A clean procedure for the synthesis of chromeno[4,3-b]benzo[f]quinoline and quinolino[4,3-b]benzo[f]quinoline derivatives in aqueous media

Article abstract of DOI:10.1246/cl.2005.1316

A short and simple synthesis of chromeno[4,3-b]benzo[f]-quinoline and quinolino[4,3-b]benzo[f]quinoline derivatives were accomplished in high yields via the reaction of N-benzilidenenaphthalen-2-amine and 4-hydroxycoumarin or 4-hydroxyquinolin-2-one in aq

Full text of DOI:10.1246/cl.2005.1316

1316
Chemistry Letters Vol.34, No.10 (2005)
A Clean Procedure for the Synthesis of Chromeno[4,3-b]benzo[ f]quinoline
and Quinolino[4,3-b]benzo[ f]quinoline Derivatives in Aqueous Media
Xiang-Shan Wang,ꢀy;yy;yyy Mei-Mei Zhang,y Zhao-Sen Zeng,y Da-Qing Shi,y;yy Shu-Jiang Tu,y;yy
Xian-Yong Wei,yyy and Zhi-Min Zongyyy
yDepartment of Chemistry, Xuzhou Normal University, Xuzhou Jiangsu 221116, P. R. China
yyThe Key Laboratory of Biotechnology on Medical Plant of Jiangsu Province, Xuzhou 221116, P. R. China
yyySchool of Chemical Engineering, China University of Mining and Technology, Xuzhou Jiangsu 221008, P. R. China
(Received June 16, 2005; CL-050774)
A short and simple synthesis of chromeno[4,3-b]benzo[ f]-
quinoline and quinolino[4,3-b]benzo[ f]quinoline derivatives
were accomplished in high yields via the reaction of N-benzili-
denenaphthalen-2-amine and 4-hydroxycoumarin or 4-hydroxy-
quinolin-2-one in aqueous media catalyzed by TEBAC. The
structures were established by spectroscopic data and further
confirmed by X-ray diffraction analysis.
Table 1. The results on the reaction of 1 and 2 in water at
100 ꢁC12
Entry
Ar
X
Time/h
Yields/%
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
3q
3r
4-BrC6H4
2-ClC6H4
3-ClC6H4
4-ClC6H4
2,4-Cl2C6H3
3,4-Cl2C6H3
4-HOC6H4
4-(CH3)2NC6H4
2-NO2C6H4
4-CH3OC6H4
2-ClC6H4
O
O
O
O
O
O
O
O
O
8
93.3
94.0
90.2
87.8
90.9
95.0
92.3
95.2
90.5
92.7
94.2
90.2
93.2
97.0
92.5
93.5
91.6
87.8
12
12
12
10
10
12
12
8
10
8
8
8
8
It is known that many quinoline1 or chromene2 containing
compounds exhibit a wide spectrum of pharmacological activi-
ties. To the best of our knowledge, only a few examples3 of het-
eroaromatic rings containing quinoline and chromene in a mole-
cule have been mentioned in the literature, furthermore their
syntheses are all performed in the ordinary organic solvent. It
was reported that chromenoquinolines and their derivatives were
possessing biological and pharmacological activities,4 such as
bacteriostatic activity,5 glucocorticoid modulators,6 anti-inflam-
matory effects,7 and selective progesterone receptor modula-
tors.8 Because of the toxic and volatile nature of many organic
solvents, we investigated the synthesis of these potential active
compounds under environmentally friendly conditions. Particu-
larly, we focused our attention on the use of water as reaction
medium. They were considered very promising and attractive
substitutes for volatile organic solvents and were widely used
in the green chemistry area, since Breslow,9 who showed that hy-
drophobic effects could strongly enhance the rate of several or-
ganic reactions, rediscovered the use of water as a solvent in or-
ganic chemistry in 1980s. There has been growing recognition
that water is an attractive medium for many organic reactions10
because it is less expensive, less dangerous and environment-
friendly. As part of our current studies on the development of
new routes to heterocyclic systems,11 we now report an efficient
and clean synthetic route to chromeno[4,3-b]benzo[ f]quinoline
and quinolino[4,3-b]benzo[ f]quinoline derivatives in aqueous
media catalyzed by TEBAC (triethylbenzyl ammonium chlo-
ride).
O
NH
NH
NH
NH
NH
NH
NH
NH
4-ClC6H4
3,4-Cl2C6H3
2,4-Cl2C6H3
4-FC6H4
4-BrC6H4
4-CH3OC6H4
3-ClC6H4
8
10
12
10
When the reaction of N-benzilidenenaphthalen-2-amine 1
and 4-hydroxycoumarin or 4-hydroxyquinolin-2-one 2 was per-
Figure 1. The crystal structure of the product 3a.
formed in water in the presence of TEBAC at 100 ꢁC, high yields
of chromeno[4,3-b]benzo[ f]quinoline or quinolino[4,3-b]-
benzo[ f]quinoline derivatives were obtained (Scheme 1).
In order to apply this reaction to a laboratory synthesis, var-
ious kinds of N-benzilidenenaphthalen-2-amine and 2 were sub-
jected to form the corresponding chromeno[4,3-b]benzo[ f] qui-
noline or quinolino[4,3-b]benzo[ f]quinoline derivatives 3, and
representative examples are shown in Table 1. All of the N-ben-
Ar
O
OH
Ar
N
CH
X
TEBA
Water
+
N
H
O
X
1
2
3
Scheme 1.
Copyright Ó 2005 The Chemical Society of Japan

Chemistry Letters Vol.34, No.10 (2005)
1317
G. Cruciani, H. Weber, H. Lemoine, A. Derix, C. Weichel, and
M. Clementi, J. Med. Chem., 42, 981 (1999). c) M. J. Chen,
Y. M. Lee, J. R. Sheu, C. T. Hu, and M. H. Yen, J. Pharm. Pharma-
col., 50, 83 (1998).
a) R. Martinez, E. Cortes, R. A. Toscano, and L. J. Alfaro, J. Heter-
ocycl. Chem., 27, 1273 (1990). b) C. Bandyopadhyay, S. K. Ranabir,
R. Partra, and S. Banerjee, J. Chem. Res., 2003, 459. c) E. B. A.
Hafez, M. H. Elnagdi, A. G. A. Elagamey, and F. M. A. A.
El-Taweel, Heterocycles, 26, 903 (1987).
H2O
O
X
Ar
OH
Ar CH
+
O
N
N
H
O
X
3
H2N
Ar
NH2
O
O
+
OH2
Ar
4
5
N. V. Kumar and S. P. Rajendran, Asian J. Chem., 15, 111 (2003).
Y. Liu, Y. Ding, and Y. Liu, Huaxue Yanjiu Yu Yingyong, 7, 430
(1995).
X
O
O
X
6
a) S. W. Elmore, J. K. Pratt, M. J. Coghlan, Y. Mao, B. E. Green,
D. D. Anderson, M. A. Stashko, C. W. Lin, D. Falls, M. Nakane,
L. Miller, C. M. Tyree, J. N. Miner, and B. Lane, Bioorg. Med.
Chem. Lett., 14, 1721 (2004). b) Y. Y. Ku, T. Grieme, P. Raje,
P. Sharma, H. E. Morton, M. Rozema, and S. A. King, J. Org.
Chem., 68, 3238 (2003).
HO
H
N
-H2O
3
X
O
Ar
Scheme 2.
7
8
P. R. Kym, M. E. Kort, M. J. Coghlan, J. L. Moore, R. Tang,
and J. D. Ratajczyk, J. Med. Chem., 46, 1016 (2003).
L. Zhi, C. M. Tegley, B. Pio, J. P. Edward, M. Motamedi, T. D.
Jones, K. B. Marschke, D. E. Mais, B. Risek, and W. T. Schrader,
J. Med. Chem., 46, 4104 (2003).
zilidenenaphthalen-2-amine gave expected products in high
yields and purity. The products 3 were completely characterized
by IR, H NMR, and elemental analyses. The analyses were in
1
9
a) R. Breslow and D. C. Rideout, J. Am. Chem. Soc., 102, 7816
(1980).
agreement with their structures. The IR spectra for 3a exhibited
sharp bands at 3310 cmꢂ1 (NH) and 1657 cmꢂ1 (C=O). The
1H NMR spectrum of 3a exhibited a singlet identified methine
(5.91) along with multiplets (7.28–8.40) for aromatic protons.
The NH proton resonance at 10.18 disappeared after addition
of D2O to the DMSO-d6 solution of 3a. In order to further con-
firm the structure of the product, the X-ray diffraction analysis13
of 3a was carried out.
10 a) R. Breslow, U. Maitra, and D. C. Rideout, Tetrahedron Lett., 24,
1901 (1983). b) R. Breslow, Acc. Chem. Res., 24, 159 (1991).
11 a) X. S. Wang, D. Q. Shi, Y. L. Li, H. Chen, X. Y. Wei, and Z. M.
Zong, Synth. Commun., 35, 97 (2005). b) X. S. Wang, D. Q. Shi,
Y. F. Zhang, S. H. Wang, and S. J. Tu, Chin. J. Org. Chem., 24,
430 (2004).
12 The general procedure is represented as follow: A suspension of a
mixture of N-benzilidenenaphthalen-2-amine 1 (2 mmol), 4-hydroxy-
coumarins or 4-hydroxyquinolin-2-one 2 (2 mmol) and TEBAC
(0.1 g) was stirred in water (10 mL) at 100 ꢁC for several hours. After
completion monitored by TLC, the reaction mixture was allowed to
cool to room temperature. The crystalline power formed recrystal-
lized from DMF and water to give pure 3. 3a: mp >300 ꢁC (Lit.3a,
378–380 ꢁC). IR (KBr, ꢀ, cmꢂ1): 3310, 3056, 1657, 1621, 1588,
1570, 1527, 1511, 1478, 1430, 1404; 1H NMR (DMSO-d6, ꢁ):
5.91 (s, 1H, CH), 7.30 (d, J ¼ 8:8 Hz, 2H, ArH), 7.37–7.40 (m,
4H, ArH), 7.46–7.50 (m, 2H, ArH), 7.64–7.68 (m, 1H, ArH), 7.73
(d, J ¼ 8:8 Hz, 2H, ArH), 7.88 (d, J ¼ 7:6 Hz, 1H, ArH), 7.91–
7.98 (m, 2H, ArH), 8.39 (d, J ¼ 7:2 Hz, 1H, ArH), 10.18 (s, 1H,
NH); Anal. Calcd for C26H16BrNO2: C, 68.74; H, 3.55; N, 3.08%;
Found: C, 68.92; H, 3.54; N, 3.13%. 3k: mp >300 ꢁC; IR (KBr, ꢀ,
cmꢂ1): 3648, 3329, 3064, 1667, 1639, 1621, 1590, 1570, 1531,
1460, 1406; 1H NMR (DMSO-d6, ꢁ): 6.32 (s, 1H, CH), 7.03–7.08
(m, 2H, ArH), 7.26–7.35 (m, 4H, ArH), 7.44–7.51 (m, 3H, ArH),
7.71 (d, J ¼ 8:8 Hz, 1H, ArH), 7.82 (d, J ¼ 8:0 Hz, 1H, ArH),
7.83 (d, J ¼ 8:8 Hz, 1H, ArH), 8.26 (d, J ¼ 8:4 Hz, 1H, ArH),
8.35 (d, J ¼ 8:0 Hz, 1H, ArH), 9.65 (s, 1H, NH), 11.15 (s, 1H,
NH); Anal. Calcd for C26H17ClN2O: C, 76.37; H, 4.19; N, 6.85%.
Found: C, 76.22; H, 4.18; N, 6.90%.
Though the detailed mechanism of the above reaction has
not been clarified yet, the formation of 3 can be explained by
the possible mechanism presented in Scheme 2.
In the further study, we find the product 3a can be obtained
in 82% yield by three-component reaction of 4-bromobenzalde-
hyde, 2-aminonaphthalene, and 2 in water at 100 ꢁC in the pres-
ence of TEBAC.14 This result possibly indicates that the cleav-
age of the C=N bond maybe take place in the mechanism men-
tioned above. But it should be noted that in this three-component
reaction the starting material of solid 4-bromobenzaldehyde al-
ways stays in the bottom of the condenser when the reaction tem-
perature is controlled above 80 ꢁC, which reduces the reaction
yield badly, meanwhile the reaction time is long.
In addition, in order to show the general scope of this reac-
tion, we also tried the reaction of 2 with other Schiff base con-
taining substituented aniline, such as p-toluidine. But we could
not get the expected pyrido[3,2-c]chromene derivative, we think
a possible reason is that the activity of p-toluidine is less than
that of 2-aminonaphthalene.
13 Crystal data for 3a: C26H16BrNO2; Mr ¼ 454:31, orange-yellow
block crystals, 0:59 ꢃ 0:34 ꢃ 0:15 mm3, monoclinic, space group
In conclusion, an efficient green chemistry method for the
synthesis of chromeno[4,3-b]benzo[ f]quinoline and quinolino
[4,3-b]benzo[ f]quinoline derivatives. Compared to other meth-
ods,3 this new method has the advantages of high yields, mild
reaction conditions, easy work-up, inexpensive reagents and
environmentally friendly procedure.
ꢀ
P21=c, a ¼ 7:3681ð8Þ, b ¼ 13:5483ð14Þ, c ¼ 19:662ð3Þ A, ꢂ ¼
Fð000Þ ¼ 920, ꢃ(Mo Kꢄ) = 2.153 mmꢂ1
100:372ð4Þꢁ, V ¼ 1930:7ð4Þ A , Z ¼ 4, Dcalcd ¼ 1:563 gꢄcmꢂ3
.
. Intensity data were
ꢀ 3
collected on Rigaku Mercury diffractometer using ! scan mode
with 3:01ꢁ < ꢅ < 27:48ꢁ. 4412 unique reflections were measured
and 3827 reflections with I > 2ꢆðIÞ were used in the refinement.
Structure solved by direct methods and expanded using Fourier
techniques. R ¼ 0:0446, wR ¼ 0:0968.
We are grateful to the Foundation (04KJB150139) of the
Education Committee of Jiangsu Province for financial support.
14 The general three-component reaction procedure for 3a is described
as follows: A suspension of a mixture of 4-bromobenzaldehyde
(2 mmol), 2-aminonaphthalene (2 mmol), 4-hydroxycoumarin 2
(2 mmol), and TEBAC (0.1 g) was stirred in water (10 mL) at
100 ꢁC for 24 h. The reaction mixture was allowed to cool to room
temperature. The solid was purified by column chromatogaraphy
on silica gel (200–300 mesh) using petroleum ether (bp 60–
90 ꢁC)–acetone (1:1) as eluent to give 3a in 82% yield.
References and Notes
1
A. Arcadi, M. Chiarini, S. D. Giuseppe, and F. Marinelli, Synlett,
2003, 203.
2
a) H. Horino, T. Mimura, K. Kagechika, M. Ohta, H. Kubo, and
M. Kitagawa, Chem. Pharm. Bull., 46, 602 (1998). b) R. Mannhold,
Published on the web (Advance View) August 28, 2005; DOI 10.1246/cl.2005.1316