Green synthesis of 1,8-dioxo-octahydroxanthene derivatives using catalytic amount of H2SO4 in water

Article abstract of DOI:10.1080/00397910903162825

An green and convenient approach to the synthesis of 3,6,9-aryl-1,8-dioxo- 1,2,3,4,5,6,7,8-octahydroxanthene derivatives from appropriate aromatic aldehydes and 5-aryl-1,3-cyclo-hexanedione in the presence of two drops of concentrated H₂SO₄ as a catalyst in water is described. This method provides several advantages such as environmental friendliness, low cost, excellent yields, and simple workup procedure. Copyright

Full text of DOI:10.1080/00397910903162825

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Green Synthesis of 1,8-Dioxo-
octahydroxanthene Derivatives Using
Catalytic Amount of H2SO4 in Water
Rui-Hua Wang a , Bin Cui a , Wen-Tao Zhang a & Guang-Fan Han a
a School of Material Science and Engineering , Jiangsu University of
Science and Technology , Zhenjiang, Jiangsu, China
Published online: 17 May 2010.
To cite this article: Rui-Hua Wang , Bin Cui , Wen-Tao Zhang & Guang-Fan Han (2010) Green Synthesis
of 1,8-Dioxo-octahydroxanthene Derivatives Using Catalytic Amount of H2SO4 in Water, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
40:12, 1867-1872, DOI: 10.1080/00397910903162825
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Synthetic Communications1, 40: 1867–1872, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903162825
GREEN SYNTHESIS OF
1,8-DIOXO-OCTAHYDROXANTHENE DERIVATIVES
USING CATALYTIC AMOUNT OF H2SO4 IN WATER
Rui-Hua Wang, Bin Cui, Wen-Tao Zhang, and
Guang-Fan Han
School of Material Science and Engineering, Jiangsu University of Science
and Technology, Zhenjiang, Jiangsu, China
An green and convenient approach to the synthesis of 3,6,9-aryl-1,8-dioxo-1,2,3,4,5,6,7,8-
octahydroxanthene derivatives from appropriate aromatic aldehydes and 5-aryl-1,3-cyclo-
hexanedione in the presence of two drops of concentrated H2SO4 as a catalyst in water
is described. This method provides several advantages such as environmental friendliness,
low cost, excellent yields, and simple workup procedure.
Keywords: 5-Aryl-1,3-cyclohexadione; octahydroxanthene derivatives; water
INTRODUCTION
With increasing environmental concerns and the regulatory constraints faced
in the chemical and pharmaceutical industries, development of environmentally
benign organic reactions has become a crucial and demanding research area in
modern organic chemical research.[1] Recently, organic reactions in water without
use of harmful organic solvents have attracted much attention because water is a
cheap, safe, and environmentally benign solvent.[2–4] In the course of our investiga-
tions to develop new synthetic methods in water, we examined the synthesis of 3,6,9-
aryl-1,8-dioxo-1,2,3,4,5,6,7,8-octahydroxanthene derivatives in water, a green solvent.
It is known that 1,8-dioxo-1,2,3,4,5,6,7,8-octahydroxanthene and its deriva-
tives are very useful compounds. The derivatives occupy a prominent position in
medicinal chemistry,[5] and they have also been used as laser technology,[6]
pH-sensitive fluorescent materials,[7] and dyes.[8]
It has been reported that the reaction of aromatic aldehyde and 5,5-
dimethyl-1,3-cyclohexanedione can obtain 3,3,6,6-tetramethyl-9-aryl-1,8-dioxo-1,
2,3,4,5,6,7,8-octahydroxanthene and their derivatives in many methods.[9–13] How-
ever, the use of 5-aryl-1,3-cyclohexanedione as a reactant and two drop of concen-
trated H2SO4 as a catalyst for the one-pot synthesis of the 3,6,9-aryl-1,8-dioxo-1,2,
3,4,5,6,7,8-octahydroxanthene and their derivatives in water has not been reported.
Received April 22, 2009.
Address correspondence to Guang-Fan Han, School of Material Science and Engineering,
Jiangsu University of Science and Technology, Zhenjiang, Jiangsu 212003, China. E-mail: gf552002@
yahoo.com.cn
1867

