Synthesis of 1 -(phenylsulfanyl/phenoxy)-3H-naptho[1,2,3-de]quinoline-2,7- diones

Article abstract of DOI:10.1002/hc.20399

A convenient method is devised to synthesize 1-(phenylsulfanyllphenoxy)-3 H-naptho[1,2,3-de]quinoline-2,7-dione analogs in high yield for the first time by condensation of 2-bromo-N-(9,10-dixo-dihydro-anthracen-1-yl)-acetamide with benzenethiol/phenol usi

Full text of DOI:10.1002/hc.20399

Heteroatom Chemistry
Volume 19, Number 2, 2008
Synthesis of 1-(Phenylsulfanyl/Phenoxy)-3H-
naptho[1,2,3-de]quinoline-2,7-diones
Jagan Reddy Etukala1 and J. S. Yadav2
1College of Pharmacy and Pharmaceutical Sciences, Florida A&M University,
Tallahassee, FL 32307
2Indian Institute of Chemical Technology, Organic Chemistry Division-I, Hyderabad 500 007, India
Received 7 July 2006; revised 3 April 2007
F-inhibition assays [4]. Also, multidrug resistance to
ABSTRACT: A convenient method is devised to syn-
antitumor agents, which are structurally dissimilar
thesize 1-(phenylsulfanyl/phenoxy)-3H-naptho[1,2,3-
and having different intracellular targets, is the
de]quinoline-2,7-dione analogs in high yield for
major problem in cancer therapy. The multidrug
the first time by condensation of 2-bromo-N-(9,10-
resistance phenomenon is associated with the
dixo-dihydro-anthracen-1-yl)-acetamide with ben-
presence of membrane proteins, which belong to
ꢀ
C
zenethiol/phenol using potassium carbonate.
2008
the ATP-binding cassette family transporters that
are responsible for the active drug efflux leading
to the decreased intracellular accumulation [4].
The prolonged clinical use of chemotherapeutic
agents often causes the appearance of multidrug
resistance toward numerous antitumor compounds
[6]. This effect currently constitutes one of the
major problems in clinical chemotherapy and has
not yet been successfully solved. Many efforts have
been directed toward the search for new benzan-
thone analogs, anthracenedione derivatives with
increased effectiveness against multidrug resistance
tumor cell lines. The majority of DNA-intercalating
anticancer drugs possess linear or angular poly-
cyclic chromophores. An increasing number of
examples of “fused” tetracyclic systems have been
reported, including the azonafides 3 [7,8], imida-
zoacridones 4 [9–11], pyrimido[5,6,1-de]acridines
Wiley Periodicals, Inc. Heteroatom Chem 19:221–
227, 2008; Published online in Wiley InterScience
(www.interscience.wiley.com). DOI 10.1002/hc.20399
INTRODUCTION
Respiratory syncytial virus (RSV) infections occur
all over the world, and each year RSV infections
cause more than 125,000 hospitalizations and about
2500 deaths. RSV infects nearly all children by age 2
years, and it causes considerable illness and death in
certain high-risk pediatric populations. Historically,
treatment for RSV has been symptomatic, and
developing a safe and effective vaccine has been a
challenge. Therefore, research efforts have turned to
passive immunization as the best option to control
RSV infections. Benzanthrone analogs [1–3] in
(shown in Fig. 1) 1 and 2 have been reported to have
variable antiviral activity against RSV, with EC50
values ranging from 00.03 to 57 µg/mL in in vitro
5
[12], benzo[e]pyrimidines 6,7 [13,14], and
3(H)-naptho[1,2,3-de]quinoline-2,7-dione 1,2 [15].
Although the presence of a fused heterocyclic ring is
essential to overcome the multidrug resistance, ap-
propriate substituents were necessary to achieve the
optimal results. In the present context, because of
the industrial production of synthetic dyes that may
contain nitrogen analogs of polycyclic aromatic
Correspondence to: Jagan Reddy Etukala; e-mail: jaganreddy.
etukala@famu.edu.
Contract grant sponsor: Council of Scientific & Industrial
Research, New Delhi, India.
c
ꢀ
hydrocarbons,
benzo[de]anthracen-7-one
[16]
2008 Wiley Periodicals, Inc.
221

222 Etukala and Yadav
FIGURE 1 Examples of fused tetracyclic systems.
(benzanthrone) derivatives are interesting com-
pounds owing to their excellent color characteristics
and high photostability [17]. They have been widely
used as dyes for polymers [18], textiles [19], daylight
fluorescent pigments [20], and laser dyes [21].
The main aim of the search for new structures
within the mentioned groups is not only to develop
novel synthetic compounds with antiviral and anti-
tumor activities but also to overcome the major un-
desirable properties of related anthracycline antibi-
otics, their cytotoxicity (peroxidating activity), and
the ability to induce resistance. Although the ratio-
nale for the design of nonperoxidating compounds
has been recently proposed, the clear concepts for
the development of agents active on resistant tumor
cells are still lacking. The synthesis of novel struc-
tural types of benzanthrones, anthracenedione, acri-
dine, and their analogs could be a way to find the
desired leads.
in 9 and the carbonyl carbon in 13 allows the re-
giospecific introduction of a wide range of phenols
and benzenethiols, bearing both electron donor and
electron-withdrawing substituents.
