One-pot synthesis of 9-arylxanthenediones and 9-pyrazoloxanthenediones using [DBU]OAc

Article abstract of DOI:10.1134/S1070363217040247

The synthesis of 9-aryl-1H-xanthene-1,8(2H)-dione derivatives starting from benzaldehydes or synthesized pyrazolcarbaldehydes and dimedone in the presence of 2,3,4,5,7,8,9,10-octahydropyrido[1,2-a]-[1,3]diazepin-1-ium acetate in high yields is reported. T

Full text of DOI:10.1134/S1070363217040247

ISSN 1070-3632, Russian Journal of General Chemistry, 2017, Vol. 87, No. 4, pp. 816–820. © Pleiades Publishing, Ltd., 2017.
One-Pot Synthesis of 9-Arylxanthenediones
and 9-Pyrazoloxanthenediones Using [DBU]OAc1
M. Nikpassanda* and L. Zare Fekrib
a Department of Chemistry, Young Researchers and Elite Сlub, Rasht Branch, Islamic Azad University, Rasht, Iran
*e-mail: Nikpassand@iaurasht.ac.ir
b Department of Chemistry, Payame Noor University, PO Box 19395-3697, Tehran, Iran
Received January 11, 2016
Abstract—The synthesis of 9-aryl-1H-xanthene-1,8(2H)-dione derivatives starting from benzaldehydes or
synthesized pyrazolcarbaldehydes and dimedone in the presence of 2,3,4,5,7,8,9,10-octahydropyrido[1,2-a]-
[1,3]diazepin-1-ium acetate in high yields is reported. The synthesis provides several advantages, including
short reaction time, simple work-up, and environmental friendliness.
Keywords: xanthene, one- pot reaction, ionic liquid, solvent free
DOI: 10.1134/S1070363217040247
The synthesis of xanthene derivatives has been of
considerable interest to chemists, because such com-
pounds are widely used in medicine and pharmaceutics
as antiviral [1] and antibacterial agents [2], as well as
photosensitizers for photodynamic theraphy and
antagonists of zoxazolamine [2, 3], and anti-inflam-
matory drugs [4]. Furthermore, the use of xanthenes as
staining dyes [5, 6], fluorescent probes [7], and laser
dyes [8] has been reported.
for clean synthesis, since they are easy to recycle, lack
flammability, and possess almost no effective vapor
pressure. Compared with classical molecular solvents,
ionic liquids are environmentally benign reaction
media [27].
In continuation of our ongoing studies on the
synthesis of heterocyclic and pharmaceutical com-
pounds by mild and practical protocols [28‒31], in the
present work we developed a synthesis of xanthene
derivatives using various benzaldehydes 1 or syn-
thesized pyrazolcarbaldehyde 4 [28] (2 mmol) and
dimedone 2 (4 mmol) in the presence of the ionic
liquid [DBU]OAc (2,3,4,5,7,8,9,10-octahydropyrido-
[1,2-a][1,3]diazepin-1-ium acetate) (Scheme 1, Table 1).
Many synthetic approaches to xanthene derivatives
have been developed, including trapping of benzynes
by phenols [9], cyclodehydration [10], and cyclocon-
densation between 2-tetralone and o-hydroxybenzal-
dehydes [11], as well as condensation of aromatic
aldehydes and dimedone in the presence of InCl3.4H2O
[12], NaHSO4·SiO2 [13], silica sulfuric acid [14],
TiO2/SO42– [15], ZrOCl2·8H2O [16], FeCl3·6H2O [17],
Dowex-50W [18], Fe3+-montmorillonite [19], amberlyst-
15 [20] and alumina sulfuric acid [21] as solid acid
catalysts. In addition, the synthesis of other xanthene-
dione derivatives, catalyzed by a Preyssler-type
heteropoly acid [22], HPA/SiO2 [23], and HPWA/
MCM-41 [24] has been recently reported.
To check the efficiency of catalyst, the model
reaction between benzaldehydes 1 and dimedone 2 in
the presence of different catalysts was carried out. All
the reactions were carried out with catalytic amounts
of catalysts. As shown in Table 1, the results gained
with 0.1 mmol of [DBU]OAc (Table 1) were to a great
extent satisfactory.
Table 1 showed other interesting points in that the
ability and efficiency of catalyst NaY Zeolite, nano-
Fe3O4 and K10 montmorillonite are somehow similar,
while ionic liquid [DBU]OAc was more efficient for
the synthesis of 9-aryl-1H-xanthene-1,8(2H)-diones.
The [DBU]OAc, rather than other catalysts, can
accelerate the reaction time.
Ionic liquids are being more and more widely used
in modern synthetic chemistry because of their
interesting properties [25, 26]. Ionic liquids offer an
attractive alternative to conventional organic liquids
1 The text was submitted by the authors in English.
816

ONE-POT SYNTHESIS OF 9-ARYLXANTHENEDIONES
817
Scheme 1. Synthesis of 9-aryl-1H-xanthene-1,8(2H)-diones 3a–3j using [DBU]OAc.
CHO
X
O
O
[DBU]OAc
+
O
O
60°C
X
1a−1j
2
O
3a−3j
3: X= H (a); 4-NO2 (b); 3-NO2 (c); 4-Cl (d); 3-Cl (e); 2-Cl (f); 4-Br (g); 3-Br (h); 4-CH3O (i); 3-CH3O (j).
Scheme 2. Synthesis of 9-aryl-1H-xanthene-1,8(2H)-diones 5a–5d using [DBU]OAc.
O
O
Ar
CHO
+
Ar
O
O
[DBU]OAc
N
O
N
60°C
4a−4d
2
5a−5d
5: Ar = 3-NO2C6H4 (a); 4-ClC6H4 (b); 3-HOC6H4 (c); 3-CH3OC6H4 (d).
All of compounds 5 are new. Structure of products
5a–5d were characterized by IR, NMR and Elemental
analyses. For example, singlet peaks about 7.78–
AlkO) were employed and reacted well to give the
corresponding xanthenes 3a–3j in yields ranging from
82 to 97% (Table 1).
1
8.02 ppm in H NMR spectra are related to pyrazolic
Thus, we developed an efficient and convenient
procedure for the mild synthesis of 9-aryl-1H-xanthene-
diones and 9-pyrazoloxanthenediones by a one-step
reaction of aldehydes and dimedone, catalyzed by
[DBU]OAc as a reusable catalyst. The remarkable
advantages offered by this method include: nontoxic,
easily handled, and reusable catalyst; simple work-up
procedure; short reaction time; high yields of products
of a better purity; and environmental safety (non-toxic
catalyst and no hazardous solvents are used). To the
best of our knowledge, this is the first report on the
synthesis of 9-aryl-1H-xanthene-1,8(2H)-diones using
[DBU]OAc.
protons. So, saturated protons in pyran,s rings were
shown in about 5.19–5.26 ppm as singlet peaks.
With the best catalyst in hand, we moved to study
the effects of the catalyst amount on the model reac-
tion (Table 1, compounds 3b and 3i). It was found that
0.1 mmol of [DBU]OAc was enough to bring the
reaction to completion, while 0.05 mmol of the catalyst
was not enough. With a higher amount of the catalyst,
no significant change in the reaction yields was observed.
The washed [DBU]OAc was dried for reuse in
subsequent reactions. It was shown that after six runs
[DBU]OAc was as active as the fresh catalyst (Table 2).
EXPERIMENTAL
Several aldehydes could be converted to the
corresponding products in good to high yield using
[DBU]OAc. Aldehydes containing electron-acceptor
(NO2 or Hal) and electron-donor groups (OH and
Chemicals were purchased from Merck and Fluka
and used as received. The melting points were
measured on an Electrothermal 9100 apparatus and
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 87 No. 4 2017

