Facile and efficient synthesis of xanthenedione derivatives promoted by niobium pentachloride

Article abstract of DOI:10.1515/chempap-2016-0098

Xanthenedione derivatives were synthesised in one-pot reactions between arylaldehyde derivatives and 1, 3-cyclohexanedione promoted by niobium pentachloride. This new method is simple, cost-effective, high-yielding with a good variety of substrates genera

Full text of DOI:10.1515/chempap-2016-0098

Chemical Papers 70 (12) 1658–1664 (2016)
DOI: 10.1515/chempap-2016-0098
ORIGINAL PAPER
Facile and efficient synthesis of xanthenedione derivatives promoted
by niobium pentachloride
Willian H. dos Santos, Luiz C. Da Silva-Filho*
Department of Chemistry, Faculty of Sciences, S˜ao Paulo State University (UNESP),
Av. Eng. Luiz Edmundo Carrijo Coube, 14-01, Bairro: Vargem Limpa, 17033-360, Bauru, S˜ao Paulo, Brazil
Received 5 January 2016; Revised 5 May 2016; Accepted 16 May 2016
Xanthenedione derivatives were synthesised in one-pot reactions between arylaldehyde derivatives
and 1,3-cyclohexanedione promoted by niobium pentachloride. This new method is simple, cost-
effective, high-yielding with a good variety of substrates generality, and can be conducted within
reasonable reaction times.
c
ꢀ 2016 Institute of Chemistry, Slovak Academy of Sciences
Keywords: niobium pentachloride, Lewis acid, xanthenedione derivatives, one-pot reactions
Introduction
and rhodomyrtosone I (II ) extracted from Rhodomyr-
tus tomentosa (Hiranrat et al., 2012; Hiranrat & Ma-
habusarakam, 2008; Limsuwan et al., 2009; Sianglum
et al., 2011; Visutthi et al., 2011), together with the
compound known as BF-6 (III ) extracted from the
leaves of Baeckea frutescens (Makino & Fujimoto,
1999) are examples of natural xanthenediones (Fig. 1).
Xanthene derivatives can be prepared by several
methods: cyclodehydration (Bekaert et al., 1992), the
trapping of benzynes by phenols (Knight & Little,
2001), the palladium-catalysed cyclisation of poly-
cyclic aryltriflate esters (Wang & Harvey, 2002),
a simple and efficient procedure for the synthesis
of xanthene derivatives through one-pot condensa-
tion of 2-naphthol with aryl aldehydes in the pres-
ence of niobium pentachloride (Bartolomeu et al.,
2014), the condensation of cyclohexane-1,3-diones and
aromatic aldehydes in the presence of solid acids
Y(NO3)3 · 6H2O and SnCl2 ·2H2O (Karami et al.,
2013a), amongst others (Horning & Horning, 1946;
John et al., 2006; Saini et al., 2006; Zhang & Tao 2008;
Zhang & Liu, 2008; Wang et al., 2008; Urinda et al.,
2009; Lu¨ et al., 2009; Maleki et al., 2011; Soleimani
et al., 2011; Pramanik & Bhar, 2012; Dharma Rao et
al., 2012; Karami et al., 2013b, 2013a, 2014; Li et al.,
2013; Cao et al., 2013; Shirini et al., 2013; Napoleon
& Khan 2014; Napoleon et al., 2014; Iniyavan et al.,
Among the various classes of natural compounds,
xanthene derivatives have received special attention
since many of these compounds have biological and
therapeutic properties (Chibale et al., 2003; El-Brashy
et al., 2004). Xanthene derivatives are recognised for
their use as sensitising dyes (Bhowmik & Ganguly,
2005), in photodynamic therapy to destroy tumour
cells (Ormond & Freeman, 2013), in laser technolo-
gies (Ahmad et al., 2002) and in pH-sensitive fluo-
rescent materials for the visualisation of biomolecules
(Knight & Stephens, 1989). Research has focused
on secondary metabolites of the genus Allanblackia
(Locksley & Murray, 1971; Nkengfack et al., 2002)
and the significant increase in the number of stud-
ies stems from the fact that many of these secondary
metabolites, such as xanthones, benzophenones and
pentacyclic triterpenes, exhibit biological, pharmaco-
logical, anti-inflammatory, antimicrobial, antifungal,
HIV-inhibitory and cytotoxic properties (Fuller et al.,
1999; Peres et al., 2000; Peres & Nagem, 1997). The
plants of the genus Allanblackia, which belong to the
family Clusiaceae, are found in large forests in the west
and south of the province of Cameroon, where they
are used to treat respiratory diseases, toothache and
diarrhoea (Fobane et al., 2014). Rhodomyrtone A (I)
*Corresponding author, e-mail: lcsilva@fc.unesp.br
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1659
Fig. 1. Examples of natural xanthenediones.
Fig. 2. Synthesis of xanthenedione derivatives.
2014; Shirini et al., 2014, 2015; Preetam et al., 2015;
Ilangovan et al., 2011). However, some of these meth-
ods involve long reaction times, extreme reaction con-
ditions, expensive reagents and unsatisfactory yields,
hence the improvement of these syntheses has been the
target of several studies. One-pot reactions are effec-
tive for carrying out numerous transformations and
forming several bonds in a single pot while, at the
same time, eliminating several purification steps, min-
imising chemical waste generation and saving time.
Such advantages have significant relevance in mod-
ern synthetic methodology (D’Souza & Mu¨ller, 2007;
Isambert & Lavilla, 2008).
As part of the present investigation of the use of
NbCl5 as a promoter in organic reactions, this work
describes a new route for the preparation of xan-
thenedione derivatives (VIa–VIn) through a one-pot
reaction between aldehyde derivatives (Va–Vn) and
1,3-cyclohexanedione (IV) promoted by niobium pen-
tachloride (Fig. 2).
