Synthesis, Structure, and Biological Activities of 10-Substituted 3,3,6,6-Tetramethyl-9-Aryl-3,4, 6,7,9,10-hexahydroacridine-1,8(2H,5H)-dione Derivatives

Article abstract of DOI:10.1002/jhet.2925

A series of 10-substituted-3,3,6,6-tetramethyl-9-aryl-3,4,6,7,9,10-hexahydroacridine-1,8(2H,5 H)-dione derivatives 2 were synthesized by reaction of compounds 1 with amines. The compounds 1 were effectively prepared by 5,5-dimethylcyclohexane-1,3-dione an

Full text of DOI:10.1002/jhet.2925

Month 2017
Synthesis, Structure, and Biological Activities of 10-Substituted 3,3,6,6-
Tetramethyl-9-Aryl-3,4, 6,7,9,10-hexahydroacridine-1,8(2H,5H)-dione
Derivatives
*
Fang-Ming Wang,
Lei Zhou, Jun-Feng Li, Dan Bao, and Li-Zhuang Chen
School of Environmental and Chemical Engineering, Jiangsu University of Science and Technology, Zhenjiang, Jiangsu
212003, China
*
E-mail: wangfmzj@qq.com
Received January 19, 2017
DOI 10.1002/jhet.2925
Published online 00 Month 2017 in Wiley Online Library (wileyonlinelibrary.com).
A series of 10-substituted-3,3,6,6-tetramethyl-9-aryl-3,4,6,7,9,10-hexahydroacridine-1,8(2H,5 H)-dione
derivatives 2 were synthesized by reaction of compounds 1 with amines. The compounds 1 were effectively
prepared by 5,5-dimethylcyclohexane-1,3-dione and aldehydes in the presence of a little amount of L-proline
as catalyst at room temperature. All the compounds were characterized by IR, MS, and 1H NMR. The crystal
data of 1b and 2d were collected by X-ray single-crystal diffraction, and compounds 2b and 2d exhibited
better inhibitory activity against HepG2 cells.
J. Heterocyclic Chem., 00, 00 (2017).
INTRODUCTION
temperature [19]. Surprisingly, herein, we report a series
compounds of tetraketones 1, which were synthesized by
condensation of 5,5-dimethylcyclohexane-1,3-dione with
aldehydes under similar conditions. And these
tetraketones could be further converted to acridinedione
derivatives 2 by keto-enol tautomerism, cyclization, and
substituted reactions (Scheme 1). Furthermore, we
obtained crystal structures of compounds 1b and 2d by
X-ray single-crystal diffraction and investigated their
biological activities against HepG2 cells.
Acridinediones are important heterocyclic compounds,
which possess photochemical properties [1,2], biological
activities [3,4], and pharmacological activities [5]. They
are widely used as anticancer [6,7], antibacterial [8], DNA
probe [9], antitumor [10], and so on. Therefore, many
studies have been carried out on acridinedione
derivatives [11–13]. Tetraketones are extensively used as
important precursors for the synthesis of various
acridinediones. Tetraketones were first described by
Merling [14] in 1894, during his pioneering work of
synthesizing the cyclohexane-1,3-dione from resorcinol.
Then, several reports have appeared to attempt efficient
synthesis of tetraketones [15–18].
RESULTS AND DISCUSSION
All the compounds were characterized by IR, MS, and 1H
NMR. In the 1H NMR data of 1a–1b,there existed a single
peak for one proton at δ: 5.62–5.87, which should be
attributed to the peak shifts at 7-position. Accordingly, there
existed broad absorption bands around 1594–1619 cmꢀ1
Earlier, we have reported a series of 3,4,5,6,7,8a,9,10a-
octahydro-1H-xanthene- 1,8(2H)-diones by condensation
of 1,3-cyclohexanedione with aldehydes in the presence
of a little amount of L-proline as a catalyst at room
© 2017 Wiley Periodicals, Inc.

F.-M. Wang, L. Zhou, J.-F. Li, D. Bao, and L.-Z. Chen
Vol 000
Scheme 1. Synthesis of the title compounds (R1 = 20-Cl; 40-CH3; R2 = -H; -C6H5; 4″-ClC6H5). R1 = 20-Cl; 40-CH3; R2 = -H; -C6H5; 4″-ClC6H5. (1)
methanol/ethanol mixture (1:1), L-proline, r.t., 1.5–4 h; (2) substituted ammonium, acetic acid, reflux, 24 h.
which may be ascribed to typical absorptions of the group
(C═O) in IR spectra of 1a–1b. In H NMR spectrum of
group (N―H) in IR spectra of 2a and 2d. In the ESI-MS
spectrum, the ion adducts were usually observed as the
primary fragment peaks for compounds 2a–2f.
The compounds of 1b and 2d were completely dissolved
in ethanol. Three days later, the crystals were obtained
through slow evaporation of solvent. The crystal
structures of 1b and 2d were unequivocally confirmed
with X-ray diffraction (Fig. 1a and b). Crystallographic
data of 1b and 2d were collected using a Bruker SMART
APEX II CCD-based diffractometer with graphite-
1
compounds 2a–2f, the single peaks at δ: 4.72–5.33 were
attributed to the proton shifts at 9-position. There also were
the single peaks at 7.26–7.27 which should be the peak of
the group (N―H). And the IR spectrum of these
compounds, the absorption bands at 1640 and 1656 cmꢀ1
were the typical absorptions of carbonyl group (C═O). In
addition, there existed a broad absorption peak at 3464–
3441 cmꢀ1, which should be the typical absorptions of the
Figure 1. Molecular structure of compounds 1b and 2d (H atoms omitted for clarity). [Color figure can be viewed at wileyonlinelibrary.com]
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2017
Synthesis Structure and Biological Activities of 10-Substituted 3,3,6,6-
Tetramethyl-9-Aryl-3,4, 6,7,9,10-hexahydroacridine-1,8(2H,5H)-dione Derivatives
monochromatic MoKα radiation (λ = 0.71073 Å) at 291(2)
K (Table 1). Data reductions and absorption corrections
were performed with SAINT and SADABS software
packages [20], respectively. Structures were solved by
direct methods using the SHELXL-97 software package
[21]. Non-hydrogen atoms were refined anisotropically
using the full-matrix least-squares method on F2. All
hydrogen atoms were placed at calculated positions and
refined riding on the parent atoms.
The selected bond lengths, bond angles, and torsion
angles for compounds 1b and 2d are listed in Table 2. As
shown in Fig. 1c and d, in the crystal structure of 1b, the
result shows that the C1―C2 and C17―C24 bond
lengths are 1.361(3) and 1.366(3)Ǻ, respectively. The
Table 1
Crystallographic data for compounds 1b and 2d.
Identification code
1b
2d
Empirical formula
Ccdc nos.
Formula weight
Temperature
C
24H30O4
C24H29NO2
1440030
363.48
1440031
382.48
291(2) K
291(2)K
Wavelength
0.71073 Å
0.71073 Å
Crystal system, space group
Unit cell dimensions
Monoclinic, P21/c
a = 9.3003(15) Å, α = 90°
b = 11.7726(19)Å, β = 102.363(2)°
c = 20.118(3) Å, γ = 90°
2151.6(6) Å3
Orthorhombic, Pna21
a = 14.0296(11) Å, α = 90°
b = 14.5931(12)Å, β = 90°
c = 10.4643(9) Å, γ = 90°
2142.4(3)Å3
Volume
Z
4
4
Calculated density
Absorption coefficient
F(000)
1.181 g·cmꢀ3
1.127 g·cmꢀ3
0.079 mmꢀ1
824
0.071 mmꢀ1
784
Crystal size
0.20 × 0.18 × 0.15 mm
2.832° to 25.999°.
4199/2147
0.20 × 0.15 × 0.10 mm
2.01° to 26.000°.
