Design, synthesis and antiviral potential of 14-aryl/heteroaryl-14H- dibenzo[a, j]xanthenes using an efficient polymer-supported catalyst

Article abstract of DOI:10.3390/molecules17067543

Polyethyleneglycol bound sulfonic acid (PEG-OSO₃H), a chlorosulphonic acid-modified polyethylene glycol was successfully used as an efficient and eco-friendly polymeric catalyst in the synthesis of 14-aryl/heteroaryl-14H-dibenzo[a, j]xanthenes

Full text of DOI:10.3390/molecules17067543

Molecules 2012, 17, 7543-7555; doi:10.3390/molecules17067543
OPEN ACCESS
molecules
ISSN 1420-3049
www.mdpi.com/journal/molecules
Article
Design, Synthesis and Antiviral Potential of
14-Aryl/Heteroaryl-14H-dibenzo[a,j]xanthenes
Using an Efficient Polymer-Supported Catalyst
Kalla Reddi Mohan Naidu 1, Balam Satheesh Krishna 2, Mungara Anil Kumar 3,
Palanisamy Arulselvan 4, Shaik Ibrahim Khalivulla 5 and Ola Lasekan 1,*
1
Department of Food Technology, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia
2
Department of Chemistry, Sri Venkateswara University, Tirupati 517502, India
3
Department of Nanomaterial Chemistry, Dongguk University, Gyeongju 780-714, Korea
4
Laboratory of Vaccines and Immunotherapeutics, Institute of Bioscience, Universiti Putra Malaysia,
43400 UPM Serdang, Selangor, Malaysia
5
Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, UCSI University,
No.1, Jalan Menera Gading, 56000 Cheras, Kuala Lumpur, Malaysia
* Author to whom correspondence should be addressed; E-Mail: lasekan@food.upm.edu.my;
Tel.: +603-8946-8535; Fax: +603-8948-5970.
Received: 11 May 2012; in revised form: 8 June 2012 / Accepted: 11 June 2012 /
Published: 18 June 2012
Abstract: Polyethyleneglycol bound sulfonic acid (PEG-OSO3H), a chlorosulphonic
acid-modified polyethylene glycol was successfully used as an efficient and eco-friendly
polymeric catalyst in the synthesis of 14-aryl/heteroaryl-14H-dibenzo[a,j]xanthenes
obtained from the reaction of 2-naphthol and carbonyl compounds under solvent-free
conditions with short reaction times and excellent yields. The biological properties of these
synthesized title compounds revealed that compounds 3b, 3c, 3f and 3i showed highly
significant anti-viral activity against tobacco mosaic virus.
Keywords: aryl aldehydes; 2-naphthol; PEG-OSO3H; neat reaction; xanthenes; tobacco
mosaic virus