Companhia Brasileira de Metalurgia e Minera¸c˜ao
(CBMM, Brasil) and re-crystallised by sublimation
following the procedure detailed in the supplemen-
tary data; this method is described in the litera-
ture (Alves, 1986). Thin-layer chromatography was
performed on 0.2 mm Merck 60F254 silica gel alu-
minium sheets (Germany), with visualisation using a
vanillin/methanol/water/sulphuric acid mixture. In-
frared (IR) spectra were recorded using a Bruker Ver-
tex 70 Fourier Transform Spectrometer (Germany)
equipped with a Bruker Platinum ATR unit (Ger-
many). A Bruker DRX 400 spectrometer was em-
ployed for generating the NMR spectra (CDCl3 as
a solvent) using tetramethylsilane as internal refer-
ence. HR-MS analyses were performed on an LCMS-
IT-TOF mass spectrometer (Shimadzu, Japan). The
melting points of the synthesised compounds were de-
termined by differential scanning calorimetry (DSC).
DSC measurements were performed using a Mettler-
Toledo model DSC 1 stare system.
Niobium pentachloride is a stronger Lewis acid cur-
rently attracting interest as a reagent in organic syn-
thesis; it has found applications as an effective catalyst
in a variety of organic reactions (Andrade, 2004; Guo
et al., 2011; Hou et al., 2010b, 2010a, 2011a, 2011b;
Lacerda et al., 2012; Oshiro et al., 2015; Bartolomeu
et al., 2014, 2015).
General procedure for syntheses of xanthene-
dione derivatives (VIa–VIm)
To a solution of NbCl5 (67.5 mg, 0.25 mmol) in an-
hydrous CH3CN (2.0 mL), maintained under N2 atmo-
sphere (Table 1), a solution of 1,3-cyclohexanedione
(IV; 224 mg, 2.0 mmol) and the respective ary-
laldehyde (Va–Vn; 1.0 mmol) in anhydrous CH3CN
(3.0 mL) were added. The reaction mixture was stirred
under reflux for 2 h. Next, the reaction mixture was
poured into water (10.0 mL) at 0◦C and the precip-
itate was filtered and washed with a mixture of ace-
tone/water (ϕr = 1 : 1). The products were dissolved
Experimental
The solvents were distilled with CaH2. All chemi-
cals were purchased from Sigma–Aldrich (USA) and
used without further purification, with the excep-
tion of NbCl5. The NbCl5 used was supplied by
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Table 1. Optimisation of one-pot reaction between IV and Va promoted by NbCl5a,b
Entry
NbCl5 (mole %)
Solvent
Time (h)
Yieldc (%)
1a
2a
0
DCM
DCM
DCM
DCM
DCE
DCE
DCE
DCE
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
24
2
2
2
24
2
2
2
24
2
2
–
10
25
50
0
10
25
50
0
25
50
10
25
50
15
22
19
–
18
45
33
–
90
77
25
87
75
3a
4a
5a
6a
7a
8a
9a
10a
11a
12b
13b
14b
2
2
2
a) Reaction conditions: 1,3-cyclohexanedione (IV) (2.0 mmol), benzaldehyde (Va) (1.0 mmol) and NbCl5 (0–50 mole %) in
dichloromethane (DCM; 3.0 mL), 1,2-dichloroethane (DCE; 3.0 mL) or CH3CN (3.0 mL) under reflux, in an N2 atmosphere;
b) reaction conditions: IV (2.0 mmol), Va (1.0 mmol) and NbCl5 (25–50 mole %) in CH3CN (3.0 mL) under reflux, in an N2
atmosphere; c) isolated yields by re-crystallisation.
Table 2. Results for synthesis of xanthenedione derivatives (VIa–VIn)
M.p/◦C
Compound R
Appearence Yield (%)a ΔHfusion (J g−1) Purity (%)
Found
Reportedb
Va
Vb
Vc
Vd
Ve
Vf
Vg
Vh
Vi
Vj
Vk
Vl
Vm
Vn
C6H5
4-CH3C6H4
4-COOHC6H4
4-OCH3C6H4
2-OCH3C6H4
white solid 87 (VIa)
white solid 77 (VIb)
white solid 66 (VIc)c
white solid 73 (VId)
white solid 65 (VIe)
–135.86
–127.38
–75.79
–103.81
–74.24
–118.16
–89.98
–82.34
–73.43
–65.57
–84.72
–71.01
–77.81
–
99
98
99
99
96
98
99
98
99
97
98
98
98
–
263.9 261–264 (Shirini et al., 2013)
253.1 249–251 (Shirini et al., 2013)
281.8 –
193.4 203–204 (Shirini et al., 2013)
212.2 216–218 (Maleki et al., 2012)
239.0 225–227 (John et al., 2006)
281.2 281–283 (Shirini et al., 2013)
255.3 248–250 (Shirini et al., 2013)
251.1 283–285 (Shirini et al., 2013)
250.0 255–256 (Li et al., 2013)
4-OH-3-OCH3C6H3 white solid 80 (VIf)
3-NO2C6H4
4-NO2C6H4
4-BrC6H4
2-BrC6H4
4-C6H5C6H4
C4H3S
white solid 57 (VIg)
white solid 61 (VIh)
white solid 64 (VIi)
white solid 55 (VIj)
white solid 70 (VIk)
white solid 69 (VIl)c
white solid 54 (VIm)
white solid 78 (VIn)
211.6 196–198 (Iniyavan et al., 2015)
210.1
–
4-(CH3)2NC6H4
4-COH-C6H4
233.2 218–220 (Napoleon et al., 2014)
> 325.0 > 300.00 (Kaya et al., 2011)
a) Yields of isolated products by re-crystallisation; b) products known in the literature and their melting points were compared
with values already reported; c) product not described in the literature.
in 10.0 mL of hot ethanol, and cooled in a freezer to
afford the compounds (VIa–VIn). The full experimen-
tal details and spectroscopic characterisations (1H and
13C NMR, DSC, infrared and mass spectrometry) for
compounds (VIa–VIm) can be found in the Supple-
mentary Data section of this article’s web page.
the reaction conditions. The reaction was conducted
by heating under reflux, in an N2 atmosphere (Table 1,
entries 1–11) or in an air atmosphere (Table 1, entries
12–14). The results are summarised in Table 1.