1868
R.-H. WANG ET AL.
=
Scheme 1. Compounds a–f: R1 ¼ phenyl; R2 ¼ H; R H, 2-Cl, 4-Cl, 3-OMe, 4-OMe; g–l: R1 ¼ 4-methoxy-
=
=
phenyl, R2 ¼ H; R H, 2-Cl, 4-Cl, 3-OMe, 4-OMe, 4-N(CH3)2; and m and n: R1 ¼ Me; R2 ¼ Me; R H, 4-Cl.
In this article, we report a clean and highly efficient route for the one-pot synthesis of
their products and derivatives using inexpensive and commercially available con-
centrated H2SO4 as a catalyst in water. This a novel one-pot combination using
water as a green solvent not only preserves the simplicity but also consistently gives
the corresponding products in good to excellent yields (Scheme 1).
RESULTS AND DISCUSSION
The synthetic pathway is shown in Scheme 1. The 5-aryl-1,3-cyclohexanediones
1 were prepared as building blocks from aromatic aldehyde, acetone, and dimethyl
molanate. The 3,6,9-aryl-1,8-dioxo-1,2,3,4,5,6,7,8-octahydroxanthene and their deri-
vatives 3a–n were obtained by condensation reaction of 5-aryl-1,3-cyclohexanediones
1 with appropriate aromatic aldehydes using two drops of concentrated H2SO4 as a
catalyst in water.
1
The data of H NMR, mass spectra (MS), and infrared (IR) shown in the
experimental section are in accordance with the chemical structures of the target
1
compounds. In the H NMR spectrum of compound 3a, the single proton peaks
at d 4.90 were the characteristic absorption proton peak of the 9-H. The structures
of these compounds were further supported ꢀb1y their IR spectra. Typical absorption
bands at 1701 cmꢀ1 for (C O) and 1120 cm for (C-O) were observed.
=
As shown in Table 1, a series of aromatic aldehydes 2 were reacted with 5-aryl-
1,3-cyclohexanedione 1 in the presence of two drops of concentrated H2SO4 in water
at 70–80 ꢁC, and the reaction proceed smoothly to afford the corresponding products
3 in good yields. All aromatic aldehydes containing electron-withdrawing groups
(such as halide) or electron-donating groups (such as methoxy, N,N-dimethyl) were
employed and reacted well to give the corresponding product 3 in good to excellent
yield under these reaction conditions, so we conclude that no obvious effects of
electrons and nature of substituents on the aromatic ring were observed.
Taking the reaction of 4-chlorobenzaldehyde as an example, we investigated
the effect of the amount of catalyst on the reaction, which plays a crucial role in

