Synthesis of a new library of pyrano-phenazine derivatives via a novel three-component protocol

Article abstract of DOI:10.1002/hlca.201300006

The pyrano-phenazine derivatives 6 were synthesized by an efficient procedure using the reaction between benzo[a]phenacin-5-ols with the condensation product of an aldehyde with Meldrum's acid in the presence of a catalytic amount of Et₃N at ambient temperature. The procedure is very simple, and products could be separated from the reaction media by simple filtration. High functional-group tolerance both in the benzo[a]phenazin-5-ol and aldehyde moieties, facile reaction procedure, medium-to-high yields, and simple separation of the products from the reaction media are the advantages of this route. Copyright

Full text of DOI:10.1002/hlca.201300006

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Helvetica Chimica Acta – Vol. 97 (2014)
Synthesis of a New Library of Pyrano-phenazine Derivatives via a Novel
Three-Component Protocol
by Ahmad Shaabani*, Rahim Ghadari, and Masoud Arabieh
Faculty of Chemistry, Shahid Beheshti University, G.C. P.O. Box 19396-4716, Tehran, Iran (phone: þ 98-
1-29902800; fax þ 98-21-22431663; e-mail: a-shaabani@sbu.ac.ir)
2
The pyrano-phenazine derivatives 6 were synthesized by an efficient procedure using the reaction
between benzo[a]phenacin-5-ols with the condensation product of an aldehyde with Meldrumꢀs acid in
the presence of a catalytic amount of Et N at ambient temperature. The procedure is very simple, and
3
products could be separated from the reaction media by simple filtration. High functional-group
tolerance both in the benzo[a]phenazin-5-ol and aldehyde moieties, facile reaction procedure, medium-
to-high yields, and simple separation of the products from the reaction media are the advantages of this
route.
Introduction. – Phenazines are among the important scaffolds, and they exhibit
several biological features including cytotoxicity [1 – 6], genotoxicity [7], inhibition of
the cyclooxygenase [8], interactions of serum albumins [9], antimicrobial activity [10],
and anti-inflammatory activities [11]. These compounds are important because of their
structural properties as well. Thermodynamic properties [12], molecular interaction of
phenazine dyes with Triton X-100 [13], reduction mechanism of phenazine [14],
biosensors sensitive to H O , glucose, and lactose [15][16], and anion radical properties
2
2
[
17] of different phenazine derivatives have been studied. Because of the above
mentioned properties, different methods for the synthesis of phenazines have been
reported [6][18 – 25].
Results and Discussions. – Due to the biological and physical importance of the
phenazine derivatives, and continuing our studies on multi-component reactions [26 –
2
1
8], herein we report a novel two-step procedure toward the synthesis of the 1-phenyl-
H-benzo[a]pyrano[2,3-c]phenazin-3(2H)-one derivatives. The first step consists in the
condensation reaction between a diamine 1 and 1,4-dihydro-2-hydroxynaphthalene-
,4-dione (2) to afford benzo[a]phenazin-5-ols 3 [29][30] (Scheme 1). The latter were
1
used as C-nucleophiles to react with the condensation product of aldehyde 4 with
Meldrumꢀs acid (¼2,2-dimethyl-1,3-dioxane-4,6-dione; 5) to furnish the desired
products 6a – 6v. The procedure is very simple, and the products could be separated
from the reaction media by filtration with high purity and in high yields, and no further
purification is needed (Scheme 1).
In a pilot experiment, benzene-1,2-diamine (1a) and 2 were stirred in AcOH for
24 h at room temperature to yield compound 3a [29]. The product was separated and
washed with H O to remove any acid residue. Then, 3 was added to a mixture of 4-
2
bromobenzaldehyde (4a) and 5 in the presence of a catalytic amount of Et N in MeCN/
3
ꢁ
2014 Verlag Helvetica Chimica Acta AG, Zꢂrich

Helvetica Chimica Acta – Vol. 97 (2014)
Scheme 1. Synthesis of Products 6a – 6v
229
EtOH 3 :1 at room temperature. After 24 h, the precipitated product was separated by
filtration and washed with H O (10 ml) and AcOEt (5 ml), and then recrystallized
2
from EtOH/H O. Product 6a was obtained as a yellow powder in 86% yield. The
2
1
13
structure of the compound was deduced from the IR, H- and C-NMR, and MS data.
For example, the H-NMR spectrum of 6a exhibited an ABM system as a broad doublet
1
2
for the CHH at 3.20 ppm (J ¼ 16), a doublet of doublet for the CHH at 3.68 ppm ( J ¼
3
1
8, J ¼ 9), a doublet for the CH at 5.53 ppm (J ¼ 9), as well as two doublets for the
aromatic H-atoms at 7.26 and 7.45 ppm (J ¼ 6), a multiplet for the seven aromatic H-
atoms at 7.95 – 8.39 ppm, and a doublet at 9.36 (J ¼ 5) for one aromatic H-atom.
To extend the chemical library, a variety of diamines 1 with an electron-releasing
group (4-methylbenzene-1,2-diamine (1b)), an electron-withdrawing group (4-nitro-
benzene-1,2-diamine (1c)), and halogen substituents (4,5-dichlorobenzene-1,2-diamine
(1d)) were used instead of 1a (Scheme 1). Also, reactions with different aldehydes with
electron-withdrawing and electron-donating functional groups conducted to further
extend the chemical library. The synthesized products 6a – 6v are presented in
Scheme 1.
The effect of the solvent in the second step of the reaction has also been
investigated. As indicated in Table 1, the reaction occurred very efficiently in mixed
solvents MeCN/EtOH and MeCN/MeOH (Entries 5 and 6). In contrast, in the case of
pure MeCN as a solvent, the reaction did not proceed efficiently because of the very

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Helvetica Chimica Acta – Vol. 97 (2014)
low solubility of the benzo[a]phenazin-5-ols 3; when EtOH or DMF was used as a
solvent, the reaction led to impure products and more purification steps were needed to
obtain pure compounds, resulting in lower yields.
Table 1. Effect of Solventsa)
Entry
Solvent
Ratio
Yield [%]
1
2
3
4
5
6
7
8
EtOH
MeOH
MeCN
DMF
MeCN/EtOH
MeCN/MeOH
MeCN/MeOH/DMF
MeCN/EtOH/DMF
–
–
–
–
25
35
10
42
86
90
68
85
3 : 1
3 : 1
3 : 1 : 1
3 : 1 : 1
a) 4-Bromobenzaldehyde (4a; 1 mmol), Meldrumꢀs acid (5; 1 mmol), and benzo[a]phenazin-5-ol (3a;
mmol), in the presence of 10 mol-% Et N, at ambient temperature, for 24 h.
1
3
The effect of various catalysts instead of Et N in the reaction has been investigated
3
as well. Four usual basic catalysts have been considered. The results were compiled in
Table 2. The data revealed that Et N was the best catalyst with respect to the reaction
3
yield. It is worth mentioning that the reaction did not proceed in the absence of a
catalyst.
Table 2. Effect of Catalystsa)
Entry
Catalyst
–
Amount [mol-%]
Yield [%]
1
2
3
4
5
6
7
8
9
–
15
10
5
10
5
10
5
10
5
–
86
86
74
73
70
70
67
55
43
Et N
3
Et N
3
Et N
3
Piperidine
Piperidine
Pyridine
Pyridine
b
DBU )
1
0
DBU
a) 4-Bromobenzaldehyde (4a; 1 mmol), Meldrumꢀs acid (5; 1 mmol), and benzo[a]phenazin-5-ol (3a;
b
1
7
mmol) in MeCN/EtOH 3 : 1 (8 ml), at ambient temperature, for 24 h. ) 1,8-Diazabicyclo[5.4.0]undec-
-ene
Although we have not studied the mechanistic aspects of the above mentioned
reaction, a plausible pathway could be considered as shown in Scheme 2. The product of
the first step could be obtained via two successive condensation reactions between 1
and 2, in AcOH. The second step included the condensation between an aldehyde 4 and
Meldrumꢀs acid (5) in the presence of a catalytic amount of Et N; then, the Michael-
3
type addition of 3 to the intermediate 7 led to the intermediate 8, and an intramolecular

Helvetica Chimica Acta – Vol. 97 (2014)
Scheme 2. Proposed Pathway
231
cyclization along with simultaneous elimination of acetone and CO , gave the
2
appropriate products 6a – 6v.
Conclusions. – In summary, we have developed a facile, straightforward, and
efficient three-component approach for the synthesis of phenazine derivatives 6 from
readily available starting materials. The procedure is very simple, and products could be
separated from reaction media by simple filtration. The presented procedure displays
good functional-group tolerance, and the benzo[a]phenazin-5-ols 3 or aldehydes 4
containing electron-donating and electron-withdrawing functional groups could be
used in the reaction successfully. We hope that this approach may be of value in search
of novel synthetic fragments with unique properties for medicinal chemistry.
We gratefully acknowledge the financial support from the Research Council of Shahid Beheshti
University.

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Helvetica Chimica Acta – Vol. 97 (2014)
Experimental Part
General. All chemicals were obtained from Fluka or Merck, and were applied without further
purification. M.p.: Electrothermal-9100 apparatus. IR Spectra: Bomem-MBFT-IR spectrophotometer; in
ꢀ
1
1
13
KBr; ˜n in cm . H- and C-NMR spectra: Bruker-DRX-300-Avance spectrometer; in (D )DMSO; d in
6
ppm rel. to Me Si as internal standard, J in Hz. MS: Shimadzu-GCMS-QP-1100EX mass spectrometer; at
4
7
0 eV; in m/z (rel. %). Elemental analyses: Elementaranalysensysteme GmbH VarioEL, CHNS mode.
Synthesis of Benzo[a]phenazin-5-ol (3a) [29]. To a magnetically stirred soln. of benzene-1,2-diamine
(1a; 0.11 g, 1 mmol) in AcOH (5 ml), 1,4-dihydro-2-hydroxynaphthalene-1,4-dione (2; 0.17 g, 1 mmol)
was added. The precipitated product was separated by filtration after 24 h. The product was washed with
H O (10 ml) to remove any acid residue. The desired product was obtained as an orange powder. Yield:
2
1
0
7
1
.22 g (88%). M.p. 2948 (dec.). IR (KBr): 3425, 1633, 1592. H-NMR (300 MHz): 7.17 (br. s, 1 arom. H);
13
.80 – 8.31 (m, 7 arom. H); 9.25 (br. s, 1 arom. H); 11.53 (s, OH). C-NMR (75 MHz): 98.2; 114.9; 125.7;
25.9; 127.1; 130.0; 130.4; 131.9; 132.1; 132.6; 132.9; 136.0; 136.4; 140.9; 145.2; 172.7. Anal. calc. for
C H N O (246.27): C 78.03, H 4.09, N 11.38; found: C 78.08, H 4.13, N 11.32.
16
10
2
9
-Methylbenzo[a]phenazin-5-ol (3b). Yield: 0.23 g (91%). Orange powder. M.p. 2738 (dec.). IR
1
(
KBr): 3421, 1638, 1589. H-NMR (300 MHz): 2.60 (s, Me); 7.15 (s, 1 arom. H); 7.65 – 8.29 (m, 6 arom.
H); 9.22 (br. s, 1 arom. H); 11.42 (br. s, OH). MS: 260 (100, M ), 231 (30). Anal. calc. for C H N O
þ
17
12
2
(
260.09): C 78.44, H 4.65, N 10.76; found: C 78.39, H 4.67, N 10.71.
9
-Nitrobenzo[a]phenazin-5-ol (3c) [30]. Yield: 0.22 g (76%). Orange powder. M.p. 2828 (dec.). IR
1
(
KBr): 3426, 1631, 1583. H-NMR (300 MHz): 7.04 (s, 2 arom. H); 7.86 – 8.32 (m, 4 arom. H); 8.81 (br. s, 1
arom. H); 9.08 (br. s, 1 arom. H); 11.80 (br. s, OH). MS: 291 (100, M ), 245 (65), 216 (45). Anal. calc. for
þ
C H N O (291.06): C 65.98, H 3.11, N 14.43; found: C 65.91, H 3.08, N 14.39.
16
9
3
3
9
,10-Dichlorobenzo[a]phenazin-5-ol (3d). Yield: 0.26 g (83%). Orange powder. M.p. 2978 (dec.).
1
IR (KBr): 3431, 1627, 1580. H-NMR (300 MHz): 7.09 (s, 1 arom. H); 7.90 – 8.47 (m, 5 arom. H); 9.12 (d,
þ
J ¼ 3, 1 arom. H); 11.74 (br. s, OH). MS: 314 (100, M ), 286 (60), 251 (25). Anal. calc. for C H Cl N O
16
8
2
2
(
314.00): C 60.98, H 2.56, N 8.89; found: C 60.90, H 2.59, N 8.76.
Synthesis of 1-(4-Bromophenyl)-1,2-dihydro-3H-benzo[a]pyrano[2,3-c]phenazin-3-one (6a). Com-
pound 3a (0.25 g, 1 mmol) was added to a magnetically stirred mixture of 4-bromobenzaldehyde (4a;
.18 g, 1 mmol) and Meldrumꢀs acid (5; 0.14 g, 1 mmol) in MeCN/EtOH 3 :1 (8 ml) in the presence of
0
Et N (10 mol-%), and the mixture was stirred for 24 h. The precipitated product was separated by
3
filtration and washed with H O (10 ml) and AcOEt (5 ml), and recrystallized from EtOH/H O 3 :1 to
2
2
1
give 6a (0.39 g, 86%). Yellow powder. M.p. 3358 (dec.). IR (KBr): 1786, 1487, 1412. H-NMR (300 MHz):
2
3
3
3
.20 (br. d, J ¼ 16, 1 H of CH ); 3.68 (dd, J ¼ 18, J ¼ 9, 1 H of CH ); 5.53 (d, J ¼ 9, CH); 7.26 (d, J ¼ 6, 2
2
2
3
1
3
arom. H); 7.45 (d, J ¼ 6, 2 arom. H); 7.95 – 8.39 (m, 7 arom. H); 9.36 (d, J ¼ 5, 1 arom. H). C-NMR
(
1
1
75 MHz): 35.2; 36.9; 115.4; 116.8; 117.6; 117.9; 118.1; 118.5; 119.8; 122.4; 126.2; 126.5; 127.5; 128.1; 129.0;
þ
81
31.0; 131.4; 134.6; 134.9; 144.0; 149.3; 158.8; 177.3. MS: 456 (40, M ( Br)), 428 (60), 411 (25), 271 (100),
67 (50). Anal. calc. for C H BrN O (455.31): C 65.95, H 3.32, N 6.15; found: C 65.91, H 3.30, N 6.19.
25
15
2
2
1
-(4-Chlorophenyl)-1,2-dihydro-3H-benzo[a]pyrano[2,3-c]phenazin-3-one (6b). Yield: 0.38 g
1
(
(
92%). Yellow powder. M.p. 3208 (dec.). IR (KBr): 3436, 1783, 1630, 1488. H-NMR (300 MHz): 3.20
3
br. d, J ¼ 19, 1 H of CH ); 3.70 (dd, J ¼ 19, J ¼ 6.5, 1 H of CH ); 5.53 (br. d, J ¼ 6.5, CH); 7.26 (d, J ¼ 8, 2
2
2
13
arom. H); 7.46 (d, J ¼ 8, 2 arom. H); 7.95 – 8.37 (m, 7 arom. H); 9.36 (d, J ¼ 5, 1 arom. H). C-NMR
(
1
75 MHz): 36.0; 36.5; 116.2; 116.5; 117.4; 117.5; 118.0; 119.5; 119.8; 122.5; 126.2; 126.5; 128.0; 129.5;
þ
31.0; 131.4; 134.5; 134.9; 136.7; 141.1; 149.2; 158.7; 177.3. MS: 410 (50, M ), 345 (20), 271 (100), 167
(
30). Anal. calc. for C H ClN O (410.08): C 73.08, H 3.68, N 6.82; found: C 73.12, H 3.64, N 6.83.
