DABCO-catalyzed Five-component Domino Protocol for the Synthesis of Novel Benzo[a]pyrazolo[4’,3’:5,6]pyrano[2,3-c]phenazines in PEG-400 as an Efficient Green Reaction Medium

Full text of DOI:10.1080/00304948.2020.1765297

Organic Preparations and Procedures International
The New Journal for Organic Synthesis
ISSN: 0030-4948 (Print) 1945-5453 (Online) Journal homepage: https://www.tandfonline.com/loi/uopp20
DABCO-catalyzed Five-component Domino
Protocol for the Synthesis of Novel
Benzo[a]pyrazolo[4’,3’:5,6]pyrano[2,3-c]phenazines
in PEG-400 as an Efficient Green Reaction Medium
Afshin Yazdani-Elah-Abadi, Mojtaba Lashkari & Razieh Mohebat
To cite this article: Afshin Yazdani-Elah-Abadi, Mojtaba Lashkari & Razieh Mohebat
(2020): DABCO-catalyzed Five-component Domino Protocol for the Synthesis of
Novel Benzo[a]pyrazolo[4’,3’:5,6]pyrano[2,3-c]phenazines in PEG-400 as an Efficient
Green Reaction Medium, Organic Preparations and Procedures International, DOI:
10.1080/00304948.2020.1765297
To link to this article: https://doi.org/10.1080/00304948.2020.1765297
Published online: 12 Jul 2020.
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ORGANIC PREPARATIONS AND PROCEDURES INTERNATIONAL
https://doi.org/10.1080/00304948.2020.1765297
EXPERIMENTAL PAPER
DABCO-catalyzed Five-component Domino Protocol for the
Synthesis of Novel Benzo[a]pyrazolo[4’,3’:5,6]pyrano[2,3-
c]phenazines in PEG-400 as an Efficient Green
Reaction Medium
Afshin Yazdani-Elah-Abadia, Mojtaba Lashkarib, and Razieh Mohebatc
b
aDepartment of Biology, Science and Art University, Yazd, Iran; Faculty of Science, Velayat University,
c
Iranshahr, Iran; Department of Chemistry, Yazd Branch, Islamic Azad University, Yazd, Iran
ARTICLE HISTORY Received 20 December 2017; Accepted 12 November 2019
Currently green chemistry techniques are attracting wide attention due to their environ-
mental, health, and economic benefits. These green techniques include the use of poly-
ethylene glycol (PEG-400), multi-component reactions (MCRs), microwave reactions,
aqueous media, reusable catalysts and ionic liquids.1–5
In this context, multi-component domino reactions (MDRs) in which more than two
components are combined in a single synthetic operation to generate the desired prod-
uct, without the isolation of any intermediate, have considerable interest as parts of an
efficient bond-forming strategy.6–10 The development of novel MDRs using PEG-400
solvent medium for the design and synthesis of new bioactive heterocycles is an import-
ant topic in the drug discovery process.11–14
Phenazines are a large group of N-containing heterocycles, including more than 100
different compounds of natural origin and over 6000 synthetic compounds. Phenazine
natural products are isolated as secondary metabolites from Pseudomonas, Streptomyces,
and a number of other bacterial genera from soil or marine habitats.15–18 Phenazines
possess significant biological properties including antibiotic, antimicrobial, antimalarial,
antiparasitic and antitumor activities.15–18 Synthetic phenazines, such as NC-190, XR-
11576 and XR-5944 (Figure 1) were reported to display antiproliferative effects against a
variety of human cancer cell lines.19–23 Pyridophenazinediones and their derivatives
have also shown antitumor activity.24,25 Fluorescent phenazine derivatives have been
applied as photo-sensitizers in photodynamic therapy (PDT)26 in which the combin-
ation of light and photo-sensitizer produces highly reactive oxygen species near the
tumor to selectively destroy the targeted tissue.
Pyrazoles have become increasingly important to the pharmaceutical, chemical, and
agricultural industries in recent years.27–29 These five membered heterocycles possess
antimicrobial, anticancer, analgesic, anti-inflammatory, antitubercular, antidepressant,
antihelmintic, anticonvulsant, antipyretic, anti-oxidant and herbicidal properties.30,31
The pyran moiety embraces a number of important pharmaceuticals and natural
products such as alkaloids, carbohydrates, polyether antibiotics, iridoids and
CONTACT Razieh Mohebat
mohebat@iauyazd.ac.ir
Department of Chemistry, Yazd Branch, Islamic Azad
University, Yazd, Iran
ß 2020 Taylor & Francis Group, LLC

2
A. YAZDANI-ELAH-ABADI ET AL.
Figure 1. Biologically active phenazine derivatives.
pheromones.32 Pyran and fused 4H–pyran derivatives have attracted much attention
because of their antibacterial,33 antifungal,34 antimicrobial,35 anticoagulant36 and antitu-
mor37 activities. They could potentially be useful in the treatment of neurodegenerative
diseases, including Parkinson’s and Alzheimer’s diseases, Down’s syndrome, and AIDS-
associated dementia, as well as for the treatment of schizophrenia.38 Optical brighteners,
laser dyes, fluorescence markers, cosmetics, and potent biodegradable agrochemicals39
are well known pyrans.
