Pd-catalyzed C-H Arylation: A General Route for the Synthesis of Benzo[b]carbazolenaphthoquinones

Article abstract of DOI:10.1002/jhet.2832

A short, efficient and general methodology for benzo[b]carbazolenaphthoquinones was developed via Pd-catalyzed C-H arylation process. This methodology was successfully applied to the synthesis of highly biologically active compound 5H–benzo[b]carbazole-6,

Full text of DOI:10.1002/jhet.2832

Month 2017
Pd-catalyzed C-H Arylation: A General Route for the Synthesis of
Benzo[b]carbazolenaphthoquinones
Arabinda Mandal,a Suresh Kumar Mondal,b Akash Jana,b Susanta Kumar Manna,a Sk Asraf Ali,b and
a
*
Shubhankar Samanta
aDepartment of Chemistry, Bidhannagar College, Kolkata 700064, India
bDepartment of Chemistry, Haldia Govt. College, Haldia 721657, India
*
E-mail: chemshubha@gmail.com
Additional Supporting Information may be found in the online version of this article.
Received March 18, 2016
DOI 10.1002/jhet.2832
Published online 00 Month 2017 in Wiley Online Library (wileyonlinelibrary.com).
A short, efficient and general methodology for benzo[b]carbazolenaphthoquinones was developed via Pd-
catalyzed C-H arylation process. This methodology was successfully applied to the synthesis of highly bio-
logically active compound 5H–benzo[b]carbazole-6,11-diones. Additionally, one-pot synthesis of benzo[b]
phenazine-6,11(5H,12H)-dione derivatives was also explored in aqueous medium.
J. Heterocyclic Chem., 00, 00 (2017).
INTRODUCTION
biological properties. In most of the cases this moiety was
prepared through palladium catalyzed oxidative cyclization
of 2-(arylamino)naphthalene-1,4-dione derivative [6].
However, this reaction includes long time, lower yield
and limited variation of substrate. The use of highly
expensive palladium (II) acetate in excess amount is
another drawback for this oxidative arylation 5a.
Palladium catalyzed C-H arylation protocol is well
established for the synthesis of various carbocycle and
heterocycles [7]. Interestingly, we have first reported the
synthesis of carbazolenaphthoquinone using this protocol.
One reported method cited for the synthesis of 5H–
benzo[b]carbazole-6,11-diones from 2-[3-(2-nitrophenyl)-
2-oxopropyl]benzaldehydes which involves several steps
[8]. Claisen condensation followed by Fischer indole
Compounds containing the naphthoquinone group
represent important biologically active molecules that are
widespread in nature [1]. The presence of carbazole unit
attached with naphthoquinone are of considerable interest
due to their biological point of view, and for their potential
in synthesis [2]. Benzo[b]carbazolequinone derivatives,
which exhibited good cytotoxicity against human cervical
cancer cell line (SiHa), belongs to the kynamicin family
of antibiotics and shows antitumor activity (Fig. 1) [3].
The alkaloid calothrixin B, elipticinequinone is the
carbazolequinone which have antitumor, psychotropic,
anti-inflammatory, antihistaminic, antibiotic and anti-
oxidative activities (Fig. 1) [4]. Hence, the synthesis of
carbazolenaphthoquinone continues to be a vigorously
active research area. Again, anti-carcinogenic benzo[b]
carbazole-6,11-diones units facilitate interaction with
nucleic acids preventing them from carrying out their
role in the replication and recombination of these acids [5].
Recently, substituted carbazolenaphthoquinone has also
become recognized as building block to study their
cyclisation [9], anionic [4
+ 2] cycloaddition of
furoindolones with arynes and quinolethers 4a were the
other alternatives for their preparation. Even though
numerous methods are available for the synthesis of
benzo[b]carbazolequinone [10], there is still
a
considerable need for the development of more versatile
synthetic routes toward highly substituted benzo[b]
© 2017 Wiley Periodicals, Inc.

A. Mandal, S. K. Mondal, A. Jana, S. K. Manna, S. A. Ali, and S. Samanta
Vol 000
Figure 1. Biologically active quinone related compounds.
carbazoquinone, especially with respect to tolerance of a
wider variety of functional groups.
1 with aniline 2a in aqueous medium at 50–60°C
(Table 1, entry 1) [13].
The efficiency and functional group tolerance of this
procedure have been fully demonstrated by synthesizing
RESULTS AND DISCUSSION
a
number of functionalized 2-bromo-3-(arylamino)
naphthalene-1,4-diones 3a-3 m bearing mono or di-
substitutions of methyl, methoxy, amine, hydroxyl,
bromo in the aromatic amines 2. The conjugated addition
was highly sensitive towards substitution impacting rate
and the product yields (Table 1). The electron donating
substituent on the aromatic amines took 15–30 min for
conjugated addition reaction (entries 1–9 & 11–13)
whereas moderate withdrawing substituent needs (entry-
10, 2j) 70 minutes for completing the reaction. However,
strong electron withdrawing (nitro, chloro) or
heterocyclic (pyridine, isoquinoline) substituted amines
failed to afford any C-H arylation precurrsor under
identical condition. Alternatively, ortho substituted amine
2 k (Table 1, Entry 11) gave poor yield compare to m- or
p-substituted amines (entries 1–9).
During course of our research, a different result was
found with aromatic di-amines 5a (Table 2). The
sequential displacements of the two bromines in the
quinone ring by the amine group led to benzo[b]
phenazine-6,11(5H,12H)-dione 6a with moderate yield
within 1.5 hours (Table 2). Encouraged by this success,
we extended this reaction by using other diamines with
Previously our group established
a pathway of
synthesizing pyranapthoquinones and its related natural
product pentalogin via palladium catalyzed Heck reation
[11]. In continuation of our endeavor in heterocyclic
synthesis [12], we hereby wish to communicate a
synthetic route of benzo[b]carbazolenaphthoquinone
derivatives 4 by Pd catalyzed C-H arylation of 2-bromo-
3-(arylamino)naphthalene-1,4-diones
3
(Scheme 1).
Moreover, we have developed benzo[b]phenazine-
6,11(5H,12H)-dione derivatives 6 via two component
coupling reaction of 2,3-dibromonaphthalene-1,4-dione
with o-phenelenediamine derivatives in water medium
(Scheme 1).
Our initial focus was to synthesize biologically active
5H–benzo[b]carbazole-6,11-dione 4a which display anti-
neoplastic activity, cytotoxic and DNA intercalative
effects. In this connection, our preliminary strategy was
aimed at the synthesis of the D ring in presence of A and
B rings (Scheme 1). Subsequently, C ring was to be
constructed by palladium catalysed C-H arylation
process. Accordingly, the precursor 3a for C-H arylation
was achieved by the conjugative addition followed by
elimination reaction of 2,3-dibromo-1,4-naphthoquinone
both
donating
and
withdrawing
substituents.
Consequently, we got derivatives of benzo[b]phenazine-
Scheme 1. Synthetic strategies for benzo[b]phenazine-6,11(5H,12H)-dione 6 and benzo[b]carbazolenaphthoquinone derivatives 4.
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Pd-catalyzed C-H arylation
Table 1
Synthesis of C-H arylation precursors.
Entry
Substrate2
R1
R2
R3
-H
-H
-H
-H
-H
-Me
-OMe
-OH
-NH2
-H
-H
-OMe
-Me
R4
Time (min)
Yield of 3(%)
1
2
3
4
5
6
7
8
9
10
11
12
13
2a
2b
2c
2d
2e
2f
2 g
2 h
2i
-H
-H
-H
-H
-H
-H
-H
-H
-H
-H
-H
-H
-H
-H
-H
-H
-H
-H
-H
-H
-H
-H
-H
-H
30
25
17
16
15
28
20
17
17
70
20
17
54
98
78
79
80
83
69
70
75
77
50
62
77
63
-Me
-OMe
-OH
-NH2
-H
-H
-H
-H
2j
-Br
-H
2 k
2 l
2 m
-OMe
-OMe
-H
-H
-OH
Reaction conditions. Dibromonaphthalene-1,4-dione 1(1 mmol), Aromatic Amines 2 (1.1 mmol), H2O (3 mL), Time15–70 min.