25 15 2 2
1
,2-Dihydro-1-(4-methoxyphenyl)-3H-benzo[a]pyrano[2,3-c]phenazin-3-one (6c). Yield: 0.30 g
1
(
(
75%). Yellow powder. M.p. 3178 (dec.). IR (KBr): 3435, 1783, 1631, 1600. H-NMR (300 MHz): 3.20
br. d, J ¼ 15, 1 H of CH ); 3.63 (br. s, MeO, 1 H of CH ); 5.50 (d, J ¼ 6, CH); 6.82 (d, J ¼ 6.5, 2 arom. H);
2
2
13
7.21 (d, J ¼ 6.5, 2 arom. H); 7.96 – 8.39 (m, 7 arom. H); 9.37 (d, J ¼ 6, 1 arom. H). C-NMR (75 MHz):
3
1
6.0; 36.5; 116.2; 116.5; 117.4; 117.5; 118.0; 119.5; 119.8; 122.5; 126.2; 126.5; 128.0; 129.5; 131.0; 131.4;
þ
34.5; 134.9; 136.7; 141.3; 149.2; 158.7; 177.3. MS: 406 (50, M ), 378 (100), 271 (75), 182 (30). Anal. calc.
for C H N O (406.13): C 76.83, H 4.46, N 6.89; found: C 76.86, H 4.41, N 6.92.
26
18
2
3

Helvetica Chimica Acta – Vol. 97 (2014)
233
1
-(3-Bromophenyl)-1,2-dihydro-3H-benzo[a]pyrano[2,3-c]phenazin-3-one (6d). Yield: 0.36 g
1
(
80%). Yellow powder. M.p. 3378 (dec.). IR (KBr): 3437, 1783, 1401. H-NMR (300 MHz): 3.23 (br.
2
3
d, J ¼ 15, 1 H of CH ); 3.68 (dd, J ¼ 18, J ¼ 9, 1 H of CH ); 5.55 (d, J ¼ 6, CH); 7.23 – 8.37 (m, 11 arom.
2
2
13
H); 9.37 (d, J ¼ 9, 1 arom. H). C-NMR (75 MHz): 35.2; 36.4; 116.6; 116.7; 116.9; 117.2; 117.5; 117.9;
1
1
3
18.1; 118.5; 119.6; 121.8; 126.2; 126.5; 128.9; 130.1; 131.1; 131.4; 132.4; 134.6; 134.9; 143.2; 149.4; 158.8;
þ
77.2. MS: 454 (25, M ), 428 (50), 271 (100), 167 (30). Anal. calc. for C H BrN O (454.03): C 65.95, H
.32, N 6.15; found: C 65.92, H 3.36, N 6.17.
25
15
2
2
1
-(2-Bromophenyl)-1,2-dihydro-3H-benzo[a]pyrano[2,3-c]phenazin-3-one (6e). Yield: 0.38 g
1
(
83%). Yellow powder. M.p. 3028 (dec.). IR (KBr): 3437, 1779, 1468. H-NMR (300 MHz): 3.02 (br.
2
3
d, J ¼ 16, 1 H of CH ); 3.75 (dd, J ¼ 18, J ¼ 9, 1 H of CH ); 5.81 (d, J ¼ 9, CH); 6.88 (br. s, 1 arom. H);
2
2
13
7
3
1
.11 (br. s, 2 arom. H); 7.74 – 8.30 (m, 8 arom. H); 9.35 (d, J ¼ 4, 1 arom. H). C-NMR (75 MHz): 35.4;
6.9; 116.0; 116.5; 116.9; 117.4; 117.9; 118.1; 118.7; 119.2; 121.2; 126.4; 126.9; 128.9; 130.6; 131.7; 131.8;
þ
32.1; 133.1; 134.0; 143.4; 149.7; 158.7; 176.5. MS: 454 (5, M ), 375 (80), 333 (100), 271 (45). Anal. calc.
for C H BrN O (454.03): C 65.95, H 3.32, N 6.15; found: C 65.97, H 3.33, N 6.19.
25
15
2
2
1
,2-Dihydro-1-(4-nitrophenyl)-3H-benzo[a]pyrano[2,3-c]phenazin-3-one (6f). Yield: 0.36 g (86%).
1
Yellow powder. M.p. 3148 (dec.). IR (KBr): 3435, 1774, 1462. H-NMR (300 MHz): 3.20 (br. d, J ¼ 15,
2
3
1
H of CH ); 3.70 (d, J ¼ 15, J ¼ 7.5, 1 H of CH ); 5.58 (d, J ¼ 6, CH); 7.33 (s, 4 arom. H); 7.98 (d, J ¼ 6, 4
2
2
13
arom. H); 8.17 (s, 1 arom. H); 8.34 (d, J ¼ 6, 2 arom. H); 9.36 (d, J ¼ 5, 1 arom. H). C-NMR (75 MHz):
3
1
5.4; 36.8; 112.9; 114.1; 119.7; 120.3; 122.1; 122.3; 123.2; 123.7; 124.1; 124.2; 126.2; 126.5; 130.2; 131.1;
þ
31.1; 134.5; 134.8; 145.6; 149.4; 158.8; 177.4. MS: 421 (5, M ), 410 (60), 382 (100), 365 (30). Anal. calc.
for C H N O (421.11): C 71.25, H 3.59, N 9.97; found: C 71.20, H 3.52, N 9.91.