Molecules 2012, 17
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1. Introduction
Viral plant diseases originated from tobacco mosaic virus (TMV) are considered serious threats to
modern agriculture worldwide. TMV is known to infect nine plant families and at least 125 individual
species, such as tobacco, tomato, pepper, cucumbers and a number of ornamental flowers. The
potential yield losses can fluctuate from 5 to 90%, depending on the strain/severity of TMV such as the
total time of infection, the optimal temperature during disease development/progression and the
presence of other plant diseases. It is found that in certain fields 90−100% of the plants show mosaic
or leaf necrosis by harvesting time. Several investigations have shown that TMV can modify plant
phenotypes by destruction of mitochondria followed by damage of plant quality. As a result of this
sequence, plant virus is also known as “plant cancer” and is difficult to prevent. So far, there are
neither effective chemical treatments that fully protect plants from TMV infection nor any other factor
that eliminates TMV from infected plants under field conditions [1].
In recent years polymer-supported compounds used as supported catalysts, reagents and scavengers
have drawn the attention of researchers [2]. The utility of polymer-supported catalysts is well-recognized
with their advantages like ease of workup, simple separation of products from the catalysts, economy
and easily use in industrial processes [3]. The high reactivity, lack of diffusion phenomena, analytical
simplicity and solubility profile of polyethylene glycols (PEGs with MW > 2,000 Da) as mostly
soluble in polar solvents and insoluble in a few non-polar solvents have established them as good
catalysts in homogeneous solid supported catalysis [4]. Rather than catalyst they are also used as a
solvent for high temperature reactions as they melt at low temperatures [5]. Among them PEG-OSO3H
is a good example of solid supported organic acid catalyst that is functionalized with mild acidity,
non-volatility and non-corrosiveness and also recognized as a good surfactant. It is reported that
PEG-OSO3H had been used for the synthesis of 3,4-dihydropyrimidones via the Biginelli reaction [5],
regioselective ring opening of epoxides with thiocyanate anion [6], Beckmann rearrangement and
dehydration of oximes [7] and synthesis of bis(indolyl)methanes and 4,4'-(arylmethylene)-bis(3-
methyl-1-phenyl-1H-pyrazol-5-ols) [8].
Aryl-14H-dibenzo[a,j]xanthenes are reported as important antibacterial, antiviral and
anti-inflammatory agents [9–11]. In addition to their biological applications they also applied in
photodynamic therapy [12], in industries as dyes, in laser technology and as fluorescent materials for
visualization of biomolecules [13–15]. These benzoxanthenes were synthesized from the reaction of
2-naphthol with formamide [16], β-hydroxynaphthyl carbinol with resorcinol [17], and from the action
of hot alkali on 2-naphthyl oxide [18]. The xanthene synthesis is catalyzed by some catalysts like
p-toluenesulfonic acid [19], sulfamic acid [20], AcOH/H2SO4 [15], iodine [21,22], K5CoW12O40·3H2O [23],
cyanuric chloride [24], LiBr [25], HClO4·SiO2 [26], KAl(SO4)2·12H2O [27], silica sulfuric acid [28]
and Yb(OTf)3 [29]. However, there is a need to find new catalysts and green methods to minimize the
drawbacks of existing methods such as poor yields, prolonged reaction times, toxic organic solvents,
excess reagents, catalysts and harsh reaction conditions so here we are reporting PEG-OSO3H as a
catalyst for this reaction and to the best of our knowledge, this is also the first investigation on the
anti-TMV bioactivity of xanthenes designed in this article.

Molecules 2012, 17
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2. Results and Discussion
2.1. Chemistry
To examine non-hazardous methods for the transformations which occur in organic synthesis herein
we report a highly versatile and efficient synthesis of aryl/heteroaryl-14H-dibenzo[a,j]xanthenes 3a–i
(Scheme 1) from two equivalents of 2-naphthol (1) and one equivalent of various aryl aldehydes 2a–i,
and catalytic amounts of a polymer-supported acidic catalyst. In a typical reaction, a 2:1 mixture of 1
and 2a and a catalytic amount of PEG-OSO3H (1 mol %) was placed in a 50 mL flat-bottomed flask
and heated for 30–60 min on a hot plate at 60–65 °C under solvent free condition to produce 3a in
excellent yield. The same reactions conditions were applied for the synthesis of the remaining series of
compounds 2b–i as presented in Scheme 1 and summarized in Table 1.
Scheme 1. Synthesis of 14-aryl/heteroaryl-14H-dibenzo[a,j]xanthenes.
a. Synthesis of 14-aryl-14H-dibenzo[a,j]xanthene from -naphthol and Various aryl aldehydes
R-CHO
OH
R
(2a-i)
2
(1)
O
(3a-i)
b. Synthesis of 1,4-bis(7H-dibenzo[c,h]xanthen-7-yl)piperazine from -naphthol and piperazine-1,4-dicarbaldehyde
O
CHO
N
OH
OH
CHO
N
2
4
N
N
N
N
CHO
O
(4)
O
(5)
(6)
c. Synthesis of 9,9-dimethyl-12-(pyridin-2-yl)-9,10-dihydro-8H-benzo[a]xanthen-11(12H)-one from -naphthol,
picolinaldehyde and 5,5-dimethylcyclohexane-1,3-dione
N
CHO
O
N
OH
(7)
O
O
(1)
(9)
O
(8)
Reaction Conditions: Neat, 60-65 °C
Catalyst: PEG-SO3H