Table 2
A green synthetic approach of benzo[b]phenazine-6,11(5H,12H)-dione derivatives 6.
Entry
Substrate 5
R1
R2
Time (h)
Yield of (6 )%
1
2
3
4
5
5a
5b
5c
5d
5e
-H
-H
-Cl
-H
-Me
-H
-Cl
-Cl
-Me
-Me
1.5
3
4
1.3
1.2
70
63
59
67
69
Reaction conditions. Dibromonaphthalene-1,4-dione 1(1 mmol), Aromatic diamines 5 (1.1 mmol), H2O (3 mL), Time 1.2–4 h.
6,11(5H,12H)-dione 6 through two conjugative reaction
with moderate to good yields (59–70)% in water medium.
Our next study was directed towards cyclization of
model substrate 2-bromo-3-(phenylamino)naphthalene-
1,4-dione 3a to our projected target molecule 4a. A
preliminary experiment with 3a utilizing PdCl2(PPh3)2 as
the catalyst and sodium acetate as base in DMF solvent
at 120°C afforded 4a in 59% yield (Scheme 2).
general protocol with high yield. Therefore, different
catalysts and bases were screened for improving the
reaction efficiency (Table 3, entries 1–10).
Scheme 2. Synthesis of biologically active 5H–benzo[b]carbazole-6,11-
diones 4a.
The formation of this compound through C-H arylation
encouraged us to optimize the reaction condition to give a
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A. Mandal, S. K. Mondal, A. Jana, S. K. Manna, S. A. Ali, and S. Samanta
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Table 3
Optimum condition for C-H arylationa.
Entry
catalyst
Pd(OAc)2
Pd(OAc)2
PdCl2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2
Ligand
Base
Time (h)
Yield
1
2
3
4
5
6
7
8
9
10
__
PPh3
PPh3
__
NaOAc
Cs2CO3
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
CS2CO3
NaOAc
24
24
24
3
4
24
5
6
3
24
Dec
0
0
80b
89
0
__
Xanthpos
Dppp
__
__
BINAP
PdCl2
52
67
57
0
Pd2(dba)3
PdCl2(PPh3)2
PdCl2
Reaction conditions. Substrate 3 l (1 mmol), Catalyst (10 mol%), Base (1.1 mmol), Solvent ( 4 mL). Tempa 120°C, Tempb 100°C,dec: decomposed
Table 4
Palladium Catalyzed C-H arylation.
Reaction conditions. Substrate 3 (1 mmol), PdCl2(PPh3)2 (10 mol%), NaOAc (1.1 mmol), Solvent (4 mL), Temperature120°C, Time 4 h.
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Scheme 3. Plausible mechanism for Pd (0) catalyzed cyclization.
We selected model substrate 2-(3, 5-dimethoxyphe-
nylamino)-3-bromonaphthalene-1,4-dione 3 l for this
arylation reaction which contain higher electron density
in aryl amine part. When we applied our previous
reaction condition PdCl2(PPh3)2 10 mol%, NaOAc
1.1 mmol and DMF solvent at 120°C then we got our
desired product with 89% yield within 4 hours (Table 3,
Entry 5) but under identical condition at 100°C reduced
the yield of 4 l. The addition of ligand PPh3 was
found to be unproductive in the cyclization in
presence of Pd(OAc)2 or PdCl2 (entries 2,3), where as
significant breakthrough come in case of dppp [1,3-
Bis(diphenylphosphino)propane] ligand (entry 7). Other
ligands, such as BINAP [1,10-Binaphthalene]-2,20-
diylbis[diphenylphosphine], Xanthpos [4,5-Bis(diphenyl-
phosphino)-9,9-dimethylxanthene] did not afford our
desired product. Only 67% yield of 4 l was achieved
when Pd2(dba)3 acted as the catalyst.
