Ultrasound-promoted one-pot synthesis of 7-aryl-7,10,11,12- tetrahydrobenzo[c]acridin-8(9H)-one derivatives

Article abstract of DOI:10.1080/00397911.2010.517610

A series of 7-aryl-7,10,11,12-tetrahydrobenzo[c]acridin-8(9H)-one derivatives were synthesized via the three-component coupling from aromatic aldehydes, 1-naphthylamine, and 5,5-dimethylcyclohexane-1,3-dione catalyzed by stannous chloride dihydrate (SnCl<

Full text of DOI:10.1080/00397911.2010.517610

This article was downloaded by: [University of Illinois Chicago]
On: 18 May 2013, At: 23:15
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An
International Journal for Rapid
Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/lsyc20
Ultrasound-Promoted One-Pot
Synthesis of 7-Aryl-7,10,11,12-
tetrahydrobenzo[c]acridin-8(9H)-one
Derivatives
Hongjun Zang a , Yong Zhang a , Yingming Mo a & Bowen Cheng a
a Department of Material Science and Chemistry Engineering, Tianjin
Polytechnic University, Tianjin Municipal Key Laboratory of Fiber
Modification and Functional Fiber, Tianjin, China
Published online: 27 Jul 2011.
To cite this article: Hongjun Zang , Yong Zhang , Yingming Mo & Bowen Cheng (2011): Ultrasound-
Promoted One-Pot Synthesis of 7-Aryl-7,10,11,12-tetrahydrobenzo[c]acridin-8(9H)-one Derivatives,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic
Chemistry, 41:21, 3207-3214
To link to this article: http://dx.doi.org/10.1080/00397911.2010.517610
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-and-conditions
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden.
The publisher does not give any warranty express or implied or make any representation
that the contents will be complete or accurate or up to date. The accuracy of any
instructions, formulae, and drug doses should be independently verified with primary
sources. The publisher shall not be liable for any loss, actions, claims, proceedings,
demand, or costs or damages whatsoever or howsoever caused arising directly or
indirectly in connection with or arising out of the use of this material.

Synthetic Communications1, 41: 3207–3214, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.517610
ULTRASOUND-PROMOTED ONE-POT SYNTHESIS OF
7-ARYL-7,10,11,12-TETRAHYDROBENZO[c]ACRIDIN-
8(9H)-ONE DERIVATIVES
Hongjun Zang, Yong Zhang, Yingming Mo, and Bowen Cheng
Department of Material Science and Chemistry Engineering, Tianjin
Polytechnic University, Tianjin Municipal Key Laboratory of Fiber
Modification and Functional Fiber, Tianjin, China
GRAPHICAL ABSTRACT
Abstract A series of 7-aryl-7,10,11,12-tetrahydrobenzo[c]acridin-8(9H)-one derivatives
were synthesized via the three-component coupling from aromatic aldehydes, 1-naphthyla-
mine, and 5,5-dimethylcyclohexane-1,3-dione catalyzed by stannous chloride dihydrate
(SnCl2 ꢀ 2H2O) under ultrasonic irradiation at room temperature. The products were
isolated in good yields within short reaction times.
Keywords Acridine; dimedone; 1-naphthylamine; one-pot reaction; ultrasonic irradia-
tion
INTRODUCTION
The acridine derivatives have been known since the 19th century, when they
were first used as pigments and dyes.[1] They are considered to be important che-
motherapeutics as they have shown fungicidal, bactericidal, and antimalarial
effects,[2] and multihydroacridineone derivatives have been reported to have high
fluorescence efficiency and can be used as fluorescent molecular probes for monitor-
ing of polymerization processes.[3] They are also increasingly receiving attention
because of their likeness in properties with those of 1,4-dihydropyridines, which have
similarities in structure to biologically important compounds such as nicotinamide
adenine dinucleotide (NADH) and nicotinamide adenine dinucleotide phosphate
(NADPH).[4] As a consequence, the interest of organic chemists in the synthesis or
structural modifications of acridinedione derivatives remains high. Recently, some
Received September 8, 2009.
Address correspondence to Bowen Cheng, Department of Material Science and Chemistry
Engineering, Tianjin Polytechnic University, Tianjin Municipal Key Laboratory of Fiber Modification
and Functional Fiber, 300160 Tianjin, China. E-mail: chemhong@126.com, bowen@tjpu.edu.cn
3207

3208
H. ZANG ET AL.
Scheme 1. Synthesis of 7-aryl-7,10,11,12-tetrahydrobenzo[c]acridin-8(9H)-one derivatives.
developments for the synthesis of 7-aryl-7,10,11,12-tetrahydrobenzo[c]acridin-8(9H)-
one derivatives have been reported, such as by refluxing naphthylamine, dimedone,
and aldehyde in benzene,[5] EtOH,[6] H2O catalyzed by benzyltriethylammonium
chloride (TEBA),[7] or under microwave irradiation.[8] These methods all have their
own merits and shortcomings. Some methods are not very satisfactory because of
drawbacks such as poor yields, high reaction temperature, and long reaction time.
Stannous chloride dihydrate (SnCl2 ꢀ 2H2O) is widely used as a reducing agent and
as a Lewis acid catalyst, and its dihydrate has been employed as a mild reagent
for the deprotection of acetals.[9]
In recent years, ultrasonic irradiation has been extensively applied in organic
reactions because of its special sonochemical effect. The advantages of ultrasonic
procedures, such as good yields, short reaction times, and mild reaction conditions,
are well documented.[10] As we know, the temperature of hot spots caused by the col-
lapse of acoustic caves is generally more than several hundred degrees, and this
energy can be transferred to the organic molecules and absorbed to dramatically
raise their intrinsic energy. Because of the thermal effect of ultrasonic waves, much
larger amounts of molecules can meet the demand for the active energy in a given
reaction, leading to the apparent improvement of the reaction efficiency with
increased rates and reduced reaction time. It is also observed that reactions under
ultrasonic irradiation are commonly easier to work up than those in conventional
stirring methods. Herein we describe our example for the synthesis of 7-aryl-
7,10,11,12 -tetrahydrobenzo[c]acridin-8(9H)-one derivatives from corresponding
aldehydes, 1-naphthylamine, and dimedone using SnCl2 ꢀ 2H2O in EtOH under ultra-
sonic irradiation at room temperature (Scheme 1).
RESULTS AND DISCUSSION
We first screened various solvents for the synthesis of 7-aryl-7,10,11,12-
tetrahydrobenzo[c]acridin-8(9H)-one derivatives. The 4-chlorobenzaldehyde was
selected as a representative reactant to optimize the reaction conditions (Table 1).
We examined the effect of different solvents such as water, CHCl3, CH2Cl2,
ClCH2CH2Cl, dimethylformamide (DMF), tetrahydrofuran (THF), CH3CN,
1,4-dioxane, and EtOH on a model reaction under ultrasonic irradiation at room
temperature. The results are listed in Table 1 (entries 1–9). The reaction using EtOH
as solvent gave the best result (Table 1, entry 9). To demonstrate the effect of
ultrasound, the synthesis of 4a, which is treated as a model, was investigated under
stirring and reflux conditions (Table 1, entries 9–11). Under stirring and reflux con-
ditions, the reaction can be completed within 1 and 2 h respectively, giving 4a in 77%
and 89% yields, whereas under ultrasonic irradiation (Table 1, entry 9), 4a was

SYNTHESIS OF BENZO[c]ACRIDINE DERIVATIVES
3209
Table 1. Effect of different solvents for synthesis of 4a using SnCl2 ꢀ 2H2O
Entrya
Solvent
Condition
Time (h)
Yield (%)b
1
2
Water
CH2Cl2
CHCl3
rt
1
1
1
1
1
1
1
1
1
1
2
47
51
59
62
63
56
77
81
97
77
89
rt
3
rt
4
ClCH2CH2Cl
DMF
THF
rt
5
rt
6
rt
7
CH3CN
1,4-Dioxane
EtOH
rt
8
rt
9
rt
10
11
EtOH
EtOH
Stirring, rt
Reflux, 80 ꢁC
aReaction conditions: 1 mmol 1-naphthylamine, 1 mmol 4-chlorobenzaldehyde, 1 mmol dimedone,
0.2 mmol SnCl2 ꢀ 2H2O, and 10 ml solvent.
bIsolated yield.
obtained in 97% yield within 1 h. It was apparent that the ultrasonic irradiation
accelerated this transformation under milder conditions. The reason may be that
the phenomenon of cavitation is produced by ultrasound. The effects of various cat-
alysts such as FeCl3, ZnCl2, NaHSO4, NH2SO3H, SnCl4 ꢀ 5H2O, and SnCl2 ꢀ 2H2O or
the absence of the catalyst were studied for this conversion, and the results are pre-
sented in Table 2. Of these catalysts, SnCl2 ꢀ 2H2O was found to be the most effective
in terms of conversion. We selected the EtOH as solvent, using SnCl2 ꢀ 2H2O under
ultrasonic irradiation conditions for the one-pot reaction of aldehydes, 1-naphthyla-
mine, and dimedone, and put corresponding 7-aryl-7,10,11,12-tetrahydro-
benzo[c]acridin-8(9H)-one derivatives at room temperature.
Next, various aromatic aldehydes were tested under the optimized reaction
conditions (Scheme 1), and the results are listed in Table 3. In all cases, 7-aryl-
7,10,11,12-tetrahydrobenzo[c]acridin-8(9H)-one derivatives were obtained in good
yields. In the present procedure, aromatic aldehydes carrying either electron-
donating or electron-withdrawing substituents in the benzene ring reacted very well.
The present method was convincingly superior to the reported methods with respect
to yield and reaction time.
Table 2. Effects of various catalysts on the preparation of 4a under ultrasonic
irradiation at room temperature
Entry
Catalyst
Time (h)
Yield (%)a
1
2
3
4
5
6
7
No
FeCl3
ZnCl2
1
1
1
1
1
1
1
90
89
91
86
90
89
97
NaHSO4
NH2SO3H
SnCl4
SnCl2 ꢀ 2H2O
aIsolated yield.

3210
H. ZANG ET AL.
Table 3. Synthesis of 7-aryl-7,10,11,12-tetrahydrobenzo[c]acridin-8(9H)-one derivatives using SnCl2 ꢀ 2H2O
under ultrasonic irradiation at room temperature
No.
Ar
Time (h)
Yield (%)a
Mp (ꢁC)=(lit.) (ꢁC)
4a
4b
4c
4d
4e
4f
4-ClC6H4
2-ClC6H4
C6H5
1
1
1
1
1
1
1
1
1
1
1
1
97
92
85
89
95
88
85
86
94
88
83
84
268–270 (267–269)[5]
266–268 (265–266)[8]
261–263 (258–259)[8]
285–287 (280–282)[7]
267–269 (263–265)[5]
259–261 (260–262)[5]
218–220 (220–222)[8]
285–287 (280–282)[8]
271–273 (267–269)[7]
281–283 (280–282)[5]
274–276 (270–273)[7]
281–283 (276–278)[7]
2,4-Cl2C6H3
2-CH3OC6H4
4-CH3OC6H4
2-HOC6H4
4g
4h
4i
4-HOC6H4
3-O2NC6H4
4-O2NC6H4
3-CH3O-4-OHC6H3
4-(CH3)2NC6H4
4j
4k
4l
aIsolated yield.
CONCLUSION
In conclusion, an efficient and facile method for preparation of 7-aryl-7,10,
11,12-tetrahydrobenzo[c]acridin-8(9H)-one derivatives catalyzed by SnCl2 ꢀ 2H2O
under ultrasonic irradiation at room temperature is presented. Ultrasound induces
a remarkable acceleration for reactions. The products were isolated in good yields
within short reaction times.
EXPERIMENTAL
All the chemicals were obtained from Tianjin Kermel Chemical Reagent Co.,
Ltd. and used as received. Melting points were recorded on an electrothermal appar-
atus and were uncorrected. Sonication was performed in Kunshan KQ-250B ultra-
sonic cleaner with a frequency of 40 kHz and a power of 250 W. The reaction
flasks were located in the maximum energy area in the cleaner, and the addition
or removal of water controlled the temperature of the water bath.
Typical Procedure for Preparation of Compound 4
In a 100-ml conical flask, a mixture of 1-naphthylamine (1 mmol), dimedone
(1 mmol), and respective aldehydes (1 mmol) was mixed with EtOH (10 ml), and
0.2 mmol SnCl2 ꢀ 2H2O was added. The reaction mixture was irradiated in the water
bath of the ultrasonic cleaner by an ultrasonic probe with a frequency of 40 KHz at
room temperature (25 ꢁC) for 1 h. The termination of the reaction was monitored by
thin-layer chromatography (TLC). When the reaction was over, the mixture was
poured into ice water (50 ml) and filtered to give the crude product, which was
further purified by recrystallization from EtOH (4a–4l). All products were known
compounds and were identified by comparison of their physical and spectroscopic
data with those reported.[5,7,8]

SYNTHESIS OF BENZO[c]ACRIDINE DERIVATIVES
3211
Melting Point and Spectral Data for Compounds 4a–4l
Compound 4a. White crystal; mp 268–270 ꢁC. IR (KBr, cmꢂ1): 3309, 2951,
1670, 1585, 1520, 1383, 1251, 1154, 1066, 1022, 854, 750; 1H NMR (300 MHz,
DMSO-d6): 0.98 (3H, s, CH3), 1.05 (3H, s, CH3), 2.03–2.25 (2H, dd, J ¼ 12.5 Hz,
J ¼ 12.5 Hz, CH2), 2.60–2.71 (2H, dd, J ¼ 15.2 Hz, J ¼ 15.2 Hz, CH2), 5.32 (1H, s,
CH), 7.16–7.33 (5H, m, ArH), 7.48–7.61 (2H, m, ArH), 7.48–7.61 (2H, m, ArH),
8.46 (1H, d, J ¼ 8.5 Hz, ArH), 9.38 (1H, s, NH); MS (m=z): 387. Anal. calc. for
C25H22NOCl: C, 77.41; H, 5.72; N, 3.61. Found: C, 77.43; H, 5.75; N, 3.62.
Compound 4b. White crystal; mp 266–268 ꢁC. IR (KBr, cmꢂ1): 3307, 2947,
2864, 1675, 1584, 1511, 1387, 1262, 1151, 1081, 1020, 846, 748; 1H NMR
(300 MHz, DMSO-d6): 1.02 (3H, s, CH3), 1.07 (3H, s, CH3), 2.05–2.28 (2H, dd,
J ¼ 12.5 Hz, J ¼ 12.5 Hz, CH2), 2.57–2.73 (2H, dd, J ¼ 15.0 Hz, J ¼ 15.0 Hz, CH2),
5.83 (1H, s, CH), 6.86–7.65 (8H, m, ArH), 7.88 (1H, d, J ¼ 8.5 Hz, ArH), 8.43
(1H, d, J ¼ 8.5 Hz, ArH), 9.28 (1H, s, NH); MS (m=z): 387. Anal. calc. for
C25H22NOCl: C, 77.41; H, 5.72; N, 3.61. Found: C, 77.45; H, 5.71; N, 3.64.
Compound 4c. White crystal; mp 261–263 ꢁC. IR (KBr, cmꢂ1): 3309, 2949,
1
2861, 1674, 1595, 1511, 1380, 1253, 1152, 1088, 1022, 750; H NMR (300 MHz,
DMSO-d6): 1.01 (3H, s, CH3), 1.06 (3H, s, CH3), 2.03–2.27 (2H, dd, J ¼ 12.5 Hz,
J ¼ 12.5 Hz, CH2), 2.57–2.78 (2H, dd, J ¼ 15.0 Hz, J ¼ 15.0 Hz, CH2), 5.87 (1H, s,
CH), 6.85–7.63 (9H, m, ArH), 7.78 (1H, d, J ¼ 8.5 Hz, ArH), 8.42 (1H, d, J ¼ 8.5 Hz,
ArH), 9.22 (1H, s, NH); MS (m=z): 353. Anal. calc. for C25H23NO: C, 84.95; H, 6.56;
N, 3.96. Found: C, 84.93; H, 56.51; N, 3.93.
Compound 4d. White crystal; mp 285–287 ꢁC. IR (KBr, cmꢂ1): 3310, 2949,
1685, 1586, 1517, 1487, 1397, 1261, 1151, 1087, 1023, 856, 760, 742; 1H NMR
(300 MHz, DMSO-d6): 1.01 (3H, s, CH3), 1.08 (3H, s, CH3), 2.04–2.25 (2H, dd,
J ¼ 12.5 Hz, J ¼ 12.5 Hz, CH2), 2.67–2.75 (2H, dd, J ¼ 15.0 Hz, J ¼ 15.0 Hz, CH2),
5.74 (1H, s, CH), 7.16–7.63 (7H, m, ArH), 7.85 (1H, d, J ¼ 8.5 Hz, ArH), 8.46
(1H, d, J ¼ 8.5 Hz, ArH), 9.26 (1H, s, NH); MS (m=z): 421. Anal. calc. for
C25H21NOCl2: C, 71.10; H, 5.01; N, 3.32. Found: C, 71.11; H, 5.04; N, 3.41.