4191/3029
Theta range for data collection
Reflections collected/unique
Completeness to theta = 25.00
Max. and min. transmission
Refinement method
Goodness-of-fit on F2
Final R indices [I > 2sigma(I)]
R indices (all data)
99.2%
1.89/1.00
0.986 and 0.993
Full-matrix least-squares on F2
0.992
R1 = 0.0530, wR2 = 0.1196
R1 = 0.1265, wR2 = 0.1378
0.986 and 0.993
Full-matrix least-squares on F2
1.015
R1 = 0.0486,wR2 = 0.1363
R1 = 0.0767, wR2 = 0.1555
Table 2
Selected bond lengths (Å) and bond angles (°).
Compound 1b
Bond
C(1)―C(6)
C(9)―C(17)
Distance
1.444(3)
1.511(3)
Bond
C(17)―C(24)
Distance
1.366(3)
Bond
C(1)―C(9)
Distance
1.519(3)
Angle
(°)
Angle
(°)
Angle
(°)
C(2)―C(1)―C(9)
C(6)―C(1)―C(9)
C(17)―C(9)―C(10)
C(1)―C(9)―C(10)
O(4)―C(24)―C(17)
O(2)―C(6)―C(1)
C(17)―C(9)―C(1)
C(18)―C(17)―C(9)
C(24)―C(17)―C(9)
126.42(18)
116.78(18)
113.35(18)
116.41(17)
123.9(2)
121.4(2)
114.58(17)
120.87(17)
121.9(2)
C(2)―C(1)―C(9)―C(17)
C(9)―C(1)―C(6)―C(5)
C(6)―C(1)―C(2)―O(1)
C(6)―C(1)―C(9)―C(10)
C(1)―C(9)―C(17)―C(24)
C(10)―C(9)―C(17)―C(24)
C(1)―C(9)―C(17)―C(18)
C(9)―C(17)―C(24)―O(4)
C(9)―C(17)―C(24)―C(23)
Compound 2d
81.2(2)
C(6)―C(1)―C(9)―C(17)
C(24)―C(17)―C(18)―O(3)
C(9)―C(1)―C(2)―O(1)
C(9)―C(17)―C(18)―O(3)
C(9)―C(1)―C(2)―C(3)
C(9)―C(17)―C(18)―C(19)
C(9)―C(1)―C(6)―O(2)
ꢀ95.0(2)
ꢀ173.78(19)
169.33(19)
129.5(2)
90.1(2)
ꢀ166.74(19)
ꢀ6.8(3)
9.4(3)
173.1(2)
ꢀ173.50(18)
8.4(3)
ꢀ133.0(2)
ꢀ85.8(2)
ꢀ6.1(3)
174.9(2)
Bond
C(8)―C(9)
C(9)―C(10)
Angle
Distance
1.513(4)
1.511(3)
(°)
Bond
C(10)―C(17)
C(7)―N(1)
Distance
1.349(3)
1.354(3)
(°)
Bond
C(7)―C(8)
C(17)―N(1)
Distance
1.356(3)
1.374(3)
(°)
Angle
Angle
C(8)―C(7)―N(1)
C(10)―C(17)―N(1)
N(1)― C(7)―C(8)―C(1)
C(9)―C(10)―C(17)―N(1)
121.2(2)
121.19(19)
173.5(2)
ꢀ1.4(4)
C(8)―C(9)―C(10)
C(7)―C(8)―C(9)
N(1)―C(7)―C(8)―C(9)
C(11)―C(10)―C(17)―N(1)
110.85(17)
121.81(19)
4.3(4)
C(7)―N(1)―C(17)
C(17)―C(10)―C(9)
C(6)―C(7)―C(8)―C(9)
C(9)―C(10)―C(17)―C(16)
121.76(18)
121.7(2)
―179.6(2)
179.7(3)
178.5(2)
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

F.-M. Wang, L. Zhou, J.-F. Li, D. Bao, and L.-Z. Chen
Vol 000
Table 3
Hydrogen bond lengths (Å) and bond angles (°).