With the optimized reaction conditions established
(entry 5, Table 3), the generality and scope of the present
cyclization reaction were probed. This transformation
displayed high functional group tolerance and proved to
be quite efficient methodology for preparation of multi-
substituted carbazolenaphthoquinones 4 (Table 4). The
substrate 3 with methyl, mono or bi-methoxy, hydroxyl,
and amine groups on aryl rings, gave the corresponding
carbazolenaphthoquinone derivatives in good to excellent
yields. The ortho-methoxy substituted amine 3 k gave
65% yield, suggesting that the transformation was
sensitive to steric hindrance for C-H activation. The
electronic nature of aryl ring also seems to be crucial
factor for these cyclizations. Hence, the reaction
proceeded smoothly for 3 l, 3 m than the other substrate
of 3. However, Pd-catalyzed C-H arylation was
inefficient in case of 3f and 3j. Therefore, tri-substituted
amines as variant show more satisfactory result than bi-
substituted amines for the conversion of 3 to 4.
The mechanistic pathway of palladium catalyzed
intramolecular C–H arylation is described in Scheme 3.
Oxidative addition of palladium to the C-Br bond occurs to
form an aryl–palladium intermediate A which undergoes
palladation–deprotonation followed by reductive elimina-
tion to form the carbazolenapthoquinone derivative [14].
CONCLUSION
In summary, we have accomplished novel synthetic
routefor the construction of functionalized carbazo-
lenapthoquinones via Pd-catalyzed C-H arylation. This
general method tolerates a wide range of functional
groups and shows reliability for rapid elaboration of the
readily available dibromoquinone into a variety of
substituted carbazolenapthoquinones. In addition, we
have developed preparatory method of benzo[b]
phenazine-6,11(5H,12H)-dione derivatives in aqueous
medium. Current research is focused on extending the
scope of the reaction.
EXPERIMENTAL
Typical
experimental
procedure
for
benzo[b]
carbazolenaphthoquinone derivatives (4). Compounds (3,
1.0 equiv.), NaOAc (1.1 equiv.), DMF (4 mL) were
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A. Mandal, S. K. Mondal, A. Jana, S. K. Manna, S. A. Ali, and S. Samanta
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placed in a two neck round bottom flask. After degassing
with N2, PdCl2(PPh3)2 (10 mol%) was added and heated
at 120°C for 4 h. After disappearing of starting material,
the reaction mixture was diluted with cold water and
extracted with ethyl acetate (20 mL × 3) and dried
(Na2SO4). The solvent was evaporated and the crude
product was purified by column chromatography on
Silica Gel (60–120) with the eluent petroleum ether: ethyl
8.02–8.06 (m, 2H), 12.87 (bs, 1H); 13C NMR (DMSO-d6
75 MHz) δ:55.9, 95.5, 106.5, 115.9, 118.4, 118.5, 123.7,
126.3, 132.4, 133.2, 133.7, 134.3, 134.4, 136.8, 140.3,
177.3,181.0; HRMS calcd for C17H11NO3 [M++ H]:
278.0819; found: 278.0821.
3-Hydroxy-5H-benzo[b]carbazole-6,11-dione (4h).
Red
solid: mp > 300°C;1H NMR (DMSO-d6, 300 MHz)
δ:6.66 (d, 1H, J = 9.0 Hz), 7.04 (d, 1H, J = 9.0 Hz), 7.33
(d, 1H, J = 9.0 Hz), 7.87–7.90 (m, 2H), 8.11–8.18 (m,
2H), 10.43 (s, 1H), 13.27 (s, 1H); 13C NMR (DMSO-d6
75 MHz) δ: 100.1, 121.8, 125.1, 125.6, 127.1, 127.9,
128.3, 132.3, 133.6, 134.9, 135.2, 137.6, 139.2, 146.2,
177.2, 180.2; HRMS calcd for C16H9NO3 [M++ H]:
acetate 10:1.
5H–benzo[b]carbazole-6,11-dione (4a). Orange solid: m.
p. 301–30°C.[7a] 1H NMR (DMSO-d6, 300 MHz)
δ:7.38–7.46 (m, 2H), 7.59 (d, 1H, J = 8.1 Hz), 7.85–7.87
(m, 2H), 8.10–8.12 (m, 2H), 8.21 (d, 1H, J = 7.4 Hz),
13.1 (bs, 1H); 13C NMR (DMSO-d6, 75 MHz) δ: 114.4,
117.9, 122.8, 124.5, 126.6, 127.5, 132.0, 133.1, 133.7,
134.6, 138.7, 177.9, 180.2 (Three carbon merged with
other); HRMS calcd for C16H9NO2 [M++ H]: 248.0713;
found: 248.0715.
