A novel one-pot and rapid synthesis of polyfunctionalized benzo[a]pyrimido[5’,4’:5,6] pyrido[2,3-c]phenazine derivatives under microwave irradiation

Article abstract of DOI:10.3906/kim-1710-13

A one-pot, environmentally friendly, and efficient protocol for the synthesis of novel polyfunctionalized benzo[a]pyrimido[5’,4’:5,6]pyrido[2,3-c]phenazine derivatives has been reported by a one-pot, four-component sequential reaction between 2-hydroxynaphthalene-1,4-dione, benzene-1,2-diamines, benzaldehydes, and 6-amino-1,3-dimethyluracil in the presence of p-TSA as a nontoxic, inexpensive, ecofriendly, and efficacious solid acid catalyst. Two C-C bonds, two C=N bonds, and one C-N bond, as well as two new rings, were formed in this reaction. Through this procedure, compounds with substantial biological and pharmaceutical properties are generated in a single operation. Factors such as high yields, less reaction time, operational simplicity, and lack of any dangerous reagents/solvents have made this process a green one.

Full text of DOI:10.3906/kim-1710-13

Turk J Chem
Turkish Journal of Chemistry
(2018) 42: 1008 – 1017
© TÜBİTAK
http://journals.tubitak.gov.tr/chem/
doi:10.3906/kim-1710-13
Research Article
A novel one-pot and rapid synthesis of polyfunctionalized
benzo[a]pyrimido[5’,4’:5,6] pyrido[2,3-c]phenazine derivatives under microwave
irradiation
Mahdieh TABIBIAN,, Razieh MOHEBAT∗,, Masoumeh TABATABAEE,
Department of Chemistry, Yazd Branch, Islamic Azad University, Yazd, Iran
Received: 06.10.2017
•
Accepted/Published Online: 02.04.2018
•
Final Version: 03.08.2018
Abstract: A one-pot, environmentally friendly, and efficient protocol for the synthesis of novel polyfunctionalized
benzo[a]pyrimido[5’,4’:5,6]pyrido[2,3-c]phenazine derivatives has been reported by a one-pot, four-component sequential
reaction between 2-hydroxynaphthalene-1,4-dione, benzene-1,2-diamines, benzaldehydes, and 6-amino-1,3-dimethyluracil
in the presence of p-TSA as a nontoxic, inexpensive, ecofriendly, and efficacious solid acid catalyst. Two C-C bonds,
two C=N bonds, and one C-N bond, as well as two new rings, were formed in this reaction. Through this procedure,
compounds with substantial biological and pharmaceutical properties are generated in a single operation. Factors such
as high yields, less reaction time, operational simplicity, and lack of any dangerous reagents/solvents have made this
process a green one.
Key words: Multicomponent reactions, microwave irradiation, p-TSA, benzo[a]pyrimido[5’,4’:5,6]pyrido[2,3-c]phenazine.
1. Introduction
In recent years, due to increased attention to the environment, creating compounds with a significant framework
and virtues was considered via the design of green chemical processes by the maximum structural complexity
1
and the least number of synthetic stages.
In this direction, multicomponent reactions are highly efficient processes that construct complex molecules
from simple substances. This kind of method has become valued in organic chemistry because of many advan-
tages such as structural variety, straightforward processes, being low-priced, facile performance, ecofriendliness,
reducing chemical waste in synthesis, atom economy, excellent selectivity, and minimal reaction stages with
2
excellent yields.
In addition, microwave-assisted organic synthesis has been introduced as a revolution in the preparation of
heterocyclic compounds. This nonclassic heating has resulted in the development of efficient synthetic methods
for producing drugs. The significant advantages of this technique are high yields with maximum optimal use of
3
the reactants and short time span of protocol.
4
Pyridopyrimidines as fused pyrimidines are important for pharmaceutical exponents. Some of them are
5−8
found in a number of natural compounds like DNA, RNA, and cofactors.
Many studies showed that these
9,10
compounds display various bioactivities such as anticancer, cyclin-dependent kinase 4 (CDK4) inhibition,
insecticidal, antihistaminic, antibacterial, and antiinflammatory activities.
11
12
13
14
∗Correspondence: raziehmohebat@yahoo.com
1008
This work is licensed under a Creative Commons Attribution 4.0 International License.

TABIBIAN et al./Turk J Chem
Moreover, phenazines are a worthy kind of annulated pyrazines that are produced naturally by many
15
16
bacteria and they have attracted much interest due to their pharmacological and biological characteristics
17−21
including chemopreventive, insecticidal, antibiotic, antimalarial, antiparasitic, and fungicidal activities.