Molecules 2012, 17
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Table 1. Synthesis of xanthenes catalyzed by PEG-OSO3H at 60–65 °C from 2-naphthols,
aldehydes and cyclic 1,3-dicarbonyl compounds.
Melting Point (°C)
Found Literature [Ref.]
Entry Product
R
Time (min) Yield (%) a
1
2
3a
3b
20
15
96
92
181–182
310–312
182–183 [30]
311–313 [30]
3
4
5
6
7
3c
3d
3e
3f
22
18
24
21
25
96
91
95
90
93
290–291
203–205
163–164
286–287
173–174
292–293 [30]
204–205 [30]
163–165 [31]
287–288 [30]
172–173 [30]
MeO
Cl
3g
8
9
3h
3i
30
20
85
97
206–207
178–179
208–210 [32]
-
10
11
5
6
25
30
90
94
183–184
185–187
-
-
12
9
32
92
179–181
-
N
a Isolated yield.
During our study on the dehydration of 2-naphthol by various aldehydes under solvent-free
condition at 80 °C, we made an interesting observation that 5 mL of PEG-600 catalyzed the reaction.
2-Naphthol underwent dehydration with benzaldehyde leading to aryl or heteroaryl-14H-dibenzo
[a,j]xanthenes after long reaction times and the yields were very low.
The same method was employed in the presence of catalytic amount of chlorosulphonic
acid supported PEG-6000 (1 mol %) and we found it as an efficient catalyst which brought this
reaction to completion at 65 °C in the absence of solvent. Blank experiments have shown that the
chlorosulphonoic acid alone could not bring about this transformation. In addition, it was observed that
only 1 mol % of PEG-OSO3H is sufficient for the formation of xanthenes. Encouraged by the results
obtained for benzaldehyde and other aldehydes, the reaction was further studied under the current

Molecules 2012, 17
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catalytic conditions with a variety of carbonyl (aromatic and heterocyclic aldehydes) compounds.
All the carbonyl substrates reacted smoothly with 2-naphthol to produce xanthenes (Table 1) in high
yields under these reaction conditions (60–65 °C; 30–60 min). The electronic nature of the substituent
in the aromatic ring did not show any noticeable effect on this conversion.
Additionally, we also investigated the recyclability of PEG–OSO3H for three consecutive cycles
(fresh + 3 cycles) for the synthesis of 14-phenyl-14H-dibenzo[a,j]xanthenes (3a). 2-Naphthol was
treated with benzaldehyde in the presence of 1 mol % catalyst under neat conditions for 20 min. After
completion of the reaction, PEG–OSO3H was extracted with water and reused after the evaporation of
aqueous layer under reduced pressure. The above sequence was repeated three times to produce the
product 3a in good yields without any significant loss in the catalytic activity of PEG–OSO3H (Table 2).
Table 2. Recyclability of the PEG–OSO3H for the one-pot condensation reaction of
2-naphthol with benzaldehyde under neat condition.
Entry
Recovery
Time/min
Yields a (%)
1
2
3
4
0
1
2
3
20
20
20
20
96
95
93
92
a Isolated yields for xanthene (3a) after each cycle.
The same reaction procedure was followed for the synthesis of remaining xanthene derivatives, i.e.,
monofunctionalized xanthene derivative 4-(14H-dibenzo[a,j]xanthen-14-yl)piperazine-1-carbaldehyde
(5) and bifunctionalized xanthene derivative 7-(1-(14H-dibenzo[a,j]xanthen-14-yl)piperidin-4-yl)-7H-
dibenzo[c,h]phenoxazine (6) from the reaction of piperazine-1,4-dicarbaldehyde with 2-naphthol.
Similarly 9,9-dimethyl-12-(pyridin-2-yl)-9,10-dihydro-8H-benzo[a]xanthen-11(12H)-one (9) was also
synthesized from the reaction of 2-naphthol, 2-picolinaldehyde and 5,5-dimethylcyclohexane-1,3-
dione as given in Scheme 1. Preliminary data for these compounds were provided in Table 1.
2.2. Biology
Ningnanmycin is a commercial antiviral agent, isolated from Strepcomces noursei var.
xichangensisn by the Chengdu Institute of Biology, Chinese Academy of Sciences. It is a kind of
well-known microbial pesticide that imparts its action by destruction of the coat protein of TMV,
thereby inducing plant host resistance pathways. It is more effective in the treatment of plants against
TMV than the other accessible commercial agents used in the agro-pharmaceutical industry [33].
However, the use of this agent for field trials is largely very limited by its photosensitivity and water
stickiness [34]. Therefore, further extensive investigations needs to be conducted in this related area for
the development of a highly efficient, economical, novel, and environmentally benign antiviral agent.
In this present investigation, we used ningnanmycin as a positive control for comparison of viral
activities. In this study it was observed that basic xanthene moiety of compounds showed highly
significant anti-viral activity against tobacco mosaic virus replication, as depicted in Figure 1, most of
our designed compounds exhibited good antiviral properties.

Molecules 2012, 17
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Figure 1. The anti-TMV activity of the synthesized compounds.
60
50
40
30
20
10
0
Compound
The basic polynuclear structural framework (tetracyclic and pentacyclic nuclei) in all synthesized
compounds containing an alkenyl functionality in conjugation to the oxygen atom of the xanthene
nucleus is the basic structural requirement for the exhibition of antiviral activity which was previously
reported for the compounds with the basic skeletons like fluorenone and anthraquinone derivatives.
Similarly the abovementioned structural features were also attributed the antiviral activity of the
compounds in the present study. Further, on comparison of all these analogues, 3b afforded potent
viral activity which is comparable to that of ningnanmycin. However, in most cases, the piperazine-
1,4-dicarbaldehyde had no distinct influence on the antiviral activity. In addition, the introduction of
electron-withdrawing groups (3b, 3c, 3f, 3g and 3i) resulted in higher antiviral potential than the
corresponding analogues with electron-donating groups (3d, 3e and 3h). The corresponding compound
6 showed lower inhibitory efficiency, which is possibly due, in part, to the relatively rigid structure.
On the basis of these observed results it may be speculated that the antiviral activity of xanthenes
group of compounds are primarily due to the presence of nitrogenous groups, which can prevent/
manage the host plant from initial infection/ replication by virus.
3. Experimental
3.1. General
All chemicals were purchased from Sigma-Aldrich and were used without further purification. IR
1
13
spectra were recorded on a Perkin-Elmer 683 spectrophotometer using KBr optics. H- and C-NMR
spectra were recorded on Bruker Avance 300 MHz NMR spectrometer operating at 300 MHz for
13
1H-NMR and 75 MHz for C-NMR. NMR data recorded in CDCl3 and referenced to TMS (1H and
13C). Mass spectra were recorded on a JEOL GCMATE II GC-MS spectrometer at SAIF, IIT Madras
(Chennai, India).
3.2. Catalyst Preparation
At 0 °C, chlorosulfonic acid (1.16 g, 10 mmol) was added to a solution of PEG-6000 (6.0 g,
1 mmol) in 5 mL of CH2Cl2. Then the resulting solution was stirred at room temperature overnight,
and the solution was concentrated under vacuum. Then diethyl ether (5 mL) was added and the