264.0662; found: 264.0663.
3-amino-5H-benzo[b]carbazole-6,11-dione (4i). Blackish
red solid: mp > 300°C;1H NMR (DMSO-d6, 300 MHz)
δ:5.61(s, 2H), 6.59 (s, 1H), 6.68–6.72 (m, 1H), 7.54–7.60
(m, 1H), 7.73–7.82 (m, 2H), 7.99–8.02 (m, 2H), 12.34 (s,
1H); 13C NMR (DMSO-d6 75 MHz) δ: 94.4, 115.8,
116.1, 119.1, 126.1, 126.2, 129.1, 129.3, 131.9, 132.0,
132.5, 133.5, 141.6, 149.8, 176.4, 181.2; HRMS calcd
2-Methyl-5H-benzo[b]carbazole-6,11-dione (4b).
Orange
solid: mp252–253°C;[7a] 1H NMR (DMSO-d6, 300 MHz)
δ:2.47 (s, 3H), 7.27–7.33 (m, 1H), 7.44 (d, 1H,
J = 8.4 Hz), 7.81–7.86 (m, 2H), 7.93 (s, 1H), 8.00–8.11
(m, 2H), 13.00 (s, 1H); 13C NMR (DMSO-d6, 75 MHz)
δ: 21.4, 113.8, 118.4, 121.3, 124.6, 125.7, 126.5, 126.6,
129.6, 130.9, 133.1, 135.4, 138.4, 139.2, 178.4, 180.2
(One carbon merged with other) ; HRMS calcd for
for C16H10N2O2 [M++ H]: 263.0822; found: 263.0824.
4-methoxy-5H-benzo[b]carbazole-6,11-dione (4k). Orange
solid: mp > 250°C;1HNMR (DMSO-d6, 300 MHz) δ:3.95
(s, 3H), 6.96 (d, 1H, J = 7.8 Hz),7.29 (t, 1H, J = 8.1 Hz),
7.75–7.86 (m, 3H), 8.06–8.10 (m, 2H), 13.23 (s, 1H); 13C
NMR (DMSO-d6 75 MHz) δ: 56.2, 107.3, 114.7, 118.4,
125.4, 125.9, 126.5 (2C), 129.6, 133.2, 133.7, 134.5,
134.6, 137.4, 148.0, 177.6, 180.9; HRMS calcd for
C17H11NO3 [M++ H]: 278.0819; found: 278.0817.
C17H11NO2 [M++ H]: 261.0790; found: 261.0792.
2-methoxy-5H-benzo[b]carbazole-6,11-dione (4c). Orange
solid: mp 300–301°C;1H NMR (DMSO-d6, 300 MHz) δ:
3.84 (s, 3H), 7.06 (d, 1H, J = 8.0 Hz), 7.47 (d, 1H,
J = 8.0 Hz), 7.58 (s, 1H), 7.78–7.83 (m, 2H), 8.05–8.09
(m, 2H), 12.98 (s, 1H); 13C NMR (DMSO-d6 75 MHz) δ:
55.3, 102.1, 114.9, 116.9, 118.3, 124.8, 125.9, 132.7,
133.1, 133.4, 134.1, 134.2, 136.9, 156.9, 177.1, 180.2,
(One carbon merged with other); HRMS calcd for
C17H11NO3 [M++ H]: 278.0819; found: 278.0817.
1,3-dimethoxy-5H-benzo[b]carbazole-6,11-dione(4l).
