Photoredox halogenation of quinolones: The dual role of halo-fluorescein dyes

Article abstract of DOI:10.1039/d1ob00538c

An efficient C-3 halogenation of quinolin-4-ones is reported with halogenated fluorescein dyes which serve both as a halogen source and photocatalyst. This reaction shows broad substrate scope and gives good to excellent yields of C-3 brominated/iodinated

Full text of DOI:10.1039/d1ob00538c

Organic &
Biomolecular Chemistry
View Article Online
View Journal
PAPER
Photoredox halogenation of quinolones: the dual
role of halo-fluorescein dyes†
Cite this: DOI: 10.1039/d1ob00538c
Ritu, Sharvan Kumar, Parul Chauhan and Nidhi Jain
*
An efficient C-3 halogenation of quinolin-4-ones is reported with halogenated fluorescein dyes which
serve both as a halogen source and photocatalyst. This reaction shows broad substrate scope and gives
good to excellent yields of C-3 brominated/iodinated quinolones with eosin Y/rose bengal in green light
under ambient conditions. The mechanistic investigations suggest a radical pathway involving the oxi-
dative dehalogenation of the dye in the presence of air.
Received 19th March 2021,
Accepted 20th April 2021
DOI: 10.1039/d1ob00538c
rsc.li/obc
and antibacterial activities, and they also act as xanthine
oxidase inhibitors.7,8 Recently, 3-halogenated quinolin-4-ones
Introduction
Visible light photoredox catalysis has opened a new avenue for were used as building blocks for constructing biologically
synthetic organic chemists to execute chemical reactions active molecules via cross-coupling9,10 and C–N bond for-
under mild and environmentally friendly conditions.1 mation.11 In the literature, C–3(H) halogenation of quinolin-4-
Recently, economically and ecologically benign fluorescein ones has been reported via electrophilic addition of bromine
`
dyes such as eosin Y and rose bengal have been used as and iodine with pyridinium tribromide/NBS/NIS or molecular
alternatives to transition-metal based photocatalysts in light bromine and iodine.12 These reactions require an additional
mediated transformations involving single electron transfer metal catalyst and base, a toxic halogenating source, and a dry
(SET) and energy transfer pathways.2 The use of halo-fluor- solvent, and struggle with the lower reactivity of molecular
escein dyes as photocatalysts has spanned a broad range of bromine and iodine as halides.
reactions including oxidation, reduction, cyclization, cross-
Inspired by the recent report on the bromination of ani-
coupling, addition and many more.3 However, the use of these lines13 with eosin Y activated by selectfluor and as a continu-
dyes as a halogen source in visible light has not been reported. ation of our research towards exploring new synthetic strat-
The introduction of the halogen atom into biologically egies for the C-3 functionalization of quinolin-4-ones,14 we
active scaffolds is one of the most important transformations investigated the bromination of quinolin-4-ones with eosin Y
in organic synthesis.4 Usually, halogenations with various under visible light conditions (Scheme 1b). To the best of our
halogenating reagents have been reported using metal/metal knowledge, there is no report where halo-fluorescein dyes have
salt or oxidant/salt.5 Though useful, most of these methods been employed as halogenating reagents in visible light.
are associated with limitations such as the use of toxic metals,
high temperature, harsh reaction conditions and side product
formation. Therefore, the development of eco-friendly and
transition metal free protocols for the halogenation of biologi-
cally active moieties is highly desirable. There are a few recent
reports in which the halogenation of alkanes, arenes and het-
eroarenes has been carried out in visible light in the presence
of an external oxidant, photocatalyst and halogenating reagent
(Scheme 1a).6
Quinolin-4-ones possess a broad range of biological activi-
ties, such as anticancer, antimalarial, anti-HIV, antioxidant,
Department of Chemistry, Indian Institute of Technology, New Delhi-110016, India.
E-mail: njain@chemistry.iitd.ac.in; Tel: +91 11-2659-1562
†Electronic supplementary information (ESI) available: Copies of 1H NMR, 13C
NMR and HRMS for all the synthesized compounds, and UV-Vis studies. See
DOI: 10.1039/d1ob00538c
Scheme 1 Halogenation reactions in visible light.
This journal is © The Royal Society of Chemistry 2021
Org. Biomol. Chem.

View Article Online
Paper
Organic & Biomolecular Chemistry
(∼452 nm). No product formation was seen in the dark (entry
14), confirming the role of light in mediating the reaction.
With the best conditions in hand, the reaction scope was
Results and discussion
We commenced our studies by the reaction of 2-phenyl quino-
lin-4-one (1a) with commercially available eosin Y/rose bengal investigated by varying the substituents on the 2-aryl ring of
in acetonitrile under air and a green LED. 50% of the C-3 bro- quinolin-4-one (Table 2). We presume that the presence of an
minated product (2a) and 42% of the C-3 iodinated product electron donating group on the 2-aryl ring tends to increase
(3a) were isolated using eosin Y and rose bengal, respectively the HOMO of the electron donor intermediate, thus giving
(Table 1, entry 1). Pleased with the result, screening of higher product yields. In contrast, electron withdrawing
different solvents was carried out to improve the product yield groups do not improve the HOMO level resulting in relatively
(entries 2–8). DMF was found to be the best solvent, furnishing lower product yields. As expected, we found that the electron
2a in 90% yield and 3a in 85% yield (entry 3).
donating methyl and methoxy groups at the C-4 position of
Next, the stoichiometry of the dyes was optimized. It was the 2-aryl ring afforded C-3 brominated products in 79% and
found that a lower yield of products 2a (85%) and 3a (74%) 83% yields, respectively (2b and 2c). With benzyloxy and
was obtained with 25 mol% of the dye (entry 9). With 50 mol% phenyl groups, the desired products 2d and 2e were obtained
of the dye, 100% conversion of the starting material was in 62% and 65% yields, respectively. C-4 halogenated deriva-
observed though some unreacted dye was recovered at the end tives (bromo, chloro and fluoro) afforded the corresponding
of the reaction. To confirm if air was essential for the reaction, products in 85–93% yields (2f–2h). Notably, it was observed
it was carried out under a nitrogen atmosphere. As expected, that with C-3 substitution on the 2-aryl ring, lower product
the desired products 2a and 3a did not form in the absence of yields (2i–2l) were obtained. This may be attributed to the low
air (entry 10). Replacing air with an O2 balloon did not help HOMO level of the electron donor reaction intermediate. The
much and the desired products 2a and 3a were obtained in 2-phenyl ring of quinolone substituted with dimethoxy, ethoxy-
91% and 84% yields, respectively (entry 11). Furthermore, it methoxy, bromomethoxy and trimethoxy substituents gave the
was found that the presence of a small quantity of water in the desired products in 78–90% yields (2m–2q). Bromination of
reaction did not affect the product yield substantially (entry C2–H and C2–methyl substituted quinolones gave the desired
12) but on increasing the amount of water (>15%), moderate products 2r and 2s in 81% and 75% yields, respectively.
to poor yields were obtained. Changing the source of light Furthermore, even the N-protected 1-ethylquinolin-4(1H)-one
from a green to a blue LED did not bring about any change in showed good compatibility and the brominated product 2t was
the product yield (entry 13) but the time required by the reac- obtained in 86% yield. Next, we tested the substrate scope with
tion to undergo completion increased to 14 h. This might be 2-CO2Me substituted quinolone derivatives (8-methyl,
due to the weak absorption of eosin Y in the blue light region 5-methoxy, 5-chloro) and in all cases, the desired products
(2u–2x) were formed in low yields. Again, the electron with-
Table 1 Optimization of the reaction conditionsa
Table 2 Substrate scope for brominationa
Entry
Fluorescein dye
Solvent
Yieldb (2a/3a)
1
2
3
4
5
6
7
8
Eosin Y/rose bengal
Eosin Y/rose bengal
Eosin Y/rose bengal
Eosin Y/rose bengal
Eosin Y/rose bengal
Eosin Y/rose bengal
Eosin Y/rose bengal
Eosin Y/rose bengal
Eosin Yc,d/rose bengalc,d
Eosin Y/rose bengal
Eosin Y/rose bengal
Eosin Y/rose bengal
Eosin Y/rose bengal
Eosin Y/rose bengal
CH3CN
DMSO
DMF
DMA
Toluene
DCM
Methanol
THF
DMF
DMF
DMF
50/42
80/51
90/85
54/50
23/10
11/25
53/22
50/62
85/74, 91/86
NR/NR
91/84
87/74
88/76
9
10e
11f
12g
13h
14i
DMF
DMF
DMF
NR/NR
a Reaction conditions: 1a (0.5 mmol), eosin Y/rose bengal (35 mol%,
0.175 mmol), solvent (5 mL), a green LED, rt, 10 h, air. b Isolated yield.
c 25 mol% dye. d 50 mol% dye. e Under N2. f Under O2 (balloon). g 10% a Reaction conditions: 1 (0.5 mmol), eosin Y (0.175 mmol), DMF
H2O added. h Blue LED, 14 h. i Reaction carried out in the dark.
(5 mL), a green LED, rt, 10 h, air.
Org. Biomol. Chem.
This journal is © The Royal Society of Chemistry 2021

View Article Online
Organic & Biomolecular Chemistry
Paper
drawing nature of the 2-CO2Me group decreases the HOMO
level and hence the yield.
The substrate scope for iodination of various quinolin-4-
ones was investigated with rose bengal (Table 3). The C-4 posi-
tion of the 2-phenyl ring substituted with groups such as
methyl, methoxy and chloro gave the desired iodinated pro-
ducts in 77%, 88% and 92% yields, respectively (3b–3d).
However, 3-chloro and 3,4 dimethoxy groups on the 2-aryl ring
gave the iodinated products in 68% and 84% yields, respect-
ively (3e and 3f). Furthermore, unsubstituted quinolone, and
2-Me and 2-COOMe substituted derivatives also yielded the
iodinated products (3g–3i) in moderate yields.
To understand the mechanistic pathway, control experi-
ments, and EPR and UV-Vis studies were performed. A dose
dependent quenching with 2,2,6,6-tetramethylpiperidine-1-
oxyl (TEMPO) showed a complementary decrease in the
product yield. Furthermore, a quinolone–TEMPO adduct was
also observed, confirming the generation of the quinolyl
radical in light (Fig. S1, ESI†). The EPR spectroscopy of the
reaction mixture at room temperature showed a signal with a g
value of 2.00352 and a line width ΔH = 3.44G, validating the
formation of radical species (Fig. S2, ESI†). Time dependent
UV-Vis absorption spectra of the reaction mixture in DMF
showed a decrease in the intensity of the main absorption
band of eosin Y at 536 nm, and the appearance of a new peak
at 463 nm. This pointed out towards the co-existence of
Scheme 2 Plausible mechanism.
product of terpinene was obtained with no change in the yield
of halogenated products, confirming the energy transfer
hypothesis (Fig. S4, ESI†).
Based on the experimental evidence and previous
literature,14,15 we propose
a
radical-mediated reaction
initiation followed by oxidative dehalogenation of the dye, as
shown in Scheme 2. The reaction starts with proton abstrac-
tion by quinolone from the hydrogenated eosin Y (EYH2) in
the presence of green LED. EYH2 gets excited to a higher
energy state and increases the acidity of the –COOH and –OH
protons of EYH2, thus facilitating the proton transfer.16 This
results in the formation of the dianionic excited form of eosin
Y (EY2−*) and positively charged hydroxy quinoline (4a). On
reacting with other quinolone molecules or the basic solvent,
4a forms the zwitterion (4a′) which is comparatively electron
rich (Scheme S1, ESI†). Furthermore, an electron transfer from
4a′ to EY2−* takes place, resulting in the formation of semi-
reduced EY3•− and the quinolyl radical cation (4b).15d Next, the
EY3•− gets excited in light to form the excited semi-reduced
EY3•−* which then undergoes oxidative debromination by
different debrominated eosin
Y species in the reaction
mixture, generated through oxidative degradation (Fig. S3,
ESI†). We hypothesized that the oxidative debromination and
degradation of eosin Y proceeded via excitation of semi-
reduced eosin Y (EY3•−) followed by energy transfer from
excited semi-reduced eosin Y (EY3•−*) to 3O2, resulting in a
high energy 1O2. To confirm this, 1O2 trapping experiment
with terpinene15 was carried out. As expected, a peroxidized
Table 3 Substrate scope for iodinationa
3
transferring its energy to O2 and furnishes a free Br• radical.
The resultant high energy 1O2 reacts with EY2−–Br•/EY2− and
breaks the eosin Y chromophore.15a The generated Br• radical
reacts with the quinolyl radical cation (4b) and yields the
desired brominated product 2 via deprotonation.
Conclusions
In conclusion, we demonstrate the commercially available halo-
fluorescein dyes as highly practical and atom economical halo-
genating reagents for oxidative halogenation of quinolin-4-ones
under metal-free conditions. The fluorescein dyes play the dual
role of a halogen source and photocatalyst in visible light. The
mechanistic investigations suggest the reaction to follow a radical
pathway and reveal the crucial role of oxygen in the photodegra-
dative halo-radical formation, thus enabling a highly efficient,
mild and regioselective halogenation protocol.
a Reaction conditions: 1 (0.5 mmol), rose bengal (0.175 mmol), DMF
(5 mL), a green LED, rt, 10 h, air.
This journal is © The Royal Society of Chemistry 2021
Org. Biomol. Chem.

View Article Online
Paper
Organic & Biomolecular Chemistry
172.2, 160.9, 150.1, 139.4, 132.5, 131.1, 127.6, 125.7, 124.4,
123.3, 118.9, 114.2, 105.9, 55.9.
Experimental
General
2-(4-(Benzyloxy)phenyl)-3-bromoquinolin-4(1H)-one
(2d).
1H NMR and 13C NMR spectra were recorded on a 400 MHz New, isolated as a white solid, 62%, 126 mg, mp 268–270 °C.
(1H 400 MHz, 13C 100 MHz) and 500 MHz spectrometer (1H 1H NMR (400 MHz, DMSO) δ 12.24 (s, 1H), 8.22 (s, 1H),
500 MHz, 13C 125 MHz) using DMSO-d6 as the solvent and 7.79–7.69 (m, 2H), 7.63 (d, J = 8.4 Hz, 2H), 7.55 (d, J = 7.2 Hz,
tetramethylsilane (TMS) as the internal standard at room 2H), 7.47 (t, J = 7.6 Hz, 3H), 7.41 (dd, J = 10.4, 14.4 Hz, 1H),
temperature. Chemical shifts are in δ (ppm) relative to TMS. 7.26 (d, J = 8.4 Hz, 2H), 5.29 (s, 2H). 13C NMR (100 MHz,
Coupling constants (J) are in Hz and splitting patterns are DMSO) δ 172.3, 160.1, 150.3, 139.7, 137.2, 132.5, 131.2, 128.9,
described as singlet (s), doublet (d), triplet (t) and multiplet 128.4, 128.2, 127.9, 125.9, 124.4, 123.4, 119.0, 115.1, 106.1,
(m). Melting points were determined on melting point appar- 69.8. HRMS (ESI, m/z) calcd for C22H16BrNO2 [M + Na]+
atus and are uncorrected. High resolution mass spectra 428.0257, found 428.0256.
(HRMS) were recorded on a mass spectrometer using electro-
2-([1,1′-Biphenyl]-4-yl)-3-bromoquinolin-4(1H)-one (2e). New,
spray ionization-time-of-flight (ESI-TOF) reflectron experi- isolated as a white solid, 65%, 122 mg, mp 242–244 °C. 1H
ments. Reactions were monitored on silica gel TLC plates. All NMR (400 MHz, DMSO) δ 12.38 (s, 1H), 8.19 (d, J = 7.6 Hz, 1H),
glass apparatus was oven dried prior to use. Flash chromato- 7.90 (d, J = 7.9 Hz, 2H), 7.78 (d, J = 7.4 Hz, 2H), 7.72 (dd, J =
graphy was performed over silica gel (100–200 Mesh). All 18.8, 8.1 Hz, 4H), 7.54 (t, J = 7.1 Hz, 2H), 7.49–7.39 (m, 2H).
chemicals and reagents were obtained from Aldrich (USA) and 13C NMR (100 MHz, DMSO) δ 172.3, 150.1, 142.2, 139.7, 139.5,
Alfa Aesar (England) and were used without further purifi- 134.4, 132.6, 130.4, 130.2, 129.6, 128.5, 127.3, 127.1, 125.7,
cation. All starting materials (1) are known compounds and 124.6, 123.4, 119.0. HRMS (ESI, m/z) calcd for C21H14BrNO [M
were synthesized using reported procedures.17–19
+ Na]+ 398.0150, found 398.0150.
3-Bromo-2-(4-bromophenyl)quinolin-4(1H)-one
(2f).21
Isolated as a white solid, 85%, 160 mg. 1H NMR (400 MHz,
DMSO) δ 12.31 (s, 1H), 8.16 (d, J = 8.0 Hz, 1H), 7.80 (d, J = 8.0
Hz, 2H), 7.75–7.68 (m, 1H), 7.65 (d, J = 8.4 Hz, 1H), 7.59 (d, J =
7.6 Hz, 2H), 7.41 (t, J = 7.2 Hz, 1H). 13C NMR (100 MHz,
DMSO) δ 172.1, 149.2, 139.5, 134.6, 132.7, 131.9, 131.7, 125.7,
124.6, 124.0, 123.4, 119.0, 105.8.
General procedure for the synthesis of products 2a–2x and 3a–
3i
A
solution of 2-phenylquinolin-4(1H)-one 1a (110 mg,
0.5 mmol) and eosin Y or rose bengal (0.175 mmol) was taken
in DMF (5 mL) and stirred under a green LED for 10 h at RT.
The reaction was diluted with water (60 mL) and the aqueous
layer was extracted with ethyl acetate (3 × 15 mL). The organic
layer was dried over sodium sulphate (anhydrous) and evapor-
ated under reduced pressure to give the desired product 2a
and 3a in 90% and 85% yields respectively after flash
chromatography.
3-Bromo-2-(4-chlorophenyl)quinolin-4(1H)-one
(2g).20
Isolated as a white solid, 93%, 154 mg. 1H NMR (400 MHz,
DMSO) δ 12.32 (s, 1H), 8.17 (d, J = 7.6 Hz, 1H), 7.72 (d, J = 7.2
Hz, 1H), 7.68 (s, 5H), 7.43 (t, J = 7.2 Hz, 1H). 13C NMR
(100 MHz, DMSO) δ 172.1, 149.2, 139.6, 135.3, 134.3, 132.6,
131.5, 128.9, 125.8, 124.6, 123.4, 119.0, 105.8.
3-Bromo-2-(4-fluorophenyl)quinolin-4(1H)-one
(2h).20
Physical properties and characterization data of the
synthesized compounds
Isolated as a white solid, 88%, 139 mg. 1H NMR (500 MHz,
DMSO) δ 12.38 (s, 1H), 8.17 (d, J = 6.0 Hz, 1H), 7.76–7.69 (m,
3-Bromo-2-phenylquinolin-4(1H)-one (2a).20 Isolated as a 3H), 7.67 (d, J = 6.4 Hz, 1H), 7.46 (d, J = 7.2 Hz, 2H), 7.43 (dd, J
white solid, 90%, 135 mg. H NMR (400 MHz, DMSO) δ 12.31 = 5.6, 4.0 Hz, 1H). 13C NMR (125 MHz, DMSO) δ 172.2, 164.3,
1
(s, 1H), 8.18 (d, J = 7.6 Hz, 1H), 7.71 (d, J = 6.4 Hz, 2H), 7.62 (d, 162.3, 149.4, 139.4, 132.7, 132.1, 125.8, 124.6, 123.5, 119.0,
J = 8.4 Hz, 5H), 7.43 (t, J = 6.4 Hz, 1H). 13C NMR (100 MHz, 116.0, 115.8, 105.9.
DMSO) δ 172.2, 150.4, 139.6, 135.5, 132.6, 130.4, 129.6, 128.9,
125.7, 124.4, 123.5, 119.0, 105.9.
3-Bromo-2-(3-bromophenyl)quinolin-4(1H)-one (2i). New,
isolated as a white solid, 71%, 133 mg, mp 250–252 °C. 1H
3-Bromo-2-(p-tolyl)quinolin-4(1H)-one (2b). New, isolated as NMR (400 MHz, DMSO) δ 12.35 (s, 1H), 8.18 (d, J = 7.2 Hz, 1H),
a white solid, 79%, 124 mg, mp 214–216 °C. 1H NMR 7.88 (s, 1H), 7.81 (d, J = 7.2 Hz, 1H), 7.73 (d, J = 6.4 Hz, 1H),
(400 MHz, DMSO) δ 12.24 (s, 1H), 8.17 (d, J = 7.6 Hz, 1H), 7.70 7.66 (d, J = 7.6 Hz, 2H), 7.56 (t, J = 7.6 Hz, 1H), 7.43 (t, J = 6.4
(d, J = 8.4 Hz, 2H), 7.53 (d, J = 7.6 Hz, 2H), 7.41 (d, J = 6.8 Hz, Hz, 1H). 13C NMR (100 MHz, DMSO) δ 172.1, 148.8, 139.4,
3H), 2.43 (s, 3H). 13C NMR (100 MHz, DMSO) δ 172.2, 150.4, 137.5, 133.2, 132.7, 132.0, 131.1, 128.8, 125.7, 124.6, 123.4,
140.2, 139.5, 132.7, 132.6, 129.4, 129.4, 125.8, 124.5, 123.4, 121.9, 119.0, 106.2. HRMS (ESI, m/z) calcd for C15H9Br2NNaO
118.9, 105.8, 21.4. HRMS (ESI, m/z) calcd for C16H13BrNO [M + [M + Na]+ 401.8923, found 401.8923.
H]+ 314.0175, found 314.0175.
3-Bromo-2-(4-methoxyphenyl)quinolin-4(1H)-one
3-Bromo-2-(3-chlorophenyl)quinolin-4(1H)-one (2j). New,
(2c).20 isolated as a white solid, 64%, 106 mg, mp 265–267 °C. 1H
Isolated as a white solid, 83%, 137 mg. 1H NMR (400 MHz, NMR (400 MHz, DMSO) δ 12.36 (s, 1H), 8.18 (d, J = 8.0 Hz, 1H),
DMSO) δ 3.85 (s, 3H), 7.14 (d, J = 8.48 Hz, 2H), 7.39 (t, J = 6.48 7.81–7.71 (m, 2H), 7.67 (d, J = 7.6 Hz, 2H), 7.63 (d, J = 3.2 Hz,
Hz, 1H), 7.58 (d, J = 8.44 Hz, 2H), 7.66–7.72 (m, 2H), 8.15 (d, J 2H), 7.44 (t, J = 7.2 Hz, 1H). 13C NMR (100 MHz, DMSO) δ
= 8.0 Hz, 1H), 12.19 (s, 1H); 13C NMR (100 MHz, DMSO) δ 172.2, 148.8, 139.5, 137.3, 133.5, 132.7, 130.8, 130.3, 129.3,
Org. Biomol. Chem.
This journal is © The Royal Society of Chemistry 2021

View Article Online
Organic & Biomolecular Chemistry
Paper
128.5, 125.7, 124.6, 123.5, 119.0, 105. HRMS (ESI, m/z) calcd
3-Bromo-2-(3,4,5-trimethoxyphenyl)quinolin-4(1H)-one (2q).
New, isolated as a white solid, 87%, 169 mg, mp 254–256 °C.
for C15H9BrClNNaO [M + Na]+ 355.9448, found 355.9447.
3-Bromo-2-(3-fluorophenyl)quinolin-4(1H)-one (2k). New, 1H NMR (500 MHz, DMSO) δ 12.27 (s, 1H), 8.16 (d, J = 8.1 Hz,
isolated as a white solid, 69%, 109 mg, mp 260–262 °C. 1H 1H), 7.83–7.59 (m, 2H), 7.41 (t, J = 8.5 Hz, 1H), 6.97 (s, 2H),
NMR (400 MHz, DMSO) δ 12.39 (s, 1H), 8.18 (d, J = 6.8 Hz, 1H), 3.84 (s, 6H), 3.75 (s, 3H). 13C NMR (125 MHz, DMSO) δ 172.4,
7.73 (d, J = 6.0 Hz, 1H), 7.68 (d, J = 7.2 Hz, 2H), 7.58 (d, J = 7.6 153.5, 150.7, 139.3, 139.1, 132.5, 130.8, 125.7, 124.4, 123.3,
Hz, 1H), 7.47 (dd, J = 19.2, 120.4 Hz, 3H). 13C NMR (100 MHz, 118.9, 107.3, 105.7, 60.6, 56.7. HRMS (ESI, m/z) calcd for
DMSO) δ 172.1, 163.3, 160.9, 149.1, 139.5, 137.3, 132.7, 131.2, C18H16BrNNaO4 [M + Na]+ 412.0155, found 412.0154.
131.1, 125.9, 125.7, 124.6, 123.4, 119.0, 117.4, 117.2, 116.8,
3-Bromoquinolin-4(1H)-one (2r).22 Isolated as a white solid,
1
116.6, 106.2. HRMS (ESI, m/z) calcd for C15H9BrFNNaO [M + 81% yield, 90 mg. H NMR (400 MHz, DMSO) δ 12.42 (s, 1H),
Na]+ 339.9744, found 339.9744.
8.48 (s, 1H), 8.15 (d, J = 7.6 Hz, 1H), 7.69 (d, J = 6.8 Hz, 1H),
3-Bromo-2-(3-methoxyphenyl)quinolin-4(1H)-one (2l). New, 7.63 (d, J = 8.0 Hz, 1H), 7.40 (t, J = 6.8 Hz, 1H). 13C NMR
isolated as a white solid, 74%, 122 mg, mp 238–240 °C. 1H (100 MHz, DMSO) δ 171.8, 140.6, 139.7, 132.3, 125.7, 124.7,
NMR (500 MHz, DMSO) δ 12.32 (s, 1H), 8.18 (d, J = 8.5 Hz, 1H), 124.4, 119.0, 104.6.
7.75–7.67 (m, 2H), 7.52 (t, J = 8.0 Hz, 1H), 7.46–7.39 (m, 1H),
3-Bromo-2-methylquinolin-4(1H)-one (2s).23 Isolated as a
7.20 (d, J = 8.0 Hz, 2H), 7.16 (dd, J = 8.0, 9.0 Hz, 1H), 3.85 (s, white solid, 75% yield, 89 mg. 1H NMR (400 MHz, DMSO) δ
3H). 13C NMR (125 MHz, DMSO) δ 172.2, 159.4, 150.1, 139.4, 12.15 (s, 1H), 8.10 (d, J = 9.6 Hz, 1H), 7.68 (t, J = 6.8 Hz, 1H),
136.6, 132.5, 130.1, 125.7, 124.5, 123.4, 121.7, 119.0, 115.9, 7.56 (d, J = 8.0 Hz, 1H), 7.36 (t, J = 6.8 Hz, 1H), 2.57 (s, 3H). 13
C
115.1, 105.7, 55.8. HRMS (ESI, m/z) calcd for C16H12BrNNaO2 NMR (100 MHz, DMSO) δ 171.5, 149.0, 139.2, 132.4, 126.1,
[M + Na]+ 351.9944, found 351.9944.
124.2, 123.3, 118.2, 106.4, 22.0.
3-Bromo-2-(3,4-dimethoxyphenyl)quinolin-4(1H)-one (2m).
3-Bromo-1-ethylquinolin-4(1H)-one (2t). New, isolated as a
1
New, isolated as a white solid, 90%, 162 mg, mp 208–210 °C. white solid, 86%, 108 mg, mp 198–200 °C. H NMR (400 MHz,
1H NMR (400 MHz, DMSO) δ 12.22 (s, 1H), 8.16 (d, J = 6.4 Hz, DMSO) δ 8.65 (s, 1H), 8.4 (d, J = 8.4 Hz, 1H), 7.84–7.74 (m, 2H),
1H), 7.70 (s, 2H), 7.41 (s, 1H), 7.26 (s, 1H), 7.18 (d, J = 9.4 Hz, 7.51–7.42 (m, 1H), 4.36 (q, J = 7.2 Hz, 2H), 1.36 (t, J = 7.2 Hz,
2H), 3.86 (s, 3H), 3.83 (s, 3H). 13C NMR (100 MHz, DMSO) δ 3H). 13C NMR (100 MHz, DMSO) δ 171.3, 144.7, 139.1, 132.8,
172.2, 150.5, 150.2, 148.6, 139.4, 132.4, 127.6, 125.7, 124.4, 126.7, 125.6, 124.6, 117.3, 104.3, 47.8, 14.9. HRMS (ESI, m/z)
123.3, 122.4, 118.9, 113.3, 111.8, 105.9, 56.2, 56.2. HRMS (ESI, calcd for C11H10BrNO [M + Na]+ 273.9838, found 273.9837.
m/z) calcd for C17H15BrNO3 [M
+
H]+ 360.0230, found
Methyl-3-bromo-4-oxo-1,4-dihydroquinoline-2-carboxylate (2u).
360.0230.
New, isolated as a white solid, 50% yield, 70 mg, mp 220–222 °C.
3-Bromo-2-(3,5-dimethoxyphenyl)quinolin-4(1H)-one (2n). 1H NMR (400 MHz, DMSO) δ 12.76 (s, 1H), 8.15 (d, J = 8.4 Hz,
New, isolated as a white solid, 81%, 145 mg, mp 228–230 °C. 1H), 7.79–7.70 (m, 2H), 7.45 (dd, J = 14.8, 8.0 Hz, 1H), 4.01 (s,
1H NMR (400 MHz, DMSO) δ 12.32 (s, 1H), 8.17 (d, J = 7.2 Hz, 3H). 13C NMR (100 MHz, DMSO) δ 172.1, 162.6, 141.0, 139.0,
1H), 7.70 (s, 2H), 7.41 (s, 1H), 6.78 (s, 2H), 6.72 (s, 1H), 3.82 (s, 133.3, 125.7, 125.3, 123.8, 119.4, 103.6, 54.4. HRMS (ESI, m/z)
6H). 13C NMR (100 MHz, DMSO) δ 172.1, 160.8, 150.2, 139.4, calcd for C11H8BrNO3 [M + Na]+ 303.9580, found 303.9579.
137.2, 132.7, 125.7, 124.6, 123.5, 119.0, 107.6, 105.7, 101.9,
Methyl-3-bromo-8-methyl-4-oxo-1,4-dihydroquinoline-2-carbox-
56.0. HRMS (ESI, m/z) calcd for C17H15BrNO3 [M + H]+ ylate (2v). New, isolated as a white solid, 55% yield, 81 mg, mp
360.0230, found 360.0230.
3-Bromo-2-(3-ethoxy-4-methoxyphenyl)quinolin-4(1H)-one
130–132 °C. 1H NMR (400 MHz, DMSO) δ 11.75 (s, 1H), 8.05 (s,
1H), 7.60 (s, 1H), 7.36 (s, 1H), 3.99 (s, 3H), 2.54 (s, 3H). 13C
(2o). New, isolated as a white solid, 84%, 157 mg, mp NMR (100 MHz, DMSO) δ 172.1, 162.6, 143.0, 137.9, 134.1,
190–192 °C. 1H NMR (400 MHz, DMSO) δ 12.19 (s, 1H), 8.16 127.7, 125.0, 124.1, 123.7, 102.6, 54.0, 17.8. HRMS (ESI, m/z)
(d, J = 8.0 Hz, 1H), 7.70 (s, 2H), 7.48–7.35 (m, 1H), 7.25 (s, 1H), calcd for C12H10BrNO3 [M + Na]+ 317.9736, found 317.9736.
7.16 (d, J = 3.6 Hz, 2H), 4.13 (q, J = 5.1 Hz, 2H), 3.83 (s, 3H),
Methyl-3-bromo-6-methoxy-4-oxo-1,4-dihydroquinoline-2-carbox-
1.38 (t, J = 5.2 Hz, 3H). 13C NMR (100 MHz, DMSO) δ 172.4, ylate (2w). New, isolated as a white solid, 63% yield, 98 mg, mp
150.2, 149.7, 148.8, 139.4, 132.5, 127.6, 125.7, 124.4, 123.3, 210–212 °C. 1H NMR (400 MHz, DMSO) δ 12.77 (s, 1H), 7.70
122.4, 118.9, 113.4, 112.7, 105.8, 64.2, 56.1, 15.5. HRMS (ESI, (d, J = 4.4 Hz, 1H), 7.51 (s, 1H), 7.42 (d, J = 6.4 Hz, 1H), 4.00 (s,
m/z) calcd for C18H16BrNNaO3 [M + Na]+ 396.0206, found 3H), 3.87 (s, 3H). 13C NMR (100 MHz, DMSO) δ 172.1, 163.0,
396.0204.
141.0, 139.0, 133.3, 125.7, 125.3, 123.8, 119.4, 103.6, 54.4.
3-Bromo-2-(3-bromo-4-methoxyphenyl)quinolin-4(1H)-one (2p). HRMS (ESI, m/z) calcd for C12H10BrNO4 [M + Na]+ 333.9685,
New, isolated as a white solid, 78%, 158 mg, mp 238–240 °C. found 333.9685.
1H NMR (500 MHz, DMSO) δ 12.29 (s, 1H), 8.16 (d, J = 8.0 Hz,
Methyl-3-bromo-6-chloro-4-oxo-1,4-dihydroquinoline-2-carboxy-
1H), 7.90 (d, J = 2.0 Hz, 1H), 7.72 (t, J = 7.5 Hz, 1H), 7.67 (d, J = late (2x). New, isolated as a white solid, 48%, 75 mg, mp
8.5 Hz, 2H), 7.42 (t, J = 7.0 Hz, 1H), 7.32 (d, J = 9.0 Hz, 1H), 218–220 °C. 1H NMR (400 MHz, DMSO) δ 12.91 (s, 1H), 8.08 (s,
3.96 (s, 3H). 13C NMR (125 MHz, DMSO) δ 172.2, 157.1, 148.7, 1H), 7.86–7.72 (m, 2H), 4.01 (s, 3H). 13C NMR (100 MHz,
139.3, 133.8, 132.6, 130.8, 128.8, 125.8, 124.5, 123.3, 119.0, DMSO) δ 171.2, 162.6, 141.1, 137.8, 133.4, 129.9, 124.6, 124.6,
112.7, 110.6, 106.0, 57.1. HRMS (ESI, m/z) calcd for 122.0, 104.1, 54.3. HRMS (ESI, m/z) calcd for C11H7BrClNNaO3
C16H11Br2NNaO2 [M + Na]+ 431.9028, found 431.9029.
[M + Na]+ 337.9190, found 337.9190.
This journal is © The Royal Society of Chemistry 2021
Org. Biomol. Chem.

View Article Online
Paper
3-Iodo-2-phenylquinolin-4(1H)-one (3a).20 Isolated as a white
Organic & Biomolecular Chemistry
Methyl-3-iodo-4-oxo-1,4-dihydroquinoline-2-carboxylate (3i).
solid, 85%, 147 mg. 1H NMR (400 MHz, DMSO) δ 12.32 (s, 1H), New, isolated as a white solid, 54%, 89 mg, mp 182–184 °C. 1H
8.16 (d, J = 8.0 Hz, 1H), 7.75–7.64 (m, 2H), 7.58 (s, 5H), 7.41 (t, NMR (400 MHz, DMSO) δ 12.71 (s, 1H), 8.12 (d, J = 7.2 Hz, 1H),
J = 8.0 Hz, 1H). 13C NMR (100 MHz, DMSO) δ 174.0, 153.5, 7.75 (d, J = 6.8 Hz, 1H), 7.68 (d, J = 8.0 Hz, 1H), 7.45 (s, 1H),
139.7, 138.3, 132.6, 130.3, 129.4, 128.8, 125.9, 124.6, 121.3, 3.99 (s, 3H). 13C NMR (100 MHz, DMSO) δ 174.0, 163.6, 144.4,
118.8, 86.3.
139.3, 133.4, 126.0, 125.4, 121.8, 119.1, 82.0, 54.1. HRMS (ESI,
3-Iodo-2-(p-tolyl)quinolin-4(1H)-one (3b). New, isolated as a m/z) calcd for C11H8INNaO3 [M + Na]+ 351.9441, found
white solid, 77% yield, 139 mg, mp 224–226 °C. 1H NMR 351.9441.
(400 MHz, DMSO) δ 8.14 (s, 1H), 7.68 (s, 2H), 7.45 (s, 2H), 7.38
(s, 3H), 2.42 (s, 3H). 13C NMR (100 MHz, DMSO) δ 173.9, 154.1,
140.2, 139.8, 135.9, 132.3, 129.3, 129.2, 125.9, 124.4, 121.5, Conflicts of interest
119.2, 86.3, 21.4. HRMS (ESI, m/z) calcd for C16H12INNaO [M +
There are no conflicts to declare.
Na]+ 383.9856, found 383.9856.
3-Iodo-2-(4-methoxyphenyl)quinolin-4(1H)-one
(3c).20
Isolated as a white solid, 88%, 144 mg. 1H NMR (400 MHz,
DMSO) δ 12.21 (s, 1H), 8.14 (d, J = 8.0 Hz, 1H), 7.74–7.62 (m,
2H), 7.53 (d, J = 8.8 Hz, 2H), 7.40 (t, J = 8.0 Hz, 1H), 7.13 (d, J =
8.4 Hz, 2H), 3.86 (s, 3H). 13C NMR (100 MHz, DMSO) δ 174.0,
160.7, 153.3, 139.8, 132.5, 131.1, 130.7, 125.9, 124.5, 121.2,
118.7, 114.1, 86.6, 55.9.
Acknowledgements
The authors thank FIRP-IIT Delhi for financially supporting
this work and DST-FIST for funding the ESI-HRMS facility at
IIT Delhi. Ritu thanks DST for the INSPIRE fellowship.
2-(4-Chlorophenyl)-3-iodoquinolin-4(1H)-one (3d).20 Isolated
as a white solid, 92% yield, 175 mg. 1H NMR (400 MHz,
DMSO) δ 12.36 (s, 1H), 8.15 (d, J = 8.4 Hz, 1H), 7.71 (d, J = 6.8
Hz, 1H), 7.64 (d, J = 11.2 Hz, 5H), 7.41 (t, J = 6.4 Hz, 1H). 13C
NMR (100 MHz, DMSO) δ 174.1, 152.5, 140.1, 137.2, 135.0,
132.8, 131.5, 128.9, 126.1, 125.1, 121.7, 118.8, 86.4.
References
1 (a) M. Reckenthaler and A. G. Griesbeck, Adv. Synth. Catal.,
2013, 355, 2727–2744; (b) J. Xuan and W.-J. Xiao, Angew.
Chem., Int. Ed., 2012, 51, 6828–6838; (c) C. K. Prier,
D. A. Rankic and D. W. C. MacMillan, Chem. Rev., 2013,
113, 5322–5363; (d) N. A. Romero and D. A. Nicewicz,
Chem. Rev., 2016, 116, 10075–10166.
2 (a) S. Sharma and A. Sharma, Org. Biomol. Chem., 2019, 17,
4384–4405; (b) V. Srivastava and P. P. Singh, RSC Adv., 2017,
7, 31377–31392; (c) M. Uygur and O. G. Mancheno, Org.
Biomol. Chem., 2019, 17, 5475.
3 (a) Q. Xia, Z. Shi, J. Yuan, Q. Bian, Y. Xu, B. Liu, Y. Huang,
X. Yang and H. Xu, Asian J. Org. Chem., 2019, 8, 1933–1941;
(b) M. K. Bogdos, E. Pinard and J. A. Murphy, Beilstein
J. Org. Chem., 2018, 14, 2035–2064; (c) H. Zhang and A. Lei,
Asian J. Org. Chem., 2018, 7, 1164–1177; (d) R. Pawlowski,
F. Stanek and M. Stodulski, Molecules, 2019, 24, 1533.
4 (a) L.-X. Wang, D.-X. Wang, Z.-T. Huang and M.-X. Wang,
J. Org. Chem., 2010, 75, 741–747; (b) X. Yu, J. Wang, Z. Xu,
Y. Yamamoto and M. Bao, Org. Lett., 2016, 18, 2491–2494.
5 (a) F. Sabuzi, G. Pomarico, B. Floris, F. Valentini, P. Galloni
and V. Conte, Coord. Chem. Rev., 2019, 385, 100–136;
(b) I. Saikia, A. J. Borah and P. Phukan, Chem. Rev., 2016,
116, 6837–7042; (c) H. Firouzabadi, N. Iranpoor and
S. Kazemi, Can. J. Chem., 2009, 87, 1675–1681;
(d) F. M. Moghaddam, G. Tavakoli, B. Saeednia, P. Langer
and B. Jafari, J. Org. Chem., 2016, 81, 3868–3876;
(e) X.-T. Ma and S.-K. Tian, Adv. Synth. Catal., 2013, 355,
337–340; (f) H. Y. Kim, S. Lee, S. Kim and K. Oh, Org. Lett.,
2015, 17, 450–453; (g) J. Yin, C. E. Gallis and
J. D. Chisholm, J. Org. Chem., 2007, 72, 7054–7057.
2-(3-Chlorophenyl)-3-iodoquinolin-4(1H)-one (3e). New, iso-
1
lated as a white solid, 68%, 129 mg, mp 230–232 °C. H NMR
(500 MHz, DMSO) δ 12.39 (s, 1H), 8.15 (d, J = 8.0 Hz, 1H),
7.77–7.71 (m, 1H), 7.69 (s, 1H), 7.67–7.65 (m, 2H), 7.63 (d, J =
8.0 Hz, 1H), 7.55 (d, J = 7.5 Hz, 1H), 7.43 (t, J = 7.5 Hz, 1H). 13
C
NMR (125 MHz, DMSO) δ 174.0, 152.0, 140.0, 139.7, 133.3,
132.7, 130.9, 130.2, 129.2, 128.4, 125.9, 124.8, 121.3, 118.8,
86.4. HRMS (ESI, m/z) calcd for C15H9ClINNaO [M + Na]+
403.9310, found 403.9310.
2-(3,4-Dimethoxyphenyl)-3-iodoquinolin-4(1H)-one
(3f).
New, isolated as a white solid, 84%, 171 mg, mp 170–172 °C.
1H NMR (400 MHz, DMSO) δ 12.21 (s, 1H), 8.14 (d, J = 8.0 Hz,
1H), 7.77–7.60 (m, 2H), 7.39–7.37 (m, 1H), 7.20 (s, 1H), 7.14 (s,
2H), 3.86 (s, 3H), 3.83 (s, 3H). 13C NMR (100 MHz, DMSO) δ
174.0, 153.2, 150.4, 148.6, 139.7, 132.5, 130.6, 125.9, 124.5,
122.3, 121.2, 118.7, 113.4, 111.7, 86.5, 56.2, 56.1. HRMS (ESI,
m/z) calcd for C17H14INNaO3 [M + Na]+ 429.9911, found
429.9920.
3-Iodoquinolin-4(1H)-one (3g).22 Isolated as a white solid,
1
76%, 103 mg. H NMR (400 MHz, DMSO) δ 12.23 (s, 1H), 8.51
(d, J = 6.4 Hz, 1H), 8.11 (d, J = 8.0 Hz, 1H), 7.69 (dd, J = 14.0,
8.4 Hz, 1H), 7.59 (d, J = 8.0 Hz, 1H), 7.39 (t, J = 6.4 Hz, 1H). 13
C
NMR (100 MHz, DMSO) δ 173.6, 145.1, 139.9, 132.4, 125.9,
124.6, 122.9, 118.8, 81.0.
3-Iodo-2-methylquinolin-4(1H)-one (3h).24 Isolated as
a
white solid, 70%, 71 mg. 1H NMR (400 MHz, DMSO) δ 12.18 (s,
1H), 8.08 (dd, J = 8.0, 8.0 Hz, 1H), 7.68–7.65 (m, J = 8.4, 7.1, 1.4
Hz, 1H), 7.56 (d, J = 8.0 Hz, 1H), 7.41–7.30 (m, 1H), 2.64 (s,
3H). 13C NMR (100 MHz, DMSO) δ 173.3, 151.8, 139.3, 132.4,
125.9, 124.3, 121.0, 118.1, 86.5, 26.6.
6 (a) H. Singh, C. Sen, T. Sahoo and S. C. Ghosh,
Eur. J. Chem., 2018, 4748–4753; (b) D. Petzold and B. Konig,
Adv. Synth. Catal., 2018, 360, 626–630; (c) Y. Zhao, Z. Li,
Org. Biomol. Chem.
This journal is © The Royal Society of Chemistry 2021

View Article Online
Organic & Biomolecular Chemistry
Paper
C. Yang, R. Lin and W. Xia, Beilstein J. Org. Chem., 2014, 10,
622–627; (d) B. Ma, F. Lu, H. Yang, X. Gu, Z. Li, R. Li,
H. Pei, D. Luo, H. Zhang and A. Lei, Asian J. Org. Chem.,
2019, 8, 1–6; (e) V. A. Schmidt, R. K. Quinn, A. T. Brusoe
and E. J. Alexanian, J. Am. Chem. Soc., 2014, 136, 14389–
P. J. McDermott, L. A. Howell, A. Maxwell and M. Searcey,
MedChemComm, 2016, 7, 1387–1391.
9 (a) S. Venkataraman, D. K. Barange and M. Pal, Tetrahedron
Lett., 2006, 47, 7317–7322; (b) V. L. M. Silva and
A. M. S. Silva, Tetrahedron, 2014, 70, 5310–5320.
14392; (f) C. Q. O’Broin, P. Fernandez, C. Martinez and 10 (a) S. Kumar and N. Ahmed, RSC Adv., 2015, 5, 77075;
K. Muniz, Org. Lett., 2016, 18, 436–439; (g) D. A. Rogers,
R. G. Brown, Z. C. Brandeburg, E. Y. Ko, M. D. Hopkins,
(b) M. J. Mphahlele and V. Mtshemla, J. Heterocycl. Chem.,
2008, 45, 1343.
G. LeBlanc and A. A. Lamar, ACS Omega, 2018, 3, 12868– 11 D. Audisio, S. Messaoudi, J.-F. Peyrat, J.-D. Brion and
12877. M. Alami, J. Org. Chem., 2011, 76, 4995–5005.
7 (a) S. Cretton, S. Dorsaz, A. Azzollini, Q. Favre-Godal, 12 (a) M. J. Mphahlele, M. S. Nwamadi and P. Mabeta,
L. Marcourt, S. N. Ebrahimi, F. Voinesco, E. Michellod,
D. Sanglard, K. Gindro, J.-L. Wolfender, M. Cuendet and
P. Christen, J. Nat. Prod., 2016, 79, 300–307;
(b) R. C. Jadulco, C. D. Pond, R. M. V. Wagoner, M. Koch,
O. G. Gideon, T. K. Matainaho, P. Piskaut and
L. R. Barrows, J. Nat. Prod., 2014, 77, 183–187;
(c) G. P. Miley, S. Pou, R. Winter, A. Nilsen, Y. Li, J. X. Kelly,
A. M. Stickles, M. W. Mather, I. P. Forquer, A. M. Pershing,
K. White, D. Shackleford, J. Saunders, G. Chen, L.-M. Ting,
K. Kim, L. N. Zakharov, C. Donini, J. N. Burrows,
J. Heterocycl. Chem., 2006, 43, 255; (b) B. Boganyi and
J. Kaman, Tetrahedron, 2013, 69, 9512–9519;
(c) S. Venkataraman, D. K. Barange and M. Pal, Tetrahedron
Lett., 2006, 47, 7317–7322; (d) W. D. Hong, P. D. Gibbons,
S. C. Leung, R. Amewu, P. A. Stocks, A. Stachulski, P. Horta,
M. L. S. Cristiano, A. E. Shone, D. Moss, A. Ardrey,
R. Sharma, A. J. Warman, P. T. P. Bedingfield, N. E. Fischer,
G. Aljayyoussi, S. Mead, M. Caws, N. G. Berry, S. A. Ward,
G. A. Biagini, P. M. O’Neill and G. L. Nixon, J. Med. Chem.,
2017, 60, 3703–3726.
A. B. Vaidya, S. A. Charman and M. K. Riscoe, Antimicrob. 13 P. B. Huang, Y. Zhao, C. Yang, Y. Gao and W. Xia, Org. Lett.,
Agents Chemother., 2015, 59, 5555–5560. 2017, 19, 3799–3802.
8 (a) Y.-H. Chang, M.-H. Hsu, S.-H. Wang, L.-J. Haung, 14 P. Chauhan, Ritu, Preeti, S. Kumar and N. Jain, Eur. J. Org.
K. Qian, S. L. Morris-Natschke, E. Hamel, S.-C. Kuo and Chem., 2019, 4334.
K.-H. Lee, J. Med. Chem., 2009, 52, 4883–4891; (b) Y. Xia, 15 (a) A. Alvarez-Martin, S. Trashin, M. Cuykx, A. Covaci,
Z.-Y. Yang, P. Xia, T. Hackl, E. Hamel, A. Mauger, J.-H. Wu
and K.-H. Lee, J. Med. Chem., 2001, 44, 3932–3936;
(c) L.-C. Chou, M.-T. Tsai, M.-H. Hsu, S.-H. Wang,
T.-D. Way, C.-H. Huang, H.-Y. Lin, K. Qian, Y. Dong,
K.-H. Lee, L.-J. Huang and S.-C. Kuo, J. Med. Chem., 2010,
53, 8047–8058; (d) A. Nilsen, G. P. Miley, I. P. Forquer,
M. W. Mather, K. Katneni, Y. Li, S. Pou, A. M. Pershing,
A. M. Stickles, E. Ryan, J. X. Kelly, J. S. Doggett, K. L. White,
D. J. Hinrichs, R. W. Winter, S. A. Charman,
K. D. Wael and K. Janssens, Dyes Pigm., 2017, 145, 376–384;
(b) K. Kimura, T. Miwa and M. Imamura, Chem. Commun.,
1968, 1619–1621; (c) K. Kimura, T. Miwa and M. Imamura,
Bull. Chem. Soc. Jpn., 1970, 43, 1337–1342; (d) E. F. Zwicker
and L. I. Grossweiner, J. Phys. Chem., 1963, 67, 549–555;
(e) T. Lazarides, T. McCormick, P. Du, G. Luo, B. Lindley
and R. Eisenberg, J. Am. Chem. Soc., 2009, 131, 9192;
(f) Ritu, C. Sharma, S. Kumar and N. Jain, Org. Biomol.
Chem., 2020, 18, 2921–2928.
L. N. Zakharov, I. Bathurst, J. N. Burrows, A. B. Vaidya and 16 (a) M. Majek, F. Filace and A. J. V. Wangelin, Beilstein
M. K. Riscoe, J. Med. Chem., 2014, 57, 3818–3834;
(e) S. Charoensutthivarakul, W. D. Hong, S. C. Leung,
P. D. Gibbons, P. T. P. Bedingfield, G. L. Nixon,
A. S. Lawrenson, N. G. Berry, S. A. Ward, G. A. Biagini and
P. M. O’Neill, MedChemComm, 2015, 6, 1252–1259;
(f) Y. Zhang, J. A. Clark, M. C. Connelly, F. Zhu, J. Min,
W. A. Guiguemde, A. Pradhan, L. Iyer, A. Furimsky, J. Gow,
T. Parman, F. E. Mazouni, M. A. Phillips, D. E. Kyle,
J. Mirsalis and R. K. Guy, J. Med. Chem., 2012, 55, 4205–
4219; (g) B. Gatto, O. Tabarrini, S. Massari, G. Giaretta,
S. Sabatini, C. D. Vecchio, C. Parolin, A. Fravolini,
M. Palumbo and V. Cecchetti, ChemMedChem, 2009, 4,
J. Org. Chem., 2014, 10, 981; (b) S. Daly, A. Kulesza,
G. Night, L. Macaleese, R. Antoine and P. Dugourd, J. Phys.
Chem. A, 2016, 120, 3484; (c) V. R. Batistela, D. S. Pellosi,
F. D. de Souza, W. F. da Costa, S. M. de, O. Santin, V. R. de
Souza, W. Caetano, H. P. M. de Oliveira, I. S. Scarminio and
N. Hioka, Spectrochim. Acta, Part A, 2011, 79, 889;
(d) M. Ekimova, F. Hoffmann, G. Bekçioğlu-Neff,
A. Rafferty, O. Kornilov, E. T. J. Nibbering and
D. Sebastiani, J. Am. Chem. Soc., 2019, 141, 14581;
(e) D. D. Rosebrook and W. W. Brandt, J. Phys. Chem., 1966,
70, 3857; (f) P. S. Sherin, N. P. Gritsan and
Y. P. Tsentalovich, Photochem. Photobiol. Sci., 2009, 8, 1550.
935–938; (h) M. Sato, T. Motomura, H. Aramaki, 17 H. Ma, C. Guo, Z. Zhan, G. Lu, Y. Zhang, X. Luo, X. Cui and
T. Matsuda, M. Yamashita, Y. Ito, H. Kawakami, G. Huang, New J. Chem., 2017, 41, 5280–5283.
Y. Matsuzaki, W. Watanabe, K. Yamataka, S. Ikeda, 18 X. Xu, R. Sun, S. Zhang, X. Zhang and W. Yi, Org. Lett.,
E. Kodama, M. Matsuoka and H. J. Shinkai, J. Med. Chem., 2018, 20, 1893–1897.
2006, 49, 1506–1508; (i) J. Greeff, J. Joubert, S. F. Malan and 19 J. Pinto, V. L. M. Silva, A. M. G. Silva, L. M. N. B. F. Santos
S. V. Dyk, Bioorg. Med. Chem., 2012, 20, 809–818; and A. M. S. Silva, J. Org. Chem., 2015, 80, 6649–6659.
( j) G. S. Bisacchi, J. Med. Chem., 2015, 58, 4874–4882; 20 M. J. Mphahlele, M. S. Nwamadi and P. Mabeta,
(k) M. J. Austin, S. J. Hearnshaw, L. A. Mitchenall,
J. Heterocycl. Chem., 2006, 43, 255.
This journal is © The Royal Society of Chemistry 2021
Org. Biomol. Chem.

View Article Online
Paper
Organic & Biomolecular Chemistry
21 M. J. Mphahlele, J. Chem. Res., 2002, 43, 196–198.
22 B. Boganyl and J. Kaman, Tetrahedron, 2013, 69, 9512–
9519.
23 R. M. Cross, A. Monastyrskyi, T. S. Mutka, J. N. Burrows,
D. E. Kyle and R. Manetsch, J. Med. Chem., 2010, 53, 7076–
7094.
24 A. Nilsen, G. P. Miley, I. P. Forquer, M. W. Mather,
K. Katneni, Y. Li, S. Pou, A. M. Pershing, A. M. Stickles,
E. Ryan, J. X. Kelly, J. S. Doggett, K. L. White,
D. J. Hinrichs, R. W. Winter, S. A. Charman,
L. N. Zakharov, I. Bathurst, J. N. Burrows, A. B. Vaidya and
M. K. Riscoe, J. Med. Chem., 2014, 57, 3818–3834.
Org. Biomol. Chem.
This journal is © The Royal Society of Chemistry 2021