In this paper, we describe the synthe-
sis of 1-(phenylsulfanyl/phenoxy)-3H-naptho[1,2,3-
de]quinoline-2,7-dione derivatives, which are mod-
ified with an additional quinolinone ring incorpo-
rated into the chromophore. A series of compounds
bearing [(substituted phenylsulfanyl/phenoxy)] side
chain at position 1 to the chromophore moiety
have been obtained. These derivatives are struc-
turally related to the antitumor agent benzanthrone
and mitoxantrone. The presence of phenylsulfanyl/
phenoxy side chain could modify the physio-
chemical properties and solubility of the above-
mentioned derivatives and enhance their cytotoxic
activity. Therefore, 1-(phenylsulfanyl/phenoxy)-3H-
naptho[1,2,3-de]quinoline-2,7-dione analogs have
been synthesized.
In this section, for the first time we report
the synthesis of 1-(phenylsulfanyl/phenoxy)-3H-
naptho[1,2,3-de]quinoline-2,7-dione from easily
accessible 2-aminoanthraquinone. As a result of our
studies, we found a heterocyclization method to
synthesize a series of 1-(phenylsulfanyl/phenoxy)-
3H-naptho[1,2,3-de]quinoline-2,7-dione using mild
basic conditions. The synthetic pathways leading
RESULTS AND DISCUSSION
Although many methods for the synthesis of ben-
zanthrones have already been published, no one has
used the strategy adopted in this work. Our strategy
has the following advantages: (i) It is easier to intro-
duce the substituent at the first position of the ben-
zanthrone ring. (ii) The reactivity of the β-carbon
SCHEME 1
Heteroatom Chemistry DOI 10.1002/hc

Synthesis of 1-(Phenysulfanyl/Phenoxy)-3H-naptho[1,2,3-de]quinoline-2,7-diones 223
SCHEME 2
to 1-(phenylsulfanyl/phenoxy)-3H-naptho[1,2,3-de]-
quninoline-2,7-dione derivatives are shown in
Schemes 1 and 2. The formation of the compounds
(Table 1, entries 11a–i) can be rationalized in terms
of the reaction of 2-aminoanthraquinone in N,N-
dimethylformaide and 1,4-dixane in the ratio of 1:1
with bromoacetyl bromide that afford (2-bromo-N-
(9,10-dixo-dihydro-anthracen-1-yl)acetamide. This
intermediate compound was further treated with
various benzenethiols and substituted phenols in
the presence of anhydrous potassium carbonate in
acetone to give 1-(phenylsulfanyl)-3H-naptho[1,2,3-
de]quinoline-2,7-dione. Whereas, phenols formed
N-(9,10-dioxo-9,10-dihydro-anthracen-1-yl)-2-phen-
oxy acetamides when further treated with sodium
methoxide in methanol and furnished the desired
product 1-phenoxyl-3H-naptho[1,2,3-de]quinoline-
2,7-dione (Table 2). It is noteworthy that when ben-
zenethiols were allowed to react with 2-bromo-N-
(9,10-dioxo-dihydro-anthracen-1-yl)acetamide, the
CONCLUSION
In conclusion, we have developed a convenient
procedure to obtain new heteropolycycles as 1-
(phenylthio/phenoxy)-3H-naptho[1,2,3-de]quinoline-
2,7-dione, derived from 2-aminoanthraquinone,
thiophenols, and phenols involving the isolation
of
N-(9,10-dioxo-9,10-dihydro-anthracen-1-yl)-2-
phenoxy acetamide intermediates. We hope that the
new benzanthrones described here will contribute to
a combinatorial library of benzanthone derivatives,
and also aim to determine a more potent drug
and its action pathway as a respiratory syncytial
virus and antitumor agent. The evaluation of bi-
ological activity is being investigated and is to be
unraveled.
EXPERIMENTAL
Unless otherwise indicated, all the common reagents
and solvents were used as obtained from commercial
suppliers without further purification. The melting
points were determined on a Mel-Temp 3.0 melting
expected
N-(9,10-dioxo-9,10-dihydro-anthracen-
1-yl)-2-phenylthio acetamides were not isolated,
instead the reaction proceeded on to the next
step and directly yielded cyclized products 1-
(phenylsulfanyl)-3H-naptho[1,2,3-de]quinoline-2,7-
dione. This can be rationalized because the sulfur
atom renders the hydrogen atom of the adjacent
group highly acidic, and a carbanion is formed
readily in the presence of potassium carbonate, thus
facilitating the quinolinone ring formation.
1
point apparatus and uncorrected. H NMR spectra
were determined on a Varian 300 MHz spectrom-
eter, and the chemical shifts are reported in parts
per million (δ, ppm). Tetramethylsilane is used as an
internal standard. Elemental analyses were carried
out by Atlantic Microlab, GA.