SYNTHESIS OF 1,8-DIOXO-OCTAHYDROXANTHENE
1869
Table 1. Synthesis of 1,8-dioxo-1,2,3,4,5,6,7,8-octahydroxanthene in water
Entry
R1
R2
R
Mp (ꢁC)
Yield (%)
3a
3b
3c
3d
3e
3f
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
H
H
H
212–213
199–200
189–190
187–188
207–208
216–217
238–239
240–241
266–268
196–198
236–238
228–229
194–196
226–228
84
88
93
91
93
92
88
89
94
92
95
94
90
94
2-Cl
4-Cl
H
H
3-OMe
4-OMe
4-N(CH3)2
H
H
H
3g
3h
3i
4-OCH3C6H4
4-OCH3C6H4
4-OCH3C6H4
4-OCH3C6H4
4-OCH3C6H4
4-OCH3C6H4
Me
H
H
2-Cl
4-Cl
H
3j
H
3-OMe
4-OMe
4-N(CH3)2
H
3k
3l
H
H
3m
3n
Me
Me
Me
4-Cl
the success of the reaction in terms of the rate and the yields. For example, the
reaction could not be carried out in absence of the catalyst. It was found that two
drops of concentrated H2SO4 (about 0.1 mL) in 40 mL water at 70–80 ꢁC for 3 h
can give the corresponding product in good to excellent yields. When the amount
of catalyst was increased, it gave very poor yield (less than 65%). These data
indicated that the two drops of concentrated H2SO4 is suitable for this reaction.
CONCLUSION
In summary, we have described a general and highly efficient procedure for the
one-pot preparation of 3,6,9-aryl-1,8-dioxo-1,2,3,4,5,6,7,8-octahydroxanthene cata-
lyzed by two drops of concentrated H2SO4 in water. It is possible to apply tenets
of green chemistry to the generation of interesting products using aqueous media
methods that are less expensive and less toxic than those with organic solvents.
The catalyst is very cheap and nontoxic, and we used a very small amount. More-
over, the procedure offers several advantages including excellent yields, low cost,
operational simplicity, clean reactions, and minimal environmental effects, which
make it a useful and attractive process for the synthesis of these compounds.
EXPERIMENTAL
Melting points were determined on an electrothermal apparatus, and the
temperature was not calibrated. Microanalysis was performed on a Perkin-Elmer
2400 microanalytical instrument. IR spectra were recorded as thin films on KBr
using a Perkin-Elmer 1700 spectrophotometer. The NMR spectra were recorded
on a Bruker ARX-300 spectrometer. Sample solutions were prepared in CDCl3 or
dimethylsulfoxide (DMSO) containing tetramethylsilane (TMS) as an internal
reference. Mass spectra were recorded on a JMS-DX300 at 70 eV.
All chemical reagents were commercially available and purified with
standard methods before use. Solvents were dried in routine ways and redistilled.

1870
R.-H. WANG ET AL.
5-Aryl-1,3-cyclohexanedione 1 were obtained from aromatic aldehyde, acetone, and
dimethyl malonate according to the literature[14] method with slight modifications.
General Procedure
A mixture of an 5-aryl-1,3-cyclohexanedione (1.10 mmol), aromatic aldehyde
(2.5 mmol), and H2SO4 (0.1 mL) in water (40 mL) was stirred at 70–80 ꢁC for 2 h.
Then the mixture was cooled to room temperature; the solid was filtered off
and washed with water. The crude products were purified by recrystallization by
ethanol (95%).
Data of Compounds
Compound 3a. 1H NMR (CDCl3, 300 MHz): 2.69–2.89 (m, 4H, 4-H þ 5-H),
2.91–3.04 (m, 4H, 2-H þ 7-H), 3.27 (m, 2H, 3-H þ 6-H), 4.90 (s, 1H, 9-H), 7.11–7.42
(m, 15H, Ph-H); IR (KBr) t: 1701, 1622, 1545, 1509, 1120 cmꢀ1; MS (70 eV) m=z (%):
447.25 (Mþ þ 1, 100). Anal. calcd. for C31H26O3: C, 83.38; H, 5.87. Found: C, 83.41;
H, 5.85.
Compound 3b. 1H NMR (CDCl3, 300 MHz): 2.51–2.63 (m, 4H, 4-H þ 5-H),
2.83–2.97 (m, 4H, 2-H þ 7-H), 3.30 (m, 2H, 3-H þ 6-H), 5.13 (s, 1H, 9-H), 7.09–7.49
(m, 14H, Ph-H); IR (KBr) t: 1705, 1643, 1570, 1512, 1127 cmꢀ1; MS (70 eV) m=z (%):
481.05 (Mþ þ 1, 100), 369.16 (86). Anal. calcd. for C31H25ClO3: C, 77.41; H, 5.24.
Found: C, 77.45; H, 5.23.
Compound 3c. 1H NMR (CDCl3, 300 MHz): 2.60–2.76 (m, 4H, 4-H þ 5-H),
2.82–2.91 (m, 4H, 2-H þ 7-H), 3.32 (m, 2H, 3-H þ 6-H), 4.88 (s, 1H, 9-H), 7.12–7.42
(m, 14H, Ph-H); IR (KBr) t: 1752, 1624, 1590, 1505, 1122 cmꢀ1; MS (70 eV) m=z (%):
480.98 (Mþ þ 1, 100). Anal. calcd. for C31H25ClO3: C, 77.41; H, 5.24. Found: C,
77.44; H, 5.22.
Compound 3d. 1H NMR (CDCl3, 300 MHz): 2.59–2.75 (m, 4H, 4-H þ 5-H),
2.81–2.99 (m, 4H, 2-H þ 7-H), 3.43 (m, 2H, 3-H þ 6-H), 3.82 (s, 3H, OCH3), 5.53
(s, 1H, 9-H), 6.92–7.42 (m, 14H, Ph-H); IR (KBr) t: 1753, 1625, 1513, 1118 cmꢀ1
;
MS (70 eV) m=z (%): 477.50 (Mþ þ 1, 100). Anal. calcd. for C32H28O4: C, 80.65;
H, 5.92. Found: C, 80.68; H, 5.91.
Compound 3e. 1H NMR (CDCl3, 300 MHz): 2.58–2.70 (m, 4H, 4-H þ 5-H),
2.84–2.94 (m, 4H, 2-H þ 7-H), 3.29 (m, 2H, 3-H þ 6-H), 3.77 (s, 3H, OCH3), 4.85
(s, 1H, 9-H), 6.78–6.86 (m, 2H, 9-Ph-H), 7.18–7.39 (m, 12H, Ph-H); IR (KBr) t:
1708, 1625, 1511, 1121 cmꢀ1; MS (70 eV) m=z (%): 475.29 (M–– 1, 100), 219.64
(48). Anal. calcd. for C32H28O4: C, 80.65; H, 5.92. Found: C, 80.69; H, 5.90.
Compound 3f. 1H NMR (CDCl3, 300 MHz): 2.52–2.65 (m, 4H, 4-H þ 5-H),
2.71–2.80 (m, 4H, 2-H þ 7-H), 2.92 (s, 3H, N-CH3), 2.93 (s, 3H, N-CH3), 3.28 (m,
2H, 3-H þ 6-H), 4.82 (s, 1H, 9-H), 6.67–6.73 (m, 2H, 9-Ph-H), 7.11–7.39 (m, 12H,
Ph-H); IR (KBr) t: 1708, 1611, 1543, 1503, 1119 cmꢀ1; MS (70 eV) m=z (%):
490.44 (M– þ 1, 100). Anal. calcd. for C33H31NO3: C, 80.95; H, 6.38; N, 2.86. Found:
C, 80.98; H, 6.39; N, 2.84.