Molecules 2012, 17
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precipitated product was filtered and washed with diethyl ether three times to afford the purified
PEG-OSO3H [7].
3.3. General Procedure for the Synthesis of 14-(4-Chloro-3-nitrophenyl)-14H-dibenxo[a,j]xanthenes
3a–i
2-Naphthol (1, 0.29 g, 2 mmol) and benzaldehyde (2a, 0.10 g, 1 mmol) were mixed in the presence
of PEG-OSO3H catalyst. The resulting mixture was then stirred for 30 min at 60–65 °C. After the
completion of the reaction (as indicated by TLC), the reaction mixture was poured into ice water and the
obtained solid was collected by filtration, washed with water and then dried. The obtained solid was
recrystallised from hot ethanol.
The physical and spectral data of known compounds 3a–h were found to be in agreement with the
reported data [30–32] while the characterization data of newly synthesized products 3i, 5, 6 and 9 are
given below.
After completion of the reaction, water was added to the reaction mixture and was shaken to
dissolve PEG-OSO3H in it. Then in order to recover the catalyst, water was evaporated under reduced
pressure, and the resulting solid was washed with diethyl ether, and dried. The recovered catalyst was
reused four times for the subsequent reactions without loss of potentiality in catalytic activity [35].
14-Phenyl-14H-dibenzo[a,j]xanthene (3a). Pale yellow solid, m.p.: 181–182 °C. IR (KBr) vmax: 3068,
3020, 2885, 1620, 1590, 1512, 1488, 1457, 1402, 1252, 1080, 1025, 965, 825, 745, 700 cm−1. 1H-NMR
(CDCl3):  8.40 (d, J = 8.4 Hz, 2H), 7.82 (d, J = 7.9 Hz, 2H), 7.79 (d, J = 8.8 Hz, 2H), 7.58 (t, J = 7.7 Hz,
2H), 7.53 (d, J = 7.5 Hz, 2H), 7.49 (d, J = 8.8 Hz, 2H), 7.41–7.00 (m, 5H), 6.49 (s, 1H, Ar-CH).
13C-NMR (CDCl3):  148.1, 145.5, 131.4, 131.8, 128.7, 128.2, 128.1, 126.8, 126.5, 126.3, 124.2,
122.3, 117.1, 117.5, 38.3. EI-MS: m/z (%) 358 (M+); Anal. Calcd. for C27H18O: C, 90.47; H, 5.06.
Found: C, 90.41; H, 5.14.
14-(4-Nitrophenyl)-14H-dibenzo[a,j]xanthene (3b). Yellow solid, m.p.: 310–312 °C. IR (KBr) vmax
:
3062, 2931, 1629, 1595, 1527, 1453, 1401, 1346, 1200, 1141, 1108, 1015, 965, 850, 828, 810,
743 cm−1. 1H-NMR (CDCl3):  8.30 (d, J = 8.5 Hz, 2H), 7.98 (d, J = 8.7 Hz, 2H), 7.85–7.45 (m, 12H,
13
ArH), 6.60 (s, 1H, Ar-CH). C-NMR (CDCl3):  152.5, 148.0, 145.8, 135.1, 130.9, 130.7, 129.7,
128.6, 127.3, 124.7, 123.5, 123.0, 117.8, 116.2, 36.5. EI-MS: m/z (%) 403 (M+). Anal. Calcd. for
C27H17NO3: C, 80.38; H, 4.25; N, 3.47. Found: C, 80.30; H, 4.35; N, 3.55.
14-(2-Nitrophenyl)-14H-dibenzo[a,j]xanthene (3c). Yellow solid, m.p.: 290–291 °C. IR (KBr) vmax
:
3402, 3056, 2928, 1615, 1594, 1524, 1352, 1243, 1140, 815, 750 cm−1. 1H-NMR (CDCl3):  8.59–7.15
13
(m, 16H), 7.54 (s, 1H). C-NMR (CDCl3):  150.1, 147.8, 141.3, 134.5, 132.7, 132.0, 130.5, 129.8,
129.6, 129.2, 128.1, 127.6, 125.5, 125.1, 124.5, 122.9, 118.5, 118.1, 33.1. EI-MS: m/z (%) 403 (M+).
Anal. Calcd. for C27H17NO3: C, 80.38; H, 4.25; N, 3.47. Found: C, 80.23; H, 4.31; N, 3.54.
14-(4-Methoxyphenyl)-14H-dibenzo[a,j]xanthene (3d). Yellow solid, m.p.: 203–205 °C. IR (KBr) vmax
:
3041, 2913, 1615, 1582, 1511, 1465, 1433, 1404, 1250, 1122, 1088, 968, 825, 805, 748 cm−1. 1H-NMR
(CDCl3):  8.41 (d, J = 8.3 Hz, 2H), 7.83 (d, J = 8.2 Hz, 2H), 7.72 (d, J = 8.3 Hz, 2H), 7.58–6.71 (m,

