An efficient synthesis of polyhydroacridine derivatives by the three-component reaction of aldehydes, amines and dimedone in ionic liquid

Article abstract of DOI:10.1002/jhet.5570450303

(Chemical Equation Presented) In this paper the preparation of 3,3,6,6-tetramethyl-9,10-diaryl-1,2,3,4,5,6,7,8,9,10-decahydroacridine-1, 8-dione derivatives from aldehydes, aromatic amines and 5,5-dimethyl-1,3- cyclohexanedione in 1-n-butyl-3-methylimidaz

Full text of DOI:10.1002/jhet.5570450303

May-Jun 2008
653
An Efficient Synthesis of Polyhydroacridine Derivatives by the
Three-component Reaction of Aldehydes, Amines and Dimedone in
Ionic Liquid
Da-Qing Shi,a,b,c,* Sai-Nan Ni,b Fang-Yang,b Jing-Wen Shi,b Guo-Lan Dou,b Xiao-Yue
Li,b Xiang-Shan Wang b,c
a College of Chemistry and Chemical Engineering, Key Laboratory of Organic Synthesis of Jiangsu Province,
Suzhou University, Suzhou 215123, P. R. China
b Department of Chemistry, Xuzhou Normal University, Xuzhou 221116, P. R. China
c Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province Xuzhou Normal University,
Xuzhou 221116, P. R. China
E-mail: dqshi@263.net
Received January 18, 2007
O
Ar1
O
Ar2 NH2
N
Ar2
O
O
[bmim]Br
90oC
Ar1 CHO
+
2
O
R
O
NH4OAc
N
H
In this paper the preparation of 3,3,6,6-tetramethyl-9,10-diaryl-1,2,3,4,5,6,7,8,9,10-decahydroacridine-
1,8-dione derivatives from aldehydes, aromatic amines and 5,5-dimethyl-1,3-cyclohexanedione in 1-n-
butyl-3-methylimidazolium bromide ([bmim]Br) is described. The structures of these compounds were
characterized by elemental analysis, IR and 1H NMR spectra and further confirmed by single crystal X-ray
diffraction analysis.
J. Heterocyclic Chem., 45, 653 (2008).
INTRODUCTION
and some enzymic reactions [21] can be carried out in
ionic liquid.
Multi-component reactions (MCRs), in which multiple
reactions are combined into one synthetic operation, have
been used extensively to form carbon-carbon bonds in
synthetic chemistry [1]. Such reactions offer a wide range
of possibilities for the efficient construction of highly
complex molecules in a single procedural step. Thus
avoiding the complicate purification operations and
allowing savings of both solvents and reagents. In the past
decade there have been tremendous development in three-
and four-component reactions and great efforts continue
to be made to develop new MCRs [2-4].
1,4-Dihydropyridines (1,4-DHPs) are well-known
compounds because of their biological activities [22-24].
Recently there have been many methods reported for the
synthesis of tricyclic compounds containing 1,4-
dihydropyridines, such as acridine derivatives, from
aldehydes, dimedone and aromatic amines by traditional
heating in organic solvents [25], or in water catalyzed by
4-dodecylbenzenesulfonic acid (DBSA) [26], or improved
under microwave irradiation [27]. However, they were
reacted in organic solvents or had low solubility in water
and none of the acridine compounds contained N-aryl
substituted with electron-withdrawing groups at the para-
position was obtained. As a consequence of our interest in
green synthesis [28-30], herein, we would like to report a
highly efficient method for the synthesis of a series of
polyhydroacridine derivatives by the three-component
reaction of aldehydes, aromatic amines and dimedone in
ionic liquid.
Recently, the replacement of current chemical process
with more environmentally benign alternatives is an
increasingly attractive goal in organic synthesis. In this
field, room temperature ionic liquid have been the subject
of considerable current interest as environmentally benign
reaction media in organic synthesis because of their
unique properties of nonvolatility, nonflammability and
recyclability, among others [5-7]. Numerous chemical
reactions, such as hydrogenation [8-10], regioselective
alkylation [11], Friedel-Crafts reactions [12-14],
dimerization of alkenes [15], Diels-Alder reactions [16],
Michael reactions [17], Cross-coupling reactions [18-20]
RESULTS AND DISCUSSION
When the three-components of aromatic aldehyde 1,
5,5-dimethyl-1,3-cyclohexamedione
2
and aromatic
amine 3 were treated in an ionic liquid 1-n-butyl-3-
methylimidazolium bromide ([bmim]Br) at 90 °C for a

654
D.-Q. Shi, S.-N. Ni, F.-Yang, J.-W. Shi, G.-L. Dou, X.-Y. Li and X.-S. Wang
Vol 45
Scheme 2
few hours (Scheme 1), the desired 3,3,6,6-tetramethyl-
9,10-diaryl-1,2,3,4,5,6,7,8,9,10-decahydro-acridin-1,8-
dione derivatives 4 were obtained in high yields (70% -
99%) (Table 1).
Ar
N
O
O
[bmim]Br
90oC
O
O
O
O
OHC
R
CHO
+ 4
+
2
Ar NH2
R
Scheme 1
5
2
3
O
Ar1
O
O
O
N
Ar
6
[bmim]Br
90oC
Ar2 NH2
+
Ar1 CHO
2
+
N
Ar2
Table 2
1
2
3
4
Synthesis of 6 in [bmim]Br.
Product
R
Ar
Time (h)
Yield (%)
Table 1
Synthesis of 4 in [bmim]Br.
6a
6b
6c
6d
1,3-C6H4
1,3-C6H4
1,3-C6H4
1,4-C6H4
4-CH3OC6H4
4-CH3C6H4
C6H5
3.5
2.5
2.5
3
93
90
93
87
Product
Ar1
Ar2
Time
(h)
Yield
(%)
4-CH3C6H4
To expand the reaction scope of aldehyde and
dimedone with amine, we tried the reaction of 1 and 2
with ammonium acetate 7, the desired products 8 were
obtained in high yields (Scheme 3). The reaction time is
shorter than that of the other methods [31-34].
Results are summarized in Table 3.
4a
4b
4c
4d
4e
4f
4-BrC6H4
4-CH3OC6H4
4-CH3OC6H4
4-CH3OC6H4
4-CH3OC6H4
4-CH3OC6H4
4-CH3OC6H4
4-CH3OC6H4
4-CH3OC6H4
4-CH3OC6H4
4-CH3OC6H4
3-Cl-4-
3
2
96
99
92
98
92
80
96
87
85
87
3,4-OCH2OC6H3
4-CH3C6H4
3,4-(CH3O)2C6H3
4-(CH3)2NC6H4
4-ClC6H4
4
2
2.5
4.5
2
4g
4h
4i
3,4-Cl2C6H3
4-HOC6H4
4
Scheme 3
2.5
3.5
4j
4-BrC6H4
O
R
O
O
O
CH3C6H3
[bmim]Br
90oC
4k
4l
4-ClC6H4
3-Cl-4-
3.5
3
88
89
R
CHO
NH4OAc
+
+
2
CH3C6H3
3-Cl-4-
N
H
4-CH3C6H4
CH3C6H3
1
2
7
8
4m
4n
4o
4p
4q
4r
Thiophen-2-yl
Pyrid-3-yl
4-CH3OC6H4
4-CH3OC6H4
C6H5
4
4.5
3.5
3.5
4
79
83
85
88
86
70
Table 3
Synthesis of 8 in [bmim]Br.
4-ClC6H4
4-ClC6H4
4-CH3OC6H4
4-CH3C6H4
4-FC6H4
4-ClC6H4
Product
R
Time
(min)
15
Yield m. p. (lit. m.
(%)
85
p.) (˚C)
2-CH3C6H4
4
8a
8b
8c
8d
8e
8f
4-CH3C6H4
>300
(>300[35]
272-274
)
As shown in Table 1, this method could be applied not
only to aromatic aldehydes with either electron-
withdrawing groups (such as halide groups) or electron-
donating groups (such as alkyl, hydroxyl groups), but also
to heterocyclic aldehydes. Furthermore, it was particularly
noteworthy that the method could be applied to aromatic
amine with either electron-donating groups (such as alkyl,
alkoxyl groups) or electron-withdrawing groups (such as
halide groups), which highlighted the wide scope of this
three-component reaction. Therefore, we concluded that
the electronic nature of the substituents of aldehydes and
anilines has no significant effect on this reaction.
4-CH3OC6H4
4-BrC6H4
15
30
30
30
15
90
93
92
90
97
(270-272 [36]
>300
)
(>300[35]
261-263
)
3,4-(CH3O)2C6H3
4-(CH3)2NC6H4
4-HOC6H4
(260-262 [37]
269-271
)
)
(264-266 [36]
>300
(>300[35]
)
8g
8h
3,4-Cl2C6H3
2,4-Cl2C6H3
50
60
92
93
>300
(>300[33
297-299
(298-300 [37]
)
8i
4-ClC6H4
40
93
)
8j
8k
2,4-(CH3O)2C6H3
3,4-OCH2OC6H3
20
30
87
86
As expected, when the aromatic aldehydes 1 was
replaced by dicarboxaldehydes 5, another series of
bis(decahydroacridine-1,8-dione) 6 were obtained under
the same reaction conditions (Scheme 2). The results are
summarized in Table 2.
>300
(>300[35]
)
8l
Pyrid-3-yl
Thiophen-2-yl
isobutyl
80
90
70
90
76
92
70
60
8m
8n
8o
isopropyl

May-Jun 2008
An Efficient Synthesis of Polyhydroacridine Derivatives
655
The formation of 4, 6 and 8 were characterized by
spectroscopic analysis. Thus, the IR spectra of compounds
4, 6 and 8 measured in potassium bromide pellets show
one band of the elongation vibrations of the C=O groups
at about 1640 cm-1 and one band of NH groups at about
Though the detailed mechanism of these reactions has
not been clarified yet, the formation of 4 can be explained
by the possible mechanism presented in Scheme 4. The
reaction occurs via an initial formation of the imine from
the condensation of aldehyde and amine, which suffers
nucleophilic attack by 5,5-dimethyl-1,3-cyclohexanedione
and loses amine to give the intermediate [A].
Condensation of another 5,5-dimethyl-1,3-cyclo- hexane-
dione and amine are taken place and to give another
intermediate enamines [B]. Then, the Michael additation,
cyclization and dehydration between intermediates [A]
and [B] are taken place and to give products 4.
1
3200 cm-1 for compounds 8. In the H NMR spectra of
compounds 4, 6 and 8 measured in dimethyl-d6 sulfoxide
were observed two signals of CH3 groups at about 0.7-1.0
ppm, the signal of CH group at about 4.9 ppm. The
structures of 4b and 8h were further confirmed by single
crystal X-ray diffraction analysis. Figure 1 and Figure 2
show the molecular structures of 4b and 8h, respectively.
The crystallographic data of these compounds are
summarized in Table 4.
Scheme 4
Ar1 CHOH
Ar1
C
H
N
Ar2
Ar2
Ar2 NH2
+
NH
Ar1
O
HO
O
H
O
Ar1
C N
Ar2
+
H
Ar2
NH
Ar1
O
O
HC
HO
O
Ar2 NH2
C
H
Ar1
+
A
HN Ar2
O
O
Ar2 NH2
Ar2 NH
O
+
O
B
O
O
Ar1
O
OH
C
Ar1
+
H
N
Ar2
Figure 1. X-ray structure of 4b.
O
A
B
Ar1
O
O
Ar1
O
O
NH
Ar2
N
O
OH
Ar2
O
Ar1
O
N
Ar2
4
Evidence supporting this proposed mechanism came
from the observation that when 9a and 2 were treated
under same reaction conditions, the expected product 4a
was obtained in a yield similar to that obtained in the one-
pot reaction (Scheme 5).
Figure 2. X-ray structure of 8h.

656
D.-Q. Shi, S.-N. Ni, F.-Yang, J.-W. Shi, G.-L. Dou, X.-Y. Li and X.-S. Wang
Vol 45
Scheme 5
EXPERIMENTAL
Br
Melting points were determined in open capillaries and are
uncorrected. IR spectra were recorded on Tensor 27
a
spectrometer in KBr. 1H NMR and 13C NMR spectra were
measured on a Bruker DPX-400 MHz spectrometer using TMS
as internal standard and DMSO-d6 as solvent. Microanalyses
were carried out on a Perkin-Elmer 2400 II instrument. X-ray
diffraction was recorded on a Siemens P4 diffractometer.
General Procedure for the Three-component Reaction of
Aldehydes 1, 5,5-Dimethyl-1,3-cyclohexanedione (2), and
Aromatic Amines 3. A dry 50 mL flask was charged with
aromatic aldehyde 1 (1 mmol), 5,5-dimethyl-1,3-cyclohexane-
dione 2 (2 mmol), aromatic amine 3 (1 mmol) and [bmim]Br (10
mL). The mixture was stirred at 90 °C for 2-4.5 h to complete
the reaction (monitored by TLC), then cooled to room
temperature. The yellow solid was collected by filtration and
washed with water. The filtrate of [bmim]Br was then recovered
for reuse by drying at 80 °C several hours in a vacuum. The
crude product was purified by recrystallization from 95 % EtOH
to give 4.
3,3,6,6-Tetramethyl-9-(4-bromophenyl)-10-(4-methoxy-
phenyl)-1,2,3,4,5,6,7,8,9,10-decahydroacridine-1,8-dione (4a).
This compound was obtained as solid with mp 247-248 °C; ir
(potassium bromide): 2959, 1638, 1572, 1511, 1484, 1360,
1295, 1250, 1221, 1174, 1143, 1121, 1067, 1032, 1010, 846
cm-1; 1H nmr (DMSO-d6): δ 0.72 (s, 6H, 2 × CH3), 0.89 (s, 6H, 2
× CH3), 1.80 (d, J = 17.6 Hz, 2H, 2 × CH), 2.00 (d, J = 16.0 Hz,
2H, 2 × CH), 2.19 (d, J = 16.0 Hz, 2H, 2 × CH), 2.20 (d, J =
17.6 Hz, 2H, 2 × CH), 3.86 (s, 3H, CH3O), 5.00 (s, 1H, CH),
7.13 (d, J = 8.8 Hz, 2H, ArH), 7.25 (d, J = 8.4 Hz, 2H, ArH),
7.28-7.39 (m, 2H, ArH), 7.44 (d, J = 8.4 Hz, 2H, ArH). 13C nmr
(DMSO-d6): δ 26.88, 29.95, 32.49, 32.61, 50.22, 56.16, 113.18,
115.67, 115.82, 119.42, 130.50, 131.46, 131.54, 146.38, 151.77,
160.01, 195.73. Anal. Calcd. for C30H32BrNO3: C, 67.41; H,
6.03; N, 2.62. Found: C, 67.59; H, 5.97; N, 2.71.