D―H···A
d(D―H)
d(H···A)
Compound 1b
d(D···A)
∠DHA
O(1)―H(1)···O(3)a
0.85
0.85
0.98
0.98
0.93
1.73
1.84
2.30
2.47
2.58
2.568(2)
2.678(3)
2.802(3)
2.911(3)
3.095(3)
169
169
111
107
115
O(4)―H(4)···O(2)b
C(9)―H(9A) ···O(2)c
C(9)―H(9A) ···O(4)d
C(11)―H(11A) ···O(2)e
Compound 2d
1.89
N(1)―H(1) ···O(2)f
0.86
2.737(3)
169
Symmetry codes: a: 1/2 + x, ꢀ3/2 ꢀ y, z
Table 4
compounds 1 with amines. The compounds 1 were
effectively prepared by 5,5-dimethylcyclohexane-1,3-dione
and aldehydes through the Knoevenagel, Michael, and
cyclization reactions in the presence of a very small amount
of L-proline as catalyst at room temperature. All the
The IC50 and inhibitory activity of compounds.
HepG2 (IC50)
Inhibition rate (%) at
Sample
(μmol/L)
100 μmol/L
1a
1b
2a
2b
2c
2d
2e
2f
>100
>100
>100
54.04
>100
>100
>100
54.50
23.05
12.79
26.88
85.27
12.21
21.22
19.34
81.30
1
compounds were characterized by IR, MS, and H NMR.
And crystals of 1b and 2d were obtained and determined by
X-ray single-crystal diffraction. In addition, these
compounds exhibited inhibitory activity against HepG2
cells. And the inhibitory activity of the compounds 2b and
2f was higher than the other compounds. It would be very
useful to the further study on the biological activities on this
family compounds.
compound 1b exists during the keto-enol tautomerization.
And the two cyclohexene rings (C1 > C6, C17 > C24)
adopt a half-boat conformation. As to compound 2d, the
acridine ring (C1 > C17) has a nearly chair conformation.
In the crystal of 1b, neighboring molecular formed
dimers by weak C―H···π intermolecular interactions
along b-axis (Fig. 1c). The distances between C19 to
benzyl ring (C10 > C15) were 3.6091(21) Ǻ. And there
also existed weak C―H···π intermolecular interactions
between C8 and benzyl ring (C10 > C15) to bind these
columns along the a-axis. However, the packing modes
of 2d were very different with 1b. There existed one
hydrogen bond (Table 3) that binds these moleculars
packed in column mode along the a-axis (Fig. 1d). In
addition, two weak C―H···π bonds along the c-axis were
found, and the distances between C12 to pyridyl ring
(C7 > C11 > N1) and C15 to benzyl ring (C18 > 24)
were 3.7104(31) and 3.7753(40) Ǻ, respectively. All
these intermolecular interactions bound the molecular in
1b and 2d to the three-dimensional supermolecular
structures.
BIOLOGICAL ACTIVITY
The HepG2 cells were inoculated in 96-well microtest
plates and treated with various concentrations of
compounds over a 48-h time period; the HepG2 cell
viability quantification was tested with MTT assay. The
experiment was performed according to the reference
[22]. Half inhibitory concentration (IC50) refers to the
drug concentration when the number of live cells reduced
to half correspondingly. IC50 could be calculated by the
application point inclined method [23].