818
NIKPASSAND, ZARE FEKRI
Table 1. Synthesis of 9-aryl-1H-xanthene-1,8(2H)-diones 3a–3j and 5a–5d in the presence of [DBU]OAc
Comp. no.
X or Ar
Time, min
60 (180)b (420)e
30 (180)b (90)f
45 (180)c
45 (240)d
60 (240)d
60 (120)b
30
Yield, %a
87 (75)b (65)e
97 (72)b (75)f
88 (72)c
89 (68)d
82 (68)d
95 (82)b
95
mp, °C (published mp °C)
206–208 (205 [32])
226–228 (222–224 [32])
165–167 (165–166 [32])
232–234 (231–233 [33])
183–185 (183–185 [33])
224–226 (226–227 [32])
241–243 (240–242 [32])
189–191 (190–192 [32])
241–243 (242–243 [32])
259–261 (261–263 [32])
263–265
3a
3b
3c
3d
3e
3f
H
4-NO2
3-NO2
4-Cl
3-Cl
2-Cl
3g
3h
3i
4-Br
3-Br
60
95
4-CH3O
3-CH3O
3-NO2C6H4
4-ClC6H4
3-HOC6H4
4-CH3OC6H4
90 (150)f
45 (240)d
60 (180)b (420)e
60 (180)c
90 (240)d
90 (120)b
82 (70)f
86 (68)d
94 (75)b (65)e
85 (72)c
82 (68)d
90 (82)b
3j
5a
5b
5c
5d
281–283
271–273
270–272
a
Yield based upon the starting aldehyde. b In the presence of 0.1 g of NaY Zeolite. c In the presence of 0.1 g of nano-Fe3O4. d In the
presence of 0.1 g of K10 montmorillonite. e In the thermal condition without catalyst. f In the presence of 0.05 mmol of [DBU]OAc.
reported uncorrected. The IR spectra were recorded on
identity and purity of the products were confirmed by
1
1
a Shimadzu FTIR-8400S spectrometer. The H NMR
IR, H NMR, 13C NMR, and elemental analysis.
and 13C NMR spectra were obtained on a Bruker DRX
500 Avance spectrometer in CDCl3 and DMSO-d6
internal standard TMS. Elemental analysis was
performed on a Carlo-Erba EA1110CNNO-S analyzer.
Reaction progress was monitored by TLC on silica gel
(60 GF254 Merck) in ethyl acetate–n-hexane (1 : 2).
Physicochemical characteristics and spectra of product
3a–3j correspond to published data [34–37].
3,3,6,6-Tetramethyl-9-[3-(3-nitrophenyl)-1-phenyl-
1H-pyrazol-4-yl]-3,4,5,6,7,9-hexahydro-1H-xanthene-
1,8(2H)-dione (5a). Yield 94%, white solid; mp 263–
265°C. IR spectrum (KBr), ν, cm−1: 3380, 3051, 2954,
1643, 1496, 1414. 1H NMR spectrum (500 MHz, CDCl3),
δ, ppm: 0.93 s (6H, CH3), 1.02 s (6H, CH3), 1.98–2.28
m (8H, CH2), 5.22 s (1H, CH), 7.27 t (J = 8.0 Hz, 1H),
7.43 t (J = 7.6 Hz, 2H), 7.66 d (J = 8.0 Hz, 1H), 7.70 d
(J = 8.0 Hz, 1H), 7.89 (s, 1H), 8.24 dd (J = 8.2,
1.6 Hz, 1H), 8.57 d (J = 8.0 Hz, 1H), 9.0 s (1H).
Found, %: C 71.51; H 5.78; N 7.84. C32H31N3O5.
Calculated, %: C 71.49; H 5.81; N 7.82.
Synthesis of compounds 3 and 5 (general
procedure). Benzaldehyde 1 (2 mmol) or pyrazolal-
dehyde 4 (2 mmol), dimedone 2 (4 mmol), and
[DBU]OAc (0.1 mmol) were heated at 60°C for 30–
120 min. After the reaction had been complete, the
reaction mixture was allowed cool down to room
temperature, poured into crashed ice, and stirred for 5
min. The precipitate that formed was filtered off,
recrystallized from ethanol, and dried to obtain
compound 3 or 5, respectively, as a powder. The
9-[3-(4-Chlorophenyl)-1-phenyl-1H-pyrazol-4-yl]-
3,3,6,6-tetramethyl-3,4,5,6,7,9-hexahydro-1H-xanthene-
1,8(2H)-dione (5b). Yield 85%, white solid; mp 281–
283°C. IR spectrum (KBr), ν, cm−1: 3446, 3068, 2958,
1647, 1502, 1614, 1022. 1H NMR spectrum (500 MHz,
CDCl3), δ, ppm: 0.94 s (6H, CH3), 1.00 s (6H, CH3),
2.08–2.22 m (8H, CH2), 5.19 s (1H, CH), 7.25 t (J =
7.2 Hz, 1H), 7.39–7.48 m (5H), 7.65 d (J = 8.2 Hz,
2H), 7.78 s (1H), 8.08 d (J = 8.2 Hz, 2H). Found, %: C
Table 2. Evaluation of reusability of [DBU]OAc in the
synthesis of compound 3a
Run no.
1
2
3
4
5
6
Time, min
Yield, %
60
87
60
88
60
87
60
86
60
87
60
86
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 87 No. 4 2017

ONE-POT SYNTHESIS OF 9-ARYLXANTHENEDIONES
819
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72.89; H 5.91; N 5.29. C32H31ClN2O3. Calculated, %:
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9-[3-(3-Hydroxyphenyl)-1-phenyl-1H-pyrazol-4-
yl]-3,3,6,6-tetramethyl-3,4,5,6,7,9-hexahydro-1H-
xanthene-1,8(2H)-dione (5c). Yield 82%, white solid;
mp 271-273°C. IR spectrum (KBr), ν, cm−1: 3409,
3066, 2954, 1649, 1463, 1506, 1220. 1H NMR
spectrum (500 MHz, CDCl3), δ, ppm: 0.93 s (6H,
CH3), 1.00 s (6H, CH3), 2.00–2.20 m (8H, CH2), 5.26 s
(1H, CH), 6.83 d (J = 7.2 Hz, 1H), 7.21-7.25 m (3H),
7.37 t (J = 7.6 Hz, 3H),7.65 d (J = 8.0 Hz, 2H), 8.02 s
(1H). Found, %: C 75.54; H 6.31; N 5.49. C32H32N2O4.
Calculated, %: C 75.57; H 6.34; N 5.51.
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xanthene-1,8(2H)-dione (5d). Yield 90%, white solid;
mp 270–272°C. IR spectrum (KBr), ν, cm−1: 2954,
1645, 1471, 1502, 1608. 1H NMR spectrum (500 MHz,
CDCl3), δ, ppm: 0.89 s (6H, CH3), 0.95 s (6H, CH3),
1.95–2.18 m (8H, CH2), 3.78 s (3H, OCH3), 5.21 s
(1H, CH), 6.98 d (J = 8.8 Hz, 2H), 7.22 t (J = 7.8 Hz,
1H), 7.40 t (J = 8.0 Hz, 2H), 7.65 d (J = 8.0 Hz, 2H),
7.78 s (1H), 8.02 d (J = 7.8 Hz, 2H). Found, %: C
75.88; H 6.54; N 5.38. C33H34N2O4. Calculated, %: C
75.84; H 6.56; N 5.36.
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support.
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