O
O
O
[bmim]Br
90 o
OCH3
+
2
Br
C
N
H
C
O
N
OCH3
Table 4
Crystallographic Data for 4b and 8h.
4b
8h
Empirical formula
Formula weight
Temperature (K)
Wavelength (Å)
Crystal system
Space group
a (Å)
C31H35NO4
485.60
296(2)
0.71073
Monoclinic
P21/c
C23H25Cl2NO2
418.34
298(2)
0.71073
Monoclinic
P21/c
9.826(3)
19.866(5)
11.471(3)
90
12.089(2)
11.447(2)
19.742(3)
90
b (Å)
c (Å)
α (°)
β (°)
101.00(1)
90
111.929(4)
90
γ (°)
V (Å3)
2681.74(81)
4
1.203
2077.3(10)
4
1.338
Z
Dcalc. (Mg/m3)
Absorption coefficient
(mm-1)
0.079
0.331
F (000)
1040
880
Crystal size (mm)
θ Range (°)
Limiting indices
0.58 × 0.38 ×0.30
1.72 to 25.50
0 ≤ h ≤ 14
0 ≤ k ≤ 13
-23 ≤ l ≤ 23
5706
0.34 × 0.29 ×0.16
2.05 to 25.01
-10 ≤ h ≤ 11
-23 ≤ k ≤ 23
-13 ≤ l ≤ 8
10831
3,3,6,6-Tetramethyl-9,10-bis(4-methoxyphenyl)-1,2,3,4,5,6,
7,8,9,10-decahydroacridine-1,8-dione (4b). This compound
was obtained as solid with mp 210-211 °C; ir (potassium
bromide): 2955, 2838, 1647, 1607, 1575, 1508, 1458, 1440,
1421, 1362, 1296, 1221, 1174, 1140, 1120, 1030, 1000, 850, 837
cm-1; 1H nmr (DMSO-d6): δ 0.73 (s, 6H, 2 × CH3), 0.89 (s, 6H, 2
× CH3), 1.79 (d, J = 17.2 Hz, 2H, 2 × CH), 1.99 (d, J = 16.0 Hz,
2H, 2 × CH), 2.18 (d, J = 16.0 Hz, 2H, 2 × CH), 2.19 (d, J =
17.2 Hz, 2H, 2 × CH), 3.69 (s, 3H, CH3O), 3.86 (s, 3H, CH3O),
4.98 (s, 1H, CH), 6.80 (d, J = 8.8 Hz, 2H, ArH), 7.12 (d, J = 8.8
Hz, 2H, ArH), 7.20 (d, J = 8.8 Hz, 2H, ArH), 7.36 (s, 2H, ArH).
Anal. Calcd. for C31H35NO4: C, 76.67; H, 7.26; N, 2.88. Found:
C, 76.78; H, 7.15; N, 2.94.
Reflections collected
Independent reflections
Data / restraints /
parameters
4988
4988 / 0 / 332
3666
3666 / 0 / 253
Goodness-of-fit on F2
Final R indices [I > 2 σ
(I)]
0.908
1.012
R1 = 0.0383
wR = 0.0854
R1 = 0.0693
wR = 0.0923
0.143 and -0.134
R1 = 0.0551
wR = 0.1264
R1 = 0.1201
wR = 0.1631
0.407 and -0.493
R indices (all data)
Largest diff. Peak and
hole (e·Å-3)
3,3,6,6-Tetramethyl-9-(3,4-methylenedioxylphenyl)-10-(4-
methoxyphenyl)-1,2,3,4,5,6,7,8,9,10-decahydroacridine-1,8-
dione (4c). This compound was obtained as solid with mp 227-
229 °C; ir (potassium bromide): 2954, 2903, 2842, 1639, 1574,
1510, 1478, 1440, 1360, 1295, 1250, 1222, 1140, 1121, 1087,
In conclusion, a series of 3,3,6,6-tetramethyl-9,10-
diaryl-1,2,3,4,5,6,7,8,9,10-decahydroacridine-1,8-diones
and 3,3,6,6-tetramethyl-9-aryl-1,2,3,4,5,6,7,8,9,10-deca-
hydroacridine-1,8-diones were synthesized by three-
component reaction of aldehydes, 5,5-dimethyl-1,3-
cyclohexanedione and aromatic amines or ammonium
acetate in [bmim]Br. The advantages of this method are
easier work-up, milder reaction conditions, high yields
and environmentally benign procedure.
1
999, 943, 921, 867, 850, 815, 805, 780 cm-1; H nmr (DMSO-
d6): δ 0.75 (s, 6H, 2 × CH3), 0.89 (s, 6H, 2 × CH3), 1.81 (d, J =
17.2 Hz, 2H, 2 × CH), 2.02 (d, J = 16.0 Hz, 2H, 2 × CH), 2.18
(d, J = 16.0 Hz, 2H, 2 × CH), 2.19 (d, J = 17.2 Hz, 2H, 2 × CH),
3.85 (s, 3H, CH3O), 4.96 (s, 1H, CH), 5.94 (s, 2H, OCH2O),
6.74-6.79 (m, 3H, ArH), 7.13 (d, J = 8.8 Hz, 2H, ArH), 7.18-
7.38 (m, 2H, ArH). Anal. Calcd. for C31H33NO5: C, 74.53; H,
6.66; N, 2.80. Found: C, 74.48; H, 6.69; N, 2.86.

May-Jun 2008
An Efficient Synthesis of Polyhydroacridine Derivatives
657
3,3,6,6-Tetramethyl-9-(4-methylphenyl)-10-(4-methoxy-
phenyl)-1,2,3,4,5,6,7,8,9,10-decahydroacridine-1,8-dione (4d).
This compound was obtained as solid with mp 247-248 °C; ir
(potassium bromide): 2959, 2841, 1640, 1575, 1511, 1466,
1424, 1360, 1310, 1294, 1277, 1245, 1213, 1175, 1141, 1120,
= 2.0 Hz, 1H, ArH), 7.54 (d, J = 8.4 Hz, 1H, ArH). Anal. Calcd.
for C30H31Cl2NO3: C, 68.70; H, 5.96; N, 2.67. Found: C, 68.82;
H, 6.04; N, 2.75.
3,3,6,6-Tetramethyl-9-(4-hydroxyphenyl)-10-(4-methoxy-
phenyl)-1,2,3,4,5,6,7,8,9,10-decahydroacridine-1,8-dione (4i).
