An efficient ultrasound-promoted method for the one-pot synthesis of 7,10,11,12-tetrahydrobenzo[c]acridin-8(9H)-one derivatives

Article abstract of DOI:10.1016/j.ultsonch.2009.11.003

A new, efficient and general method for preparation of 7,10,11,12-tetrahydrobenzo[c]acridin-8(9H)-one derivatives using ultrasound irradiation is reported. Under ultrasound, the reaction time is short, the yields are high and the reaction conditions are m

Full text of DOI:10.1016/j.ultsonch.2009.11.003

Ultrasonics Sonochemistry 17 (2010) 495–499
Contents lists available at ScienceDirect
Ultrasonics Sonochemistry
journal homepage: www.elsevier.com/locate/ultsonch
Short Communication
An efficient ultrasound-promoted method for the one-pot synthesis
of 7,10,11,12-tetrahydrobenzo[c]acridin-8(9H)-one derivatives
a
b
a
Hongjun Zang a, , Yong Zhang , Yaping Zang , Bo-Wen Cheng
*
a Department of Material Science and Chemistry Engineering, Tianjin Polytechnic University, Tianjin Municipal Key Laboratory of Fiber Modification and Functional Fiber,
Tianjin 300160, China
b School of Chemical Engineering, Shandong Institute of Light Industry, 250353 Jinan, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 12 August 2009
Received in revised form 5 November 2009
Accepted 8 November 2009
Available online 13 November 2009
A new, efficient and general method for preparation of 7,10,11,12-tetrahydrobenzo[c]acridin-8(9H)-one
derivatives using ultrasound irradiation is reported. Under ultrasound, the reaction time is short, the
yields are high and the reaction conditions are mild.
Ó 2009 Elsevier B.V. All rights reserved.
Keywords:
1-Naphthylamine
Dimedone
Acridine
Ultrasound irradiation
One-pot reaction
1. Introduction
merits and shortcomings. Some methods are not very satisfactory
due to drawbacks such as low yields, high reaction temperature
The acridine derivatives have been known since the 19th cen-
tury where they were first used as pigments and dyes [1]. They
are considered to be important chemotherapeutics as they have
shown fungicidal, bactericidal, antimalarial effects [2] and multihy-
droacridineone derivatives have been reported to have high fluo-
rescence efficiency and can be used as fluorescent molecular
probes for monitoring of polymerization process [3]. Also the acri-
dine derivatives have been applied for the treatment of protozoal
infections caused by Plasmodium microorganisms [4]. The impor-
tance of those derived of acridines has grown due to recently their
antineoplasmic properties [5] as the acridine-4-carboxamides [6],
which are in clinical trial [7]. They are also increasingly receiving
attention due to their likeness in properties with those of 1,4-dihy-
dropyridines,which have similarities in structure to the biologically
important compounds such as NADH and NADPH [8]. As a
consequence, the interest of organic chemists in the synthesis or
structure modifications of acridinedione derivatives remains high.
Recently, there are many other methods available for the
construction of benzoacridine derivatives, for instance, by
refluxing appropriate naphthylamine, dimedone and aldehyde in
benzene [9], EtOH [10,11], H2O catalyzed by TEBA [12,13] or under
microwave irradiation [14,15]. These methods all have their own
and long reaction time.
Ultrasound has increasingly been used in organic synthesis. A
large number of ultrasonic reactions can be carried out in higher
yield, shorter reaction time or milder conditions [16–19]. As we
know that the temperature of hot spots caused by the collapse of
acoustic caves is generally as high as more than several hundred de-
grees, this energy can be transferred to the organic molecules and
absorbed by them to dramatically raise their intrinsic energy. Due
to the thermal effect of ultrasound wave, therefore, much larger
amount 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 ultrasound irradiation are
commonly easier to work-up than those in conventional stirring
methods. To our best knowledge, there is no report in literature
on preparation of 7,10,11,12-tetrahydrobenzo[c]acridin-8(9H)-one
derivatives using ultrasound irradiation. Herein, we report the
results of the synthesis of 7,10,11,12-tetrahydrobenzo[c]acridin-
8(9H)-one derivatives from corresponding aldehydes, 1-naphthyl-
amine and dimedone in EtOH under ultrasound irradiation.