TABLE 1 Synthetic Data of 1-(Phenylsulfanyl)-3H-naptho[1,2,3-de]quinoline-2,7-dione (11a–i)
Entry
Amide (9) Ar
Product (11)
Time (h)
Melting Point (◦C)
Yield (%)a
1
2
3
3
4
5
6
7
8
C6H5
11a
11b
11c
11d
11e
11f
11g
11h
11i
12
12
10
11
12
10
11
11
12
223–225
315–317
297–299
201–203
185–187
158–160
261–263
286–288
301–303
95
88
90
87
89
90
92
94
88
2-Cl-C6H4
4-Cl-C6H4
2-F-C6H4
3-F-C6H4
4-F-C6H4
3-CH3O-C6H4
4-CH3O-C6H4
4-CF3-C6H4
aIsolated yields.
Heteroatom Chemistry DOI 10.1002/hc

224 Etukala and Yadav
TABLE 2 Synthetic Data of 1-(Phenoxy)-3H-naptho[1,2,3-de]quinoline-2,7-dione (14a–i)
Entry
Amide (13) Ar
Product (14)
Time (h)
Melting Point (◦C)
Yield (%)a
1
2
3
4
5
6
7
8
9
C6H5
4-CH3CO-C6H4
4-Br-C6H4
14a
14d
14b
14c
14e
14g
14f
12
10
11
11
12
11
10
12
12
196–198
217–219
230–232
239–241
243–245
257–259
266–268
183–185
167–169
92
96
90
85
90
89
91
88
90
4-O2N-C6H4
3-Cl-4-CH3-C6H3
2,4,6-(Br)3-C6H2
2,4,6-(Cl)3-C6H2
3,5-(CF3S)2-C6H3
2,3,4,5,6-F5C6
14h
14i
aIsolated yields.
143.88, 135.94, 135.59, 132.13, 132.36, 131.21,
130.82, 129.80, 129.69, 129.53, 129.43, 128.29,
128.28, 127.62, 124.60, 124.01, 123.17, 121.52,
115.40. Anal. Calcd for C22H13NO2S: C, 74.35; H,
3.69; N, 3.94. Found: C, 74.21; H, 3.57; N, 3.85.
General Procedure
Synthesis of 2-Bromo-N-(9,10-dioxo-9,10-dihydro-
anthracen-1-yl)acetamide (9). To a solution of 2-
aminoanthraquinone (15 g, 67.19 mmol) in a round-
bottom flask, dimethyl formamide (35 mL) and 1,4-
dioxane (35 mL) were added, which was cooled
to 0◦C. Then, bromoacetylbromide (6.44 mL, 73.90
mmol) was slowly added, so that temperature did not
rise to 1◦C. At the end of the addition, the tempera-
ture was maintained at 0◦C for further 15 min, and
then the mixture was stirred for overnight at room
temperature. The contents of the flask were poured
into water (400 mL), and the resulting precipitate
was filtered, washed with water (3 × 100 mL), dried.
Then orange-colored solid was obtained.
Synthesis of N-(9,10-Dioxo-9,10-dihydro-anthracen-
1-yl)-2-phenoxy-acetamide (13a). To
a solution
of 2-bromo-N-(9,10-dioxo-9,10-dihydro-anthracen-
1-yl)-acetamide (547 mg, 1.59 mmol) and phenol
(150 mg, 1.59 mmol) in acetone (10 mL), K2CO3
(439 gm, 3.18 mmol) and KI (26.3 mg, 0.159 mmol)
were added. Then, the reaction mixture was refluxed
for 12 h. After that the reaction mixture was cooled
to room temperature, and acetone was removed on
rotary vapor. It was diluted with water (15 mL)
and neutralized with 10% aqueous hydrochloric acid
(10 mL).The resulting solid was separated through
filtration, washed with water (2 × 20 mL), and dried.
Then, orange-colored solid was obtained.
Yield, 95.13%; mp 188-190◦C; 1H NMR (300
MHz, CDCl3), δ (ppm): 13.10 (s, 1H), 9.10 (d, 1H,
J = 7.5 Hz), 8.40–8.20 (m, 2H), 8.14 (d, 1H, J = 7.5
Hz), 7.85–7.75 (m, 3H), 4.30 (s, 2H).
1
Yield, 90%; mp 187–189◦C; H NMR (300 MHz,
Synthesis of 1-Phenylsulfanyl-3H-naphtho[1,2,3-
de]quinoline-2,7-dione (11a). To
a solution of
CD3OD), δ (ppm) 13.04 (s, NH), 9.10 (d, 1H, J = 7.5
Hz), 8.20–8.40 (m, 3H), 8.10 (d, 1H, J = 7.6 Hz),
7.70–7.90 (m, 4H), 7.60 (d, 1H, J = 7.5 Hz), 7.40 (t,
1H, J = 7.6 Hz), 7.00 (d, 1H, J = 7.5 Hz), 4.30 (s, 2H).
2-bromo-N-(9,10-dioxo-9,10-dihydro-anthracen-1-
yl)-acetamide (547 mg, 1.59 mmol) and benzenethiol
(175 mg, 1.59 mmol) in acetone (10 mL), K2CO3
(439 mg, 3.18 mmol) and KI (26.3 mg, 0.159
mmol) were added. Then, the reaction mixture was
refluxed for 12 h. There after, the reaction mixture
was cooled to room temperature and acetone
was removed on rotary vapor. The brown color
precipitate was diluted with water (15 mL) and
neutralized with 10% aqueous hydrochloric acid
(10 mL). The brown-colored solid was separated
through filtration, washed with water (2 × 20 mL),
and dried.
Synthesis
of
1-Phenoxy-3H-naphtho[1,2,3-
de]quinoline-2,7-dione (14a). A mixture of anhy-
drous methanol (3 mL) and sodium metal (13 gm,
0.54 mmol) was stirred at 0◦C, and the solution of N-
(9,10-dihydro-anthracen-1-yl)-2-phenoxy-acetamide
(100 mg, 0.27 mmol) in methanol (2 mL) was added
to the mixture dropwise at the same temperature
(0◦C). Stirring was continued for another 10 min at
room temperature, and then the reaction mixture
was refluxed for 12 h. The reaction mixture was
cooled to room temperature and poured into ice
cold water (15 mL), and it was neutralized with
10% aqueous hydrochloric acid (10 mL). The
1H NMR (300 MHz, DMSO-d6), δ (ppm): 12.80
(s, NH), 8.20 (d, 2H, J = 6.6 Hz), 8.10 (d, 2H, J = 6.0
Hz), 7.76–7.94 (m, 3H), 7.50 (t, 1H, J = 8.1 Hz), 7.36
(d, 2H, J = 7.2 Hz), 7.15 (d, 2H, J = 6.9 Hz). 13C
NMR (300 MHz, DMSO-d6),: 178.90, 163.84, 148.82,
Heteroatom Chemistry DOI 10.1002/hc

Synthesis of 1-(Phenysulfanyl/Phenoxy)-3H-naptho[1,2,3-de]quinoline-2,7-diones 225
orange-colored solid was filtered, washed with
1-(3-Fluoro-phenylsulfanyl)-3H-naphtho[1,2,3-
de]quinoline-2,7-dione (11e). 1H NMR (300 MHz,
DMSO-d6), δ (ppm): 12.40 (s, 1H, NH), 8.70 (d, 1H,
J = 7.5 Hz), 8.18–8.24 (dd, 2H, J = 1.8, 9.0 Hz), 8.0
(d, 1H, J = 7.2 Hz), 7.74–7.80 (t, 1H, J = 7.5 Hz),
7.60–7.70 (m, 2H), 7.10–7.20 (m, 2H), 7.04–7.08 (d,
1H, J = 8.1 Hz), 6.88–6.96 (m, 1H). 13C NMR (300
MHz, DMSO-d6): 178.90, 163.84, 161.55, 148.82,
143.88, 138.01, 135.59, 132.36, 132.13, 131.21,
130.82, 129.21, 128.82, 128.29, 127.62, 124.60,
124.01, 123.17, 122.87, 121.52, 116.33, 115.40. Anal.
Calcd for C22H12FNO2S: C, 70.76; H, 3.24; N, 3.75.
Found: C, 70.67; H, 3.15; N, 3.66.
water (2 × 20 mL), and dried.
1H NMR (300 MHz, CD3OD), δ (ppm): 12.60
(s, NH, 1H)), 8.20 (d, 2H, J = 6.8 Hz), 8.10
(d, 2H, J = 6.4 Hz), 7.80–8.00 (m, 3H), 7.50 (t,
1H, J = 7.9 Hz), 7.40 (d, 2H, J = 7.5 Hz), 7.20
(d, 2H, J = 7.2 Hz).13C NMR (300 MHz, DMSO-
d6): 178.90, 158.05, 155.53, 154.42,152.76, 136.08,
134.54, 133.13, 132.59, 130.43, 129.08, 129.06,
128.94, 127.83, 125.23, 122.45, 121.67, 120.80,
116.01, 115.98, 113.01, 103.01. Anal. Calcd for
C22H13NO3: C, 77.87; H, 3.86; N, 4.13. Found: C,
77.72; H, 3.75; N, 4.02.
1-(4-Fluoro-phenylsulfanyl)-3H-naphtho[1,2,3-
de]quinoline-2,7-dione (11f). 1H NMR (300 MHz,
DMSO-d6), δ (ppm): 12.40 (s, 1H, NH), 8.60 (d,
1H, J = 7.5 Hz), 8.18 (dd, 1H, J = 2.1, 9.3 Hz),
8.00 (dd, 1H, J = 1.5, 7.2 Hz), 7.70–7.80 (t, 1H,
J = 7.8 Hz), 7.56–7.68 (m, 3H), 7.20–7.30 (m, 2H),
6.90–7.00 (t, 2H, J = 9.0 Hz).13C NMR (300 MHz,
DMSO-d6): 178.90, 164.05, 163.84, 148.82, 143.88,
138.78, 138.72, 135.59, 132.30, 132.13, 131.21,
130.82, 128.29, 127.85, 127.62, 124.60, 124.01,
123.17, 121.52, 115.71, 115.69, 115.40. Anal. Calcd
for C22H12FNO2S: C, 70.76; H, 3.24; N, 3.75. Found:
C, 70.64; H, 3.19; N, 3.63.