Considering the abovementioned points and as part of our research on the development of environ-
22−25
mentally friendly methods for the synthesis of heterocyclic compounds
, we would like to describe a
highly effectual and precipitous process through the four-component sequential condensation reaction be-
tween 2-hydroxynaphthalene-1,4-dione 1, benzene-1,2-diamines 2, benzaldehyde compounds 4, and 6-amino-
1,3-dimethyluracil 5 in the presence of p-TSA as a green catalyst for the synthesis of novel benzo[a]pyrimido
[5’,4’:5,6]pyrido[2,3-c]phenazine derivatives 6 under conventional heating or microwave irradiation (Scheme 1).
Scheme 1. Synthesis of benzo[a]pyrimido[5’,4’:5,6]pyrido[2,3-c]phenazine derivatives. Structures of 4a–4i are listed in
Table 2.
2. Results and discussion
In order to determine the suitable catalyst for the synthesis of pyridopyrimidine compounds, a one-pot,
four-component condensation reaction was carried out utilizing 2-hydroxy-1,4-naphthoquinone (1) (1 mmol),
benzene-1,2-diamine (2a) (1 mmol), 4-chloro-3-nitrobenzaldehyde (4a) (1 mmol), and 6-amino-1,3-dimethyluracil
(5) (1 mmol) in the presence of Lewis acids, protic liquid acids, and solid acids (Scheme 2).
Initially, in order to increase the efficiency and reduce byproducts, 2-hydroxy-1,4-naphthoquinone (1) and
benzene-1,2-diamine (2a) were blended in the presence of various catalysts for the synthesis of benzo[a]phenazin-
5-ol (3). In the next step, 4-chloro-3-nitrobenzaldehyde (4a) and 6-amino-1,3-dimethyluracil (5) were mixed
with a 1:1 ratio for the synthesis of novel 16-(4-chloro-3-nitrophenyl)-2,4-dimethyl-5,16-dihydrobenzo[a]pyrimido
[5’,4’:5,6]pyrido[2,3-c]phenazine-1,3(2H ,4H)-dione (6a). As indicated in Table 1, the best efficiency and yields
were achieved with 20% mol of p-TSA under solvent-free conditions.
The reaction was repeated for the synthesis of 6a–6k in the presence of p-TSA as a suitable catalyst.
As expected, the products were obtained with high yields (Table 2).
1
13
Heterocyclic compounds 6a–6k were confirmed by IR, H and C NMR, elemental analysis, and mass
spectrometry. The structure of product 6a is discussed as a representative spectrum with the NMR spectroscopy
1009

TABIBIAN et al./Turk J Chem
Scheme 2. Synthesis of 16-(4-chloro-3-nitrophenyl)-2,4-dimethyl-5,16-dihydrobenzo[a]pyrimido[5’,4’:5,6]pyrido[2,3-
c]phenazine-1,3(2H ,4H)-dione (6a).
Table 1. Optimization of the four-component sequential reaction conditions of 2-hydroxy-1,4-naphthoquinone, benzene-
1,2-diamine, 4-chloro-3-nitrobenzaldehyde, and 6-amino-1,3-dimethyluracil in the case of various catalysts under different
thermal conditions.
a
a
Conventional heating
Entry Catalyst (mol%) T (◦C) Time (min) Yield (%)
Microwave irradiation
Power (W)
b
c
b
Time (min) Yield (%)
1
2
3
4
5
6
7
8
None
100
100
100
100
100
100
100
70
40
30
30
30
30
30
30
40
30
30
30
-
300
300
300
300
300
300
300
180
15
10
10
10
10
10
10
15
10
10
10
-
FeCl3 (15)
ZnCl2 (15)
ꢀHCl (15)
CH3CO2 (15)
CF3CO2H (15)
p-TSA (15)
p-TSA (15)
p-TSA (20)
p-TSA (10)
p-TSA (15)
56
48
65
77
62
88
67
88
79
87
62
57
68
80
67
94
75
92
83
90
9
10
11
100
100
140
300
300
450
a
b
c
The reaction was achieved through thermal (∆) and microwave irradiation (MW) under solvent-free conditions.
Isolated yields.
The reaction was conducted at various microwave powers (180–450 W) at 70–140 ◦ C.
1
data. The H NMR spectrum of 6a displayed two singlets at δ = 3.34 and 3.49 ppm for the two methyl groups,
one singlet for the allylic methine at δ = 5.33 ppm, and another one at δ = 10.08 ppm for the NH group, which
was exhibited through the absorption of IR at 3430 cm−1 . In addition, when isobutyraldehyde as an aliphatic
aldehyde was mixed with 3 and 5, reaction between these three materials did not occur.