2. Results and discussion
In our initial research, 4-chlorobenzaldehyde was selected
* Corresponding author. Tel.: +86 22 2401 9762; fax: +86 22 2452 8055.
E-mail address: chemhong@126.com (H. Zang).
as
a
representative reactant in order to optimize the
1350-4177/$ - see front matter Ó 2009 Elsevier B.V. All rights reserved.
doi:10.1016/j.ultsonch.2009.11.003

496
H. Zang et al. / Ultrasonics Sonochemistry 17 (2010) 495–499
Table 1
In order to apply this reaction to a library synthesis, dimedone
was treated with 1-naphthylamine and various aldehydes under
ultrasound irradiation at 25–30 °C which successfully yielded the
Effect of different solvents for synthesis of 4a under ultrasound irradiation at 25–
30 °C.
Entrya
Solvent
Time (h)
Yield (%)b
corresponding
7,10,11,12-tetrahydrobenzo[c]acridin-8(9H)-one
derivatives 4a–4l (Scheme 1). As shown in Table 3, in all cases,
7,10,11,12-tetrahydrobenzo[c]acridin-8(9H)-one derivatives were
obtained in good yields. In the present procedure, aromatic alde-
hyde carrying either electron-donating or electron-withdrawing
substituents in benzene ring reacted very well. Although the
differences in the transformation times are slight, generally the
electron-deficient substituents (Table 3, entries 5–8, 11 and 12)
were superior to the electron-rich ones (Table 3, entries 9, 10) in
this regard. And the longer reaction times were observed for the
substrates bearing electron-donating groups (Table 3, entries 7, 8,
11 and 12). The present method was convincingly superior to the
reported methods with respect to yield, reaction time, simplicity
and safety.
1
2
3
4
5
6
7
8
Water
CHCl3
ClCH2CH2Cl
DMF
THF
CH3CN
1,4-Dioxane
EtOH
1
1
1
1
1
1
1
1
36
53
60
58
51
63
71
91
a
Reaction conditions: 1 mmol 1-naphthylamine, 1 mmol 4-chlorobenzaldehyde
and 1 mmol dimedone and 10 ml solvent.
b
Isolated yield.
Table 2
Comparison of the yields for the synthesis of 4a as a model.
3. Experimental
Entry
Condition
Time (h)
Yield (%)a
3.1. Materials and methods
1
2
3
4
5
Ultrasonic in ethanol at 25–30 °C
Stirring in ethanol at 25–30 °C
Stirring in ethanol at 50 °C
Stirring in ethanol at 50 °C
Reflux in ethanol at 80 °C
1
1
1
5
2
91
75
82
87
All the chemicals were obtained from Tianjin Kermel Chemical
Reagent Co., Ltd. and used as received. Melting points were re-
corded on an electrothermal apparatus and were uncorrected. Son-
ication was performed in Kunshan KQ-250B ultrasonic cleaner
with a frequency of 40 kHz and a power 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.
85 [15]
a
Isolated yield.
reaction conditions. We conducted the one-pot three-compo-
nent condensation reaction of 1-naphthylamine, 4-chlo-
robenzaldehyde and dimedone in the presence of various
solvents. We examined the effect of different solvents such
as water, CHCl3, ClCH2CH2Cl, DMF, THF, CH3CN, 1,4-dioxane
and EtOH on a model reaction under ultrasound irradiation at
25–30 °C. The results were listed in Table 1. The reaction
using EtOH as solvent gave the best result (Table 1, entry 8).
The reaction failed to give poor yields in water,
CHCl3, ClCH2CH2Cl, DMF, THF, CH3CN and 1,4-dioxane (Table 1,
entries 1–7).
To demonstrate the effect of ultrasound, the synthesis of 4a as a
model was investigated under stirring and reflux conditions. The
results were shown in Table 2. Under stirring and reflux conditions,
the reaction can be completed within 1 h, 2 h and 5 h, respectively,
to give 4a in 75%, 82%, 87% and 85% yield. Whereas under ultra-
sonic irradiation (Table 2, entry 1), 4a was obtained in 91% yield
within 1 h. It was apparent that the ultrasound irradiation acceler-
ates this transformation under milder conditions. The reason may
be the phenomenon of cavitations produced by ultrasound [20]. As
shown in Tables 1 and 2, we selected the EtOH as solvent under
ultrasound irradiation conditions for the one-pot reaction of
aldehydes, 1-naphthylamine and dimedone to give corresponding
7,10,11,12-tetrahydrobenzo[c]acridin-8(9H)-one derivatives at
25–30 °C.