1-(2-Chloro-phenylsulfanyl)-3H-naphtho[1,2,3-
de]quinoline-2,7-dione (11b). 1H NMR (300 MHz,
DMSO-d6), δ (ppm): 12.50 (s, NH), 8.66 (d, 1H,
J = 8.1 Hz), 8.18 (d, 1H, J = 7.2 Hz), 8.02 (d, 1H,
J = 7.2 Hz), 7.98 (t, 1H, J = 7.5 Hz), 7.58–7.70 (m,
3H), 7.40 (d, 1H, J = 8.1 Hz), 7.00–7.16 (m, 3H). 13
C
NMR (300 MHz, DMSO-d6): 178.90, 163.84, 143.88,
148.82, 135.65, 135.36, 134.97, 133.25, 132.36,
132.13, 131.21, 130.82, 130.58, 129.00, 128.29,
127.62, 127.41, 124.63, 124.60, 123.17, 121.52,
115.17. Anal. Calcd for C22H12ClNO2S: C, 67.78; H,
3.10; N, 3.59. Found: C, 67.66; H, 3.53; N, 3.41.
1-(4-Chloro-phenylsulfanyl)-3H-naphtho[1,2,3-
de]quinoline-2,7-dione (11c). 1H NMR (300 MHz,
DMSO-d6), δ (ppm): 12.40 (s, NH), 8.60 (d, 1H,
J = 7.5 Hz), 8.12 (d, 1H, J = 9.0 Hz), 7.98 (d, 1H,
J = 7.2 Hz), 7.70 (t, 1H, J = 7.5 Hz), 7.50–7.66 (m,
3H), 7.10 (d, 2H, J = 9.0 Hz), 6.68 (d, 2H, J = 8.7
Hz). 13C NMR (300 MHz, DMSO-d6): 178.90, 163.84,
148.82, 143.88, 135.65, 135.63, 135.59, 135.57,
132.91, 132.36, 132.13, 131.21, 130.82, 128.50,
128.46, 128.29, 127.62, 124.60, 124.01, 123.52,
121.17, 115.40. Anal. Calcd for C22H12ClNO2S: C,
67.78; H, 3.10; N, 3.59. Found: C, 67.63; H, 3.55; N,
3.47.
1-(3-Methoxy-phenylsulfanyl)-3H-naphtho[1,2,3-
de]quinoline-2,7-dione (11g). 1H NMR (300 MHz,
CD3OD), δ (ppm): 12.40 (s, 1H, NH), 8.60 (d, 1H,
J = 7.7 Hz), 8.12 (d, 1H, J = 7.5 Hz), 8.00 (d, 1H, J =
7.2 Hz), 7.70 (t, 1H, J = 7.5 Hz), 7.64–7.50 (m, 3H),
7.24 (t, 1H, J = 7.8 Hz), 6.67–6.80 (m, 2H), 6.60 (d,
1H, J = 7.5 Hz), 3.80 (s, 3H). 13C NMR (300 MHz,
DMSO-d6): 178.90, 163.84, 159.44, 148.82, 143.88,
135.59, 135.49, 132.36, 132.13, 131.21, 130.82,
129.44, 128.42, 128.29, 127.62, 124.60, 124.01,
123.17, 121.52, 118.42, 115.40, 114.42, 55.09. Anal.
Calcd for C23H15NO3S: C, 71.67; H, 3.92; N, 3.63.
Found: C, 71.55; H, 3.81; N, 3.54.
1-(2-Fluoro-phenylsulfanyl)-3H-naphtho[1,2,3-
de]quinoline-2,7-dione (11d). 1H NMR (300 MHz,
DMSO-d6), δ 12.40 (s, NH), 8.70 (d, 1H, J = 7.5 Hz),
8.20 (d, 1H, J = 7.2 Hz), 8.00 (d, 1H, J = 7.5 Hz),
7.80 (t, 1H, J = 7.5 Hz), 7.60–7.75 (m, 3H), 7.10–7.20
(m, 2H), 7.00 (d, 1H, J = 8.0 Hz), 6.80–6.90 (m, 1H).
13C NMR (300 MHz, DMSO-d6): 178.90, 167.57,
163.84, 148.88, 143.82, 138.72, 134.60, 132.36,
132.24, 132.13, 131.21, 130.82, 128.29, 127.62,
125.87, 124.60 123.17, 122.96, 121.52, 118.18,
115.52, 114.42. Anal. Calcd for C22H12FNO2S: C,
70.76; H, 3.24; N, 3.75. Found: C, 70.63; H, 3.17; N,
3.69.
