Synthesis, photooxygenation, and characterization of new angular furoquinolinone derivatives, a new furocoumarin bioisoster

Article abstract of DOI:10.1002/jccs.202000455

Synthesis of angular furoquinolinone derivatives with a new skeleton structure was accomplished via Williamson reaction of hydroxyquinolinones with α-haloketones, such as 3-chloro-2-butanone and phenacyl bromide, followed by treatment with polyphosphoric

Full text of DOI:10.1002/jccs.202000455

Received: 13 October 2020
DOI: 10.1002/jccs.202000455
Revised: 2 January 2021
Accepted: 4 January 2021
O R I G I N A L A R T I C L E
Synthesis, photooxygenation, and characterization of new
angular furoquinolinone derivatives, a new furocoumarin
bioisoster
Sameh Elgogary1,2
| Hoda Abd Elghafar2 | Mohammad Mashaly2
1Chemistry Department, Faculty of
Abstract
Science, Jazan University, Jazan, Saudi
Arabia
Synthesis of angular furoquinolinone derivatives with a new skeleton structure
was accomplished via Williamson reaction of hydroxyquinolinones with
α-haloketones, such as 3-chloro-2-butanone and phenacyl bromide, followed
by treatment with polyphosphoric acid (PPA). The synthesized angular
furoquinolinones were photooxygenated in chloroform or dimethyl formamide
and in the presence of tetraphenylporphyrin (TPP) as a singlet oxygen sensi-
tizer (1O2). The photooxygenation reactions furnished the photocleaved prod-
uct through the [2 + 2] cycloaddition reaction. All photoproducts were
isolated and fully characterized by spectral analyses.
2Chemistry Department, Faculty of
Science, Damietta University, New
Damietta, Egypt
Correspondence
Sameh Elgogary, Chemistry Department,
Faculty of Science, Jazan University,
Jazan 2079, Saudi Arabia.
Email: selgogary@gmail.com
K E Y W O R D S
DNA and Williamson reaction, furocoumarins, furoquinolinones, photooxygenation, psoralen
1 | INTRODUCTION
induce ISC with DNA because of their geometry.17,18
Angelicin
bioisosters,
namely,
furoquinolinones,
Linear furocoumarins are also known as psoralens and
are commonly used in PUVA therapy (psoralen plus
UVA radiation) for the care of many human skins.1–3
The efficacy and potency of these photochemotherapeutic
agents depend on their ability to photobind with DNA.
Although PUVA therapy confirms that it is successful,
some undesirable side effects are existing, such as persis-
tent erythema4 genotoxicity,5 phototoxicity, and a possi-
ble risk of skin cancer.6 These adverse side effects are
primarily due to psoralen inter-strand crosslinks (ISC)
with DNA rather than by monofunctional adducts,7 as a
result of their bifunctional character (photoactive
α-pyrone and furan sites).
1,4,6,8-tetramethylfuro[2,3-h]quinolin-2(1H)-one
(FQ),14,19–21 with replacement of the pyrone oxygen atom
by nitrogen, have the inability to induce ISC with DNA
and are characterized by highly strong antiproliferative
activity (Figure 1). Moreover, FQ showed evident skin
phototoxicity and marked genotoxicity.20,22
Continuing our interest in synthesizing new biologically
important furocoumarin derivatives,23–25 our approach in
this work has been directed toward synthesizing new angu-
lar furoquinolinones as bioisosters of furocoumarin and
studying the mechanism of photooxygenation.
A wide range of structurally modified psoralens have
been attempted to obtain furocoumarins that are primar-
ily monofunctional to reduce the side effects and to
improve the photobinding properties.8–16 One of the most
powerful ways to achieve this is using angular fur-
ocoumarins such as angelicins, which are unable to
2 | RESULTS AND DISCUSSION
Hydroxyquinolinones 1–3 were synthesized according to
the literature procedure by condensing ethyl acetoacetate
with m-aminophenol,26 o-anisidine,27 and p-anisidine,28
respectively, while 4-hydroxyquinolinone 4 was formed
J Chin Chem Soc. 2021;1–8.
http://www.jccs.wiley-vch.de
© 2021 The Chemical Society Located in Taipei & Wiley-VCH GmbH
1

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ELGOGARY ET AL.