3.2. General procedure
To a mixture of substituted 1-naphthylamine (1 mmol), dime-
done (1 mmol) and 4-chlorobenzaldehyde (1 mmol) in 10 ml of
ethanol was added and reaction mixture was exposed to ultra-
sound irradiation a 100 ml conical flask at 25–30 °C, stirring in a
100 ml round flask at 25–30 °C, stirring in a 100 ml round flask
at 50 °C or reflux in a 100 ml round flask at 80 °C, respectively.
These results were shown in Table 2. The progress of reaction
was followed by TLC. After completion of reaction, the mixture
was poured into ice-water (50 ml), filtered to give the crude prod-
uct, which was further purified by recrystallization from EtOH.
A mixture of 1-naphthylamine (1 mmol), dimedone (1 mmol),
and respective aldehydes (1 mmol) in 10 ml of ethanol was taken
in a 100 ml conical flask and the reaction mixture was irradiated
in the water bath of the ultrasonic cleaner at 25–30 °C for a period
as indicated in Table 3. The course of the reaction was followed by
TLC. After completion of reaction, the mixture was poured into ice-
water (50 ml), 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 for authentic
samples [21].
Ar
O
NH2
O
O
EtOH
+
+
ArCHO
u.s., r.t.
N
H
2
3
1
4
Scheme 1. Synthesis of 7,10,11,12-tetrahydrobenzo[c]acridin-8(9H)-one derivatives.

H. Zang et al. / Ultrasonics Sonochemistry 17 (2010) 495–499
497
Table 3
Synthesis of 7,10,11,12-tetrahydrobenzo[c]acridin-8(9H)-one derivatives under ultrasound irradiation at 25–30 °C.
Entry
1
Ar
Product
Time (h)
1
Yield a(%)
90
M.p. (°C)
M.p. (Lit) (°C)
4-ClC6H4
4a
268–270
267–269 [9]
Cl
O
N
H
2
3
4
2-ClC6H4
4b
4c
4d
1
1
1
91
85
87
266–268
261–263
285–287
265–266 [14]
258–259 [14]
280–282 [13]
Cl
O
N
H
C6H5
O
N
H
2,4-Cl2C6H3
Cl
Cl
O
N
H
5
2-CH3OC6H4
4e
1
86
267–269
263–265 [9]
OCH3
O
N
H
6
4-CH3OC6H4
4f
1
85
259–261
260–262 [9]
OCH3
O
N
H
7
2-HOC6H4
4g
1.5
83
218–220
220–222 [14]
OH
O
N
H
8
4-HOC6H4
4h
1.5
85
285–287
280–282 [14]
OH
O
N
H
(continued on next page)

498
H. Zang et al. / Ultrasonics Sonochemistry 17 (2010) 495–499
Table 3 (continued)
Entry
9
Ar
Product
Time (h)
Yield a(%)
90
M.p. (°C)
M.p. (Lit) (°C)
3-O2NC6H4
4i
1
271–273
267–269 [13]
NO2
O
N
H
10
11
12
4-O2NC6H4
4j
1
87
81
83
281–283
274–276
281–283
280–282 [9]
270–273 [15]
276–278 [13]
NO2
O
N
H
3-CH3O-4-OHC6H3
4k
1.5
OH
OCH3
O
N
H
4l
4-(CH3)2NC6H4
1.5
H3C
CH3
N
O
N
H
a
Isolated yield.
[6] G.J. Atwell, G.W. Rewcastle, B.C. Bagueley, W.A. Denny, Potential antitumor
agents 50. In vivo solid-tumor activity of derivatives of N-[2-(dimethylamino)
ethyl]acridine-4-carboxamide, J. Med. Chem. 30 (1987) 664.
[7] M.R. Mc Crystal, B.D. Evans, V.J. Harvey, P.I. Thompson, D.J. Porter, B.C. Baguley,
Phase I study of the cytotoxic agent N-[2-(dimethylamino) ethyl]acridine-4-
carboxamide, Cancer Chemother. Pharmacol. 44 (1999) 39.