For a better perception of the process presented, a suggested mechanism for the sequential one-pot
synthesis of benzo[a]pyrimido[5’,4’:5,6]pyrido[2,3-c]phenazines is proposed in Scheme 3. First, the organiza-
tion of benzo[a]phenazin-5-ol (3a) can be explained via a condensation of 4-hydroxy-1,2-naphthoquinone (1)
and benzene-1,2-diamine (2a). Then the efficient Knoevenagel condensation of benzo[a]phenazin-5-ol (3a) and
aryladehyde 4 created product 8. Lastly, compound 6a was offered by a sequence of facile Michael addi-
2,26
tion/cyclization/dehydration reactions between 8 and 6-amino-1,3-dimethyluracil 5 (Scheme 3).
In conclusion, we have developed a novel highly efficient synthesis of pyrimidine-based pyrido[2,3-
c]phenazine derivatives through the one-pot, four-component sequential reaction of 2-hydroxynaphthalene-1,4-
1010

TABIBIAN et al./Turk J Chem
Table 2. Synthesis of benzo[a]pyrimido[5’,4’:5,6]pyrido[2,3-c]phenazine derivatives.
a
Time (min) Yield (%)
Entry Ar
Diamine Product
b
c
b
c
∆
MW
∆
MW
1
2
3
4
5
6
7
8
9
10
4-Cl-3-NO2C6H3
2-BrC6H4
3-CH3OC6H4
2a
2a
2a
6a
6b
6c
6d
6e
6f
6g
6h
6i
30 10
30 10
40 15
50 15
40 15
30 10
40 10
40 15
30 10
30 10
30 10
88 94
82 86
76 81
74 78
80 84
85 90
81 85
79 84
84 89
72 76
87 93
2-OH-3-CH3OC6H3 2a
2-CH3OC6H4
2,4-Cl2C6H3
2-OH-5-NO2C6H4
2-OHC6H4
2-ClC6H4
2,4-Cl2C6H3
2,4-Cl2C6H3
2a
2a
2a
2a
2a
2b
2c
6j
6k
11
a
Isolated yields.
The times and yields of reactions under thermal (∆) conditions at 100 ◦C.
The times and yields of reactions under microwave irradiation (300 W, 100 ◦C) conditions.
b
c
Scheme 3. Suggested mechanism for the one-pot synthesis of benzo[a] pyrimido[5’,4’:5,6]pyrido[2,3-c]phenazines.
1011

TABIBIAN et al./Turk J Chem
dione, benzene-1,2-diamine, arylaldehyde, and 6-amino-1,3-dimethyluracil in the presence of p-TSA as a green
catalyst under microwave irradiation conditions. Novelty, available materials, operational simplicity, use of
inexpensive and nontoxic catalyst without any byproduct in solvent-free conditions, and most importantly the
existence of heterocyclic frames with high biological properties in the product are features of this method.
3. Experimental
3.1. General procedures
All materials utilized including solvents and reactants were obtained from Aldrich and Merck, which did
not require purification. Elemental analyses were performed using a Costech ECS 4010 CHNS-O analyzer.
IR spectra were recorded on a Shimadzu IR-470 spectrometer. Mass spectra were recorded on an Agilent
Technology (HP) spectrometer operating at an ionization potential of 70 eV. Melting points were measured on
1
13
an Electrothermal 9100 apparatus. H NMR and C NMR were determined on Bruker 400 MHz spectrometer
in CDCl3 as the solvent. All reactions were carried out using a laboratory microwave oven (MicroSYNTH,
Milestone Company, Italy). Thin-layer chromatography (TLC) was performed on silica-gel Polygram SILG/UV
254 plates.
3.2. General procedure for the synthesis of benzo[a]pyrimido[5,4’:5,6]pyrido[2,3-c] phenazine deriva-
tives
At the beginning, a mixture of equimolar amounts of 2-hydroxynaphthalene-1,4-dione (1) (1 mmol), benzene-
1,2-diamine 2 (1 mmol), and p-TSA (20 mol%) was stirred under solvent-free microwave irradiation (300 W for
100 ◦ C) or conventional heating (100 ◦ C) conditions. The reaction was completed in less than 6 min with the
formation of orange solid 3. Then arylaldehyde 4 (1 mmol) and 6-amino-1,3-dimethyluracil 5 (1 mmol) were
added to orange product 3 under microwave irradiation or conventional heating at the right temperature and
appropriate time as illustrated in Table 2. The creation of product 6 was confirmed by TLC and the reaction
mixture was cooled, washed with ethanol (10 mL), filtered, and dried to obtain solid pure powder 6.