Accordingly, heterocycles having benzo[a]phenazine, pyrazole and pyran moieties are
important targets in synthetic organic chemistry. Some biologically active pyrano-fused
benzophenazine and pyrazole derivatives40–44 are shown in Figure 2.
In continuing our studies on the green synthesis of heterocyclic compounds,45,46 we now
report an environmentally friendly method for the synthesis of novel benzo[a]pyrano[2,3-
c]phenazine and pyrazole analogues 8 through a domino, five-component condensation
reaction between 2-hydroxynaphthalene-1,4-dione 1, aromatic 1,2-diamines 2, hydrazine 4,
ethyl acetoacetate 5, and benzaldehydes 7 catalyzed by 1,4-diazabicyclo[2.2.2]octane
(DABCO) in polyethylene glycol (PEG-400) at 70 ꢀC (Scheme 1).
To investigate the best conditions for the synthesis of our new phenazines, we carried
out the five-component domino reaction between 1 (1 mmol), o-phenylenediamine 2a
(1 mmol), hydrazine hydrate 4a (1.2 mmol), 5 (1 mmol) and 4-chlorobenzaldehyde 7a
(1 mmol) in EtOH as a model. To minimize the formation of byproducts, the 2-hydroxy-
naphthalene-1,4-dione and o-phenylenediamine were mixed under reflux conditions until,
in less than 5 minutes, an orange solid of benzo[a]phenazin-5-ol 3a was formed without
using any catalyst. Separately, hydrazine hydrate and ethyl acetoacetate were mixed at 70 ꢀC
under solvent-free conditions to produce a white solid of 3-methyl-2-pyrazolin-5-one 6a
(<5 min). Eventually, the obtained 3-methyl-2-pyrazolin-5-one and 4-chlorobenzaldehyde
were added into the initial reaction system and the reaction mixture was refluxed. The
desired product 8a was not obtained when the reaction was carried out under catalyst-free
conditions for 90 minutes (Table 1, entry 1). However, 8a was obtained in 71% yield when
the reaction was conducted in the presence of triethylamine (20 mol%) in EtOH (Table 1,
entry 2).

ORGANIC PREPARATIONS AND PROCEDURES INTERNATIONAL
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Figure 2. Biologically and pharmaceutically active pyrano-fused benzophenazine and pyrazole
derivatives.
Scheme 1. DABCO-catalyzed domino synthesis of 1-methyl-15-aryl-3,15-dihydrobenzo[a]pyrazo-
lo[4’,3’:5,6]pyrano[2,3-c]phenazines (8a-k) using PEG-400 medium.
Several catalysts were subsequently evaluated in the reaction, including triethylamine,
1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), L-proline, p-toluenesulfonic acid (PTSA) and
DABCO; these were all added in substoichiometric amounts (20 mol%) and the reac-
tions were carried out in ethanol under reflux conditions. The reaction went smoothly
in the presence of DABCO affording higher yield (75%) within 60 min (Table 1, entry
6). To select the best solvent for the reaction, the synthesis of compound 8a was exam-
ined in water and PEG-400 (Table 1, entries 7 and 8). Higher yields were obtained
when the reaction was carried out in PEG-400 (Table 1, entry 8). The reaction was per-
formed at different temperatures to determine the optimum reaction temperature. The
reaction was conducted with 20 mol% DABCO in PEG-400 at 90, 70 and 50 ꢀC, and the
desired product 8a was formed in yields of 82%, 80% and 73%, respectively (Table 1,
entries 8-10). Finally, the loading of DABCO was selected, and 10 mol% of DABCO was
the optimal (Table 1, entries 9, 11, 12).

4
A. YAZDANI-ELAH-ABADI ET AL.
Table 1. Optimization of reaction conditions for the synthesis of compound 8aa.