The IC50 and inhibitory activity of compounds were
listed in Table 4; it was found that at a concentration of
100 μmol/L, precursors 1a and 1b exhibited weak
inhibitory activity, while compound 1a (Inhibition
rate = 23.05%) showed more potent than compound 1b
(Inhibition rate = 12.79%). It suggests that groups on the
phenyl ring have an influence on cell proliferation. In order
to improve inhibitory activity, we tried to synthesize a
series of acridinedione derivatives (compounds 2a–2f). We
hope that changing the group on the nitrogen atom could
help enhancing inhibitory activity. The results showed that
at a concentration of 100 μmol/L, the inhibition rate of
compounds 2a, 2c, 2d, and 2e may be very low, and even
sometimes may be negative. However, the inhibition rate
of compounds 2b (85.27%) and 2f (81.30%) was higher
CONCLUSIONS
In conclusion, we synthesized a series of 10-substituted-
3,3,6,6-tetramethyl-9-aryl-3,4,6,7,9,10-hexahy dro-acridine-
1,8(2H,5H)-dione derivatives 2 through the reaction of
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2017
Synthesis Structure and Biological Activities of 10-Substituted 3,3,6,6-
Tetramethyl-9-Aryl-3,4, 6,7,9,10-hexahydroacridine-1,8(2H,5H)-dione Derivatives
than the other compounds. In summary, these test data
change irregularly; there is no direct relationship between
compounds' structure and inhibitory activity. It may have
the following reasons: (1) the number of cells in each hole
in a large number of differences does not conform to the
requirements of the experiment error range; (2) influence
of drugs on cell inhibition rate does not conform to the
normal distribution as expected.
1250 (m), 1164 (s), 819 (m). Anal. calcd for
C24H30O4: C, 75.36; H, 7.91; found: C, 75.24; H,
7.84%. MS (ESI) m/z: 383.2 (M + H)+.
9-(2-Chlorophenyl)-3,3,6,6-tetramethyl-3,4,6,7,9,10-hexahyd
roacridine-1,8(2H,5H)-dione (2a). Yield: 75%. m.p. 288–
1
290°C; H NMR (DMSO-d6, 400 MHz) δ: 0.99 (s, 6H,
-2CH3), 1.09 (s, 6H, ꢀ2CH3), 2.06–2.47 (m, 8H, 2a-H,
7a-H, 2b-H, 7b-H, 4a-H, 5a-H, 4b-H, 5b-H), 5.33 (s, 1H,
9-H), 7.02–7.50 (m, 4H, Ph―H); IR (KBr): 3464 (br),
2954 (w), 1649 (s), 1575 (s), 1364 (s) 1207 (m), 1151 (m).
Anal. calcd for C23H26ClNO2: C, 71.96; H, 6.83; N, 3.65;
found: C, 71,88; H, 6.75; N, 3,60%. MS (ESI) m/z: 384.1
(M + H)+.
EXPERIMENTAL
All the chemicals were analytical reagent grade and
purchased from commercial sources, which were used
directly without further purification. Thin-layer
chromatography was performed on 10 × 3 cm Silica gel
TLC-GF254 foils. Elemental analysis was performed with
a Vario EL III elemental analyzer. Melting points were
9-(2-Chlorophenyl)-3,3,6,6-tetramethyl-10-phenyl-3,4,6,7,9,10-
hexahydroacridine-1,8(2H,5H)-dione (2b). Yield: 78%; m.p.
1
228–230°C. H NMR (DMSO-d6, 400 MHz) δ: 0.63 (s,
6H, -2CH3), 0.75 (s, 6H, -2CH3), 1.62–1.66 (m, 2H, 2a-H,
7a-H), 1.82–1.86 (m, 2H, 2b-H, 7b-H), 2.02–2.07 (m, 4H,
4a-H, 5a-H, 4b-H, 5b-H), 5.17 (s, 1H, 9-H), 6.98–7.31 (m,
4H, Ph―H); R2: 7.34–7.52 (m, 5H, Ph―H); IR (KBr):
3437 (br), 2936 (w), 1641 (s), 1575 (m), 1356 (s), 1220(s),
1144(m), 800 (m). Anal. calcd for C29H30ClNO2: C,
75.72; H, 6.57; N, 3.04; found: C, 75.66; H, 6.49; N,
3.00%. MS (ESI) m/z: 460.2 (M + H)+.
determined on
a capillary tube method, and the
temperature was not calibrated. Infrared spectra were
recorded as thin films on KBr using a Digilab FTS 2000
1
spectrophotometer. H NMR spectra were recorded on a
Bruker AVANCE III 400 spectrometer. The electrospray
ionization mass spectrometry (ESI-MS) was determined
on an Aglient-6100 equipment.