3.2.1. 16-(4-Chloro-3-nitrophenyl)-2,4-dimethyl-5,16-dihydrobenzo[a]pyrimido[5’,4’:5,6]pyrido
[2,3-c]phenazine-1,3(2H,4H)-dione (Table 2, entry 1)
Red powder, yield under ∆: 0.484 g (88%), under MW: 0.517 g (94%), mp 271–273 ◦ C; IR (KBr) (ν
,
max
cm−1): 3430, 3035, 2900, 1685, 1652, 1585, 1559, 1526, 1498, 1351, 1275, 1145, 1058, 761; H NMR (400 MHz,
CDCl3): δ 3.34 (s, 3H, NCH3), 3.81 (s, 3H, NCH3), 5.33 (s, 1H, CH), 7.29–7.44 (m, 1H, ArH), 7.51–7.57 (m,
1H, ArH), 7.62 (d, J = 8.0 Hz, 1H, ArH), 7.67 (d, J = 8.0 Hz, 1H, ArH), 7.84–8.18 (m, 1H, ArH), 8.34 (d, J =
8.0 Hz, 1H, ArH), 8.38–8.42 (m, 1H, ArH), 8.45 (d, J = 8.4 Hz, 1H, ArH), 8.52–8.74 (m, 1H, ArH), 9.06–9.12
1
13
(m, 1H, ArH), 9.34–9.42 (m, 1H, ArH), 10.08 (s, 1H, NH) ppm; C NMR (100 MHz, CDCl3): δ 28.6, 30.6
(2CH3), 35.7 (CH), 86.7, 117, 124.0, 124.5, 125.1, 125.9, 126.4, 128.5, 129.1, 129.5, 129.8, 130.0, 130.4, 130.6,
130.7, 131.3, 132.6, 137.0, 139.4, 140.3, 142.6, 143.6, 150.6, 154.9 (Colefinic and Carom), 157.5, 161.5 (2C=O)
+
ppm; MS (m/z, %): 550 (M , 4); Anal. Calcd for C29 H19 ClN6 O4 : C, 63.22; H, 3.48; N, 15.25 %. Found: C,
63.41; H, 3.32; N, 15.19 %.
1012

TABIBIAN et al./Turk J Chem
3.2.2. 16-(2-Bromophenyl)-2,4-dimethyl-5,16-dihydrobenzo[a]pyrimido[5’,4’:5,6]pyrido[2,3-c]phe-
nazine-1,3(2H,4H)-dione (Table 2, entry 2)
Dark orange powder, yield under ∆: 0.451 g (82%), under MW: 0.473 g (86%), mp 249–250 ◦ C; IR (KBr)
1
(νmax , cm−1): 3365, 3035, 2905, 1686, 1657, 1586, 1560, 1499, 1452, 1344, 1266, 1130, 1046, 754; H NMR
(400 MHz, CDCl3): δ3.38 (s, 3H, NCH3), 3.73 (s, 3H, NCH3), 5.33 (s, 1H, CH), 7.11–7.28 (m, 1H, ArH),
7.51–7.62 (m, 5H, ArH), 7.83–7.90 (m, 1H, ArH), 8.37 (d, J = 8.0 Hz, 1H, ArH), 8.50–8.52 (m, 1H, ArH),
13
8.60–8.62 (m, 1H, ArH), 9.09–9.10 (m, 1H, ArH), 9.39–9.42 (m, 1H, ArH), 10.39 (s, 1H, NH) ppm; C NMR
(100 MHz, CDCl3): δ28.5, 29.6 (2CH3), 36.6 (CH), 87.8, 116.9, 123.8, 124.8, 125.0, 126.0, 127.1, 127.2, 127.9,
128.3, 128.7, 128.9, 129.6, 129.8, 130.2, 130.5, 130.8, 131.3, 131.6, 133.0, 135.1, 137.8, 145.7, 154.4 (Colefinic
+
and Carom), 157.7, 163.8 (2C=O) ppm; MS (m/z, %): 549 (M , 2); Anal. Calcd for C29 H20 BrN5 O2 : C,
63.28; H, 3.66; N, 12.27 %. Found: 63.45; H, 3.52; N, 12.31 %.