1-(4-Methoxy-phenylsulfanyl)-3H-naphtho[1,2,3-
de]quinoline-2,7-dione (11h). 1H NMR (300 MHz,
CD3OD), δ (ppm): 12.40 (s, 1H, NH), 8.60 (d, 1H,
J = 7.7 Hz), 8.12 (d, 1H, J = 7.5 Hz), 7.98 (d, 1H,
J = 7.2 Hz), 7.70 (t, 1H, J = 7.5 Hz), 7.64–7.50 (m,
3H), 7.20 (d, 2H, J = 9.0 Hz), 6.68 (d, 2H, J = 8.7
Hz), 3.60 (s, 3H). 13C NMR (300 MHz, DMSO-d6):
178.90, 163.84, 161.84, 148.88, 143.82, 138.92,
138.90, 135.59, 132.36, 132.13, 130.82, 131.21,
128.29, 127.62, 126.16, 124.60, 124.01, 123.17,
121.52, 115.40, 114.92, 114.90, 55.26. Anal. Calcd
for C23H15NO3S: C, 71.67; H, 3.92; N, 3.63. Found:
C, 71.59; H, 3.85; N, 3.50.
Heteroatom Chemistry DOI 10.1002/hc

226 Etukala and Yadav
1-(4-Trifluoromethyl-phenylsulfanyl)-3H-naphthao-
[1,2,3-de]quinoline-2,7-dione (11i). 1H-NMR (300
MHz, DMSO-d6): δ (ppm): 12.50 (s, 1H, NH), 8.74
(d, 1H, J = 7.2 Hz), 8.22 (d, 1H, J = 6.9 Hz), 8.04 (d,
1H, J = 7.5 Hz), 7.78 (t, 1H, J = 7.5 Hz), 7.72–7.62
(m, 3H), 7.50 (d, 2H, J = 8.4 Hz), 7.42 (d, 2H,
J = 8.1 Hz). 13C NMR (300 MHz, DMSO-d6):178.90,
163.84, 148.82, 143.88, 139.98, 137.07, 137.05,
135.59, 132.36, 132.13, 131.58, 131.21, 130.82,
128.29, 127.62, 124.60, 124.43, 124.41, 124.14,
124.01, 123.17, 121.52, 115.40. Anal. Calcd for
C23H12F3NO2S: C, 65.24; H, 2.86; N, 3.31. Found: C,
65.17; H, 2.74; N, 3.19.
N-(9,10-Dioxo-9,10-dihydro-anthracen-1-yl)-2-(2,
4,6-trichloro-phenoxy)-acetamide (13g). Yield, 85%;
mp 205–207◦C; 1H NMR (300 MHz, CDCl3), δ (ppm):
13.10 (s, 1H, NH), 9.10 (d, 1H, J = 7.5 Hz), 8.10–8.20
(m, 2H), 8.00 (d, 1H, J = 7.7 Hz), 7.60–7.80 (m, 3H),
7.30 (s, 1H), 7.10 (s, 1H), 4.60 (s, 2H).
2-(3,5-Bis-trifluorosulfanyl-phenoxy)-N-(9,10-dioxo-
9,10-dihydro-anthracen-1-yl-)-acetamide (13h). 1H
NMR (300 MHz, CDCl3), δ (ppm): 13.50 (s, 1H, NH),
8.56 (d, 1H, J = 9.0 Hz), 8.34 (d, 1H, J = 6.0 Hz),
8.24 (d, 1H, J= 7.6 Hz), 8.14 (d, 1H, J = 7.5 Hz),
7.94 (t, 1H, J = 7.5 Hz), 7.80 (t, 1H, J = 7.5 Hz), 7.66
(s, 2H), 7.55 (t, 1H, J = 6.0 Hz), 7.30 (s, 1H), 4.45 (s,
2H).
N-(9,10-Dioxo-9,10-dihydro-anthracen-1-yl)-2-
(4-acetyl-phenoxy)-acetamide (13b). Yield, 92%;
mp 201–203◦C; 1H NMR (300 MHz, CDCl3), δ (ppm):
12.60 (s, NH), 9.20 (d, 1H, J = 7.5 Hz), 8.20–8.30
(m, 2H), 8.10 (d, 1H, J = 7.6 Hz), 7.70–7.90 (m, 3H),
7.60 (d, 1H, J = 8.9 Hz), 7.40 (t, 1H, J = 7.8 Hz),
7.00 (d, 2H, J = 8.7 Hz), 4.30 (s, 2H), 1.40 (s, 3H).
N-(9,10-Dioxo-9,10-dihydro-anthracen-1-yl)-2-
pentafluorophenyloxy-acetamide (13i). Yield, 92%;
mp 224–225◦C; 1H NMR (300 MHz, DMSO-d6), δ
(ppm): 12.60 (s, 1H, NH), 9.00 (dd, 1H, J = 1.2, 9.6
Hz), 8.18–8.22 (m, 1H), 8.12–8.16 (m, 1H), 7.88–7.98
(m, 4H), 4.60 (s, 2H).