Red
solid: mp 294–300°C;1H NMR (DMSO-d6, 300 MHz) δ:
3.80 (s, 3H), 3.88 (s, 3H), 6.37(s, 1H), 6.54 (s,
1H),7.75–7.83 (m, 2H), 8.01–8.08 (m, 2H), 12.83 (s,1H);
13C NMR (DMSO-d6 75 MHz) δ: 55.9, 56.0, 89.1, 96.1,
110.0, 119.3, 125.7, 127.0, 132.1, 133.2, 134.4, 135.0,
136.6, 140.3, 156.2, 161.3, 177.8, 178.3; HRMS calcd
2-hydroxy-5H-benzo[b]carbazole-6,11-dione (4d).
Red
solid: mp > 300°C;1H NMR (DMSO-d6, 300 MHz)
δ:7.36–7.43 (m, 1H), 7.49–7.87 (m, 2H), 7.92 (d, 2H,
J = 7.5 Hz), 8.03 (d, 2H, J = 7.5 Hz), 9.29 (s, 1H), 12.01
(s, 1H); 13C NMR (DMSO-d6 75 MHz) δ:103.6, 110.9,
111.6, 113.5, 125.9, 126.6, 127.3, 130.7, 133.1, 133.2,
135.5, 145.8, 147.0, 153.8, 181.9, 182.9; HRMS calcd
for C18H13NO4 [M++ H]: 308.0925; found: 308.0924.
2-Hydroxy-3-methyl-5H-benzo[b]carbazole-6,11-dione
(4m).
Red solid:mp > 300°C;1H NMR (DMSO-d6,
300 MHz) δ:2.71 (s, 3H), 6.68 (s, 1H), 6.99 (s, 1H),
7.72–7.77 (m, 2H), 7.80–7.85 (m, 2H), 9.45(s, 1H), 11.97
(s, 1H); 13CNMR (DMSO-d6 75 MHz) δ:16.4, 101.2,
115.4, 123.4, 125.3, 125.7, 126.5, 127.4, 129.2, 130.9,
132.9, 133.3, 135.3, 147.6, 153.9, 182.2, 182.5;
HRMS calcd for C17H11NO3 [M++ H]: 278.0819; found:
278.0816.
for C16H9NO3 [M++ H]: 264.0662; found: 264.0665
2-amino-5H-benzo[b]carbazole-6,11-dione (4e). Blackish
red solid: mp 220–223°C; 1H NMR (DMSO-d6,
300 MHz) δ: 5.65(bs, 2H), 6.59–6.91(m, 3H), 7.73–
8.03(m,4H),12.34(s,1H); 13C NMR(DMSO-d6 75 MHz)
δ: 94.47, 116.15, 123.28, 126.09, 126.24, 126.48, 129.12,
133.97, 134.38, 134.58, 135.18, 139.56, 141.58, 149.63,
176.41, 181.19; HRMS calcd for C16H10N2O2 [M++ H]:
Typical experimental procedure for of benzo[b]phenazine-
6,11(5H,12H)-dione (6).
Compound 1(1 mmol) and 5
(1.1 mmol) were placed in a two necked round bottomed
flask. After that, water (3 mL) was added and the reaction
mixture was allowed to stir at 50–60°C and the progress
of the reaction was monitored by TLC. After the
disappearance of starting material, the reaction mixture
was extracted with ethyl acetate and dried over Na2SO4.
263.0822; found: 263.0821.
3-Methoxy-5H-benzo[b]carbazole-6,11-dione (4g). Yellow
1
solid: mp 260–262°C; H NMR (DMSO-d6, 300 MHz)
δ:3.82(s,3H), 6.95–7.00 (m, 3H), 7.77–7.84 (m, 2H),
Journal of Heterocyclic Chemistry
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Pd-catalyzed C-H arylation
Then, the combine organics was purified by column
chromatography.
Benzo[b]phenazine-6,11(5H,12H)-dione (6a). Red solid:
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Soc Perkin Trans 1 1983, 2409.
mp > 300°C;1H NMR (DMSO-d6, 300 MHz) δ:6.67 (d,
2H, J = 8.1 Hz) 6.91 (d, 2H, J = 8.1 Hz), 7.93 (m, 2H),
8.23–8.38 (s, 2H), 9.04 (s, 2H); 13C NMR (DMSO-d6
75 MHz) δ: 123.2 (2C), 124.5 (2C), 129.5 (2C), 131.6
(2C), 139.5 (2C), 152.4 (2C), 153.8 (2C), 174.9 (2C);
HRMS calcd for C16H10N2O2: [M++ H]: 263.0822;
found: 263.0820.