The results in Table 1 show that the reactions with
0 mole % and 10 mole % of NbCl5 lead to no or in-
significant yields, independent of the solvent used. The
use of 25 mole % of NbCl5 afforded the best yields
in the three solvents tested, of which the acetonitrile
showed the best yields (87 % in 2 h) (Table 1, entry
13). With 50 mole % of NbCl5, the product started to
degrade and other products were formed, resulting in
a reduction in yield (Table 1, entries 11 and 14). From
these results, a time of 2 h, 25 mole % of NbCl5 and
air atmosphere (Table 1, entry 13) were established
as optimal for the other reactions performed.
Results and discussion
First, the one-pot reaction between IV (2.0 mmol)
and benzaldehyde (Va; 1.0 mmol), in the presence
of different concentrations (0 mole %, 10 mole %,
25 mole % or 50 mole %) of niobium pentachloride
and different types of anhydrous solvents (acetonitrile,
dichloromethane and 1,2-dichloroethane), was used as
a model in order to develop a protocol for optimising
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Table 3. Spectral data of compounds (VIa–VIm)
1661
Compound
Spectral data
VIa
IR, ν˜/cm−1: 2948, 2889, 1650, 1618, 1494, 1450, 1421, 1359, 1200, 1172, 1130, 1012, 958
1H NMR (CDCl3, 400 MHz), δ: 7.33–7.29 (m, 2H), 7.23 (dd, J = 6.9 Hz (2×), 2H), 7.13 (m, 1H), 4.83 (s, 1H),
2.70–2.52 (m, 4H), 2.41–2.30 (m, 4H), 2.08–1.96 (m, 4H)
13C NMR (CDCl3, 100 MHz), δ: 196.5, 163.9, 144.3, 128.4, 128.1, 126.4, 116.9, 36.9, 31.6, 27.1, 20.3
HRMS (ESI), m/z: Calcd. for C19H18O3 [M + Na]+: 317.1148, found 317.1129
IR, ν˜/cm−1: 3030, 2952, 2892, 1650, 1614, 1510, 1452, 1417, 1355, 1338, 1232, 1197, 1172, 1012, 954
1H NMR (CDCl3, 400 MHz), δ: 7.19 (d, J = 8.1 Hz, 2H), 7.04 (d, J = 8.1 Hz, 2H), 4.78 (s, 1H), 2.68–2.52 (m, 4H),
2.41–2.30 (m, 4H), 2.29–2.25 (m, 4H)
13C NMR (CDCl3, 100 MHz), δ: 196.6, 163.8, 141.5, 135.9, 128.8, 128.2, 117.0, 37.0, 31.2, 27.1, 21.1, 20.3
HRMS (ESI), m/z: Calcd. for C20H20O3 [M + Na]+: 331.1305, found 331.1308
IR, ν˜/cm−1: 3531, 2948, 2887, 1720, 1670, 1650, 1604, 1427, 1361, 1272, 1203, 1174, 1130, 1110, 1014, 958
1H NMR (CDCl3, 400 MHz), δ: 7.55 (d, J = 8.3 Hz, 2H), 7.01 (d, J = 8.3 Hz, 2H), 4.45 (s, 1H), 2.39-2.27 (m, 4H),
2.04-1.97 (m, 4H), 1.77-1.64 (m, 4H)
13C NMR (CDCl3, 100 MHz), δ: 196.4, 168.0, 164.5, 149.3, 129.4, 128.9, 128.3, 115.9, 36.8, 31.7, 26.9, 20.1
HRMS (ESI), m/z: Calcd. for C20H18O5 [M + Na]+: 361.1046, found 361.1032
IR, ν˜/cm−1: 2956, 2889, 2838, 1650, 1616, 1510, 1459, 1440, 1427, 1378, 1357, 1334, 1257, 1234, 1201, 1168, 1132,
1029, 956
1H NMR (CDCl3, 400 MHz), δ: 7.22 (d, J = 8.8 Hz, 2H), 6.77 (d, J = 8.8 Hz, 2H), 4.77 (s, 1H), 3.74 (s, 3H),
2.68–2.53 (m, 4H), 2.42–2.29 (m, 4H), 1.95–2.09 (m, 4H)
VIb
VIc
VId
13C NMR (CDCl3, 100 MHz), δ: 196.6, 163.7, 158.0, 136.7, 129.3, 117.1, 113.5, 55.1, 36.9, 30.8, 27.1, 20.3
HRMS (ESI), m/z: Calcd. for C20H20O4 [M + Na]+: 347.1254, found 347.1252
IR, ν˜/cm−1: 2943, 2873, 2831, 1650, 1620, 1488, 1467, 1454, 1429, 1382, 1357, 1334, 1290, 1245, 1207, 1176, 1134,
1116, 1045, 1027, 958
VIe
1H NMR (CDCl3, 400 MHz), δ: 7.39 (dd, J = 7.6 Hz, 1.8 Hz, 1H), 7.19–7.04 (m, 1H), 6.88 (ddd, J = 7.5 Hz, 7.5 Hz,
1.0 Hz, 1H), 6.80 (d, J = 8.3 Hz, 1H), 4.91 (s, 1H), 3.81 (s, 3H), 2.65–2.47 (m, 4H), 2.36–2.25 (m, 4H), 2.05–1.91
(m, 4H)
13C NMR (CDCl3, 100 MHz), δ: 196.7, 164.3, 158.0, 131.9, 131.5, 127.8, 120.5, 115.3,111.6 55.7, 37.0, 29.2, 27.1,
20.4
HRMS (ESI), m/z: Calcd. for C20H20O4 [M + Na]+: 347.1254, found 347.1242