N-(9,10-Dioxo-9,10-dihydro-anthracen-1-yl)-2-
(4-bromo-phenoxy)-acetamide (13c). Yield, 92%;
mp 205–207◦C; 1H NMR (300 MHz, CDCl3), δ (ppm):
13.30 (s, 1H, NH), 9.20 (d, 1H, J = 7.5 Hz), 8.40–8.22
(m, 2H), 8.10 (d, 1H, J = 7.5 Hz), 7.85–7.75 (m, 3H),
7.50 (d, 2H, J = 9.0 Hz), 7.06 (d, 2H, J = 8.7 Hz),
4.62 (s, 2H).
1-(4-Acetylhenoxy)-3H-naphtho[1,2,3-de]quinoline-
2,7-dione (14b). 1HNMR: (300 MHz, CDCl3), δ
(ppm): 8.20 (t, 3H, J = 7.8 Hz), 7.60 (m, 4H), 7.50
(t, 2H, J = 7.5 Hz), 7.00 (d, 2H, J = 9.0 Hz), 6.80 (s,
NH), 1.20 (s, 3H). 13C NMR (300 MHz, DMSO-d6):
197.80, 178.90, 157.95, 155.53, 154.42, 152.76,
136.08, 135.46, 134.54, 133.13, 132.59, 130.43,
129.73, 129.71, 128.94, 127.83, 125.23, 122.45,
120.80, 114.91, 114.89, 113.01, 103.01, 26.31. Anal.
Calcd for C24H15NO4: C, 75.58; H, 3.96; N, 3.67.
Found: C, 75.47; H, 3.85; N, 3.58.
N-(9,10-Dioxo-9,10-dihydro-anthracen-1-yl)-2-
(4-nitro-phenoxy)-acetamide (13d). Yield, 86%; mp
1
175–177◦C; H NMR (300 MHz, CD3OD), δ (ppm):
12.90 (s, 1H, NH), 9.40 (d, 1H, J = 7.5 Hz), 8.60–8.40
(m, 2H), 8.30 (d, 1H, J = 7.5 Hz), 8.05–7.90 (m, 3H),
7.80 (d, 2H, J = 8.8 Hz), 7.20 (d, 2H, J = 8.70 Hz),
4.30 (s, 2H).
1-(4-Bromophenoxy)-3H-naphtho[1,2,3-de]quino-
line-2,7-dione (14c). 1HNMR (300 MHz, CDCl3), δ
(ppm): 8.20 (t, 3H, J = 7.8 Hz), 7.80 (m, 3H), 7.60
(d, 1H, J = 8.8 Hz), 7.50 (t, 2H, J = 7.5 Hz), 7.00 (d,
2H, J = 9.0 Hz), 6.80 (s, NH). 13C NMR (300 MHz,
DMSO-d6): 178.90, 155.53, 155.26, 154.42, 152.76,
136.08, 134.54, 133.13, 132.59, 132.15, 132.13,
130.43, 128.94, 127.83, 125.23, 122.45, 121.20,
121.19, 120.80, 114.56, 113.01, 103.01. Anal. Calcd
for C22H12BrNO3: C, 63.18; H, 2.89; N, 3.35. Found:
C, 63.07; H, 2.77; N, 3.28.
2-(3-Chloro-4-methyl-phenoxy)-N-(9,10-dioxo-9,
10-dihydro-anthracen-1-yl)-acetamide (13e). Yield,
1
90%; mp 210–211◦C; H NMR (300 MHz, CDCl3),
δ (ppm): 13.20 (s, 1H, NH), 9.20 (d, 1H, J = 7.5
Hz), 8.40–8.20 (m, 2H), 8.10 (d, 1H, J = 7.5 Hz),
7.84–7.72 (m, 3H), 7.34 (d, 1H, J = 7.2 Hz), 7.10 (d,
1H, J = 1.8 Hz), 6.85 (s, 1H, NH), 4.70 (s, 2H), 2.40
(s, 3H).
1-(4-Nitrophenoxy)-3H-naphtho[1,2,3-de]quino-
line-2,7-dione (14d). 1HNMR (300 MHz, CDCl3), δ
(ppm): 8.20 (t, 3H, J = 7.8 Hz), 7.80 (m, 3H), 7.60
(d, 1H, J = 9.0 Hz), 7.50 (t, 2H, J= 7.5 Hz), 7.00 (d,
2H, J = 9.0 Hz), 6.80 (s, NH). 13C NMR (300 MHz,
DMSO-d6): 178.90, 160.03, 155.53, 154.42, 152.76,
146.17, 136.08, 134.54, 133.13, 132.59, 130.43,
128.94, 127.83, 126.68, 126.64, 125.23, 122.45,
N-(9,10-Dioxo-9,10-dihydro-anthracen-1-yl)-2-(2,
4,6-tribromo-phenoxy)-acetamide (13f). Yield, 83%;
mp 231–233◦C; 1H NMR (300 MHz, CDCl3), δ (ppm):
13.20 (s, 1H, NH), 9.10 (d, 1H, J = 7.5 Hz), 8.20–8.10
(m, 2H), 8.00 (d, 1H, J = 7.5 Hz), 7.80–7.60 (m, 3H),
7.28 (s, 1H), 7.14 (s, 1H), 4.60 (s, 2H).
