Acetic acid as an efficient catalyst for synthesis of 1,8-dioxo-octahydroxanthenes and 1,8-dioxo-decahydroacridines

Article abstract of DOI:10.1007/s11164-013-1516-2

1,8-Dioxo-octahydroxanthenes have been synthesized in good yields by reaction of arylaldehydes and dimedone in the presence of a catalytic amount of acetic acid, without use of any additional co-catalyst, under solvent-free, thermal conditions. We also re

Full text of DOI:10.1007/s11164-013-1516-2

Res Chem Intermed
DOI 10.1007/s11164-013-1516-2
Acetic acid as an efficient catalyst for synthesis
of 1,8-dioxo-octahydroxanthenes and 1,8-dioxo-
decahydroacridines
•
Nourallah Hazeri Amin Masoumnia
•
•
Malek Taher Mghsoodlou Sajjad Salahi
•
•
Mehrnoosh Kangani Samira Kianpour
•
•
Shiva Kiaee Jasem Abonajmi
Received: 5 August 2013 / Accepted: 15 December 2013
Ó Springer Science+Business Media Dordrecht 2014
Abstract 1,8-Dioxo-octahydroxanthenes have been synthesized in good yields by
reaction of arylaldehydes and dimedone in the presence of a catalytic amount of
acetic acid, without use of any additional co-catalyst, under solvent-free, thermal
conditions. We also report preparation of 1,8-dioxo-decahydroacridines by reaction
of arylaldehydes, dimedone, and amines or ammonium acetate under solvent-free,
thermal conditions in the presence of the same catalyst.
Keywords Acetic acid Á 1,8-Dioxo-octahydroxanthenes Á 1,8-Dioxo-
decahydroacridines Á Dimedone
Introduction
Xanthenes have a variety of biological properties including antibacterial, antiviral,
and anti-inflammatory activity [1]. In particular, the xanthenedione structure is
present in several natural products [2], and xanthenediones are valuable synthons
because of the inherent reactivity of their pyran ring [3]. Xanthenes are also very
useful and important organic compounds widely used as dyes [4], in laser
technology [5], and in fluorescent materials for visualization of biomolecules [6].
For many years substituted acridines have been used quite successfully as
antimalarials [7], and several have led to excellent results in cancer chemotherapy
[8]. These derivatives are frequently used in industry, especially for production of
dyes [9, 10]. In addition to these properties, analogues of acridine have been shown
N. Hazeri (&) Á A. Masoumnia Á M. T. Mghsoodlou Á S. Salahi Á M. Kangani Á
S. Kianpour Á S. Kiaee Á J. Abonajmi
Department of Chemistry, University of Sistan and Baluchestan, P.O. Box 98135–674, Zahedan,
Iran
e-mail: nhazeri@chem.usb.ac.ir
123

N. Hazeri et al.
to have very long-lasting efficiency and interesting electrochemical behavior [11] in
interactions with DNA.
Development of synthetic procedures that are environment-friendly, simple,
efficient, and cost effective is an ever-challenging objective. Many catalysts, for
example p-toluenesulfonic acid [12], p-dodecylbenzenesulfonic acid [13], InCl3–
ionic liquid [14], Fe3? montmorillonite [15], NaHSO4–SiO2 or silicon tetrachloride
[16], amberlyst-15 [17], silica–sulfuric acid [18], and TEBAC (benzyltriethylam-
monium chloride) [19], under microwave irradiation [20], in ionic liquids [21] have
been used for synthesis of xanthenediones and acridines; these compounds have also
been prepared from 9,10-diarylacridine-1,8-diones by use of p-dodecylbenzene-
sulfonic acid (DBSA) in water [22] and ZnO [23] as catalysts. However, some of
these methods involve use of expensive reagents, hazardous organic solvents, and
tedious workup. Acetic acid is an inexpensive and commercially available
compound that can be used in the laboratory without special precautions.