3.2.3. 16-(3-Methoxyphenyl)-2,4-dimethyl-5,16-dihydrobenzo[a]pyrimido[5’,4’:5,6]pyrido[2,3-c]
phenazine-1,3(2H,4H)-dione (Table 2, entry 3)
Brown powder, yield under ∆: 0.381 g (76%), under MW: 0.406 g (81%), mp 223–225 ◦ C; IR (KBr) (ν
,
max
cm−1): 3375, 3020, 2915, 1685, 1656, 1578, 1490, 1441, 1356, 1250, 1137, 1041, 757; H NMR (400 MHz,
CDCl3): δ 3.32 (s, 3H, NCH3), 3.67 (s, 3H, OCH3), 3.72 (s, 3H, NCH3), 5.32 (s, 1H, CH), 7.03–7.29 (m, 1H,
ArH), 7.43–7.58 (m, 1H, ArH), 7.65 (t, J = 7.6 Hz, 1H, ArH), 7.70–7.96 (m, 3H, ArH), 8.04 (d, J = 8.0 Hz,
1H, ArH), 8.16–8.30 (m, 1H, ArH), 8.36 (d, J = 7.6 Hz, 1H, ArH), 8.43 (d, J = 8.0 Hz, 1H, ArH), 8.54–8.56
1
13
(m, 1H, ArH), 9.12–9.34 (m, 1H, ArH), 10.00 (s, 1H, NH) ppm; C NMR (100 MHz, CDCl3): δ28.6, 30.4
(2CH3), 35.2 (CH), 58.3 (OCH3), 87.4, 110.2, 112.2, 118.1, 119.3, 121.5, 123.6, 124.6, 124.8, 125.2, 126.0, 128.9,
129.3, 129.6, 130.2, 131.2, 131.7, 131.9, 134.2, 139.1, 140.5, 143.1, 150.9, 153.2 (Colefinic and Carom), 159.5,
+
168.1 (2C=O) ppm; MS (m/z, %): 501 (M , 6); Anal. Calcd for C30 H23 N5 O3 : C, 71.84; H, 4.62; N, 13.96
%. Found: C, 71.98; H, 4.73; N, 13.91 %.
3.2.4. 16-(2-Hydroxy-3-methoxyphenyl)-2,4-dimethyl-5,16-dihydrobenzo[a]pyrimido[5’,4’:5,6]
pyrido[2,3-c]phenazine-1,3(2H,4H)-dione (Table 2, entry 4)
Green powder, yield under ∆: 0.383 g (74%), under MW: 0.403 g (78%), mp 225–226 ◦ C; IR (KBr) (ν
,
max
cm−1): 3460, 3025, 2900, 1693, 1645, 1580, 1451, 1405, 1369, 1334, 1278, 1088, 1027, 745; H NMR (400 MHz,
1
CDCl3): δ3.30 (s, 3H, NCH3), 3.72 (s, 3H, OCH3), 3.75 (s, 3H, NCH3), 5.88 (s, 1H, CH), 6.81–9.35 (m, 11H,
13
ArH), 9.74 (s, 1H, OH), 10.90 (s, 1H, NH) ppm; C NMR (100 MHz, CDCl3): δ28.2, 31.0 (2CH3), 36.4 (CH),
58.4 (OCH3), 84.5, 110.3, 120.8, 122.9, 124.6, 125.2, 126.2, 128.1, 128.5, 128.6, 129.1, 129.2, 129.6, 129.7, 130.0,
131.0, 132.3, 138.5, 140.6, 141.6, 142.4, 148.5, 150.9, 153.2 (Colefinic and Carom), 162.1, 165.7 (2C=O) ppm;
+
MS (m/z, %): 517 (M , 2); Anal. Calcd for C30 H23 N5 O4 : C, 69.62; H, 4.48; N, 13.53 %. Found: C, 69.85;
H, 4.35; N, 13.48 %.
1013

TABIBIAN et al./Turk J Chem
3.2.5. 16-(2-Methoxyphenyl)-2,4-dimethyl-5,16-dihydrobenzo[a]pyrimido[5’,4’:5,6]pyrido[2,3-c]
phenazine-1,3(2H,4H)-dione (Table 2, entry 5)
Brown powder, yield under ∆: 0.401 g (80%), under MW: 0.421 g (84%), mp 188–190 ◦ C; IR (KBr) (ν
,
max
cm−1): 3430, 3030, 2915, 1698, 1665, 1578, 1545, 1491, 1407, 1362, 1249, 1045, 745; H NMR (400 MHz,
CDCl3): δ3.33 (s, 3H, NCH3), 3.66 (s, 3H, OCH3), 3.72 (s, 3H, NCH3), 5.20 (s, 1H, CH), 7.06 (dd, J1 = 7.6
Hz, J2 = 1.6 Hz, 1H, ArH), 7.06 (d, J = 8.0 Hz, 1H, ArH), 7.13–7.23 (m, 1H, ArH), 7.29–7.33 (m, 1H, ArH),
7.46–7.52 (m, 1H, ArH), 7.84–7.90 (m, 2H, ArH), 8.33–8.37 (m, 1H, ArH), 8.51–8.60 (m, 1H, ArH), 8.71–8.95
1
13
(m, 1H, ArH), 9.18–9.34 (m, 1H, ArH), 9.40 (d, J = 7.6 Hz, 1H, ArH), 10.52 (s, 1H, NH) ppm; C NMR
(100 MHz, CDCl3): δ28.6, 30.3 (2CH3), 35.3 (CH), 55.7 (OCH3), 83.9, 105.3, 110.3,116.7, 120.7, 122.2, 124.3,
126.9, 127.4, 127.8, 128.2, 128.8, 128.9, 129.0, 129.4, 129.6, 129.7, 129.9, 130.3, 130.9, 131.6, 140.6, 151.0, 153.3
+
(Colefinic and Carom), 157.5, 159.0 (2C=O) ppm; MS (m/z, %): 501 (M , 5); Anal. Calcd for C30 H23 N5 O3 :
C, 71.84; H, 4.62; N, 13.96 %. Found: C, 71.61; H, 4.80; N, 14.02 %.
3.2.6. 16-(2,4-Dichlorophenyl)-2,4-dimethyl-5,16-dihydrobenzo[a]pyrimido[5’,4’:5,6]pyrido[2,3-c]
phenazine-1,3(2H,4H)-dione (Table 2, entry 6)
Dark red powder, yield under ∆: 0.459 g (85%), under MW: 0.486 g (90%), mp 231–232 ◦ C; IR (KBr) (ν
,
max
cm−1): 3350, 3040, 2895, 1667, 1638, 1584, 1560, 1499, 1452, 1361, 1277, 1140, 1057, 757; H NMR (400 MHz,
CDCl3): δ3.38 (s, 3H, NCH3), 3.82 (s, 3H, NCH3), 5.33 (s, 1H, CH), 7.29–7.41 (m, 1H, ArH), 7.52–7.62 (m,
1H, ArH), 7.75 (d, J = 8.0 Hz, 1H, ArH), 7.82–7.92 (m, 2H, ArH), 8.12–8.14 (m, 1H, ArH), 8.30 (t, J = 8.0
Hz, 1H, ArH), 8.37 (d, J = 9.2 Hz, 1H, ArH), 8.50–8.65 (m, 1H, ArH), 8.73 (dd, J1 = 7.2 Hz, J2 = 1.2 Hz, 1H,
1
13
ArH), 9.22–9.29 (m, 1H, ArH), 10.43 (s, 1H, NH) ppm; C NMR (100 MHz, CDCl3): δ28.7, 29.6 (2CH3),
34.3 (CH), 87.2, 112.2, 122.6, 124.7, 125.0, 126.0, 126.4, 127.3, 128.9, 129.4, 129.7, 129.8, 130.0, 130.2, 130.8,
131.4, 131.7, 138.5, 140.8, 141.3, 145.6, 146.6, 150.7, 153.9 (Colefinic and Carom), 154.0, 165.2 (2C=O) ppm;
+
MS (m/z, %): 539 (M , 7); Anal. Calcd for C29 H19 Cl2 N5 O2 : C, 64.46; H, 3.54; N, 12.96 %. Found: C,
64.70; H, 3.68; N, 12.90 %.
3.2.7. 16-(2-Hydroxy-5-nitrophenyl)-2,4-dimethyl-5,16-dihydrobenzo[a]pyrimido[5’,4’:5,6]pyrido
[2,3-c]phenazine-1,3(2H,4H)-dione (Table 2, entry 7)
Red powder, yield under ∆: 0.431 g (81%), under MW: 0.452 g (85%), mp: 235–237 ◦ C; IR (KBr) (ν
,
max
cm−1): 3350, 3050, 2925, 1686, 1585, 1558, 1521, 1443, 1335, 1274, 1147, 1056, 763; H NMR (400 MHz,
CDCl3): δ3.39 (s, 3H, NCH3), 3.75 (s, 3H, NCH3), 5.33 (s, 1H, CH), 7.15 (d, J = 8.0 Hz, 1H, ArH), 7.36 (t,
J = 8.4 Hz, 1H, ArH), 7.44 (t, J = 7.6 Hz, 1H, ArH), 7.54 (d, J = 8.8 Hz, 1H, ArH), 7.60 (t, J = 6.8 Hz,
1H, ArH), 7.80-8.18 (m, 3H, ArH), 8.27–8.53 (m, 1H, ArH), 9.12–9.18 (m, 1H, ArH), 9.32–9.41 (m, 1H, ArH),
1
13
10.15 (s, 1H, NH), 10.89 (s, 1H, OH) ppm; C NMR (100 MHz, CDCl3): δ28.6, 30.5 (2CH3), 35.1 (CH), 86.9,
117.0, 125.4, 126.0, 126.5, 128.4, 128.9, 129.1, 129.8, 130.2, 130.3, 130.5, 131.4, 131.8, 136.9, 140.1, 140.6, 141.0,
141.7, 144.8, 145.5, 148.7, 150.7, 155.0 (Colefinic and Carom), 157.5, 164.7 (2C=O) ppm; MS (m/z, %): 532
+
(M , 2); Anal. Calcd for C29 H20 N6 O5 : C, 65.41; H, 3.79; N, 15.78 %. Found: C, 65.23; H, 3.92; N, 15.74 %.
