Kai Gong et al. / Chinese Journal of Catalysis 36 (2015) 1249–1255
1251
1H, CH), 7.08–7.12 (t, 1H, ArH), 7.19–7.23 (t, 2H, ArH),
7.28–7.30 (d, 2H, ArH); 13C NMR (100 MHz, CDCl3): δ 196.42,
162.26, 144.11, 128.40, 128.07, 126.39, 115.68, 50.75, 40.88,
32.23, 31.85, 29.31, 27.35.
Compound 3i: white crystals, mp 217–219 °C (216–218 °C
[13]). FT-IR (KBr, cm−1): 3444, 2962, 2874, 1677, 1625, 1511,
1468, 1412, 1391, 1360, 1198, 1166, 1140, 1126, 1001, 840; 1H
NMR (300 MHz, CDCl3): δ 0.99 (s, 6H, CH3), 1.10 (s, 6H, CH3),
2.14–2.25 (m, 7H, CH2 and Ar-CH3), 2.45 (s, 4H, CH), 4.71 (s, 1H,
CH), 7.02 (d, J = 8.0 Hz, 2H, ArH), 7.17 (d, J = 8.0 Hz, 2H, ArH);
13C NMR (100 MHz, CDCl3): δ 196.45, 162.11, 141.21, 135.79,
128.81, 128.26, 115.78, 50.78, 40.89, 32.23, 31.45, 29.30, 27.40,
21.09.
Compound 3u: yellow crystals, mp 286–287 °C. FT-IR (KBr,
cm−1): 3428, 2923, 2850, 1659, 1606, 1591, 1521, 1423, 1384,
1361, 1347, 1174, 1128; 1H NMR (400 MHz, CDCl3): δ 1.94–2.11
(m, 4H, CH2), 2.34–2.37 (m, 4H, CH2), 2.57–2.73 (m, 4H, CH2),
4.88 (s, 1H, CH), 7.48 (d, J = 8.0 Hz, 2H, ArH), 8.09 (d, J = 8.0 Hz,
2H, ArH); 13C NMR (100 MHz, CDCl3): δ 196.46, 164.59, 151.73,
146.48, 129.44, 123.46, 115.77, 36.83, 32.23, 27.16, 20.24.
Compound 3y: yellow crystals, mp 288–290 °C. FT-IR (KBr,
cm−1): 3382, 2949, 1662, 1610, 1597, 1515, 1446, 1430, 1387,
1361, 1275, 1242, 1207, 1193, 1172, 1130, 961, 835, 632, 609;
1H NMR (400 MHz, CDCl3): δ 1.97–2.07 (m, 4H, CH2), 2.28–2.41
(m, 4H, CH2), 2.56–2.67 (m, 4H, CH2), 4.74 (s, 1H, CH), 4.81 (bs,
1H, Ar−OH), 6.67 (d, J = 8.0 Hz, 2H, ArH), 7.16 (d, J = 8.0 Hz, 2H,
ArH); 13C NMR (100 MHz, CDCl3): δ 196.77, 163.79, 154.05,
136.84, 129.57, 117.07, 115.02, 36.99, 30.79, 27.15, 20.33.
The reaction of benzaldehyde (1a) with dimedone (2a) was
initially selected as a model reaction to optimize the reaction
conditions for the formation of 1,8-dioxo-octahydroxanthenes
using a variety of solvents, temperatures, reactions times and
catalyst loadings. The results of these optimization experiments
are summarized in Table 1. These results showed that none of
the desired 1,8-dioxo-octahydroxanthene product was detected
when a mixture of benzaldehyde and dimedone was heated at
100 °C for 120 min in the absence of the catalyst (Table 1, entry
1). Furthermore, no activity was observed in the presence of
β-CD (Table 1, entry 2). When SBE-β-CD was used as the cata-
lyst, the product was obtained in low yield (Table 1, entry 3).
Pleasingly, however, the use of a small amount of β-CD-BSA as
the catalyst gave the desired product in excellent yield over a
much shorter reaction time (Table 1, entry 4). The best result
was achieved when the reaction was carried out with a 1 mol%
loading of β-CD-BSA (Table 1, entry 5). The use of a higher
loading of the catalyst did not lead to further improvements in
the yield or reaction time (Table 1, entry 6).
The results of the optimization experiments indicated that
the nature of the solvent had a significant impact on the out-
come of the reaction (Table 1, entries 7–14). It is noteworthy
that the use of a non-polar solvent such as toluene or cyclo-
hexane gave moderate yields of the desired product (65% and
70%, respectively). The use of a polar aprotic solvent such as
THF or MeCN led to a slight improvement in the yield (76% and
85%, respectively). In the absence of a solvent, the reaction
proceeded smoothly to give the desired product in a yield of
86%, although an extended reaction time of 60 min was re-
quired. Performing the reaction in a polar solvent therefore
afforded improved yields of the product as well as enhancing
the reaction rate. The use of polar protic solvents such as water
and ethanol accelerated the reaction within a minimum reac-
tion time at 100 °C to give the desired product 3a in 93% and
91% yields, respectively. According to the principles of green
chemistry, water was selected as the best reaction medium for
further evaluation. Based on these experiments, the optimal
3. Results and discussion
A schematic illustration of the steps involved in the prepa-
ration for β-CD-BSA is shown in Scheme 2. Briefly, commercial-
ly available β-CD was reacted with 1,4-butane sultone in a
NaOH solution to afford sulfobutyl ether β-cyclodextrin, which
was treated with acidic resin to give β-CD-BSA. The resulting
β-CD-BSA material was characterized by FT-IR spectroscopy
1
and H NMR. The average degree of substitution for the sul-
Table 1
fobutyl ether group on the β-CD-BSA material was found to be
Optimization of the reaction conditions for the synthesis of 3a.
7 [37].
T
Catalyst
(mol%)
Time
(min)
120
30
30
30
30
30
60
100
100
60
60
60
Yielda
(%)
NR b
NR b
56
85
93
93
86
65
70
76
85
82
91
90
Entry
Solvent
OH
(°C)
100
100
100
100
100
100
100
100
O
O
HO
1
2
3
4
5
6
7
8
H2O
H2O
H2O
H2O
H2O
H2O
—
Toluene
0
O
OH
HO
OH
β-CD (1)
O
OH
HO
HO
O
SBE-β-CD (1)
β-CD-BSA (0.5)
β-CD-BSA (1)
β-CD-BSA (2)
β-CD-BSA (1)
β-CD-BSA (1)
β-CD-BSA (1)
β-CD-BSA (1)
β-CD-BSA (1)
β-CD-BSA (1)
β-CD-BSA (1)
β-CD-BSA (1)
OH
O
O
OH
O
HO
β-CD
OH
OH
O
OH
OH
HO
OH
HO
OH
OH
O
O
O
OH
OH
OH
O
OH
O
O
O
O
O
HO
O
O
9
Cyclohexane Reflux
NaOH/H2O
O
O
10
11
12
13
14
THF
MeCN
DMF
Reflux
Reflux
100
Reflux
100
1,4-butane
sultone
cation exchange
resin
HO
OH
CH3CH2OH
HOCH2CH2OH
30
30
HO3S
NaO3S
O
O
O
SBE-β-CD
β-CD-BSA
Reaction conditions: benzaldehyde (2 mmol), dimedone (4 mmol),
solvent-free or solvent (2 mL).
OH
a Isolated yield.
Scheme 2. Synthesis of β-CD-BSA.
b No reaction was observed.