In continuation of our research on multicomponent reactions based on acetic acid
[24], we report herein some applications of acetic acid for synthesis of 1,8-dioxo-
octahydroxanthenes and 1,8-dioxo-decahydroacridines (Scheme 1).
Experimental
Melting points and FT-IR spectra of all compounds were measured on an
Electrothermal 9100 apparatus and a Jasco FT/IR-460plus spectrometer, respec-
1
tively. H NMR spectra were obtained on Bruker DRX-300 and DRX-400 Avance
instruments with CDCl3 and DMSO as solvent. All reagents and solvents were
obtained from Fluka and Merck and were used without further purification.
O
Ar
O
O
3a-q
O
HOAc ( 0.2 mL )
Ar-CHO
+
2
O
Solvent-Free
80 oC
1
2
Ar
O
O
RNH2 or NH4OAC
4
3
N
R'
R' = R or H
5a-v
Scheme 1 Preparation of 1,8-dioxo-octahydroxanthenes and 1,8-dioxo-decahydroacridines
123

Acetic acid as an efficient catalyst
General procedure for synthesis of 1,8-dioxo-octahydroxanthenes
Acetic acid (0.2 mL) was added to a magnetically stirred mixture of aromatic
aldehyde (1 mmol) and 5,5-dimethyl-1,3-cyclohexanedione (2 mmol). The mixture
was heated at 80 °C and the reaction was monitored by TLC. After completion of
the reaction, Et2O (10 mL) was added and the mixture was filtered. The solid
residue was recrystallized from ethanol (98 %) to afford the pure product in good
yield.
The pure products were characterized by comparison of their physical data
1
(melting points, and IR and H NMR spectral data) with literature data for known
compounds [23, 26]. All the products were known. Selected spectroscopic data for
some of these are listed below:
3,4,6,7-Tetrahydro-3,3,6,6-tetramethyl-9-phenyl-2H-xanthene-1,8(5H,9H)-dione
1
(3a): H NMR (300 MHz, (CDCl3): d (ppm) = 1.00 (s, 6H, CMe2); 1.11 (s, 6H,
CMe2); 2.14–2.27 (q, J = 16.30 Hz, 4H, 2CH2); 2.47 (s, 4H, 2CH2); 4.67 (s, 1H,
CH); 7.01–7.32 (m, 5H, Ar).
3,4,6,7-Tetrahydro-3,3,6,6-tetramethyl-9-(2-chlorophenyl)-2H-xanthene-1,8(5H,
9H)-dione (3c): 1H NMR (300 MHz, (CDCl3): d (ppm) = 0.95 (s, 6H, CMe2); 1.03 (s,
6H,CMe2); 2.12 (s, 4H, 2CH2); 2.38 (s, 4H, 2CH2); 4.82 (s, 1H, CH); 7.02–7.33 (m,
4H, Ar).
3,4,6,7-Tetrahydro-3,3,6,6-tetramethyl-9-(4-hydroxyphenyl)-2H-xanthene-1,8
(5H,9H)-dione (3f): 1H NMR (300 MHz, (CDCl3): d (ppm) = 0.93 (s, 6H, CMe2);
1.03 (s, 6H,CMe2); 2.14 (s, 4H, 2CH2); 2.40 (s, 4H, 2CH2); 4.16 (s, 1H, CH);
6.55–7.05 (m, 4H, Ar); 7.19 (br, 1H, OH).
3,4,6,7-Tetrahydro-3,3,6,6-tetramethyl-9-(3,4-dimethoxyphenyl)-2H-xanthene-
1,8(5H,9H)-dione (3j): 1H NMR (300 MHz, (CDCl3): d (ppm) = 0.93 (s, 6H,
CMe2); 1.03 (s, 6H,CMe2); 2.13 (s, 4H, 2CH2); 2.39 (s, 4H, 2CH2); 3.71 (s, 3H,
OCH3); 3.77 (s, 3H, OCH3); 4.62 (s, 1H, CH); 6.66–6.82 (m, 3H, Ar).