Molecules 2012, 17
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13
10H, ArH), 6.51 (s, 1H), 3.70 (s, 3H). C-NMR (CDCl3):  158.2, 149.5, 137.1, 134.2, 131.4, 130.1,
129.6, 129.2, 127.8, 124.9, 123.1, 118.6, 117.8, 114.5, 54.1, 37.4. EI-MS: m/z (%) 388 (M+). Anal.
Calcd. for C28H20O2: C, 86.57; H, 5.19. Found: C, 86.44; H, 5.23.
14-(3-Methoxyphenyl)-14H-dibenzo[a,j]xanthene (3e). Yellow solid, m.p.: 163–164 °C. IR (KBr) vmax
:
3013, 2951, 2936, 1594, 1487, 1453, 1439, 1400, 1250 cm−1. 1H-NMR (CDCl3)  8.38 (d, 2H, J = 8.4 Hz).
7.80–7.72 (m, 4H), 7.65–7.31 (m, 6H), 7.01–6.53 (m, 4H), 6.41 (s, 1H), 3.61 (s, 3H). 13C-NMR
(CDCl3):  152.6, 148.8, 146.4, 131.3, 131.0, 129.2, 128.8, 128.5, 126.7, 124.3, 122.8, 120.8, 118.4,
117.1, 115.2, 111.4, 55.6, 38.3, Anal.Calcd. for C28H20O2: C, 86.45; H, 5.06. Found: C, 86.53; H, 5.14.
14-(4-Chlorophenyl)-14H-dibenzo[a,j]xanthene (3f). Brown solid, m.p.: 286–287 °C. IR (KBr) vmax
:
3050, 2926, 1620, 1594, 1456, 1438, 1393, 1242, 1061, 960, 826, 778, 695 cm−1. 1H-NMR (CDCl3): 
13
8.45 (d, J = 8.5 Hz, 2H), 8.01 (d, J = 8.7 Hz, 2H), 7.88–7.50 (m, 12H), 7.46 (s, 1H). C-NMR
(CDCl3):  156.1, 147.5, 132.3, 131.2, 129.8, 128.1, 128.6, 127.0, 126.8, 126.5, 124.7, 119.3, 118.2,
117.8, 33.3. EI-MS: m/z (%) 392 (M+). Anal. Calcd. for C27H17ClO: C, 82.54; H, 4.36. Found: C,
82.42; H, 4.41.
14-(3-Chlorophenyl)-14H-dibenzo[a,j]xanthene (3g). Brown solid, m.p.: 173–174 °C. IR (KBr) vmax
:
3053, 2924, 1621, 1592, 1508, 1455, 1430, 1398, 1245, 1064, 959, 815, 775, 748, 691 cm−1. 1H-NMR
13
(CDCl3):  8.30–6.96 (m, 16H, ArH), 6.45 (1H, s). C-NMR (CDCl3):  148.1, 146.3, 134.2, 131.6,
131.0, 129.6, 129.1, 128.1, 128.0, 127.2, 126.8, 126.4, 124.5, 122.4, 118.1, 116.4, 37.6. EI-MS: m/z
(%) 392 (M+). Anal. Calcd. for C27H17ClO: C, 82.54; H, 4.36. Found: C, 82.47; H, 4.43.
14-(4-Hydroxy-3-methoxyphenyl)-14H-dibenzo[a,j]xanthene (3h). Yellow solid, m.p.: 206–207 °C. IR
1
(KBr) vmax: 3020, 2399, 1593, 1508, 1431, 1215 cm−1. H-NMR (CDCl3): 8.39 (d, 2H, J = 8.30 Hz),
7.76–7.84 (m, 4H), 7.37–7.58 (m, 6H), 7.12–7.16 (m, 1H), 6.82 (d, 1H, J = 2.14 Hz), 6.71 (d, 1H,
13
J = 8.0 Hz),3.64 (s, 3H), 6.42 (s, 1H), 5.32 (s, 1H). C-NMR (CDCl3): 151.9, 150.5, 147.5, 140.2,
134.7, 134.3, 132.0, 129.9, 127.5, 126.0, 124.2, 121.1, 120.8, 117.5, 114.6, 58.9, 40.8. Anal. Calcd. for
C28H20O3: C, 83.15; H, 4.98. Found: C, 83.02; H, 4.88.
14-(4-Chloro-3-nitrophenly)-14H-dibenxo[a,j]xanthene (3i). Yellow solid, m.p.: 178–179 °C. IR
(KBr) vmax: 3157, 1412, 1231, 820, 746 cm−1. 1H-NMR (CDCl3):  8.24–7.24 (m, 15H, Ar-H), 6.54 (s,
1H, Ar-CH). 13C-NMR (CDCl3):  151.6, 147.2, 142.3, 132.3, 128.1, 127.1, 126.1, 125.4, 122.6,
122.1, 117.6, 114.3, 125.1, 134.2, 129.6, 124.2, 46.1. EI-MS: 476 (M+K).
3.4. Procedure for the Synthesis of 4-(14H-Dibenzo[a,j]xanthen-14-yl)piperazine-1-carbaldehyde (5)
2-Naphthol (1, 0.29 g, 2 mmol) and piperazine-1,4-dicarbaldehyde (4, 0.14 g, 1 mmol) were mixed
in the presence of PEG-OSO3H catalyst (1 mol %). The resulting mixture was then stirred for 30 min
at 60–65 °C. After the completion of the reaction (as indicated by TLC), the reaction mixture was
poured into ice water and the obtained solid was collected by filtration, washed with water and then
1
dried. Green solid, m.p.: 183–184 °C. IR (KBr) νmax: 3153, 1614, 1410, 1234, 746 cm−1. H-NMR
(CDCl3):  7.83 (s, 1H, –CHO), 7.36–6.60 (m, 12H, Ar-H), 5.87 (s, 1H, Ar-CH), 1.35–1.20 (m, 8H,

