2H-Pyrano[3,2-c]quinolin-2-ones: their convenient synthesis and selected reactions

Article abstract of DOI:10.1007/s11696-017-0319-0

Abstract: Despite the structure attractiveness of 2H-pyrano[3,2-c]quinolin-2-ones 3 their synthesis is not sufficiently developed. Only 35 pyranoquinolinones 3 are registered in the SciFinder database. Unavailability of 3 limits their chemistry exploitation, physical and biological studies. We have developed a convenient and general methodology for the synthesis of 3. Sixteen novel 2H-pyrano[3,2-c]quinolin-2-ones 3 were prepared by a cyclocondensation of easily available 4-oxo-1,4-dihydroquinoline-3-carbaldehydes 1 with monosubstituted acetic acids 2 (-aryl, -arylthio and -heteroaryl). To support chemistry exploitation of pyranoquinolinones 3, oxoquinolinylphenylacrylic acids 4 were obtained by hydrolysis of 3 with NaOH (92–98%). A simple oxidation of 3 by MCPBA was performed to provide oxopyranoquinoline N-oxide 5 (71%). Convenient rearrangement of 5 in refluxing Ac₂O curried out 2H-pyrano[3,2-c]quinoline-2,5(6H)-dione 6 in 87% yield. Moreover, some of the prepared pyranoquinolinones 3 possess intensive blue fluorescence properties. Here we described the simple and general synthesis that allows availability of 2H-pyrano[3,2-c]quinolin-2-ones 3. Some transformations of 3 to the novel heterocyclic compounds 4–6 were performed as well in good yields (71–98%). The synthesis of 6 from 3 was not yet described. The developed methodology for the synthesis of 3–6 can stimulate their further physical and pharmacological studies. Graphical Abstract: [Figure not available: see fulltext.].

Full text of DOI:10.1007/s11696-017-0319-0

Chem. Pap.
DOI 10.1007/s11696-017-0319-0
ORIGINAL PAPER
2H-Pyrano[3,2-c]quinolin-2-ones: their convenient synthesis
and selected reactions
1
1
2
1
•
ˇ
•
•
•
Mat u´ sˇ Cakurda Pavol Koi sˇ Gabriela Addov a´ Margita L a´ cov a´
1
,3
Andrej Boh a´ cˇ
Received: 19 August 2017 / Accepted: 9 October 2017
Ó Institute of Chemistry, Slovak Academy of Sciences 2017
Abstract Despite the structure attractiveness of
2H-pyrano[3,2-c]quinolin-2-ones 3 their synthesis is not suf-
oxidation of 3 by MCPBA was performed to provide oxopy-
ranoquinoline N-oxide 5 (71%). Convenient rearrangement of
5 in refluxing Ac O curried out 2H-pyrano[3,2-c]quinoline-
ficiently developed. Only 35 pyranoquinolinones 3 are re-
gistered in the SciFinder database. Unavailability of 3 limits
their chemistry exploitation, physical and biological studies.
Wehavedevelopedaconvenientandgeneralmethodologyfor
the synthesis of 3. Sixteen novel 2H-pyrano[3,2-c]quinolin-
2
2,5(6H)-dione6 in87%yield.Moreover, someoftheprepared
pyranoquinolinones 3 possess intensive blue fluorescence
properties. Here we described the simple and general syn-
thesis that allows availability of 2H-pyrano[3,2-c]quinolin-2-
ones 3. Some transformations of 3 to the novel heterocyclic
compounds 4–6 were performed as well in good yields
(71–98%). The synthesis of 6 from 3 was not yet described.
The developed methodology for the synthesis of 3–6 can
stimulate their further physical and pharmacological studies.
2
-ones 3 were prepared by a cyclocondensation of
easily available 4-oxo-1,4-dihydroquinoline-3-carbaldehydes
with monosubstituted acetic acids 2 (-aryl, -arylthio and -
1
heteroaryl). To support chemistry exploitation of pyra-
noquinolinones 3, oxoquinolinylphenylacrylic acids 4 were
obtained by hydrolysis of 3 with NaOH (92–98%). A simple
ˇ
The authors Mat u´ sˇ Cakurda and Margita L a´ cov a´ also contributed to
writing this paper.
Electronic supplementary material The online version of this
article (doi:10.1007/s11696-017-0319-0) contains supplementary
material, which is available to authorized users.
&
Andrej Boh a´ cˇ
andrej.bohac@fns.uniba.sk
1
Department of Organic Chemistry, Faculty of Natural
Sciences, Comenius University in Bratislava, Mlynska´
dolina, Ilkovi cˇ ova 6, 842 15 Bratislava, Slovakia
2
3
Institute of Chemistry, Faculty of Natural Sciences,
Comenius University in Bratislava, Mlynsk a´ dolina,
Ilkovi cˇ ova 6, 842 15 Bratislava, Slovakia
Biomagi, Ltd., Mamateyova 26, 851 04 Bratislava, Slovakia
123

Chem. Pap.
Graphical Abstract
Keywords 2H-Pyrano[3,2-c]quinolin-2-one Á (Z)-3-(4-
Oxo-1,4-dihydroquinolin-3-yl)-2-phenylacrylic acid Á 2-
Oxo-2H-pyrano[3,2-c]quinoline 6-oxide Á Quinoline N-
oxide Á 2H-Pyrano[3,2-c]-quinoline-2,5(6H)-dione Á
Cyclocondensation Á Fluorescence
(Chugger and Trivedi 1972). Other derivatives of 3
were prepared from 2,3-dihydroquinolin-4(1H)-one in
72% yield (Peruncheralathan et al. 2004), from
3-acetylquinolin-4(3H)-one in 70% yield (Ghorab et al.
2001), from quinolin-4(1H)-ones or quinoline in 43% yield
(
Nesterova et al. 1995, 1993). Some of compounds 3 were
prepared from substituted 4-hydroxyquinoline in 79%
(Soliman and Said 1991), by hydrolysis of substituted
Introduction
2
H-pyrano[3,2-c]quinolin-2-ones (Thakore and Trivedi
Synthesis and properties of 2H-pyrano[3,2-c]quinolin-2-
ones 3 (Fig. 1) are described in the literature very insuffi-
ciently. Therefore, exploitations of 3 in life and material
sciences are very limited. The scientific database (The
SciFinder 2017) has registered only 35 derivatives of 3,
nineteen of them were prepared from 4-hydroxyquinolines
in 66% yield (Anukumari et al. 2015), at 180–205 °C in
1980) or from derivatives of 4-hydroxyquinoline and
4-hydroxyquinoline-3-carbaldehyde in 88 and 99% yield,
resp (Narasimhan and Bhagwat 1979). Even though
4-hydroxyquinoline (quinolin-4-ol) and quinolin-4(1H)-one
are tautomers, both structures (used separately) can be
found in the literature as a starting material. To perform
good quality literature searches both tautomers should be
considered.
7
2–90% yields (Mohtat et al. 2013), at 180–230 °C within
.5–4 days in 10–66% yields. Compounds 3 were also
2
Low availability of 2H-pyrano[3,2-c]quinolin-2-ones 3
could be a reason of their only few biological studies. Four
compounds of 3 were studied in antibacterial/fungicide
(Ghorab et al. 2001) or neuromuscular and psychotropic
synthesized from 4-hydroxyquinoline-3-carbaldehyde at
0–140 °C within 2–11 days in 7–8% yields (Galariniotou
et al. 2007) or at 110 °C within 16 h by Et N in Ac O
6
3
2
Fig. 1 The structures and names of heterocyclic compounds 1, 3–6
1
23

Chem. Pap.
Scheme 1 The synthesis of
4-oxo-1,4-dihydroquinoline-3-
carbaldehydes 1(a,b)
assays (Nesterova et al. 1995). As we show in this paper
also other interesting heterocyclic compounds 4–6 (Fig. 1)
can be easily prepared from pyranoquinolinones 3.
General procedure A—the synthesis
of quinolinecarbaldehydes 1(a,b)
According to the SciFinder database, 3-(4-oxo-1,4-di-
hydroquinolin-3-yl)-2-phenylacrylic acids 4 and N-oxides
possessing 2-oxo-2H-pyrano[3,2-c]quinolines 5 are com-
pletely unknown. There are 79 registered 2H-pyrano[3,2-
A formylation mixture was prepared from 41.2 mL
(444.4 mmol, 6.00 mol eq) of POCl that was added dropwise
3
to 90.0 mL of DMF (abs) at 0 °C. Resulted solution was stirred
for 15 min under Ar at rt. Then 9.0 mL (74.0 mmol,
1.00 mol eq) of 1-(2-aminophenyl)ethanone was added drop-
wise to the stirred formylation mixture within 30 min and the
mixture heated to 60 °C for 16 h (instead of 4 h, described
previously in the literature) (Seixas et al. 2011). Then, the
mixture was cooled to rt by adding 400 g of crashed ice in
c]quinoline-2,5(6H)-diones
6
with 28 preparations,
whereby none of them starts from 3 as we performed here.
Until now, only eighteen derivatives of 6 were studied in
anti-infective, antitumor and hormone antagonist assays
(
The SciFinder database 2017). Therefore, we decided to
develop general synthesis of 3 to make this kind of rare
heterocyclic compounds accessible for further biological
and material studies. Additionally we aimed to explore
chemistry potential of 3 via selected transformations to
prepare different heterocyclic compounds 4–6.
200 mL H O and the reaction neutralized to pH 7 by solid
2
NaHCO . Precipitated yellow product was filtered off, dissolved
3
in CHCl , extracted with water. A separated organic layer was
3
dried over Na SO , filtered, concentrated by RVO and HV.
2
4
Crystallization from EA with charcoal bleaching provided
.50 g (44.4 mmol, 60%) of 4-chloroquinoline-3-carbaldehyde
8
in form of a white solid material. A suspension of the crude
4-chloroquinoline-3-carbaldehyde in 80 mL of HCOOH (54%
aqueous) was hydrolyzed at 50 °C within 2 h. The mixture was
cooled down and left in refrigerator overnight. The formed solid
product was filtered off, washed with H O, Et O and dried under
Experimental
Materials
2
2
Melting points were measured using Kofler apparatus or
1
Barnstead Electrothermal IA9200 and are uncorrected. H-
HV. The 1,4-dihydro-4-oxoquinoline-3-carbaldehyde (1a) was
obtained as a white solid 7.15 g (41.23 mmol, 93 or 56% overall
yield) and used for further synthetic step (Scheme 1).
1
3
and C-NMR spectra were recorded on Varian Gemini
300/600 MHz and 75/150 MHz, respectively), chemical
(
shifts are given in parts per million (ppm), tetramethylsi-
lane was used as an internal standard and DMSO-d6 as the
solvent, unless otherwise specified. The abbreviation dm in
4
-Oxo-1,4-dihydroquinoline-3-carbaldehyde (1a)
The compound 1a was prepared in 56% overall yield fol-
lowing the General procedure A. The quinolinecarbalde-
hyde 1a is described previously in the literature (Seixas
et al. 2011). For physico-chemical characteristics of 1a see
the Supporting Information.
1
the H NMR spectra means doublet of multiplet. It
describes more complex couplings observed at some of
aromatic hydrogens. IR spectra were acquired on FT-IR-
ATR REACT IR 1000 (ASI Applied Systems) with dia-
mond probe and MTS detector. Mass spectra were per-
formed on LC–MS (Agilent Technologies 1200 Series
equipped with Mass spectrometer Agilent Technologies
6-Bromo-4-oxo-1,4-dihydroquinoline-3-
carbaldehyde (1b)
6
100 Quadrupole LC–MS). The course of the reactions was
followed by TLC analysis (Merck Silica gel 60 F254). UV
lamp (254 nm) and iodine vapours were used for the
visualization of TLC spots. Starting chemicals were pur-
chased from Sigma-Aldrich, Fluorochem, Alfa Aesar or
Acros vendors. Used abbreviations EA, FLC and TLC
mean ethyl acetate, flash liquid chromatography and thin
layer chromatography, resp.
The compound 1b was prepared according to the General
procedure A, starting from 1.58 g (7.4 mmol, 1.00 mol eq)
of 1-(2-amino-5-bromophenyl)ethanone. The crude product
1.04 g (4.13 mmol, 90%) of 1b was obtained as a light
brown solid material. The compound 1b is not described
previously in the literature.
123

Chem. Pap.
M.p.: 326.0–326.2 °C (dec) [HCOOH, 54% aq].
80%). The compound 3a is not described previously in the
literature.
DMSO-d (300 MHz)
M.p.: 233.8–234.9 °C [Ac O].
6
2
1
2.79 (br)
H
N
7
.61 (8.8)
7
.90 (8.8, 2.3)
8
1
8.50 (6.6)
7
6
2
5
H 10.15
Br
8
.25 (2.3)
O
O
1b
1
H-NMR (300 MHz, DMSO-d ) d 12.79 (br d, 1H, J (2,
6
NH) = 6.6 Hz included, –NH–), 10.15 (s, 1H, –CHO), 8.50 (d,
1
H-NMR (300 MHz, CDCl ) d 9.03 (s, 1H, H–C(5)),
.52 (ddd, 1H, J (7, 8) = 8.4 Hz, J (7, 9) = 1.4 Hz, J (7,
1H, J (2, NH) = 6.6 Hz, H–C(2)), 8.25 (d, 1H, Hz, J (5,
7) = 2.3 Hz, H–C(5)), 7.90 (dd, 1H, J (7, 8) = 8.8 Hz, J (5,
7) = 2.3 Hz, H–C(7)), 7.61 (d, 1H, J (7, 8) = 8.8 Hz, H–
3
8
1
0) = 0.6 Hz, H–C(7)), 8.16 (ddd, 1H, J (9, 10) = 8.4 Hz,
J (8, 10) = 1.2 Hz, J (7, 10) = 0.6 Hz, H–C(10)), 8.02 (s,
C(8)).
13
1
H, H–C(4)), 7.86 (ddd, 1H, J (9, 10) = 8.4 Hz, J (8,
) = 7.0 Hz, J (7, 9) = 1.4 Hz, H–C(9)), 7.77 (dm, 2H,
C-NMR (75 MHz, DMSO-d ) d 188.5 (–CHO), 174.9
6
9
(
(
(
C(4)), 143.6 (C(2)), 138.4 (C(7)), 135.8 (C(4b)), 129.2
C(5)), 127.4 (C(4a)), 121.9 (C(3)), 118.2 (C(6)), 116.5
C(8)).
among others J (2 , 3 ) = 8.4 Hz, H–C (2)), 7.72 (ddd,
A
A
A
1H, J (7, 8) = 8.4 Hz, J (8, 9) = 7.0 Hz, J (8,
-
1
1
0) = 1.2 Hz, H–C(8)), 7.53–7.45 (m, 3H, H–C (3–4)).
A
IR (neat, m in cm ): 3199 (w), 3155 (m), 3064 (s), 3027
s), 3027 (s), 2986 (s), 2944 (s), 2905 (s), 2867 (s), 1701
m), 1679 (s, C=O), 1620 (s, –CHO), 1608 (s), 1573 (s),
1
3
C-NMR (75 MHz, CDCl ) d 159.4 (C(2)=O), 155.9
(
(
3
(C(4b)), 149.0 and 148.9 (C(5) and C (4)), 137.6 (C(4)),
A
1
2
34.1 (C (1)), 131.6 (C(3)), 129.5, 129.3 and 128.7,
A
1
551 (m), 1519 (s), 1459 (m), 1411 (m), 1375 (w), 1345
m), 1296 (m), 1264 (w), 1198 (w), 1166 (w), 1131 (w),
071 (w), 989 (w), 962 (w), 868 (w), 825 (m), 786 (m), 747
9 128.6 and 2 9 128.4 (C (2,3) from terminal phenyl,
A
(
ring A), 127.7, 122.0 (C(10)), 117.6 (C(6b)), 111.4 (C(4a)).
-
1
1
IR (neat, m in cm ): 3047 (m), 1718 (s, C=O), 1682
m), 1628 (m), 1598 (w), 1564 (w), 1501 (m), 1445 (m),
(
w), 695 (w), 660 (w), 624 (w).
(
Anal. calcd for C H BrNO (252.06): C, 47.65; H,
2
1
0
6
1
414 (w), 1394 (m), 1289 (w), 1088 (m), 1024 (m), 1010
m), 958 (m), 950 (m), 907 (m), 897 (m), 789 (m), 762 (m),
2
.40; N, 5.56. Found: C, 47.92; H, 2.44; N, 5.87.
(
742 (m), 691 (m), 681 (m), 663 (w), 626 (w).
?
ESI MS: m/z 274.1 [M ? H] .
General procedure B—the synthesis of 2H-
pyrano[3,2-c]quinolin-2-ones 3(a-h, j-q)
Anal. calcd for C H NO (273.29): C, 79.11; H, 4.06;
11
1
8
2
N, 5.13. Found: C, 79.25; H, 4.11; N, 5.07.
A mixture of 100.0 mg (0.58 mmol, 1.00 mol eq) 1,4-di-
hydro-4-oxoquinoline-3-carbaldehyde 1a together with
8
General procedure C—the synthesis of (Z)-3-(4-oxo-
7.0 mg (0.639 mmol, 1.10 mol eq) of phenylacetic acid
1
4
,4-dihydroquinolin-3-yl)-2-phenylacrylic acids
(a,b)
(
(
2a) and 8.00 mg (0.639 mmol, 0.10 mol eq) of K CO3
2
abs) was stirred in 3 mL of freshly distilled Ac O at
2
1
30 °C for 4 h. After cooling the reaction mixture to rt, the
A suspension of 100 mg (0.366 mmol, 1.00 mol eq) 3a in
mL of 1.4 M aq NaOH solution was refluxed within 5 h.
solid product 3a was filtered off, washed with H O
2 9 5 mL), Et O (1 9 5 mL) and dried under vacuum to
2
2
5
(
yield 129 mg (0.46 mmol, 80%) of 3a (Scheme 2). Here
we are showing physico-chemical characteristics for the
compound 3a. The characteristics for all sixteen novel
compounds 3 together with their spectral figures are pub-
lished in the Supporting Information.
After cooling to rt the mixture was extracted with CHCl3
(
3 9 3 mL), water layer separated and treated by 1.0 M aq
solution of HCl to pH 4. A precipitated light yellow solid
material was filtered off, washed with H O, Et O and dried
2
2
by vacuum to afford 98.0 mg (0.336 mmol, 92%) of 4a. By
the same conditions 4b was prepared in 98% yield
3
-Phenyl-2H-pyrano[3,2-c]quinolin-2-one (3a) was pre-
pared following the General procedure B (130 °C/4 h)
yielding a pale yellow crude product 127 mg (0.46 mmol,
(Scheme 3). Physico-chemical characteristics for the
compound 4a are stated below. The compound 4b is
characterized in the Supporting Information.
1
23

Chem. Pap.
Scheme 2 The synthesis of the
pyranoquinolinones 3(a-h, j-q)
J (5, 7) = 1.5 Hz, H–C(7)), 7.56 (dm, 1H, J (7,
8
2
7
) = 8.4 Hz, w1/2 = 2.2 Hz, H–C(8)), 7.46–7.40 (m, 4H,
9 H–C(2 ) and 2 9 H–C(3 )), 7.38 (m H–C(4 )),
A
A
A
.34 (ddm, 1H, J (5, 6) = 8.4 Hz, J (6, 7) = 7.0 Hz,
w1 = 2.2 Hz, H–C(6)), 7.13 (s, 1H, H–C(C(3))=C).
/2
1
3
C-NMR (75 MHz, DMSO-d ): d 175.5 (C(4)), 171.0
6
(–COOH), 139.5, 138.3, 138.0, 133.4, 132.4, 129.0, 128.1,
1
26.6, 125.9, 125.4, 124.6, 124.3, 118.9, 116.5.
-
1
Scheme 3 The hydrolysis of pyranoquinolinones 3 to Z-regioisomers
of quinolinylphenylacrylic acids 4
IR (neat) m/cm : 3816 (w), 3751 (w), 3674 (w), 3215
w), 3046 (w), 3004 (w), 2356 (m), 2335 (w), 2191 (w),
145 (w), 2023 (w), 2006 (w), 1995 (w), 1820 (w), 1676
(
2
(
Z)-3-(4-oxo-1,4-dihydroquinolin-3-yl)-2-phenylacrylic
(s) (C=O), 1629 (s), 1579 (m), 1549 (s), 1492 (s), 1474 (s),
1347 (m), 1307 (m), 1288 (m), 1226 (m), 1203 (s), 1153
acid (4a)
(m), 1112 (m), 1003 (m), 942 (m), 898 (m), 859 (m), 820
The compound 4a was prepared according to the General
procedure C in 92% yield (Scheme 3).
(m), 777 (s), 753 (s), 693 (s), 659 (m), 625 (m).
-
ESI MS: m/z 290.0 [M - H] .
Anal. calcd for C H NO (291.30): C, 74.22; H, 4.50;
18 13 3
The compound 4a is not described previously in the
literature.
N, 4.81. Found: C, 74.55; H, 4.68; N, 5.12.
?
M.p.: [ 244 °C (dec) [H O ].
3
2-Oxo-3-phenyl-2H-pyrano[3,2-c]quinolone 6-oxide (5)
DMSO-d (300 MHz)
6
12.12 (6.5)
To a solution of 100 mg (0.366 mmol, 1.00 mol eq) 3a in
5 mL CHCl , 109 mg (0.476 mmol, 1.40 mol eq, C 77%
7
.56 (8.4, w1/2 2.2)
H
1
N
3
8.17 (6.5)
.13
7
.69 (8.4, 7.0, 1.5) 7 8
.34 (8.4, 7.0, w1/2 2.2 )
2
purity) of MCPBA was added and the mixture stirred at
reflux for 2 h. Then the reaction mixture was diluted with
6
5
7
7
8.17 (m)
a
15 mL of CHCl and washed with sat aq solution of NaHCO
3 3
O
2
A4
a
HOOC
1
(2 9 10 mL). The organic layer was separated, dried over
Na SO , filtered and the solvent removed by vacuum. The
3
13.14 (br)
7.38 (m)
2
4
crude product was purified by FLC [SiO , from CHCl to
2
3
4a
a: 7.46 - 7.40 (4H)
CHCl /MeOH (98/2)] to yield 75.0 mg (0.26 mmol, 71%) of
3
2
-oxo-3-phenyl-2H-pyrano[3,2-c]quinolone 6-oxide (5) as a
yellow solid material (Scheme 4). The compound 5 is not
described previously in the literature.
1
H-NMR (300 MHz, DMSO-d6)
d
13.14 (br s,
1
8
H, –COOH), 12.12 (d, 1H, J (NH, 2) = 6.5 Hz, –NH–),
.17 (d, 1H, J (NH, 2) = 6.5 Hz, H–C(2)), 8.17 (m, 1H, H–
M.p.: [ 246 °C (dec) [MeOH].
C(5)), 7.69 (dd, 1H, J (7, 8) = 8.4 Hz, J (6, 7) = 7.0 Hz,
123

Chem. Pap.
Scheme 4 The MCPBA oxidation of the pyranoquinolinone 3a to the
pyranoquinoline N-oxide 5
Scheme 5 The convenient rearrangement of the pyranoquinoline
N-oxide 5 to the pyranoquinolinedione 6
consumption of the starting material 5 (monitored by TLC)
the mixture was cooled to rt and stirred for additional 1 h.
A precipitated solid material was filtered off, washed with
Ac O, Et O and dried by vacuum to afford 96.0 mg
O-
DMSO-d (300 MHz)
6
8
.61 (8.4, w1/2 2.6)
+
N
8
.94
7
.99 (8.4, 7.1) 8 7
.91 (7.9, 7.1)
2
2
5
9
(0.332 mmol, 87%) of 6 as a light yellow solid material
Scheme 5). The compound 6 is registered in the SciFinder
7
10
8.28
(
4
3
8.39 (7.9, w1/2 2.6)
a
O1
database under CAS (98986-64-2), but no characterization
and no synthesis are available.
2
7.75 (8.5, m)
a
1
3
A4
M.p.: [ 390 °C (dec) [Ac O].
O
2
a: 7.53 - 7.46 (3H)
1
H-NMR (300 MHz, DMSO-d ): d 8.94 (s, 1H, H–
6
C(5)), 8.61 (dm, 1H, J (7, 8) = 8.4 Hz, w1/2 = 2.6 Hz, H–
C(7)), 8.39 (dm, 1H, J (9, 10) = 7.9 Hz, w1/2 = 2.6 Hz,
H–C(10)), 8.28 (s, 1H, H–C(4)), 7.99 (dd, 1H, J (7,
8
) = 8.4 Hz, J (8, 9) = 7.1 Hz, H–C(8)), 7.91 (dd, 1H,
J (9, 10) = 7.9 Hz, J (8, 9) = 7.1 Hz, H–C(8)), 7.75 (dm,
2
7
2
H, among others J (2 , 3 ) = 8.5 Hz, 2 9 H–C (3)),
A A A
.53–7.46 (m, 3H, among others J (2 , 3 ) = 8.5 Hz,
A
A
9 H–C (2), H–C (4)).
A
A
13
1
C-NMR (75 MHz, CDCl ): d 159.1 (C(2)(=O)), 146.6
H-NMR (600 MHz, DMSO-d ): d 12.13 (s, 1H, –NH–),
6
3
(
C(4b)), 141.5 (C(6a)), 137.6 C(5)), 134.5 (C(4)), 133.2,
8.12 (s, 1H, H–C(4)), 8.39 (dm, 1H, J (9, 10) = 8.4 Hz, w1/
= 2.2 Hz, H–C(10)), 8.0 (dd, 1H, J (7, 8) = 8.4 Hz, J (7,
2
1
1
32.7, 130.5, 129.6, 129.0, 128.91, 128.90, 122.9, 120.3,
19.4, 112.9 (C(7)).
1
9) = 1.2 Hz, H–C(7)), 7.91 (ddd, 1H, J (9, 10) = 8.3 Hz,
J (8, 9) = 7.3 Hz, J (7, 9) = 1.2 Hz, H–C(9)), 7.74 (dm,
-
IR (neat) m/cm : 3039 (w), 2917 (w), 1719 (s, C=O),
615 (w), 1579 (w), 1515 (w), 1468 (w), 1445 (m), 1398
1
2H, J (2
J (7, 8) = 8.4 Hz, J (8, 9) = 7.3 Hz, J (8, 10) = 1.5 Hz,
H–C(8)), 7.47 (dm, 2H, J (2 , 3 ) = 8.5 Hz, 2 9 H–
(2)), 7.42 (m, 1H, H–C (4)).
C-NMR (150 MHz, DMSO-d
A A A
, 3 ) = 8,5 Hz, 2 9 H–C (3)), 7.66 (ddd, 1H,
(
(
(
(
s), 1334 (m), 1268 (w), 1219 (s, N–O), 1189 (m), 1161
m), 1146 (m), 1079 (m), 1041 (s), 1013 (m), 954 (w), 890
s), 782 (s), 769 (s), 721 (s), 709 (s), 692 (s), 674 (s), 656
s).
A
A
C
A
1
A
3
): d 159.7, 159.4, 158.6,
6
?
ESI MS: m/z 290.0 [M ? H] .
139.3, 137.0, 134.6, 133.4, 129.2, 128.9, 128.7, 126.0,
Anal. calcd for C H NO (289.28): C, 74.73; H, 3.83;
1
123.4, 122.9, 116.5, 112.2, 109.0.
8
11
3
-1
N, 4.84 Found: C, 74.97; H, 4.12; N, 5.06.
IR (neat) m/cm : 3329 (w) (–NH–), 3017 (w), 2964 (w),
816 (m), 2344 (w), 2113 (w), 1900 (w), 1730 (s) (C=O), 1660
2
3
-Phenyl-2H-pyrano[3,2-c]quinoline-2,5(6H)-dione (6)
(s) (C=O), 1558 (s), 1502 (s), 1440 (s), 1408 (s), 1294 (m),
258 (m), 1080 (m), 1010 (m), 890 (s), 760 (s), 750 (s), 690 (s).
Anal. calcd for C18 (289.28): C, 74.73; H, 3.83;
N, 4.84 Found: C, 75.01; H, 4.19; N, 5.12.
1
A solution of 100 mg (0.380 mmol, 1.00 mol eq) 5 was
dissolved in 8 mL of Ac O and refluxed within 4 h. After
H11NO
3
2
1
23

Chem. Pap.
Results and discussion
unsubstituted compound 3a (uF = 0.63) compare to the
other derivatives 3b (\ 0.01) and 3f (0.04) in MeOH (for
more details see the Supporting Information).
A simple synthesis of 1,4-dihydro-4-oxoquinoline-3-car-
baldehydes 1(a,b) was performed. The synthesis of a
brominated analogue 1b is not described previously in the
literature (Scheme 1).
Conclusion
The sixteen novel pyrano[3,2-c]quinolin-2-ones 3(a–h,
j–q) were prepared by heating of appropriate quino-
linecarbaldehyde 1 with an appropriate acetic acid
derivative 2 in Ac O by catalysis of K CO (abs) at
Here we described the convenient synthesis of
2H-pyrano[3,2-c]quinolin-2-ones 3 starting from easily
available quinolinecarbaldehydes 1 and monosubstituted
acetic acids 2 (-aryl, -arylthio and -heteroaryl). Sixteen
novel compounds 3 were prepared by the above metho-
dology to confirm its general exploitation. Some examples
of chemistry transformations of 3 yielding the novel hete-
rocyclic compounds 4–6 were performed in good yields
(71–98%). The compounds 4–6 are not described previ-
ously in the literature and the synthesis of compounds 6
from 3 is novel as well. All together 24 compounds were
prepared and well physico-chemical characterized in the
Supporting Information. Additionally we observed that
some of the pyranoquinolinones 3 possess intensive blue
fluorescence properties. The presented synthesis of pyra-
noquinolinones 3 and their transformations to the com-
pounds 4–6 can accelerate further physical and biological
studies of these heterocyclic compounds.
2
2
3
100–140 °C within 3–6 h. The pyranoquinolinones 3 were
easily isolated from their mixtures as they precipitated
within the reaction in a good yield and purity (Scheme 2).
4-(2-Oxo-2H-pyrano[3,2-c]quinolin-3-yl)benzoic acid (3i)
was prepared in 97% yield by hydrolysis of 3h in refluxing
1
.4 M aq solution of NaOH within 5 h.
In the all performed cyclocondensations (Scheme 2)
Ac O was used as a reactant and as a solvent. In each case
2
the free AcOH was formed as a side product and could
compete with 2 in a reaction with quinolinecarbaldehyde 1
1
2
to give an unsubstituted side product 3x (R =R : H).
However, the compound 3x was never observed in any of
our products 3(a–h, j–q). Moreover, we performed a
reaction between 1a and acetic acid instead of 2 by the
same reaction conditions. In this case no product 3x was
formed even by heating of the mixture at 140 °C overnight.
To support the chemistry exploitation of 2H-pyrano[3,2-
c]quinolin-2-ones 3, hydrolysis of two derivatives 3(a,h)
was performed to yield oxoquinolinylphenylacrylic acids
Acknowledgements This research was supported by the Comenius
University in Bratislava UK/416/2015, theBiomagi, Ltd., VEGA
1
/0634/13 and ITMS 26240220007.
4
(a,b) in excellent 92–98% yields (Scheme 3). Z-geometry
of both products 4(a,b) was proved by NOESY-1D NMR
experiments that confirmed an interaction between H–C(3)
from an acrylic acid with both hydrogens: H–C(2) from a
quinolin-4(1H)-one part and an ortho hydrogen from a
phenyl substituent joint to the acrylic acid.
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23