1
by condensing N-methylaniline with diethyl malonate.29
Williamson reaction of 1–4 with 3-chloro-2-butanone in
acetone and in the presence of K2CO3 at reflux tempera-
ture gave keto ethers 5, 9, 12, and 13 in 60, 42, 60, and
54% yield, respectively (Scheme 1).
to carbonyl group at 1,724.05 cm−1. The H NMR of this
compound revealed that new signals corresponding to
aliphatic protons resonate at δ 4.95 (1H, q, J = 6.3 Hz),
2.20 (3H, s) and 1.51 (3H, d, J = 6.3 Hz) for 10-H, 30-H,
and 40-H, respectively.
The structure of keto ether 5, for example, was con-
firmed by the appearance of new absorption band related
Cyclization of compounds 5, 9, 11, and 13 were
accomplished by treatment with polyphosphoric acid
(PPA)
affording
the
corresponding
angular
furoquinolinone derivatives 6, 10, 12, and 14,
respectively(Scheme 1). The structures of angular
furoquinolinone derivatives 6, 10, and 12 were proven
and verified for the reaction products based on their ele-
mental and spectral (IR, 1H-NMR, and MS) analyses
(cf. Experimental). The presence of ortho coupling of the
two aromatic protons as doublet (H-5 and H-6, in 6 and
10 with coupling constant 8.4 Hz, and H-7 and H-8, in 12
FIGURE 1 Structure of psoralen, angelicin and angelicin
bioisosters (FQ)
1
with coupling constant 8.7 Hz) in H-NMR spectra of
SCHEME 1 Synthesis of
angular furoquinolinone
derivatives

ELGOGARY ET AL.
3
these compounds indicating the exclusive cyclization to
the angular furoquinolinone skeleton. Moreover, the
structure of 14 was verified by spectral and elemental
analyses (cf. Experimental). 1H-NMR spectrum of 14
exhibited three singlet signals at δ 3.78, 2.41, and
2.35 ppm assigned to three methyl moieties (each signal
integrating for three protons), while 13C-NMR spectrum
of 14 showed three signals of these methyl groups at δ
28.96, 11.54, and 8.9 ppm. Finally, mass spectrum of com-
pound 14 detected the molecular ion M+ as the base peak
at m/z 227 (100%).
conditions, the dioxetane (B) was easily photolyzed to
give 19 through broken O-O and C-C bonds, (Scheme 2).
The photocleaved product 19 was separated and fully
distinguished by IR, 1H-NMR, and mass spectroscopy
(cf. Experimental). IR spectrum of 19 showed two new
bands at 1,758.76 and 1,690 cm−1 for two new carbonyl
function indicating the photooxidation of furan moiety
double bond.
Further elucidation of the photoproduct 19 was
acquired through acid hydrolysis to afford 8-Acetyl-
7-hydroxy-4-methyl-2H-quinolin-2-one (21). Also, the
hydrolyzed product 21 was acquired through Fries
rearrangement of 22 which was prepared by acetylation
of 6,[15] (Scheme 2). Similarly, under the conditions of
photooxygenation (DMF/TPP/1O2) the photooxygenation
reaction of furoquinolinone derivative 8 gave the photo-
cleaved product 8-benzoyl-7-hydroxy-4-methylquinoline
−2(1H)-one (23) through the photooxidation of furan
moiety double bond (Scheme 3).
Similarly, hydroxquinolinone derivatives 1 and 4 reacted
with phenacyl bromide affording the keto ether 7 and 15,
respectively. Cyclization of 7 and 15 by using PPA provided
the corresponding 4-methyl-9-phenylfuro[2,3-h]quinolin-2
(1H)-one (8) and 5-methyl-3-phenylfuro [3, 2-c] quinolin-4
(5H)-one (16), respectively (Scheme 1). The structures of 7,
1
8, 15, and 16 were elucidated through the spectral (IR, H-
NMR, and MS) analyses (cf. Experimental).
The photooxygenation of the angular furoquinolinone
derivative 6 in DMF at room temperature and in the pres-
ence of singlet oxygen sensitizer such as tetraphenylporphine
(TPP) furnished 8-acetyl-4-methyl-2-oxo-1, 2-dihydroquinolin
−7-yl acetate (19) while the allylic hydroperoxide 20 did not
obtain, (Scheme 2).
The mechanism of the photoproduct 19 formation
was accomplished by the formation of dioxetane (B) via
[2 + 2] cycloaddition of the furan moiety double bond
with singlet oxygen. Under the photooxygenation
The structure of 23 was proven as the reaction prod-
uct by the spectral analyses (cf. Experimental). IR spec-
trum of 23 showed characteristic broad stretching bands
at 3,579.23 and 3,328.53 cm−1 for the OH and NH group,
respectively. Also, 1H-NMR spectrum of 23 displayed
strongly downfield signals at δ 12.85 and 11.83 ppm that
can be exchanged with D2O assigned to OH and NH pro-
tons, respectively. The molecular ion M+ of compound 23
was observed at m/z 279 (100%) as the base peak in mass
spectrum.
Photooxygenation reaction of 14 in chloroform
yielded the photocleaved product 3-acetyl-1-methyl-
2-oxo-1,2-dihydroquinolin-4-yl acetate (24). The structure
of 24 was established by elemental and spectral analyses
(cf. Experimental) and further confirmed via acid hydro-
lysis to afford 3-Acetyl-4-hydroxy-1-methyl quinolin-2
(1H)-one (25), which was obtained by acetylation of
4,30,31 (Scheme 4).
SCHEME 2 Photooxygenation of 6
SCHEME 3 Photooxygenation of 8

4
ELGOGARY ET AL.
impact (EI) mass spectra. Finally, PERKIN-ELMER
2400 C, H Elemental Analyzer was used to perform the
Elemental analyses.
3.1 | 4-methyl-7-(3-oxobutan-2-yloxy)-2H-
quinolin-2-one (5)
Hydroxquinolinone 1 (2 g, 11.4 mmol) was dissolved in
dry acetone (70 ml) then anhydrous potassium carbonate
(1.0 M equiv) and 3-chloro-2-butanone (1.2 g, 11.3 mmol)
were added and refluxed for 24 hr. The undissolved salt
was filtered off and the solvent was reduced to its half
under reduced pressure and added to ice/water (200 ml).
The resulting solid ppt. was filtered off, washed with
water, and recrystallized from ethanol to provide white
crystals of 5. Yield 1.2 g (60%) m.p.162–164ꢀC. IR (KBr
cm−1): 3,328.53 (NH), 2,973.74 (=CH), 2,915.84 (–CH),
SCHEME 4 Photooxygenation of 14
1
1,724.05 (CO), 1,670.05 (CO) and 1,620 (C=C). H NMR
(300 MHz, DMSO-d6): δ 11.70 (1H, s, NH), 7.61 (1H, s),
7.32 (1H, d, J = 8.4 Hz), 6.90 (1H, d, J = 8.4 Hz), 6.45
(1H, s), 4.95 (1H, q, J = 6.3 Hz), 2.52 (3H, s), 2.20 (3H, s)
and 1.51 (3H, d, J = 6.3 Hz). MS (m/z, %): 245 (M+,
53.64), 217 (M+-CO, 0.48), 203 (M+-C2H2O, 14.09),
202 (M+-C2H3O, 100), 188 (M+ -C3H5O, 2.056), 174
(M+ -C4H7O, 11.25) and 158.05 (M+ -C4H7O2, 5.90).
3.2 | 4,8,9-trimethylfuro[2,3-h]quinolin-2
(1H)-one (6)
SCHEME 5 Photooxygenation of 16
Compound 5 (1 g, 4.081 mmol) and polyphosphoric acid
(PPA) (5 g) were warmed up to 80ꢀC for 4 hr. The reac-
tion mixture was left to cool and was added to a large
amount of ice/water. The resulting precipitate was fil-
tered and purified by recrystallized from ethanol to give
6. Yield 0.4 g (43%), white crystals, m.p. 230ꢀC. IR (KBr
cm−1): 3,305.39 (NH), 3,135.69 (=CH), 2,989.12 (–CH),
1,662.34 (CO) and 1,560 (C=C). 1H NMR (300 MHz,
DMSO-d6): δ 11.67(1H, s, NH), 7.56 (1H, d, J = 8.4 Hz),
7.16 (1H, d, J = 8.4 Hz), 6.36 (1H, s), 2.67 (3H, s), 2.39
(3H, s), and 2.13 (3H, s). MS (m/z, %): 227 (M+, 100), 212
(M+–CH3, 20.87), 198.80 (M+ -CO, 8.20), 198 (M+ –CHO,
17.66), 171 (M+ –C3H4O, 5.95) and 170 (M+ –C3H5O,
29.07). Anal.Calcd for C14H13NO2 (227): C, 73.99, H,
5.77, N, 6.16. Found: C, 74.11, H, 5.91, N, 5.83.
Similarly, the photooxygenation reaction of furoquinolinone
derivative 16 furnished 3-benzoyl-4-hydroxy-1-methylquinolin-2
(1H)-one (26) as photocleaved product. Structure of
compound 26 was unambiguously confirmed by benzo-
ylation of compound 4 to supply compound 27 followed
by Fries rearrangement at 155ꢀC to produce 26,32
(Scheme 5).
3 | EXPERIMENTAL
Gallenkamp melting point apparatus was used for testing
the melting points (open capillary tubes) and all melting
1
points were uncorrected. For H NMR spectra, Varian
Mercury-VX-300 (300 MHz) and a BRUKER (600 MHz)
ultra-shield Avance III spectrometers, were used by using
(TMS) as an internal stander and DMSO or CDCl3 as sol-
vents. Chemical shifts were denoted as δ ppm. IR spectra
were enrolled on a Jasco 4,100 FTIR spectrophotometer
(KBr pellet). Also, Shimadzu GCMS-QP 1000 EX mass
spectrometer at 70 eV was used to record the electron
3.3 | 4-methyl-7-(2-oxo-2-phenylethoxy)
quinolin-2(1H)-one (7)
Compound 7 was synthesized from hydroxquinolinone
1 (1 g, 5.7 mmol) and phenacyl bromide (1.14 g,

ELGOGARY ET AL.
5
5.7 mmol) using the method given for 5. Yield 0.8 g
(47.9%), white crystals (ethanol), m.p. 182ꢀC. IR (KBr
cm−1): 3,328.53 (NH), 3,062.41 (=CH), 2,962.13 (–CH),
1,697.05 (CO), 1,635.34 (CO) and 1,550.49 (C=C). 1H
NMR (300 MHz, DMSO-d6): δ 11.32 (1H, s, NH), 8.01
(2H, d, J = 8.7 Hz), 7.71 (1H, s), 7.56 (3H, m), 6.86 (1H, d,
J = 8.7 Hz), 6.77 (1H, d, J = 8.7 Hz), 6.20 (1H, s), 5.62
(2H, s) and 2.34 (3H, s). MS (m/z, %): 293 (M+, 25.72),
278 (M+-CH3, 0.08), 265 (M+-CO, 0.16), 188 (M+-C7H5O,
0.58), 174 (M+-C8H7O, 0.03), 158 (M+-C8H7O2, 1.22), 130
(M+-C9H7O3, 6.78), 106 (M+-C12H11O2, 8.3) and 105 (M+-
C12H12O2, 98.79). Anal.Calcd for C18H15NO3 (293): C,
73.72, H, 5.11, N, 4.77. Found: C, 74.14, H, 5.65, N, 4.24.
s, NH), 7.17 (1H, d, J = 8.4 Hz), 7.10 (1H, d, J = 8.4 Hz),
6.43 (1H, s), 2.49 (3H, s), 1.82 (3H, s), and 1.25 (3H, s).
13C NMR (75 MHz, CDCl3) ppm: 162.6, 151.19, 150.4,
149.0, 131.6, 125.4, 122.1, 120.5, 116.9, 110.2, 108.8, 17.4,
10.7 and 7.8. MS (m/z, %): 227 (M+, 100), 213 (M+-CH2,
7.86), 212 (M+-CH3, 23) 199.05 (M+ -CO, 8.53) 198.05
(M+ –C2H5, 18.85), 184.05 (M+ –C2H3O, 12.36) and 170
(M+ –C3H5O, 4.21).
3.7 | 4-methyl-6-(3-oxobutan-2-yloxy)
quinolin-2(1H)-one (11)
Compound 11 was prepared from 3 (2 g, 11.4 mmol) and
3-chloro-2-butanone (1.2 g, 11.3 mmol) by the framework
indicated for 5. Yield 1.2 g (60%), gray powder (ethanol),
m.p. 154ꢀC. IR (KBr cm−1): 3,328.53 (NH), 2,973.74
(=CH), 2,915.84 (–CH), 1,724 (CO), 1,670.05 (CO) and
1,620 (C=C). 1H NMR (300 MHz, DMSO-d6): δ 11.70
(1H, s, NH), 7.61 (1H, s), 7.32 (1H, d, J = 8.7 Hz), 6.90
(1H, d, J = 8.7 Hz), 6.45 (1H, s), 4.95 (1H, q, J = 6.6 Hz),
2.52 (3H, s), 2.20 (3H, s) and 1.51 (3H, d, J = 6.6 Hz). MS
(m/z, %): 245 (M+, 53.64), 203 (M+-C2H2O, 14.09), 202
(M+-C2H3O, 100), 188 (M+ -C3H5O, 2.56), 174.05 (M+-
C4H7O, 11.25) and 158.05 (M+-C4H7O2, 5.90).
3.4 | 4-methyl-9-phenylfuro[2,3-h]
quinolin-2(1H)-one (8)
Compound 8 was obtained from 4-methyl-7-(2-oxo-
2-phenylethoxy) quinolin-2(1H)-one 7 (1.0 g, 3.4 mmol)
by the technique indicated for 6. Yield 0.6 g (64%), white
crystals (ethanol), m.p.193–195ꢀC. IR (KBr cm−1):
3,328.53 (NH), 3,062.41 (=CH), 2,962.13 (–CH), 1,635.34
1
(CO) and 1,550.49 (C=C). H NMR (300 MHz, DMSO-
d6): δ 8.79 (1H, s), 8.74 (1H, d, J = 8.1 Hz), 8.24 (1H, d,
J = 8.1 Hz), 8.08 (1H, s), 7.67–7.52 (5H, m), 6.51 (1H, s)
and 2.85 (3H, s) MS (m/z, %): 275 (M+, 28.83), 247(M+-
CO, 2.44), 246 (M+-CHO, 5.84), 199.1 (M+-C6H6, 1.57)
and 169.05(M+-C7H6O, 1.59).
3.8 | 1,2,9-trimethylfuro[3,2-f]quinolin-7
(6H)-one (12)
Compound 12 was prepared from 11 (1.0 g, 4.08 mmol) by
the framework provided for 6. Yield 0.6 g (55%), white crys-
tals (ethanol), m.p. 270ꢀC. IR (KBr cm−1): 3,316.96 (NH),
3,116.4 (=CH), 2,969.84 (–CH), 1,654.62 (CO) and 1,600
(C=C). 1H NMR (600 MHz, DMSO-d6): δ 11.63 (1H, s, NH),
7.64 (1H, d, J = 8.7 Hz), 7.22 (1H, d, J = 8.7 Hz), 6.40 (1H,
s), 2.67 (3H, s), 2.42 (3H, s) and 2.36 (3H, s). 13C NMR (150
MHz, DMSO-d6) ppm: 161.1, 155.0, 153.1, 152.3, 151.8,
126.4, 116.2, 115.7, 114.7, 115.0, 111.2, 23.5, 13.1, and 11.7.
MS (m/z, %): 227 (M+, 100), 212 (M+-CH3, 12.25), 199 (M+
-CO, 15.36), 198 (M+ -C2H5, 37.25), 185 (M+ -C2H2O, 7.35),
184 (M+ -C2H3O, 22.97) and 170 (M+ -C3H5O, 53.91.
3.5 | 4-methyl-8-(3-oxobutan-2-yloxy)
quinolin-2(1H)-one (9)
Compound 9 was prepared from 2 (1 g, 5.7 mmol) and
3-chloro-2-butanone (0.61 g, 5.7 mmol) by the framework
given for 5. Yield 0.6 g (42%), brown crystals (ethanol),
m.p. 95ꢀC. IR (KBr cm−1): 3,313.11 (NH), 3,046.98
(=CH), 2,985.27 (–CH), 1,650 (CO) and 1,581.34 (C=C).
1H NMR (300 MHz, CDCl3): δ 8.19 (1H, s, NH), 7.33 (1H, d,
J = 7.8 Hz), 7.26 (1H, t, J = 7.8 Hz), 7.12 (1H, d,
J = 7.8 Hz), 6.52 (1H, s), 4.14 (1H, q, J = 6.6 Hz), 2.47
(3H, s), 1.73 (3H, s) and 1.53 (3H, d, J = 6.6 Hz).
3.9 | 1-methyl-4-(3-oxobutan-2-yloxy)
quinolin-2(1H)-one (13)
3.6 | 2,3,6-trimethylfuro[3,2-h]quinolin-8
(9H)-one (10)
Compound 13 was prepared from 4 (2 g, 11.4 mmol) and
3-chloro-2-butanone (0.61 g, 5.7 mmol) using the method
provided for 5. Yield 1.5 g (54%), yellow crystals (etha-
nol), m.p.120ꢀC. IR (KBr cm−1): 3,031.55 (=CH), 2,992.98
(–CH), 1,712.48 (CO), 1,639.2 (CO) and 1,589.06 (C=C).
1H NMR (300 MHz, CDCl3): δ 8.06 (1H, d, J = 8.7 Hz),
Compound 10 was prepared from 9 (1.0 g, 4.08 mmol)
using the method provided for 6. Yield 0.6 g (55%), brown
powder (ethanol), m.p.200–202ꢀC. IR (KBr cm−1): 3,421
(NH), 3,070.12 (=CH), 2,927.41 (–CH), 1,650.77(CO) and
1
1,589.06 (C=C). H NMR (300 MHz, CDCl3): δ 8.20 (1H,

6
ELGOGARY ET AL.
7.62 (1H, t, J = 8.7 Hz), 7. 36 (1H, d, J = 8.7 Hz), 7.26
(1H, t, J = 8.7 Hz), 5.94 (1H, s), 4.81 (1H, q, J = 6.6 Hz),
3.67 (3H, s), 2.25 (3H, s) and 1.64 (3H, d, J = 6.6 Hz). MS
(m/z, %): 245 (M+, 100), 202 (M+ -C2H3O, 75.38), 188
(M+ -C3H5O, 11.45), 175 (M+-C4H6O, 7.44), 174 (M+-
C4H7O, 25.85), 158.05 (M+-C4H7O2, 17.83), 133.1 (M+-
C6H8O2, 2.47) and 105.05 (M+-C7H8O3, 4.70).
yellow powder (ethanol), m.p. 245–247ꢀC.IR (KBr cm−1):
306 2.41 (=CH), 2,958.27 (–CH), 1,654.62 (CO), 1,592.91
(C=C) and 1,207.22 (C-N).1H NMR (300 MHz, CDCl3):
δ 8.15 (1H, d, J = 8.1 Hz), 7.79 (1H, d, J = 8.1 Hz), 7.74 (1H,
s), 7.46–7.38 (5H, m), 7.35 (1H, t, J = 8.1 Hz), 7.34 (1H, t,
J = 8.1 Hz) and 3.79 (3H, s). 13C NMR (75 MHz, CDCl3)
ppm: 162.2, 159.84, 148.35, 139.65, 137.77, 136.47, 128.17,
129.9, 129.54 (2C), 128.8, 127.59 (2C), 124.19, 115.83, 115.24,
112.37 and 29.12. MS (m/z, %): 275 (M+, 13.59), 274 (M+-H,
4.26), 247 (M+-CO, 0.66) 197(M+-C6H6, 0.23), 170 (M+-
PhCO, 0.37) and 169.1 (M+-C7H6O, 0.37).
3.10 | 2, 3, 5-trimethylfuro [3, 2-c]
quinolin-4(5H)-one (14)
Compound 14 was prepared from 13 (1.0 g, 4.08 mmol) by
the framework applied for 6. Yield 0.6 g (64%), yellow crys-
tals (ethanol), m.p. 135ꢀC. IR (KBr cm−1): 3,050.83 (=CH),
2,915.84 (–CH), 1,658.48 (CO), 1,627.63 (C=C) and 1,230.36
(C-N). 1H NMR (300 MHz, CDCl3): δ 7.94 (1H, d,
J = 8.7 Hz), 7.53 (1H, t, J = 8.7 Hz), 7.41 (1H, d,
J = 8.7 Hz), 7.26 (1H, t, J = 8.7 Hz), 3.78 (3H, s), 2.41 (3H,
s) and 2.35 (3H, s). 13C NMR (75 MHz, CDCl3) ppm:
160.35, 153.3, 149.8, 137.6, 128.6, 122.06, 120.7, 115.6,
114.87, 114.05, 113.29, 28.96, 11.54 and 8.9. MS (m/z, %):
227 (M+, 100), 211.90 (M+ -CH3, 21.35), 199 (M+ -CO,
13.02), 197.95 (M+-C2H5, 13.90) and 184 (M+-C2H3O,
16.40). Anal.Calcd for C14H13NO2 (227): C, 73.99, H,
5.77, N, 6.16. Found: C, 73.14, H, 5.13, N, 6.16.
3.13 | General procedure of the
photooxygenation of furoquinolinone
A solution of the synthesized furoquinolinone (1 g) and
(2 mg) of TPP in DMF (30 mL) was irradiated by sodium
lamp at room temperature. A constant stream of dry oxygen
(g) was allowed to pass via the reaction mixture at a slow
rate to prevent the loss of solvent within the irradiation.
The irradiated solution was observed by TLC for the
vanishing of reactants and the solvent was evaporated at
20ꢀC/15 Torr. The isolated photo-products were purified
using column chromatography on silica gel by eluting with
a 30% mixture of petroleum ether 40–60 and ethyl acetate.
3.11 | 1-methyl-4-(2-oxo-2-phenylethoxy)
quinolin-2(1H)-one (15)
3.14 | Photooxygenation of 6
The irradiation of 6 (1 g, 4.4 mmol) with the general pro-
cedure of the photooxygenation, afforded 8-acetyl-
4-methyl-2-oxo-1, 2-dihydroquinolin −7-yl acetate (19) as
photoproduct. Yield 0.6 g (63%), brown crystal, m.
p. 184ꢀC. IR (KBr cm−1): 3,328.53 (NH), 3,077.83 (=CH),
2,992.98 (–CH), 1,758.76 (CO), 1,690(CO), 1,666.2 (CO)
Compound 15 was prepared from 4 (1 g, 5.7 mmol) and
phenacyl bromide (1.14 g, 5.7 mmol) by the framework
applied for 5. Yield 0.8 g (47.9%), white crystals (ethanol), m.
p. 210ꢀC. IR (KBr cm−1): 3,062.41 (=CH), 2,958.27 (–CH),
1,697.05 (CO), 1,650.77 (CO), 1,589.06 (C=C) and 1,234.22
(C–N). 1H NMR (300 MHz, CDCl3): δ 8.14 (1H, d,
J = 8.7 Hz), 7.98 (2H, d, J = 8.7 Hz), 7.64 (1H, t, J = 8.7 Hz),
7.61 (2H, t, J = 8.7 Hz), 7.52 (1H, t, J = 8.7 Hz), 7.35 (1H, d,
J = 8.7 Hz), 7.24 (1H, t, J = 8.7 Hz), 5.95 (1H, s), 5.44 (2H, s)
and 3.65 (3H, s). 13C NMR (75 MHz, CDCl3) ppm: 191.87,
163.45, 161.05, 139.8, 134.27, 134.09, 131.53, 129.03, 127.93,
123.69, 121.92, 116.15, 114.07, 97.58, 70.14 and 29.14. MS
(m/z, %): 293 (M+, 93.64), 278 (M+-CH3, 0.21), 265 (M+-CO,
0.61), 216 (M+-C6H5, 0.16), 188 (M+-C7H5O, 12.09), 174
(M+-C8H7O, 6.19) and 158 (M+-C8H7O2, 5.93).
1
and 1,608.34 (C=C). H NMR (300 MHz, DMSO-d6): δ
11.99 (1H, s, NH), 8.05 (1H, d, J = 8.4 Hz), 7.27 (1H, d,
J = 8.4 Hz), 6.44 (1H, s), 2.62 (3H, s), 2.47 (3H, s) and
2.34 (3H, s). MS (m/z, %): 259 (M+, 9.54), 217 (M+-
C2H2O, 73.91), 216 (M+-CH3CO, 1.15), 203 (M+-C3H4O,
12.2), 202 (M+ -C3H5O, 100), 189 (M+ -C3H2O2, 1.99),
174.05 (M+ -C4H5O2, 4.93) and 146 (M+ -C5H5O3, 6.87).
3.15 | 8- Acetyl-7-hydroxy- 4- methyl- 2H-
quinolin-2-one (21) (acid hydrolysis of 19)
3.12 | 5-methyl-3-phenylfuro [3, 2-c]
quinolin-4(5H)-one (16)
A solution of 19 (0.5 g, 1.93 mmol) in hydrochloric acid
(20 ml) was refluxed for 30 min., cool in air to obtain a
solid product, filtered off, and recrystallized from ethanol
to afford 8-Acetyl-7-hydroxy-4-methyl-2H-quinolin-2-one
(21). Yield 0.3 g (71.6%), m.p.259ꢀC (lit.[15] 259–262ꢀC).
Compound 16 was prepared from 15 (1.0 g, 3.4 mmol)
according to the method given for 6. Yield 0.6 g (64%),

ELGOGARY ET AL.
7
3.16 | Photooxygenation of 8
Yield 0.6 g (59%), brown powder (ethanol), m.p. 174–176ꢀC
(lit.32 174–176ꢀC).
The irradiation of 8 (0.5 g, 1.82 mmol) with the same
general procedure of the photooxygenation, yielded
8-benzoyl-7-hydroxy-4-methylquinoline
−2(1H)-one
4 | CONCLUSIONS
(23). Yield 0.2 g (39%), yellow powder, m.p. 275–276ꢀC.
IR (KBr cm−1): 3,579.23 (OH), 3,328.53 (NH), 1,754.9
(CO), 1,697.05 (CO) and 1,635.34 (C=C). H NMR (300
New skeleton structures of angular furoquinolinone were
synthesized through Williamson reaction of hydro-
xyquinolinone with 3-chloro-2-butanone or phenacyl bro-
mide followed by cyclization with polyphosphoric acid
(PPA). The photooxygenation reactions of synthesized
angular furoquinolinones were performed in chloroform or
dimethyl formamide and in the presence of
tetraphenylporphyrin (TPP) as singlet oxygen sensitizer
(1O2). The photooxygenation reactions afforded the photo-
cleaved product through [2 + 2] cycloaddition reaction.
1
MHz, DMSO-d6): δ 12.85(1H, s) 11.83 (1H, s), 7.93 (2H,
d, J = 8.4 Hz), 7.65 (2H, d, J = 7.5 Hz), 7.58 (1H, t,
J = 7.2 Hz), 7.50 (2H, t, J = 6.3 Hz), 6.35 (1H, s), and
2.48 (3H, s). MS (m/z, %), 279 (M+, 100%), 278 (M+-H,
85.46), 250.05 (M+-CHO, 7.32), 202.05 (M+- C6H5,
48.33), 201(M+- C6H6, 27.62), 174.05 (M+-C7H5O,
6.08), 173.05 (M+-C7H6O, 8.14), 146.05 (M+-C8H5O2,
12.58), 145 (M+-C8H6O2, 9.07), 105.05 (PhCO, 54.43)
and 77 (Ph, 96.51).
ACKNOWLEDGMENTS
This research did not receive any specific funding.
3.17 | Photooxygenation of 14
ORCID
Compound 14 (0.5 g, 2.86 mmol) was irradiated in CHCl3
with the same general procedure of the photooxygenation
affording 3-acetyl-1-methyl-2-oxo-1,2-dihydroquinolin-
4-yl acetate (24). Yield 0.3 g (40.5%), pale yellow powder
(ethanol), m.p. 130ꢀC. IR (KBr cm−1): 3,046.98 (=CH),
2,985.27 (–CH), 1,774.19 (CO), 1,697.05 (CO), 1,643.05
Sameh Elgogary https://orcid.org/0000-0002-0465-4023
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How to cite this article: Elgogary S, Abd
Elghafar H, Mashaly M. Synthesis,
photooxygenation, and characterization of new
angular furoquinolinone derivatives, a new
furocoumarin bioisoster. J Chin Chem Soc. 2021;
1–8. https://doi.org/10.1002/jccs.202000455