This compound was obtained as solid with mp > 300 °C; ir
(potassium bromide): 3234, 2960, 2873, 1634, 1593, 1567, 1510,
1452, 1366, 1313, 1295, 1251, 1213, 1168, 1142, 1121, 1107,
1
1029, 1000, 849, 835 cm-1; H nmr (DMSO-d6): δ 0.72 (s, 6H, 2
× CH3), 0.89 (s, 6H, 2 × CH3), 1.79 (d, J = 17.6 Hz, 2H, 2 ×
CH), 1.99 (d, J = 16.0 Hz, 2H, 2 × CH), 2.18 (d, J = 16.0 Hz,
2H, 2 × CH), 2.20 (d, J = 17.6 Hz, 2H, 2 × CH), 2.22 (s, 3H,
CH3), 3.86 (s, 3H, CH3O), 5.00 (s, 1H, CH), 7.04 (d, J = 7.6 Hz,
2H, ArH), 7.13 (d, J = 8.0 Hz, 2H, ArH), 7.18 (d, J = 8.0 Hz,
2H, ArH), 7.20-7.40 (m, 2H, ArH). Anal. Calcd. for C31H35NO3:
C, 79.28; H, 7.51; N, 2.98. Found: C, 79.35; H, 7.43; N, 3.06.
3,3,6,6-Tetramethyl-9-(3,4-dimethoxyphenyl)-10-(4-meth-
oxyphenyl)-1,2,3,4,5,6,7,8,9,10-decahydroacridine-1,8-dione
(4e). This compound was obtained as solid with mp 247-248 °C;
ir (potassium bromide): 2955, 2837, 1636, 1573, 1510, 1465,
1419, 1363, 1311, 1294, 1248, 1213, 1174, 1138, 1024, 977,
928, 853, 815, 775, 754 cm-1; 1H nmr (DMSO-d6): δ 0.75 (s, 6H,
2 × CH3), 0.89 (s, 6H, 2 × CH3), 1.81 (d, J = 17.2 Hz, 2H, 2 ×
CH), 2.02 (d, J = 16.0 Hz, 2H, 2 × CH), 2.19 (d, J = 16.0 Hz,
2H, 2 × CH), 2.21 (d, J = 17.2 Hz, 2H, 2 × CH), 3.69 (s, 3H,
CH3O), 3.71 (s, 3H, CH3O), 3.85 (s, 3H, CH3O), 5.00 (s, 1H,
CH), 6.79-6.84 (m, 3H, ArH), 7.14 (s, 3H, ArH), 7.37 (s, 1H,
ArH). Anal. Calcd. for C32H37NO5: C, 74.54; H, 7.23; N, 2.72.
Found: C, 74.63; H, 7.19; N, 2.64.
1
1030, 1001, 887, 844, 745 cm-1; H nmr (DMSO-d6): δ 0.72 (s,
6H, 2 × CH3), 0.88 (s, 6H, 2 × CH3), 1.78 (d, J = 17.2 Hz, 2H, 2 ×
CH), 1.99 (d, J = 16.0 Hz, 2H, 2 × CH), 2.17 (d, J = 16.0 Hz, 2H,
2 × CH), 2.18 (d, J = 17.2 Hz, 2H, 2 × CH), 3.85 (s, 3H, CH3O),
4.93 (s, 1H, CH), 6.61 (d, J = 8.4 Hz, 2H, ArH), 7.07 (d, J = 8.4
Hz, 2H, ArH), 7.12 (d, J = 8.4 Hz, 2H, ArH), 7.21 (s, 1H, ArH),
7.36 (s, 1H, ArH), 9.09 (s, 1H, OH). Anal. Calcd. for C30H33NO4:
C, 76.41; H, 7.05; N, 2.97. Found: C, 76.59; H, 6.97; N, 3.06.
3,3,6,6-Tetramethyl-9-(4-bromophenyl)-10-(3-chloro-4-
methylphenyl)-1,2,3,4,5,6,7,8,9,10-decahydroacridine-1,8-
dione (4j). This compound was obtained as solid with mp 293-
295 °C; ir (potassium bromide): 2957, 1652, 1603, 1567, 1495,
1372, 1301, 1264, 1224, 1176, 1143, 1117, 1068, 1055, 1009, 923,
887, 838, 775, 731, 708 cm-1; 1H nmr (DMSO-d6): δ 0.73 (s, 6H, 2
× CH3), 0.90 (s, 6H, 2 × CH3), 1.80 (d, J = 16.0 Hz, 2H, 2 × CH),
2.01 (d, J = 16.0 Hz, 2H, 2 × CH), 2.18 (d, J = 16.0 Hz, 4H, 4 ×
CH), 2.44 (s, 3H, CH3), 4.99 (s, 1H, CH), 7.27 (d, J = 8.4 Hz, 2H,
ArH), 7.34-7.37 (m, 1H, ArH), 7.43 (d, J = 8.4 Hz, 2H, ArH), 7.59
(d, J = 8.0 Hz, 2H, ArH). 13C nmr (DMSO-d6): δ 19.40, 26.17,
29.19, 31.96, 40.87, 49.51, 112.61, 125.79, 129.77, 129.85,
130.57, 130.69, 136.95, 137.01, 145.34, 150.12, 150.83, 151.19,
194.74. Anal. Calcd. for C30H31BrClNO2: C, 65.17; H, 5.65; N,
2.53. Found: C, 65.28; H, 5.60; N, 2.57.
3,3,6,6-Tetramethyl-9-(4-(dimethylamino)phenyl)-10-(4-
methoxyphenyl)-1,2,3,4,5,6,7,8,9,10-decahydroacridine-1,8-
dione (4f). This compound was obtained as solid with mp 274-
276 °C; ir (potassium bromide): 2961, 1652, 1603, 1577, 1518,
1461, 1370, 1295, 1250, 1223, 1169, 1132, 1113, 1026, 999,
1
979, 945, 887, 850, 827, 778, 745 cm-1; H nmr (DMSO-d6): δ
3,3,6,6-Tetramethyl-9-(4-chlorophenyl)-10-(3-chloro-4-methyl-
phenyl)-1,2,3,4,5,6,7,8,9,10-decahydroacridine-1,8-dione (4k).
This compound was obtained as solid with mp 288-290 °C; ir
(potassium bromide): 2958, 2870, 1642, 1601, 1578, 1489, 1472,
1361, 1301, 1261, 1221, 1176, 1143, 1122, 1089, 1054, 1014,
1000, 924, 887, 840 cm-1; 1H nmr (DMSO-d6): δ 0.72 (s, 6H, 2 ×
CH3), 0.89 (s, 6H, 2 × CH3), 1.80 (d, J = 16.0 Hz, 2H, 2 × CH),
2.00 (d, J = 16.0 Hz, 2H, 2 × CH), 2.18 (d, J = 16.0 Hz, 4H, 4 ×
CH), 2.44 (s, 3H, CH3), 5.00 (s, 1H, CH), 7.27-7.34 (m, 5H, ArH),
7.59 (d, J = 8.0 Hz, 2H, ArH). Anal. Calcd. for C30H31Cl2NO2: C,
70.86; H, 6.15; N, 2.75. Found: C, 70.92; H, 6.11; N, 2.84.
