

Full text of DOI:10.1016/S1872-2067(11)60393-8

CHINESE JOURNAL OF CATALYSIS
Volume 33, Issue 6, 2012
Online English edition of the Chinese language journal
Cite this article as: Chin. J. Catal., 2012, 33: 982–985.
ARTICLE
Mild and Highly Efficient Method for Synthesis of
14-Aryl(alkyl)-14H-dibenzo[a,j]xanthenes and
1,8-Dioxooctahydroxanthene Derivatives
Using Pentafluorophenyl Ammonium Triflate
as a Novel Organocatalyst
Samad KHAKSAR*, Nosratollah BEHZADI
Chemistry Department, Ayatollah Amoli Branch, Islamic Azad University, Amol, Iran
Abstract: A simple and facile synthesis of 14-aryl and alkyl-14H-dibenzo[a,j]xanthenes and 1,8-dioxooctahydroxanthene derivatives has
been successfully developed by treatment of ꢀ-naphthol or dimedone with aldehydes under mild conditions in the presence of a penta-
fluorophenyl ammonium triflate (PFPAT) organocatalyst. These catalytic condensation reactions represent green chemical processes and
the PFPAT organocatalyst is air-stable, cost-effective, easy to handle, and easily removed from the reaction mixtures.
Key words: pentafluorophenyl ammonium triflate; organocatalyst; xanthene; ꢀ-naphthol
14-Substituted-14H-dibenzo[a,j]xanthene derivatives have
been found to possess a broad spectrum of biological activities,
including antibacterial [1], anti-inflammatory [2], and antiviral
activities [3]. Furthermore, these compounds have been used in
photodynamic therapy [4] and as antagonists for paralyzing the
action of zoxazolamine [5,6]. These compounds have also been
used as dyes [7,8], in laser technology [9], and in fluorescent
materials for visualization of biomolecules [10] and as pH
sensitive fluorescent materials for the visualization of bio-
molecules [11]. Classically, xanthene derivatives were synthe-
sized either by the reaction of aryloxymagnesium halides with
triethylorthoformate [12], the trapping of benzynes with phe-
nols [13], or by the reaction of ꢀ-naphthol with
2-naphthol-1-methanol [14], formamide [15], carbon monox-
ide [16], and aldehydes or acetals [17–30]. Unfortunately,
many of these existing methodologies suffer from one or more
disadvantages such as prolonged reaction times, low yields, use
of harmful organic solvents, requirement for an excess of
catalyst/reagents, and harsh reaction conditions. Pentafluoro-
phenyl ammonium triflate (PFPAT) has emerged as a highly
efficient and effective potential Brønsted acid catalyst, im-
parting high levels of regio- and chemo-selectivity in a variety
of chemical transformations, because of its low toxicity, air and
water compatibility, operational simplicity, and remarkable
ability to suppress side reactions in acid sensitive substrates
[31,32]. In a continuation of our investigations on the
development of novel synthetic methodologies [33–39], we
herein report a new, convenient, mild, and efficient procedure
for the synthesis of 14-aryl(alkyl)-14H-dibenzo[a,j]xanthenes
and 1,8-dioxooctahydroxanthene derivatives catalyzed by
PFPAT as an effective and novel organocatalyst requiring only
mild reaction conditions (Scheme 1).
R
OH
O
2
4aꢀ4m
PFPAT (10 mol%)
toluene, 25ꢀ30 oC, 3ꢀ5 h
or
2
3
RCHO
+
O
2
O
1
O
R
O
O
ꢀ
5a 5k
Scheme 1. Synthesis of xanthene derivatives.
Received 29 December 2011. Accepted 20 March 2012.
*Corresponding author. Fax: +98-121-2517071; E-mail: S.khaksar@iauamol.ac.ir; Samadkhaksar@yahoo.com
This work was supported by the Islamic Azad University, Ayatollah Amoli Branch.
Copyright © 2012, Dalian Institute of Chemical Physics, Chinese Academy of Sciences. Published by Elsevier BV. All rights reserved.
DOI: 10.1016/S1872-2067(11)60393-8

Samad KHAKSAR et al. / Chinese Journal of Catalysis, 2012, 33: 982–985
1 Experimental
Table 1 The synthesis of 14-(4-nitrophenyl)-14H-dibenzo[a,j] xanthene
using different catalysts
1.1 General procedure for the preparation of 14-aryl
(alkyl)-14H-dibenzo[a,j]xanthenes
Time
(h)
2.5
20
2.5
Yield
(%)
85
93
90
Temperature
(oC)
90
Catalyst
Ref.
Iodine
p-TsOH
Sulfamic acid
H2SO4/SiO2
[TEBSA][HSO4]
[24]
[18]
[26]
[27]
[28]
A toluene solution (3 ml) of aldehyde (1 mmol) and
ꢀ-naphthol (2 mmol) was mixed with PFPAT (10 mol%), and
the resulting mixture was stirred for the appropriate reaction
time. Upon completion of the reaction, as indicated by TLC,
the organic phase was washed with 1 mol/L aqueous NaOH
solution (1 ml). The organic phase was then collected and the
solvent removed in vacuo to give the crude product, which was
purified by recrystallization from hot ethanol to afford pure
product.
reflux
125
125
1
97
93
5 min
120
H14[NaP5W30O110
]
1
2
3
3
6
99
95
98
98
90
110
r.t.
r.t.
[29]
[30]
this work
this work
this work
Sc[N(SO2C8F17)2]3
PFPAT (10 mol%)
PFPAT (20 mol%)
PFPAT (5 mol%)
75
r.t.
1.2 General procedure for the preparation of
1,8-dioxooctahydroxanthenes
most efficient of all the catalysts tested, in terms of time, yield,
and temperature (Table 1). A survey of possible solvents re-
vealed toluene to be the best choice. It is worthy of note that the
toluene was used directly without rigorous drying. Low yields
were obtained when CH2Cl2 or water was employed as the
solvent. Some dependence on the amount of PFPAT used was
also observed. A satisfactory result was obtained in the pres-
ence of 10 mol% PFPAT and no discernible improvement was
noted when the catalyst loading was increased to 20 mol%. A
decrease in the catalyst loading to 5 mol%, however, led to a
reduction in product yield.
A toluene solution (3 ml) of aldehyde (1 mmol) and
5,5-dimethyl-1,3-cyclohexanedione (2 mmol) was mixed with
PFPAT (10 mol%), and the resulting mixture was stirred for the
appropriate reaction time. Upon completion of the reaction, as
indicated by TLC, the organic phase was washed with 1 mol/L
aqueous NaOH solution (1 ml). The organic phase was then
collected and the solvent removed in vacuo to give a crude
product, which was purified by recrystallization from hot
ethanol to afford pure product. Spectroscopic data for selected
examples are listed as follows.
Using these optimized reaction conditions, the scope and
efficiency of this approach was explored for the synthesis of a
wide
variety
of
substituted
14-aryl-
and
14-(4-Chlorophenyl)-14H-dibenzo[a,j]xanthene (4a). Yel-
low solid; mp 291–292 °C (lit. 290–291 °C). IR (KBr, cm–1): ꢁ
3066, 2922, 1622, 1590, 1514, 1456, 1397, 1245, 1237, 1209,
1140. 1H NMR (400 MHz, DMSO-d6): ꢂ 6.76 (s, 1H), 7.18 (d, J
= 6.8 Hz, 2H), 7.46–7.64 (m, 10H), 8.92 (d, J = 7.79 Hz, 2H),
8.66 (d, J = 7.6 Hz, 2H). 13C NMR (100 MHz, DMSO-d6): ꢂ
36.3, 117.4, 118.1, 123.4, 123.7, 125.0, 127.4, 128.8, 129.1,
129.6, 130.1, 131.1, 131.2, 144.8, 148.4.
9-Phenyl-3,3,6,6-tetramethyl-1,2,3,4,5,6,7,8-octahydroxant
hene-1,8-dione (5g). White solid; mp 204–205 °C (lit. 204–206
°C). IR (KBr, cm–1): ꢁ 2954, 1664, 1364, 1199. 1H NMR (400
MHz, DMSO-d6): ꢂ 0.90 (s, 6H), 1.04 (s, 6H), 2.09 (d, J = 16.1
Hz, 2H), 2.27 (d, J = 16.2 Hz, 2H), 2.53 (d, J = 17.1 Hz, 2H),
2.58 (d, J = 17.7 Hz, 2H), 4.53 (s, 1H), 7.10 (t, J = 7.0 Hz, 1H),
7.18 (d, J = 7.0 Hz, 2H), 7.21 (t, J = 7.20 Hz, 2H). 13C NMR
(100 MHz, DMSO-d6): ꢂ 27.7, 29.6, 32.3, 32.6, 41.3, 51.2,
116.1, 126.8, 128.4, 128.8, 144.5, 162.7, 196.8.