Heteroatom Chemistry DOI 10.1002/hc

Synthesis of 1-(Phenysulfanyl/Phenoxy)-3H-naptho[1,2,3-de]quinoline-2,7-diones 227
120.80, 120.38, 120.36, 113.01, 103.01. Anal. Calcd
for C22H12N2O5: C, 68.75; H, 3.15; N, 7.29. Found: C,
68.67; H, 3.01; N, 7.18.
1-(Perfluorophenoxy)-3H-naphtho[1,2,3-de]quino-
line-2,7-dione (14i). 1HNMR (CDCl3), δ (ppm): 8.20
(t, 1H, J = 7.8 Hz), 7.60 (m, 4H), 7.50 (t, 2H, J = 7.5
Hz), 7.00 (d, 2H, J = 9.0 Hz), 6.80 (s, NH). 13C
NMR (300 MHz, DMSO-d6): 178.90, 154.42, 152.76,
143.87, 143.30, 143.28, 137.66, 136.08, 135.65,
133.13, 132.59, 132.57, 131.29, 131.27, 130.43,
128.94, 127.83, 125.23, 122.45, 120.80, 111.05,
103.01. Anal. Calcd for C22H8F5NO3: C, 61.55; H,
1.88; N, 3.26. Found: C, 61.47; H, 1.74; N, 3.55.
1-(3-Chloro-4-methyl-phenoxy)-3H-naphtho[1,2,
3-de]quinoline-2,7-dione (14e). 1HNMR (300 MHz,
CDCl3), δ (ppm): 8.20 (t, 3H, J = 7.8 Hz), 7.80 (m,
3H), 7.60 (d, 1H, J = 9.0 Hz), 7.40 (t, 1H, J = 7.5 Hz),
6.80 (s, 1H, NH), 2.35 (s, 3H). 13C NMR (300 MHz,
DMSO-d6): 178.90, 158.00, 155.53, 154.76, 152.42,
136.08, 134.54, 133.13, 132.87, 132.59, 132.54,
130.43, 130.19, 128.94, 127.83, 125.23, 122.45,
120.80, 116.72, 113.63, 113.01, 103.01, 19.90. Anal.
Calcd for C23H14ClNO3: C, 71.23; H, 3.64; N, 3.61.
Found: C, 69.93; H, 3.37; N, 3.28.
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1-(2,4,6-Tribromophenoxy)-3H-naphtho[1,2,3-
de]quinoline-2,7-dione (14f). 1HNMR (CDCl3),
δ (ppm): 8.20 (t, 2H, J = 7.8 Hz), 7.60 (m, 3H),
7.50 (t, 2H, J = 7.5 Hz), 7.00 (d, 2H, J = 9.0 Hz),
6.80 (s, NH). 13C NMR (300 MHz, DMSO-d6):
178.90, 154.70, 154.42, 153.75, 152.76, 136.08,
134.56, 133.85, 133.83, 133.13, 132.59, 130.43,
128.94, 127.83, 125.23, 122.45, 120.80, 119.60,
116.22, 116.20, 113.04, 103.01. Anal. Calcd for
C22H10Br3NO3: C, 45.87; H, 1.75; N, 2.43. Found: C,
45.76; H, 1.67; N, 2.33.
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1-(2,4,6-Trichlorophenoxy)-3H-naphtho[1,2,3-
de]quinoline-2,7-dione (14g). 1HNMR (300 MHz,
CDCl3), δ (ppm): 8.20 (t, 3H, J = 7.8 Hz), 7.60 (m,
4H), 7.50 (t, 2H, J = 7.5 Hz), 7.00 (d, 2H, J = 9.0
Hz), 6.80 (s, NH). 13C NMR (300 MHz, DMSO-d6):
178.90, 156.76, 154.42, 152.76, 144.86, 136.08,
134.08, 133.13, 132.59, 131.08, 130.43, 129.77,
129.75, 128.94, 127.89, 127.87, 127.83, 125.32,
122.45, 120.80, 112.56, 103.01. Anal. Calcd for
C22H10Cl3NO3: C, 59.69; H, 2.28; N, 3.16. Found: C,
59.58; H, 2.19; N, 3.07.
1-(3,5-Bis(trifluoromethylthio)phenoxy)-3H-naphtho-
[1,2,3-de]quinoline-2,7-dione (14h). 1HNMR (300
MHz, CDCl3), δ (ppm): 8.20 (t, 2H, J = 7.8 Hz), 7.60
(m, 4H), 7.50 (t, 2H, J = 7.5 Hz), 7.00 (d, 2H, J = 9.0
Hz), 6.80 (s, NH). 13C NMR (300 MHz, DMSO-d6):
178.90, 169.19, 155.53, 154.42, 152.76, 136.08,
134.54, 134.24, 134.22, 133.12, 131.49, 131.47,
132.59, 130.43, 128.94, 127.83, 127.32, 125.23,
122.45, 120.80, 114.41, 114.39, 113.01, 103.01. Anal.
Calcd for C24H11F6NO3S2: C, 53.43; H, 2.06; N, 2.60.
Found: C, 53.36; H, 1.95; N, 2.55.
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Heteroatom Chemistry DOI 10.1002/hc