0.74 (s, 6H, 2 × CH3), 0.89 (s, 6H, 2 × CH3), 1.79 (d, J = 17.2
Hz, 2H, 2 × CH), 1.99 (d, J = 16.0 Hz, 2H, 2 × CH), 2.17 (d, J =
16.0 Hz, 2H, 2 × CH), 2.19 (d, J = 17.2 Hz, 2H, 2 × CH), 3.22
(s, 6H, (CH3)2N), 3.86 (s, 3H, CH3O), 4.92 (s, 1H, CH), 6.61 (d,
J = 8.4 Hz, 2H, ArH), 7.10-7.14 (m, 4H, ArH), 7.20-7.36 (m,
2H, ArH). Anal. Calcd. for C32H38N2O3: C, 77.08; H, 7.68; N,
5.62. Found: C, 77.23; H, 7.62; N, 5.58.
3,3,6,6-Tetramethyl-9-(4-chlorophenyl)-10-(4-methoxy-
phenyl)-1,2,3,4,5,6,7,8,9,10-decahydroacridine-1,8-dione (4g).
This compound was obtained as solid with mp 274-276 °C; ir
(potassium bromide): 2956, 1646, 1572, 1510, 1471, 1360,
1295, 1242, 1222, 1169, 1143, 1120, 1036, 1003, 934, 886, 846,
798, 750, 718, 700, 662 cm-1; 1H nmr (DMSO-d6): δ 0.74 (s, 6H,
2 × CH3), 0.87 (s, 6H, 2 × CH3), 1.79 (d, J = 17.2 Hz, 2H, 2 ×
CH), 1.94 (d, J = 16.4 Hz, 2H, 2 × CH), 2.15 (d, J = 16.4 Hz,
4H, 4 × CH), 3.86 (s, 3H, CH3O), 5.27 (s, 1H, CH), 7.08-7.17
(m, 3H, ArH), 7.22-7.38 (m, 4H, ArH), 7.50 (d, J = 8.0 Hz, 1H,
ArH). Anal. Calcd. for C30H32ClNO3: C, 73.53; H, 6.58; N, 2.86.
Found: C, 73.66; H, 6.51; N, 2.82.
3,3,6,6-Tetramethyl-9-(4-methylphenyl)-10-(3-chloro-4-
methylphenyl)-1,2,3,4,5,6,7,8,9,10-decahydroacridine-1,8-dione
(4l). This compound was obtained as solid with mp 248-250 °C; ir
(potassium bromide): 2957, 2869, 1642, 1602, 1578, 1495, 1472,
1361, 1301, 1260, 1221, 1177, 1143, 1122, 1053, 999, 886, 835,
715, 702 cm-1; 1H nmr (DMSO-d6): δ 0.73 (s, 6H, 2 × CH3), 0.89
(s, 6H, 2 × CH3), 1.79 (d, J = 16.0 Hz, 2H, 2 × CH), 2.00 (d, J =
16.0 Hz, 2H, 2 × CH), 2.17 (d, J = 16.0 Hz, 4H, 4 × CH), 2.22 (s,
3H, CH3), 2.44 (s, 3H, CH3), 4.99 (s, 1H, CH), 7.02-7.05 (m, 3H,
ArH), 7.19 (d, J = 8.0 Hz, 2H, ArH), 7.31 (s, 1H, ArH), 7.59 (d, J
= 8.0 Hz, 1H, ArH). Anal. Calcd. for C31H34ClNO2: C, 76.29; H,
7.02; N, 2.87. Found: C, 76.40; H, 6.98; N, 2.94.
3,3,6,6-Tetramethyl-9-(3,4-dichlorophenyl)-10-(4-methoxy-
phenyl)-1,2,3,4,5,6,7,8,9,10-decahydroacridine-1,8-dione (4h).
This compound was obtained as solid with mp 209-211 °C; ir
(potassium bromide): 2959, 1645, 1573, 1513, 1456, 1376,
1294, 1250, 1206, 1169, 1132, 1027, 932, 876, 847, 779, 745,
702, 673 cm-1; 1H nmr (DMSO-d6): δ 0.73 (s, 6H, 2 × CH3), 0.89
(s, 6H, 2 × CH3), 1.83 (d, J = 17.2 Hz, 2H, 2 × CH), 2.03 (d, J =
16.0 Hz, 2H, 2 × CH), 2.20 (d, J = 16.0 Hz, 2H, 2 × CH), 2.21
(d, J = 17.2 Hz, 2H, 2 × CH), 3.86 (s, 3H, CH3O), 5.00 (s, 1H,
CH), 7.14 (d, J = 7.2 Hz, 2H, ArH), 7.24 (s, 1H, ArH), 7.27 (dd,
J1 = 2.0 Hz, J2 = 8.4 Hz, 1H, ArH), 7.37 (s, 1H, ArH), 7.45 (d, J
3,3,6,6-Tetramethyl-9-(thiophen-2-yl)-10-(4-methoxyphenyl)-
1,2,3,4,5,6,7,8,9,10-decahydroacridine-1,8-dione (4m). This
compound was obtained as solid with mp 240-242 °C; ir
(potassium bromide): 3064, 2959, 2837, 1651, 1573, 1506,
1441, 1371, 1293, 1264, 1213, 1173, 1121, 1074, 1030, 997,
1
980, 921, 888, 843, 820, 772, 744, 699 cm-1; H nmr (DMSO-
d6): δ 0.78 (s, 6H, 2 × CH3), 0.91 (s, 6H, 2 × CH3), 1.78 (d, J =
17.6 Hz, 2H, 2 × CH), 2.07 (d, J = 16.0 Hz, 2H, 2 × CH), 2.23

658
D.-Q. Shi, S.-N. Ni, F.-Yang, J.-W. Shi, G.-L. Dou, X.-Y. Li and X.-S. Wang
Vol 45
(d, J = 16.0 Hz, 2H, 2 × CH), 2.24 (d, J = 17.6 Hz, 2H, 2 × CH),
3.85 (s, 3H, CH3O), 5.37 (s, 1H, CH), 6.79 (d, J = 3.2 Hz, 1H,
ArH), 6.87 (dd, J1 = 3.2 Hz, J2 = 5.6 Hz, 1H, ArH), 7.12 (s, 3H,
ArH), 7.22 (d, J = 5.6 Hz, 1H, ArH), 7.37-7.43 (m, 1H, ArH).
Anal. Calcd. for C28H31NO3S: C, 72.85; H, 6.77; N, 3.03. Found:
C, 72.82; H, 6.85; N, 3.06.
3,3,6,6-Tetramethyl-9-(4-methylphenyl)-10-(2-methyl-
phenyl)-1,2,3,4,5,6,7,8,9,10-decahydroacridine-1,8-dione (4r).
This compound was obtained as solid with mp 242-245 °C; ir
(potassium bromide): 3050, 2950, 1638, 1577, 1510, 1492,
1472, 1423, 1360, 1298, 1258, 1222, 1176, 1140, 1120, 1020,
1
998, 937, 920, 835, 767, 739, 717, 668 cm-1; H nmr (DMSO-
d6): δ 0.75 (s, 6H, 2 × CH3), 0.87 (s, 6H, 2 × CH3), 1.50 (d, J =
17.2 Hz, 2H, 2 × CH), 1.99 (d, J = 16.4 Hz, 2H, 2 × CH), 2.16-
2.26 (m, 10H, 2 × CH3, 4 × CH), 5.03 (s, 1H, CH), 7.02 (d, J =
8.0 Hz, 2H, ArH), 7.21 (d, J = 8.0 Hz, 2H, ArH), 7.34 (d, J = 8.0
Hz, 1H, ArH), 7.39-7.46 (m, 1H, ArH), 7.47-7.52 (m, 2H, ArH).