Molecules 2012, 17
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–N–CH2). 13C-NMR (CDCl3): d 153.4, 151.3, 136.6, 127.3, 123.4, 121.7, 120.0, 119.40, 119.0, 116.6,
+
111.8, 56.6, 55.5, 32.1. EI-MS: 394 (M+), 412 (M+NH4 ).
3.5. Procedure for the Synthesis of 7-(1-(14H-dibenzo[a,j]xanthen-14-yl)piperidin-4-yl)-7H-dibenzo-
[c,h]phenoxazine (6)
2-Naphthol (1, 0.58 g, 4 mmol) and piperazine-1,4-dicarbaldehyde (4, 0.14 g, 1 mmol) were mixed in
presence of PEG-OSO3H catalyst (1 mole%). The resulting mixture was then stirred for 30 min at
60–65 °C. After the completion of the reaction (as indicated by TLC), the reaction mixture was poured
into ice water and the obtained solid was collected by filtration, washed with water and then dried.
1
Light greenish solid, m.p.: 185–187 °C; IR (KBr) vmax: 3157, 1412, 1231, 820, 746 cm−1; H-NMR
(CDCl3):  8.26–7.35 (m, 24H, Ar-H), 7.25 (s, 2H, Ar-CH), 1.40–1.6 (m, 8H, –N–CH2); APCI-MS:
+
664 (M+NH4 ).
3.6. Procedure for the Synthesis of 9,9-Dimethyl-12-(pyridin-2-yl)-9,10-dihydro-8H-benzo[a]xanthen-
11(12H)-one (9)
2-Naphthol (1, 0.14 g, 1 mmol), 2-picolinaldehyde (7, 0.10 g, 1 mmol) and 5,5-dimethylcyclo-
hexane-1,3-dione (8, 0.14 g, 1 mmol) were mixed in presence of PEG-OSO3H catalyst (1 mol %). The
resulting mixture was then stirred for 30 min at 60–65 °C. After the completion of the reaction (as
indicated by TLC), the reaction mixture was poured into ice water and the obtained solid was collected
by filtration, washed with water and then dried. White solid, m.p.: 179–181 °C. IR (KBr) vmax: 2950,
1
1670, 1630, 1545, 1350, 1220, 1150, 102 cm−1. H-NMR (CDCl3):  6.55–8.05 (m, 10H, ArH), 5.62
13
(s, 1H, CH), 2.55 (s, 2H, CH2), 2.26 (s, 2H, CH2) 1.10 (s, 3H, CH3), 0.99 (s, 3H, CH3). C-NMR
(CDCl3):  197.6, 164.1, 149.4, 148.2, 133.8, 132.1, 132.0, 129.5, 128.9, 128.8, 127.4, 125.2, 124.3,
118.8, 117.5, 115.2, 112.9, 51.5, 41.9, 41.1, 34.1, 32.8, 29.7, 27.9. EI-MS (%): 355 (M+).
3.7. Antiviral Activity
3.7.1. Purification of Tobacco Mosaic Virus (TMV)
Using Goodings’ method [36], the upper leaves of Nicotiana tabacum L inoculated with TMV were
selected and ground in a phosphate buffer, then filtered through double layer pledget. The filtrate was
centrifuged at 10,000 g, treated twice with PEG and centrifuged again. The whole experiment was
carried at 4 °C. Absorbance values were measured at 260 nm using an ultraviolet spectrophotometer:
 (dilution ratio )
A260
Virus concentrat ion 
0.1%, 260 nm
E
1cm
3.7.2. Curative Effect of Compounds against TMV in Vivo
Growing leaves on Nicotiana tabacum, L of the same ages were selected. TMV (concentration of
6 × 10−3 mg/mL) was dipped to inoculate the whole leaves. Then the leaves were washed with water
and dried. The compound solution was smeared on the left side and the solvent was smeared on the