25
15
3
4
1
-(4-Fluorophenyl)-1,2-dihydro-3H-benzo[a]pyrano[2,3-c]phenazin-3-one (6g). Yield: 0.36 g
1
(
92%). Yellow powder. M.p. 3058 (dec.). IR (KBr): 3435, 1770, 1465. H-NMR (300 MHz): 3.20 (br.
2
3
d, J ¼ 15, 1 H of CH
2
); 3.70 (dd, J ¼ 15, J ¼ 6, 1 H of CH ); 5.56 (br. d, J ¼ 6, CH); 7.27 (d, J ¼ 6, 2 arom.
2
13
H); 7.46 (d, J ¼ 6, 2 arom. H); 7.96 – 8.38 (m, 7 arom. H); 9.37 (d, J ¼ 6, 1 arom. H). C-NMR (75 MHz):
3
1
6.2; 36.7; 116.0; 116.1; 116.4; 117.6; 117.9; 121.1; 122.8; 123.4; 124.2; 126.5; 127.5; 128.3; 129.6; 131.9;
þ
32.2; 134.5; 134.7; 144.0; 149.3; 159.8; 177.9. MS: 394 (10, M ), 320 (10), 292 (15), 91 (100). Anal. calc.
for C H FN O (394.11): C 76.13, H 3.83, N 7.10; found: C 76.18, H 3.87, N 7.14.
25
15
2
2
1
-(4-Bromophenyl)-1,2-dihydro-11-methyl-3H-benzo[a]pyrano[2,3-c]phenazin-3-one (6h). Yield:
1
0
(
.36 g (77%). Yellow powder. M.p. 2948 (dec.). IR (KBr): 3440, 1779, 1634, 1485. H-NMR
2
3
300 MHz): 2.64 (s, Me); 3.8 (br. d, J ¼ 12, 1 H of CH ); 3.66 (dd, J ¼ 12, J ¼ 6, 1 H of CH ); 5.55 (d,
2
2
J ¼ 6, CH); 7.26 (d, J ¼ 6, 2 arom. H); 7.45 (d, J ¼ 6, 2 arom. H); 7.77 – 8.29 (m, 5 arom. H); 9.33 (d, J ¼ 3, 1
13
arom. H). C-NMR (75 MHz): 23.8; 33.3; 35.8; 116.0; 116.6; 117.4; 118.9; 119.8; 121.6; 126.2; 126.5;
þ
1
2
3
28.1; 129.2; 129.4; 130.0; 131.3; 131.4; 134.4; 135.2; 141.1; 149.8; 156.9; 177.0. MS: 468 (20, M ), 440 (50),
85 (100), 174 (30). Anal. calc. for C H BrN O (468.05): C 66.54, H 3.65, N 5.97; found: C 66.59, H
.60, N 5.93.
26
17
2
2
1
,2-Dihydro-11-methyl-1-(4-nitrophenyl)-3H-benzo[a]pyrano[2,3-c]phenazin-3-one (6i). Yield:
1
0
(
(
3
1
.40 g (92%). Yellow powder. M.p. 3148 (dec.). IR (KBr): 3443, 1782, 1640, 1516. H-NMR
2
3
300 MHz): 2.57 (s, Me); 3.26 (br. d, J ¼ 18, 1 H of CH ); 3.72 (dd, J ¼ 18, J ¼ 8, 1 H of CH ); 5.65
2
2
13
d, J ¼ 8, CH); 7.57 – 8.31 (m, 10 arom. H); 9.29 (d, J ¼ 4, 1 arom. H). C-NMR (75 MHz): 22.2; 36.6;
7.7; 112.1; 112.3; 115.6; 122.4; 122.5; 123.4; 124.7; 125.8; 126.2; 126.5; 127.2; 128.9; 130.8; 131.7; 134.8;
þ
35.3; 144.6; 155.0; 161.2; 168.9; 179.5. MS: 435 (60, M ), 407 (90), 285 (100), 180 (20). Anal. calc. for
C H N O (435.12): C 71.72, H 3.94, N 9.65; found: C 71.70, H 3.97, N 9.60.
26
17
3
4
1
-(3-Bromophenyl)-1,2-dihydro-11-methyl-3H-benzo[a]pyrano[2,3-c]phenazin-3-one (6j). Yield:
1
0
(
8
1
1
.39 g (85%). Yellow powder. M.p. 3278 (dec.). IR (KBr): 3444, 1781, 1396. H-NMR (300 MHz): 2.58
2
3
s, Me); 3.17 (br. d, J ¼ 15, 1 H of CH ); 3.60 (dd, J ¼ 15, J ¼ 8, 1 H of CH ); 5.52 (d, J ¼ 8, CH); 7.22 –
2
2
13
.22 (m, 10 arom. H); 9.28 (d, J ¼ 6, 1 arom. H). C-NMR (75 MHz): 21.6; 36.2; 36.7; 112.1; 112.4; 116.6;
17.9; 119.2; 119.3; 120.3; 120.8; 122.9; 123.0; 126.2; 126.4; 130.5; 131.9; 132.2; 134.4; 134.5; 135.9; 146.4;
þ
47.9; 149.6; 158.1; 177.0. MS: 468 (40, M ), 440 (50), 285 (100), 174 (20). Anal. calc. for C H BrN O
26
17
2
2
(
468.05): C 66.54, H 3.65, N 5.97; found: C 66.58, H 3.62, N 5.91.
,2-Dihydro-11-methyl-1-(3-nitrophenyl)-3H-benzo[a]pyrano[2,3-c]phenazin-3-one (6k). Yield:
1
1
0
2
.38 g (89%). Yellow powder. M.p. 2988 (dec.). IR (KBr): 3430, 1778, 1465. H-NMR (300 MHz):
2
3
.72 (s, Me); 3.25 (br. d, J ¼ 15, 1 H of CH ); 3.68 (dd, J ¼ 15, J ¼ 9, 1 H of CH ); 5.60 (br. d, J ¼ 9, CH);
2
2

2
34
Helvetica Chimica Acta – Vol. 97 (2014)
7
1
1
.22 – 8.36 (m, 10 arom. H); 9.37 (d, J ¼ 3, 1 arom. H). 13C-NMR (75 MHz): 22.6; 36.1; 36.8; 114.3; 117.2;
17.6; 119.1; 122.3; 126.4; 126.6; 129.4; 131.3; 131.5; 134.2; 135.0; 137.2; 137.4; 138.3; 139.4; 140.4; 146.5;
þ
46.9; 149.2; 155.0; 158.7; 177.3. MS: 435 (15, M ), 359 (20), 282 (100), 174 (30). Anal. calc. for
C H N O (435.12): C 71.72, H 3.94, N 9.65; found: C 71.68, H 3.98, N 9.60.
26
17
3
4
1
,2-Dihydro-11-methyl-1-(2-nitrophenyl)-3H-benzo[a]pyrano[2,3-c]phenazin-3-one (6l). Yield:
1
0
2
7
1
1
.39 g (80%). Yellow powder. M.p. 3118 (dec.). IR (KBr): 3430, 1778, 1466. H-NMR (300 MHz):
2
3
.60 (s, Me); 3.10 (br. d, J ¼ 15, 1 H of CH ); 3.95 (dd, J ¼ 15, J ¼ 6, 1 H of CH ); 5.84 (d, J ¼ 6, CH);
2
2
13
.22 – 8.38 (m, 10 arom. H); 9.29 (d, J ¼ 6, 1 arom. H). C-NMR (75 MHz): 26.7; 35.4; 37.1; 112.2; 112.4;
15.3; 117.2; 119.5; 120.2; 122.7; 122.9; 125.6; 126.8; 128.1; 128.5; 131.4; 132.7; 139.6; 139.7; 140.0; 140.1;
þ
44.2; 155.0; 161.1; 168.4; 179.5. MS: 435 (15, M ), 323 (100), 241 (15), 75 (10). Anal. calc. for
C H N O (435.12): C 71.72, H 3.94, N 9.65; found: C 71.67, H 3.89, N 9.61.
26
17
3
4
1
-(4-Fluorophenyl)-1,2-dihydro-11-methyl-3H-benzo[a]pyrano[2,3-c]phenazin-3-one (6m). Yield:
1
0
2
.34 g (84%). Yellow powder. M.p. 3178 (dec.). IR (KBr): 3432, 1770, 1469. H-NMR (300 MHz):
2
3
.64 (s, Me); 3.20 (br. d, J ¼ 15, 1 H of CH ); 3.70 (dd, J ¼ 15, J ¼ 6, 1 H of CH ); 5.54 (br. d, J ¼ 9, CH);
2
2
7
.26 (d, J ¼ 6, 2 arom. H); 7.46 (d, J ¼ 6, 1 arom. H); 7.81 – 8.31 (m, 6 arom. H); 9.33 (d, J ¼ 3, 1 arom. H).
13
C-NMR (75 MHz): 26.1; 33.7; 35.2; 113.1; 113.7; 114.6; 114.8; 115.8; 116.0; 118.2; 120.9; 124.8; 126.1;
þ
1
28.8; 130.2; 130.4; 131.1; 132.0; 133.3; 134.2; 144.9; 156.7; 160.1; 181.6. MS: 408 (5, M ), 382 (30), 363
(
60), 323 (70), 138 (100). Anal. calc. for C H FN O (408.13): C 76.46, H 4.20, N 6.86; found: C 76.41, H
26 17 2 2
4
.17, N 6.81.
1
-(4-Bromophenyl)-1,2-dihydro-11-nitro-3H-benzo[a]pyrano[2,3-c]phenazin-3-one (6n). Yield:
1
0
(
.37 g (75%). Yellow powder. M.p. 2948 (dec.). IR (KBr): 3441, 1779, 1689, 1628. H-NMR
2
3
300 MHz): 3.20 (br. d, J ¼ 15, 1 H of CH ); 3.69 (dd, J ¼ 15, J ¼ 6, 1 H of CH ); 5.51 (d, J ¼ 9, CH);
2
2
7
.30 (d, J ¼ 9, 2 arom. H); 7.47 (d, J ¼ 6, 2 arom. H); 8.01 – 8.64 (m, 6 arom. H); 9.29 (d, J ¼ 6, 1 arom. H).
13
C-NMR (75 MHz): 34.6; 35.0; 112.4; 112.6; 113.0; 114.4; 119.3; 121.6; 125.2; 126.5; 128.2; 129.2; 129.6;
þ
1
30.9; 131.0; 132.3; 132.8; 133.5; 135.6; 141.9; 148.1; 158.8; 178.3. MS: 500 (20, M ), 470 (40), 315 (100),
1
58 (20). Anal. calc. for C H BrN O (499.02): C 60.02, H 2.82, N 8.40; found: C 60.04, H 2.84, N 8.37.