13C nmr (DMSO-d6): δ 18.41, 21.22, 26.37, 30.33, 32.37, 41.84,
50.24, 113.59, 128.16, 128.44, 128.90, 130.32, 130.81, 131.98,
135.18, 137.00, 138.10, 144.24, 150.50, 195.66. Anal. Calcd. for
C31H35NO2: C, 82.08; H, 7.78; N, 3.09. Found: C, 82.21; H,
7.74; N, 3.15.
General Procedure for the Three-component Reaction of
Dicarboxyldehydes 5, 5,5-Dimethyl-1,3-cyclohexanedione (2),
and Aromatic amines 3. A dry 50 mL flask was charged with
dicarboxaldehyde 5 (1 mmol), 5,5-dimethyl-1,3-cyclohexane-
dione 2 (4 mmol), aromatic amine 3 (2 mmol) and [bmim]Br (10
mL). The mixture was stirred at 90 °C for 2.5-3 h to complete
the reaction (monitored by TLC), then cooled to room
temperature. The yellow solid was filtered off and washed with
water. The crude product was purified by recrystallization from
95 % EtOH to give 6.
3,3,6,6-Tetramethyl-9-(pyridine-3-yl)-10-(4-methoxyphenyl)-
1,2,3,4,5,6,7,8,9,10-decahydroacridine-1,8-dione (4n). This
compound was obtained as solid with mp 231-232 °C; ir
(potassium bromide): 2956, 1641, 1575, 1508, 1473, 1426,
1362, 1294, 1248, 1222, 1170, 1144, 1123, 1108, 1027, 1003,
853, 716 cm-1; 1H nmr (DMSO-d6): δ 0.71 (s, 6H, 2 × CH3), 0.89
(s, 6H, 2 × CH3), 1.83 (d, J = 17.6 Hz, 2H, 2 × CH), 2.01 (d, J =
16.0 Hz, 2H, 2 × CH), 2.20 (d, J = 16.0 Hz, 4H, 4 × CH), 3.86
(s, 3H, CH3O), 5.01 (s, 1H, CH), 7.13 (d, J = 7.2 Hz, 2H, ArH),
7.28-7.37 (m, 3H, ArH), 7.65-7.67 (m, 1H, ArH), 8.31 (s, 1H,
ArH), 8.52 (s, 1H, ArH). Anal. Calcd. for C29H32N2O3: C, 76.29;
H, 7.06; N, 6.14. Found: C, 76.37; H, 7.01; N, 6.09.
3,3,6,6-Tetramethyl-9-(4-chlorophenyl)-10-phenyl-1,2,3,4,
5,6,7,8,9,10-decahydroacridine-1,8-dione (4o). This compound
was obtained as solid with mp 231-233 °C; ir (potassium
bromide): 3060, 2957, 2931, 2869, 1640, 1592, 1576, 1490,
1472, 1452, 1361, 1300, 1276, 1262, 1221, 1176, 1143, 1120,
1088, 1012, 980, 939, 888, 940, 771, 704 cm-1; 1H nmr (DMSO-
d6): δ 0.71 (s, 6H, 2 × CH3), 0.82 (s, 6H, 2 × CH3), 1.76 (d, J =
17.6 Hz, 2H, 2 × CH), 2.01 (d, J = 16.0 Hz, 2H, 2 × CH), 2.20
(d, J = 16.0 Hz, 2H, 2 × CH), 2.21 (d, J = 17.6 Hz, 2H, 2 × CH),
5.03 (s, 1H, CH), 7.29-7.35 (m, 4H, ArH), 7.38-7.48 (m, 2H,
ArH), 7.55-7.66 (m, 3H, ArH). 13C nmr (DMSO-d6): δ 26.82,
29.91, 32.43, 32.64, 50.21, 113.26, 128.43, 128.55, 130.08,
130.13, 130.78, 130.95, 139.03, 145.80, 151.19, 195.71. Anal.
Calcd. for C29H30ClNO2: C, 75.72; H, 6.57; N, 3.04. Found: C,
75.82; H, 6.64; N, 2.98.
9,9'-(1,3-Phenylene)bis(10-(4-methoxyphenyl)-3,3,6,6-
tetramethyl-1,2,3,4,5,6,7,8,9,10-decahydroacridine-1,8-dione)
(6a). This compound was obtained as solid with mp 278-280 °C;
ir (potassium bromide): 2956, 2870, 1638, 1574, 1511, 1471,
1
1364, 1294, 1250, 1222, 1174, 1142, 1121, 1027, 846 cm-1; H
nmr (DMSO-d6): δ 0.70 (s, 12H, 4 × CH3), 0.88 (s, 12H, 4 ×
CH3), 1.81 (d, J = 17.6 Hz, 4H, 4 × CH), 1.93 (d, J = 16.0 Hz,
4H, 4 × CH), 2.17 (d, J = 16.0 Hz, 4H, 4 × CH), 2.21 (d, J =
17.6 Hz, 4H, 4 × CH), 3.86 (s, 6H, 2 × CH3O), 5.02 (s, 2H, 2 ×
CH), 7.01-7.14 (m, 7H, ArH), 7.32-7.45 (m, 3H, ArH), 7.58-
7.66 (m, 2H, ArH). 13C nmr (DMSO-d6): δ 26.85, 30.27, 32.49,
41.75, 50.40, 56.12, 113.62, 115.49, 115.59, 115.64, 125.37,
128.16, 131.88, 146.54, 151.28, 159.90, 195.47. Anal. Calcd. for
C54H60N2O6: C, 77.85; H, 7.26; N, 3.36. Found: C, 77.97; H,
7.15; N, 3.42.
9,9'-(1,3-Phenylene)bis(10-(4-methylphenyl)-3,3,6,6-tetra-
methyl-1,2,3,4,5,6,7,8,9,10-decahydroacridine-1,8-dione) (6b).
This compound was obtained as solid with mp 261-263 °C; ir
(potassium bromide): 2954, 2869, 1639, 1576, 1512, 1469,
1365, 1300, 1260, 1221, 1176, 1142, 1121, 1019, 999, 919, 889,
845, 814, 734, 703 cm-1; 1H nmr (DMSO-d6): δ 0.70 (s, 12H, 4 ×
CH3), 0.88 (s, 12H, 4 × CH3), 1.79 (d, J = 17.2 Hz, 4H, 4 × CH),
1.93 (d, J = 16.0 Hz, 4H, 4 × CH), 2.17 (d, J = 16.0 Hz, 4H, 4 ×
CH), 2.21 (d, J = 17.2 Hz, 4H, 4 × CH), 2.43 (s, 6H, 2 × CH3),
5.03 (s, 2H, 2 × CH), 7.01-7.12 (m, 3H, ArH), 7.35-7.44 (m, 7H,
ArH), 7.49-7.60 (m, 2H, ArH). Anal. Calcd. for C54H60N2O4: C,
80.96; H, 7.55; N, 3.50. Found: C, 81.04; H, 7.47; N, 3.58.