[8] N. Srividya, P. Ramamurthy, P. Shanmugasundaram, V.T. Ramakrishnan,
Synthesis, characterization, and electrochemistry of some acridine-1.8-dione
dyes, J. Org. Chem. 61 (1996) 5083.
[9] E. Cortés, R. Martínez, J.G. Avila, R.A. Toscano, 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. 25 (1988) 895.
[10] I. Lielbriedis, S.R. Trusov, E. Gudriniece, Latv. P.S.R. Zinat. Akad. Vestis, Kim. Ser.
39 (1971);
4. Conclusion
In conclusion, a new, fast, general, and facile method for
preparation of 7,10,11,12-tetrahydrobenzo[c]acridin-8(9H)-one
derivatives under ultrasound irradiation is presented. Ultrasounds
induce a remarkable acceleration for reactions. The salient features
of this protocol were mild reaction conditions, higher yields of
products and shorter reaction time.
Acknowledgment
I. Lielbriedis, S.R. Trusov, E. Gudriniece, Chem. Abstr. 75 (1971) 35674y.
[11] R. Martínez, E. Cortés, R.A. Toscano, 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-tetrahydro-
benz[a]acridin-11-ones. Structure correction of 1,2,3,4,5, 6-hexahydro and
1,2,3,4-tetrahydro-2,2-dimethyl-5-aryl-6-aza-9,10-benzophenanthren-4-ones,
J. Heterocycl. Chem. 27 (1990) 363.
The project was supported by the Tianjin National Natural Sci-
ence Foundation (No. 07JCYBJC02200).
References
[12] X.S. Wang, M.M. Zhang, Z.S. Zeng, D.Q. Shi, S.J. Tu, X.Y. Wei, Z.M. Zong, A simple
and clean procedure for the synthesis of polyhydroacridine and quinoline
derivatives: reaction of Schiff base with 1,3-dicarbonyl compounds in aqueous
medium, Tetrahedron Lett. 46 (2005) 7169.
[1] A. Albert, The Acridines, second ed., Edward Arnold Ltd., London, 1996.
[2] (a) A. Nasim, T. Brychcy, Genetic effects of acridine compounds, Mutat. Res.
Rev. Genet. Toxicol. 65 (1979) 261;
U. Thull, B. Testa, Screening of unsubstituted cyclic compounds as inhibitors of
monoamine oxidases, Biochem. Pharmacol. 47 (1994) 2307.
[3] R. Popielarz, S.K. Hu, D.C. Neckers, Applicability of decahydroacridine-1,8-
dione derivatives as fluorescent probes for monitoring of polymerization
processes, J. Photochem. Photobiol. A. Chem. 110 (1997) 79.
[13] X.S. Wang, M.M. Zhang, Z.S. Zeng, D.Q. Shi, S.J. Tu, X.Y. Wei, Z.M. Zong, 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.
[14] V. Nadaraj, S.T. Selvi, S. Mohan, Microwave-induced synthesis and anti-
microbial activities of 7,10,11,12-tetrahydrobenzo[c]acridin-8(9H)-one
derivatives, Eur. J. Med. Chem. 44 (2009) 976.
[4] J. Barbe, Bulletin 1st Acrival Meeting on Chemotherapy of Trypanosomatidae,
Marseilles, France, 1992, p. 63.
[5] P.C. Schofield, I.G.C. Robertson, J.W. Paxton, Metabolism of N-[2-(dimethyl-
amino)ethyl] acridine-4-carboxamide in cancer patients undergoing a phase I
clinical trial, Cancer Chemother. Pharmacol. 44 (1999) 51.
[15] S.J. Tu, R.H. Jia, B. Jiang, Y. Zhang, J.Y. Zhang, An efficient one-pot synthesis of
polyhydrobenzoacridine-1-one derivatives under microwave irradiation
without catalyst, J. Heterocycl. Chem. 43 (2006) 1621.

H. Zang et al. / Ultrasonics Sonochemistry 17 (2010) 495–499
499
[16] T.J. Mason, D. Peters, Practical Sonochemistry, second ed., EllisHorwood,
London, 2002.