Compound 4e. White crystal; mp 267–269 ꢁC. IR (KBr, cmꢂ1): 3295, 2952,
1
2886, 1681, 1589, 1518, 1497, 1412, 1260, 1171, 1143, 1026, 845, 809, 765, 747; H
NMR (300 MHz, DMSO-d6): 1.03 (3H, s, CH3), 1.10 (3H, s, CH3), 2.08–2.23 (2H,
dd, J ¼ 8.5 Hz, J ¼ 8.5 Hz, CH2), 2.59–2.74 (2H, dd, J ¼ 15.0 Hz, J ¼ 15.0 Hz,
CH2), 3.81 (3H, s, CH3O), 5.84 (1H, s, CH), 6.81–7.65 (8H, m, ArH), 7.83 (1H, d,
J ¼ 8.5 Hz, ArH), 8.42 (1H, d, J ¼ 8.5 Hz, ArH), 9.25 (1H, s, NH); MS (m=z): 383.
Anal. calc. for C26H25NO2: C, 81.43; H, 6.57; N, 3.65. Found: C, 81.41; H, 6.51;
N, 3.64.
Compound 4f. White crystal; mp 259–261 ꢁC. IR (KBr, cmꢂ1): 3302, 2950,
2885, 1683, 1591, 1510, 1493, 1419, 1385, 1261, 1156, 1020, 835, 809, 762, 749;
1H NMR (300 MHz, DMSO-d6): 1.01 (3H, s, CH3), 1.09 (3H, s, CH3), 2.05–2.26
(2H, dd, J ¼ 8.5 Hz, J ¼ 8.5 Hz, CH2), 2.63–2.75 (2H, dd, J ¼ 15.0 Hz, J ¼ 15.0 Hz,
CH2), 3.78 (3H, s, CH3O), 5.76 (1H, s, CH), 6.75–7.65 (8H, m, ArH), 7.86 (1H, d,
J ¼ 8.5 Hz, ArH), 8.43 (1H, d, J ¼ 8.5 Hz, ArH), 9.27 (1H, s, NH); MS (m=z):

3212
H. ZANG ET AL.
383. Anal. calc. for C26H25NO2: C, 81.43; H, 6.57; N, 3.65. Found: C, 81.48; H,
6.55; N, 3.68.
Compound 4g. White crystal; mp 218–220 ꢁC. IR (KBr, cmꢂ1): 3305, 3178,
2945, 1685, 1590, 1515, 1491, 1389, 1267, 1154, 1023, 837, 760, 742; 1H NMR
(300 MHz, DMSO-d6): 1.02 (3H, s, CH3), 1.10 (3H, s, CH3), 2.04–2.26 (2H, dd,
J ¼ 8.5 Hz, J ¼ 8.5 Hz, CH2), 2.62–2.73 (2H, dd, J ¼ 15.0 Hz, J ¼ 15.0 Hz, CH2),
5.86 (1H, s, CH), 6.82–7.69 (8H, m, ArH), 7.76 (1H, d, J ¼ 8.5 Hz, ArH), 8.35
(1H, d, J ¼ 8.5 Hz, ArH), 9.22 (1H, s, NH),13.07 (1H, s, OH); MS (m=z): 383. Anal.
calc. for C25H23NO2: C, 81.27; H, 6.27; N, 3.79. Found: C, 81.28; H, 6.25; N, 3.73.
Compound 4h. White crystal; mp 285–287 ꢁC. IR (KBr, cmꢂ1): 3309, 3156,
2942, 1683, 1595, 1522, 1494, 1384, 1265, 1159, 1023, 835, 767, 740; 1H NMR
(300 MHz, DMSO-d6): 1.00 (3H, s, CH3), 1.09 (3H, s, CH3), 2.06–2.25 (2H, dd,
J ¼ 8.5 Hz, J ¼ 8.5 Hz, CH2), 2.65–2.74 (2H, dd, J ¼ 15.0 Hz, J ¼ 15.0 Hz, CH2),
5.82 (1H, s, CH), 6.84–7.66 (8H, m, ArH), 7.78 (1H, d, J ¼ 8.5 Hz, ArH), 8.34
(1H, d, J ¼ 8.5 Hz, ArH), 9.24 (1H, s, NH), 13.04 (1H, s, OH); MS (m=z): 383. Anal.
calc. for C25H23NO2: C, 81.27; H, 6.27; N, 3.79. Found: C, 81.25; H, 6.22; N, 3.77.
Compound 4i. White crystal; mp 271–273 ꢁC. IR (KBr, cmꢂ1): 3308, 2952,
1678, 1591, 1526, 1495, 1381, 1354, 1268, 1152, 1087, 1028, 815, 762, 732; 1H
NMR (300 MHz, DMSO-d6): 0.99 (3H, s, CH3), 1.10 (3H, s, CH3), 2.05–2.28 (2H,
dd, J ¼ 8.5 Hz, J ¼ 8.5 Hz, CH2), 2.71–2.77 (2H, dd, J ¼ 15.0 Hz, J ¼ 15.0 Hz,
CH2), 5.74 (1H, s, CH), 7.34–7.86 (7H, m, ArH), 7.98–8.05 (2H, m, ArH), 8.45
(1H, d, J ¼ 8.5 Hz, ArH), 9.31 (1H, s, NH); MS (m=z): 398. Anal. calc. for
C25H22N2O3: C, 75.36; H, 5.57; N, 7.03. Found: C, 75.35; H, 5.51; N, 7.09.
Compound 4j. White crystal; mp 281–283 ꢁC. IR (KBr, cmꢂ1): 3310, 2957,
1670, 1594, 1523, 1495, 1384, 1352, 1269, 1149, 1083, 1030, 811, 760, 722; 1H
NMR (300 MHz, DMSO-d6): 0.99 (3H, s, CH3), 1.11 (3H, s, CH3), 2.06–2.26 (2H,
dd, J ¼ 8.5 Hz, J ¼ 8.5 Hz, CH2), 2.69–2.75 (2H, dd, J ¼ 15.0 Hz, J ¼ 15.0 Hz,
CH2), 5.76 (1H, s, CH), 7.15–7.74 (7H, m, ArH), 7.95–8.03 (2H, m, ArH), 8.40
(1H, d, J ¼ 8.5 Hz, ArH), 9.29 (1H, s, NH); MS (m=z): 398. Anal. calc. for
C25H22N2O3: C, 75.36; H, 5.57; N, 7.03. Found: C, 75.30; H, 5.54; N, 7.06.
Compound 4k. White crystal; mp 274–276 ꢁC. IR (KBr, cmꢂ1): 3302, 2959,
1574, 1510, 1498, 1394, 1263, 1144, 1093, 812, 768, 650; 1H NMR (300 MHz,
DMSO-d6): 1.02 (3H, s, CH3), 1.10 (3H, s, CH3), 2.07–2.28 (2H, dd, J ¼ 8.5 Hz,
J ¼ 8.5 Hz, CH2), 2.65–2.76 (2H, dd, J ¼ 15.0 Hz, J ¼ 15.0 Hz, CH2), 3.76 (3H, s,
CH3O), 5.48 (1H, s, CH), 6.98–7.51 (7H, m, ArH), 7.85 (1H, d, J ¼ 8.5 Hz, ArH),
8.43 (1H, d, J ¼ 8.5 Hz, ArH), 8.69 (1H, s, OH), 9.27 (1H, s, NH); MS (m=z): 399.
Anal. calc. for C26H25NO3: C, 78.17; H, 6.31; N, 3.51. Found: C, 78.24; H, 6.39;
N, 3.42.
Compound 4l. White crystal; mp 281–283 ꢁC. IR (KBr, cmꢂ1): 3298, 2954,
1
1679, 1578, 1514, 1391, 1261, 1146, 1063, 957, 827, 798, 752; H NMR (300 MHz,
DMSO-d6): 1.01 (3H, s, CH3), 1.09 (3H, s, CH3), 2.05–2.26 (2H, dd, J ¼ 8.5 Hz,
J ¼ 8.5 Hz, CH2), 2.67–2.75 (2H, dd, J ¼ 15.0 Hz, J ¼ 15.0 Hz, CH2), 2.86 (6H, s,
2NCH3), 5.51 (1H, s, CH), 7.03–7.65 (8H, m, ArH), 7.83 (1H, d, J ¼ 8.5 Hz,

SYNTHESIS OF BENZO[c]ACRIDINE DERIVATIVES
3213
ArH), 8.46 (1H, d, J ¼ 8.5 Hz, ArH), 9.22 (1H, s, NH); MS (m=z): 396. Anal. calc. for
C27H28N2O: C, 81.78; H, 7.12; N, 7.06. Found: C, 81.70; H, 7.14; N, 6.99.
ACKNOWLEDGMENT
The project was supported by the Tianjin National Natural Science Foun-
dation (Nos. 11JCZDJC21300) and (NSFC 51076174).
REFERENCES
1. Albert, A. The Acridines, 2nd ed.; Edward Arnold Publication Ltd.: London, 1996.
2. (a) Nasim, A.; Brychcy, T. Genetic effects of acridine compounds. Mutat. Res.=Rev.
Genet. Toxicol. 1979, 65, 261–288; (b) Thull, U.; Testa, B. Screening of unsubstituted cyc-
lic compounds as inhibitors of monoamine oxidases. Biochem. Pharmacol. 1994, 47, 2307.
3. Popielarz, R.; Hu, S. K.; Neckers, D. C. Applicability of decahydroacridine-1,8-dione
derivatives as fluorescent probes for monitoring of polymerization processes. J. Photo-
chem. Photobiol. A: Chem. 1997, 110, 79–83.
4. Srividya, N.; Ramamurthy, P.; Shanmugasundaram, P.; Ramakrishnan, V. T. Synthesis,
characterization, and electrochemistry of some acridine-1,8-dione dyes. J. Org. Chem.
1996, 61, 5083–5089.
´
´
5. Cortes, E.; Martınez, R.; Gavila, J.; Toscano, R. A. Synthesis and spectra of 7-(o-
and p-R-phenyl)-10,10-dimethyl-8,9,10,11-tetrahydrobenz[c]acridin-8-ones: Structure
correction of 1,2,3,4-tetrahydro-2,2-dimethyl-5-aryl-6-aza-7,8-benzophenanthren-4-ones.
J. Heterocycl. Chem. 1988, 25, 895–899.
6. (a) Lielbriedis, I.; Trusov, S. R.; Gudriniece, E.; Latv, P. S. R. Zinat. Akad. Vestis, Kim.
Ser. 1971, 39; Chem. Abstr. 1971, 75, 35674y; (b) Martınez, R.; Cortes, E.; Toscano, R. A.
´ ´
Synthesis and spectra of 12-(o- and p-R-phenyl)-9,9-dimethyl-7,8,9,10,11,12-hexahydro
and 8,9,10,11-tetrahydrobenz[a]acridin-11-ones: Structure correction of 1,2,3,4,5,6-hexa-
hydro and 1,2,3,4-tetrahydro-2,2-dimethyl-5-aryl-6-aza-9,10-benzophenanthren-4-ones.
J. Heterocycl. Chem. 1990, 27, 363–366.
7. (a) Wang, X. S.; Zhang, M. M.; Zeng, Z. S.; Shi, D. Q.; Tu, S. J.; Wei, X. Y.; Zong, Z. M.
A simple and clean procedure for the synthesis of polyhydroacridine and quinoline deri-
vatives: Reaction of Schiff base with 1,3-dicarbonyl compounds in aqueous medium.
Tetrahedron Lett. 2005, 46, 7169–7173; (b) Wang, X. S.; Zhang, M. M.; Zeng, Z. S.;
Shi, D. Q.; Tu, S. J.; Wei, X. Y.; Zong, Z. M. A clean procedure for synthesis of benzo[-
c]acridine derivatives: Reaction of N-arylidenenaphthalen-1-amine with 5,5-dimethyl-1,3-
cyclohexadione in aqueous medium. Arkivoc 2006, 117–123.
8. (a) Nadaraj, V.; Selvi, S. T.; Mohan, S. Microwave-induced synthesis and anti-microbial
activities of 7,10,11,12-tetrahydrobenzo[c]acridin-8(9H)-one derivatives. Eur. J. Med.
Chem. 2009, 44, 976–980; (b) Tu, S. J.; Jia, R. H.; Jiang, B.; Zhang, Y.; Zhang, J. Y.
An efficient one-pot synthesis of polyhydrobenzoacridine-1-one derivatives under micro-
wave irradiation without catalyst. J. Heterocycl. Chem. 2006, 43, 1621–1627.
9. (a) Varma, R. S.; Kabalka, G. W. Reduction of nitroalkenes with stannous chloride in
non-acidic and non-aqueous medium: Synthesis of a-substituted oximes. Chem. Lett.
1985, 2, 243–244; (b) Ford, K. L.; Roskamp, E. J. An improved procedure for the depro-
tection of acetals with tin dichloride dehydrate. J. Org. Chem. 1993, 58, 4142–4143; (c)
Yasuda, M.; Sugawa, Y.; Yamamoto, A.; Shibata, I.; Baba, A. Allylic tin(IV)–tin(II)
chloride–acetonitrile as a novel system for allylation of carbonyls or imines. Tetrahedron
Lett. 1996, 37, 5951–5954; (d) Yasuda, M.; Okamoto, K.; Sako, T.; Baba, A. Highly
stereoselective addition to alkoxy or hydroxy ketones using an a-stannyl ester–stannous

3214
H. ZANG ET AL.
chloride system in a chelation-controlled manner. Chem. Commun. 2001, 157–158; (e)
Yasuda, M.; Hirata, K.; Nishino, M.; Yamamoto, A.; Baba, A. Diastereoselective
addition of c-substituted allylic nucleophiles to ketones: Highly stereoselective synthesis
of tertiary homoallylic alcohols using an allylic tributylstannane=stannous chloride sys-
tem. J. Am. Chem. Soc. 2002, 124, 13442–13447; (f) Reid, M.; Taylor, R. J. K. A stannous
chloride–induced deacetalisation–cyclisation process to prepare the ABC ring system of
’upenamide. Tetrahedron Lett. 2004, 45, 4181–4183; (g) Menard-Moyon, C.; Taylor, R.
J. K. Stereoselective syntheses of the octahydropyrano[2,3-b]pyridine DE core of ’upena-
mide via a stannous chloride–induced deacetalisation–cyclisation procedure. Eur. J. Org.
Chem. 2007, 22, 3698–3706; (h) Cayley, A. N.; Gallagher, K. A.; Menard-Moyon, C.;
Schmidt, J. P.; Diorazio, L. J.; Taylor, R. J. K. Preparation of novel polycyclic hetero-
cycles using a tin(II) chloride dihydrate–mediated deacetalisation–bicyclisation sequence.
Synthesis 2008, 23, 3846–3856; (i) Yasuda, M.; Azuma, T.; Tsuruwa, K.; Babu, S. A.;
Baba, A. Highly stereoselective synthesis of vicinal diols by stannous chloride–mediated
addition of hydroxyallylic stannanes to aldehydes. Tetrahedron Lett. 2009, 50, 3209–3212.
10. (a) Li, J. T.; Bian, Y. J.; Zang, H. J.; Li, T. S. Pinacol coupling of aromatic aldehydes and
ketones using magnesium in aqueous ammonium chloride under ultrasound. Synth. Com-
mun. 2002, 32, 547–551; (b) Zhang, Z. H.; Li, J. J.; Li, T. S. Ultrasound-assisted synthesis
of pyrroles catalyzed by zirconium chloride under solvent-free conditions. Ultrason. Sono-
chem. 2008, 15, 673–676; (c) Zang, H. J.; Wang, M. L.; Cheng, B. W.; Song, J.
Ultrasound-promoted synthesis of oximes catalyzed by a basic ionic liquid [bmIm]OH.
Ultrason. Sonochem. 2009, 16, 301–303; (d) Mahdavinia, G.; Rostamizadeh, H. S.; Amani,
A. M.; Emdadi, Z. Ultrasound-promoted greener synthesis of aryl-14-H-dibenzo[a,j]-
xanthenes catalyzed by NH4H2PO4=SiO2 in water. Ultrason. Sonochem. 2009, 16, 7–10.