9,9'-(1,3-Phenylene)bis(10-phenyl-3,3,6,6-tetramethyl-1,2,
3,4,5,6,7,8,9,10-decahydroacridine-1,8-dione) (6c). This
compound was obtained as solid with mp > 300 °C; ir
(potassium bromide): 3059, 2956, 2870, 1657, 1592, 1491,
1452, 1368, 1297, 1260, 1220, 1176, 1142, 1120, 1081, 1021,
1000, 979, 888, 813 cm-1; 1H nmr (DMSO-d6): δ 0.70 (s, 12H, 4
× CH3), 0.87 (s, 12H, 4 × CH3), 1.76 (d, J = 17.6 Hz, 4H, 4 ×
CH), 1.94 (d, J = 16.0 Hz, 4H, 4 × CH), 2.18 (d, J = 16.0 Hz,
4H, 4 × CH), 2.22 (d, J = 17.6 Hz, 4H, 4 × CH), 5.04 (s, 2H, 2 ×
3,3,6,6-Tetramethyl-9-(4-chlorophenyl)-10-(4-fluoro-
phenyl)-1,2,3,4,5,6,7,8,9,10-decahydroacridine-1,8-dione (4p).
This compound was obtained as solid with mp 296-298 °C; ir
(potassium bromide): 2955, 2933, 2869, 1639, 1577, 1541, 1507,
1486, 1472, 1417, 1361, 1302, 1279, 1262, 1220, 1177, 1144,
1
1118, 1086, 1012, 980, 888, 861, 840, 805, 743 cm-1; H nmr
(DMSO-d6): δ 0.72 (s, 6H, 2 × CH3), 0.89 (s, 6H, 2 × CH3), 1.77
(d, J = 17.6 Hz, 2H, 2 × CH), 2.01 (d, J = 16.0 Hz, 2H, 2 × CH),
2.19 (d, J = 16.0 Hz, 2H, 2 × CH), 2.20 (d, J = 17.6 Hz, 2H, 2 ×
CH), 5.02 (s, 1H, CH), 7.28-7.34 (m, 4H, ArH), 7.43-7.59 (m,
4H, ArH). 13C nmr (DMSO-d6): δ 26.82, 29.91, 32.41, 32.64,
50.21, 113.37, 128.54, 130.11, 133.10, 135.14, 136.28, 135.32,
135.39, 145.81, 151.26, 195.73. Anal. Calcd. for C29H29ClFNO2:
C, 72.87; H, 6.12; N, 2.93. Found: C, 72.94; H, 6.08; N, 2.97.
3,3,6,6-Tetramethyl-9-(4-methoxyphenyl)-10-(4-chloro-
phenyl)-1,2,3,4,5,6,7,8,9,10-decahydroacridine-1,8-dione (4q).
This compound was obtained as solid with mp 269-271 °C; ir
(potassium bromide): 3052, 2953, 2837, 1641, 1578, 1508,
1491, 1473, 1439, 1361, 1299, 1259, 1220, 1173, 1141, 1120,
1105, 1089, 1037, 1016, 999, 886, 864, 850, 834, 816, 780, 740,
1
720 cm-1; H nmr (DMSO-d6): δ 0.73 (s, 6H, 2 × CH3), 0.89 (s,
6H, 2 × CH3), 1.76 (d, J = 17.2 Hz, 2H, 2 × CH), 2.00 (d, J =
16.0 Hz, 2H, 2 × CH), 2.18 (d, J = 16.0 Hz, 2H, 2 × CH), 2.19
(d, J = 17.2 Hz, 2H, 2 × CH), 3.69 (s, 3H, CH3O), 4.97 (s, 1H,
CH), 6.80 (d, J = 8.8 Hz, 2H, ArH), 7.12 (d, J = 8.8 Hz, 2H,
ArH), 7.38-7.53 (m, 2H, ArH), 7.69 (d, J = 8.8 Hz, 2H, ArH).
Anal. Calcd. for C30H32ClNO3: C, 73.53; H, 6.58; N, 2.86.
Found: C, 73.65; H, 6.63; N, 2.89.

May-Jun 2008
An Efficient Synthesis of Polyhydroacridine Derivatives
659
CH), 7.03-7.11 (m, 3H, ArH), 7.46-7.65 (m, 11H, ArH). Anal.
Calcd. for C52H56N2O4: C, 80.80; H, 7.30; N, 3.62. Found: C,
80.96; H, 7.20; N, 3.69.
ArH), 7.48 (dd, J1 = 1.2 Hz, J2 = 7.6 Hz, 1H, ArH), 8.24 (d, J =
4.4 Hz, 1H, ArH), 8.37 (s, 1H, ArH), 9.42 (s, 1H, NH). Anal.
Calcd. for C22H26N2O2: C, 75.40; H, 7.48; N, 7.99. Found C,
75.62; H, 7.40; N, 8.05.
9,9'-(1,4-Phenylene)bis(10-(4-methoxyphenyl)-3,3,6,6-tetra
methyl-1,2,3,4,5,6,7,8,9,10-decahydroacridine-1,8-dione) (6d).
This compound was obtained as solid with mp > 300 °C; ir
(potassium bromide): 2956, 2870, 1637, 1576, 1510, 1466,
1419, 1363, 1293, 1249, 1213, 1175, 1142, 1120, 1022, 979,
888, 846, 824 cm-1; 1H nmr (DMSO-d6): 0.66 (s, 12H, 4 × CH3),
0.87 (s, 12H, 4 × CH3), 1.79 (d, J = 17.6 Hz, 4H, 4 × CH), 1.99
(d, J = 16.0 Hz, 4H, 4 × CH), 2.16 (d, J = 16.0 Hz, 4H, 4 × CH),
2.18 (d, J = 17.6 Hz, 4H, 4 × CH), 3.86 (s, 6H, 2 × CH3O), 5.01
(s, 2H, 2 × CH), 7.12-7.41 (m, 12H, ArH). Anal. Calcd. for
C54H60N2O6: C, 77.85; H, 7.26; N, 3.36. Found: C, 78.02; H,
7.19; N, 3.48.
General Procedure for the Three-component Reaction of
Aldehydes 1, 5,5-Dimethyl-1,3-cyclohexanedione (2), and
Ammonium Acetate (2). A dry 50 mL flask was charged with
aldehyde 1 (1 mmol), 5,5-dimethyl-1,3-cyclohexanedione (2
mmol), ammonium acetate (10 mmol) and [bmim]Br (10 mL).
The mixture was stirred at 90 °C for 15-90 min to complete the
reaction (monitored by TLC), then cooled to room temperature.
The yellow solid was filtered off and washed with water. The
crude product was purified by recrystallization from 95 % EtOH
to give 8.
3,3,6,6-Tetramethyl-9-(thiophen-2-yl)-1,2,3,4,5,6,7,8,9,10-
decahydroacridine-1,8-dione (8m). This compound was
obtained as solid with mp > 300 °C; ir (potassium bromide):
3278, 3211, 3065, 2956, 2931, 2872, 1638, 1625, 1602, 1482,
1395, 1371, 1250, 1218, 1168, 1140, 1122, 1031, 1003, 980,
887, 850, 716, 690 cm-1; 1H nmr (DMSO-d6): δ 0.94 (s, 6H, 2 ×
CH3), 1.03 (s, 6H, 2 × CH3), 2.08 (d, J = 16.0 Hz, 2H, 2 × CH),
2.22 (d, J = 16.0 Hz, 2H, 2 × CH), 2.32 (d, J = 17.2 Hz, 2H, 2 ×
CH), 2.45 (d, J = 17.2 Hz, 2H, 2 × CH), 5.15 (s, 1H, CH), 6.65
(d, J = 3.2 Hz, 1H, ArH), 6.80 (dd, J1 = 3.2 Hz, J2 = 4.8 Hz, 1H,
ArH), 7.14 (d, J = 4.8 Hz, 1H, ArH), 9.45 (s, 1H, NH). Anal.
Calcd. for C21H25NO2S: C, 70.95; H, 7.09; N, 3.94. Found C,
71.07; H, 7.15; N, 3.82.
3,3,6,6-Tetramethyl-9-(isobutyl)-1,2,3,4,5,6,7,8,9,10-deca-
hydroacridine-1,8-dione (8n). This compound was obtained as
solid with mp 254-256 °C; ir (potassium bromide): 3277, 3209,
3065, 2954, 2871, 1637, 1617, 1602, 1479, 1425, 1380, 1276,
1219, 1168, 1142, 1122, 1001, 978, 941, 886, 752, 729, 677
1
cm-1; H nmr (DMSO-d6): δ 0.81 (d, J = 6.8 Hz, 6H, 2 × CH3),
0.95 (t, J = 6.8 Hz, 2H, CH2), 1.00 (s, 6H, 2 × CH3), 1.02 (s, 6H,
2 × CH3), 1.29-1.36 (m, 1H, CH), 2.07 (d, J = 16.0 Hz, 2H, 2 ×
CH), 2.17 (d, J = 16.4 Hz, 2H, 2 × CH), 2.25 (d, J = 17.2 Hz,
2H, 2 × CH), 2.38 (d, J = 17.2 Hz, 2H, 2 × CH), 3.82 (t, J = 6.8
Hz, 1H, CH), 9.18 (s, 1H, NH). 13C nmr (DMSO-d6): δ 23.07,
23.61, 23.84, 26.19, 29.27, 31.87, 46.31, 50.41, 111.78, 149.65,
194.32. Anal. Calcd. for C21H31NO2: C, 76.55; H, 9.48; N, 4.25.
Found C, 76.72; H, 9.43; N, 4.28.
3,3,6,6-Tetramethyl-9-(3,4-dichlorophenyl)-1,2,3,4,5,6,7,8,
9,10-decahydroacridine-1,8-dione (8g). This compound was
obtained as solid with mp > 300 °C; ir (potassium bromide):
3177, 3061, 2957, 2810, 1647, 1611, 1491, 1396, 1362, 1259,
1
1221, 1142, 1029, 1009, 977, 880, 830, 762, 733, 701 cm-1; H
nmr (DMSO-d6): δ 0.87 (s, 6H, 2 × CH3), 1.01 (s, 6H, 2 × CH3),
2.01 (d, J = 16.0 Hz, 2H, 2 × CH), 2.19 (d, J = 16.0 Hz, 2H, 2 ×
CH), 2.35 (d, J = 16.8 Hz, 2H, 2 × CH), 2.47 (d, J = 16.8 Hz,
2H, 2 × CH), 4.78 (s, 1H, CH), 7.12 (dd, J1 = 1.6 Hz, J2 = 8.4
Hz, 1H, ArH), 7.31 (d, J = 1.6 Hz, 1H, ArH), 7.46 (d, J = 8.4
Hz, 1H, ArH), 9.43 (br. s, 1H, NH). 13C nmr (DMSO-d6): δ
27.16, 29.64, 32.83, 33.66, 50.80, 111.20, 128.60, 128.64,
130.29, 130.62, 130.73, 148.73, 150.51, 195.07. Anal. Calcd. for
C23H25Cl2NO2: C, 66.03; H, 6.02; N, 3.35. Found: C, 66.21; H,
5.97; N, 3.42.
3,3,6,6-Tetramethyl-9-(isopropyl)-1,2,3,4,5,6,7,8,9,10-deca-
hydroacridine-1,8-dione (8o). This compound was obtained as
solid with mp 283-284 °C; ir (potassium bromide): 3286, 3197,
3069, 2955, 2922, 2880, 1641, 1620, 1603, 1482, 1448, 1394,
1370, 1315, 1298, 1250, 1223, 1170, 1140, 1119, 1004, 975,
1
888, 745, 681 cm-1; H nmr (DMSO-d6): δ 0.64 (d, J = 6.8 Hz,
6H, 2 × CH3), 1.03 (s, 6H, 2 × CH3), 1.05 (s, 6H, 2 × CH3), 1.50-
1.53 (m, 1H, CH), 2.11 (d, J = 16.0 Hz, 2H, 2 × CH), 2.18 (d, J
= 16.4 Hz, 2H, 2 × CH), 2.27 (d, J = 17.2 Hz, 2H, 2 × CH), 2.39
(d, J = 17.2 Hz, 2H, 2 × CH), 3.80 (t, J = 4.0 Hz, 1H, CH), 9.12
(s, 1H, NH). 13C nmr (DMSO-d6): δ 19.84, 27.24, 30.12, 31.68,
32.42, 35.49, 51.21, 110.09, 151.56, 195.63. Anal. Calcd. for
C20H29NO2: C, 76.15; H, 9.27; N, 4.44. Found C, 76.33; H, 9.25;
N, 4.39.
3,3,6,6-Tetramethyl-9-(2,4-dimethoxyphenyl)-1,2,3,4,5,6,7,
8,9,10-decahydroacridine-1,8-dione (8j). This compound was
obtained as solid with mp 267-269 °C; ir (potassium bromide):
3193, 3068, 2954, 2835, 1638, 1603, 1485, 1397, 1367, 1295,
1
1267, 1224, 1171, 1157, 1145, 1126, 1043, 930, 828 cm-1; H
nmr (DMSO-d6): δ 0.82 (s, 6H, 2 × CH3), 1.00 (s, 6H, 2 × CH3),
1.88 (d, J = 16.0 Hz, 2H, 2 × CH), 2.11 (d, J = 16.0 Hz, 2H, 2 ×
CH), 2.21 (d, J = 16.8 Hz, 2H, 2 × CH), 2.40 (d, J = 16.8 Hz,
2H, 2 × CH), 3.64 (s, 3H, CH3O), 3.67 (s, 3H, CH3O), 4.84 (s,
1H, CH), 6.31 (dd, J1 = 2.4 Hz, J2 = 8.4 Hz, 1H, ArH), 6.35 (d, J
= 2.4 Hz, 1H, ArH), 7.05 (d, J = 8.4 Hz, 1H, ArH), 9.17 (br. s,
1H, NH). Anal. Calcd. for C25H31NO4: C, 73.32; H, 7.63; N,
3.42. Found: C, 73.46; H, 7.58; N, 3.44.
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