Molecules 2012, 17
7552
right side for control. The local lesion numbers were then recorded 3–4 days after inoculation [37]. For
each compound, three repetitions were conducted. The inhibition rate of the compound was then
calculated according to the following formula (‘av’ means average):
av.local lesion numbers of control
(not treated with compound)


 (av.local lesion numbers smeared with drugs)




Inhibition rate(%) 
100
av.local lesion numbers of control (not treated with compound)
4. Conclusions
Polyethyleneglycol sulphonic acid (PEG–OSO3H) has been successfully applied as an efficient,
environmentally benign polymeric catalyst for the synthesis of a series of 14-aryl-14H-
dibenzo[a,j]xanthenes through one-pot condensation reaction of 2-naphthol with various aromatic
aldehydes under solvent-free conditions at 60 °C. This synthetic protocol offers several advantages,
including short reaction times, solvent-free conditions, recyclability of the catalyst and high isolated
yields of the products. The present investigations concluded that our synthesized xanthenes may have
potential as novel chemical compounds with biologically active nitrogenous groups for the
development of new anti-viral agents for controlling plant disease caused by TMV and/or other
viruses. Results in our work, especially the synthesis of xanthene compounds with an eco-friendly
catalyst may help to improve the method of application and possible utilization of this group of
compounds in the control of plant virus diseases. Furthermore, extensive investigation in terms of the
specific molecular mechanism responsible for anti-viral property of the title compounds is ongoing.
Acknowledgments
The authors are grateful to Research University Grant Scheme (RUGS), University Putra Malaysia,
43400 Serdang, Selangor, Malaysia.
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Sample Availability: Samples of thecompounds 3a–3i, 5, 6 and 9 are available from the authors.
© 2012 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article
distributed under the terms and conditions of the Creative Commons Attribution license
(http://creativecommons.org/licenses/by/3.0/).