3,4,6,7-Tetrahydro-3,3,6,6-tetramethyl-9-(4-nitrophenyl)-2H-xanthene-1,8(5H,9H)-
dione (3k): 1H NMR (300 MHz, (CDCl3): d (ppm) = 0.99 (s, 6H, CMe2); 1.13 (s, 6H,
CMe2); 2.14–2.29 (q, J = 16.35 Hz, 4H, 2CH2); 2.51 (s, 4H, 2CH2); 4.83 (s, 1H,CH);
7.48 (d, J = 8.68, 2H, Ar); 8.10 (d, J = 8.68, 2.H, Ar).
3,4,6,7-Tetrahydro-3,3,6,6-tetramethyl-9-(3-nitrophenyl)-2H-xanthene-1,8(5H,9H)-
1
dione (3l): H NMR (300 MHz, (CDCl3): d (ppm) = 0.93 (s, 6H, CMe2); 1.04 (s,
6H,CMe2); 2.14 (s, 4H, 2CH2); 2.44 (s, 4H, 2CH2); 4.77 (s, 1H, CH); 7.20–7.94 (m,
4H, Ar).
3,4,6,7-Tetrahydro-3,3,6,6-tetramethyl-9-(4-(dimethylamino)phenyl)-2H-xanthene-
1,8(5H,9H)-dione (3n): 1H NMR (300 MHz, (CDCl3): d (ppm) = 1.01 (s, 6H, CMe2);
1.10 (s, 6H,CMe2); 2.14–2.27 (q, J = 16.29 Hz, 4H, 2CH2); 2.46 (s, 4H, 2CH2); 2.88
(s, 4H, NMe2), 4.67 (s, 1H, CH); 6.63–7.14 (m, 4H, Ar).
3,4,6,7-Tetrahydro-3,3,6,6-tetramethyl-9-(4-methylphenyl)-2H-xanthene-1,8(5H,
9H)-dione (3o): 1H NMR (300 MHz, (CDCl3): d (ppm) = 0.95 (s, 6H, CMe2); 1.02
(s, 6H,CMe2); 2.12 (s, 4H, 2CH2); 2.22 (s, 4H, 2CH2); 2.37 (s, 1H, CH3); 4.66 (s,
1H, CH); 6.97–7.19 (m, 4H, Ar).
123

N. Hazeri et al.
General procedure for synthesis of 1,8-dioxo-decahydroacridines
A primary aromatic aldehyde (1 mmol) was added to amixture of an amine or
ammonium acetate (1 mmol) and 5,5-dimethyl-1,3-cyclohexanedione (2 mmol) in
HOAc (0.2 mL). The reaction was conducted under the conditions described above.
After completion of the reaction, Et2O (10 mL) was added and the mixture was
filtered. The solid residue was recrystallized from ethanol (99 %) to afford the pure
product in good yield.
The pure products were characterized by comparison of their physical data
1
(melting points, and IR and H NMR spectral data) with literature data for known
compounds [29, 30]. All the products were known. Selected spectroscopic data for
some of these are listed below:
3,3,6,6-Tetramethyl-9-(phenyl)-10-phenyl-1,2,3,4,5,6,7,8,9,10-decahydroacri-
dine-1,8-dione (5a): 1H NMR (400 MHz, (CDCl3): d (ppm) = 0.80 (s, 6H,
CMe2); 0.94 (s, 6H,CMe2); 1.83 (d, J = 16 Hz, 2H, 2CH); 2.09 (d, J = 16 Hz,
2H, 2CH); 2.16 (d, J = 16 Hz, 2H, 2CH); 2.20 (d, J = 16 Hz, 2H, 2CH); 5.30 (s,
1H, CH); 7.08–7.28 (m, 5H, Ar); 7.44–7.60 (m, 5H, Ar).
3,3,6,6-Tetramethyl-9-(4-chlorophenyl)-10-phenyl-1,2,3,4,5,6,7,8,9,10-decahydro-
acridine-1,8-dione (5b): 1H NMR (400 MHz, (CDCl3): d (ppm) = 0.80 (s, 6H,
CMe2); 0.94 (s, 6H,CMe2); 1.82 (d, J = 16 Hz, 2H, 2CH); 2.08 (d, J = 16 Hz, 2H,
2CH); 2.16 (d, J = 16 Hz, 2H, 2CH); 2.20 (d, J = 16 Hz, 2H, 2CH); 5.25 (s,
1H,CH); 7.19–7.28 (m, 4H, Ar); 7.37–7.60 (m, 5H, Ar).
3,3,6,6-Tetramethyl-9-(4-chlorophenyl)-10-(4-methoxyphenyl)-l-1,2,3,4,5,6,7,8,9,10-
1
decahydroacridine-1,8-dione (5c): H NMR (400 MHz, (CDCl3): d (ppm) = 0.81 (s,
6H, CMe2); 0.95 (s, 6H,CMe2); 1.86 (d, J = 16 Hz, 2H, 2CH); 2.08 (d, J = 16 Hz, 2H,
2CH); 2.16 (d, J = 16 Hz, 2H, 2CH); 2.20 (d, J = 16 Hz, 2H, 2CH); 3.92 (s, 3H, Me);
5.24 (s, 1H, CH); 7.04–7.14 (m, 4H, Ar); 7.19–7.38 (m, 4H, Ar).
3,3,6,6-Tetramethyl-9-(phenyl)-10-(4-methoxyphenyl)-l-1,2,3,4,5,6,7,8,9,10-
decahydroacridine-1,8-dione (5d): 1H NMR (400 MHz, (CDCl3): d (ppm) = 0.81 (s,
6H, CMe2); 0.95 (s, 6H, CMe2); 1.87 (d, J = 16 Hz, 2H, 2CH); 2.08 (d, J = 16 Hz,
2H, 2CH); 2.16 (d, J = 16 Hz, 2H, 2CH); 2.20 (d, J = 16 Hz, 2H, 2CH); 3.92 (s,
3H, Me); 5.28(s, 1H, CH); 7.04–7.16 (m, 5H, Ar); 7.22–7.44 (m, 4H, Ar).
3,3,6,6-Tetramethyl-9-(4-chlorophenyl)-10-(4-chlorophenyl)-l-1,2,3,4,5,6,7,8,9,10-
1
decahydroacridine-1,8-dione (5m): H NMR (400 MHz, (DMSO): d (ppm) = 0.71
(s, 6H, CMe2); 0.88 (s, 6H, CMe2); 1.78 (d, J = 20 Hz, 2H, 2CH); 2.00 (d,
J = 16 Hz, 2H, 2CH); 2.18 (d, J = 16 Hz, 2H, 2CH); 2.19 (d, J = 20 Hz, 2H, 2CH);
5.01 (s, 1H, CH); 7.27–7.33 (m, 4H, Ar); 7.49–7.68(m, 4H, Ar).
3,3,6,6-Tetramethyl-9-(4-chlorophenyl)-10-(4-nitrophenyl)-l-1,2,3,4,5,6,7,8,9,10-
decahydroacridine-1,8-dione (5o): 1H NMR (400 MHz, (CDCl3): d (ppm) = 0.81 (s,
6H, CMe2); 0.98 (s, 6H, CMe2); 1.78 (d, J = 20 Hz, 2H, 2CH); 2.07 (d, J = 20 Hz,
2H, 2CH); 2.16 (d, J = 16 Hz, 2H, 2CH); 2.22 (d, J = 16 Hz, 2H, 2CH); 5.25 (s,
1H, CH); 7.22-7.24 (d, J = 8 Hz, 2H, Ar); 7.35–7.37(d, J = 8 Hz, 2H, Ar);
7.48–7.50 (d, J = 8 Hz, 2H, Ar); 8.46–8.48 (d, J = 8 Hz, 2H, Ar).
3,4,6,7-Tetrahydro-3,3,6,6-tetramethyl-9-phenylacridine-1,8(2H,5H,9H,10H)-
1
dione (5p): H NMR (400 MHz, (DMSO): d (ppm) = 0.86 (s, 6H, CMe2); 1.00
(s, 6H, CMe2); 1.98 (d, J = 16 Hz, 2H, 2CH); 2.17 (d, J = 16 Hz, 2H, 2CH);
123

Acetic acid as an efficient catalyst
2.37 (d, J = 16 Hz, 2H, 2CH); 2.45 (d, J = 16 Hz, 2H, 2CH); 4.82 (s, 1H, CH);
7.07–7.16 (m, 5H, Ar); 9.29 (s, 1H, NH).
3,4,6,7-Tetrahydro-3,3,6,6-tetramethyl-9-(3-nitrophenyl)acridine-1,8(2H,5H,9H,
1
10H)-dione (5s): H NMR (400 MHz, (CDCl3): d (ppm) = 0.99 (s, 6H, CMe2);
1.12 (s, 6H, CMe2); 2.18 (d, J = 16 Hz, 2H, 2CH); 2.27 (d, J = 16 Hz, 2H, 2CH);
2.32 (d, J = 16 Hz, 2H, 2CH); 2.43 (d, J = 16 Hz, 2H, 2CH); 5.19 (s, 1H, CH);
6.33 (s, 1H, NH); 7.38–78.07 (m, 4H, Ar).
3,4,6,7-Tetrahydro-3,3,6,6-tetramethyl-9-(4-hydroxyphenyl)acridine-1,8(2H,5H,
9H,10H)-dione (5t): 1H NMR (400 MHz, (DMSO): d (ppm) = 0.87 (s, 6H, CMe2);
1.00 (s,6H,CMe2); 1.98 (d, J = 16 Hz, 2H, 2CH); 2.15 (d, J = 16 Hz, 2H, 2CH);
Table 1 Optimization of the
Entry
T (°C)
Time (min)
Yield (%)a
temperature for synthesis of 1,8-
dioxo-octahydroxanthenes in the
presence acetic acid as catalyst
under solvent-free conditions
1
2
3
4
5
r.t
70
70
30
5
38
78
94
95
95
40
60
80
100
a
Yields refer to pure isolated
5
product
Table 2 Synthesis of 1,8-dioxo-octahydroxanthenes using acetic acid as catalyst under thermal
conditions
Entry
Ar
Product
Time (min)
Yield (%)a
MP (°C) Ref.b
1
Ph
3a
3b
3c
3d
3e
3f
5
10
7
95
81
85
98
70
85
94
90
97
79
94
90
91
90
93
–
200–203 [23]
227–229 [15]
224–226 [23]
243–245 [25]
248–250 [23]
220–222 [15]
240–242 [15]
175–178 [26]
195–197 [26]
175–177 [23]
222–225 [26]
175–177 [23]
219–221 [27]
224–226 [23]
214–216 [15]
–
2
4-ClC6H4
3
2-ClC6H4
4
2,4-Cl2C6H3
4-OHC6H4
3-OHC6H4
4-MeOC6H4
3-MeOC6H4
2,4-(MeO)2C6H3
3,4-(MeO)2C6H3
4-NO2C6H4
3-NO2C6H4
4-CNC6H4
4-N(Me)2C6H4
4-MeC6H4
CH3(CH2)5
CH3(CH2)6
15
15
15
12
25
20
12
5
5
6
7
3g
3h
3i
8
9
10
11
12
13
14
15
16
17
3j
3k
3l
14
5
3m
3n
3o
3p
3q
20
10
24
24
–
–
– No reaction
a
Isolated yield
b
All the products are known compounds and were characterized from their spectroscopic (1H NMR and
FT-IR) properties
123

N. Hazeri et al.
2.30 (d, J = 16 Hz, 2H, 2CH); 2.42 (d, J = 16 Hz, 2H, 2CH); 4.70 (s, 1H, CH);
6.51–6.53 (d, J = 8 Hz, 2H, Ar); 6.92–6.94 (d, J = 8 Hz, 2H, Ar).
Results and discussion
To prepare 1,8-dioxo-octahydroxanthenes more efficiently by optimizing the time,
temperature, and amount of catalyst, reaction of 5,5-dimethyl-1,3-cyclohexanedione
and benzaldehyde was selected as model system and catalyst reactivity at different
temperatures (r.t., 40, 60, 80, and 100 °C) and different amounts of catalyst were
investigated. The best result was obtained by conducting the reaction with a 2:1
molar ratio of 5,5-dimethyl-1,3-cyclohexanedione to benzaldehyde, in the presence
of HOAc (0.2 mL) at 80 °C under solvent-free conditions (Table 1).
Table 3 Synthesis of 1,8-dioxo-decahydroacridines by reaction of dimedone, aromatic aldehydes, and
primary amines in the presence of HOAc at 80 °C
Entry Ar
Amine
Product Time (min) Yield (%)a MP (°C) Ref.b
1
Ph
Ph
Ph
5a
5b
10
8
92
92
88
77
91
96
89
89
91
97
85
83
94
86
95
97
90
95
92
98
95
93
–
248–250 [29]
240–242 [29]
250–252 [30]
215–217 [30]
210–212 [30]
259–261 [22]
[300 [22]
2
4-Cl C6H4
4-Cl C6H4
Ph
3
4-OMe C6H4 5c
4-OMe C6H4 5d
4-OMe C6H4 5e
8
4
15
24
12
20
14
22
5
5
4-OMe C6H4
Ph
6
4-Me C6H4
4-Me C6H4
4-Me C6H4
4-Me C6H4
4-Me C6H4
4-Me C6H4
5f
7
2,4-Cl C6H4
4-Cl C6H4
3-NO3 C6H4
4-OH C6H4
2-Cl C6H4
5g
5h
5i
8
262–264 [22]
275–276 [22]
[300 [22]
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
5j
5k
5l
5
289–291 [22]
268–270 [22]
280–282 [31]
[300 [31]
3-OMe-4-OH C6H3 4-Me C6H4
30
10
14
17
8
4-Cl C6H4
2-Cl C6H4
4-Cl C6H4
Ph
4-Cl C6H4
4-NO2 C6H4
4-NO2 C6H4
NH4OAC
NH4OAC
NH4OAC
NH4OAC
NH4OAC
NH4OAC
NH4OAC
NH4OAC
5m
5n
5o
5p
5q
5r
5s
5s
5t
[300 [31]
280–282 [32]
[300 [32]
4-NO2 C6H4
2,3-(OMe)2 C6H4
3-NO3 C6H4
4-Me C6H4
4-OH C6H4
2-thienyl
5
14
14
10
15
20
24
[300 [32]
[300 [32]
[300 [32]
[300 [32]
5u
5v
[300 [32]
CH3(CH2)5
–
– No reaction
a
Isolated yield
b
All the products are known compounds and were characterized from their spectroscopic (1H NMR and
FT-IR) properties
123

Acetic acid as an efficient catalyst
These optimized conditions were used to investigate the scope and efficiency of
the reaction for synthesis of a wide variety of substituted 1,8-dioxo-octahydrox-
anthenes (Table 2). Interestingly, a variety of arylaldehydes including those with
electron-withdrawing or releasing substituents (ortho, meta, and para-substituted)
participated well in this reaction and gave the desired products in good to excellent
yield. We then investigated the aliphatic aldehydes n-heptanal and n-octanal instead
of aryl aldehydes in the reaction. The starting materials were recovered almost
intact; only traces of product were formed, without any side products, after 24 h
(Table 2, Entries 16, 17).