[17] J.L. Luche, Synthetic Organic Sonochemistry, Plenum Press, New York, 1998.
[18] J.T. Li, Y.J. Bian, H.J. Zang, T.S. Li, Pinacol coupling of aromatic aldehydes and
ketones using magnesium in aqueous ammonium chloride under ultrasound,
Synth. Commun. 32 (2002) 547.
[19] H.J. Zang, M.L. Wang, B.W. Cheng, J. Song, Ultrasound-promoted synthesis of
oximes catalyzed by a basic ionic liquid [bmIm]OH, Ultrason. Sonochem. 16
(2009) 301.
[20] J.T. Li, S.X. Wang, G.F. Chen, T.S. Li, Some applications of ultrasound irradiation
in organic synthesis, Curr. Org. Synth. 2 (2005) 415.
[21] Physical and spectroscopic data for 4a–4l:10,10-Dimethyl-7-(4-chlorophenyl)-
7,10,11,12-tetrahydrobenzo[c]acridin-8(9H)-one (4a): cM.p. 268–270 °C. IR (KBr,
cmÀ1): 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 = 12.5 Hz, J = 12.5 Hz, CH2), 2.60–2.71 (2H, dd, J = 15.2 Hz, J = 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 = 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.
d6): 1.01 (3H, s, CH3), 1.09 (3H, s, CH3), 2.05–2.26 (2H, dd, J = 8.5 Hz, J = 8.5 Hz,
CH2), 2.63–2.75 (2H, dd, J = 15.0 Hz, J = 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 = 8.5 Hz, ArH), 8.43 (1H, d,
J = 8.5 Hz, ArH), 9.27 (1H, s, NH); Ms (m/z): 383; Anal. Calc. for C26H25NO2: C,
81.43; H, 6.57; N, 3.65; Found: C, 81.48; H, 6.55; N, 3.68.10,10-Dimethyl-7-(2-
hydroxyphenyl)-7,10,11,12-tetrahydrobenzo[c]acridin-8(9H)-one (4g): White
crystal; M.p. 218–220 °C. IR (KBr, cmÀ1): 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 = 8.5 Hz,
J = 8.5 Hz, CH2), 2.62–2.73 (2H, dd, J = 15.0 Hz, J = 15.0 Hz, CH2), 5.86 (1H, s,
CH), 6.82–7.69 (8H, m, ArH), 7.76 (1H, d, J = 8.5 Hz, ArH), 8.35 (1H, d,
J = 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,
3.73.10,10-Dimethyl-7-(4-hydroxyphenyl)-7,10,11,12-
tetrahydrobenzo[c]acridin-8(9H)-one (4h): White crystal; M.p. 285–287 °C. IR
(KBr, cmÀ1): 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 = 8.5 Hz, J = 8.5 Hz, CH2), 2.65–2.74 (2H, dd,
J = 15.0 Hz, J = 15.0 Hz, CH2), 5.82 (1H, s, CH), 6.84–7.66 (8H, m, ArH), 7.78
(1H, d, J = 8.5 Hz, ArH), 8.34 (1H, d, J = 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, 3.77.10,10-Dimethyl-7-(3-nitrophenyl)-7,10,11,12-
tetrahydrobenzo[c]acridin-8(9H)-one (4i): White crystal; M.p. 271–273 °C. IR
(KBr, cmÀ1): 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 = 8.5 Hz, J = 8.5 Hz, CH2), 2.71–2.77 (2H,
dd, J = 15.0 Hz, J = 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 = 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.