SYNTHESIS OF 1,8-DIOXO-OCTAHYDROXANTHENE
1871
Compound 3g. 1H NMR (DMSO, 300 MHz): 2.47–2.49 (m, 4H, 4-H þ 5-H),
2.78–2.79 (m, 4H, 2-H þ 7-H), 2.82 (m, 2H, 3-H þ 6-H), 3.68 (s, 6H, OCH3), 4.76
(s, 1H, 9-H), 6.82 (m, 13H, Ph-H); IR (KBr) t: 1683, 1625, 1512, 1129 cmꢀ1; MS
(70 eV) m=z (%): 506.11 (M, 100). Anal. calcd. for C33H30O5: C, 78.24; H, 5.97.
Found: C, 78.27; H, 5.93.
Compound 3h. 1H NMR (DMSO, 300 MHz): 2.49–2.59 (m, 4H, 4-H þ 5-H),
2.80 (m, 4H, 2-H þ 7-H), 2.89 (m, 2H, 3-H þ 6-H), 3.71 (s, 6H, OCH3), 4.92 (s, 1H,
9-H), 6.79 (m, 12H, Ph-H); IR (KBr) t: 1748, 1683, 1618, 1504, 1131 cmꢀ1; MS
(70 eV) m=z (%): 540.50 (M, 100). Anal. calcd. for C33H29ClO5: C, 73.26; H, 5.40.
Found: C, 73.29; H, 5.36.
Compound 3i. 1H NMR (DMSO, 300 MHz): 2.52–2.56 (m, 4H, 4-H þ 5-H),
2.79 (m, 4H, 2-H þ 7-H), 2.87 (m, 2H, 3-H þ 6-H), 3.73 (s, 6H, OCH3), 4.59 (s, 1H,
9-H), 6.91 (m, 12H, Ph-H); IR (KBr) t: 1750, 1671, 1624, 1507, 1127 cmꢀ1; MS
(70 eV) m=z (%): 540.5 (M, 100). Anal. calcd. for C33H29ClO5: C, 73.26; H, 5.40.
Found: C, 73.28; H, 5.38.
Compound 3j. 1H NMR (DMSO, 300 MHz): 2.59–2.63 (m, 4H, 4-H þ 5-H),
2.74–2.76 (m, 4H, 2-H þ 7-H), 2.76 (m, 2H, 3-H þ 6-H), 3.64 (s, 3H, OCH3), 3.71
(s, 6H, OCH3), 4.62 (s, 1H, 9-H), 6.70 (m, 12H, Ph-H); IR (KBr) t: 1732, 1681,
1621, 1509, 1107 cmꢀ1; MS (70 eV) m=z (%): 536 (M, 100). Anal. calcd. for
C34H32O6: C, 76.10; H, 6.01. Found: C, 76.15; H, 6.00.
Compound 3k. 1H NMR (DMSO, 300 MHz): 2.51–2.57 (m, 4H, 4-H þ 5-H),
2.72–2.75 (m, 4H, 2-H þ 7-H), 2.79 (m, 2H, 3-H þ 6-H), 3.65 (s, 3H, OCH3), 3.71
(s, 6H, OCH3), 4.59 (s, 1H, 9-H), 6.73 (m, 12H, Ph-H); IR (KBr) t: 1747, 1688,
1619, 1510, 1125 cmꢀ1; MS (70 eV) m=z (%): 535.33 (M– ꢀ 1, 100). Anal. calcd. for
C34H32O6: C, 76.10; H, 6.01. Found: C, 76.17; H, 5.99.
Compound 3l. 1H NMR (DMSO, 300 MHz): 2.49–2.61 (m, 4H, 4-H þ 5-H),
2.81–2.96 (m, 4H, 2-H þ 7-H), 2.99 (s, 6H, N(CH3)2), 3.02 (m, 2H, 3-H þ 6-H), 3.71
(s, 6H, OCH3), 4.53 (s, 1H, 9-H), 6.82 (m, 12H, Ph-H); IR (KBr) t: 1710, 1685, 1617,
1506, 1132 cmꢀ1; MS (70 eV) m=z (%): 549 (M, 100). Anal. calcd. for C35H35NO5: C,
76.48; H, 6.42; N, 2.55. Found: C, 76.51; H, 6.41; N, 2.53.
Compound 3m. 1H NMR (DMSO, 300 MHz): 0.87 (s, 6H, 2-CH3), 1.08
(s, 6H, 2-CH3), 2.09 (m, 2H, 4-H), 2.21 (m, 2H, 5-H), 2.52 (m, 2H, 2-H), 2.61
(m, 2H, 7-H), 4.63 (s, 1H, 9-H), 7.20 (m, 5H, Ph-H); IR (KBr) t: 1745, 1621,
1506, 1126 cmꢀ1; MS (70 eV) m=z (%): 351.09 (Mþ þ 1, 100). Anal. calcd. for
C23H26O3: C, 78.83; H, 7.48. Found: C, 78.89; H, 7.45.
Compound 3n. 1H NMR (DMSO, 300 MHz): 0.89 (s, 6H, 2-CH3), 1.03
(s, 6H, 2-CH3), 2.05 (d, J ¼ 16.20 Hz, 2H, 4-H), 2.23 (d, J ¼ 16.20 Hz, 2H, 5-H),
2.49 (m, 4H, 2-H þ 7-H), 4.49 (s, 1H, 9-H), 7.16 (m, 4H, Ph-H); IR (KBr) t: 1726,
1622, 1508, 1128 cmꢀ1; MS (70 eV) m=z (%): 383.28 (M– – 1, 100). Anal. calcd. for
C23H25ClO3: C, 71.77; H, 6.55. Found: C, 71.81; H, 6.51.

1872
R.-H. WANG ET AL.
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