In continuation our research on application of this catalyst, we attempted the
synthesis of 1,8-dioxo-decahydroacridines. First, we optimized the amount of
catalyst in the reaction between benzaldehyde (1.0 mmol), dimedone (2.0 mmol),
and amine or ammonium acetate. The best result was obtained by use of 0.2 mmol
acetic acid at 80 °C. Next, aromatic aldehydes, dimedone, and amines were reacted
under the optimized conditions (Table 3). A wide range of substituted and
structurally diverse aldehydes enabled synthesis of the corresponding products in
high to excellent yields. We then investigated the aliphatic aldehyde n-heptanal
instead of benzaldehyde in the reaction. The starting materials were recovered
O
R
R
H
+H
OH
OH R
OH
R
O
OH
-H
H
O
O
O
(I)
OH
O
R
O
O
O
H
OH
OH
-H2O
R
+H
O
O
O
O
-H
(II)
O
R
O
R
O
R
O
O
+H
O
H
O
O
OH
OH
OH
(III)
O
R
O
O
H
O
R
O
O
-H2O
-H
OH2
Scheme 2 Mechanism suggested for synthesis of 1,8-dioxo-octahydroxanthenes catalyzed by acetic acid
123

N. Hazeri et al.
Table 4 Comparison of this method with other methods for synthesis of compounds 3a and 5a
Entry Product Catalyst
Conditions
Time
Yield (%) Ref.
1
3a
3a
3a
5a
3a
5a
3a
3a
3a
5a
5a
3a
5a
Fe3? Montmorillonite
NaHSO4.SiO2
Silica chloride
Amberlyst-15
TMSCl
Ethanol 100 °C
CH3CN reflux
6 (h)
6.5 (h)
6 (h)
5 h
94
90
93
81
84
83
94
98
92.8
96
86
95
[15]
2
[16]
3
CH3CN reflux
[16]
4
Solvent-free/50 °C
CH3CN/DMF reflux 8 (h)
[17]
5
[24]
6
SiO2-Pr-SO3H Acetic acid Solvent-free/120 °C 2 h
TSILs
[32]
7
TSILs, H2O, 100 °C 1 (h)
Solvent free 120 °C 9 (h)
Solvent free 140 °C 0.5 (h)
[33]
8
SmCl3
[34]
9
PPA–SiO2
CAN
[35]
10
11
12
13
PEG 400/50 °C
4 h
[29]
[Hmim]TFA
HOAc
Solvent-free/80 °C
Solvent free 80 °C
Solvent free 80 °C
4.5 h
5 (min)
[36]
This work
This work
HOAc
10 (min) 92
almost intact; only traces of product were formed, without any side products, after
24 h (Table 3, Entry 23).
The mechanism suggested, on the basis of the literature [28], for formation of the
products is shown in Scheme 2. One molecule of 5,5-dimethyl-1,3-cyclohexane-
dione first condenses with activated aldehyde (I) to afford intermediate (II). Another
molecule of 5,5-dimethyl-1,3-cyclohexanedione then reacts with (II) by Michael
addition to give the intermediate (III). Finally, cyclodehydration of (III) gives the
expected products, 1,8-dioxo-octahydroxanthenes. As shown in Scheme 2, aliphatic
aldehydes cannot form stable intermediates by this mechanism. Thus, only traces of
product were obtained.
In Table 4 results from this research are compared with results from methods
previously reported for synthesis of compounds 3a and 5a. The comparison shows
that, from the perspective of reaction times and yields, acetic acid is most efficient
catalyst.
Conclusion
In summary, we have demonstrated that 1,8-dioxo-octahydroxanthenes and 1,8-
dioxo-decahydroacridines can be successfully synthesized in acetic acid as catalyst.
The experimental procedure is quite simple and convenient, without use of
hazardous and expensive organic solvents. The reaction conditions are also
amenable to scale-up. All these features make this procedure an attractive addition
to existing methods.
Acknowledgments We gratefully acknowledge financial support from the Research Council of
University of Sistan and Baluchestan, Iran.
123

Acetic acid as an efficient catalyst
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