9-(2-Chlorophenyl)-10-(4-chlorophenyl)-3,3,6,6-tetramethyl-
Generalprocedure. 5,5-Dimethyl-1,3-cyclohexanedione
(40 mmol) and the aromatic aldehydes (20 mmol) were
dissolved in the mixture of methanol (20 mL) and ethanol
(20 mL), stirring for 3–4 h at room temperature, using a
little of L-proline (the molar ratio is 0.5%) as catalyst after
the reaction completed; the pure solid products 1a–b were
obtained by filtration and then washed with ethanol. The
compounds 2a–f can be obtained from derivatives 1 (1 mmol)
and some of substituted ammonium (1.2 mmol) which
include ammonium acetate, aniline, p-chloroaniline, and
naphthylamine in acetic acid (10 mL) under reflux for 24 h.
The crude products were purified by column chromatography
with the eluentethylacetate/cyclohexane = 1:3.
3,4,6,7,9,10-hexahydroacridine-1,8(2H,5H)-dione (2c). Yield:
73%; m.p. > 300°C; H NMR (DMSO-d6, 400 MHz) δ:
1
0.64 (s, 6H, ꢀ2CH3), 0.77 (s, 6H, -2CH3), 1.64–1.68 (m,
2H, 2a-H, 7a-H), 1.82–1.89 (m, 3H, 2b-H, 7b-H, 4a-H),
2.02–2.06 (m, 3H, 5a-H, 4b-H, 5b-H), 5.16 (s, 1H, 9-H),
7.00–7.60 (m, 4H, Ph―H); R2: 7.00–7.60 (m, 4H,
Ph―H); IR (KBr): 3455 (br), 2955 (w), 1641 (s), 1566
(m), 1372 (s), 1241 (m), 1139 (m), 820 (m). Anal. calcd
for C29H29Cl2NO2: C, 70.44; H, 5.91; N, 2.83; found: C,
70.31; H, 5.80; N, 2.72%. MS (ESI) m/z: 494.2 (M + H)+.
3,3,6,6-Tetramethyl-9-(p-tolyl)-3,4,6,7,9,10-hexahydroacridine-
1,8(2H,5H)-dione(2d).
Yi-eld: 80%; m.p. > 300°C; 1H
NMR (DMSO-d6, 400 MHz) δ: 0.97 (s, 6H, -2CH3), 1.08
(s, 6H, -2CH3), 2.15–2.31 (m, 8H, 2a-H, 7a-H, 2b-H, 7b-
H, 4a-H, 5a-H, 4b-H, 5b-H), 5.04 (s, 1H, 9-H), 6.99–7.22
(m, 4H, Ph―H), 7.27 (br, 1H, 10-NH); R1: 2.35 (s, 3H,
40-CH3); IR (KBr): 3441 (br), 2962 (w), 1648 (s), 1578 (s),
1377 (s), 1224 (m), 1144 (m). Anal. calcd for C24H29NO2:
C, 79.30; H, 8.04; N, 3.85; found: C, 79.19; H, 8.00; N,
3.72%. MS(ESI) m/z: 364.2 (M + H)+.
2,20-((2-Chlorophenyl)methylene)bis(5,5-dimethylcyclohexane-
1
1,3-dione) (1a). Yield: 94%; m.p. 196–198°C; H NMR
(DMSO-d6, 400 MHz) δ: 1.08 (m, 12H, -4CH3), 2.24–
2.52 (m, 8H, 4a-H, 60a-H, 4b-H, 60b-H, 6a-H, 40a-H, 6b-
H, 40b-H), 5.62 (s, 1H, 7-H), 7.09 (m, 2H, 2-H, 20-H),
7.12–7.39 (m, 4H, Ph―H); IR (KBr): 3455 (br), 2955
(w), 1619 (s), 1518 (m), 1346 (s), 1227 (s), 1147 (s), 833
(m). Anal. calcd for C23H27ClO4: C, 68.56; H, 6.75;
found: C, 68.44; H, 6.54%. MS (ESI) m/z: 403.1 (M + H)+.