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TABIBIAN et al./Turk J Chem
3.3. 16-(2-Hydroxyphenyl)-2,4-dimethyl-5,16-dihydrobenzo[a]pyrimido[5’,4’:5,6]pyrido[2,3-c]phe- nazine-
1,3(2H,4H)-dione (Table 2, entry 8)
Orange powder, yield under ∆: 0.386 g (79%), under MW: 0.410 g (84%), mp 244–246 ◦ C; IR (KBr) (ν
,
max
cm−1): 3495, 3025, 2900, 1696, 1644, 1581, 1485, 1444, 1401, 1327, 1283, 1145, 1052, 755; H NMR (400 MHz,
CDCl3): δ3.35 (s, 3H, NCH3), 3.71 (s, 3H, NCH3), 5.89 (s, 1H, CH), 6.87 (td, J1 = 8.4 Hz, J2 = 1.2 Hz,
1H, ArH), 7.14 (dd, J1 = 8.2 Hz, J2 = 1.2 Hz, 1H, ArH), 7.26 (dd, J1 = 8.4 Hz, J2 = 1.2 Hz, 1H, ArH),
7.68–7.71 (m, 1H, ArH), 7.80–7.92 (m, 4H, ArH), 8.18–8.20 (m, 1H, ArH), 8.33–8.40 (m, 1H, ArH), 8.60 (dd, J1
= 8.6 Hz, J2 = 0.8 Hz, 1H, ArH), 9.28 (dd, J1 = 8.0 Hz, J2 = 0.8 Hz, 1H, ArH), 10.42 (s, 1H, NH), 10.60 (s,
1
13
1H, OH) ppm; C NMR (100 MHz, CDCl3): δ28.5, 30.9 (2CH3), 36.5 (CH), 89.1, 115.1, 119.1, 124.2, 124.9,
125.1, 125.2, 127.9, 128.0, 128.3, 128.6, 129.3, 129.4, 129.8, 129.9, 130.1, 131.3, 139.7, 140.7, 141.5, 143.4, 150.3,
+
151.4, 154.0 (Colefinic and Carom), 154.6, 165.1 (2C=O) ppm; MS (m/z, %): 487 (M , 3); Anal. Calcd for
C29 H21 N5 O3 : C, 71.45; H, 4.34; N, 14.37 %. Found: C, 71.20; H, 4.45; N, 14.41 %.
3.3.1. 16-(2-Chlorophenyl)-2,4-dimethyl-5,16-dihydrobenzo[a]pyrimido[5’,4’:5,6]pyri- do[2,3-c]phe-
nazine-1,3(2H,4H)-dione (Table 2, entry 9)
Red powder,yield under ∆: 0.424 g (84%), under MW: 0.449 g (89%), mp 251–252 ◦ C; IR (KBr): 3365, 3040,
1
2915, 1688, 1665, 1585, 1559, 1529, 1499, 1356, 1267, 1123, 1046, 748; H NMR (400 MHz, CDCl3): δ3.35 (s,
3H, NCH3), 3.73 (s, 3H, NCH3), 5.33 (s, 1H, CH), 7.06 (td, J1 = 8.2 Hz, J2 = 1.6 Hz, 1H, ArH), 7.11–7.29
(m, 1H, ArH), 7.39 (dd, J1 = 8.8 Hz, J2 = 1.2 Hz, 1H, ArH), 7.43–7.62 (m, 2H, ArH), 7.82–7.89 (m, 2H, ArH),
8.13 (d, J = 8.0 Hz, 1H, ArH), 8.30 (t, J = 8.4, 1H, ArH), 8.37 (d, J = 7.6 Hz, 1H, ArH), 9.08–9.10 (m, 1H,
13
ArH), 9.38–9.41 (m, 1H, ArH), 10.52 (s, 1H, NH) ppm; C NMR (100 MHz, CDCl3): δ28.5, 30.5 (2CH3),
35.0 (CH), 88.0, 116.8, 124.3, 124.8, 124.9, 126.0, 126.8, 127.1, 127.7, 128.2, 129.8, 130.2, 130.3, 130.4, 131.3,
131.6, 133.6, 135.0, 136.4, 137.0, 140.0, 145.8, 150.9, 154.0 (Colefinic and Carom), 157.8, 163.9 (2C=O) ppm;
+
MS (m/z, %): 505 (M , 2); Anal. Calcd for C29 H20 ClN5 O2 : C, 68.84; H, 3.98; N, 13.84 %. Found: C, 68.58;
H, 3.83; N, 13.93 %.
3.3.2. 16-(2,4-Dichlorophenyl)-2,4-dimethyl-12-nitro-5,16-dihydrobenzo[a]pyrimido[5’,4’:5,6]pyri-
do[2,3-c]phenazine-1,3(2H,4H)-dione (Table 2, entry 10)
Brown powder, yield under ∆: 0.421 g (72%), under MW: 0.445 g (76%), mp 236–238 ◦ C; IR (KBr): 3430,
1
3050, 2900, 1666, 1617, 1582,1555, 1512, 1451, 1331,1144, 1048, 774; H NMR (400 MHz, CDCl3): δ3.37 (s,
3H, NCH3), 3.82 (s, 3H, NCH3), 5.36 (s, 1H, CH), 6.99 (d, 1H, J = 8.4 HZ), 7.05–7.29 (m, 2H, ArH), 7.38–7.42
(m, 1H, ArH), 7.46–7.60 (m, 1H, ArH), 7.90–7.96 (m, 1H, ArH), 8.40–8.62 (m, 2H, ArH), 8.96–9.39 (m, 2H,
13
ArH), 10.45 (s, 1H, NH) ppm; C NMR (100 MHz, CDCl3) δ 28.7, 30.5 (2CH3), 37.9 (CH), 84.6, 117.0, 124.6,
125.8, 126.7, 127.6, 128.8, 129.0, 130.2, 130.3, 130.6, 131.3, 131.6, 132.1, 133.2, 133.7, 134.4, 135.7, 137.3, 139.3,
+
140.8, 143.0, 148.4, 150.8 (Colefinic and Carom), 158.9, 163.5 (2C=O) ppm; MS (m/z, %): 584 (M , 6); Anal.
Calcd for C29 H18 Cl2 N6 O4 : C, 59.50; H, 3.10; N, 14.36 %. Found: C, 59.41; H, 3.26; N, 14.46 %.
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TABIBIAN et al./Turk J Chem
3.3.3. 16-(2,4-Dichlorophenyl)-2,4,13-trimethyl-5,16-dihydrobenzo[a]pyrimido[5’,4’:5,6]pyrido[2,3-
c]phenazine-1,3(2H,4H)-dione (Table 2, entry 11)
Dark orange powder, yield under ∆: 0.482 g (87%), under MW: 0.515 g (93%), mp: 216–218 ◦ C; IR (KBr):
1
3425, 3025, 2900, 1666, 1584, 1556, 1522, 1498, 1340, 1141, 1063, 769; H NMR (400 MHz, CDCl3): δ2.67 (s,
3H, CH3), 3.31 (s, 3H, NCH3), 3.75 (s, 3H, NCH3), 6.18 (s, 1H, CH), 7.29–7.48 (m, 2H, ArH), 7.65–8.52 (m,
13
5H, ArH), 8.08–9.32 (m, 3H, ArH), 10.06 (s, 1H, NH) ppm; C NMR (100 MHz, CDCl3): δ22.0 (CH3), 28.7,
30.5 (2CH3), 34.8 (CH), 88.8, 124.0, 124.4, 124.5, 124.7, 124.9, 125.9, 129.0, 129.2, 129.8, 130.1, 130.3, 131.1,
131.2, 131.5, 131.7, 132.0, 132.8, 133.8, 140.4, 140.6, 147.9, 150.6, 153.5 (Colefinic and Carom), 156.9, 164.6
+
(2C=O) ppm ; MS (m/z, %): 553 (M , 7); Anal. Calcd for C30 H21 Cl2 N5 O2 : C, 59.50; H, 3.10; N, 14.36 %.
Found: C, 59.36; H, 3.28; N, 14.42 %.
Acknowledgment
We gratefully acknowledge the financial support from the Research Council of the Islamic Azad University of
Yazd, Iran.
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