2-chlorobenzo[b]phenazine-6,11(5H,12H)-dione (6b). Red
[3] (a) Ravichandiran, P.; Jegan, A.; Premnath, D.; Periasamy, V. S.;
Muthusubramanian, S.; Vasanthkumar, S. Bioorg Chem 2014, 53, 24; (b)
Sieveking, I.; Thomas, P.; Estévez, J. C.; Quiñones, N.; Cuéllar, M. A.;
Villena, J.; Espinosa-Bustos, C.; Fierro, A.; Tapia, R. A.; Maya, J. D.;
López-Muñoz, R.; Cassels, B. K.; Estévez, R. J.; Salas, C. O. Bioorg Med
Chem 2014, 22, 4609; (c) Echavarren, A. M.; Tamayo, N.; Frutos, O. D.;
Garcia, A. Tetrahedron 1997, 53, 16835. (d) Knidker, E.-J.; Sullivan, N. Tet-
rahedron 1994, 50, 10893.
[4] (a) Treus, M.; Salas, C. O.; Gonazalez, M. A.; Estevez, J. C.;
Tapia, R. A.; Estevez, R. J Tetrahedron 2010, 66, 9986; (b) Mal, D.;
Senapati, B. K.; Pahari, P. Synlett 2005, 6, 994; (c) Dalton, L. K.;
Demerac, S.; Elmes, B. C.; Lode, J. W.; Swan, J. M.; Teitei, T.
Aust J Chem 1967, 20, 2715; (d) Diaz, M.; Cobas, A.; Guitian, E.;
Castedo, L. Eur J Org Chem 2001 4543; (e) Ishikura, M.; Hino, A.;
Yaginuma, T.; Agata, I.; Katagiri, N. Tetrahedron 2001, 56, 193; (f)
Fernadez, M.; Barcia, C.; Estevez, J. C.; Estevez, R. J.; Castedo, L.
Synlett 2004 267; (g) Richards, R. W.; Rothschild, J. M.; Willis, A. C.;
De-chazal, N. M.; Kirk, J.; Kirk, K.; Saliba, K.; Smith, G. D. Tetrahedron
1999, 55, 13513.
solid:mp > 300°C;1H NMR (DMSO-d6, 300 MHz) δ:
7.86–7.93 (m, 3H), 8.18–8.24 (m, 2H), 8.30–8.36
(m, 2H), 9.25 (s, 2H); Solubility of the sample in common
deuterated solvent (such as DMSO-d6, methanol-d4,
acetone-d6) is not sufficient to record the 13C NMR
spectra; HRMS calcd for C16H9ClN2O2 [M++ H]:
297.0433; found: 297.0431.
2,3-dichlorobenzo[b]phenazine-6,11(5H,12H)-dione (6c). Red
solid: mp > 300°C;1H NMR (DMSO-d6, 300 MHz)
δ:7.85 (s, 1H),7.86 (s, 1H), 8.27(m, 4H), 9.02 (bs, 2H);
Solubility of the sample in common deuterated solvent
(such as DMSO-d6, methanol-d4, acetone-d6) is not
sufficient to record the 13C NMR spectra; HRMS calcd
for C16H8Cl2N2O2[M++ H]: 331.0043; found: 331.0041.
2-methylbenzo[b]phenazine-6,11(5H,12H)-dione (6d). Red
[5] Cheng, C. C. In Progress in Medicinal Chemistry, Structural
Aspects of Antineoplastic Agents – A New Approach; Ellis, G. P.; West,
G. B. Eds.; Elsevier: Amsterdam, 1988; Vol 25.
solid: mp > 300°C;1H NMR (DMSO-d6, 300 MHz) δ:2.58
(s, 3H), 7.72 (s, 1H), 7.86–7.89 (m, 3H), 7.98–7.11(m,
1H),8.31–8.35(m, 2H), 9.13(bs, 2H); Solubility of the
sample in common deuterated solvent (such as DMSO-d6,
methanol-d4, acetone-d6) is not sufficient to record the 13C
NMR spectra; HRMS calcd for C17H12N2O2[M++ H]:
[6] (a) Sridharan, V.; Martín, M. A.; Menéndez, J. C. Eur J Org
Chem 2009 4614; (b) Illos, R. A.; Shamir, D. L.; Shimon, J. W.;
Zilbermann, I.; Bittner, S. Tetrahedron Lett 2006, 47, 5543;
(c) Corral, J.-M.; Castro, M.-A.; Gordaliza, M.; Martin, M.-L.; Gamito,
A.-M.; Cuevas, C.; Feliciano, A. S. Bioorg Med Chem 2006, 14, 2816.
[7] (a) Saget, T.; Perez, D.; Cramer, N. Org Lett 2013, 15,
1354; (b) Nervig, C. S.; Waller, P. J.; Kalyani, D. Org Lett 2012,
14, 4838; (c) Nandi, D.; Jhou, Y.-M.; Lee, J.-Y.; Kuo, B.-C.;
Liu, C.-Y.; Huang, P.-W.; Lee, H. M. J Org Chem 2012, 77, 9384;
(d) Kamikawa, K.; Takemoto, I.; Takemoto, S.; Matsuzaka, H. J Org
Chem 2007, 72, 7406.
277.0979; found: 277.0977.
2,3-dimethylbenzo[b]phenazine-6,11(5H,12H)-dione (6e). Red
solid: mp > 300°C;1H NMR (DMSO-d6, 300 MHz) δ:2.62
(s, 6H),7.86–7.91 (m, 3H), 8.04–8.16 (m, 2H),8.36
(s, 1H),9.16 (bs, 2H); Solubility of the sample in common
deuterated solvent (such as DMSO-d6, methanol-d4,
acetone-d6) is not sufficient to record the 13C NMR spectra;
HRMS calcd for C18H14N2O2 [M++ H]: 291.1135; found:
291.1134.
[8] Fernández, M. Synthesis 2009, 18, 3051.
[9] Indumathi, T.; Fronczek, F. R.; Prasad, K. J. R. Tetrahedron
Lett 2014, 55, 5361.
[10] (a) Patil, P.; Nimonkar, A.; Akamanchi, K. G.
J Org
Chem 2014, 79, 2331; (b) Barcia, J.-C.; Cruces, J.; Est vez, J. C.;
Est vez, R.-J.; Castedo, L. Tetrahedron Lett 2002, 43, 5141; (c)
Otero, J.-M.; Barcia, J.-C.; Salas, C.-O.; Thomas, P.; Est vez, J.-C.;
Est vez, R. J. Tetrahedron 2012, 68, 1612; (d) Otero, J.-M.; Barcia, J.-C.;
Estevez, J.-C.; Est vez, R.-J. Tetrahedron: Asymmetry 2005, 16, 11; (e)
Asche, C.; Frank, W.; Albertb, A.; Kucklaender, U. Bioorg Med Chem
2005, 13, 819.
Acknowledgments. Financial support from DST (SB/FT/CS-
189/2012) and chemistry department of Haldia Govt. College is
gratefully acknowledged. We are specially thanks to department
of chemistry IIT kharagpur and the other faculty members of
Haldia Govt. College.
[11] Nandi, S.; Singha, R.; Samanta, S.; Ray, J. K. Tetrahedron Lett
2012, 53, 2659.
[12] (a) Manna, S. K.; Mondal, S. K.; Ahmed, A.; Mandal, A.;
Jana, A.; Ikbal, M.; Samanta, S.; Ray, J. K. RSC Adv 2014, 4, 2474;
(b) Mondal, S. K.; Manna, S. K.; Mandal, A.; Samanta, S.; Ray, J. K.
Tetrahedron Lett 2014, 55, 6411; (c) Manna, S. K.; Mandal, A.;
Mondal, S. K.; Samanta, S.; Ray, J. K.; Baidya, M. Syn Com 2015,
45, 625.
REFERENCES AND NOTES
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5896.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet