8
H. Gu ꢀe douar et al. / C. R. Chimie xxx (2017) 1e9
obtained from 9d; yield: 75%; orange needles; mp 203
H-6), 7.83e7.84 (m, 2H), 8.20e8.30 (m, 3H), 8.52 (d,
J ¼ 7.8 Hz, 1H, H-2), 9.17 (s, 1H, H-4), 9.34 (d, J ¼ 8.4 Hz, 1H,
ꢁ
1
e204 C. H NMR (300 MHz, CDCl
.01 (s, 3H, CO CH
3
):
d
¼ 2.72 (s, 3H, CH
3
);
13
4
2
3
), 7.32 (d, J ¼ 7.5 Hz, 1H, H-7), 7.61 (t,
H-5); C NMR (75 MHz, CDCl
3
):
d
¼ 27.41 (CH
3
), 52.32
J ¼ 7.8 Hz, 1H, H-6), 7.99 (d, J ¼ 7.8 Hz, 1H), 8.06 (d,
J ¼ 8.1 Hz, 1H), 8.18 (d, J ¼ 8.1 Hz, 1H, H-5), 8.65 (s, 1H, H-4);
3
(OCH ), 121.62 (CH), 125.32 (CH), 126.34 (CH), 127.77 (CH),
128.59 (C), 129.29 (2CH), 129.46 (CH), 129.80 (CH), 129.86
(CH), 131.29 (C), 132.46 (C), 132.80 (C), 133.01 (CH), 133.72
(C), 140.43 (C), 140.98 (C), 141.46 (C), 141.89 (C), 145.43 (C),
13
C NMR (75 MHz, CDCl
3
):
d
¼ 22.86 (CH
3 3
), 52.29 (OeCH ),
122.47 (CH), 125.42 (CH), 128.69 (C), 129.17 (CH), 129.32
(
(
1
CH), 132.62 (C), 133.74 (CH), 134.58 (CH), 135.63 (C), 135.77
C), 136.38 (C), 145.02 (C), 165.21 (C]O), 180.81 (C]O),
167.01 (C]O); HRMS (MALDI-TOF) calcd for C23
[M þ H] : 353.1290. Found: 353.1284.
H
16
N
2
O
2
þ
82.02 (C]O); HRMS (MALDI-TOF) calcd for C17
12
H O
4
þ
[M þ H] : 281.0814. Found: 281.0812.
4
.4.6. Synthesis of 9,10-diethoxyphenanthrene 12
A mixture of 9,10-phenanthrenequinone 10a (2.4 mmol;
equiv), Bu NBr (1.53 mmol), and Na (13.80 mmol) in
O (10 mL) and THF (10 mL) was shaken for 5 min. Then,
4
.4.5. General procedure for synthesis of phenazine derivatives
Phenanthrenequinone 10aed (0.48 mmol; 1 equiv) and
,2-diaminobenzene (0.52 mmol; 1.1 equiv) were sus-
1
H
4
2 2 4
S O
2
1
0
.53 mL of bromoethane (7.20 mmol; 3 equiv) was added
dropwise, followed by aqueous solution of KOH (35.66 mmol,
in 10 mL of H O). The resulting mixture was shaken for about
days, poured into H O (75 mL), and extracted with EtOAc.
The extracts were washed twice with H O and then brine,
dried over MgSO , and filtered. The solvent was removed
under reduced pressure giving 9,10-diethoxyphenanthrene
pended onto 1.64 mL of a 1:2 glacial AcOH/anhydrous EtOH
solution. After heating to reflux for 3 h, the color of the
mixture changes from orange to yellow. Once cooled to
room temperature, the solids were transferred to 20 mL of
water and then suction-filtered, copiously washed with
water, then EtOH, and finally hexane.
2
2
2
2
4
1
1
2 as a yellow oil in 86% yield. H NMR (300 MHz, CDCl
3
):
4
.4.5.1. Dibenzo[a,c]phenazine 11a. Following the general
d
¼ 1.64 (t, J ¼ 6.9 Hz, 6H, 2CH ), 4.44 (q, J ¼ 6.9 Hz, 4H, 2CH ),
3
2
procedure, 11a was obtained from 10a; yield: 85%; pale yel-
low needles; mp 225e226 C. H NMR (300 MHz, CDCl
d
7.65e7.76 (m, 4H), 8.40 (dd, J ¼ 1.8 Hz, J ¼ 8.4 Hz, 2H, H-1 and
ꢁ
1
13
3
):
H-8), 8.71 (dd, J ¼ 1.2 Hz, J ¼ 9 Hz, 2H, H-4 and H-5); NMR
C
¼ 7.69e7.86 (m, 6H), 8.28e8.34(m, 2H), 8.53(dd, J
1
¼1.5 Hz,
(75 MHz, CDCl ):
d
¼ 15.55 (2CH ), 68.60 (2CH ), 121.96
3
3
2
1
3
J
(
(
2
¼ 9 Hz, 2H), 9.38 (dd, J
75 MHz, CDCl ):
¼ 122.87 (2CH), 126.25 (2CH), 127.88
2CH),129.43 (2CH),129.70 (2CH),130.26 (2CH),130.28 (2C),
32.02 (2C]N), 142.15 (2C), 142.40 (2 ]CeN) [37a].
1
¼1.2 Hz, J
2
¼ 7.2 Hz, 2H); C NMR
(2CH), 122.19 (2CH), 125.28 (2CH), 126.32 (2CH), 128.24 (2C),
129.34 (2C), 142.69 (2C]O).
3
d
1
4
.4.7. Synthesis of 3,6-diacetyl-9,10-diethoxyphenanthrene 13
In a 50 mL three-necked flask fitted with an HCl trap, the
4
.4.5.2. 3-Methyldibenzo[a,c]phenazine 11b. Following the
9
,10-diethoxyphenanthrene 12 (0.37 mmol; 1 equiv) was
dissolved in 5 mL of anhydrous CH Cl and acetyl chloride.
The mixture was stirred for 5 min and cooled in an ice bath.
The cooling bath was removed, then AlCl (0.75 mmol;
equiv) was added in portions to the stirred solution.
Thereafter, the mixture was stirred at room temperature for
5 min and carefully poured onto crushed ice. The aqueous
layer was extracted twice with CH Cl , and the combined
organic layers were washed successively with water and
aqueous Na CO , dried over MgSO , and filtered. The solvent
general procedure, 11b was obtained from 10b; yield: 88%;
2
2
ꢁ
1
pale yellow powder; mp 206e207 C. H NMR (300 MHz,
CDCl ): ), 7.53 (d, J ¼ 8,1 Hz, 1H), 7.70
¼ 2.63 (s, 3H, eCH
e7.83 (m, 4H), 8.20e8.40 (m, 3H), 8.51 (d, J ¼ 7.8 Hz, 1H),
3
d
3
3
2
13
9
(
1
(
.24 (d, J ¼ 8.1 Hz, 1H), 9.37 (d, J ¼ 7.5 Hz, 1H); C NMR
75 MHz, CDCl ): ),122.79 (CH),123.06 (CH),
¼ 22.09 (eCH
26.27 (CH), 127.72 (2CH), 127.98 (C), 128.67 (CH), 129.25
CH), 129.35 (CH), 129.44 (CH), 129.56 (CH), 130.13 (CH),
30.43 (C), 132.03 (2C), 140.42 (C), 142.00 (C), 142.21 (C),
3
d
3
1
2
2
1
2
3
4
142.30 (]CeN), 142.59 (]CeN); HRMS (MALDI-TOF) calcd
was evaporated, and the residual solid was shaken with
MeOH, filtered, and washed with MeOH to give the 3,6-
diacetyl-9,10-diethoxyphenanthrene 13 in 91% yield as a
þ
for C21
H N
14 2
[M þ H] : 295.1235. Found: 295.1230 [37b].
ꢁ
1
4
.4.5.3. 3,6-Dibromodibenzo[a,c]phenazine
11c. Following
3
pale yellow solid; mp 164e165 C. H NMR (300 MHz, CDCl ):
the general procedure, 11c was obtained from 10c; yield:
d
¼ 1.54 (t, J ¼ 6.9 Hz, 6H, 2CH ), 2.83 (s, 6H, 2CH ), 4.38 (q,
3
3
ꢁ
1
9
(
8
6%; lemon yellow powder; mp 319e320 C. H NMR
300 MHz, 2% CF CO H/CDCl ):
¼ 8.05 (d, J ¼ 8.7 Hz, 2H),
¼ 3.3 Hz, J ¼ 6.6 Hz, 2H, H-2 and H-7), 8.64 (d,
J ¼ 6.9 Hz 4H, 2CH ), 8.20e8.25 (m, 2H, H-2 and H-7), 8.35 (d,
2
3
2
3
d
J ¼ 8.4 Hz, 2H, H-1 and H-8), 9.34 (s, 2H, H-4 and H-5); NMR
13
.26 (dd, J
1
2
C (75 MHz, CDCl ):
d
¼ 15.35 (2CH ), 26.47 (2CH ), 68.80
3
3
3
J ¼ 6.6 Hz, 2H), 8.71 (s, 2H, H-4 and H-5), 9.16 (d, J ¼ 9 Hz,
(2CH ), 122.56 (2CH), 123.08 (2CH), 125.70 (2CH), 127.96 (2C),
132.69 (2C), 134.11 (2C), 144.27 (2CeO), 197.49 (2C]O).
2
1
3
2
H); C NMR (75 MHz, 2% CF
3
CO
2
H/CDCl
3
):
d
¼ 122.68
(
(
2CeBr), 125.03 (2CH), 126.79 (2CH), 127.65 (2CH), 129.89
2C), 132.80 (2C), 133.14 (2CH), 134.67 (2CH), 136.13 (2C),
4
.4.8. Synthesis of 3-acetyl-9,10-diethoxyphenanthrene 14
138.30 (2 ]CeN) [37c].
AlCl (0.37 mmol; 1 equiv) was added carefully to a so-
3
lution of 9,10-diethoxyphenanthrene 12 (0.37 mmol;
4
.4.5.4. Methyl 8-methyldibenzo[a,c]phenazine-3-carboxylate
1 equiv) and acetyl chloride in anhydrous CH Cl . The
2
2
1
1d. Following the general procedure, 11d was obtained
mixture was stirred at room temperature for 2 h, diluted
with CH Cl , and then poured onto crushed ice. After
ꢁ
from 10d; yield: 91%; pale yellow powder; mp 200e201 C.
2
2
1
H NMR (300 MHz, CDCl
3
):
d
¼ 3.34 (s, 3H, CH
3
), 4.05 (s, 3H,
washing with saturated NaHCO and brine, then drying with
3
CO
2
CH
3
), 7.53 (d, J ¼ 6.9 Hz, 1H, H-7), 7.63 (t, J ¼ 7.8 Hz, 1H,
MgSO4 and after evaporation of the solvent, the 3-acetyl-
Please cite this article in press as: H. Gu eꢀ douar, et al., Synthesis and characterization of phenanthrene derivatives with anticancer