25
14
3
4
1
-(2,4-Dimethoxyphenyl)-1,2-dihydro-11-nitro-3H-benzo[a]pyrano[2,3-c]phenazin-3-one (6o).
1
Yield: 0.33 g (68%). Yellow powder. M.p. 3328 (dec.). IR (KBr): 3434, 1777, 1603, 1512. H-NMR
(
300 MHz): 3.00 (br. d, J ¼ 18, 1 H of CH ); 3.48 (br. s, MeO, 1 H of CH ); 3.83 (s, MeO); 5.55 (d, J ¼ 6,
2
2
13
CH); 6.34 – 9.15 (m, 9 arom. H); 9.35 (d, J ¼ 6, 1 arom. H). C-NMR (75 MHz): 34.9; 36.8; 55.4; 57.8;
1
1
12.7; 114.9; 115.1; 115.2; 116.4; 119.5; 122.6; 124.2; 129.4; 130.3; 130.9; 132.5; 132.6; 134.5; 136.1; 136.4;
þ
37.2; 137.5; 142.8; 149.4; 155.9; 158.8; 179.4. MS: 481 (100, M ), 453 (90), 436 (70), 220 (60). Anal. calc.
for C H N O (481.13): C 67.36, H 3.98, N 8.73; found: C 67.32, H 3.93, N 8.75.
27
19
3
6
1
,2-Dihydro-11-nitro-1-(2-nitrophenyl)-3H-benzo[a]pyrano[2,3-c]phenazin-3-one (6p). Yield:
1
0
(
.37 g (80%). Yellow powder. M.p. 3088 (dec.). IR (KBr): 3430, 1783, 1642, 1525. H-NMR
2
3
300 MHz): 3.16 (br. d, J ¼ 18, 1 H of CH ); 3.93 (dd, J ¼ 15, J ¼ 9, 1 H of CH ); 5.81 (d, J ¼ 8.4,
2
2
13
CH); 6.25 – 8.65 (m, 10 arom. H); 9.25 (d, J ¼ 9, 1 arom. H). C-NMR (75 MHz): 34.9; 36.7; 113.2; 113.3;
1
1
14.1; 115.4; 116.3; 118.8; 119.9; 120.4; 122.9; 125.4; 126.6; 126.9; 130.7; 131.1; 131.2; 133.3; 133.6; 135.5;
þ
46.9; 148.6; 149.9; 158.2; 174.7. MS: 466 (5, M ), 428 (100), 400 (90), 341 (20). Anal. calc. for
C H N O (466.09): C 64.38, H 3.03, N 12.01; found: C 64.31, H 3.00, N 12.06.
25
14
4
6
1
,2-Dihydro-11-nitro-1-(4-nitrophenyl)-3H-benzo[a]pyrano[2,3-c]phenazin-3-one (6q). Yield:
1
0
3
.37 g (81%). Yellow powder. M.p. 2988 (dec.). IR (KBr): 3435, 1774, 1469. H-NMR (300 MHz):
2
3
.23 (br. d, J ¼ 18, 1 H of CH ); 3.73 (dd, J ¼ 17, J ¼ 9, 1 H of CH ); 5.54 (d, J ¼ 6, CH); 7.32 (d, J ¼ 9, 2
2
2
13
arom. H); 7.48 (d, J ¼ 9, 1 arom. H); 8.02 – 8.96 (m, 6 arom. H); 9.34 (d, J ¼ 6, 1 arom. H). C-NMR
(
1
75 MHz): 34.9; 36.5; 112.6; 112.9; 113.1; 113.2; 114.5; 115.4; 119.6; 120.5; 121.4; 126.4; 126.5; 132.0;
þ
32.5; 132.6; 132.7; 134.7; 134.8; 143.2; 149.5; 155.9; 177.8. MS: 466 (10, M ), 403 (20), 360 (40), 334
(
100). Anal. calc. for C H N O (466.09): C 64.38, H 3.03, N 12.01; found: C 64.32, H 3.09, N 12.06.
25 14 4 6
1
-(4-Bromophenyl)-11,12-dichloro-1,2-dihydro-3H-benzo[a]pyrano[2,3-c]phenazin-3-one (6r).
1
Yield: 0.36 g (68%). Yellow powder. M.p. 2918 (dec.). IR (KBr): 3430, 1783, 1617. H-NMR
2
3
(
300 MHz): 3.20 (br. d, J ¼ 15, 1 H of CH ); 3.67 (dd, J ¼ 15, J ¼ 6, 1 H of CH ); 5.44 (d, J ¼ 6, CH);
2
2
7
.28 (d, J ¼ 6, 2 arom. H); 7.45 (d, J ¼ 6, 2 arom. H); 8.03 – 8.71 (m, 5 arom. H); 9.30 (d, J ¼ 5, 1 arom. H).
13
C-NMR (75 MHz): 35.1; 36.7; 113.2; 114.1; 119.7; 121.3; 122.1; 122.3; 123.7; 123.8; 124.1; 125.2; 126.2;

Helvetica Chimica Acta – Vol. 97 (2014)
235
þ
1
26.5; 130.2; 131.1; 131.6; 133.5; 134.8; 145.3; 149.4; 158.9; 178.3. MS: 524 (30, M ), 496 (70), 339 (100),
2
01 (20). Anal. calc. for C H BrCl N O (521.95): C 57.28, H 2.50, N 5.34; found: C 57.21, H 2.52, N 5.36.
