Dual behavior of 2-tetralone: A new approach for the synthesis of 5-aryl-7,8,13,14-tetrahydrodibenzo[a,i]phenanthridine

Article abstract of DOI:10.1002/jhet.191

(Chemical Equation Presented) The one-pot reaction of 2-tetralone with ammonium acetate and substituted benzaldehydes affords in a good yield of 5-aryl-7,8,13,14-tetrahydrodibenzo[a,i]phenanthridine or 2,4-diaryl-6,7-benzo-3- azabicyclo[3.3.1]nonan-9-one.

Full text of DOI:10.1002/jhet.191

1142
Dual Behavior of 2-Tetralone: A New Approach for the Synthesis
Vol 46
of 5-Aryl-7,8,13,14-tetrahydrodibenzo[a,i]phenanthridine
Kulathu Iyer Sathiyanarayanan,a* Natesan Sundaramurthy Karthikeyan,a
Paduthapillai Gopal Aravindan,b Seenan Shanthi,a Ravindranath S. Rathore,c
and Chang Woo Leed
aChemistry Division, School of Science and Humanities, VIT University, Vellore 632 014, India
bPhysics Division, School of Science and Humanities, VIT University, Vellore 632 014, India
cSchool of Biotechnology, Devi Ahilya University, Indore 452 001, India
dCollege of Environment and Applied Chemistry, Kyung Hee University, Yongin 449-701, Korea
*E-mail: sathiya_kuna@hotmail.com
Received February 16, 2009
DOI 10.1002/jhet.191
Published online 2 November 2009 in Wiley InterScience (www.interscience.wiley.com).
The one-pot reaction of 2-tetralone with ammonium acetate and substituted benzaldehydes affords in
a good yield of 5-aryl-7,8,13,14-tetrahydrodibenzo[a,i]phenanthridine or 2,4-diaryl-6,7-benzo-3-azabicy-
clo[3.3.1]nonan-9-one. The course of the reaction seems to be dictated by the position of the
substituents present on the benzaldehyde ring.
J. Heterocyclic Chem., 46, 1142 (2009).
INTRODUCTION
overall yield [15]. In this study, we found that one-step
reaction of benzaldehyde or 4-substituted benzaldehydes,
ammonium acetate, and 2-tetralone gave 5-aryl-
7,8,13,14-tetrahydrodibenzo[a,i]phenanthridine (Scheme
1). On the other hand, the one-step reaction of 2-substi-
tuted benzaldehydes, ammonium acetate, and 2-tetralone
gave 2,4-diaryl-6,7-benzo-3-azabicyclo[3.3.1]nonan-9-
ones (Scheme 2).
Phenanthridines, an important class of heterocyclic
compounds in medicinal chemistry, are attractive syn-
thetic targets due to their widespread occurrence in
nature and broad range of biological activities, including
anti-tumor and anti-viral activities [1–7]. Phenanthridine
derivatives exhibit interesting pharmacological proper-
ties related to the planarity of the system. Benzophenan-
thridines are reported as compounds with topoisomerase
I-targeting activity and cytotoxicity [8].
In spite of their importance, only very few of them
involve less than a few steps [16,20–22]. On the contrary,
this study involves single step. Hence, the authors wish to
explore a new and more versatile synthetic route for
5-aryl-7,8,13,14-tetrahydrodibenzo [a,i]phenanthridine.
The preparation of 5-phenyltetrahydrodibenzo[a,i]phe-
nanthridine (4) and 2,4-diaryl-6,7-benzo-3-azabicy-
clo[3.3.1]nonan-9-one (5) was accomplished by the pro-
cedure reported by Noller and Baliah [23] through a
simple three-compound reaction involving ammonium
acetate (2), benzaldehyde (1), and 2-tetralone (3). We
tried to carry out the Mannich reaction as reported in
the article. However, we ended up with 5-aryl-
7,8,13,14-tetrahydrodibenzo[a,i]phenanthridine in the
case of parent benzaldehyde and para-substituted benzal-
dehydes. However, ortho-substituted benzaldehydes
yielded 2,4-diaryl-6,7-benzo-3-azabicyclo[3.3.1]nonan-9-
ones. The two reactions are not competing with each
In addition, the high charge mobility of this heterocy-
clic system provides pronounced photoconducting, opto-
electrical switching, and photovoltaic properties [9–11],
which are key features in the field of dye lasers and
electroluminescence [12,13]. Therefore, during the last
few years, phenanthridines have gained much attention
because of their promising applications in the develop-
ment of optical materials, information recordings, such
as, holography, lithographic plates for printing, and elec-
tric equipment [14].
The literature preparations of the phenanthridine ring
system have disadvantages, such as, lengthy syntheses,
low yields, and structurally complicated precursors
[8,15–20]. Even a synthesis involving a few steps from
simple precursors such as formaldehyde and 2-methyl-
benzonitrile affords benzo[c]phenanthridine in a 6%
C
V
2009 HeteroCorporation

