Facile, ONE-POT, THREE-component synthesis of benzo[a]NAPHTHACENE-8,13- DIONES

Article abstract of DOI:10.1080/00397911.2010.524961

One-pot synthesis of 14-aryl-14H-7-oxa-benzo[a]naphthacene-8,13-diones was developed by the reaction of 2-hydroxynaphthalene-1,4-dione, aromatic aldehydes, and 2-naphthol in the presence of acetic acid. The structures of these compounds were identified by elemental analyses, infrared, 1H NMR, and mass.Copyright Taylor & Francis Group, LLC.

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Facile, One-Pot, Three-Component
Synthesis of Benzo[a]naphthacene-8,13-
diones
Vakiti Srinivas a & Vedula Rajeswar Rao a
a Department of Chemistry, National Institute of Technology,
Warangal, India
Accepted author version posted online: 20 Jul 2011.Published
online: 06 Oct 2011.
To cite this article: Vakiti Srinivas & Vedula Rajeswar Rao (2012) Facile, One-Pot, Three-
Component Synthesis of Benzo[a]naphthacene-8,13-diones, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 42:3, 388-393, DOI:
10.1080/00397911.2010.524961
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Synthetic Communications1, 42: 388–393, 2012
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.524961
FACILE, ONE-POT, THREE-COMPONENT SYNTHESIS
OF BENZO[a]NAPHTHACENE-8,13-DIONES
Vakiti Srinivas and Vedula Rajeswar Rao
Department of Chemistry, National Institute of Technology, Warangal, India
GRAPHICAL ABSTRACT
Abstract One-pot synthesis of 14-aryl-14H-7-oxa-benzo[a]naphthacene-8,13-diones was
developed by the reaction of 2-hydroxynaphthalene-1,4-dione, aromatic aldehydes, and
2-naphthol in the presence of acetic acid. The structures of these compounds were identified
1
by elemental analyses, infrared, H NMR, and mass.
Keywords Benzo[a]naphthacene-8,13-diones; lawsone; 2-naphthol
INTRODUCTION
The chemistry of quinones is of considerable interest, because this class of com-
pounds includes many natural products and numerous important synthetic
products.[1,2] Quinone derivatives may be toxic to cells by a number of
mechanisms[3,4] including redox arylation, intercalation, induction of DNA strand
breaks, generation of free radicals, and alkylation via quinone methide formation.[5]
As a consequence, the molecular frameworks of a great number of pharmaceuticals
and biologically important compounds contain a quinone moiety. Their importance
in pharmocological activity is also attributed to the inhibition of special proteins,
such as bacterial topoisomerase II-DNA gyrase (antibacterial),[6] mammalian topoi-
somerases I and II (antitumor),[7] and HIV-1 integrase and proteinase (antiviral).[8]
Representative examples of this class of compounds are well-known anticancer drugs
of the anthracycline series-doxorubicine and mitoxanthrone. The action of these
compounds is believed to occur via topoisomerase II inhibition.[7]
Compounds containing the quinone group represent an important class of bio-
logically active molecules that are widespread in nature.[9] However, to the best of
Received August 4, 2010.
Address correspondence to V. Rajeswar Rao, Department of Chemistry, National Institute of
Technology, Warangal 506 004, A.P., India. E-mail: vrajesw@yahoo.com
388

BENZO[a]NAPHTHACENE-8,13-DIONES
389
our knowledge, there are no reports on the synthesis of 14H-7-oxa-benzo
[a]naphthacene-8,13-dione ring systems. The development of multicomponent reac-
tions (MCRs) designed to produce elaborate biologically active compounds
has become an important area of research in organic, combinatorial, and medicinal
chemistry.[10–13] The MCR strategy offers significant advantages over convent-
ional linear synthesis because of its flexible, convergent, and atom-efficient nat-
ure.[14,15] In continuation of our earlier work on the synthesis of heterocyclic
quinones,[16,17] we report
a one-pot synthesis of 14-aryl-14H-7-oxa-benzo
[a]naphthacene-8,13-dione.
RESULTS AND DISCUSSION
The one-pot, three-component reaction of lawsone 1 with various aromatic
aldehydes 2 in the presence of 2-naphthol 3 proceeded rapidly in glacial acetic acid
at 60–80 ꢀC to afford 14-aryl-14H-7-oxa-benzo[a]naphthacene-8,13-dione 4 in good
yields (Scheme 1).
A plausible mechanism for the formation of products 4 is proposed in
Scheme 2. Acid-catalyzed condensation between 1 and 2 will give an intermediate
5. The intermediate 5 on reaction with 3 gave another intermediate 6. The intermedi-
ate formed in situ 6 undergoes cyclization to give the final product 4. The newly pre-
pared compounds revealed the presence of 1,4-quinone moiety by the reduction and
aerial oxidation test with Zn=AcOH. The structures of products 4 were established
1
on the basis of their elemental analyses, infrared (IR), H and 13C NMR, and mass
1
spectral data. The H NMR spectrum of 4a exhibited one singlet for CH of pyranr-
ine at d 6.04 ppm and a multiplet observed at d 7.52–8.28 ppm was assigned to aro-
matic protons. The proton decoupled 13C NMR spectrum of 4a displayed 27 distinct
resonance signals, in agreement with the proposed structure. The quinone carbonyls
appeared downfield at 182.0 and 182.9 respectively. The mass spectrum of 4a showed
a molecular ion peak at m=z 434 [M þ H] (Table 1).
Scheme 1. One-pot, three-component reaction of 2-hydroxy-1,4-naphthoquinone, aromatic aldehyde, and
2-naphthol.

390
V. SRINIVAS AND V. R. RAO
Scheme 2. Mechanism of the reaction.
Table 1. One-pot, three-component reaction of 2-hydroxy-1,4-naphthoquinone,
aromatic aldehyde, and 2-naphthol
Entry
Ar
Yield (%)a
4a
4b
4c
4d
4e
4f
m-Nitrophenyl
p-Chlorophenyl
p-Methylphenyl
94
92
95
93
91
96
90
93
96
p-Methoxyphenyl
o-Hydroxy-m-methoxyphenyl
m,m,p-Trimethoxyphenyl
N,N-Dimethylaminophenyl
Phenyl
4g
4h
4i
2-Naphthyl
aIsolated yields.
CONCLUSION
In conclusion, we have carried out a three-component synthetic method for
preparation of some benzo[a]naphthacene-8,13-diones. This method has several
advantages such as readily available starting materials, easy workup, and good yields
of the products.
EXPERIMENTAL
Melting points were determined in open capillaries with a Cintex melting-point
apparatus (Mumbai, India). Melting points are uncorrected, and CHNS analysis was
done on a Carlo Erba EA 1108 automatic elemental analyzer. The purity of the com-
pounds was checked by thin-layer chromatographic (TLC) plates (E. Merek, Mumbai,
India), and IR spectra (KBr) were recorded on a Bruker WM-4(X) spectrometer (577
model). 1H NMR spectra were recorded on a Bruker WM 400-MHz spectrometer in d
ppm using tetramethylsilane (TMS) as internal standard. Mass spectra (EI-MS) were
determined on a Perkin-Elmer (SCIEX API-2000, ESI) instrument at 12.5 eV.

BENZO[a]NAPHTHACENE-8,13-DIONES
391
General Procedure for the Synthesis of 14-Aryl-14H-
7-oxa-benzo[a]naphthacene-8,13-dione (4)
A mixture of lawsone (1 mmol), aromatic aldehyde (1 mmol), and 2-naphthol
(1 mmol) was stirred at 60–80 ꢀC for 5 h. The progress of the reaction was monitored
by TLC (20% methanol in chloroform). After completion of the reaction, the solid
separated was filtered and washed with water. The crude product was purified by
recrystallization from ethanol to give 4.
Data
14-(3-Nitrophenyl)-14H-7-oxa-benzo[a]naphthacene-8,13-dione (4a). Yel-
low powder, mp > 300 ꢀC; IR (KBr) (nmax=cmꢁ1): 3070 (C-H), 1698 (C O), 1650
=
1
=
=
(C O), 1527 (C C); H NMR (400 MHz, DMSO-d6) (d ppm): 6.04 (1H, s, CH of
pyran ring), 7.52–8.28 (14H, m, ArH). Anal. calcd. for C27H15NO5: C, 74.82; H,
3.49; N, 3.23%. Found: C, 72.77; H, 3.45; N, 3.19%.
14-(4-Chlorophenyl)-14H-7-oxa-benzo[a]naphthacene-8,13-dione (4b). Yel-
low solid, mp > 300 ꢀC; IR (KBr) (nmax=cmꢁ1): 2911 (C-H), 1703 (C O), 1665
=
1
=
=
(C O), 1576 (C C); H NMR (400 MHz, DMSO-d6) (d ppm): 5.83 (1H, s, CH of
pyran ring), 7.26–8.27 (14H, m, ArH). Anal. calcd. for C27H15ClO3: C, 76.69; H,
3.58%. Found: C, 76.61; H, 3.52%.
14-(4-Methylphenyl)-14H-7-oxa-benzo[a]naphthacene-8,13-dione (4c). Orange
powder, mp > 300 ꢀC; IR (KBr) (nmax=cmꢁ1): 2914 (C-H), 1703 (C O), 1665 (C O),
=
=
1
=
1575 (C C); H NMR (400 MHz, DMSO-d6) (d ppm): 2.13 (3H, s, CH3), 5.76 (1H, s,
CH of pyran ring), 6.99–8.27 (14H, m, ArH). Anal. calcd. for C28H18O3: C, 83.57; H,
4.51%. Found: C, 83.52; H, 4.48%.
14-(4-Methoxylphenyl)-14H-7-oxa-benzo[a]naphthacene-8,13-dione (4d). Yel-
low powder, mp > 300 ꢀC; IR (KBr) (nmax=cmꢁ1): 2931 (C-H), 1702 (C O), 1666
=
(C O), 1580 (C C); 1H NMR (400 MHz, DMSO-d6) (d ppm): 3.69 (3H, s,
OCH3), 5.97 (1H, s, CH of pyran ring), 6.75 (2H, d, J ¼ 8.8 Hz, ArH), 7.13 (2H,
d, J ¼ 8.8 Hz, ArH), 7.75–7.98 (10H, m, ArH). Anal. calcd. for C28H18O4: C,
80.37; H, 4.34%. Found: C, 80.31; H, 4.39%.
=
=
14-(2-Hydroxy-3-methoxylphenyl)-14H-7-oxa-benzo[a]naphthacene-8,
13-dione (4e). Yellow powder, mp > 300 ꢀC; IR (KBr) (nmax=cmꢁ1): 2938 (C-H),
1
=
=
=
1683 (C O), 1656 (C O), 1575 (C C); H NMR (400 MHz, DMSO-d6) (d ppm):
3.88 (3H, s, OCH3), 5.75 (1H, s, CH of pyran ring), 6.68–6.70 (1H, m, ArH),
6.96–7.07 (2H, m, ArH), 7.78–8.07 (10H, m, ArH). Anal. calcd. for C28H18O5: C,
77.41; H, 4.18%. Found: C, 77.36; H, 4.39%.
14-(3,3,4-Trimethoxylphenyl)-14H-7-oxa-benzo[a]naphthacene-8,13-dione
(4f). Yellow powder, mp > 300 ꢀC; IR (KBr) (nmax=cmꢁ1): 2937 (C-H), 1708 (C O),
=
1
=
=
1673 (C O), 1592 (C C); H NMR (400 MHz, DMSO-d6) (d ppm): 3.63 (9H, s,
OCH3), 5.98 (1H, s, CH of pyran ring), 6.52 (2H, s, ArH), 7.77–7.99 (10H, m,
ArH). Anal. calcd. for C30H22O6: C, 75.30; H, 4.63%. Found: C, 75.25; H, 4.69%.

392
V. SRINIVAS AND V. R. RAO
14-(4-N,N-Dimethylaminophenyl)-14H-7-oxa-benzo[a]naphthacene-8,13-
dione (4g). Brown powder, mp > 300 ꢀC; IR (KBr) (nmax=cmꢁ1): 3069 (C-H), 1693
1
=
=
=
(C O), 1656 (C O), 1587 (C C); H NMR (400 MHz, DMSO-d6) (d ppm): 2.50
(6H, s, N-CH3), 3.95 (1H, s, CH of pyran ring), 6.78–8.10 (14H, m, ArH). Anal.
calcd. for C29H21NO3: C, 80.72; H, 4.91; N, 3.25%. Found: C, 80.65; H, 3.19; N,
3.20%.
14-Phenyl-14H-7-oxa-benzo[a]naphthacene-8,13-dione (4h). Orange pow-
der, mp > 300 ꢀC; IR (KBr) (nmax=cmꢁ1): 3021 (C-H), 1697 (C O), 1654 (C O),
=
=
1
=
1571 (C C); H NMR (400 MHz, DMSO-d6) (d ppm): 5.81 (1H, s, CH of pyran
ring), 7.08–8.28 (15H, m, ArH). Anal. calcd. for C27H16O3: C, 83.49; H, 4.15%.
Found: C, 83.41; H, 4.12%.
14-(2-Naphthyl)-14H-7-oxa-benzo[a]naphthacene-8,13-dione (4i). Orange
powder, mp > 300 ꢀC; IR (KBr) (nmax=cmꢁ1): 2918 (C-H), 1673 (C O), 1636 (C O),
=
=
1
=
1574 (C C); H NMR (400 MHz, DMSO-d6) (d ppm): 5.99 (1H, s, CH of pyran
ring), 7.40–8.31 (17H, m, ArH). Anal. calcd. for C31H18O3: C, 84.92; H, 4.14%.
Found: C, 84.91; H, 4.10%.
ACKNOWLEDGMENT
We thank the University Grants Commission, New Delhi [F. no. 32-201=2006
(SR)] for financial support.
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