25
13
2
2
2
1
1,12-Dichloro-1,2-dihydro-1-(4-methylphenyl)-3H-benzo[a]pyrano[2,3-c]phenazin-3-one (6s).
1
Yield: 0.35 g (76%). Yellow powder. M.p. 2968 (dec.). IR (KBr): 3432, 1783, 1610, 1521. H-NMR
2
3
(
300 MHz): 2.10 (s, Me); 3.10 (br. d, J ¼ 15, 1 H of CH ); 3.63 (dd, J ¼ 15, J ¼ 6, 1 H of CH ); 5.45 (d,
2
2
J ¼ 6, CH); 7.07 (d, J ¼ 6, 2 arom. H); 7.15 (d, J ¼ 6, 2 arom. H); 8.03 – 8.68 (m, 5 arom. H); 9.28 (d, J ¼ 5, 1
13
arom. H). C-NMR (75 MHz): 23.2; 34.9; 36.8; 112.1; 112.4; 113.5; 113.9; 114.5; 115.1; 119.3; 120.6;
þ
1
4
6
22.1; 126.2; 126.0; 130.2; 131.4; 132.7; 134.5; 134.9; 146.2; 149.4; 158.8; 160.8; 177.5. MS: 459 (30, M ),
96 (70), 339 (100), 201 (20). Anal. calc. for C H Cl N O (458.06): C 67.99, H 3.51, N 6.10; found: C
7.92, H 3.53, N 6.16.
26
16
2
2
2
1
-(3-Bromophenyl)-11,12-dichloro-1,2-dihydro-3H-benzo[a]pyrano[2,3-c]phenazin-3-one (6t).
1
Yield: 0.43 g (82%). Yellow powder. M.p. 3148 (dec.). IR (KBr): 3437, 1773, 1639. H-NMR
2
3
(
300 MHz): 3.29 (br. d, J ¼ 18, 1 H of CH ); 4.31 (dd, J ¼ 18, J ¼ 9, 1 H of CH ); 5.51 (d, J ¼ 9, CH);
2
2
13
7
1
1
.19 – 8.67 (m, 9 arom. H); 9.29 (d, J ¼ 6, 1 arom. H). C-NMR (75 MHz): 33.7; 35.2; 112.1; 113.7; 113.8;
14.4; 114.8; 115.2; 117.0; 117.9; 118.1; 120.8; 124.1; 126.8; 128.0; 130.2; 130.8; 131.2; 132.4; 133.1; 134.1;
þ
48.7; 156.6; 162.8; 181.7. MS: 524 (30, M ), 496 (70), 339 (100), 201 (20). Anal. calc. for
C H BrCl N O (521.95): C 57.28, H 2.50, N 5.34; found: C 57.32, H 2.53, N 5.37.
25
13
2
2
2
1
1,12-Dichloro-1,2-dihydro-1-phenyl-3H-benzo[a]pyrano[2,3-c]phenazin-3-one (6u). Yield: 0.41 g
1
(
(
1
1
92%). Yellow powder. M.p. 3258 (dec.). IR (KBr): 3431, 1785, 1634, 1444. H-NMR (300 MHz): 3.21
2
3
br. d, J ¼ 18, 1 H of CH ); 3.70 (dd, J ¼ 18, J ¼ 8.0, 1 H of CH ); 5.46 (br. d, J ¼ 8.0, CH); 7.20 – 8.44 (m,
2
2
13
0 arom. H); 9.10 (d, J ¼ 5, 1 arom. H). C-NMR (75 MHz): 34.5; 36.6; 112.1; 112.8; 113.7; 113.9; 115.4;
19.7; 121.5; 122.7; 125.5; 126.4; 127.3; 130.3; 130.6; 131.2; 131.4; 134.2; 135.3; 146.3; 148.6; 159.4; 177.4.
þ
MS: 444 (50, M ), 416 (100), 339 (90), 201 (10). Anal. calc. for C H Cl N O (444.04): C 67.43, H 3.17, N
25
14
2
2
2
6
.29; found: C 67.40, H 3.11, N 6.34.
1,12-Dichloro-1,2-dihydro-1-(4-nitrophenyl)-3H-benzo[a]pyrano[2,3-c]phenazin-3-one (6v).
Yield: 0.41 g (84%). Yellow powder. M.p. 2988 (dec.). IR (KBr): 3438, 1771, 1469. 1H-NMR
1
2
3
(
300 MHz): 3.21 (br. d, J ¼ 15, 1 H of CH ); 3.70 (dd, J ¼ 15, J ¼ 6, 1 H of CH ); 5.47 (br. d, J ¼ 6,
2
2
CH); 7.29 (d, J ¼ 9, 2 arom. H); 7.48 (d, J ¼ 9, 2 arom. H); 8.02 – 8.63 (m, 5 arom. H); 9.25 (d, J ¼ 9, 1
13
arom. H). C-NMR (75 MHz,): 34.4; 36.6; 116.5; 116.6; 116.9; 117.3; 117.6; 122.2; 123.0; 124.0; 124.4;
þ
1
26.6; 127.9; 128.1; 129.8; 131.4; 132.2; 135.5; 135.8; 145.0; 149.3; 159.7; 177.5. MS: 489 (10, M ), 4434
(
10), 323 (100), 246 (10). Anal. calc. for C H C N O (489.03): C 61.24, H 2.67, N 8.57; found: C 61.29, H
25 13 l2 3 4
2
.62, N 8.51.
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Received January 4, 2013