IR, ν˜/cm−1: 3313, 2950, 2925, 1662, 1641, 1618, 1510, 1467, 1454, 1434, 1380, 1359, 1272, 1230, 1203, 1170, 1151,
1118, 1039, 1012, 956
VIf
1H NMR (CDCl3, 400 MHz), δ: 7.08 (d, J = 2.0 Hz, 1H), 6.75 (d, J = 8.1, Hz, 1H), 6.55 (dd, J = 8.1 Hz, 2.0 Hz,
1H), 5.49 (s, 1H), 4.74 (s, 1H), 3.92 (s, 3H), 2.68–2.53 (m, 4H), 2.44–2.31 (m, 4H), 2.07–1.95 (m, 4H)
13C NMR (CDCl3, 100 MHz), δ: 196.8, 163.8, 145.9, 144.1, 136.6, 119.7, 117.0, 113.9, 112.4, 55.9, 37.0, 31.0, 27.1,
20.2
HRMS (ESI), m/z: Calcd. for C20H20O5 [M + Na]+: 363.1203, found 363.1202
IR, ν˜/cm−1: 2954, 2890, 2823, 1650, 1620, 1521, 1415, 1384, 1348, 1253, 1234, 1201, 1170, 1130, 1080, 1014, 958
1H NMR (CDCl3, 400 MHz), δ: 8.06–7.96 (m, 2H), 7.84 (ddd, J = 7.8 Hz, 1.3 Hz (2×) Hz, 1H), 7.44–7.38 (m, 1H),
4.89 (s, 1H), 2.76–2.56 (m, 4H), 2.42–2.29 (m, 4H), 2.12–1.94 (m, 4H)
13C NMR (CDCl3, 100 MHz), δ: 196.6, 164.6, 148.3, 146.4, 135.9, 128.7, 122.6, 121.7, 115.7, 36.8, 31.9, 27.1, 20.2
HRMS (ESI), m/z: Calcd. for C19H17NO5 [M + Na]+: 362.0999, found 362.0988
IR, ν˜/cm−1: 2946, 2925, 2871, 1656, 1606, 1593, 1517, 1458, 1425, 1384, 1346, 1247, 1232, 1199, 1170, 1126, 1058,
1012, 956
1H NMR (CDCl3, 400 MHz), δ: 8.10 (d, J = 8.8 Hz, 2H), 7.48 (d, J = 8.8 Hz, 2H), 4.88 (s, 1H), 2.70–2.59 (m, 4H),
2.39–2.30 (m, 4H), 2.02–1.96 (m, 4H)
13C NMR (CDCl3, 100 MHz), δ: 196.4, 164.5, 151.6, 141.4, 133.6, 129.4, 128.0, 126.9, 123.4, 115.8, 36.8, 32.2, 27.1,
20.2
VIg
VIh
HRMS (ESI), m/z: Calcd. for C19H17NO5 [M + H]+: 340.1179, found 340.1188
IR, ν˜/cm−1: 2987, 2900, 1656, 1616, 1486, 1458, 1417, 1405, 1382, 1357, 1230, 1201, 1168, 1126, 1070, 1088, 958
1H NMR (CDCl3, 400 MHz), δ: 7.34 (d, J = 8.3 Hz, 2H), 7.18 (d, J = 8.3 Hz, 2H), 4.76 (s, 1H), 2.67–2.51 (m, 4H),
2.41–2.30 (m, 4H), 2.09–1.93 (m, 4H)
13C NMR (CDCl3, 100 MHz), δ: 196.5, 164.0, 143.4, 131.2, 130.2, 120.3, 116.4, 36.8, 31.4, 27.1, 20.3
HRMS (ESI), m/z: Calcd. for C19H17BrO3 [M + H]+: 373.0434, found 373.0454
IR, ν˜/cm−1: 2985, 2950, 2877, 1660, 1620, 1467, 1429, 1378, 1357, 1336, 1234, 1199, 1176, 1130, 1010, 958
1H NMR (CDCl3, 400 MHz), δ: 7.46–7.41 (m, 2H), 7.24–7.18 (m, 1H), 7.02–6.96 (m, 1H), 5.02 (s, 1H), 2.66–2.54
(m, 4H), 2.37–2.30 (m, 4H), 2.04–1.99 (m, 4H)
13C NMR (CDCl3, 100 MHz), δ: 196.6, 164.4, 141.4, 133.5, 128.0, 126.9, 115.0, 36.9, 34.0, 27.1, 20.2, 0.0
HRMS (ESI), m/z: Calcd. for C19H17BrO3 [M + H]+: 373.0434, found 373.0461
IR, ν˜/cm−1: 2983, 2906, 1660, 1618, 1483, 1450, 1432, 1380, 1357, 1228, 1201, 1174, 1126, 1088, 956
1H NMR (CDCl3, 400 MHz), δ: 7.57–7.51 (m, 2H), 7.49–7.36 (m, 6H), 7.34–7.28 (m, 1H), 4.87 (s, 1H), 2.75–2.49
(m, 4H), 2.47–2.32 (m, 4H), 2.14–1.96 (m, 4H)
13C NMR (CDCl3, 100 MHz), δ: 196.6, 163.9, 143.4, 141.2, 139.3, 128.8, 128.6, 127.0, 126.9, 116.8, 36.9, 31.3, 27.2,
20.3
HRMS (ESI), m/z: Calcd. for C25H22O3 [M + H]+: 371.1642, found 371.1654
VIi
VIj
VIk
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Table 3. (continued)
Compound
Spectral data
VIl
IR, ν˜/cm−1: 3301, 2948, 2885, 1650, 1616, 1450, 1421, 1382, 1350, 1315, 1284, 1205, 1172, 1132, 1012, 958
1H NMR (CDCl3, 400 MHz), δ: 7.05 (dd, J = 5.1 Hz, 1.3 Hz, 1H), 6.93 (dd, J = 3.5 Hz, 0.5 Hz, 1H), 6.84 (dd, J =
5.1 Hz, 3.5 Hz, 1H), 5.19 (s, 1H), 2.72–2.60 (m, 4H), 2.54–2.41 (m, 4H), 2.10–2.01 (m, 4H)
13C NMR (CDCl3, 100 MHz), δ: 196.4, 164.2, 148.4, 126.8, 125.0, 123.5, 116.4, 36.9, 27.1, 26.1, 20.6
HRMS (ESI), m/z: Calcd. for C17H16O3S [M + Na]+: 323.0712, found 323.0706
IR, ν˜/cm−1: 2941, 2889, 2804, 1718, 1689, 1656, 1612, 1521, 1456, 1452, 1386, 1357, 1226, 1174, 1124, 1066, 1010,
954.
VIm
1H NMR (CDCl3, 400 MHz), δ: 7.19–7.13 (m, 2H), 6.63–6.59 (m, 2H), 4.72 (s, 1H), 2.87 (s, 6H), 2.67–2.55 (m, 4H),
2.38–2.31 (m, 4H), 2.04–1.95 (m, 4H)
13C NMR (CDCl3, 100 MHz), δ: 196.7, 163.5, 149.2, 132.7, 130.4, 129.3, 128.9, 117.3, 112.4, 112.2, 111.6, 40.6, 40.4,
37.0, 27.2, 20.3
HRMS (ESI), m/z: Calcd. for C21H23NO3 [M + H]+: 338.1751, found 338.1747
IR, ν˜/cm−1: 2948, 1669, 1619, 1504, 1453, 1359, 1233, 1175, 1130, 958, 809, 615.
1H NMR (CDCl3, 400 MHz), δ: 7.08 (s, 4H), 4.73 (s, 2H), 2.67–2.50 (m, 8H), 2.41–2.26 (m, 8H), 2.04–1.98 (m, 8H)
13C NMR (CDCl3, 100 MHz), δ: 196.7, 164.0, 141.9, 128.0, 117.0, 36.9, 30.8, 27.1, 20.1
VIn
After optimisation of the reaction conditions, other
arylaldehydes (Vb–Vn) were allowed to react in the
presence of 25 mole % of NbCl5 and anhydrous
CH3CN. The products obtained were purified by re-
crystallisation in ethanol and characterised by spec-
troscopic and spectrometric methods (1H-NMR, 13C-
NMR, IR and MS). The spectral data were compared
with those in the literature (John et al., 2006; Li et al.,
2013; Iniyavan et al., 2015; Shirini et al., 2015, 2014,
2013; Pramanik & Bhar, 2012; Napoleon & Khan,
2014; Maleki et al., 2012). The results are summarised
in Tables 2 and 3.
The results in Table 2 show that, by using 25
mole % equivalent of NbCl5 and a reaction time of
2 h, it was possible to obtain xanthenedione deriva-
tives (VIa–VIn) with good yields (55–87 %). Large
yield differences were not observed by changing the
benzaldehyde derivative and the compound (VIc) is
not described in the literature. Through differential
scanning calorimetric analysis (DSC), it was possible
to determine the melting points, purity and enthalpy
of fusion of the synthesised compounds, in accordance
with the ASTM method (ASTM, 2014). The method
employed for re-crystallisation afforded the products
of high purity (above 97 %, with the exception of com-
pound VIc).
25 mole % of NbCl5 and acetonitrile as a solvent under
reflux, in an air atmosphere, for 2 h, affording good
yields of the products.
Conclusions
A simple and efficient procedure was developed
for preparing a variety of 9-aryl-3,4,5,6,7,9-hexahydro-
1H-xanthene-1,8(2H)-dione derivatives by the reac-
tions of various arylaldehydes with 1,3-cyclohexane-
dione in the presence of niobium pentachloride and
anhydrous acetonitrile as solvent under reflux, in an
air atmosphere, for 2 hours, affording good yields of
the products.
Acknowledgements. The authors would like to thank Fun-
dac¸a˜o de Amparo a` Pesquisa do Estado de S˜ao Paulo
(FAPESP), Conselho Nacional de Desenvolvimento Cientí-
fico e Tecnológico (CNPq), Coordenadoria de Aperfei¸coamento
de Pessoal do Nível Superior (CAPES), and Pró-Reitoria de
Pesquisa da UNESP (PROPe-UNESP) for their financial sup-
port. The authors would also like to thank CBMM – Companhia
Brasileira de Metalurgia e Minerac¸a˜o for the NbCl5 samples.
The authors would also like to express their special thanks to
N. B. Dias and M. S. Palma from the S˜ao Paulo State Univer-
sity in Rio Claro for their HR-MS analyses, and to Bannach,
G., Guerra, R. B., Ferreira, L. T. and Alarcon, R. T. for their
DSC analyses.
To promote a scale-up in the process of synthesis-
ing xanthenedione derivatives, two reactions were also
effected using 10.0 mmol of arylaldehyde (Va or Vc)
in the presence of 2.5 mmol of NbCl5. The yields ob-
tained were similar to the experiments performed with
(1.0 mmol), 85 % for product VIa and 67 % for prod-
uct VIc, after re-crystallisation. These results showed
that niobium pentachloride is an excellent catalyst
for the scale-up process and large-scale applications
of these xanthenedione derivatives.
Supplementary data
Supplementary data associated with this article
can be found in the online version of this paper (DOI:
10.1515/chempap-2016-0098).
References
Ahmad, M., King, T. A., Ko, D. K., Cha, B. H., & Lee,
J. (2002). Performance and photostability of xanthene and
pyrromethene laser dyes in sol-gel phases. Journal of Physics
D: Applied Physics, 35, 1473–1476. DOI: 10.1088/0022-
3727/35/13/303.
In summary, a simple and efficient procedure
for the synthesis of xanthenedione derivatives is
described. The reactions were carried out using
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Download Date | 10/11/16 11:56 AM

W. H. dos Santos, L. C. Da Silva-Filho/Chemical Papers 70 (12) 1658–1664 (2016)
1663
Alves, O. L. (1986). Técnicas de síntese em atmosfera inerte.
Química Nova, 9, 276–281. (in Portuguese)
Andrade, C. K. Z. (2004). Niobium pentachloride in organic
synthesis: Applications and perspectives. Current Organic
Synthesis, 1, 333–353.
ASTM (2014). Standard test method for purity by differential
scanning calorimetry. West Conshohocken, PA, USA: ASTM
International. DOI: 10.1520/e0928-08r14.
Bartolomeu, A. A., Menezes, M. L., & Silva-Filho, L. C.
(2014). Efficient one-pot synthesis of 14-aryl-14H-dibenzo
[a, j]xanthene derivatives promoted by niobium pentachlo-
ride. Chemical Papers, 68, 1593–1600. DOI: 10.2478/s11696-
014-0597-8.
Bartolomeu, A. A., Menezes, M. L., & Silva-Filho, L. C. (2015).
Chemoselective condensation of β-naphthol, dimethyl mal-
onate, and aromatic aldehydes promoted by niobium pen-
tachloride. Synthetic Communications, 45, 1114–1126. DOI:
10.1080/00397911.2014.999341.
Bekaert, A., Andrieux, J., & Plat, M. (1992). New total syn-
thesis of bikaverin. Tetrahedron Letters, 33, 2805–2806. DOI:
10.1016/s0040-4039(00)78863-0.
Bhowmik, B. B., & Ganguly, P. (2005). Photophysics of xan-
thene dyes in surfactant solution. Spectrochimica Acta Part
A: Molecular and Biomolecular Spectroscopy, 61, 1997–2003.
DOI: 10.1016/j.saa.2004.07.031.
Cao, Y., Yao, C., Qin, B., & Zhang, H. (2013). Solvent-free
synthesis of 14-aryl-14H-dibenzo[a,j]xanthenes catalyzed by
recyclable and reusable iron(III) triflate. Research on Chem-
ical Intermediates, 39, 3055–3062. DOI: 10.1007/s11164-012-
0818-0.
Chibale, K., Visser, M., van Schalkwyk, D., Smith, P. J., Sar-
avanamuthu, A., & Fairlamb, A. H. (2003). Exploring the
potential of xanthene derivatives as trypanothione reductase
inhibitors and chloroquine potentiating agents. Tetrahedron,
59, 2289–2296. DOI: 10.1016/s0040-4020(03)00240-0.
Dharma Rao, G. B., Kaushik, M. P., & Halve, A. K. (2012).
An efficient synthesis of naphtha[1,2-e]oxazinone and 14-
substituted-14H-dibenzo[a,j]xanthene derivatives promoted
by zinc oxide nanoparticle under thermal and solvent-
free conditions. Tetrahedron Letters, 53, 2741–2744. DOI:
10.1016/j.tetlet.2012.03.085.
D’Souza, D. M., & Mu¨ller, T. J. J. (2007). Multi-component
syntheses of heterocycles by transition-metal catalysis.
Chemical Society Reviews, 36, 1095–1108. DOI: 10.1039/
b608235c.
El-Brashy, A. M., El-Sayed Metwally, M., & El-Sepai, F. A.
(2004). Spectrophotometric determination of some fluoro-
quinolone antibacterials by binary complex formation with
xanthene dyes. II Farmaco, 59, 809–817. DOI: 10.1016/j.
farmac.2004.07.001.
cient catalyst for one-pot synthesis of α-aminophosphonates
under solvent-free conditions. Applied Organometallic Chem-
istry, 25, 47–53. DOI: 10.1002/aoc.1687.
Hou, J. T., Liu, Y. H., & Zhang, Z. H. (2010b). NbCl5 as an
efficient catalyst for rapid synthesis of quinoxaline deriva-
tives. Journal of Heterocyclic Chemistry, 47, 703–706. DOI:
10.1002/jhet.388.
Hou, J. T., Chen, H. L., & Zhang, Z. H. (2011a). Rapid and ef-
ficient trimethylsilyl protection of hydroxyl groups catalyzed
by niobium(V) chloride. Phosphorus, Sulfur, and Silicon and
the Related Elements, 186, 88–93. DOI: 10.1080/10426507.
2010.482544.
Hou, J. T., Gao, J. W., & Zhang, Z. H. (2011b). An effi-
cient and convenient protocol for the synthesis of diaminotri-
arylmethanes. Monatshefte fu¨r Chemie – Chemical Monthly,
142, 495–499. DOI: 10.1007/s00706-011-0461-2.
Horning, E. C., & Horning, M. G. (1946). Methone derivatives
of aldehydes. The Journal of Organic Chemistry, 11, 95–99.
DOI: 10.1021/jo01171a014.
Ilangovan, A., Malayappasamy, S., Muralidharan, S., & Maru-
thamuthu, S. (2011). A highly efficient green synthesis of 1,8-
dioxo-octahydroxanthenes. Chemistry Central Journal, 5, 81.
DOI: 10.1186/1752-153x-5-81.
Iniyavan, P., Sarveswari, S., & Vijayakumar, V. (2015). Micro-
wave-assisted clean synthesis of xanthenes and chromenes
in [bmim][PF6] and their antioxidant studies. Research
on Chemical Intermediates, 41, 7413–7426. DOI: 10.1007/
s11164-014-1821-4.
Isambert, N., & Lavilla, R. (2008). Heterocycles as key sub-
strates in multicomponent reactions: The fast lane towards
molecular complexity. Chemistry – A European Journal, 14,
8444–8454. DOI: 10.1002/chem.200800473.
John, A., Yadav, P. J. P., & Palaniappan, S. (2006). Clean
synthesis of 1,8-dioxo-dodecahydroxanthene derivatives cat-
alyzed by polyaniline-p-toluenesulfonate salt in aqueous me-
dia. Journal of Molecular Catalysis A: Chemical, 248, 121–
125. DOI: 10.1016/j.molcata.2005.12.017.
Karami, B., Zare, Z., & Eskandari, K. (2013a). Molybdate sul-
fonic acid: preparation, characterization, and application as
an effective and reusable catalyst for octahydroxanthene-
1,8-dione synthesis. Chemical Papers, 67, 145–154. DOI:
10.2478/s11696-012-0263-y.
Karami, B., Eskandari, K., Gholipour, S., & Jamshidi, M.
(2013b). Facile and rapid synthesis of 9-aryl 1,8-dioxo¨octa-
hydroxanthenes derivatives using tungstate sulfuric acid.
Organic Preparations and Procedures International: The
New Journal for Organic Synthesis, 45, 220–226. DOI:
10.1080/00304948.2013.764790.
Karami, B., Eskandari, K., Zare, Z., & Gholipour, S. (2014).
A
new access to 1,8-dioxooctahydroxanthenes using yt-
Fobane, L., Ndam, E. N., & Mbolo, M. J. (2014). Population
structure and natural regeneration of Allanblackia floribunda
oliv. (Clusiaceae) in a forest concession of East Cameroon.
Journal of Biodiversity and Environmental Sciences, 4, 403–
408.
Fuller, R. W., Blunt, J. W., Boswell, J. L., Cardellina, J. H., &
Boyd, M. R. (1999). Guttiferone F, the first prenylated ben-
zophenone from Allanblackia stuhlmannii. Journal of Natu-
ral Products, 62, 130–132. DOI: 10.1021/np9801514.
Hiranrat, A., & Mahabusarakam, W. (2008). New acylphloro-
glucinols from the leaves of Rhodomyrtus tomentosa. Tetra-
hedron, 64, 11193–11197. DOI: 10.1016/j.tet.2008.09.054.
Hiranrat, A., Chitbankluoi, W., Mahabusarakam, W., Lim-
suwan, S., & Voravuthikunchai, S. P. (2012). A new flavel-
lagic acid derivative and phloroglucinol from Rhodomyrtus
tomentosa. Natural Product Research, 26, 1904–1909. DOI:
10.1080/14786419.2011.628666.
trium(III) nitrate hexahydrate and tin(II) chloride dihydrate
as effective and reusable catalysts. Chemistry of Heterocyclic
Compounds, 49, 1715–1722. DOI: 10.1007/s10593-014-1423-
5.
Kaya, M., Basar, E., & Colak, F. (2011). Synthesis and an-
timicrobial activity of some bisoctahydroxanthene-1,8-dione
derivatives. Medicinal Chemistry Research, 20, 1214–1219.
DOI: 10.1007/s00044-010-9459-2.
Knight, C. G., & Stephens, T. (1989). Xanthene-dye-labelled
phosphatidylethanolamines as probes of interfacial pH. Stud-
ies in phospholipid vesicles. Biochemical Journal, 258, 683–
687. DOI: 10.1042/bj2580683.
Knight, D. W., & Little, P. B. (2001). The first efficient method
for the intramolecular trapping of benzynes by phenols: a new
approach to xanthenes. Journal of the Chemical Society, 14,
1771–1777. DOI: 10.1039/b103834f.
Lacerda, V., Jr., dos Santos, D. A., da Silva-Filho, L. C., Greco,
S. J., & dos Santos, R. B. (2012). The growing impact of nio-
Hou, J. T., Gao, J. W., & Zhang, Z. H. (2010a). NbCl5: an effi-
Brought to you by | University of Exeter
Authenticated
Download Date | 10/11/16 11:56 AM

1664
W. H. dos Santos, L. C. Da Silva-Filho/Chemical Papers 70 (12) 1658–1664 (2016)
bium in organic synthesis and catalysis. Aldrichimica Acta,
45, 19–27.
Communications, 20, 17–24. DOI: 10.1016/j.catcom.2011.12.
036.
Li, P., Ma, F., Wang, P., & Zhang, Z. H. (2013). Highly ef-
ficient low melting mixture catalyzed synthesis of 1,8-dioxo-
dodecahydroxanthene derivatives. Chinese Journal of Chem-
istry, 31, 757–763. DOI: 10.1002/cjoc.201300152.
Preetam, A., Prasad, D. K., Sharma, J., & Nath, M. (2015).
Facile one-pot synthesis of oxo-xanthenes under microwave
irradiation. Current Microwave Chemistry, 2, 15–23. DOI:
10.2174/221333560201150212102647.
Limsuwan, S., Trip, E. N., Kouwen, T. R. H. M., Piersma,
S., Hiranrat, A., Mahabusarakam, W., Voravuthikunchai,
S. P., van Dijl, J. M., & Kayser, O. (2009). Rhodomyr-
tone: a new candidate as natural antibacterial drug from
Rhodomyrtus tomentosa. Phytomedicine, 16, 645–651. DOI:
10.1016/j.phymed.2009.01.010.
Saini, A., Kumar, S., & Sandhu, J. (2006). A new LiBr-
catalyzed, facile and efficient method for the synthesis of 14-
alkyl or aryl-14H -dibenzo[a,j]xanthenes and tetrahydroben-
zo[b]pyrans under solvent-free conventional and microwave
heating. Synlett, 2006, 1928–1932. DOI: 10.1055/s-2006-
947339.
Locksley, H. D., & Murray, G. (1971). Extractives from Gut-
tiferae. Part X1X. The isolation and structure of two
benzophenones, six xanthones and two biflavonoids from
the heartwood of Allanblackia floribunda Oliver. Jour-
nal of the Chemical Society C: Organic, 1966–1971. DOI:
10.1039/j39710001332.
Shirini, F., Mamaghani, M., & Atghia, S. V. (2013). Use of
nanoporous Na+-montmorillonite sulfonic acid (SANM) as
an eco-benign, efficient and reusable solid acid catalyst for
the one-pot synthesis of 14-aryl-14-H-dibenzo[a,j]xanthenes
and 1,8-dioxo-dodecahydroxanthene derivatives. Journal of
the Iranian Chemical Society, 10, 415–420. DOI: 10.1007/
s13738-012-0174-4.
Lu¨, H. Y., Li, J. J.,
& Zhang, Z. H. (2009). ZrOCl2–
8H2O: a highly efficient catalyst for the synthesis of 1,8-
dioxo-octahydroxanthene derivatives under solvent-free con-
ditions. Applied Organometallic Chemistry, 23, 165–169.
DOI: 10.1002/aoc.1488.
Makino, M., & Fujimoto, Y. (1999). Flavanones from Baeckea
frutescens. Phytochemistry, 50, 273–277. DOI: 10.1016/
s0031-9422(98)00534-2.
Shirini, F., Abedini, M., Seddighi, M., Jolodar, O. G., Sa-
farpoor, M., Langroodi, N., & Zamani, S. (2014). Intro-
duction of
a
new bi-SO3H ionic liquid based on 2,2ꢀ-
bipyridine as a novel catalyst for the synthesis of various
xanthene derivatives. RSC Advances, 4, 63526–63532. DOI:
10.1039/c4ra12361a.
Shirini, F., Langarudi, M. S. N., Seddighi, M., & Jolodar,
O. G. (2015). Bi-SO3H functionalized ionic liquid based
on DABCO as a mild and efficient catalyst for the syn-
thesis of 1,8-dioxo-octahydro-xanthene and 5-arylmethylene-
pyrimidine-2,4,6-trione derivatives. Research on Chemical
Intermediates, 41, 8483–8497. DOI: 10.1007/s11164-014-
1905-1.
Sianglum, W., Srimanote, P., Wonglumsom, W., Kittiniyom,
K., & Voravuthikunchai, S. P. (2011). Proteome analyses of
cellular proteins in methicillin-resistant Staphylococcus au-
reus treated with rhodomyrtone, a novel antibiotic candidate.
PLoS ONE, 6, e16628. DOI: 10.1371/journal.pone.0016628.
Maleki, B., Gholizadeh, M.,
& Sepehr, Z. (2011). 1,3,5-
Trichloro-2,4,6-triazinetrion: A versatile heterocycle for the
one-pot synthesis of 14-aryl- or alkyl -14H-dibenzo[a,j]xan-
thene, 1,8-dioxooctahydroxanthene and 12-aryl-8,9,10,12-
tetrahydrobenzo[a]xanthene-11-one derivatives under solvent-
free conditions. Bulletin of Korean Chemical Society, 32,
1697–1702. DOI: 10.5012/bkcs.2011.32.5.1697.
Maleki, B., Barzegar, S., Sepehr, Z., Kermanian, M., & Tayebee,
R. (2012). A novel polymeric catalyst for the one-pot syn-
thesis of xanthene derivatives under solvent-free conditions.
Journal of the Iranian Chemical Society, 9, 757–765. DOI:
10.1007/s13738-012-0092-5.
Soleimani, E., Khodaei, M. M.,
& Koshvandi, A. T. K.
Napoleon, A. A., & Khan, F. R. N. (2014). Potential anti-
tubercular and in vitro anti-inflammatory agents: 9-substi-
tuted 1,8-dioxo-octahydroxanthenes through cascade/domino
reaction by citric fruit juices. Medicinal Chemistry Research,
23, 4749–4760. DOI: 10.1007/s00044-014-1033-x.
Napoleon, A. A., Khan, F. R. N., Jeong, E. D., & Chung, E.
H. (2014). Regioselective synthesis of 3,4,6,7-tetrahydro-3,3-
dimethyl-9-phenyl-2H-xanthene-1,8(5H,9H)-diones through
ascorbic acid catalyzed three-component domino reaction.
Tetrahedron Letters, 55, 5656–5659. DOI: 10.1016/j.tetlet.
2014.08.040.
(2011). The efficient synthesis of 14-alkyl or aryl 14H-
dibenzo[a,j]xanthenes catalyzed by bismuth(III) chloride un-
der solvent-free conditions. Chinese Chemical Letters, 22,
927–930. DOI: 10.1016/j.cclet.2011.01.012.
Urinda, S., Kundu, D., Majee, A., & Hajra, A. (2009). Indium
triflate-catalyzed one-pot synthesis of 14-alkyl or aryl-14H-
dibenzo[a,j]xanthenes in water. Heteroatom Chemistry, 20,
232–234. DOI: 10.1002/hc.20539.
Visutthi, M., Srimanote, P., & Voravuthikunchai, S. P. (2011).
Responses in the expression of extracellular proteins in
methicillin-resistant Staphylococcus aureus treated with
rhodomyrtone. The Microbiological Society of Korea, 49,
956–964. DOI: 10.1007/s12275-011-1115-0.
Wang, J. Q., & Harvey, R. G. (2002). Synthesis of polycyclic
xanthenes and furans via palladium-catalyzed cyclization
of polycyclic aryltriflate esters. Tetrahedron, 58, 5927–5931.
DOI: 10.1016/s0040-4020(02)00534-3.
Nkengfack, A. E., Azebaze, G. A., Vardamides, J. C., Fomum,
Z. T., & van Heerden, F. R. (2002). A prenylated xanthone
from Allanblackia floribunda. Phytochemistry, 60, 381–384.
DOI: 10.1016/s0031-9422(02)00036-5.
Ormond, A. B.,
& Freeman, H. S. (2013). Dye sensitiz-
ers for photodynamic therapy. Materials, 6, 817–840. DOI:
10.3390/ma6030817.
Oshiro, P. B., Lima, P. S. S. G., Menezes, M. L., & Silva-Filho,
L. C. (2015). Synthesis of 4H-chromenes promoted by NbCl5
through multicomponent reaction. Tetrahedron Letters, 56,
4476–4479. DOI: 10.1016/j.tetlet.2015.05.099.
Wang, L. M., Sui, Y. Y., & Zhang, L. (2008). Synthesis of 14-
{[(un)substituted phenyl] or alkyl}-14H-dibenzo[a,j]xanthe-
nes using Yb(OTf)3 as an efficient catalyst under solvent-free
conditions. Chinese Journal of Chemistry, 26, 1105–1108.
DOI: 10.1002/cjoc.200890196.
Peres, V., & Nagem, T. J. (1997). Trioxygenated naturally
occurring xanthones. Phytochemistry, 44, 191–214. DOI:
10.1016/s0031-9422(96)00421-9.
Peres, V., Nagem, T. J., & Oliveira, F. F. (2000). Tetraoxy-
genated naturally occurring xanthones. Phytochemistry, 55,
683–710. DOI: 10.1016/s0031-9422(00)00303-4.
Zhang, Z. H., & Liu, Y. H. (2008). Antimony trichloride/SiO2
promoted synthesis of 9-ary-3,4,5,6,7,9-hexahydroxanthene-
1,8-diones. Catalysis Communications, 9, 1715–1719. DOI:
10.1016/j.catcom.2008.01.031.
Zhang, Z., & Tao, X. (2008). 2,4,6-Trichloro-1,3,5-triazine-
promoted synthesis of 1,8-dioxo-octahydroxanthenes under
solvent-free conditions. Australian Journal of Chemistry, 61,
77–79. DOI: 10.1071/ch07274.
Pramanik, A., & Bhar, S. (2012). Alumina-sulfuric acid cat-
alyzed eco-friendly synthesis of xanthenediones. Catalysis
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