10,10-Dimethyl-7-(4-nitrophenyl)-7,10,11,12-tetrahydrobenzo[c]acridin-8(9H)-
one (4j): White crystal; M.p. 281–283 °C. IR (KBr, cmÀ1): 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 = 8.5 Hz, J = 8.5 Hz, CH2), 2.69–2.75 (2H, dd, J = 15.0 Hz, J = 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 = 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, 7.06.10,10-Dimethyl-7-(4-
hydroxy-3-methoxyphenyl)-7,10,11,12-tetrahydrobenzo[c]acridin-8(9H)-one
(4k): White crystal; M.p. 274–276 °C. IR (KBr, cmÀ1): 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 = 8.5 Hz, J = 8.5 Hz,
CH2), 2.65–2.76 (2H, dd, J = 15.0 Hz, J = 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 = 8.5 Hz, ArH), 8.43 (1H, d,
J = 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,
3.42.10,10-Dimethyl-7-(4-dimethylaminophenyl)-7,10,11,12-
tetrahydrobenzo[c]acridin-8(9H)-one (4l): White crystal; M.p. 281–283 °C. IR
(KBr, cmÀ1): 3298, 2954, 1679, 1578, 1514, 1391, 1261, 1146, 1063, 957, 827,
798, 752; 1H NMR (300 MHz, DMSO-d6): 1.01 (3H, s, CH3), 1.09 (3H, s, CH3),
2.05–2.26 (2H, dd, J = 8.5 Hz, J = 8.5 Hz, CH2), 2.67–2.75 (2H, dd, J = 15.0 Hz,
J = 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 = 8.5 Hz, ArH), 8.46 (1H, d, J = 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.
10,10-Dimethyl-7-(2-chlorophenyl)-7,10,11,12-tetrahydrobenzo[c]acridin8(9H)-
one (4b): White crystal; M.p. 266–268 °C. IR (KBr, cmÀ1): 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 = 12.5 Hz,
J = 12.5 Hz, CH2), 2.57–2.73 (2H, dd, J = 15.0 Hz, J = 15.0 Hz, CH2), 5.83 (1H, s,
CH), 6.86–7.65 (8H, m, ArH), 7.88 (1H, d, J = 8.5 Hz, ArH), 8.43 (1H, d,
J = 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, 3.64.10,10-Dimethyl-7-
phenyl-7,10,11,12-tetrahydrobenzo[c]acridin-8(9H)-one (4c): White crystal;
M.p. 261–263 °C. IR (KBr, cmÀ1): 3309, 2949, 2861, 1674, 1595, 1511, 1380,
1253, 1152, 1088, 1022, 750; 1H NMR (300 MHz, DMSO-d6): 1.01 (3H, s, CH3),
1.06 (3H, s, CH3), 2.03–2.27 (2H, dd, J = 12.5 Hz, J = 12.5 Hz, CH2), 2.57–2.78
(2H, dd, J = 15.0 Hz, J = 15.0 Hz, CH2), 5.87 (1H, s, CH), 6.85–7.63 (9H, m, ArH),
7.78 (1H, d, J = 8.5 Hz, ArH), 8.42 (1H, d, J = 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, 3.93.10,10-Dimethyl-7-(2,4-dichlorophenyl)-7,10,11,12-
tetrahydrobenzo[c]acridin-8(9H)-one (4d): White crystal; M.p. 285–287 °C. IR
(KBr, cmÀ1): 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 = 12.5 Hz, J = 12.5 Hz, CH2), 2.67–2.75 (2H,
dd, J = 15.0 Hz, J = 15.0 Hz, CH2), 5.74 (1H, s, CH), 7.16–7.63 (7H, m, ArH), 7.85
(1H, d, J = 8.5 Hz, ArH), 8.46 (1H, d, J = 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.
10,10-Dimethyl-7-(2-methoxylphenyl)-7,10,11,12-tetrahydrobenzo[c]acridin-
8(9H)-one (4e): White crystal; M.p. 267–269 °C. IR (KBr, cmÀ1): 3295, 2952,
2886, 1681, 1589, 1518, 1497, 1412, 1260, 1171, 1143, 1026, 845, 809, 765,
747; 1H NMR (300 MHz, DMSO-d6): 1.03 (3H, s, CH3), 1.10 (3H, s, CH3), 2.08–
2.23 (2H, dd, J = 8.5 Hz, J = 8.5 Hz, CH2), 2.59–2.74 (2H, dd, J = 15.0 Hz,
J = 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 = 8.5 Hz, ArH), 8.42 (1H, d, J = 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, 3.64.10,10-Dimethyl-7-(4-methoxylphenyl)-
7,10,11,12-tetrahydrobenzo[c]acridin-8(9H)-one (4f): White crystal; M.p.
259–261 °C. IR (KBr, cmÀ1): 3302, 2950, 2885, 1683, 1591, 1510, 1493,
1419, 1385, 1261, 1156, 1020, 835, 809, 762, 749; 1H NMR (300 MHz, DMSO-