Entry
Catalyst
Reaction conditions
Time (min)
Yield (%)b
1
2
3
4
5
6
7
8
No catalyst
Et3N (20 mol%)
DBU (20 mol%)
EtOH, Reflux
EtOH, Reflux
EtOH, Reflux
EtOH, Reflux
EtOH, Reflux
EtOH, Reflux
H2O, Reflux
90
60
60
60
60
60
60
60
60
90
90
90
NR
71
53
58
64
75
62
82
80
73
82
67
L-Proline (20 mol%)
PTSA (20 mol%)
DABCO (20 mol%)
DABCO (20 mol%)
DABCO (20 mol%)
DABCO (20 mol%)
DABCO (20 mol%)
DABCO (10 mol%)
DABCO (5 mol%)
PEG-400, 90 ꢀC
PEG-400, 70 ꢀC
PEG-400, 50 ꢀC
PEG-400, 70 ꢀC
PEG-400, 70 ꢀC
9
10
11
12
aReaction conditions: 2-hydroxynaphthalene-1,4-dione (1 mmol), o-phenylenediamine (1 mmol), hydrazine hydrate
(1.2 mmol), ethyl acetoacetate (1 mmol) and 4-chlorobenzaldehyde (1 mmol) in the presence of different catalytic sys-
tems under various conditions.
bIsolated yields.
After extensive screening, we thus found that the optimized best yields and time pro-
files were obtained with 10 mol% of DABCO in PEG-400 at 70 ꢀC, which furnished 8a
in 82% yield within 90 minutes (Table 1, entry 11).
To explore the scope of the reaction further, the study was extended to various ben-
zene-1,2-diamines, hydrazines and different aromatic aldehydes using the optimized
conditions, and the results are presented in Table 2. All the reactions were complete in
90-120 minutes and resulted in the formation of the target structures in good yields
(mean 78%).
The structures of all the newly synthesized benzo[a]pyrazolo[40,30:5,6]pyrano[2,3-
1
c]phenazines were deduced by their satisfactory IR, H, 13C NMR, and elemental ana-
lysis data. The mass spectra of these compounds further displayed molecular ion peaks
at the appropriate m/z values.
1
For example, the H NMR spectrum of 8a exhibited one single sharp line at d 1.87,
characteristic for the methyl group; the CH proton (methine group) was observed at d
5.42 as a singlet. The aromatic protons appeared as a mixture of doublets and multiplets
around d 7.02–9.26 and one singlet was observed for the NH group at d 12.01. The 13C
NMR spectrum of 8a showed the characteristic signals due to the methyl and methine
carbons at d 10.4 and 42.3 and the carbons of the olefinic and aromatic groups reson-
ated at d 111.5–160.2. The structural assignment of compound 8a was supported by its
IR spectrum. The NH, aliphatic, C¼N and aromatic groups exhibited strong absorption
bands at 3137, 2930, 1623, 1591 and 1479 cmꢁ1
.
Since polyethylene glycol (PEG-400) has emerged as a green reaction medium with
unique properties, we were able to use PEG-400 as a recyclable medium instead of

ORGANIC PREPARATIONS AND PROCEDURES INTERNATIONAL
5
Table 2. Domino five-component synthesis of benzo[a]pyrazolo[4’,3’:5,6]pyrano[2,3-c]phenazine
derivativesa.
Entry
R1
R2
R3
Product
Time (min)
Yieldb (%)
1
2
3
4
5
6
7
8
H
H
H
H
H
H
H
Cl
Cl
Me
Me
H
H
H
H
H
Ph
Ph
H
H
Ph
H
4-Cl
4-NO2
4-CN
4-Me
4-OMe
4-Cl
4-Me
4-Cl
4-Me
4-Cl
8a
8b
8c
8d
8e
8f
8g
8h
8i
90
90
90
82
84
79
81
75
77
72
78
75
79
81
120
120
120
120
120
120
120
90
9
10
11
8j
8k
4-NO2
aReaction conditions: 2-hydroxynaphthalene-1,4-dione (1 mmol), benzene-1,2-diamine (1 mmol), hydrazine (1.2 mmol),
ethyl acetoacetate (1 mmol), benzaldehydes (1 mmol) and DABCO (10 mol%) in PEG-400 at 70 ꢀC.
bIsolated yields.
volatile organic solvents and we did this without the addition of any organic co-solvent.
We have also examined the recyclability of the PEG-400 during the synthesis of 8a.
After completion of the reaction, the reaction mixture was quenched with water and fil-
tered for separation of the crude product. The aqueous filtrate was extracted with
diethyl ether to remove any organic impurities. The aqueous layer was distilled at 90 ꢀC
for 2 h to remove water and the separated PEG-400 was reused directly for the next
run. As shown in Figure 3, only a small loss in the yield of the products was observed
through the first four runs (Figure 3).
A detailed reaction mechanism for the domino cyclocondensation of benzo[a]pyrazo-
lo[40,30:5,6]pyrano[2,3-c]phenazines 8 using DABCO is outlined in Scheme 2. The pri-
mary condensation of 2-hydroxynaphthalene-1,4-dione 1 with benzene-1,2-diamine 2 in
the presence of DABCO gives benzo[a]phenazin-5-ol 3. Then, hydrazine 4 condenses
with ethyl acetoacetate 5 to generate the pyrazolone ring 6, which is then isomerized to
intermediate 9. In this mechanism, DABCO is a catalyst to form the olefin 10, which is
readily formed in situ from the Knoevenagel condensation of aromatic aldehyde 7 with
pyrazole 9. In the presence of DABCO, benzo[a]phenazin-5-ol 3 converts to its corre-
sponding enolate form 11, to react easily with olefin 10 (Michael addition) and give
intermediate 12, which then produces 8.
To conclude, we have introduced an environmentally benign approach for the effi-
cient synthesis of novel benzo[a]pyrazolo[40,30:5,6]pyrano[2,3-c]phenazines in high
yields via a five-component domino protocol by using DABCO as a mild, effective,
non-toxic and inexpensive solid base catalyst and PEG-400 as a recyclable medium
without the addition of any organic co-solvent. The promising points for the presented
methodology are environmental acceptability, economic viability, and compliance with

6
A. YAZDANI-ELAH-ABADI ET AL.
Figure 3. Recycling and reuse of PEG-400.
green chemistry protocols. Our new compounds are likely to have biological activities,
which will be reported in due course.
Experimental section
All reagents and solvents were purchased from Merck or Aldrich and used without fur-
ther purification. Melting points and IR spectra of all compounds were determined on
1
an Electrothermal 9100 apparatus and Shimadzu IR-470 spectrometer. The H nuclear
magnetic resonance (NMR) and 13C NMR spectra were recorded in CDCl3 on a Bruker
1
DRX-300 spectrometer operating at 300 MHz for H analysis and 75 MHz for 13C ana-
lysis using TMS as an internal standard. Mass spectra were recorded on an Agilent
Technology (HP) spectrometer operating at an ionization potential of 70 eV. Elemental
analyses for C, H, and N were performed using a Heraeus CHN-O-Rapid analyzer at
the Central Research Facility of the Iranian Petroleum Company. Thin-layer chromatog-
raphy (TLC) was performed on silica-gel Polygram SILG/UV 254 plates and the solvent
for TLC was n-hexane/ethyl acetate, 2:1. An approximate Rf value for a typical product
was 0.6.
General procedure for the synthesis of novel
benzo[a]pyrazolo[4’,3’:5,6]pyrano[2,3-c]phenazine derivatives (8a-k)
2-Hydroxynaphthalene-1,4-dione 1 (1 mmol), benzene-1,2-diamine 2 (1 mmol) and
DABCO (10 mol%) were mixed in a 50 mL round-bottomed flask containing 5 mL of
PEG-400 and the contents were stirred magnetically in an oil-bath maintained at 70 ꢀC
until, in less than 5 minutes, an orange solid of benzo[a]phenazin-5-ol 3 was formed.
Separately, hydrazine 4 and ethyl acetoacetate 5 were mixed at 70 ꢀC under solvent-free
conditions to produce a white solid of pyrazolone 6 (< 5 min). Finally, the obtained
pyrazolone 6 and aryl aldehydes were added into the initial reaction system containing 3.
The reaction mixture was heated further for the appropriate time (Table 2). Upon the
completion of the reaction, monitored by TLC analysis, the reaction mixture was cooled

ORGANIC PREPARATIONS AND PROCEDURES INTERNATIONAL
7
Scheme 2. Proposed mechanism for the synthesis of benzo[a]pyrazolo[4’,3’:5,6]pyrano[2,3-c]phenazine
derivatives.
to room temperature and was quenched with H2O (5 mL). The precipitate formed was
collected by filtration at the pump, then the separated product was washed with water.
The resulting compound was subsequently recrystallized from hot EtOH to give the
pure product 8. The spectral and analytical data are presented below.

8
A. YAZDANI-ELAH-ABADI ET AL.
15-(4-Chlorophenyl)-1-methyl-3,15-dihydrobenzo[a]pyrazolo[4’,3’:5,6]pyrano
[2,3-c]phenazine (8a)
Yellow powder; yield 0.367 g (82%), mp 293-295 ꢀC; IR (KBr): ꢀmax ¼ 3337, 2930, 1623,
1
1591, 1479, 1406, 1385, 1350, 1290, 1165, 1076, 968, 749 cmꢁ1; H NMR (300 MHz,
CDCl3): d 1.87 (s, 3H, CH3), 5.42 (s, 1H, CH), 7.03 (d, 2H, J ¼ 7.8 Hz, Ar-H), 7.18 (d,
2H, J ¼ 7.8 Hz, Ar-H), 7.54-7.58 (m, 2H, Ar-H), 7.82-7.86 (m, 3H, Ar-H), 8.11-8.13 (m,
2H, Ar-H), 9.23-9.26 (m, 1H, Ar-H), 12.01 (s, 1H, NH) ppm; 13C NMR (75 MHz,
CDCl3): d 10.4 (CH3), 42.3 (CH), 111.5, 116.4, 123.5, 124.6, 126.1, 126.6, 127.4, 128.7,
129.0, 129.2, 129.6, 129.8, 130.2, 131.2, 132.7, 140.1, 141.3, 141.7, 142.8, 145.5, 146.8,
157.4 and 160.2 (Colefinic and Carom) ppm; MS (m/z, %): 448 (Mþ, 4).
Anal. Calcd for C27H17ClN4O: C, 72.24; H, 3.82; N, 12.48. Found: C, 72.51; H, 4.06;
N, 12.80.
1-Methyl-15-(4-nitrophenyl)-3,15-dihydrobenzo[a]pyrazolo[4’,3’:5,6]pyrano
[2,3-c]phenazine (8b)
Yellow powder; yield 0.386 g (84%), mp 281-282 ꢀC; IR (KBr): ꢀmax ¼ 3345, 2932, 1628,
1583, 1483, 1401, 1388, 1348, 1293, 1165, 1057, 961, 752 cmꢁ1; 1H NMR (300MHz,
CDCl3): d 1.89 (s, 3H, CH3), 5.48 (s, 1H, CH), 6.87 (d, 2H, J¼ 8.1 Hz, Ar-H), 7.06 (d, 2H,
J¼ 8.1 Hz, Ar-H), 7.38-7.43 (m, 3H, Ar-H), 7.69-7.71 (m, 2H, Ar-H), 8.05-8.09 (m, 1H, Ar-
H), 8.24-8.26 (m, 1H, Ar-H), 9.28-9.31 (m, 1H, Ar-H), 12.19 (s, 1H, NH) ppm; 13C NMR
(75 MHz, CDCl3): d 10.7 (CH3), 43.4 (CH), 110.4, 118.6, 122.7, 123.5, 125.1, 126.8, 127.2,
128.4, 129.1, 129.5, 129.9, 130.0, 130.3, 131.1, 132.2, 140.3, 140.8, 141.3, 142.8, 145.3, 146.5,
157.5 and 160.7 (Colefinic and Carom) ppm; MS (m/z, %): 459 (Mþ, 1).
Anal. Calcd for C27H17N5O3: C, 70.58; H, 3.73; N, 15.24. Found: C, 70.92; H, 3.86;
N, 15.45.
4-(1-Methyl-3,15-dihydrobenzo[a]pyrazolo[4’,3’:5,6]pyrano[2,3-c]phenazin-15-yl)
benzonitrile (8c)
Yellow powder; yield 0.347 g (79%), mp 287-289 ꢀC; IR (KBr): ꢀmax ¼ 3327, 2928, 2187,
1625, 1592, 1458, 1402, 1384, 1350, 1292, 1167, 1053, 972, 751 cmꢁ1 1H NMR
;
(300 MHz, CDCl3): d 1.90 (s, 3H, CH3), 5.54 (s, 1H, CH), 7.27-7.29 (m, 2H, Ar-H),
7.41-7.43 (m, 4H, Ar-H), 7.89-8.01 (m, 4H, Ar-H), 8.22-8.24 (m, 1H, Ar-H), 9.16-9.18
(m, 1H, Ar-H), 12.10 (s, 1H, NH) ppm; 13C NMR (75 MHz, CDCl3): d 10.1 (CH3), 42.6
(CH), 113.4, 116.7, 119.5, 123.2, 125.7, 126.2, 126.4, 128.2, 128.8, 129.1, 129.3, 129.5,
129.9, 130.2, 131.4, 132.5, 140.4, 141.5, 141.8, 142.4, 145.5, 147.0, 157.8 and 161.1
(Colefinic and Carom) ppm; MS (m/z, %): 439 (Mþ, 7).
Anal. Calcd for C28H17N5O: C, 76.52; H, 3.90; N, 15.94. Found: C, 76.77; H, 4.08; N, 15.73.
1-Methyl-15-(p-tolyl)-3,15-dihydrobenzo[a]pyrazolo[4’,3’:5,6]pyrano[2,3-c]
phenazine (8d)
Yellow powder; yield 0.347 g (81%), mp 299-301 ꢀC; IR (KBr): ꢀmax ¼ 3335, 2930, 1630,
1
1587, 1474, 1399, 1385, 1351, 1290, 1161, 1053, 975, 754 cmꢁ1; H NMR (300 MHz,

ORGANIC PREPARATIONS AND PROCEDURES INTERNATIONAL
9
CDCl3): d 1.77 (s, 3H, CH3), 2.16 (s, 3H, CH3), 5.38 (s, 1H, CH), 7.07 (d, 2H,
J ¼ 7.5 Hz, Ar-H), 7.20 (d, 2H, J ¼ 7.5 Hz, Ar-H), 7.48-7.53 (m, 3H, Ar-H), 7.94-8.00 (m,
3H, Ar-H), 8.16-8.19 (m, 1H, Ar-H), 9.26-9.29 (m, 1H, Ar-H), 11.86 (s, 1H, NH) ppm;
13C NMR (75 MHz, CDCl3): d 9.8, 20.52 (2CH3), 43.1 (CH), 113.8, 121.4, 123.7, 125.2,
125.7, 127.3, 128.7, 129.1, 129.4, 129.6, 129.8, 130.1, 131.4, 132.5, 133.3, 140.4, 141.3,
141.8, 142.4, 145.5, 146.7, 157.0 and 160.6 (Colefinic and Carom) ppm; MS (m/z, %): 428
(Mþ, 5).
Anal. Calcd for C28H20N4O: C, 78.49; H, 4.70; N, 13.08. Found: C, 78.31; H, 4.88;
N, 12.96.
15-(4-Methoxyphenyl)-1-methyl-3,15-dihydrobenzo[a]pyrazolo[4’,3’:5,6]pyrano
[2,3-c]phenazine (8e)
Yellow powder; yield 0.333 g (75%), mp 274-276 ꢀC; IR (KBr): ꢀmax ¼ 3353, 2935, 1632,
1
1595, 1458, 1422, 1383, 1328, 1269, 1168, 1053, 986, 757 cmꢁ1; H NMR (300 MHz,
CDCl3): d 1.85 (s, 3H, CH3), 3.72 (s, 3H, OCH3), 5.56 (s, 1H, CH), 7.41-7.44 (m, 5H,
Ar-H), 7.90-8.02 (m, 4H, Ar-H), 8.09-8.12 (m, 1H, Ar-H), 8.40-8.43 (m, 1H, Ar-H),
9.17-9.19 (m, 1H, Ar-H), 12.23 (s, 1H, NH) ppm; 13C NMR (75 MHz, CDCl3): d 11.2
(CH3), 57.3 (OCH3), 44.1 (CH), 112.6, 117.2, 123.8, 124.5, 126.1, 126.4, 127.3, 128.2,
129.4, 129.6, 129.9, 130.2, 131.4, 132.2, 132.9, 140.5, 141.3, 142.1, 142.8, 145.7, 146.4,
157.8 and 161.1 (Colefinic and Carom) ppm; MS (m/z, %): 444 (Mþ, 3).
Anal. Calcd for C28H20N4O2: C, 75.66; H, 4.54; N, 12.60. Found: C, 75.87; H, 4.62;
N, 12.34.
15-(4-Chlorophenyl)-1-methyl-3-phenyl-3,15-dihydrobenzo[a]pyrazolo[4’,3’:5,6]
pyrano[2,3-c]phenazine (8f)
Yellow powder; yield 0.404 g (77%), mp 243-245 ꢀC; IR (KBr): ꢀmax ¼ 2931, 1628, 1591,
1
1467, 1410, 1392, 1335, 1277, 1151, 1069, 975, 750 cmꢁ1; H NMR (300 MHz, CDCl3): d
1.90 (s, 3H, CH3), 5.64 (s, 1H, CH), 7.05 (d, 2H, J ¼ 7.5 Hz, Ar-H), 7.15 (d, 2H,
J ¼ 7.5 Hz, Ar-H), 7.48-7.54 (m, 5H, Ar-H), 7.79-7.84 (m, 3H, Ar-H), 8.03-8.06 (m, 2H,
Ar-H), 8.21-8.23 (m, 1H, Ar-H), 8.49-8.52 (m, 1H, Ar-H), 9.29-9.32 (m, 1H, Ar-H)
ppm; 13C NMR (75 MHz, CDCl3): d 11.3 (CH3), 44.1 (CH), 115.4, 117.8, 121.4, 122.5,
123.2 124.1, 126.4, 127.1, 127.4, 128.2, 128.4, 129.2, 129.4, 129.7, 129.8, 130.1, 130.6,
131.4, 132.7, 133.8, 140.2, 141.4, 141.8, 142.5, 145.2, 145.9, 152.8 and 158.1 (Colefinic and
C
arom) ppm; MS (m/z, %): 525 (Mþ, 6).
Anal. Calcd for C33H21ClN4O: C, 75.50; H, 4.03; N, 10.67. Found: C, 75.76; H, 3.93;
N, 10.94.
1-Methyl-3-phenyl-15-(p-tolyl)-3,15-dihydrobenzo[a]pyrazolo[4’,3’:5,6]pyrano
[2,3-c]phenazine (8g)
Yellow powder; yield 0.363 g (72%), mp 259-260 ꢀC; IR (KBr): ꢀmax ¼ 2930, 1623, 1587,
1
1471, 1407, 1385, 1332, 1258, 1150, 1065, 988, 752 cmꢁ1; H NMR (300 MHz, CDCl3): d
1.85 (s, 3H, CH3), 2.21 (s, 3H, CH3), 5.59 (s, 1H, CH), 6.81-6.83 (m, 2H, Ar-H), 6.98-

10
A. YAZDANI-ELAH-ABADI ET AL.
7.01 (m, 2H, Ar-H), 7.56-7.60 (m, 4H, Ar-H), 7.90-8.04 (m, 5H, Ar-H), 8.26-8.29 (m,
2H, Ar-H), 8.49 (d, 1H, J ¼ 7.5 Hz, Ar-H), 9.27-9.30 (m, 1H, Ar-H) ppm; 13C NMR
(75 MHz, CDCl3): d 11.0, 20.78 (2CH3), 43.6 (CH), 116.2, 117.5, 120.2, 121.6, 123.4
124.6, 125.2, 127.5, 127.9, 128.1, 128.6, 129.1, 129.4, 129.7, 129.9, 130.1, 130.4, 131.2,
132.6, 132.9, 140.3, 141.2, 141.5, 142.8, 145.3, 146.1, 152.4 and 157.4 (Colefinic and Carom
)
ppm; MS (m/z, %): 504 (Mþ, 1).
Anal. Calcd for C34H24N4O: C, 80.93; H, 4.79; N, 11.10. Found: C, 81.19; H, 4.85;
N, 11.31.
11,12-Dichloro-15-(4-chlorophenyl)-1-methyl-3,15-dihydrobenzo[a]pyrazolo[4’,3’:5,6]
pyrano[2,3-c]phenazine (8h)
Yellow powder; yield 0.403 g (78%), mp 307-309 ꢀC; IR (KBr): ꢀmax ¼ 3320, 2928, 1627,
1
1591, 1469, 1408, 1372, 1335, 1290, 1162, 1070, 976, 750 cmꢁ1; H NMR (300 MHz,
CDCl3): d 1.83 (s, 3H, CH3), 5.40 (s, 1H, CH), 6.98 (d, 2H, J ¼ 7.8 Hz, Ar-H), 7.12 (d,
2H, J ¼ 7.8 Hz, Ar-H), 7.41-7.44 (m, 2H, Ar-H), 7.62 (s, 1H, Ar-H), 7.82-7.85 (m, 1H,
Ar-H), 8.12-8.14 (m, 1H, Ar-H), 9.25-9.28 (m, 1H, Ar-H), 12.11 (s, 1H, NH) ppm; 13C
NMR (75 MHz, CDCl3): d 10.6 (CH3), 42.8 (CH), 112.6, 117.3, 123.5, 125.2, 126.3,
127.1, 128.5, 129.1, 129.4, 129.6, 129.9, 130.2, 131.6, 132.8, 137.2, 140.6, 141.7, 142.5,
145.4, 147.6, 148.6, 158.3 and 160.4 (Colefinic and Carom) ppm; MS (m/z, %): 517
(Mþ, 5).
Anal. Calcd for C27H15Cl3N4O: C, 62.63; H, 2.92; N, 10.82. Found: C, 62.50; H, 3.09;
N, 10.98.
11,12-Dichloro-1-methyl-15-(p-tolyl)-3,15-dihydrobenzo[a]pyrazolo[4’,3’:5,6]pyrano
[2,3-c]phenazine (8i)
Yellow powder; yield 0.373 g (75%), mp 269-271 ꢀC; IR (KBr): ꢀmax ¼ 3357, 2926, 1625,
1
1594, 1438, 1412, 1358, 1333, 1268, 1145, 1069, 972, 754 cmꢁ1; H NMR (300 MHz,
CDCl3): d 1.86 (s, 3H, CH3), 2.18 (s, 3H, CH3), 5.47 (s, 1H, CH), 7.47-7.52 (m, 4H, Ar-
H), 7.97-8.01 (m, 1H, Ar-H), 8.04-8.08 (m, 1H, Ar-H), 8.46-8.48 (m, 1H, Ar-H), 8.53 (s,
1H, Ar-H), 8.59 (s, 1H, Ar-H), 9.31-9.34 (m, 1H, Ar-H), 12.08 (s, 1H, NH) ppm; 13C
NMR (75 MHz, CDCl3): d 10.6, 20.50 (2CH3), 42.6 (CH), 114.2, 117.6, 122.2, 124.9,
126.6, 127.3, 128.4, 129.2, 129.4, 129.7, 129.9, 130.1, 131.4, 132.6, 138.1, 140.0, 141.5,
142.3, 145.2, 147.3, 148.7, 158.0 and 161.1 (Colefinic and Carom) ppm; MS (m/z, %): 497
(Mþ, 7).
Anal. Calcd for C28H18Cl2N4O: C, 67.61; H, 3.65; N, 11.26. Found: C, 67.83; H, 3.74;
N, 11.50.
15-(4-Chlorophenyl)-1,11,12-trimethyl-3-phenyl-3,15-dihydrobenzo[a]pyrazolo
[4’,3’:5,6]pyrano[2,3-c]phenazine (8j)
Yellow powder; yield 0.437 g (79%), mp 252-253 ꢀC; IR (KBr): ꢀmax ¼ 2930, 1630, 1594,
1
1482, 1407, 1389, 1346, 1295, 1164, 1058, 972, 749 cmꢁ1; H NMR (300 MHz, CDCl3): d
1.79 (s, 3H, CH3), 2.53 (s, 6H, 2CH3), 5.38 (s, 1H, CH), 6.85 (d, 2H, J ¼ 7.8 Hz, Ar-H),

ORGANIC PREPARATIONS AND PROCEDURES INTERNATIONAL
11
7.03 (d, 2H, J ¼ 7.8 Hz, Ar-H), 7.44-7.47 (m, 4H, Ar-H), 7.86 (s, 1H, Ar-H), 7.93-8.02
(m, 3H, Ar-H), 8.44-8.46 (m, 2H, Ar-H), 9.18-9.20 (m, 1H, Ar-H) ppm; 13C NMR
(75 MHz, CDCl3): d 11.6, 20.2, 20.3 (3CH3), 44.1 (CH), 117.2, 118.4, 121.2, 122.3, 122.8,
124.2, 125.1, 125.5, 126.2, 128.1, 129.1, 129.2, 129.4, 129.6, 130.2, 131.3, 132.5, 138.1,
140.4, 140.8, 141.4, 142.8, 145.4, 146.1, 147.2, 153.6 and 158.3 (Colefinic and Carom) ppm;
MS (m/z, %): 553 (Mþ, 4).
Anal. Calcd for C35H25ClN4O: C, 76.01; H, 4.56; N, 10.13. Found: C, 76.25; H, 4.38;
N, 10.21.
1,11,12-Trimethyl-15-(4-nitrophenyl)-3,15-dihydrobenzo[a]pyrazolo[4’,3’:5,6]
pyrano[2,3-c]phenazine (8k)
Yellow powder; yield 0.394 g (81%), mp 315-317 ꢀC; IR (KBr): ꢀmax ¼ 3345, 2935, 1632,
1
1590, 1475, 1406, 1387, 1345, 1297, 1172, 1070, 969, 750 cmꢁ1; H NMR (300 MHz,
CDCl3): d 1.85, 247, 2.49 (s, 9H, 3CH3), 5.47 (s, 1H, CH), 7.02 (d, 2H, J ¼ 7.8 Hz, Ar-
H), 7.17 (d, 2H, J ¼ 7.8 Hz, Ar-H), 7.59-7.62 (m, 2H, Ar-H), 7.86 (s, 1H, Ar-H), 8.02-
8.04 (m, 1H, Ar-H), 8.42 (dd, 1H, J1 ¼ 7.8 Hz, J2 ¼ 1.8 Hz, Ar-H), 9.24-9.27 (m, 1H,
Ar-H), 11.92 (s, 1H, NH) ppm; 13C NMR (75 MHz, CDCl3): d 10.9, 20.3, 20.5 (3CH3),
43.6 (CH), 118.1, 122.4, 124.1, 125.2, 126.5, 127.2, 128.6, 128.9, 129.2, 129.5, 129.8,
130.1, 130.3, 131.5, 132.2, 140.4, 140.8, 141.5, 144.1, 145.6, 146.2, 157.8 and 160.9
(Colefinic and Carom) ppm; MS (m/z, %): 487 (Mþ, 2).
Anal. Calcd for C29H21N5O3: C, 71.45; H, 4.34; N, 14.37. Found: C, 71.67; H, 4.41;
N, 14.54.
Acknowledgments
We gratefully acknowledge financial support from the Research Council of the University of
Science and Arts of Yazd and Islamic Azad University of Yazd, Iran.
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