An efficient synthesis of novel functionalized benzo[h]pyrano[2,3-b]quinolines and pyrano[2,3-b]quinoline derivatives via one-pot multicomponent reactions

Article abstract of DOI:10.1007/s13738-021-02376-9

In this paper, a convenient, one-pot, for the straightforward synthesis of pyrano[2,3-b]quinoline and benzo[h]pyrano[2,3-b]quinoline derivatives is presented, which includes a three-component reaction of (2-chloroquinoline-3-carbaldehyde, 2-chlorobenzo[h]quinoline-3-carbaldehyde), and 1-phenyl-2-(1,1,1-triphenyl-λ⁵- phosphanylidene)ethan-1-one (Wittig reagent) with the active methylene compounds such as (benzoylacetonitrile, dimedone, 1,3-dimethylbarbituric acid, 4-hydroxycoumarin and 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one), during the two processes of C–C bond formation (Michael addition) and intramolecular cyclization (by the attack of the oxygen atom of active methylene compounds). Advantages of this protocol include easily accessible starting materials, excellent yields (65–98%), absence of a metal catalyst and simple workup procedure (the pure products were obtained simply by washing the products with EtOH). Graphic abstract: A series of pyrano[2,3-b]quinoline and benzo[h]pyrano[2,3-b]quinoline derivatives have been synthesized in excellent yields (65–98%) via a one-pot three-component reaction of (2-chloroquinoline-3-carbaldehyde, 2-chlorobenzo[h]quinoline-3-carbaldehyde) and 1-phenyl-2-(1,1,1-triphenyl-λ⁵-phosphanylidene)ethan-1-one (Wittig reagent) with the active methylene compounds such as (benzoylacetonitrile, dimedone, 1,3-dimethylbarbituric acid, 4-hydroxycoumarin and 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one), during the two processes of C–C bond formation (Michael addition) and intramolecular cyclization (by the attack of the oxygen atom of active methylene compounds). Advantages of this protocol include easily accessible starting materials, excellent yields (65–98%), absence of a metal catalyst and simple workup procedure (the pure products were obtained simply by washing the products with EtOH). [Figure not available: see fulltext.]

Full text of DOI:10.1007/s13738-021-02376-9

Journal of the Iranian Chemical Society
https://doi.org/10.1007/s13738-021-02376-9
ORIGINAL PAPER
An efcient synthesis of novel functionalized benzo[h]pyrano[2,3‑b]
quinolines and pyrano[2,3‑b]quinoline derivatives via one‑pot
multicomponent reactions
Abdolali Alizadeh1 · Azar Rostampoor1
Received: 30 June 2021 / Accepted: 8 August 2021
© Iranian Chemical Society 2021
Abstract
In this paper, a convenient, one-pot, for the straightforward synthesis of pyrano[2,3-b]quinoline and benzo[h]pyrano[2,3-
b]quinoline derivatives is presented, which includes a three-component reaction of (2-chloroquinoline-3-carbaldehyde,
2-chlorobenzo[h]quinoline-3-carbaldehyde), and 1-phenyl-2-(1,1,1-triphenyl-λ5- phosphanylidene)ethan-1-one (Wittig rea-
gent) with the active methylene compounds such as (benzoylacetonitrile, dimedone, 1,3-dimethylbarbituric acid, 4-hydroxy-
coumarin and 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one), during the two processes of C–C bond formation (Michael addi-
tion) and intramolecular cyclization (by the attack of the oxygen atom of active methylene compounds). Advantages of
this protocol include easily accessible starting materials, excellent yields (65–98%), absence of a metal catalyst and simple
workup procedure (the pure products were obtained simply by washing the products with EtOH).
Graphic abstract
A series of pyrano[2,3-b]quinoline and benzo[h]pyrano[2,3-b]quinoline derivatives have been synthesized in excellent
yields (65–98%) via a one-pot three-component reaction of (2-chloroquinoline-3-carbaldehyde, 2-chlorobenzo[h]quinoline-
3-carbaldehyde) and 1-phenyl-2-(1,1,1-triphenyl-λ5-phosphanylidene)ethan-1-one (Wittig reagent) with the active methylene
compounds such as (benzoylacetonitrile, dimedone, 1,3-dimethylbarbituric acid, 4-hydroxycoumarin and 3-methyl-1-phenyl-
1H-pyrazol-5(4H)-one), during the two processes of C–C bond formation (Michael addition) and intramolecular cyclization
(by the attack of the oxygen atom of active methylene compounds). Advantages of this protocol include easily accessible
starting materials, excellent yields (65–98%), absence of a metal catalyst and simple workup procedure (the pure products
were obtained simply by washing the products with EtOH).
Keywords 2-Chlorobenzo[h]quinoline-3-carbaldehyde · 2-Chloroquinoline-3-carbaldehyde · Multicomponent reaction ·
1-Phenyl-2-(1,1,1-triphenyl-λ5-phosphanylidene)ethan-1-one (Wittig reagent) · Pyrano[2,3-b]quinoline · Benzo[h]
pyrano[2,3-b]quinoline
* Abdolali Alizadeh
aalizadeh@modares.ac.ir; abdol_alizad@yahoo.com
1
Department of Chemistry, Tarbiat Modares University, P.O.
Box 14115-175, Tehran, Iran
Vol.:(0123456789)
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Journal of the Iranian Chemical Society
Introduction
Multicomponent reactions (MCRs) are one of the useful
pathways in chemical synthesis as well as industrially,
which has attracted a lot of attention in recent years. It
can successfully combine complex structures from sim-
ple substrates in a one-pot reaction that does not need the
isolation of intermediate compounds, which is the highest
contributor toward the environment. Moreover, it provides
several advantages, such as short reaction periods, greater
efciency, high chemical efciency, high complexity, and
diversity of molecular [1–8]. MCRs are often selective and
also often increase the number of substrates that lead to
inefciency reactions and the production of by-products
[9].
Fig. 1 Examples of bioactive pyranoquinolines
One of the primary goals of organic and medicinal
chemistry is the design and synthesis of scafolds possess-
ing biological features. Heterocycles including nitrogen
rings are targeted molecules in synthetic and medicinal
chemistry since the nitrogen ring is a key scafold in dif-
ferent biologically active compounds. Quinoline and its
derivatives as one of the most important heterocyclic
compounds with nitrogen ring recognized, which are
widespread in medicinal agents and natural products [10,
11]. Among them, 2-chloroquinoline-3-carbaldehydes are
one of the easiest available starting materials and very
interesting compounds due to their high reactivity activ-
ity, they have an active aldehyde group in position 3, and
the substitution of chlorine in position 2, these features
provide increased reactivity, using materials containing
these structures, in a variety of multi-component reactions
including nucleophilic substitution reactions, electrophilic
substitution reactions, Diels–Alder [12], 1,3-dipolar reac-
tions [13], Knoevenagel condensation [14, 15], Ugi reac-
tion [16] and …, new heterocycles with active biological
properties have been synthesized. Many of those heterocy-
clic compounds are known as antibacterial [17, 18], anti-
infammatory [19, 20], anticancer [21], antimalarial [22],
antifungal [23], antitumor [24] and anti-parasitic activity
[25]. Recently, several reviews of multicomponent reac-
tions of these aldehydes have been reported [26, 27].
Considering the advantages mentioned, quinolines are
one of the important classes of heterocycles and have been
used as templates for the synthesis of many drugs pre-
scribed for a lot of pathologies; especially those with a
pyranoquinoline ring system are of considerable interest.
This nucleus is also frequently recognized in the structure
of numerous naturally occurring alkaloids [28] such as
findersine, oricine, and vesprisine, simulenoline, huajia-
osimuline [29–34] and synthetic compounds with inter-
esting biological and pharmacological properties. These
derivatives are important class of quinolones in which
Fig. 2 Pyranoquinoline derivatives
pyran ring is fused of quinolone ring. They have wide
applications, for example, as drugs, pharmaceuticals, and
agrochemicals, and possess a signifcant range of biologi-
cal activities, such as antileishmanial [35], antimalarial
[36], antitumor [37], antioxidant [38], anti-infammatory,
and anticancer [39] and antiallergic, psychotropic, and
estrogenic [40–42] activities. Additionally, promising
biological activities of structurally diverse pyranoquino-
lines (Fig. 1) were described in a number of recent articles
[43–45].
Recently, considerable eforts have been accomplished
to the preparation and synthetic of novel heterocyclic com-
pounds including pyranoquinolines of one-pot reactions
2-chloroquinoline-3-carbaldehydes with the methylene
active compounds, for example, synthesis 2-amino-3-cy-
ano-4-H-chromenes [46], 2-amino-4H-benzo[b]pyran [47],
and, synthesis 4H-pyrans and pyrano tacrines, of one-pot
reactions 2-chloroquinoline-3-carbaldehydes with (malo-
nonitrile, ethyl acetoacetate, and dimedone) [48]. Among
the pyranoquinolines, pyrano[2,3-b]quinoline systems are
of interest because they are linear benzaza analogs of cou-
marins, in which the pyran ring is fused to the b bond of the
quinolone ring (Fig. 2).
So far, only a few methods have been reported for the
construction of pyrano[2,3-b]quinolines, for example,
1,4-dihydropyrazolo-pyrano-[2,3-b]quinolines [49], cop-
per-catalyzed cycloaddition reactions of 2-chloroquinoline-
3-carboxaldehydes with phenylacetylene gave pyrano[4,3-b]
quinolines [50]. Recently, Zhang and coworkers reported
the synthesis of pyrano[2,3-b]quinolines from cyclopen-
tanecarboxamides mediated by concentrated H2SO4 [51] and
Bhuyan et al. have reported a one-pot synthesis of tetracy-
clic pyrano[2,3-b]quinolines via intramolecular 1,3-dipolar
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Journal of the Iranian Chemical Society
cycloaddition reactions using 1,3-dipoles such as nitrones,
nitrile oxides and nitrile imines [52]. Also, domino cycli-
zation reaction for the synthesis of 2,2a,10,11 tetrahydro-
furo[20,40:4,6]pyrano[2,3-b]quinolines and intramolecular
electrophilic cyclization of 3-homoallyl-2-quinolones with
iodine and sodium bicarbonate by B. Singh et al. has been
reported [53, 54]. Recently, Farid Abdel-Rehem Badria, and
co-workers reported the one-pot reaction of 2-chloroquino-
line-3-carbaldehyde with benzoylacetonitrile in metal-free
conditions (Scheme 1) [55].
Hereine, we report an efcient synthesis of functionalized
pyrano[2,3-b]quinoline and benzo[h]pyrano[2,3-b]quinoline
derivatives by using 2-chloroquinoline-3-carbaldehyde 1a,
2-chlorobenzo[h]quinoline-3-carbaldehyde 1b, 1-aryl-2-
(1,1,1-triphenyl-λ5-phosphanylidene)ethan-1-one (Wittig
reagent) 2 and the active methylene compounds 3 under mild
conditions in good to excellent yields (Scheme 2).
Experimental section
Melting points measured on an Electrothermal 9100 appara-
tus. IR spectra were recorded as KBr pellets on a NICOLET
FT-IR 100 spectrometer. 1H NMR (500 and 300 MHz) and
13C NMR (125 and 75 MHz) spectra were obtained using
Bruker DRX-500 AVANCE and Bruker DRX-300 AVANCE
spectrometers. NMR spectra at room temperature were
recorded in DMSO-d6. Chemical shifts are reported in parts
per million (δ) downfeld from an internal tetramethylsilane
reference. Coupling constants (J values) are reported in
Hertz (Hz), and spin multiplicities are indicated by the fol-
lowing symbols: bs (broad singlet), s (singlet), d (doublet),
Scheme 1 Reaction of 2-chloroquinoline-3-carbaldehyde with ben-
zoylacetonitrile in metal-free conditions
Scheme 2 Synthesis of pyrano[2,3-b]quinoline and benzo[h]pyrano[2,3-b]quinoline derivatives by a three-component reaction
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Journal of the Iranian Chemical Society
t (triplet), m (multiplet). Elemental analyses for C, H, and
N performed using a Heraeus CHN–O–Rapid analyzer. All
the products recrystallized from CH3CN for CHN analysis.
Mass spectra were recorded on a FINNIGAN-MATT 8430
mass spectrometer operating at an ionization potential of
20 or 70 eV. All the reagents and solvents purchased from
Merck or Aldrich without any purifcation.
C27H18N2O2 (402.44): C, 80.58; H, 4.51; N, 6.96. Found: C,
80.54; H, 4.53; N, 6.98%.
2‑(4‑Chlorophenyl)‑4‑[2‑(4‑chlorophenyl)‑2‑oxoethy
l]‑4H‑pyrano[2,3‑b]quinoline‑3‑carbonitrile (4b)
White powder, m.p=224–225 °C (dec), 0.42 g, yield: 90%.
IR (KBr) (vmax, cm−1): 2206 (CN), 1680 (C=O), 1632,
1587, 1490 (Ar), 1255, 1212 (C-O) .1H NMR (500.13 MHz,
General procedure for the one‑pot synthe‑
sis of pyrano[2,3‑b]quinoline and benzo[h]
pyrano[2,3‑b]quinolines derivatives (4a‑m)
2
DMSO-d6): 3.92 (2H, ABqd, JHH = 14.6 Hz, CH2), 4.66
3
(1H, bs, CH4), 7.55 (3H, JHH = 7.2 Hz, 2CH of Ar and
CH7 of quinoline). 7.67 (2H, d, 3JHH =7.3 Hz, 2CH of Ar),
7.73 (1H, t, 3JHH =6.5 Hz, CH8 of quinoline), 7.88 (2H, d,
3JHH =6.5 Hz, 2CH of Ar), 7.85–7.88 (2H, m, CH6 and CH9
of quinoline), 7.97 (2H, d, 3JHH =7.3 Hz, 2CH of Ar), 8.45
(1H, s, CH5 of quinoline). 13C NMR (125.75 MHz, DMSO-
d6): 32.68 (CH4), 44.70 (CH2), 88.52 (C3), 117.89 (CN),
118.13 (C4a), 126.03 (CH7 of quinoline), 127.20 (C5a of
quinoline), 127.31 (CH6 of quinoline), 127.59 (CH8 of qui-
noline), 128.78 (2CHmeta of Ar), 128.92 (2CHmeta of Ar),
129.81 (2CHortho of Ar), 129.97 (2CHortho of Ar), 130.02
(Cipso –C2), 130.44 (CH9 of quinoline), 134.85 (Cipso-CO),
136.18 (Cipso-Cl), 137.85 (CH5 of quinoline), 138.50
(Cipso-Cl), 144.92 (C9a of quinoline), 154.45 (C10a of quino-
line), 160.12 (C2), 196.12 (C=O). MS (EI, 70 eV) m/z (%):
472 (M+ +2, 4), 471 (M+ +1, 2), 470 (M+, 5), 331 (5), 320
(8), 319 (39), 318 (25), 317 (100), 267 (3), 254 (6), 253 (11),
252 (10), 251 (6), 250 (21), 216 (4), 140 (9), 139 (28), 111
(9). Anal. calcd. for C27H16Cl2N2O2 (471.33): C, 68.80; H,
3.42; N, 5.94. Found: C, 68.76; H, 3.44; N, 5.96%.
A mixture of quinolines (2-chloro quinoline-3-carbaldehyde
or 2-chloro benzo[h]quinoline-3-carbaldehyde) 1 (0.5 mmol)
and 1-aryl-2-(1,1,1-triphenyl-λ5-phosphanylidene)ethan-1-
one 2 (0.5 mmol) in 5 mL EtOH stirred for 30 min; then
active methylene compounds 3 (0.5 mmol) and triethylamine
(100 mmol%) were added and further stirred for 2–3 h at
refux temperature. After the completion of the reaction
(monitored by TLC), the resulting precipitate was fltered
and washed with EtOH, and recrystallized from EtOH to
aford the pure product as solid in good yields (4a-m).
4‑(2‑Oxo‑2‑phenylethyl)‑2‑phenyl‑4H‑pyrano[2,3‑b]
quinoline‑3‑carbonitrile (4a)
White powder, m.p = 233–234 °C (dec.), 0.38 g, yield:
95%. IR (KBr)(νmax, cm−1): 2205 (CN), 1680 (C=O), 1629,
1577, 1499 (Ar), 1256, 1207, (C-O). 1H NMR (500.13 MHz,
DMSO-d6): 3.95 (2H, ABqd, 2JHH =18.4 Hz, 3JHH =4.5 Hz,
3
CH2), 4.69 (1H, t, JHH = 4.5 Hz, CH4), 7.51 (2H, t,
3
3JHH = 7.6 Hz, 2CHmeta of Ph), 7.55 (1H, t, JHH = 7.5 Hz,
4‑[2‑(4‑Methylphenyl)‑2‑oxoethyl]‑2‑phe‑
nyl‑4H‑pyrano[2,3‑b]quinoline‑3‑carbonitrile (4c)
CHpara of Ph), 7.60 (1H, t, 3JHH =7.5 Hz, CH7 of quinoline),
7.62 (2H, 3JHH =9.5 Hz, t, 2CHmeta of PhCO), 7.64 (1H, t,
3JHH =7.4 Hz, CHpara of PhCO), 7.75 (1H, t, 3JHH =7.5 Hz,
CH8 of quinoline), 7.86 (2H, d, 3JHH =6.4 Hz, 2CHortho of
White powder, m.p = 205–207 °C (dec.), 0.39 g, yield:
93%. IR (KBr)(vmax, cm−1): 2205 (CN), 1678 (C=O),
3
1
Ph), 7.90 (1H, d, JHH = 8.3 Hz, CH9 of quinoline), 7.92
1632, 1602, 15,574, 1498 (Ar), 1249, 1205 (C-O). H
3
(1H, d, JHH = 7.9 Hz, CH6 of quinoline), 7.98 (2H, d,
NMR (500.13 MHz, DMSO-d6): 2.10 (3H, S, Me), 3.89
2
3
3JHH =7.4 Hz, 2CHortho of PhCO), 8.48 (1H, s, CH5 of qui-
noline). 13C NMR (125.75 MHz, DMSO-d6): 33.21 (CH4),
45.08 (CH2), 88.50 (C3), 118.65 (CN), 118.84 (C4a), 126.45
(CH7 of quinoline), 127.67 (C5a of quinoline), 127.79 (CH6
of quinoline), 128.06 (CH8 of quinoline), 128.42 (2CHmeta
of PhCO), 128.53 (2CHmeta of Ph), 129.19 (2CHortho of Ph),
129.21 (2CHortho of PhCO), 130.86 (CH9 of quinoline),
131.75 (Cipso of Ph), 131.96 (CHpara of Ph), 134.05 (CHpara
of PhCO), 136.67 (Cipso of PhCO), 138.21 (CH5 of quino-
line), 145.43 (C9a of quinoline), 155.07 (C10a of quinoline),
161.71 (C2), 197.54 (C=O). MS (EI, 70 eV) m/z (%): 403
(M+ +1, 12), 402 (M+, 33), 297 (21), 285 (8), 284 (61), 283
(100), 255 (8), 254 (11), 253 (12), 228 (6), 227 (9), 217
(23), 216 (64), 106 (7) 105 (60), 77 (21). Anal. calcd. for
( 2H, ABqd, JHH = 18.3 Hz, JHH = 4.3 Hz, CH2), 4.67
(1H, bs, CH4), 7.30 (2H, d, JHH = 7.7 Hz, 2CH of Ar),
3
3
7.54 (1H, t, JHH = 7.2 Hz, CHpara of Ph), 7.60 (2H, d,
3JHH = 7.3 Hz, 2CHmeta of Ph and CH7 of quinoline), 7.74
(1H, t, JHH = 7.5 Hz, CH8 of quinoline), 7.86 (2H, d,
3
3JHH =7.1 Hz, 2CHortho of Ph), 7.88 (2H, d, 3JHH =7.7 Hz,
2CH of Ar), 7.89 (1H, d, 3JHH =8.3 Hz, CH9 of quinoline),
7.91(1H, d, 3JHH =8.0 Hz, CH6 of quinoline), 8.46 (1H, s,
CH5 of quinoline). 13C NMR (125.75 MHz, DMSO-d6):
21.60 (Me), 33.29 (CH4), 44.97 (CH2), 88.52 (C3), 118.65
(CN), 118.87 (C4a), 126.44 (CH7 of quinoline), 127.67 (C5a
of quinoline), 127.79 (CH6 of quinoline), 128.05 (CH8 of
quinoline), 128.40 (2CHmeta of Ph), 128.64 (2CHmeta of Ar),
129.20 (2CHortho of Ph), 129.70 (2CHortho of Ar), 130.84
(CH9 of quinoline), 131.74 (Cipso of Ph), 131.95 (CHpara of
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Journal of the Iranian Chemical Society
Ph), 134.28 (Cipso-CO), 138.17 (CH5 of quinoline), 144.50
(Cipso-Me), 145.42 (C9a of quinoline), 155.06 (C10a of qui-
noline), 161.67 (C2), 197.02 (C=O). MS (EI, 70 eV) m/z
(%): 417 (M+ +1, 6), 416 (M+, 10), 297 (8), 284 (43), 283
(100), 255 (4), 254 (5), 253 (5), 230 (3), 217 (12), 216 (39),
120 (8), 119 (70), 105 (6), 91 (15), 77 (3). Anal. calcd. for
C28H20N2O2 (416.47): C, 80.75; H, 4.84; N, 6.73. Found: C,
80.71; H, 4.86; N, 6.75%.
quinoline), 7.80 (2H, d, 3JHH =7.8 Hz, 2 CHortho of PhCO),
3
7.83 (1H, d, JHH = 7.9 Hz, CH7 of quinoline), 8.41 (1H,
s, CH6 of quinoline). 13C NMR (75.46 MHz, DMSO-d6):
27.66 (CH12), 28.96 (Me), 29.11 (Me), 44.19 (CH2), 87.38
(C4a), 120.03 (C5a), 126.12 (CH8 of quinoline), 127.16 (CH7
and C6a of quinoline), 127.44 (CH9 of quinoline), 127.74
(2CH of PhCO), 128.56 (2CH of PhCO), 130.27 (CH10 of
quinoline), 133.29 (CHpara of PhCO), 136.27 (Cipso C=O),
138.17 (CH6 of quinoline), 144.38 (C10a of quinoline),
149.93 (C11a), 153.09 and 154.09 (C=Oamide), 161.05 (C12a),
198.09 (C=O). MS (EI, 70 eV) m/z (%): 414 (M+ + 1, 4),
413 (M+, 10), 309 (5), 308 (25), 295 (25), 294 (100), 251
(11), 238 (5), 237 (29), 209 (2), 194 (4), 166 (8), 152 (11),
140 (3), 128 (1), 105 (6), 77 (4). Anal. calcd. for C24H19NO3
(413.43): C, 69.72; H, 4.63; N, 10.16. Found: C, 69.77; H,
4.60; N, 10.14%.
3‑Dimethyl‑12‑(2‑oxo‑2‑phenylethyl)‑2,3,4,12‑tet‑
rahydro‑1H‑chromeno[2,3‑b]quinolin‑1‑one (4d)
White powder, m.p=186–187 °C (dec.), 0.39 g, yield: 98%.
IR (KBr) (νmax, cm−1): 1680 (C=O), 1638, 1499 (Ar), 1240,
1221 (C-O). 1H NMR (500.13 MHz, DMSO-d6): 0.99 (3H,
s, Me) and 1.06 (3H, s, Me), 2.25 (2H, ABq,3JHH =16.0 Hz,
2
3
4
CH2 ), 3.82 (2H, ABq, JHH = 17.7 Hz, CH2 ), 3.62 (2H,
2
3
1
ABqd, JHH = 17.2 Hz, JHH = 5.6 Hz, CH2 ), 4.49 (1H,
7‑(2‑Oxo‑2‑phenylethyl)‑6H,7H‑chromeno[3',4':5,6]
pyrano[2,3‑b]quinolin‑6‑one (4f)
bs, CH12), 7.42 (1H, t, JHH = 7.2 Hz, 2CHmeta of PhCO),
3
3
7.47 (1H, t, JHH = 7.3 Hz, CHpara of PhCO), 7.55 (1H, t,
3JHH =7.2 Hz, CH8 of quinoline), 7.67 (1H, t, 3JHH =7.2 Hz,
CH9 of quinoline), 7.79 (1H, d, 3JHH =8.3 Hz, CH7 of qui-
noline), 7.83 (2H, d, 3JHH =7.9 Hz, CH10 of quinoline), 7.83
(2H, d, 3JHH =7.2 Hz, 2CHortho of PhCO), 8.33(1H, s, CH11
of quinoline). 13C NMR (125.75 MHz, DMSO-d6): 26.95
White powder, m.p = 255–256 °C (dec.), 0.33 g, yield:
80%. IR (KBr) (νmax, cm−1): 1717 (C=O of ester), 1674
(C=O), 1649, 1627, 1609, 1579 (Ar), 1245, 1206, 1041
(C-O). 1H NMR (300.13 MHz, DMSO-d6): 3.90 (2H, ABqd,
2JHH =14.3 Hz, CH2), 4.64 (1H, bs, CH7), 7.38–7.52 (6H,
m, CH2, CH4, CH10 of quinoline, 2CHmeta of Ph and CHpara
Of Ph), 7.67 (1H, t, 3JHH =6.6 Hz, CH11 of quinoline), 7.67
(1H, t, 3JHH =6.6 Hz, CH3), 7.82 (1H, d, 3JHH =7.3 Hz, CH12
4
(CH12), 29.06 (Me), 29.21 (Me), 32.27 (C3), 40.98 (CH2 ),
1
2
45.36 (CH2 ), 50.58 (CH2 ), 111.83 (C12a), 121.57 (C11a),
126.11 (CH9 of quinoline), 127.45 (C10a), 127.67 (CH10
of quinoline), 127.88 (CH8 of quinoline), 128.66 (2CH of
PhCO), 129.10 (2CH of PhCO), 130.46 (CH7 of quinoline),
133.72 (CHpara of PhCO), 136.91 (Cipso-C=O), 138.48
(CH10 of quinoline), 145.17 (C6a of quinoline), 155.64 (C5a
of quinoline), 166.53 (C4a), 196.95 (C=O), 198.54 (C=O).
MS (EI, 70 eV) m/z (%): 397 (M+, 35), 314 (3), 313 (23),
293 (8), 292 (59), 279 (22), 278 (100), 259 (7), 258 (32),
237 (4), 236 (23), 223 (9), 222 (54), 194 (7), 180 (12), 167
(9), 166 (43), 153 (7), 152 (34), 151 (5), 140 (12), 139 (8),
125 (6), 106 (6), 105 (59), 91 (10), 77 (41), 57 (21), 56(10),
55(19). Anal. calcd. for C26H23NO3 (397.47): C, 78.57; H,
5.83; N, 3.52. Found: C, 78.52; H, 5.86; N, 3.54%.
3
of quinoline), 7.82 (2H, d, JHH = 7.3 Hz, 2CHmeta of Ph),
8.01 (1H, d, 3JHH =7.0 Hz, CH1), 8.41 (1H, s, CH8 of qui-
noline). 13C NMR (75.46 MHz, DMSO-d6): 29.81 (CH7),
1
44.00 (CH2 ), 102.83 (C6a), 113.60 (C14b), 116.47 (CH4),
119.93 (C7a), 122.38 (CH2), 124.68 (CH1), 125.95 (CH10
of quinoline), 127.15 (C8a of quinoline), 127.21 (CH9 of
quinoline), 127.45 (CH11 of quinoline), 127.80 (2CH of Ph),
128.56 (2CH of Ph), 130.22 (CH12 of quinoline), 132.61
(CH3), 133.35 (CHpara of Ph),136.09 (Cipso-CO), 138.17
(CH8 of quinoline), 144.67 (C12a), 152.05 (C13a), 154.13
(C4a), 156.24 (COO), 160.45 (C14a), 197.71 (C=O). MS (EI,
70 eV) m/z (%): 420 (M+ +1, 6), 419 (M+, 19), 316 (2), 315
(11). 314 (48), 301 (25), 300 (100), 272 (5), 216 (4), 215
(4), 189 (3), 152 (3), 121 (2), 105 (13), 77 (10), 28 (4). Anal.
calcd. for C27H17NO4 (419.43): C, 77.32; H, 4.09; N, 3.34.
Found: C, 77.38; H, 4.05; N, 3.32%.
1,3‑Dimethyl‑5‑(2‑oxo‑2‑phenylethyl)‑1,5‑dihy‑
dro‑2H‑pyrimido[5',4':5,6]pyrano[2,3‑b]quino‑
line‑2,4(3H)‑dione (4e)
White powder, m.p=256–257 °C (dec.), 0.38 g, yield: 92%.
IR (KBr)(νmax, cm−1): 1707. 1668 (C=O), 1635, 1576, 1495
2‑(3‑Methyl‑1‑phenyl‑1,4‑dihydropyrazolo[4',3':5,6]
pyrano[2,3‑b]quinolin‑4‑yl)‑1‑phenylethanone (4g)
1
(Ar), 1243, 1218, 1184 (C-O). H NMR (300.13 MHz,
DMSO-d6): 3.15 (3H, s, Me), 3.43 (3H, s, Me), 3.75 (2H,
White powder, m.p=188–189 °C (dec.), 0.41 g, yield: 95%.
IR (KBr) (νmax, cm−1): 1685 (C=O), 1627, 1597, 1516, 1494
ABqd, 2JHH =17.3 Hz, CH2), 4.53 (1H, bs, CH5), 7.41 (2H,
3
1
d, JHH = 7.2 Hz, 2CHmeta of PhCO), 7.51 (2H, m, CHpara
(Ar), 1238, 1209, 1150 (C-O). H NMR (300.13 MHz,
Of PhCO and CH8 of quinoline), 7.69 (1H, t, 3JHH =7.3 Hz,
DMSO-d6): 2.22 (3H, s, Me), 3.80—3.84 (2H, m, CH2), 4.81
3
CH9 of quinoline), 7.79 (1H, d, JHH = 8.5 Hz, CH10 of
(1H, bs, CH4), 7.33 (1H, t, 3JHH =6.7 Hz, 2CHmeta of Ph),
1 3

Journal of the Iranian Chemical Society
3
7.42 (2H, t, JHH = 7.4 Hz, CHmeta of PhCO), 7.47 (1H, t,
105 (15), 77 (3). Anal. calcd. for C31H20N2O2 (452.50): C,
82.28; H, 4.45; N, 6.19. Found: C, 82.24; H, 4.47; N, 6.21%.
3JHH =7.7 Hz, CHpara of PhCO), 7.55 (1H, t, 3JHH =6.9 Hz),
3
7.55 (2H, t, JHH = 6.9 Hz, 2CHmeta of Ph), 7.68 (1H, t,
3JHH =6.8 Hz, CH8 of quinoline), 7.82 (2H, d, 3JHH =8.3 Hz,
CH9 and CH6 of quinoline), 7.86 (4H, m, 2 CHortho of PhCO
and 2CHortho Of Ph). 8.47 (1H, s, CH5 of quinoline). 13C
NMR (75.46 MHz, DMSO-d6): 13.00 (Me), 29.13 (CH4),
45.98 (CH2), 97.87 (C3a), 120.15 (2CH of Ph), 121.09 (C4a),
125.74 (C5a of quinoline), 126.10 (CHpara Of Ph), 126.70
(CH7 Of quinoline), 127.03 (CH6 of quinoline), 127.43 (CH8
of quinoline), 127.95 (2CH of Ph), 128.62 (2CH of PhCO),
129.41 (2CH of PhCO), 130.19 (CH9 of quinoline), 133.33
(CHpara of PhCO), 136.33 (Cipso-C=O), 137.74 (CH5 of qui-
noline), 139.03 (Cipso Ph), 144.47 (C9a of quinoline), 145.20
(C3), 146.36 (10a), 155.49 (C11a), 197.65 (C=O). MS (EI,
70 eV) m/z (%): 433 (M+ + 2, 12), 432 (M+ + 1, 34), 431
(M+, 1) 327 (12), 315 (25), 314 (100), 313 (100), 312 (100),
278 (100), 298 (7), 297 (3), 273 (6), 272 (26), 271 (8), 270
(7), 269 (10), 256 (5), 255 (3), 244 (14), 243 (16), 242 (6),
217 (11), 216 (3), 196 (6), 195 (6), 193 (7), 192 (6), 191
(4), 190 (3), 168 (10), 167 (8), 166 (6), 164 (12), 141 (27),
140 (8), 118 (2), 119 (9), 106 (33), 105 (3). 92 (17), 91 (4),
79 (10), 78 (95), 77 (4), 66 (8), 52 (27). Anal. calcd. for
C28H21N3O2 (431.49): C, 77.94; H, 4.91; N, 9.74. Found:
C, 77.91; H, 4.92; N, 9.76%.
8‑[2‑(4‑Chlorophenyl)‑2‑oxoethyl]‑10‑phe‑
nyl‑8H‑benzo[h]pyrano[2,3‑b]quinoline‑9‑carboni‑
trile (4i)
White powder, m.p.=255–257 °C (dec.), 0.43 g, yield: 88%.
IR (KBr) (vmax, cm−1): 2207 (CN), 1683 (C=O), 1663, 1619,
1601, 1586 (Ar), 1263, 1220 (C-O). 1H NMR (500.13 MHz,
2
DMSO-d6): 3.93 (2H, ABqd, JHH = 18.2 Hz, CH2), 4.71
3
(1H, bs, CH8), 7.49 (2H, t, JHH = 7.6 Hz, 2CHmeta of
3
Ph), 7.62 (1H, t, JHH = 7.5 Hz, CHpara of Ph), 7.70 (2H,
d, 3JHH =7.15 Hz, 2CH of Ar), 7.74 (2H, t, 3JHH =7.5 Hz,
3
CH2 and CH3 of quinoline), 7.79 (1H, d, JHH = 8.2 Hz,
CH5 of quinoline), 7.89 (1H, d,3JHH =8.2 Hz, CH6 of qui-
noline), 7.91 (2H, d, 3JHH =7.5, 2CHortho of Ph), 7.97 (2H,
3
3
d, JHH = 6.7 Hz, 2CH of Ar), 8.01 (1H, d, JHH = 8.3 Hz,
CH4 of quinoline), 8.50 (1H, s, CH7 of quinoline), 8.98 (1H,
bs, CH1 of quinoline. 13C NMR (125.75 MHz, DMSO-d6):
32.71 (CH8), 44.66 (CH2), 88.61 (C9), 117.75 (CN), 117.93
(C7a), 123.77 (CH1 of quinoline), 124.76 (CH6 of quino-
line), 125.13 (C6a of quinoline), 126.79 (CH2 of quinoline),
127.13 (CH3 of quinoline), 128.05 (CH5 of quinoline and
2CH of Ph), 128.57 (CH4 of quinoline), 128.69 (2CH of
Ph), 128.95 (2CH of Ar), 129.69 (Cipso of Ph), 129.89 (2CH
of Ar), 130.13 (C12b), 133.49 (C4a of quinoline), 133.54
(CHpara of Ph), 136.15 (Cips-CO), 136.25 (Cipso-Cl), 137.95
(CH7 of quinoline), 143 (C12a of quinoline), 154.24 (C11a
of quinoline), 160.25 (C10), 197.12 (C=O). MS (EI, 70 eV)
m/z (%): 488 (M+ +2, 7), 487 (M+ +1, 26), 486 (M+, 71),
379 (5), 377 (10), 345 (12), 344 (47), 343 (37), 342 (100),
314 (3), 279 (14), 278 (7), 203 (5), 202 (16), 201 (7), 175
(5), 141 (28), 140 (8), 139 (84), 111 (14). Anal. calcd. for
C31H19ClN2O2 (486.95): C, 76.46; H, 3.93; N, 5.75. Found:
C, 76.42; H, 3.95; N, 5.77%.
8‑(2‑Oxo‑2‑phenylethyl)‑10‑phenyl‑8H‑benzo[h]
pyrano[2,3‑b]quinoline‑9‑carbonitrile (4h)
White powder, 0.39 g, yield: 86%. IR (KBr) (vmax, cm−1):
2204 (CN), 1679 (C=O), 1642, 1619, 1598 (Ar), 1267,
1217, (C-O). 1H NMR (500.13 MHz, DMSO-d6): 3.94 (2H,
ABqd, 2JHH =16.7 Hz, CH2), 4.71 (1H, bs, CH8), 7.49 (2H, t,
3JHH =7.6 Hz, 2CHmeta of Ph), 7.60–7.63 (4H, m, CHpara of
Ph, CHpara of PhCO and 2CHmeta of PhCO), 7.73–7.75 ( 2H,
m, CH2 and CH3 of quinoline), 7.79 ( 1H, d,3JHH =8.2 Hz,
CH5 of quinoline), 7.86–7.89 (3H, m, CH6 of quinoline
3
and 2CHortho of Ph), 7.98 (2H, d, JHH = 7.4 Hz, 2CHortho
10‑(4‑Bromophenyl)‑8‑[2‑(4‑methoxyphenyl)‑2‑ox
oethyl]‑8H‑benzo[h]pyrano[2,3‑b]quinoline‑9‑car‑
bonitrile (4j)
of PhCO), 8.01( 1H, d, JHH = 8.0 Hz, CH4 of quinoline),
3
8.50 (1H, s, CH7 of quinoline), 8.97 (1H, bs, CH1 of qui-
noline). 13C NMR (125.75 MHz, DMSO-d6): 32.70 (CH8),
44.63 (CH2), 88.07 (C9), 117.85 (CN), 118.15 (C7a), 123.77
(CH1 of quinoline), 124.77 (CH6 of quinoline), 125.09 (C6a),
126.74 (CH2 of quinoline), 127.11 (CH3 of quinoline),
128.01 (2CHmeta of PhCO), 128.05 (CH3 of quinoline and
2CHmeta of Ph), 128.56 (CH4 of quinoline), 128.70 (2CHortho
of Ph), 128.75 (2CHortho of PhCO), 129.66 (C12b), 131.36
(Cipso of Ph), 131.46 (CHpara of Ph), 133.48 (C4a), 133.54
(CHpara of PhCO), 136.19 (Cipso-CO), 137.92 (CH7 of quino-
line), 143.04 (C12a of quinoline), 154.36 (C11a of quinoline),
161.43 (C10), 197.16 (C=O). MS (EI, 70 eV) m/z (%): 453
(M+ +1, 4), 452 (M+, 10), 347 (5), 335 (5), 334 (36), 333
(100), 305 (3), 304 (6), 303 (5), 267 (4), 266 (17), 216 (6),
White powder, m.p. = 245–246 °C (dec.), 0.53 g, yield:
96%. IR (KBr) (νmax, cm−1): 2211 (CN), 1671 (C=O),
1642, 1619, 1598 (Ar), 1267, 1218 (C-O).1H NMR
(300.13 MHz, DMSO-d6): 3.78 (3H, s, OMe), 3.90
2
(2H, ABqd, JHH = 18.10 Hz, CH2), 4.65 (1H, bs, CH8),
3
6.98 (2H, d, JHH = 7.9 Hz, 2CH of Ar), 7.74 (2H, d,
3JHH = 7.5 Hz, CH2 and CH3 of quinoline), 7.78–7.88
(6H, m, 4CH of Ar and 2CH of CH4 and CH5 quino-
3
line), 7.93 (2H, d, JHH = 7.9 Hz, 2CH of Ar), 7.99 (1H,
3
d, JHH = 8.2 Hz, CH6 of quinoline), 8.45 (1H, s, CH7 of
quinoline), 8.95 (1H, bs, CH1 of quinoline). 13C NMR
(75.46 MHz, DMSO-d6): 32.78 (CH8), 44.24 (CH2), 55.52
1 3

Journal of the Iranian Chemical Society
(OMe), 88.65 (C9), 113.87 (2CH of Ar), 117.86 (CN),
117.99 (C7a), 123.76 (CH1 of quinoline), 124.76 (CH6 of
quinoline), 125.00 (Cipso-Br), 125.10 (C6a of quinoline),
126.76 (CH2 of quinoline), 127.14 (CH3 of quinoline),
128.05 (CH5 of quinoline), 128.56 (CH4 of quinoline),
129.21 (Cipso–C10), 129.66 (Cipso-CO), 130.01 (2CH of
Ar and C12b), 130.43 (2CH of Ar), 131.87 ( 2CH of Ar),
131.89 (2CH of Ar), 133.45 (C4a of quinoline), 137.86
(CH7 of quinoline), 142.92 (C12a of quinoline), 154.20
(C11a of quinoline), 160.22 (C10), 163.39 (Cipso-OMe),
195.36 (C=O). MS (EI, 70 eV) m/z (%): 562 (M+, 2), 561
(M+-1, 2),, 427 (2), 426 (3), 425 (3), 412 (30), 411 (7),
410 (30), 334 (4), 333 (16), 266 (15), 136 (10), 135 (100),
121 (7), 109 (8), 108 (8), 107 (4), 105 (4), 77 (8). Anal.
calcd. for C32H21BrN2O3 (561.42): C, 68.46; H, 3.77; N,
4.99. Found: C, 69; H, 3.79; N, 4.93%.
10,12‑Dimethyl‑8‑(2‑oxo‑2‑phenylethyl)‑8H‑b
enzo[h]pyrimido[5',4':5,6]pyrano[2,3‑b]quino‑
line‑9,11(10H,12H)‑dione (4l)
White powder, m.p=260–262 °C (dec.), 0.32 g, yield: 70%.
IR (KBr) (νmax, cm−1): 1709, 1684, 1668 (C=O), 1645,
1597, 1579 (Ar), 1222, 1259 (C-O). 1H NMR (300.13 MHz,
CDCl3): 3.38 (3H, s, Me), 3.70 (3H, s, Me), 3.71 (2H, ABqd,
3
2JHH = 17.7 Hz, JHH = 5.9 Hz, CH2), 4.76 (1H, bs, CH8),
7.39 (2H, t, 3JHH =7.3 Hz, 2CHmeta of PhCO), 7.51 (1H, t,
3
3JHH = 7.1 Hz, CHpara Of Ph), 7.60 (1H, d, JHH = 8.7 Hz,
CH5 of quinoline), 7.65–7.75 (3H, m, CH2, CH3, CH6 of
quinoline), 7.86–7.89 (3H, m, 2CHortho of PhCO and CH4
of quinoline), 8.14 (1H, s, CH7 of quinoline), 9.13 (1H, d,
3JHH = 7.3 Hz CH1 of quinoline).13C NMR (75.46 MHz,
CDCl3): 28.13 (CH12), 29.59 (Me), 29.65 (Me), 45.09 (CH2),
88.30 (C8a), 119.16 (C7a), 124.31 (CH1 of quinoline), 124.52
(CH6 of quinoline), 125.57 (C6a of quinoline), 127.08 (CH2
of quinoline), 127.47 (CH3 of quinoline), 127.82 (CH5 of
quinoline), 127.99 (2CH of PhCO), 128.58 (2CH of PhCO
and CH4 of quinoline), 130.34 (C14b of quinoline), 133.34
(CHpara of PhCO), 133.80 (C4a of quinoline), 136.49 (Cipso
C=O), 138.07 (CH7 of quinoline), 143.76 (C14a of quino-
line), 150.66 (C13a), 153.84 and 153.98 (C=Oamide), 161.95
(C12a), 197.66 (C=O). MS (EI, 70 eV) m/z (%): 465 (M+ +2,
2), 464 (M+ +1, 4), 463 (M+,12), 359 (4), 358 (15), 346 (5),
345 (33), 344 (100), 301 (6), 288 (6), 287 (30), 272 (6), 260
(3), 244 (7), 216 (6), 202 (2), 179 (1), 150 (2), 105 (5), 91
(2), 77 (3). Anal. calcd. for C28H21N3O4 (463.48): C, 72.56;
H, 4.57; N, 9.07. Found: C, 72.50; H, 4.59; N, 9.11%.
11,11‑Dime‑
thyl‑8‑(2‑oxo‑2‑phenylethyl)‑8,10,11,12‑tetrahy‑
dro‑9H‑benzo[h]chromeno[2,3‑b]quinolin‑9‑one
(4k)
White powder, m.p = 170–171 °C (dec.), 0.38 g, yield:
85%. IR (KBr) (νmax, cm−1): 1681(C=O), 1642, 1596, 1597
1
(Ar), 1211, 1259 (C-O). H NMR (500.13 MHz, DMSO-
d6): 0.99 (3H, s, Me), 1.06 (3H, s, Me), 2.24 (2H, ABq,
2
2JHH = 15.9 Hz, 2CH2), 2.57 (2H, ABq, JHH = 17.5 Hz,
CH2), 3.61 (2H, ABqd, 2JHH =17.5 Hz, 3JHH =5.4 Hz, CH2),
4.49 (1H, bs, CH8), 7.41 (2H, t, 3JHH =7.3 Hz, 2CHmeta of
3
Ph), 7.53 (1H, t, JHH = 6.7 Hz, CHpara of Ph), 7.67–7.72
(3H, m, CH2, CH3 and CH5 of quinoline), 7.80 (1H, d,
7‑(2‑Oxo‑2‑phenylethyl)‑6H,7H‑benzo[h]
chromeno[3',4':5,6]pyrano[2,3‑b]quinolin‑6‑one
(4m)
3JHH =8.2 Hz, CH6 of quinoline), 7.82 (2H, 3JHH =7.8 Hz,
3
2CHortho of Ph), 7.96 (1H, d, JHH = 8.3 Hz, CH4 of qui-
noline), 8.34 (1H, s, CH7 of quinoline), 8.93 (1H, d,
3JHH =8.3 Hz, CH1 of quinoline). 13C NMR (125.75 MHz,
DMSO-d6): 26.95 (CH8), 29.05 (Me), 29.24 (Me), 32.25
(C11), 40.98 (CH2), 45.26 (CH2), 50.58 (CH2), 111.17 (C8a),
121.08 (C7a), 124.11 (CH1 of quinoline), 125.18 (CH6 of
quinoline), 125.24 (CH6a of quinoline), 126.81 (CH2 of
quinoline), 127.43 (CH3 of quinoline), 128.25 (2CH of
Ph), 128.44 (CH5 of quinoline), 128.77 (CH4 of quino-
line), 129.08 (2CH of Ph), 130.25 (CH14b of quinoline),
133.69 (CHpara Of Ph), 133.81 (CH4a of quinoline), 136.95
(Cipso-C=O), 138.68 (CH7 of quinoline), 143.03 (C14a of
quinoline), 155.34 (C13a), 166.58 (C12a), 196.97 (C=O),
198.60 (C=O). MS (EI, 70 eV) m/z (%): 449 (M+ + 2, 3),
448 (M+ +1, 12), 447 (M+,23), 364 (4), 363 (14), 343(10),
342 (23), 330 (4), 329 (29), 328 (100), 309 (9), 308 (36), 286
(11), 273 (6), 272 (30), 244 (11), 230 (7), 217 (6), 216 (30),
215 (8), 202 (9), 189 (3), 105 (19), 77 (10). Anal. calcd. for
C30H25NO3 (447.52): C, 80.51; H, 5.63; N, 3.13. Found: C,
80.53; H, 5.65; N, 3.07%.
White powder, m.p = 281–282 °C (dec.), 0.30 g, yield:
65%. IR (KBr) (νmax, cm−1): 1705 (COO), 1684 (C=O),
1
1646, 1608, 1578 (Ar), 1258, 1205, 1151 (C-O). H NMR
(300.13 MHz, DMSO-d6): 3.84 (2H, ABqd, 2JHH =17.8 Hz,
3JHH = 6.7 Hz, CH2), 4.92 (1H, ABq,3JHH = 3.1 Hz, CH7),
7.41 (1H, t, 3JHH =7.4 Hz, CH2), 7.42 (1H, t, 3JHH =7.6 Hz,
CH4), 7.51 (2H, t, 3JHH =8.7 Hz, 2CHmeta of Ph),7.54 (1H,
t, 3JHH =8.0 Hz, CHpara of Ph),7.75 (2H, d, 3JHH =6.8 Hz,
2CHortho of Ph), 7.76–7.88 (m, 5H), 8.00 (1H, d,
3JHH =8.0 Hz, CH4 of quinoline), 8.15 (1H, d, 3JHH =7.6 Hz,
CH1), 8.51 (1H, s, CH8 of quinoline), 9.03 (1H, d,
3JHH = 6.7 Hz, CH1 of quinoline). 13C NMR (75.46 MHz,
1
CDCl3): 30.27 (CH7), 45.10 (CH2 ), 102.92 (C6a), 114.23
(C16b), 116.62 (CH4), 118.86 (C7a), 123.53 (CH2), 124.42
(CH9, and CH14 of quinoline), 124.63 (CH1), 125.49 (C8a
of quinoline), 127.01 (CH13 of quinoline), 127.25 (CH12 of
quinoline), 127.79 (CH10 of quinoline), 128.02 (2CH of Ph),
128.50 (CH11 of quinoline), 128.60 (2CH of Ph), 130.43
1 3

Journal of the Iranian Chemical Society
(C14a of quinoline), 132.43 (CH3), 133.35 (CHpara of Ph),
133.84 (C10a of quinoline), 136.43 (Cipso-CO), 138.38 (CH8
of quinoline), 144.07 (C14b), 152.78 (C15a), 154.13 (C4a),
157.87 (COO), 161.64 (C16a), 197.15 (C=O). MS (EI,
70 eV) m/z (%): 470 (M+ +1, 4), 469 (M+, 11), 365 (7), 364
(26), 352 (5), 351 (32), 350 (100), 322 (4), 265 (6), 182(6),
105 (7), 77 (3). Anal. calcd. for C31H19NO4 (469.49): C,
79.31; H, 4.08; N, 2.98. Found: C, 79.34; H, 4.10; N, 2.93%.
optimal reaction conditions, diferent solvents such as
DMF, MeCN, CH2Cl2 and catalysts, were examined to
optimize the reaction conditions. Among them, EtOH was
chosen as the best solvent for high productivity. In order
to evaluate the catalytic efciency of triethylamine, we
performed the reaction with several equivalents of trieth-
ylamine from 15 to 100%. An excessive amount of catalyst
(100 mol %) in the refux condition increased the yield
remarkably as shown in Table 1. This showed that the
catalyst concentration has an important role in optimizing
product performance.
Results and Discussion
Therefore, we chose the best conditions for the synthe-
sis of 4a-m compounds, which are as follows: use of Et3N
(100 mol %) as the base and dry EtOH as the solvent to
perform two processes Michael addition and intramolecu-
lar cyclization under refux conditions during 2–3 h. We
probed the scope of the annulation with diferent active
methylene compounds such as (benzoylacetonitrile, dime-
done, 1,3-dimethylbarbituric acid, 4-hydroxycoumarin and
3-methyl-1-phenyl-1H-pyrazol-5(4H)-one). All four active
methylene compounds led the reaction to pyrano[2,3-b]qui-
nolines with excellent yields. Unfortunately, when acetylac-
etone and ethyl acetylacetate were applied the reaction did
not proceed to yield pyrano[2,3-b]quinolines.
Initially, we started our investigations with the reaction of
aldehyde 1 and Wittig reagent 2, in ethanol solvent at room
temperature. The reaction was monitored by TLC, within
for 30 min starting materials were consumed completely and
α,β-unsaturated compound 5 was formed.
As seen in Scheme 3, there are three potential electro-
philic sites in the structure of α,β-unsaturated compound
5 and according to literature [48] chlorine atom usually
replaces by oxygen atom of active methylene compounds.
In the next step, via a one-pot reaction, the reaction mix-
ture was refuxed by adding active methylene compounds
and Et3N as base. Gratifyingly during 2–3 h a white pre-
cipitates with high efciency was observed. To fnd the
Scheme 3 Mechanistic rationale for the synthesis of 4a
1 3

Journal of the Iranian Chemical Society
Table 1 Optimization of the reaction conditionsa
Entry
Catalyst
Solvent (5 mL)
Temperature (°C)
Yield (%)b
1
2
3
4
5
6
7
8
none
EtOH
EtOH
EtOH
EtOH
EtOH
CH3CN
DMF
CH2Cl2
EtOH
EtOH
CH3CN
Refux
Refux
Refux
Refux
Refux
Refux
N.R
65
80
95
85
85
70
50
50
40
80
Et3N (15%)
Et3N (50%)
Et3N (100%)
Piperidine
Et3N
Et3N
Et3N
K2CO3
CH3COONa
Piperidine
Refux
no temperaturec
Refux
9
10
11
Refux
Refux
aReaction conditions: 2-Chloroquinoline-3-carbaldehyde (0.5 mmol), 1-phenyl-2-(1,1,1-triphenyl-λ5-phosphanylidene)ethan-1-one (0.5 mmol),
benzoylacetonitrile (0.5 mmol), solvent (5 mL) and Et3N (100 mol%) in EtOH under refux condition
bIsolated yields
cReaction performed at rt
The electronic nature of the substituent on the aro-
matic rings afected the reaction and excellent yields.
Therefore, the generality and efciency of this reaction
were deliberated using diferently substituted benzoylace-
tonitriles and substitutions on phenyl Wittig. Eventually,
products 4a-m were obtained in excellent yields. It was
clear that the reaction yield in the presence of electron-
withdrawing substituents such as Br and Cl on phenyl of
benzoylacetonitriles was better than electron-donating (Me
and OMe) substituents on phenyl it. For this purpose, we
selected electron-withdrawing substituents such as Br and
Cl on phenyl nucleophiles (benzoylacetonitriles, R2 = Ph,
p-ClC6H4, p-BrC6H4). But, the product was not observed
when a strong electron-withdrawing group such as NO2
was present on the aromatic ring of it. It was also clear
that by selecting the electron donor substitution on the aro-
matic ring of Wittig reagent, the reaction is more efcient.
Therefore, product 4j was selected as the most efcient
reaction product. The results are illustrated in Table 2.
Should be mentioned the steric efect was also exam-
ined in this scope the steric efect on the aromatic ring did
infuence the reaction efciency with a great reduction in
the isolated yield. So that by selecting substituents Cl on
ortho of the aromatic rings, no product was observed.
The structures of all the products 4a-m were deduced
from their IR, mass, 1H NMR, and 13C NMR spectra. The
mass spectrum of 4a displayed the molecular ion peak at
m/z=402, which is in agreement with the proposed struc-
ture. In the IR spectrum of 4a, absorption band at 2205 cm−1
attributed to the CN. Also, absorption band C=O in stretch-
1
ing frequencies 1680 cm−1. The H NMR spectrum of 4a
exhibited AB quartet of doublet (ABqd) at δ= 3.95 ppm
related to CH2 and δ = 4.69 ppm a triplet with J = 4.5 Hz
related to CH of the pyran ring respectively. Also, the singlet
peak at δ=8.48 ppm attributed to CH5 of quinoline. Obser-
vation of 23 distinct signals in the 1H-decoupled 13C NMR
spectrum of 4a is in agreement with the proposed structure.
The 13C-NMR data showed two peaks in the aliphatic region
at 32.21 ppm and 45.08 ppm for CH2 and CH of the pyran
ring, respectively, and a peak in 197.54 ppm for carbonyl
group.
A plausible mechanism for the synthesis of 4a is outlined in
Scheme 3. Initially, the Wittig reagent and the aldehyde moi-
ety form the α,β-unsaturated compound 5. Then, by activating
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Journal of the Iranian Chemical Society
Table 2 Synthesis of pyrano[2,3-b]quinoline and benzo[h]pyrano[2,3-b]quinolines derivatives 4a-ma
aReaction conditions: 2-Chloroquinoline-3-carbaldehyde 1a or 2-chlorobenzo[h]quinoline-3-carbaldehyde 1b, (0.5 mmol), 1-aryl-2-(1,1,1-
triphenyl-λ5-phosphanylidene)ethan-1-one 2 (0.5 mmol), active methylene compounds 3 (0.5 mmol), solvent (5 mL) and Et3N (100 mol %) in
EtOH under refux condition
methylene of benzoylacetonitrile by triethylamine, a C–C bond
is formed (Michael addition, intermediate 7). Eventually, the
oxygen atom of benzoylacetonitrile undergoes intramolecular
cyclization, leading to the formation of pyranoquinolines 4a.
materials such as (2-chloroquinoline-3-carbaldehyde or
2-chlorobenzo[h]quinoline-3-carbaldehyde), 1-aryl-2-
(1,1,1-triphenyl-λ5-phosphanylidene)ethan-1-one (Wittig
reagents) and the active methylene compounds, during the
two processes of C–C bond formation (Michael addition)
and intramolecular cyclization. Absence of a metal catalyst,
simple workup procedure and excellent yields of the prod-
ucts make it an efcient route for synthesizing pyranoquino-
line heterocycles. Considering the biological properties of
pyrano-quinolines that have been studied and mentioned in
Conclusions
In summary, we developed a convenient method for the syn-
thesis of pyrano[2,3-b]quinoline and benzo[h]pyrano[2,3-
b]quinoline derivatives from the available starting
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Journal of the Iranian Chemical Society
25. K. Kaur, M. Jain, R.P. Reddy, R. Jain, Eur. J. Med. Chem. 45,
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Supplementary Information The online version contains supplemen-
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