14-alkyl-14H-dibenzo[a,j]xanthenes and the results are sum-
marized in Table 2. The reactions of variety of structurally
diverse aldehydes with ꢀ-naphthol were investigated using the
optimized reaction conditions (Scheme 1). It was found that all
the reactions proceeded smoothly to give the corresponding
benzoxanthenes (4a–4m) in high yields (Table 2). This proto-
col tolerates aromatic aldehydes containing both elec-
tron-donating and electron-withdrawing substituents well. The
electronic effects and the nature of the substituents on the
aldehydes showed some clear trends in terms of yields and
reaction times. Aromatic aldehyde substrates with elec-
tron-withdrawing groups reacted well at faster reaction rates
than aromatic aldehyde substrates with electron-donating
groups. Ortho-substituted aromatic aldehydes, however, did
not react as smoothly, likely because of steric hindrance, and
longer reaction times were required to get the corresponding
products in high yields (Table 2, entries 2 and 7). Longer re-
action times were also required when aliphatic aldehydes were
employed for the corresponding xanthenes to be obtained in
good yields (Table 2, entries 12 and 13). We also examined the
effect of solvents, revealing that the best yield was obtained in
toluene, whereas much lower yields were observed with other
solvents, including dichloromethane and acetonitrile.
2 Results and discussion
A series of comparative experiments were initially per-
formed to assess the effectiveness of PFPAT versus other acidic
catalysts in the formation of benzoxanthene. In some cases,
data for other acidic catalysts were taken from the literature.
The results are shown in Table 1. PFPAT was found to be the
To further demonstrate the applicability of this method, the

Samad KHAKSAR et al. / Chinese Journal of Catalysis, 2012, 33: 982–985
Table 2 Synthesis of 14-aryl- and 14-alkyl-14H-dibenzo [a,j]xanthenes
in the presence of PFPAT
Table 3 Synthesis of tetramethyloctahydroxanthene-1,8-diones in the
presence of PFPAT
Entry
1
Aldehyde
CHO
Product
Time (h) Yield of 4 (%)
Entry
1
Aldehyde
CHO
Product
Time (h) Yield of 5 (%)
3
97
3
97
4a
5a
Cl
Cl
CHO
Cl
CHO
Cl
2
3
4
3
95
96
2
3
4
3
95
96
4b
4c
5b
5c
CHO
CHO
O N
O N
2
O2N
O N
2
2
CHO
CHO
4
5
4
3
90
92
4
5
4
3
90
92
5d
5e
4d
4e
CHO
CHO
F
F
CHO
CHO
6
3
92
5f
6
7
3
4
92
90
4f
Br
Br
CHO
CHO
7
8
4.5
4.5
90
90
5g
5h
4g
Br
CHO
CHO
CHO
8
9
4.5
5
90
85
4h
4i
Me
CHO
9
5
85
5i
OMe
OMe
Me
CHO
10
11
5
4
92
90
4j
10
11
4
6
92
85
5j
CHO
CHO
S
5k
4k
CHO
CHO
CHO
N
12
13
5
5
90
88
4l
4m
3 Conclusions
A simple and highly efficient method for the synthesis of
14-substituted-14H-dibenzo[a,j]xanthenes has been developed
via the condensation of ꢀ-naphthol with aldehydes catalyzed by
pentafluorophenyl ammonium triflate in toluene at room tem-
perature. The present approach offers the advantages of simple
methodology, clean and mild reaction conditions, high
atom-economy, short reaction time, low environmental impact,
wide substrate scope, high yield, and excellent product purity.
preparation of 1,8-dioxooctahydroxanthene derivatives was
also investigated. The reaction of 4-chlorobenzaldehyde with
5,5-dimethyl-1,3-cyclohexanedione in the presence of PFPAT
under similar conditions was initially investigated as a model
reaction. As expected, these substrates underwent a smooth,
one pot conversion to give the corresponding
1,8-dioxooctahydroxanthene derivatives in excellent yields
(Table 3, entry 1). With the optimized conditions in hand, to
explore the scope and generality of the reaction, we extended
our study with other structurally varied aromatic, heteroaro-
matic, and aliphatic aldehydes to prepare a series of
9-aryl/heteroaryl/alkyl-3,3,6,6-tetramethyl-1,2,3,4,5,6,7,8-octa
hydroxanthene-1,8-diones (Table 3, entries 1–11). A remark-
able feature of this improved protocol was the tolerance of the
current reaction conditions for a variety of functional groups,
including ether, alkyl, nitro, and halide groups.
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