3,3,6,6-Tetramethyl-10-phenyl-9-(p-tolyl)-3,4,6,7,9,10-
hexahydroacridine-1,8(2H,5H)-di-one (2e).
Yield:
1
2,20-(p-tolylmethylene)bis(5,5-dimethylcyclohexane-1,3-
81%; m.p. 190–192°C; H NMR (DMSO-d6, 400 MHz) δ:
0.81 (s, 6H, -2CH3), 0.94 (s, 6H, -2CH3), 1.79–1.83 (m,
2H, 2a-H, 7a-H), 2.04–2.11 (m, 3H, 2b-H, 7b-H, 4a-H),
2.15–2.18 (m, 3H, 5a-H, 4b-H, 5b-H), 5.24 (s, 1H, 9-H),
7.04–7.24 (m, 4H, Ph―H); R1: 2.26 (s, 3H, 40-CH3); R2:
7.26–7.58 (m, 5H, Ph―H); IR (KBr): 3441 (br), 2955
(m), 1656 (s), 1579 (m), 1363 (s), 1200 (m), 1136 (s), 820
1
dione) (1b). Yield: 90%; m.p. 128–130°C; H NMR
(DMSO-d6, 400 MHz) δ: 1.04 (s, 12H, -4CH3), 2.32
(m, 8H, 4a-H, 60a-H, 6a-H, 40a-H, 4b-H, 60b-H, 6b-H,
40b-H), 5.87 (s, 1H, 7-H), 6.84 (m, 2H, 2-H, 20-H),
6.93–7.02 (m, 4H, Ph―H); R1: 2.22 (s, 3H, 40 -CH3);
IR (KBr): 3457 (br), 2962 (w), 1594 (s), 1373 (s),
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

F.-M. Wang, L. Zhou, J.-F. Li, D. Bao, and L.-Z. Chen
Vol 000
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found: C, 81.83; H, 7.39; N, 3.11%. MS (ESI) m/z: 440.3
(M + H)+.
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10-(4-Chlorophenyl)-3,3,6,6-tetramethyl-9-(p-tolyl)-3,4,6,7,9,10-
hexahydroacridine-1,8(2H,5H)-dione (2f).
Yield: 72%; m.p.
1
80–82°C; H NMR (DMSO-d6, 400 MHz) δ: 1.01 (s, 6H,
ꢀ2CH3); 1.11 (s, 6H, -2CH3); 2.15–2.19 (m, 2H, 2a-H, 7a-H),
2.22–2.25 (m, 5H, 2b-H, 7b-H, 4a-H, 5a-H, 4b-H), 2.51–2.62
(m, 1H, 5b–H), 4.72 (s, 1H, 9-H), 7.02–7.18 (m, 4H, Ph―H);
R1: 2.47 (s, 3H, 40-CH3), R2: 7.20–7.44 (m, 4H, Ph―H); IR
(KBr): 3446 (br), 2955 (w), 1640 (s), 1585 (m), 1364 (s), 1224
(s), 1144(m), 844(m). Anal. calcdforC30H32ClNO2:C, 76.01;
H, 6.80; N, 2.95; found: C, 75.89; H, 6.65; N, 2.91%. MS (ESI)
m/z:474.3(M+H)+.
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Madison, WI (2000).
Acknowledgments. This work was supported by the National
Natural Science Foundation of China (Grant No. 21671084),
the Natural Science Foundation of Jiangsu Province (No.
BK20131244), Jiangsu Overseas Research and Training Program
for University Prominent Young and Middle-aged Teachers and
Presidents, and 1 P. R. of China.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet