One-pot copper-catalyzed three-component reaction: A modular approach to functionalized 2-quinolones

Article abstract of DOI:10.1039/d0ra01352h

A copper-catalyzed three-component annulation for the synthesis of functionalized 2-quinolones was developed. Three reactions including an S_N2, a Knoevenagel, and finally C-N bond formation are involved in the designed cascade reaction using 2-bromoacylarenes, 2-iodoacetamide, and nucleophiles as the three components. A new catalytic system was discovered during the study and this modular approach is highly efficient to access functionalized 2-quinolone derivatives, compatible with a broad range of functional groups, scalable, and step-economic. Further derivatization of the obtained product demonstrates the synthetic utility of this method.

Full text of DOI:10.1039/d0ra01352h

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One-pot copper-catalyzed three-component
reaction: a modular approach to functionalized 2-
Cite this: RSC Adv., 2020, 10, 7855
quinolones†
a
Ah Reum Kimab and Hee Nam Lim
*
A copper-catalyzed three-component annulation for the synthesis of functionalized 2-quinolones was
developed. Three reactions including an SN2, a Knoevenagel, and finally C–N bond formation are
involved in the designed cascade reaction using 2-bromoacylarenes, 2-iodoacetamide, and nucleophiles
as the three components. A new catalytic system was discovered during the study and this modular
approach is highly efficient to access functionalized 2-quinolone derivatives, compatible with a broad
range of functional groups, scalable, and step-economic. Further derivatization of the obtained product
demonstrates the synthetic utility of this method.
Received 21st December 2019
Accepted 13th February 2020
DOI: 10.1039/d0ra01352h
rsc.li/rsc-advances
alkynes and CO.7a Alper disclosed in 2014 the preparation of 4-
substituted 2-quinolones by the Pd-catalyzed oxidative cyclo-
carbonylation of N-monosubstituted 2-vinylanilines.7b More
recently, Jiao and coworkers found a novel Rh-catalyzed
carbonylation and annulation of N-alkyl anilines with CO and
internal alkyne through N–H and C–H activation.7c Conse-
quently, the Wu group succeeded in applying the same strategy
with an Ir catalyst, which could now tolerate halogen groups.7d
Very recently, Das developed a method to afford 3-substituted 2-
quinolones with terminal alkynes and oxalic acid as a CO source
under supported Pd-catalysis.7e
Introduction
2-Quinolones are widely used in the medicinal arena and
material science owing to their versatile biological activities1
and utility as biomaterials2 with interesting functions. They are
also found as core structures of various natural products.3 For 2-
quinolone synthesis, two traditional approaches have been well
established: the acid-assisted (Knorr)4 or base-promoted
5
¨
synthesis (Friedlander). However, the harsh acidic conditions
in the Knorr type synthesis limits the widespread application of
this reaction. In the complementary Friedlander type reaction,
¨
In addition to utilizing CO gas or its equivalent, two-
component reactions via C–H bond activation have also been
of much interests. In 2014, Jeganmohan reported a Ru-
catalyzed cyclization of anilides with acrylates or propiolates
that delivers unsubstituted 2-quinolones or 4-alkyl
substituted 2-quinolones, respectively;8a the method involves
amide-directed C–H alkenylation followed by an intra-
molecular amidation. Liu also used acetanilide as a directing
group in a Pd-catalyzed cascade reaction, but the directing
group was installed from a free aniline with acetic anhydride
and acetyl was subsequently removed during the reaction.8b
2-aminoacylarenes are common motifs that couple with malo-
nates; this has been a widely used protocol to provide
substituted 2-quinolones. In spite of the practicality and scal-
ability, it oen requires multi-step pre-functionalization to
introduce the amine moiety of arenes or it needs a long process
to install functional groups at the target position of
quinolones.6
As alternative methods, a number of synthetic procedures
have been recently demonstrated via intermolecular coupling
reaction with transition-metal (TM) complexes.7–10 Involving
C–N bond and/or C–C bond forming reaction, each protocol has
provided orthogonal bond formation and broad functional
group compatibility for the classical methods. In 2004, Kadni-
kov and Larock developed Pd-catalyzed three-component
annulation using N-substituted o-iodoanilines, internal
In
a straightforward methodology to afford N-aryl-4-substituted
quinolones by Pd-catalyzed dehydrogenative coupling
reaction with simple diarylamines and 3-substituted acrylic
acids.8c More recently, Yu explored
metal-free/base-
a similar manner, Maiti and coworkers disclosed
a
a
promoted lactamization with carbon dioxide and the 2-alke-
nylanilines.8d In 2015, Rong and Dong developed a unique
method using a Rh-catalyzed C–C bond activation strategy to
prepare 3,4-disubstituted 2-quinolones from isatins contain-
ing various directing groups.9 Besides these strategies, ben-
zynes have also been adopted for Pd-catalyzed annulation: the
Wang group used a-carbamoyl ketene dithioacetals as
aEco-Friendly New Materials Research Center, Therapeutics & Biotechnology Division,
Korea Research Institute of Chemical Technology (KRICT), 141 Gajeong-ro,
Yuseong-gu, Daejeon 34114, Republic of Korea. E-mail: heenam@krict.re.kr
bDepartment of Chemistry, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841,
Republic of Korea
† Electronic supplementary information (ESI) available. See DOI:
10.1039/d0ra01352h
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coupling partners for C–S/N–H activation10a while the Xu anions. Inspired by a previous study,11c we next screened copper
group chose N-methoxy acrylamides for C–H/N–H activa- powder-based catalytic conditions. Aer signicant efforts to
tion.10b Each protocol provides distinct mechanistic insights optimize the reaction, the use of copper powder (60–80 nm)
and useful substrate scope. Nevertheless, introducing various with 2-picolinic acid (L1) and K2CO3 was found to be most
functional groups at the 3 and/or 4-position of 2-quinolones effective with high reproducibility. It is notable that the
in one-pot from readily available reagents is still an unmet combination of copper powder with ligand are rarely reported
synthetic challenge.
for synthesis of nitrogen-incorporated small molecules. The
Our interest was to nd a convenient and practical protocol selected control experiments during optimization studies are
for the controlled synthesis of 2-quinolones containing various summarized in Table 1.
functional groups with inexpensive copper catalysts and simple
It was not surprising to observe no conversion without
starting materials. One viable way is a one-pot coupling reaction copper powder (entry 2); however, the reaction proceeded
between 2-haloacylarenes with pre-functionalized acetamides. without L1 to give 4aa in 30% yield (entry 3) and the base was
Several methods with Pd or Cu metals have been developed in essential (entry 4) with only trace product observed when the
this fashion, but the reported procedures are subject to the base was omitted. This reaction was operative at even lower
substituents at C2 position of the acetamides.11 In this view, temperatures, although the efficacy was highly reduced (entry
a unied strategy to access 3- and/or 4-substituted 2-quinolones 5). While other less polar solvents such as tetrahydrofuran,
in one-pot remains elusive.
Herein, we suggest
chloroform, and 1,4-dioxane were less productive (10–20%),
one-pot copper-catalyzed three- moderate yield (40%) was observed using toluene (entry 6).
a
component reaction12 as a new strategy for the functionalized Although the amount of Cu catalyst can be reduced to 10%, the
2-quinolone synthesis (Scheme 1). We envisioned that 2- yield was decreased (entry 7). The choice of ligand proved to be
substituted acetamides can be prepared in situ from amide 2 very important for further reaction optimization.15 A mono-
and nucleophile 3, which then react with 2-haloacylarenes 1 in dentate ligand such as 2,6-lutidine (L2) was not as good as L1
the same pot; following this sequence, the unprecedented (entry 8). Phenanthroline and bipyridine ligands (L3 and L4)
three-component reaction involving SN2, Knoevenagel and were comparable to L1 (entry 9 and 10). However, N, O-ligands
copper-catalyzed C–N bond coupling reactions can offer 3,4-
difunctionalized 2-quinolones by forming three new C–X bonds
(X ¼ carbon or heteroatoms). There are many possible reaction
Table 1 Reaction optimization for the synthesis of 4aa
pathways to give the desired product 4, however, the actual
reaction path is likely dependent on the rate of each reaction. In
principle, this modular approach will allow a diverse set of 2-
quinolones to be prepared by introducing various nucleophiles.
However, the challenge lies in securing high compatibility
between three independent reactions in which many reactants
might hamper the operation of each reaction or disable the
Yielda
catalytic activity.13
Entry
Variations from standard conditions
1
2
3
None
w/o Cu powder
w/o L1
55% (52)b
Trace
30%
Results and discussion
4
5
6
7
8
9
10
11
12
13
14
w/o K2CO3
Trace
21%
10–40%
44%
27%
48%
41%
23%
14%
44%
To realize the proposed multicomponent reaction, the
commercially available substrates 1a, 2, and 3a were chosen for
the model reaction. We initially focused on a catalytic system
with CuI and diamine ligands;14 gratifyingly, it was effective,
although the desired product 4aa was given in only low to
moderate yields (30–50%). Despite much efforts, the catalytic
system employing this frequently used copper salt was not
further improved by adopting various ligands, solvents, nor
even by targeting other copper salts with different counter
90 ꢀC instead of 110 ꢀ
C
Other nonpolar solvents instead of DMF
10 mol% Cu powder and L1 instead of 20%
L2 instead of L1
L3 instead of L1
L4 instead of L1
L5 instead of L1
L6 instead of L1
L7 instead of L1
L8 instead of L1
34%
a
Scheme 1 Proposed three-component approach for 2-quinolone
synthesis.
Determined by 1H NMR using 1,3,5-trimethoxybenzene as the internal
b
standard. Isolated yield.
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(L5, L6) were much less efficient (entry 11 and 12).16 A diamine
Next, the reaction scope with respect to sulnates was
ligand (DMEDA, L7) was also compatible with the copper surveyed (Table 3). Various arylsulnic acid sodium salts18
powder with slightly lower yield (entry 13). It was interesting to containing both electron-donating and -withdrawing groups
observe that the reaction was still working to give a reasonable were examined (4ab–4ae), all of which were amenable to the
yield in the presence of an anionic O,O-ligand (L8) that contains reaction. When alkyl sulnates containing methyl, ethyl,
an active methylene (entry 14).17
cyclopropyl, and cyclohexyl groups (4af–4ai) were employed,
With the optimized conditions in hand, we rst tested the more liphophilic quinolones were obtained. The scope was
functional group compatibility. Gratifyingly, a range of functional further extended to other heterocycles: both picoline and thio-
groups are well suited in this reaction (Table 2). For example, phene rings (4aj–4ak) survived to give the corresponding
alkyl and alkoxy substituents worked smoothly, giving moderate products albeit in low yield for the picoline substrate. To our
to good yields (4ba–4da). In the case of halides, chloride (4ea–4fa) delight, the reaction with 10-camphorsulnic acid sodium salt
showed better yield than uoride (4ga) and a triuoromethyl proceeded smoothly to provide 4al.
group (4ha). It is notable that a free hydroxy group was tolerated
Given the success using sulnates, other nucleophiles were
in the reaction to give a reasonable yield (4ia). Electron rich next examined (Scheme 2a). When sodium thiolate was
functional groups such as dialkoxy and methylenedioxy were also employed in the standard condition, 3-phenylthio-2-quinolone
compatible (4ja–4ka). The acid-sensitive MOM protecting group 5 was obtained in only 30% isolated yield; however, the yield
(4la) and redox-unstable benzyl protecting group (4ma) were was improved by adding Ca(OH)2 (55%). In addition to sulfur(II),
tolerated in this transformation. A heterocycle such as tetrazole oxygen-based nucleophiles such as sodium phenoxides also
also participated in the three-component reaction. While testing worked in the presence of a stronger base, thus affording 3-
the arene scope, the efficiency of other arylaldehydes containing aryloxy-2-quinolones 6. Notably, the use of nitrogen-based
naphthalene, pyridine, thiophene, and biologically more relevant nucleophile, N-methylphenylamine, resulted in the desired
indole was relatively low (4oa–4ra), but the products were still transformation using ketone substrate 1r, giving the 2-quino-
obtained in synthetically useful yields. Under the standard lone 7 in 44% yield.19 However, the use of other amine nucle-
conditions, ketones were much less reactive, likely due to ineffi- ophiles such as aniline and dialkylamines was unsuccessful. In
cient Knoevenagel condensation. In this case, additional use of addition, the application of the carbon-based so nucleophiles
Ca(OH)2 was discovered to promote the reaction while the driving such as malonates remains unresolved.
force is unclear. The optimization process for the ketone
The protocol was readily scalable (Scheme 2b); in the gram
substrate is summarized (see the page S3 in the ESI†). In this way, scale reaction 4aa was obtained with improved efficiency (52%
3,4-disubstituted 2-quinolones were also accessible, offering the / 62%). Next, we demonstrated the synthetic utility of the
facile entry to densely functionalized derivatives (4sa–4wa).
Table 2 Acylarene scopea
prepared quinolones (Scheme 2c). As 4aa holds many useful
functional groups, it could be further functionalized. For
instance, it was successfully transformed to 2-chloroquinoline
8. N-Benzyl quinolone 9 was obtained by the selective N-alkyl-
ation in good yield, and 9 could be further functionalized to 3,4-
disubstituted hydroquinolone 10 by Grignard-initiated Michael
addition.20 Meanwhile, the sulfonyl group can be converted to
Table 3 Sulfinate scope
a
b
Run in 1 (0.5 mmol), 2 (0.75 mmol), 3a (0.75 mmol) scale. 1 (0.5
mmol), 2 (1.0 mmol), 3a (1.0 mmol), K2CO3 (2.5 mmol), and Ca(OH)2
(2.5 mmol) were used.
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Scheme 3 A proposed mechanism. (a) Possible reaction pathways. (b)
Control experiments.
addition, the intermediate VI was found as a major resting
intermediate in the LC-trace and tlc during the entire course of
the reaction. Although the intermediate IV was not detected in
the LC-trace, a possibility cannot be excluded that the intra-
molecular Knoevenagel reaction rapidly occurs, thus not
allowing VI itself to stay on.
Scheme 2 Further scope and applications. (a) Use of other nucleo-
philes. (b) Gram scale. (c) Further applications.
To gain insights into the mechanism, we rst conducted
a control experiment using 1a and V under the standard
conditions [Scheme 3b-(1)]. Interestingly, in this two-
component reaction, the yield of 4aa was even lower than that
of the three-component reaction. The only difference was the
presence of NaI which is a by-product by SN2 reaction between 2
and 3a; NaI was indeed an important promoter of the three-
component reaction [Scheme 3b-(2)].25 As expected, the
compounds II and III were not formed in the control experiment
[Scheme 3b-(3)]. The intermediate IV was highly reactive
species. We attempted to isolate the intermediate IV by treating
II with 3a. However, a isolated product was 4aa and IV was not
traceable [Scheme 3b-(4)]. This observation, in part, supports
feasibility of path D if C–N bod forming reaction is facile. The
formation of 15 in the Scheme 3b-(5) further supports our
postulate about the path D while the efficiency for C–N bond
formation was low. Although not completely conclusive, at this
point, path E (major contribution) and D (minor contribution)
are plausible pathways to 4aa.
organotin compound 1121 which is a key intermediate for the
synthesis of 3-halogenated quinolones 1222 and 1323 and is ex-
pected as a useful platform for coupling reactions.24 The
versatile conversion of the product obtained by our method is
believed to have many implications in synthetic and medicinal
chemistry.
Possible mechanistic pathways to give 4aa are illustrated in
Scheme 3a. Depending on the reaction order, they can be clas-
sied into three ways. The rst route (path A) is deconstructive
as the resulting intermediate I cannot afford 4aa. The second
route is rstly forming the intermediate II by C–N coupling
reaction: paths B and C are conceivable to give 4aa. The third
route is initiated by a SN2 reaction between 2 and 3a, which
provides the intermediate V. The intermediate V can form 4aa
by reacting with 1a via the intermolecular C–N bond formation
followed by the Knoevenagel condensation (path D) or vise versa
(path E).
The reaction with 1a, 2, and 3a was monitored by checking
1
tlc, tracking LC-MS and H nmr experiment; we found no LC
traces corresponding to I, II, III, and IV. On the other hand, the
Conclusions
intermediate
V was clearly identied while 2 was fully
consumed within 1 hour. This indicates that the reaction
In conclusion, under the conceptually simple one-pot opera-
tion, three separate reagents reacted to synergistically form the
quickly proceeds into a two-component reaction (1a and V). In
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functionalized 2-quinolones. This was enabled by three cascade
reactions of SN2, Knoevenagel condensation, and C–N coupling
with good control over reactive intermediates. During reaction
optimization, a new catalytic system employing copper power
with 2-picolinic acid was discovered and this method highlights
streamlined preparation of biologically important 2-quinolone
derivatives. Studies to further extend the reaction scope of acyl
groups, arenes and nucleophiles is underway in our laboratory.
General procedure for 4aa–4ra (Table 1) and 4ab–4al (Table 2)
A 5 mL vial was charged with 2-bromobenzaldehyde 1 (0.50
mmol), 2-iodoacetamide 2 (138.7 mg, 0.75 mmol), a corre-
sponding sodium sulnate 3 (0.75 mmol), Cu powder (60–
80 nm, 6.4 mg, 0.10 mmol), 2-picolinic acid (12.3 mg, 0.10
mmol), K2CO3 (138.2 mg, 1.00 mmol) in dry DMF (1.5 mL). The
vial was sealed with the cap and heated at 110 ꢀC under stirring
for 48 h. Aer cooling to room temperature, the reaction
mixture was diluted with saturated NH4Cl solution and extrac-
ted with ethyl acetate (20 ꢁ 5 mL). The combined organic
solution was dried over MgSO4 and concentrated. The residue
was subjected to silica gel column chromatography
(DCM : MeOH ¼ 97 : 3 to 95 : 5 or Hex : EtOAc ¼ 1 : 1) to afford
the 2-quinolones.
Experimental section
General remarks
All reactions were carried out in 5 mL capped vials. N,N-Dime-
thylformamide (DMF) was directly used from SPS system
(Hansen, Puresolve MD) without further purication. Thin layer
chromatography (TLC) analysis was run on silica gel plates.
Purication process for 4qa (Table 1)
Spots were visualized by exposure to ultraviolet (UV) light (254 Aer cooling to room temperature, the resulting brownish
nm). High-resolution mass spectra were reported for the suspension was ltered and washed with saturated aq. NH4Cl
molecular ion [M]+. Melting points were determined with the solution. The dark yellow solid was then washed with H2O,
Mettler Toledo MP50 and the values were uncorrected. Nuclear MeOH, and DCM to afford the compound 4qa (light yellow
magnetic resonance (NMR) spectra were recorded with a Bruker solid).
(400 MHz for 1H, 100 MHz for 13C and 376 MHz for 19F).
Chemical shis for proton NMR spectra are reported in parts
per million (ppm) relative to the singlet at 7.26 ppm for chlo-
General procedure for 4sa–4wa (ketone substrates in Table 1)
A 5 mL vial was charged with ketone 1s–1w (0.50 mmol), 2-
iodoacetamide 2 (185.0 mg, 1.00 mmol), sodium benzenesul-
nate 3a (164.2 mg, 1.00 mmol), Cu powder (60–80 nm, 6.4 mg,
0.10 mmol), 2-picolinic acid (12.3 mg, 0.10 mmol), K2CO3
(172.8 mg, 1.25 mmol), and Ca(OH)2 (92.6 mg, 1.25 mmol) in
dry DMF (1.5 mL). The vial was sealed with the cap and heated
at 110 ꢀC under stirring for 48 h. Aer cooling to room
temperature, the reaction mixture was diluted with saturated
aq. NH4Cl solution and extracted with ethyl acetate (20 ꢁ 5 mL).
The combined organic solution was dried over MgSO4 and
concentrated, and subjected to silica gel column chromatog-
raphy (DCM : MeOH ¼ 97 : 3 to 95 : 5 or Hex : EtOAc ¼ 1 : 1) to
afford the 2-quinolones.
roform-d and to the quintet at 2.50 ppm for dimethylsulfoxide-
d6. Chemical shis for carbon NMR spectra are reported in
77.2 ppm with the center line of triplet for chloroform-d, in
39.5 ppm with the center line of the septet for dimethylsulf-
oxide-d6 and in 116.6 ppm, 164.2 ppm with the center line of the
quartet for triuoroacetic acid-d. Data for 1H NMR were pre-
sented as following: chemical shis (d, ppm), multiplicity (br ¼
broad, s ¼ singlet, d ¼ doublet, t ¼ triplet, dd ¼ doublet of
doublets, td ¼ triplet of doublet, m ¼ multiplet), coupling
constant (Hz), and integration. The chemical shis of peaks
found were reported for 13C NMR spectra. Infrared spectra were
recorded with a Smith Detection ATR-FTIR.
2-Bromo-5-((1-methyl-1H-tetrazol-5-yl)methoxy)benzaldehy-de
3-(Phenylsulfonyl)quinolin-2(1H)-one (4aa)
(1n)
Yield ¼ 52%; white solid; 1H NMR (400 MHz, DMSO-d6) d 7.30
(t, J ¼ 7.6 Hz, 1H), 7.35 (d, J ¼ 8.4 Hz, 1H), 7.59–7.63 (m, 2H),
7.66–7.73 (m, 2H), 7.99–8.04 (m, 3H), 8.97 (s, 1H), 12.17 (s,
1H). This spectral data is in agreement with the reported ref.
11c.
A mixture of 2-bromo-5-hydroxybenzaldehyde (1.00 g, 5.0
mmol), K2CO3 (1.04 g, 7.5 mmol) and 5-(chloromethyl)-1-
methyl-1H-tetrazole (0.79 g, 6.0 mmol) in DMSO (10 mL) was
stirred at 50 ꢀC for 4 h. Then, the reaction mixture was cooled to
room temperature, quenched with saturated NH4Cl solution,
and extracted with EtOAc (30 ꢁ 3 mL). The organic solution was
dried over MgSO4, concentrated, and subjected to column
7-Methyl-3-(phenylsulfonyl)quinolin-2(1H)-one (4ba)
chromatography (Hex : EtOAc ¼ 3 : 1) to afford the benzalde- Yield ¼ 62%; white solid; mp $ 300 ꢀC; Rf ¼ 0.3 (DCM : MeOH ¼
93 : 7) 1H NMR (400 MHz, DMSO-d6) d 2.40 (s, 3H), 7.13–7.15 (m,
ꢀ
hyde 1n (1.02 g, 69%) as white solid, mp 66–67 C.
1
Rf ¼ 0.2 (Hex : EtOAc ¼ 3 : 1); H NMR (400 MHz, CDCl3-d) 2H), 7.58–7.62 (m, 2H), 7.70 (m, 1H), 7.90 (m, 1H), 7.98–8.01 (m,
d 4.37 (s, 3H), 5.35 (s, 2H), 7.15 (dd, J ¼ 8.8 Hz and 3.1 Hz, 1H), 2H), 8.91 (s, 1H), 12.18 (s, 1H). 13C NMR (100 MHz, DMSO-d6)
7.54–7.56 (m, 2H), 10.29 (s, 1H). 13C NMR (100 MHz, CDCl3-d) d 21.7, 114.9, 115.1, 124.4, 128.3, 128.9, 129.4, 130.4, 133.6, 139.8,
d 39.8, 61.2, 114.1, 119.0, 123.7, 134.2, 135.0, 157.7, 162.1, 191.6. 141.2, 144.4, 145.0, 156.5. IR (neat) nmax 1155, 1308, 1478, 1603,
IR (neat) nmax 1010, 1162, 1224, 1684, 2876, 3066 cmꢂ1. HRMS 1649, 3144 cmꢂ1
.
HRMS[EI+] calcd for C16H13NO3S [M]+
[EI+] calcd for C10H9BrN4O2 [M]+ 295.9909, found 295.9904.
299.0616, found 299.0626.
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6-Methoxy-3-(phenylsulfonyl)quinolin-2(1H)-one (4ca)
3-(Phenylsulfonyl)-6-(triuoromethyl)quinolin-2(1H)-one
(4ha)
Yield ¼ 56%; pale yellow solid; mp $ 300 ꢀC; Rf ¼ 0.25
(DCM : MeOH ¼ 93 : 7) 1H NMR (400 MHz, DMSO-d6) d 3.81 (s, Yield ¼ 32%; white solid; mp $ 300 ꢀC; Rf ¼ 0.3 (DCM : MeOH ¼
3H), 7.28–7.36 (m, 2H), 7.59–7.63 (m, 3H), 7.70 (m, 1H), 7.99– 93 : 7) 1H NMR (400 MHz, DMSO-d6) d 7.50 (d, J ¼ 8.7 Hz, 1H), 7.60–
8.01 (m, 2H), 8.92 (s, 1H), 12.16 (s, 1H). 13C NMR (100 MHz, 7.64 (m, 2H), 7.72 (m, 1H), 7.96–8.05 (m, 3H), 8.54 (s, 1H), 9.13 (s,
DMSO-d6) d 55.6, 110.9, 116.8, 117.7, 124.0, 128.4, 128.9, 130.9, 1H), 12.55 (s, 1H). 13C NMR (100 MHz, DMSO-d6) d 116.6, 116.8,
133.6, 135.8, 139.6, 144.0, 154.6, 155.9. IR (neat) nmax 1151, 1291, 123.0 (q, JC,F ¼ 32 Hz), 124.0 (q, JC,F ¼ 270 Hz), 128.4 (q, JC,F ¼ 4 Hz),
1493, 1618, 1649, 3401 cmꢂ1. HRMS[EI+] calcd for C16H13NO4S 128.5, 129.0, 129.7 (q, JC,F ¼ 3 Hz) 132.1, 133.9, 139.3, 143.3, 144.6,
[M]+ 315.0565, found 315.0570.
156.5. 19F NMR (376 MHz, DMSO-d6) d ꢂ60.4 IR (neat) nmax 1126,
1324, 1482, 1631, 1654, 3157 cmꢂ1
. HRMS[EI+] calcd for
C16H10F3NO3S [M]+ 353.0333, found 353.0315.
6-(Pentyloxy)-3-(phenylsulfonyl)quinolin-2(1H)-one (4da)
Yield ¼ 50%; pale yellow solid; mp 279–280 ꢀC; Rf ¼ 0.25
1
6-Hydroxy-3-(phenylsulfonyl)quinolin-2(1H)-one (4ia)
(DCM : MeOH ¼ 93 : 7) H NMR (400 MHz, DMSO-d6) d 0.90
(t, J ¼ 6.9 Hz, 3H), 1.30–1.44 (m, 4H), 1.71–1.77 (m, 2H), 4.00 Yield ¼ 30%; yellow solid; mp $ 300 ꢀC; Rf ¼ 0.15
1
(t, J ¼ 6.5 Hz, 2H), 7.27–7.35 (m, 2H), 7.58–7.63 (m, 3H), 7.70 (DCM : MeOH ¼ 93 : 7) H NMR (400 MHz, DMSO-d6) d 7.18–
(t, J ¼ 7.4 Hz, 1H), 8.00 (d, J ¼ 7.8 Hz, 2H), 8.90 (s, 1H), 12.14 7.24 (m, 2H), 7.30 (s, 1H), 7.58–7.62 (m, 2H), 7.69 (t, J ¼ 7.4 Hz,
(s, 1H). 13C NMR (100 MHz, DMSO-d6) d 13.9, 21.9, 27.7, 28.2, 1H), 7.99 (d, J ¼ 7.8 Hz, 2H), 8.84 (s, 1H), 9.74 (s, 1H), 12.04 (s,
68.0, 111.5, 116.7, 117.8, 124.3, 128.4, 128.9, 130.9, 133.6, 1H). 13C NMR (100 MHz, DMSO-d6) d 113.2, 116.6, 118.0, 124.1,
135.7, 139.7, 144.0, 153.9, 155.9. IR (neat) nmax 1150, 1289, 128.4, 128.9, 130.7, 133.6, 134.6, 139.8, 143.9, 152.7, 155.8. IR
1474, 1619, 1648, 3085 cmꢂ1
C
.
HRMS[EI+] calcd for (neat) nmax 1151, 1302, 1413, 1627, 1658, 3433 cmꢂ1. HRMS
20H21NO4S [M]+ 371.1191, found 371.1187.
[EI+] calcd for C15H11NO4S [M]+ 301.0409, found 301.0410.
5-Chloro-3-(phenylsulfonyl)quinolin-2(1H)-one (4ea)
7-Dimethoxy-3-(phenylsulfonyl)quinolin-2(1H)-one (4ja)
Yield ¼ 32%; pale yellow solid; mp $ 300 ꢀC; Rf ¼ 0.4 Yield ¼ 39%; pale yellow solid; mp $ 300 ꢀC; Rf ¼ 0.15
1
(DCM : MeOH ¼ 93 : 7) H NMR (400 MHz, DMSO-d6) d 7.33 (DCM : MeOH ¼ 93 : 7) 1H NMR (400 MHz, DMSO-d6) d 3.81 (s,
(d, J ¼ 8.5 Hz, 1H), 7.46 (d, J ¼ 7.8 Hz, 1H), 7.60–7.74 (m, 4H), 3H), 3.84 (s, 3H), 6.85 (s, 1H), 7.54 (s, 1H), 7.57–7.61 (m, 2H),
8.03–8.05 (m, 2H), 8.95 (s, 1H), 12.54 (s, 1H). 13C NMR (100 7.68 (m, 1H), 7.97–8.00 (m, 2H), 8.80 (s, 1H), 12.04 (s, 1H). 13C
MHz, DMSO-d6) d 114.8, 115.1, 123.3, 128.7, 129.0, 131.9, NMR (100 MHz, DMSO-d6) d 55.8, 55.9, 97.1, 110.1, 110.6, 126.9,
133.1, 134.0, 134.7, 139.0, 139.7, 142.5, 156.0. IR (neat) nmax 128.2, 128.8, 133.4, 138.1, 140.1, 143.4, 145.6, 155.1, 156.3. IR
1155, 1319, 1444, 1571, 1612, 3078 mꢂ1. HRMS[EI+] calcd for (neat) nmax 1148, 1252, 1413, 1617, 1649, 3015 cmꢂ1. HRMS[EI+]
C
15H10ClNO3S [M]+ 319.0070, found 319.0065.
calcd for C17H15NO5S [M]+ 345.0671, found 345.0688.
6-Chloro-3-(phenylsulfonyl)quinolin-2(1H)-one (4fa)
7-(Phenylsulfonyl)-[1,3]dioxolo[4,5-g]quinolin-6(5H)-one (4ka)
Yield ¼ 45%; ivory solid; mp $ 300 ꢀC; Rf ¼ 0.25 (DCM : MeOH Yield ¼ 36%; pale brown solid; mp $ 300 ꢀC; Rf ¼ 0.2
1
¼ 93 : 7) 1H NMR (400 MHz, DMSO-d6) d 7.35 (d, J ¼ 8.9 Hz, 1H), (DCM : MeOH ¼ 93 : 7) H NMR (400 MHz, DMSO-d6) d 6.17
7.59–7.63 (t, J ¼ 7.6 Hz, 2H), 7.69–7.73 (m, 2H), 8.00 (d, J ¼ (s, 2H), 6.82 (s, 1H), 7.49 (s, 1H), 7.57–7.61 (m, 2H), 7.68 (t,
7.6 Hz, 2H), 8.16 (d, J ¼ 1.8 Hz, 1H), 8.97 (s, 1H), 12.36 (s, 1H). J ¼ 7.3 Hz, 1H), 7.98 (d, J ¼ 7.4 Hz, 2H), 8.78 (s, 1H), 12.15 (s,
13C NMR (100 MHz, DMSO-d6) d 117.4, 118.3, 126.5, 128.5, 1H). 13C NMR (100 MHz, DMSO-d6) d 94.8, 102.6, 106.6,
129.0, 129.3, 131.8, 133.7, 133.8, 139.3, 139.8, 143.7, 156.2. IR 111.8, 126.9, 128.2, 128.8, 133.4, 139.6, 140.0, 143.6, 144.1,
(neat) nmax 1158, 1312, 1477, 1617, 1649, 3455 cmꢂ1. HRMS[EI+] 153.3, 156.3. IR (neat) nmax 1152, 1245, 1444, 1629, 1650,
calcd for C15H10ClNO3S [M]+ 319.0070, found 318.9950.
2933 cmꢂ1. HRMS[EI+] calcd for C16H11NO5S [M]+ 329.0358,
found 329.0357.
6-Fluoro-3-(phenylsulfonyl)quinolin-2(1H)-one (4ga)
6-(Methoxymethoxy)-3-(phenylsulfonyl)quinolin-2(1H)-one
(4la)
Yield ¼ 29%; ivory solid; mp $ 300 ꢀC; Rf ¼ 0.25 (DCM : MeOH
1
¼ 93 : 7) H NMR (400 MHz, DMSO-d6) d 7.38 (dd, J ¼ 9.1 and
4.6 Hz, 1H), 7.58–7.63 (m, 3H), 7.71 (m, 1H), 7.93 (dd, J ¼ 8.9 Yield ¼ 46%; pale yellow solid; mp 239–240 ꢀC; Rf ¼ 0.2
1
and 2.8 Hz, 1H), 8.00 (d, J ¼ 7.5 Hz, 2H), 8.98 (s, 1H), 12.32 (s, (DCM : MeOH ¼ 93 : 7); H NMR (400 MHz, DMSO-d6) d 3.39
1H). 13C NMR (100 MHz, DMSO-d6) d 114.9 (d, JC,F ¼ 23 Hz), (s, 3H), 5.23 (s, 2H), 7.31 (d, J ¼ 9.0 Hz, 1H), 7.42 (dd, J ¼ 9.0
117.5 (d, JC,F ¼ 8 Hz), 117.8 (d, JC,F ¼ 10 Hz), 122.4 (d, JC,F ¼ 25 and 2.3 Hz, 1H), 7.58–7.62 (m, 2H), 7.67–7.71 (m, 2H), 8.00 (d,
Hz), 128.5, 129.0, 131.9, 133.8, 137.9, 139.4, 143.9 (d, JC,F ¼ 4 J ¼ 7.8 Hz, 2H), 8.91 (s, 1H), 12.18 (s, 1H). 13C NMR (100 MHz,
Hz), 156.1, 157.1 (d, JC,F ¼ 238 Hz). 19F NMR (376 MHz, DMSO- DMSO-d6) d 55.7, 94.3, 114.9, 116.7, 117.7, 124.9, 128.4, 128.9,
d6) d ꢂ119.7 IR (neat) nmax 1158, 1312, 1498, 1628, 1650, 131.1, 133.7, 136.4, 139.6, 144.1, 151.8, 156.0. IR (neat) nmax
3073 cmꢂ1. HRMS[EI+] calcd for C15H10FNO3S [M]+ 303.0365, 1152, 1312, 1495, 1625, 1649, 3144 cmꢂ1. HRMS[EI+] calcd for
found 303.0356.
C
17H15NO5S [M]+ 345.0671, found 345.0671.
7860 | RSC Adv., 2020, 10, 7855–7866
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6-(Benzyloxy)-3-(phenylsulfonyl)quinolin-2(1H)-one (4ma)
6-(Phenylsulfonyl)thieno[3,2-b]pyridin-5(4H)-one (4ra)
Yield ¼ 45%; yellow solid; mp $ 300 ꢀC; Rf ¼ 0.2 (DCM : MeOH Yield ¼ 23%; pale brown solid; mp 259–260 ꢀC; Rf ¼ 0.1
¼ 93 : 7); 1H NMR (400 MHz, DMSO-d6) d 5.15 (s, 2H), 7.29–7.36 (DCM : MeOH ¼ 93 : 7); 1H NMR (400 MHz, DMSO-d6) d 7.04 (d,
(m, 2H), 7.39–7.44 (m, 3H), 7.48–7.50 (m, 2H), 7.59–7.62 (m, J ¼ 5.4 Hz, 1H), 7.56–7.60 (m, 2H), 7.67 (t, J ¼ 7.3 Hz, 1H), 7.98
2H), 7.68–7.72 (m, 2H), 8.00 (d, J ¼ 7.8 Hz, 2H), 8.90 (s, 1H), (d, J ¼ 7.7 Hz, 2H), 8.23 (d, J ¼ 5.4 Hz, 1H), 9.04 (s, 1H), 12.72 (s,
12.18 (s, 1H). 13C NMR (100 MHz, DMSO-d6) d 69.8, 112.2, 116.8, 1H). 13C NMR (100 MHz, DMSO-d6) d 115.9, 116.6, 125.3, 128.2,
117.7, 124.4, 127.9, 128.0, 128.4, 128.5, 128.9, 131.0, 133.7, 128.8, 133.3, 139.2, 139.3, 140.1, 147.6, 156.8. IR (neat) nmax
135.9, 136.6, 139.6, 143.9, 153.6, 156.0. IR (neat) nmax 1149, 1293, 1152, 1312, 1441, 1631, 1641, 3102 cmꢂ1. HRMS[EI+] calcd for
1498, 1622, 1654, 3149 cmꢂ1. HRMS[EI+] calcd for C22H17NO4S
[M]+ 391.0878, found 391.0870.
C
13H9NO3S2 [M]+ 291.0024, found 291.0022.
4-Methyl-3-(phenylsulfonyl)quinolin-2(1H)-one (4sa)
Yield
53%; white solid; mp 282–283 ꢀC; Rf
6-((1-Methyl-1H-tetrazol-5-yl)methoxy)-3-(phenylsulfony-l)
quino lin-2(1H)-one (4na)
¼
¼
0.25
(DCM : MeOH ¼ 93 : 7); 1H NMR (400 MHz, DMSO-d6) d 3.11 (s,
3H), 7.29–7.32 (m, 2H), 7.54–7.58 (m, 2H), 7.63–7.67 (m, 2H),
7.94–7.96 (m, 2H), 8.09 (m, 1H), 11.98 (s, 1H). 13C NMR (100
MHz, DMSO-d6) d 14.8, 115.7, 119.0, 122.6, 126.9, 127.4, 128.5,
128.9, 132.9, 133.3, 139.3, 142.4, 154.6, 156.7. IR (neat) nmax
1143, 1302, 1497, 1636, 1653, 2840 cmꢂ1. HRMS[EI+] calcd for
Yield ¼ 50%; pale yellow solid; mp 274–275 ꢀC; Rf ¼ 0.1
1
(DCM : MeOH ¼ 93 : 7); H NMR (400 MHz, DMSO-d6) d 4.40
(s, 3H), 5.42 (s, 2H), 7.32 (d, J ¼ 9.1 Hz, 1H), 7.44 (dd, J ¼ 9.1
and 2.8 Hz, 1H), 7.59–7.63 (m, 2H), 7.68–7.75 (m, 2H), 8.01 (d,
J ¼ 7.8 Hz, 2H), 8.89 (s, 1H), 12.20 (s, 1H). 13C NMR (100 MHz,
DMSO-d6) d 39.6, 60.7, 112.6, 116.9, 117.6, 124.1, 128.4, 128.9,
131.1, 133.7, 136.3, 139.6, 143.9, 152.9, 156.0, 161.8. IR (neat)
nmax 1153, 1290, 1493, 1624, 1658, 3015 cmꢂ1. HRMS[EI+]
calcd for C18H15N5O4S [M]+ 397.0845, found 397.0852.
C
16H13NO3S [M]+ 299.0616, found 299.0613.
4-Cyclopropyl-3-(phenylsulfonyl)quinolin-2(1H)-one (4ta)
Yield ¼ 68%; pale yellow soild; mp 261–262 ꢀC; Rf ¼ 0.3
3-(Phenylsulfonyl)benzo[h]quinolin-2(1H)-one (4oa)
1
(DCM : MeOH ¼ 93 : 7); H NMR (400 MHz, DMSO-d6) d 0.75–
Yield ¼ 40%; pale brown solid; mp $ 300 ꢀC; Rf ¼ 0.3 0.79 (m, 2H), 1.32–1.37 (m, 2H), 2.46 (m, 1H), 7.26–7.32 (m, 2H),
(DCM : MeOH ¼ 93 : 7); 1H NMR (400 MHz, DMSO-d6) d 7.61– 7.51–7.55 (m, 2H), 7.60–7.64 (m, 2H), 7.91 (d, J ¼ 7.6 Hz, 2H),
7.65 (m, 3H), 7.69–7.74 (m, 3H), 7.92 (d, J ¼ 8.6 Hz, 1H), 7.98 8.35 (d, J ¼ 8.3 Hz, 1H), 11.99 (s, 1H). 13C NMR (100 MHz,
(d, J ¼ 8.0 Hz, 1H), 8.07 (d, J ¼ 7.7 Hz, 2H), 8.84 (d, J ¼ 8.3 Hz, DMSO-d6) d 10.2, 12.8, 115.7, 119.9, 122.3, 127.6, 127.9, 128.3,
1H), 9.04 (s, 1H), 12.59 (s, 1H). 13C NMR (100 MHz, DMSO-d6) 132.1, 132.6, 132.8, 139.2, 143.0, 156.8, 158.6. IR (neat) nmax
d 113.7, 120.9, 123.2, 123.3, 126.2, 127.0, 128.4, 128.6, 128.9, 1159, 1314, 1593, 1637, 2847, 2995 cmꢂ1. HRMS[EI+] calcd for
129.6, 129.7, 133.7, 135.1, 139.5, 139.7, 145.0, 157.1. IR (neat)
nmax 1150, 1308, 1508, 1627, 1644, 3059 cmꢂ1. HRMS[EI+] calcd
for C19H13NO3S [M]+ 335.0616, found 335.0614.
C
18H15NO3S [M]+ 325.0773, found 352.0776.
4-Phenyl-3-(phenylsulfonyl)quinolin-2(1H)-one (4ua)
Yield ¼ 55%; pale white solid; mp 287–288 ꢀC; Rf ¼ 0.35
(DCM : MeOH ¼ 93 : 7); 1H NMR (400 MHz, DMSO-d6) d 6.87 (d,
J ¼ 8.3 Hz, 1H), 7.13 (t, J ¼ 7.7 Hz, 1H), 7.37 (d, J ¼ 8.3 Hz, 1H),
7.40–7.42 (m, 2H), 7.50–7.57 (m, 5H), 7.61–7.66 (m, 2H), 7.89 (d,
J ¼ 7.6 Hz, 2H), 12.18 (s, 1H). 13C NMR (100 MHz, DMSO-d6)
d 115.5, 119.5, 122.6, 127.7, 127.9, 128.1, 128.5, 128.6, 128.8,
133.0, 133.5, 134.4, 139.9, 141.6, 155.9, 156.7. IR (neat) nmax
1149, 1306, 1653, 2851, 2876, 2982 cmꢂ1. HRMS[EI+] calcd for
3-(Phenylsulfonyl)-1,8-naphthyridin-2(1H)-one (4pa)
Yield ¼ 31%; pale yellow solid; mp $ 300 ꢀC; Rf ¼ 0.2
1
(DCM : MeOH ¼ 93 : 7); H NMR (400 MHz, DMSO-d6) d 7.37
(m, 1H), 7.60–7.64 (m, 2H), 7.72 (t, J ¼ 7.4 Hz, 1H), 8.00–8.02 (m,
2H), 8.48 (m, 1H), 8.67 (m, 1H), 9.02 (s, 1H), 12.71 (s, 1H). 13C
NMR (100 MHz, DMSO-d6) d 112.6, 119.3, 128.5, 129.0, 131.8,
133.8, 139.3, 139.5, 144.2, 151.2, 154.1, 157.2. IR (neat) nmax
1147, 1304, 1470, 1608, 1646, 3020 cmꢂ1. HRMS[EI+] calcd for
C
21H15NO3S [M]+ 361.0773, found 361.0791.
C
14H10N2O3S [M]+ 286.0412, found 286.0396.
9-Methyl-3-(phenylsulfonyl)-1,9-dihydro-2H-pyrido[2,3-b]
3-(Phenylsulfonyl)-4-(thiophen-2-yl)quinolin-2(1H)-one (4va)
indol-2-one (4qa)
Eluent used for the chromatography (Hex : EtOAc ¼ 1 : 1);
¼
0.2 yield ¼ 41%; gray solid; mp 250–251 ꢀC; Rf ¼ 0.3 (Hex : EtOAc
Yield
¼
42%; yellow solid; mp
$
300 ꢀC; Rf
(DCM : MeOH ¼ 93 : 7); H NMR (400 MHz, DMSO-d6) d 3.92 ¼ 1 : 1); 1H NMR (400 MHz, CDCl3-d) d 7.19–7.22 (m, 2H),
(s, 3H), 7.14 (t, J ¼ 7.5 Hz, 1H), 7.50 (t, J ¼ 7.8 Hz, 1H), 7.57– 7.23–7.27 (m, 2H), 7.36 (d, J ¼ 8.2 Hz, 1H), 7.46–7.49 (m, 2H),
7.62 (m, 3H), 7.67 (t, J ¼ 7.3 Hz, 1H) 8.02 (d, J ¼ 7.7 Hz, 2H), 7.54 (t, J ¼ 7.2 Hz, 1H), 7.62–7.65 (m, 2H), 8.11 (d, J ¼ 7.7 Hz,
8.08 (d, J ¼ 8.2 Hz, 1H), 8.76 (s, 1H), 12.99 (s, 1H). 13C NMR 2H), 12.78 (s, 1H). 13C NMR (100 MHz, CDCl3-d) d 116.3,
(100 MHz, TFA-d) d 30.8, 112.8, 115.4, 123.7, 124.9, 130.1, 121.2, 123.7, 127.2, 127.5, 128.4, 128.9, 129.2, 129.2, 131.2,
130.3, 130.8, 131.9, 133.7, 135.7, 137.7, 140.0, 147.4, 156.8. IR 132.7, 133.2, 133.7, 139.2, 141.7, 150.8, 159.4. IR (neat) nmax
(neat) nmax 1090, 1154, 1306, 1555 1616, 1641 cmꢂ1. HRMS 1145, 1309, 1637, 1653, 2845, 3109 cmꢂ1. HRMS[EI+] calcd for
1
[EI+] calcd for C18H14N2O3S [M]+ 338.0725, found 338.0732.
C
19H13NO3S2 [M]+ 367.0337, found 367.0339.
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2829 cmꢂ1. HRMS[EI+] calcd for C15H10FNO3S [M]+ 303.0365,
found 303.0361.
N,N-Diethyl-2-oxo-3-(phenylsulfonyl)-1,2-dihydroquinoline-4-
carboxamide (4wa)
Eluent for the chromatography (Hex : EtOAc ¼ 2 : 1 to 3 : 7);
yield ¼ 43%; pale white solid; mp 214–215 ꢀC; Rf ¼ 0.3
3-(Methylsulfonyl)quinolin-2(1H)-one (4af)
1
Yield ¼ 53%; pale white solid; mp 277–278 ꢀC; Rf ¼ 0.2
(DCM : MeOH ¼ 93 : 7); 1H NMR (400 MHz, DMSO-d6) d 3.33 (s,
3H), 7.30 (t, J ¼ 7.6 Hz, 1H), 7.40 (d, J ¼ 8.3 Hz, 1H), 7.69 (m, 1H),
7.99 (m, 1H), 8.71 (s, 1H), 12.46 (s, 1H). 13C NMR (100 MHz,
DMSO-d6) d 41.4, 115.4, 117.2, 122.8, 130.4, 131.1, 133.8, 140.6,
143.2, 157.4. IR (neat) nmax 1142, 1292, 1557, 1619, 1648,
2824 cmꢂ1. HRMS[EI+] calcd for C10H9NO3S [M]+ 223.0303,
found 223.0320.
(Hex : EtOAc ¼ 1 : 2); H NMR (400 MHz, CDCl3-d) d 1.12 (t,
J ¼ 7.1 Hz, 3H), 1.42 (t, J ¼ 7.1 Hz, 3H), 3.27–3.40 (m, 2H),
3.65 (m, 1H), 3.86 (m, 1H), 7.26–7.31 (m, 2H), 7.45–7.49 (m,
2H), 7.54 (t, J ¼ 7.3 Hz, 1H), 7.62–7.66 (m, 2H), 8.23–8.25 (m,
2H), 12.65 (s, 1H). 13C NMR (100 MHz, CDCl3-d) d 12.2, 13.2,
39.0, 43.5, 116.3, 116.8, 124.1, 125.9, 127.8, 128.6, 129.4,
133.7, 134.2, 140.0, 140.6, 151.4, 159.4, 164.5. IR (neat) nmax
1151, 1309, 1459, 1616, 1674, 2991 cmꢂ1. HRMS[EI+] calcd
for C20H20N2O4S [M]+ 384.1144, found 384.1155.
3-(Ethylsulfonyl)quinolin-2(1H)-one (4ag)
3-Tosylquinolin-2(1H)-one (4ab)
Yield ¼ 50%; off-white solid; mp 242–243 ꢀC; Rf ¼ 0.15
(DCM : MeOH ¼ 93 : 7); 1H NMR (400 MHz, DMSO-d6) d 1.15 (t,
J ¼ 7.4 Hz, 3H), 3.52 (q, J ¼ 7.4 Hz, 2H), 7.30 (t, J ¼ 7.6 Hz, 1H),
7.40 (d, J ¼ 8.3 Hz, 1H), 7.70 (m, 1H), 7.99 (d, J ¼ 7.9 Hz, 1H),
8.72 (s, 1H), 12.46 (s, 1H). 13C NMR (100 MHz, DMSO-d6) d 6.7,
46.8, 115.5, 117.3, 122.8, 128.9, 130.4, 133.9, 140.7, 144.6, 157.4.
IR (neat) nmax 1127, 1289, 1555, 1618, 1648, 2839 cmꢂ1. HRMS
[EI+] calcd for C11H11NO3S [M]+ 237.0460, found 237.0456.
Yield ¼ 62%; white solid; mp $ 300 ꢀC; Rf ¼ 0.1 (DCM : MeOH
¼ 93 : 7); 1H NMR (400 MHz, DMSO-d6) d 2.37 (s, 3H), 7.28 (m,
1H), 7.34 (d, J ¼ 8.3 Hz, 1H), 7.40 (d, J ¼ 8.2 Hz, 2H), 7.66 (m,
1H), 7.88–7.90 (m, 2H), 8.00 (d, J ¼ 7.5 Hz, 1H), 8.94 (s, 1H),
12.22 (s, 1H). 13C NMR (100 MHz, DMSO-d6) d 21.1, 115.3, 117.2,
122.7, 128.5, 129.4, 130.5, 131.0, 133.9, 136.7, 141.0, 144.2,
144.3, 156.4. IR (neat) nmax 1149, 1315, 1556, 1620, 1657,
2830 cmꢂ1. HRMS[EI+] calcd for C16H13NO3S [M]+ 299.0616,
found 299.0603.
3-(Cyclopropylsulfonyl)quinolin-2(1H)-one (4ah)
Yield ¼ 56%; pale yellow solid; mp $ 300 ꢀC; Rf ¼ 0.25
3-((4-Methoxyphenyl)sulfonyl)quinolin-2(1H)-one (4ac)
1
(DCM : MeOH ¼ 93 : 7); H NMR (400 MHz, DMSO-d6) d 1.03–
Yield ¼ 42%; pale yellow solid; mp 285–286 ꢀC; Rf ¼ 0.1
1.11 (m, 4H), 3.22 (m, 1H), 7.29 (t, J ¼ 7.6 Hz, 1H), 7.40 (d, J ¼
(DCM : MeOH ¼ 93 : 7); 1H NMR (400 MHz, DMSO-d6) d 3.84 (s, 8.3 Hz, 1H), 7.69 (t, J ¼ 7.8 Hz, 1H), 7.96 (d, J ¼ 7.9 Hz, 1H), 8.61
3H), 7.10–7.13 (m, 2H), 7.29 (t, J ¼ 7.5 Hz, 1H), 7.35 (d, J ¼ (s, 1H), 12.44 (s, 1H). 13C NMR (100 MHz, DMSO-d6) d 5.1, 30.0,
8.4 Hz, 1H), 7.67 (m, 1H), 7.93–7.95 (m, 2H), 8.00 (d, J ¼ 8.0 Hz, 115.4, 117.1, 122.8, 130.4, 130.7, 133.7, 140.6, 142.8, 157.4. IR
1H), 8.91 (s, 1H), 12.15 (s, 1H). 13C NMR (100 MHz, DMSO-d6) (neat) nmax 1142, 1287, 1618, 1654, 2867, 3006 cmꢂ1. HRMS[EI+]
d 55.8, 114.1, 115.3, 117.2, 122.7, 130.5, 130.9, 131.0, 131.4, calcd for C12H11NO3S [M]+ 249.0460, found 249.0457.
133.8, 140.9, 143.8, 156.4, 163.3. IR (neat) nmax 1150, 1263, 1496,
1619, 1648, 2998 cmꢂ1. HRMS[EI+] calcd for C16H13NO4S [M]+
3-(Cyclohexylsulfonyl)quinolin-2(1H)-one (4ai)
315.0565, found 315.0569.
Yield ¼ 27%; pale yellow solid; mp 268–269 ꢀC; Rf ¼ 0.2
(DCM : MeOH ¼ 93 : 7); 1H NMR (400 MHz, DMSO-d6) d 1.12–
3-((4-Chlorophenyl)sulfonyl)quinolin-2(1H)-one (4ad)
1.29 (m, 3H), 1.35–1.44 (m, 2H), 1.62 (d, J ¼ 12.0 Hz, 1H), 1.79
Yield ¼ 50%; off-white solid; mp 264–265 ꢀC; Rf ¼ 0.2 (d, J ¼ 12.6 Hz, 2H), 1.89 (d, J ¼ 11.5 Hz, 2H), 3.72 (m, 1H), 7.29
(DCM : MeOH ¼ 93 : 7); 1H NMR (400 MHz, DMSO-d6) d 7.29 (t, (t, J ¼ 7.5 Hz, 1H), 7.40 (d, J ¼ 8.3 Hz, 1H), 7.69 (m, 1H), 7.98 (d,
J ¼ 7.6 Hz, 1H), 7.36 (d, J ¼ 8.4 Hz, 1H), 7.66–7.70 (m, 3H), 8.02 J ¼ 7.9 Hz, 1H), 8.69 (s, 1H), 12.42 (s, 1H). 13C NMR (100 MHz,
(d, J ¼ 8.2 Hz, 3H), 8.97 (s, 1H), 12.27 (s, 1H). 13C NMR (100 DMSO-d6) d 24.2, 24.4, 24.9, 58.8, 115.4, 117.3, 122.8, 128.2,
MHz, DMSO-d6) d 115.4, 117.2, 122.8, 129.1, 130.2, 130.5, 130.7, 130.3, 133.9, 140.7, 145.1, 157.4. IR (neat) nmax 1127, 1303,
134.1, 138.4, 138.8, 141.1, 144.9, 156.4. IR (neat) nmax 1162, 1321, 1480, 1620, 1642, 2927 cmꢂ1. HRMS[EI+] calcd for C15H17NO3S
1476, 1619, 1651, 2828 cmꢂ1. HRMS[EI+] calcd for C15H10
ClNO3S [M]+ 319.0070, found 319.0057.
-
[M]+ 291.0929, found 291.0923.
3-((6-Methylpyridin-2-yl)sulfonyl)quinolin-2(1H)-one (4aj)
3-((4-Fluorophenyl)sulfonyl)quinolin-2(1H)-one (4ae)
Yield ¼ 26%; pale yellow solid; mp 275–276 ꢀC; Rf ¼ 0.2
Yield ¼ 55%; white solid; mp $ 300 ꢀC; Rf ¼ 0.2 (DCM : MeOH ¼ (DCM : MeOH ¼ 93 : 7) 1H NMR (400 MHz, DMSO-d6) d 2.43 (s,
93 : 7); 1H NMR (400 MHz, DMSO-d6) d 7.29 (t, J ¼ 7.5 Hz, 1H), 7.35 3H), 7.32 (t, J ¼ 7.6 Hz, 1H), 7.37 (d, J ¼ 8.3 Hz, 1H), 7.55 (m, 1H),
(d, J ¼ 8.3 Hz, 1H), 7.43–7.48 (m, 2H), 7.68 (m, 1H), 8.02 (d, J ¼ 7.70 (m, 1H), 8.03–8.08 (m, 3H), 9.01 (s, 1H), 12.24 (s, 1H). 13C
7.8 Hz, 1H), 8.07–8.12 (m, 2H), 8.96 (s, 1H), 12.27 (s, 1H). 13C NMR NMR (100 MHz, DMSO-d6) d 23.7, 115.5, 117.2, 120.2, 122.9,
(100 MHz, DMSO-d6) d 115.4, 116.1 (d, JC,F ¼ 23 Hz), 117.2, 122.8, 127.4, 129.1, 130.5, 134.1, 138.6, 141.0, 145.6, 156.4, 156.6,
130.5, 130.6, 131.8 (d, JC,F ¼ 10 Hz), 134.0, 135.8 (d, JC,F ¼ 3 Hz), 159.0. IR (neat) nmax 1117, 1313, 1452, 1619, 1649, 2840 cmꢂ1
.
141.0, 144.7, 156.4, 165.0 (d, JC,F ¼ 251 Hz). 19F NMR (376 MHz, HRMS[EI+] calcd for C15H12N2O3S [M]+ 300.0569, found
DMSO-d6) d ꢂ104.9 IR (neat) nmax 1147, 1319, 1488, 1621, 1657, 300.0556.
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(12.3 mg, 0.10 mmol) and K3PO4 (265.3 mg, 1.25 mmol) in dry
DMF (1.5 mL). The vial was sealed with the cap and heated at
110 C under stirring for 48 h. Aer cooling to room tempera-
ture, the reaction mixture was diluted with saturated NH4Cl
solution and extracted with ethyl acetate (20 ꢁ 5 mL). The
combined organic solution was dried over MgSO4 and concen-
trated, and subjected to silica gel column chromatography
(Hex : EtOAc ¼ 1 : 2 to 1 : 1) to afford the 2-quinolones.
3-(Thiophen-2-ylsulfonyl)quinolin-2(1H)-one (4ak)
Yield ¼ 47%; off-white solid; mp $ 300 ꢀC; Rf ¼ 0.2
ꢀ
1
(DCM : MeOH ¼ 93 : 7) H NMR (400 MHz, DMSO-d6) d 7.22
(t, J ¼ 4.4 Hz, 1H), 7.29 (t, J ¼ 7.6 Hz, 1H), 7.36 (d, J ¼ 8.4 Hz,
1H), 7.68 (t, J ¼ 7.8 Hz, 1H), 7.92 (d, J ¼ 3.8 Hz, 1H), 8.01 (d,
J ¼ 8.0 Hz, 1H), 8.08 (d, J ¼ 5.0 Hz, 1H), 8.92 (s, 1H), 12.35 (s,
1H). 13C NMR (100 MHz, DMSO-d6) d 115.4, 117.1, 122.8,
127.8, 130.6, 131.1, 134.1, 135.4, 135.8, 140.2, 140.9, 143.9,
156.4. IR (neat) nmax 1147, 1313, 1480, 1620, 1655, 2833 cmꢂ1
.
HRMS[EI+] calcd for C13H9NO3S2 [M]+ 291.0024, found
291.0024.
3-Phenoxyquinolin-2(1H)-one (6a)
Yield ¼ 37%; off-white solid; mp 209–210 ꢀC; Rf ¼ 0.4
(Hex : EtOAc ¼ 1 : 1); 1H NMR (400 MHz, DMSO-d6) d 7.03–7.05
(m, 2H), 7.12 (t, J ¼ 7.4 Hz, 1H), 7.18 (t, J ¼ 7.5 Hz, 1H), 7.33–7.39
(m, 3H), 7.45 (m, 1H), 7.53 (s, 1H), 7.61 (d, J ¼ 7.8 Hz, 1H), 12.13
(s, 1H). 13C NMR (100 MHz, DMSO-d6) d 114.8, 117.3, 119.0,
122.1, 123.2, 123.7, 127.3, 128.9, 129.8, 136.1, 145.1, 156.4,
3-(((7,7-Dimethyl-2-oxobicyclo[2.2.1]heptan-1yl)methyl)sulfo-
nyl)quino-lin-2(1H)-one (4al)
Eluent for the chromatography (Hex : EtOAc ¼ 1 : 1); yield ¼ 26%;
white solid; mp 260–261 ꢀC; Rf ¼ 0.2 (Hex : EtOAc ¼ 1 : 1); 1H NMR
(400 MHz, DMSO-d6) d 0.81 (s, 3H), 1.01 (s, 3H), 1.38 (m, 1H), 1.57
(m, 1H), 1.86 (d, J ¼ 18.4 Hz, 1H), 1.93 (m, 1H), 2.04 (t, J ¼ 4.3 Hz,
1H), 2.26–2.32 (m, 2H), 3.45 (d, J ¼ 15.2 Hz, 1H), 3.96 (d, J ¼
15.2 Hz, 1H), 7.29 (t, J ¼ 7.5 Hz, 1H), 7.41 (d, J ¼ 8.3 Hz, 1H), 7.69
(m, 1H), 7.98 (d, J ¼ 7.8 Hz, 1H), 8.65 (s, 1H), 12.40 (s, 1H). 13C
NMR (100 MHz, DMSO-d6) d 19.3, 19.4, 24.7, 26.4, 41.8, 42.0, 48.0,
49.7, 58.4, 115.4, 117.3, 122.7, 130.4, 131.8, 133.7, 140.7, 143.1,
157.6, 214.1. IR (neat) nmax 1138, 1314, 1626, 1646, 1746,
2954 cmꢂ1. HRMS[EI+] calcd for C19H21NO4S [M]+ 359.1191, found
359.1187.
157.5. IR (neat) nmax 1228, 1571, 1638, 1655, 2862, 3011 cmꢂ1
.
HRMS[EI+] calcd for C15H11NO2 [M]+ 237.0790, found 237.0802.
3-(4-Chlorophenoxy)quinolin-2(1H)-one (6b)
Yield ¼ 51%; white solid; mp 220–221 ꢀC; Rf ¼ 0.4 (Hex : EtOAc ¼
1 : 1); 1H NMR (400 MHz, DMSO-d6) d 7.05–7.07 (m, 2H), 7.19 (m,
1H), 7.34–7.40 (m, 3H), 7.46 (m, 1H), 7.62–7.64 (m, 2H), 12.19 (s,
1H). 13C NMR (100 MHz, DMSO-d6) d 114.9, 118.9, 118.9, 122.2,
124.8, 126.8, 127.5, 129.1, 129.6, 136.3, 144.5, 155.5, 157.3. IR (neat)
nmax 1226, 1430, 1479, 1654, 2854, 3013 cmꢂ1. HRMS[EI+] calcd for
C15H10ClNO2 [M]+ 271.0400, found 271.0395.
3-(Phenylthio)quinolin-2(1H)-one (5)
3-(4-Methoxyphenoxy)quinolin-2(1H)-one (6c)
A 5 mL vial was charged with 2-bromobenzaldehyde 1a
(92.5 mg, 0.50 mmol), 2-iodoacetamide 2 (185.0 mg, 1.00
mmol), sodium thiophenoxide (90%, 146.8 mg, 1.00 mmol), Cu
powder (60–80 nm, 6.4 mg, 0.10 mmol), 2-picolinic acid
(12.3 mg, 0.10 mmol), K2CO3 (172.8 mg, 1.25 mmol) and
Ca(OH)2 (92.6 mg, 1.25 mmol) in dry DMF (1.5 mL). The vial was
sealed with the cap and heated at 110 ꢀC under stirring for 48 h.
Aer cooling to room temperature, the reaction mixture was
diluted with saturated NH4Cl solution and extracted with ethyl
acetate (20 ꢁ 5 mL). The combined organic solution was dried
over MgSO4 and concentrated, and subjected to silica gel
column chromatography (DCM : MeOH ¼ 97 : 3 to 95 : 5) to
afford the quinolone 5 (69.7 mg, 55%).
Off-white solid; mp 241–242 ꢀC; Rf ¼ 0.3 (DCM : MeOH ¼
93 : 7); 1H NMR (400 MHz, DMSO-d6) d 7.11 (t, J ¼ 7.5 Hz, 1H),
7.21 (s, 1H), 7.31 (d, J ¼ 8.2 Hz, 1H), 7.41–7.45 (m, 2H), 7.48–7.56
(m, 5H), 12.14 (s, 1H). 13C NMR (100 MHz, DMSO-d6) d 115.0,
119.3, 122.2, 126.8, 129.0, 129.5, 130.0, 130.7, 132.3, 133.4,
133.7, 136.9, 159.1. IR (neat) nmax 1424, 1551, 1638, 1655, 2882,
2989 cmꢂ1. HRMS[EI+] calcd for C15H11NOS [M]+ 253.0561,
found 253.0561.
Yield ¼ 28%; pale brown solid; mp 184–185 ꢀC; Rf ¼ 0.2
1
(Hex : EtOAc ¼ 1 : 1); H NMR (400 MHz, DMSO-d6) d 3.75 (s,
3H), 6.95–6.98 (m, 2H), 7.03–7.06 (m, 2H), 7.13 (m, 1H), 7.22 (s,
1H), 7.31 (m, 1H), 7.40 (m, 1H), 7.54 (d, J ¼ 7.9 Hz, 1H), 12.11 (s,
1H). 13C NMR (100 MHz, DMSO-d6) d 55.4, 114.7, 115.0, 119.1,
119.8, 120.0, 122.1, 127.0, 128.3, 135.4, 147.0, 149.0, 155.7,
157.4. IR (neat) nmax 1224, 1497, 1569, 1654, 2847, 2995 cmꢂ1
.
HRMS[EI+] calcd for C16H13NO3 [M]+ 267.0895, found 267.0895.
4-Methyl-3-(methyl(phenyl)amino)quinolin-2(1H)-one (7)
A 5 mL vial was charged with 20-bromoacetophenone 1s
(99.5 mg, 0.50 mmol), 2-iodoacetamide 2 (138.7 mg, 0.75
mmol), N-methylaniline (0.08 mL, 0.75 mmol), CuI (19.0 mg,
0.10 mmol), 2-picolinic acid (6.2 mg, 0.05 mmol), K2CO3
(138.2 mg, 1.00 mmol) and Ca(OH)2 (74.1 mg, 1.00 mmol) in dry
DMF (1.5 mL). The vial was sealed with the cap and heated at
ꢀ
110 C under stirring for 48 h. Aer cooling to room tempera-
ture, the reaction mixture was diluted with saturated NH4Cl
solution and extracted with ethyl acetate (20 ꢁ 5 mL). The
combined organic solution was dried over MgSO4 and concen-
trated, and subjected to silica gel column chromatography
(Hex : EtOAc ¼ 2 : 1 to 1 : 1) to afford the quinolone 7 (58.1 mg,
General procedure for 6a–c
A 5 mL vial was charged with 2-bromobenzaldehyde 1a 44%).
(92.5 mg, 0.50 mmol), 2-iodoacetamide 2 (185.0 mg, 1.00
ꢀ
Pale yellow solid; mp 250–251 C; Rf ¼ 0.3 (Hex : EtOAc ¼
mmol), a corresponding sodium phenoxide (1.00 mmol), Cu 1 : 1); 1H NMR (400 MHz, DMSO-d6) d 2.31 (s, 3H), 3.12 (s,
powder (60–80 nm, 6.4 mg, 0.10 mmol), 2-picolinic acid 3H), 6.51 (d, J ¼ 8.1 Hz, 2H), 6.64 (t, J ¼ 7.2 Hz, 1H), 7.10–7.14
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1
ꢀ
(m, 2H), 7.23 (t, J ¼ 7.6 Hz, 1H), 7.35 (d, J ¼ 8.2 Hz, 1H), 7.51
Mp 77–78 C; Rf ¼ 0.1 (Hex : EtOAc ¼ 5 : 1); H NMR (400
(t, J ¼ 7.7 Hz, 1H), 7.77 (d, J ¼ 8.1 Hz, 1H), 11.85 (s, 1H). 13C MHz, CDCl3-d) d 2.28 (m, 1H), 2.40 (m, 1H), 3.83 (m, 1H), 4.24
NMR (100 MHz, DMSO-d6) d 13.6, 37.4, 111.8, 115.2, 116.5, (s, 1H), 4.99 (d, J ¼ 8.2 Hz, 1H) 5.03 (d, J ¼ 9.2 Hz, 1H), 5.12 (d, J
119.7, 121.8, 125.4, 128.9, 129.9, 134.6, 137.4, 144.9, 148.2, ¼ 10.2 Hz, 1H), 5.22 (d, J ¼ 16.1 Hz, 1H), 5.70 (m, 1H), 6.80 (d, J
159.4. IR (neat) nmax 1338, 1496, 1560, 1636, 2811, 2938 cmꢂ1
.
¼ 8.1 Hz, 1H), 7.04 (t, J ¼ 7.3 Hz, 1H), 7.11 (m, 1H), 7.21 (m,
HRMS[EI+] calcd for
264.1270.
C
17H16N2O [M]+ 264.1263, found 1H), 7.27 (m, 1H), 7.32–7.40 (m, 6H), 7.55 (t, J ¼ 7.5 Hz, 1H),
7.70 (d, J ¼ 7.8 Hz, 2H). 13C NMR (100 MHz, CDCl3-d) d 37.2,
40.0, 47.0, 70.3, 116.0, 119.6, 124.1, 125.4, 126.9, 127.5, 128.4,
2-Chloro-3-(phenylsulfonyl)quinoline (8)
128.9, 128.9, 129.0, 133.2, 134.1, 136.3, 137.8, 138.2, 161.1. IR
(neat) nmax 1147, 1308, 1601, 1665, 2927, 3069 cmꢂ1. HRMS
[EI+] calcd for C25H23NO3S [M]+ 417.1399, found 417.1403.
A mixture of compound 4aa (42.8 mg, 0.15 mmol) in POCl3 (0.35
mL, 3.75 mmol) was stirred at reux for 1 h. Then, the reaction
mixture was cooled to room temperature and quenched with
ice–water. The mixture was neutralized with 1 N NaOH (15 mL) 3-(Tributylstannyl)quinolin-2(1H)-one (11)
ꢀ
at 0 C and extracted with EtOAc (10 ꢁ 3 mL). The combined
A mixture of compound 4aa (42.8 mg, 0.15 mmol), AIBN
organic solution was dried over MgSO4, and concentrated. The
residue was subjected to column chromatography (Hex : EtOAc
¼ 6 : 1) to afford the quinoline 8 (43.4 mg, 95%) as a white solid.
Mp 150–151 ꢀC; Rf ¼ 0.4 (Hex : EtOAc ¼ 5 : 1); 1H NMR (400
MHz, CDCl3-d) d 7.52–7.56 (m, 2H), 7.64 (t, J ¼ 7.4 Hz, 1H), 7.71
(t, J ¼ 7.6 Hz, 1H), 7.91 (m, 1H), 8.00–8.06 (m, 4H), 9.23 (s, 1H).
13C NMR (100 MHz, CDCl3-d) d 126.0, 128.6, 128.7, 129.0, 129.2,
129.4, 133.1, 133.9, 134.1, 139.3, 142.2, 145.4, 149.2. IR (neat)
nmax 1140, 1319, 1444, 1571, 2927, 3078 cmꢂ1. HRMS[EI+] calcd
for C15H10ClNO2S [M]+ 303.0121, found 303.0119.
(2.5 mg, 15 mmol), SnBu3H (0.06 mL, 0.23 mmol) in dioxane (1.5
mL) was stirred at reux for 30 h. Then, the reaction mixture
was cooled to room temperature and concentrated. The residue
was subjected to a short pad of silica gel (silica gel was pre-
treated with 3% NEt3 in DCM) and rinsed with DCM to afford
the compound 11 (35.1 mg, 54%) as a white solid.
Mp 69–70 C; Rf ¼ 0.4 (DCM); H NMR (400 MHz, CDCl3-d)
d 0.89–0.92 (m, 10H), 1.15–1.19 (m, 5H), 1.33–1.42 (m, 6H),
1.58–1.66 (m, 6H), 7.17 (t, J ¼ 7.5 Hz, 1H), 7.35 (d, J ¼ 8.2 Hz,
1H), 7.44 (m, 1H), 7.52 (d, J ¼ 7.8 Hz, 1H), 7.89 (m, 1H), 12.39 (s,
1H). 13C NMR (100 MHz, CDCl3-d) d 10.1, 13.9, 27.6, 29.3, 116.0,
120.8, 122.1, 127.2, 130.0, 139.1, 139.4, 149.2, 167.8. IR (neat)
1
ꢀ
1-Benzyl-3-(phenylsulfonyl)quinolin-2(1H)-one (9)
To a stirred solution of the compound 4aa (285.3 mg, 1.00 nmax 1424, 1611, 1626, 2849, 2914, 2952 cmꢂ1
.
mmol) in THF (10 mL) was added NaH (60% dispersed in
mineral oil, 52.0 mg, 1.30 mmol) at 0 ꢀC under N2. Aer 10 min,
benzyl bromide (0.14 mL, 1.20 mmol) was added at 0 ꢀC and the
3-Chloroquinolin-2(1H)-one (12)
To a stirred solution of the compound 11 (43.4 mg, 0.10 mmol)
in THF (1 mL) was added CuCl2 (33.6 mg, 0.25 mmol) and 2,6-
lutidine (10 mL, 0.10 mmol) at room temperature. Aer 1 h, the
reaction mixture was quenched with saturated NaHCO3 solu-
tion and extracted with EtOAc (5 ꢁ 3 mL). The combined
organic solution was dried over MgSO4, and concentrated. The
residue was subjected to column chromatography
(DCM : MeOH ¼ 98 : 2) to afford the product 12 (16.0 mg, 89%)
as a white solid.
reaction mixture was stirred at room temperature for 1 h. Then,
the reaction mixture was quenched with water and extracted
with ethyl acetate. The combined organic solution was dried
over MgSO4 and concentrated. The residue was subjected to
column chromatography (Hex : EtOAc ¼ 4 : 1 to 3 : 2) to afford
the product 9 (274 mg, 73%) as a white solid.
Mp 200–201 ꢀC; Rf ¼ 0.65 (Hex : EtOAc ¼ 1 : 1); 1H NMR (400
MHz, DMSO-d6) d 5.44 (s, 2H), 7.08 (d, J ¼ 7.4 Hz, 2H), 7.18–7.27
(m, 3H), 7.36 (t, J ¼ 7.5 Hz, 1H), 7.47 (d, J ¼ 8.7 Hz, 1H), 7.60–
7.64 (m, 2H), 7.68–7.73 (m, 2H), 8.04 (d, J ¼ 7.7 Hz, 2H), 8.14 (d, J
¼ 7.8 Hz, 1H), 9.09 (s, 1H). 13C NMR (100 MHz, DMSO-d6) d 44.9,
115.5, 118.2, 123.1, 126.4, 127.2, 128.4, 128.6, 128.9, 130.0,
132.0, 133.7, 134.4, 136.0, 139.5, 140.9, 144.30, 156.2. IR (neat)
nmax 1143, 1285, 1440, 1559, 1636, 3066 cmꢂ1. HRMS[EI+] calcd
for C22H17NO3S [M]+ 375.0929, found 375.0940.
Mp 252–253 ꢀC; Rf ¼ 0.1 (DCM); 1H NMR (400 MHz, DMSO-
d6) d 7.22 (t, J ¼ 7.5 Hz, 1H), 7.34 (d, J ¼ 8.3 Hz, 1H), 7.53 (t, J ¼
7.7 Hz, 1H), 7.67 (d, J ¼ 7.9 Hz, 1H), 8.30 (s, 1H), 12.29 (s, 1H).
13C NMR (100 MHz, DMSO-d6) d 115.2, 118.8, 122.4, 125.7,
127.4, 130.6, 137.7, 137.7, 157.6. IR (neat) nmax 1203, 1429, 1637,
1654, 2921, 3006 cmꢂ1. HRMS[EI+] calcd for C9H6ClNO [M]+
179.0138, found 179.0136.
4-Allyl-1-benzyl-3-(phenylsulfonyl)-3,4-dihydroquinolin-2(1H)-
one (10)
3-Iodoquinolin-2(1H)-one (13)
To a stirred solution of the compound 9 (75.1 mg, 0.20 mmol) in A mixture of compound 11 (43.4 mg, 0.10 mmol), NaI (16.5 mg,
THF (2 mL) was added allyl magnesium bromide (1.0 M in 0.11 mmol), FeCl3 (35.7 mg, 0.22 mmol) in THF/H2O (0.2 mL/0.2
ether, 0.30 mL, 0.30 mmol) at room temperature. Aer 1 h, the mL) was stirred at rt for 1 h. Then, the reaction mixture was
reaction mixture was quenched with water and extracted with diluted with saturated NaHSO3 solution and extracted with
EtOAc (5 ꢁ 3 mL). The combined organic solution was dried ethyl acetate (5 ꢁ 3 mL). The combined organic solution was
over MgSO4, and concentrated. The residue was subjected to dried over MgSO4, and concentrated. The residue was subjected
column chromatography (Hex : EtOAc ¼ 4 : 1) to afford the to column chromatography (DCM : MeOH ¼ 98 : 2 to 97 : 3) to
product 10 (76.8 mg, 92%) as a white solid.
afford the product 12 (21.7 mg, 80%) as a white solid.
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Mp 259–260 ꢀC; Rf ¼ 0.4 (Hex : EtOAc ¼ 1 : 1); 1H NMR (400
2 (a) W. M. F. Fabian, K. S. Niederreiter, G. Uray and
W. Stadlbauer, J. Mol. Struct., 1999, 477, 209; (b)
N. S. Badgujar, M. Pazicky, P. Traar, A. Terec, G. Uray and
W. Stadlbauer, Eur. J. Org. Chem., 2006, 2715; (c)
T. L. Micotto, A. S. Brown and J. N. Wilson, Chem.
Commun., 2009, 7548; (d) R. S. Singh, A. Kumar,
S. Mukhopadhyay, G. Sharma, B. Koch and D. S. Pandey, J.
Phys. Chem. C, 2016, 120, 22605; (e) A. Joliton,
J.-M. Plancher and E. M. Carreira, Angew. Chem., Int. Ed.,
2016, 55, 2113; (f) A. S. Murugan, N. Vidhyalakshmi,
U. Yamesh and J. Annaraj, J. Mater. Chem. B, 2017, 5, 3195.
3 (a) M. F. Grundon, in The Alkaloids: Quinoline Alkaloids
Related to Anthranilic Acid, Academic Press, London, 1988,
vol. 32, p. 341; (b) J. P. Michael, Nat. Prod. Rep., 1995, 12,
465; (c) S. D. Sarker and P. G. Waterman, J. Nat. Prod.,
1995, 58, 574; (d) C. Ito, M. Itoigawa, A. Furukawa,
T. Hirano, T. Murata, N. Kaneda, Y. Hisada, K. Okuda and
H. Furukawa, J. Nat. Prod., 2004, 67, 1800.
MHz, DMSO-d6) d 7.18 (t, J ¼ 7.5 Hz, 1H), 7.31 (d, J ¼ 8.3 Hz, 1H),
7.53 (t, J ¼ 7.7 Hz, 1H), 7.64 (d, J ¼ 7.9 Hz, 1H), 8.70 (s, 1H),
12.11 (s, 1H). 13C NMR (100 MHz, DMSO-d6) d 95.9, 115.2, 120.3,
122.1, 127.0, 130.8, 138.8, 148.8, 158.8. IR (neat) nmax 1210, 1421,
1627, 1637, 2922, 3122 cmꢂ1. HRMS[EI+] calcd for C9H6INO
[M]+ 270.9494, found 270.9495.
N-(2-Formylphenyl)-2-iodoacetamide (II)
To a stirred solution of 2-iodoacetic acid (1.95 g, 10.5 mmol) in
ethyl acetate (25 mL) was added 2-aminobenzaldehyde (1.21 g,
10.0 mmol) at 0 ꢀC. Subsequently, N,N0-dicyclohexylcarbo-
diimide (2.06 g, 10.0 mmol) in EA (10 mL) was added drop-
wise to the mixture. Aer 30 min, the reaction mixture stirred at
room temperature for 10 h. Then, the resulting slurry was
ltered through a pad of Celite. The ltrate was concentrated
and was subjected to column chromatography (Hex : EtOAc ¼
7 : 1) to afford the product II (1.38 g, 48%) as a pale yellow solid.
Mp 110–111 ꢀC; Rf ¼ 0.38 (Hex : EtOAc ¼ 5 : 1); 1H NMR (400
MHz, CDCl3-d) d 3.90 (s, 2H), 7.28 (m, 1H), 7.64 (t, J ¼ 8.0 Hz,
1H), 7.71 (d, J ¼ 7.7 Hz, 1H), 8.68 (d, J ¼ 8.5 Hz, 1H), 9.94 (s, 1H),
11.52 (s, 1H). 13C NMR (100 MHz, CDCl3-d) d ꢂ0.1, 120.0, 122.0,
123.7, 136.1, 136.3, 140.5, 167.0, 195.6. IR (neat) nmax 1074, 1192,
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Conflicts of interest
There are no conicts to declare.
Acknowledgements
Financial support from the KRICT, Republic of Korea (SI1935-
10) and the National Research Foundation of Korea (NRF-
2019R1C1C1004970) are greatly appreciated. Prof. Michael
Young (The University of Toledo) is acknowledged for proof-
reading the manuscript.
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7866 | RSC Adv., 2020, 10, 7855–7866
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