November 2009
Dual Behavior of 2-Tetralone: A New Approach for the Synthesis
of 5-Aryl-7,8,13,14-tetrahydrodibenzo[a,i]phenanthridine
1143
Scheme 1
give azabicyclo[3.3.1]nonan-9-one. This is due to the
steric hindrance in the ortho-substituted benzaldehydes
and it is clearly shown in the mechanism. The aldimine
formation in ortho-substituted benzaldehydes is impossi-
ble. Once it is able to form the aldimine then only the
formation of phenanthridine is possible otherwise keto
form will react with benzaldehyde and ammonium ace-
tate to form azabicyclo[3.3.1]nonan-9-one.
other. We are getting either phenanthridine or azabicy-
clo[3.3.1]nonan-9-one only. The product formation is
exclusive. We are not getting the mixture of products.
In Mannich reaction, the active methylene group in the
2-tetralone took part, whereas in the other reaction the
enol form of 2-tetralone occurred. This reaction was
found to be very easy and useful for synthesizing phen-
anthridine because other methods now being used are
cumbersome and involve more steps (Table 1).
The mechanism for the formation of 2,4-diaryl-6,7-
benzo-3-azabicyclo[3.3.1]nonan-9-one is already well
documented [23]. We are proposing the following mecha-
nism for the formation of phenanthridine derivative. The
mechanism proposed is similar to the one reported for the
reaction between tetralone and nitrile [20]. All the struc-
tures were confirmed by single crystal X-ray analysis.
Even the structures are also confirmed by single crys-
tal X-ray analysis.
In conclusion, the authors developed two short, dis-
tinct, and complementary methods for the synthesis of
various 5-aryl-7,8,13,14-tetrahydrodibenzo[a,i]phenan-
thridine and 2,4-diaryl-6,7-benzo-3-azabicyclo[3.3.1]-
nonan-9-one with excellent yield. We believe that the
Scheme 2
The parent and para-substituted benzaldehydes give
phenanthridine, and ortho-substituted benzaldehydes
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1144
K. I. Sathiyanarayanan, N. S. Karthikeyan, P. G. Aravindan,
S. Shanthi, R. S. Rathore, and C. W. Lee
Vol 46
Table 1
2.97 (m, 4H), 3.48 (s, 1H, NH), 3.81–4.01 (s, 6H), 4.52–4.55
(d, 1H), 5.75 (d, 1H), 6.66–7.60 (m, 12H).
Reaction of 2-tetralone with benzaldehydes.
Aldehyde
Product
Yield
REFERENCES AND NOTES
Benzaldehyde (1a)
4a
4b
4c
5d
5e
86%
74%
76%
68%
65%
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EXPERIMENTAL
General procedure. 0.2M of respective benzaldehyde was
treated with 0.1M of 2-tetralone and 0.1M of ammonium ace-
tate in 15 mL of ethanol. The mixture was gently warmed in a
water bath until the color changed to orange and kept aside for
overnight at room temperature. The completion of the reaction
was identified with TLC. The solid obtained was separated and
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Spectral data
5-Phenyl-7,8,13,14-tetrahydrodibenzo[a,i]phenanthridine
(4a). Crystal; mp 170ꢀC; IR (KBr): 3057, 2833, 1606, 1549,
1
1425, 1396, 1245 cmꢁ1; H NMR (CDCl3, 400 MHz): d 2.76–
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3.20 (m, 8H), 7.00–7.53 (m, 13H); 13C NMR (CDCl3, 100
MHz): d 24.79, 27.41, 29.53, 31.38,124.68, 125.60, 126.30,
126.92, 127.25, 127.64, 127.75, 128.33, 128.68, 129.62,
129.80, 130.58, 132.77, 133.04, 136.99, 138.68, 139.43,
139.67, 140.29, 142.06, 145.65, 153.95, 158.08.
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Satsuki, M.; Shinpo, A.; Tokito, S.; Fujikawa, H.; Noda, K.; Miura,
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5-(p-Chlorophenyl)-7,8,13,14-tetrahydrodibenzo[a,i]phenan-
thridine (4b). Crystal; mp 178ꢀC; IR (KBr): 3032, 2833, 1605,
1
1549, 1425, 1358, 1245, 763 cmꢁ1; H NMR (DMSO-d6, 300
MHz): d 2.54 (m, 2H), 2.74–3.26 (m, 6H), 7.12–7.61 (m,
12H); MS (LC-MS): m/z ¼ 394 (Mþ).
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Tetrahedron Lett 2009, 50, 590.
5-(p-Methoxyphenyl)-7,8,13,14-tetrahydrodibenzo[a,i]phe-
nanthridine (4c). Crystal; mp 174ꢀC; IR (KBr) 3032, 2833,
1
1606, 1549, 1425, 1358, 1245 cmꢁ1; H NMR (DMSO-d6, 400
MHz): d 2.50–3.08 (m, 8H), 3.78 (s, 3H), 6.86–6.91 (m, 4H),
7.29–7.32 (m, 8H); MS (LGC-MS): m/z ¼ 390 (Mþ).
2,4-Di(o-chlorophenyl)-6,7-benzo-3-azabicyclo[3.3.1]nonan-
9-one (5d). Crystal; mp 230ꢀC; IR (KBr): 3309, 2846, 1711,
[20] Herrera, A.; Alvarez, R. M.; Chioua, M.; Chatt, R.; Chioua,
R.; Sanchez, A.; Almy, J. Tetrahedron 2006, 62, 2799.
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C. Bioorg Med Chem 2004, 12, 3943.
1423, 1243, 751 cmꢁ1 1H NMR (DMSO-d6, 300 MHz): d
;
2.92–3.15 (m, 4H), 3.56 (s, 1H, NH), 4.59–4.62 (d, 1H), 5.73–
5.76 (d, 1H), 6.74–7.78 (m, 12H).
2,4-Di(o-methoxyphenyl)-6,7-benzo-3-azabicyclo[3.3.1]nonan-
9-one (5e). Crystal; mp 220ꢀC; IR (KBr) 3313, 2832, 1715,
[22] Mehta, K. B.; Kumamoto, K.; Yanagisawa, K.; Kotsuki, H.
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1491, 1243 cmꢁ1
;
1H NMR (DMSO-d6, 300 MHz): d 2.48–
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet