Transition-Metal-Free One-Pot Tandem Synthesis of 4-Quinolone and 4 H -Thiochromen-4-one Derivatives Through Sequential Nucleophilic Addition-Elimination-S N Ar Reaction

Article abstract of DOI:10.1055/s-0036-1588466

4-Quinolone and 4 H -thiochromen-4-one derivatives are readily synthesized in a tandem one-pot manner in good to excellent yields. Starting from (Z)-β-chlorovinyl ketones, an intermolecular nucleo-philic addition of amines or sodium hydrogen sulfide to (Z

Full text of DOI:10.1055/s-0036-1588466

SYNTHESIS
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
© Georg Thieme Verlag Stuttgart · New York
2017, 49, A–L
paper
A
en
D. Wang et al.
Paper
Synthesis
Transition-Metal-Free One-Pot Tandem Synthesis of 4-Quinolone
and 4H-Thiochromen-4-one Derivatives Through Sequential
Nucleophilic Addition–Elimination–SNAr Reaction
Deqiang Wang
O
X
O
X
O
nucleophilic addition–
elimination
Peng Sun
SNAr
R1
Nu
R1
R1
+
Peiyun Jia
1, 2
Z
R2
3
Cl
R2
Nu
R2
Jinsong Peng*
Yixia Yue
0
0
0
0
0-
0
0
2
7-
8
2
2
4-
5
6
0
intermediates
Z = NH, NR, NOH, S
X = F, Cl, Br, OMe
R2 = aryl, alkyl
Chunxia Chen*
37 examples
Cs2CO3, DMSO, 140 °C, 20 h
one-pot tandem synthesis
up to 99% yield
Department of Chemistry and Chemical Engineering,
College of Science, Northeast Forestry University,
Harbin 150040, P. R. China
jspeng1998@nefu.edu.cn
ccx0109@nefu.edu.cn
Received: 02.04.2017
Accepted after revision: 24.05.2017
Published online: 19.07.2017
O
O
O
O
F
O
O
OH
OH
DOI: 10.1055/s-0036-1588466; Art ID: ss-2017-h0221-op
N
N
N
Abstract 4-Quinolone and 4H-thiochromen-4-one derivatives are
readily synthesized in a tandem one-pot manner in good to excellent
yields. Starting from (Z)-β-chlorovinyl ketones, an intermolecular nucleo-
philic addition of amines or sodium hydrogen sulfide to (Z)-β-chloro-
vinyl ketones was followed by elimination of chlorine anion to give
Z-enamine or thioenol intermediates, which can be transformed to
4-quinolone or 4H-thiochromen-4-one products through intramolecu-
lar SNAr reaction, respectively.
HN
oxolinic acid
ciprofloxacin
O
O
N
O
O
F
F
OH
OH
N
N
N
N
N
O
ofloxacin
Key words quinolones, 4H-thiochromen-4-ones, nucleophilic addi-
tion, elimination, SNAr, tandem synthesis, transition-metal-free
pefloxacin
Figure 1 Representative potent antibiotics containing the 4-quinolone
moiety
Nitrogen-containing heterocycles are frequently found
in a variety of biologically active molecules that can be used
in therapeutic areas.1 Specifically, 4-quinolone derivatives
have attracted considerable attention from organic and me-
dicinal chemists due to their diverse biological activity. Sev-
eral quinolone compounds, such as oxolinic acid, ciproflox-
acin, pefloxacin, and ofloxacin, have emerged as potent an-
tibiotics (Figure 1).2 More recently, certain 4-quinolone
derivatives have been explored as potent drug candidates as
antibacterial,3 antitumor,4 antimalarial,5 antidiabetic,6 anti-
viral,7 and HIV-1 integrase inhibitors.8
Given the importance of these heterocycles in medical
chemistry, the development of synthetic methodology to
access 4-quinolone derivatives is continually imperative. To
date, numerous methods have been reported for the syn-
thesis of quinolones.9 The most frequently used approaches
are based on various cyclocondensation strategies, such as
the Camps,10 Conrad–Limpach,11 Gould–Jacobs,12 and
Niementowski cyclization.13 Often these synthetic methods
are typically carried out under extremely harsh conditions,
including temperatures of 250 °C or strong acids such as
polyphosphoric acid or Eaton’s reagent. As a result, the re-
quired harsh conditions dramatically limit the substrate
scope of these transformations. To develop more milder and
novel processes for the construction of the 4-quinolone
frameworks, much effort has been focused on the develop-
ment of transition-metal-catalyzed (such as Pd,14 Cu,15 and
Au16) cyclization methodologies in the past decade. Despite
significant progress, transition-metal-catalyzed synthetic
methods are expensive and often require specially designed
ligands. Another disadvantage is the need to remove metal-
related impurities from products, an important issue in the
synthesis of pharmaceutical molecules. Transition-metal-
free C–N bond formation17 is also known to occur either by
nucleophilic aromatic substitutions18 or aryne-type inter-
mediates19 in the presence of a base.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

B
D. Wang et al.
Paper
Synthesis
formation of 4-quinolones or 4H-thiochromen-4-ones 3 in
a one-pot metal-free manner can be perceived through se-
quential nucleophilic addition–elimination–SNAr reaction
of various nucleophiles 2 (amine, ammonium hydroxide,
hydroxylamine, and hydrosulfide) to (Z)-β-chlorovinyl aro-
matic ketones 1 in the presence of base (Scheme 1). These
(Z)-β-chlorovinyl aromatic ketones, valuable synthetic in-
termediates for the synthesis of various heterocyclic com-
pounds,22 are easily accessible by iron-catalyzed regio- and
stereoselective addition of acid chlorides to alkynes.23
On the basis of our previous work in palladium-cata-
lyzed reactions,14j we envisioned that target molecules
could be obtained through base-promoted intramolecular
aromatic nucleophilic substitution of the enamine interme-
diates formed in situ with aryl halides. To explore this pro-
posed process, (Z)-β-chlorovinyl aromatic ketone 1a and n-
butylamine (2a) were chosen as model substrates. As
shown in Table 1, the reaction of 1a and 2a provided the de-
sired product 3aa in 97% yield in the presence of Cs2CO3 in
Z
R1
Cl
R1
R3NH2
NH3
R2
R2
+
HS–
O
Hal
O
Z = NR3, NH, S
3
1
2
Hal
O
R2
R1
+
Cl
Scheme 1 Retrosynthetic analysis of 4-quinolones and 4H-thio-
chromen-4-ones
As part of our continuing effort to construct heterocy-
cles via transition-metal-catalyzed20 or base-mediated21 re-
actions, we set out to design an efficient base-promoted
one-pot tandem synthesis of substituted 4-quinolone and
4H-thiochromen-4-one derivatives. Retrosynthetically, the
Table 1 Optimization of One-Pot Tandem Reaction Conditionsa
O
Cl
O
base, solvent
n-C4H9NH2
+
temperature, time
N
Ph
Cl
1a
Ph
C4H9
2a
3aa
Entry
Base
Cs2CO3
Solvent
Temp (°C)
Time (h)
Yield (%)b
1
2
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMF
140
140
140
140
140
140
140
140
140
80
20
20
20
20
20
20
20
20
20
20
20
20
8
97
7
NaHCO3
Na2CO3
K2CO3
3
9
4
13
31
37
41
72
85
12
33
44
72
81
96
93
95
36
25
trace
5
KOH
6
K3PO4
7
NaOt-Bu
KOt-Bu
NaOH
8
9
10
11
12
13
14
15
16
17
18
19
20
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
100
120
140
140
140
140
140
140
140
110
12
24
20
20
20
20
20
DMA
toluene
1,4-dioxane
THF
a Reaction conditions: 1a (0.2 mmol, 1.0 equiv), n-BuNH2 (2a; 0.24 mmol, 1.2 equiv), base (2 equiv), solvent (2 mL).
b Yield of isolated product after chromatography.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

C
D. Wang et al.
Paper
Synthesis
DMSO at 140 °C for 20 hours (Table 1, entry 1). Among the
other bases examined, KOt-Bu (entry 8) and NaOH (entry 9)
were proved to be the most efficient bases, providing the
corresponding product in 72% and 85% yield, respectively.
However, NaHCO3, Na2CO3, K2CO3, KOH, K3PO4, and NaOt-Bu
gave diminished yields from 7% to 41% (entries 2–7). A set
of experiments were then carried out to reveal the crucial
role of the reaction temperature (entries 1, 10–12). The re-
sults showed that with the increase of reaction tempera-
ture, much higher yields were obtained for this process
(97% vs 44% at 140 °C and 120 °C, entries 1 and 12). Investi-
gation of the effect of time on the reaction showed that
higher yields can be obtained by prolonging the reaction
time from 8 to 24 hours (entries 13–15). A survey of reac-
tion media showed that the use of polar solvents such as
DMSO, DMF, and DMA provided better results than those
obtained in toluene, 1,4-dioxane, and THF (entries 1, 16–
20). In addition, it is worth noting that the reaction can be
carried out on a 1.0 mmol scale without compromising the
yield. The microwave-assisted tandem cyclization provided
the corresponding product 3aa in 85% yield within 30 min-
utes at 140 °C.
With the optimized reaction conditions in hand, we
then explored the scope and generality of this one-pot tan-
dem reaction. In general, the optimized reaction conditions
(Cs2CO3/DMSO) were broadly applicable and tolerated a
wide variety of substitution patterns and functionalities
(including Me, t-Bu, MeO, F, and Cl). Using n-butylamine
(2a) as the nucleophilic reagent, the scope of (Z)-β-chlor-
ovinyl aromatic ketones was examined first. As revealed in
Table 2, a wide array of ketone substrates 1a–k was amena-
ble to the protocol, delivering N-butyl-4-quinolone deriva-
tives 3aa–ka in good to excellent yields. For substituent R1,
substrates containing either electron-donating (Table 2, en-
tries 2, 3, and 6) or electron-withdrawing groups (entries 4
and 5), or bearing para- (entries 2–4), ortho- (entry 5), or
meta-substituents (entry 6) on the aryl ring can be smooth-
ly converted into the corresponding products in excellent
yields. In addition, this method was compatible with sub-
strates substituted with alkyl groups (entry 7). The influ-
ence of the ortho-substituted halogen on the aromatic ke-
tone moiety was then investigated. All the substrates, with
different halogen substituents such as F, Cl, and Br, smooth-
ly underwent the cyclization to afford the desired product
in high to excellent yields (entries 1–11). Furthermore, di-
halo-substituted ketone substrate 1k afforded the corre-
sponding quinolones 3ka in 83% yield with competitive re-
actions specifically occurring on the fluorine atom (entry
11). The cleavage of aromatic C–O bond from alkyl aryl
ether substrate 1n was investigated, which gave the corre-
sponding cyclized product in 81% yield (entry 12). For sub-
stituent R2, 2-bromo aromatic ketones containing either
electron-donating groups (entries 8 and 9) or an electron-
withdrawing group (entry 10) at the para-position can also
be transformed into the desired products 3ha–ja. Unlike R1,
R2 has much impact on the outcomes of the reaction, with
electron rich aromatics providing higher yields than its
electron-poor analogues (entries 8–10). π-Deficient hetero-
cyclic substrate 1o is also examined, the corresponding
product 3oa can be obtained in high yield (93%, entry 13).
Additionally, 1a can be smoothly converted into the desired
products with other aliphatic amine MeNH2·H2O (2b) (en-
try 14), aniline (2c) (entry 15), and hydroxylamine hydro-
chloride (2f) (entry 16) in 78%, 64%, and 34% yield, respec-
tively.
We then demonstrated the ability of ammonium hy-
droxide as the nucleophile to undergo base-mediated se-
quential Michael addition–elimination–SNAr reaction to
form 4-quinolones. Gratifyingly, a variety of substituents
(such as Me, t-Bu, MeO, F, and Cl) on the substrates 1 were
tolerated and this one-pot tandem protocol was applicable
to the synthesis of N-unsubstituted-4-quinolone deriva-
tives 3ad–kd in 40–83% yields (Scheme 2). Similarly, the
substrates with different halogen leaving groups can be
smoothly transformed to the desired products (3ad–fd, X =
Cl; 3hd and 3jd, X = Br, 3kd, X = F). Dihalo-substituted sub-
strate 1k afforded the cyclized product 3kd in 47% yield
with SNAr specifically occurring on the fluorine atom.
O
X
O
Cl
Cs2CO3, DMSO
140 °, 20 h
R2
R1
aq NH3
+
R2
N
R1
H
X = F, Cl, Br
1
2d
3
O
O
O
N
N
H
N
H
H
Me
t-Bu
3ad, 75%
3bd, 57%
3cd, 69%
O
O
O
Cl
OMe
N
H
N
H
N
H
F
3dd, 65%
3ed, 70%
3fd, 82%
O
O
Cl
O
Me
Cl
N
H
N
H
N
H
3hd, 83%
3jd, 40%
3kd, 47%
Scheme 2 Tandem synthesis of N-unsubstituted-4-quinolone deriva-
tives. Reagents and conditions: 1 (0.2 mmol), NH4OH (2d; 1.0 mmol),
Cs2CO3 (0.4 mmol), DMSO (2 mL), 140 °C, 20 h; yield of isolated prod-
uct after chromatography is shown.
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Synthesis
Table 2 One-Pot Synthesis of N-Substituted-4-quinolone Derivativesa
O
X
O
Cl
Cs2CO3, DMSO
140 °C, 20 h
R2
R3NH2
R1
+
R2
N
R3
R1
X = F, Cl, Br, OMe
1
2
3
Entry
Substrate 1
Amine 2
Product 3
Yield (%)b
O
Cl
O
Cl
1
C4H9NH2 2a
97
N
C4H9
1a
3aa
O
Cl
O
Cl
2
C4H9NH2 2a
96
N
C4H9
Me
1b
Me
3ba
O
Cl
O
Cl
3
4
5
C4H9NH2 2a
C4H9NH2 2a
C4H9NH2 2a
97
61
85
N
t-Bu
C4H9
1c
t-Bu
3ca
O
Cl
O
Cl
N
F
C4H9
1d
F
3da
O
Cl
O
Cl
Cl
Cl
N
C4H9
1e
3ea
O
Cl
O
Cl
OMe
OMe
6
7
C4H9NH2 2a
73
74
N
C4H9
1f
3fa
O
Cl
O
Cl
C4H9NH2 2a
N
C4H9
1g
3ga
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

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Synthesis
Table 2 (continued)
Entry
Substrate 1
Amine 2
Product 3
Yield (%)b
O
Br
O
Cl
Me
8
C4H9NH2 2a
99
N
C4H9
1h
Me
Br
3ha
O
O
Cl
MeO
9
C4H9NH2 2a
70
N
C4H9
1i
OMe
Br
3ia
O
O
Cl
Cl
10
C4H9NH2 2a
58
N
1j
C4H9
Cl
Cl
3ja
Cl
O
N
O
F
Cl
11
12
13
14c
15
C4H9NH2 2a
C4H9NH2 2a
C4H9NH2 2a
MeNH2 2b
PhNH2 2c
83
81
93
78
64
C4H9
3ka
1k
O
OMe
O
Cl
N
C4H9
1n
3na (3aa)
O
Br
O
Cl
N
N
N
C4H9
1o
3oa
O
Cl
O
Cl
N
Me
1a
3ab
O
Cl
O
Cl
N
Ph
1a
3ac
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Synthesis
Entry
Substrate 1
Amine 2
Product 3
Yield (%)b
O
Cl
O
Cl
16d
NH2OH·HCl 2f
34
N
OH
1a
3af
a Reaction conditions: 1 (0.2 mmol), amine 2 (0.24 mmol), Cs2CO3 (0.4 mmol), DMSO (2 mL), 140 °C, 20 h.
b Yield of isolated product after chromatography.
c MeNH2·H2O was used.
d The starting material 1a was recovered in 40% yield.
4H-Thiochromen-4-one can be regarded as the thio ho-
mologue of the core constituent of 4-quinolones and fla-
vones. Such frameworks are as well potential drug candi-
dates as antibacterial,24 antibiotic,25 antimicrobial and anti-
fungal,26 and anticarcinogenic agents27 and serve as
building blocks for the synthesis of biological active mole-
cules. Consequently, the construction of this valuable struc-
tural unit has received considerable attention.28 Finally,
when the scope of nucleophile reagent was extended to so-
dium hydrogen sulfide, a variety of diversely substituted
4H-thiochromen-4-one derivatives can also be smoothly
obtained in good yields under the optimized conditions (Ta-
ble 3). For the olefin-linked aryl moiety, the electronic na-
ture of the aromatic motifs did not seem to affect the effi-
ciency of this transformation, both electron-donating (Table
3, entries 3–5, and 7) and electron-withdrawing (entries 6,
8, and 9) substituents can be incorporated at the para-,
meta-, and ortho-position (48–95% yields). Additionally,
substrate 1g substituted with an alkyl group can smoothly
undergo sequential nucleophilic addition–elimination–
cyclization to afford the desired product in 69% yield (entry
10). For the ketone-linked aryl moiety, substrate 1h with an
electron-donating group provided much higher yield than
1j with an electron-withdrawing group (97% vs 33%, entries
11 and 12).
Table 3 Tandem Synthesis of 4H-Thiochromen-4-one Derivativesa
O
X
O
Cl
Cs2CO3, DMSO
R2
R1
NaSH
+
R2
S
R1
140 °C, 20 h
X = Cl, Br
1
2e
3
Entry Substrates 1
Products 3
Yield (%)b Entry Substrates 1
Products 3
Yield (%)b
O
O
Cl
O
Cl
Me
Cl
O
Cl
Me
1
2
46
95
7
8
86
S
S
1a
1p
3ae
3pe
O
O
Br
O
Cl
Cl
Cl
O
O
Cl
Cl
75
95
S
S
Cl
1l
1q
3qe
3ae
Cl
O
O
Cl
Cl
O
Cl
Cl
3
78
9
S
S
Me
1b
1e
3be
3ee
Me
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Table 3 (continued)
Entry Substrates 1
Products 3
Yield (%)b Entry Substrates 1
Products 3
Yield (%)b
O
O
Cl
O
Cl
Cl
O
Cl
4
5
6
81
73
48
10
11
12
69
S
S
t-Bu
1c
1g
3ce
3ge
t-Bu
OMe
F
O
O
Br
O
Cl
Cl
Cl
O
O
Cl
Cl
Me
97
33
S
S
OMe
1m
3me
1h
3he
Me
Br
O
O
O
Cl
Cl
S
S
F
1j
1d
3de
3je
Cl
a Reaction conditions: 1 (0.2 mmol), NaSH (2e; 0.24 mmol), Cs2CO3 (0.4 mmol), DMSO (2 mL), 140 °C, 20 h.
b Yield of isolated product after chromatography.
Cl
O
Cl
Cl
O
NHPh
Ph
PhNH2 (2c)
Ph
(1)
K2CO3, solvent, 110 °C
H
H
THF: 67%
toluene: 92%
i–1
1a
O
Cl
O
NHPh
Ph
Cs2CO3, DMSO, 12 h, 140 °C
86%
(2)
N
Ph
H
i–1
Ph
3ac
H
R3
R1
X
O
Cl
X
O
N
NHR3
R1
X
O
Cl
R3NH2
elimination
R2
R1
R2
R2
H
nucleophilic addition
R3 = alkyl, aryl, H, OH
4
(Z)-5
1
base
Cs2CO3, DMSO
140 °C, 20 h
Cs2CO3
R1
R3
Cs
O
OCs
X
N
intramolecular
cyclization
O
N
R3
R1
rearomatization
R2
R2
N
R3
R1
X
7
6
3
R2
Scheme 3 Proposed mechanism for sequential nucleophilic addition–elimination–SNAr process
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

H
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Synthesis
To gain further insight into the mechanism of the reac-
tion, two sets of control experiments were conducted. First,
the reaction of 1a and aniline 2c was carried out in THF and
toluene using K2CO3 as the base, to afford the enamine in-
termediate i-1 in 67% and 92% yield, respectively (Scheme 3,
Eq. 1). Second, intermediate i-1 can be efficiently trans-
formed into 4-quinolone 3ac in DMSO with Cs2CO3 as the
base (Scheme 3, Eq. 2). On the basis of the above results, a
proposed reaction mechanism is shown in Scheme 3. The
nucleophilic addition of nucleophiles 2 to (Z)-β-chlorovinyl
aromatic ketone 1 took place to form intermediate 4, which
underwent the elimination of halogen anion in the pres-
ence of a base to give the Z-enamine intermediate 5.14j Sub-
sequently, enolization of the carbonyl group in 5 formed
imine intermediate 6 in the presence of Cs2CO3 and the spe-
cies 7 was generated via intramolecular cyclization of 6. Fi-
nally, rearomatization of 7 by elimination of CsX provided
the target product 3.29
In conclusion, we have developed an efficient protocol
for the one-pot tandem synthesis of 4-quinolone and 4H-
thiochromen-4-one derivatives in good to excellent yields.
The process is based on intermolecular nucleophilic addi-
tion of nucleophiles to (Z)-β-chlorovinyl aromatic ketones
and subsequent elimination of chlorine anion to give Z-
enamines or thioenol intermediates, completed by base-
promoted intramolecular nucleophilic aromatic substitu-
tion. The success of the reaction heavily relies on the careful
selection of proper base and solvent. The use of Cs2CO3 as
the base in polar solvents was found to be essential for the
efficient formation of products. The result presented here
should be of considerable interest for valuable synthetic
drugs for medicinal chemistry.
one (1a; 0.4 mmol, 1.0 equiv), aniline (2c; 0.48 mmol, 1.2 equiv), and
K2CO3 (110.4 mg, 0.8 mmol, 2.0 equiv), then toluene or THF (4.0 mL)
was added via syringe at r.t. The tube was sealed and kept in a pre-
heated oil bath at 110 °C for 12 h. Finally, the mixture was cooled to
r.t., quenched with H2O (5 mL), and diluted with EtOAc (10 mL). The
layers were separated and the aqueous layer was extracted with
EtOAc (2 × 5 mL). The combined organic extracts were dried (anhyd
Na2SO4), filtered, and concentrated in vacuo. The crude product was
then purified by flash chromatography on silica gel (Type H), eluting
with EtOAc/PE (1:20); white solid; yield: 122.5 mg (92%); mp 122–
124 °C.
1H NMR (CDCl3, 400 MHz): δ = 12.65 (s, 1 H), 7.59–7.56 (m, 1 H),
7.43–7.29 (m, 8 H), 7.14 (t, J = 8.0 Hz, 2 H), 7.01 (t, J = 7.2 Hz, 1 H), 6.82
(d, J = 7.6 Hz, 2 H), 5.79 (s, 1 H).
13C NMR (CDCl3, 100 MHz): δ = 190.7, 161.4, 140.9, 139.2, 135.3,
131.0, 130.5, 130.3, 129.9, 129.5, 128.8, 128.6, 128.5, 126.8, 124.5,
123.5, 100.9.
4-Quinolones and 4H-Thiochromen-4-ones 3; General Procedure
A 10 mL Schlenk tube equipped with a magnetic stirring bar was
charged with β-chlorovinyl aromatic ketone 1 (0.2 mmol, 1.0 equiv),
amine 2 (0.24 mmol, 1.2 equiv) or ammonia (2e; 1.0 mmol, 5.0 equiv)
or NaHS (2e; 0.24 mmol, 1.2 equiv), and Cs2CO3 (130.4 mg, 0.4 mmol,
2.0 equiv), then DMSO (2.0 mL) was added via syringe at r.t. The tube
was sealed and kept in a preheated oil bath at 140 °C for 20 h. Finally,
the mixture was cooled to r.t., quenched with H2O (5 mL), and diluted
with EtOAc (10 mL). The layers were separated and the aqueous layer
was extracted with EtOAc (2 × 5 mL). The combined organic extracts
were dried (anhyd Na2SO4), filtered, and concentrated in vacuo. The
crude product was then purified by flash chromatography on silica
gel (Type H), eluting with 20–60% EtOAc/PE.
1-Butyl-2-phenylquinolin-4(1H)-one (3aa)14j,15b
Light yellow solid; yield: 53.7 mg (97%); mp 73–75 °C
1H NMR (400 MHz, CDCl3): δ = 8.52 (d, J = 8.0 Hz, 1 H), 7.69 (t, J = 7.8
Hz, 1 H), 7.55–7.50 (m, 4 H), 7.42–7.39 (m, 3 H), 6.24 (s, 1 H), 4.01 (t,
J = 8.0 Hz, 2 H), 1.69–1.62 (m, 2 H), 1.20–1.11 (m, 2 H), 0.76 (t, J = 8.0
Hz, 3 H).
All chemicals were purchased from commercial supplies and used
without further purification, unless otherwise stated. Solvents were
dried and purified according to the standard procedures before use.
(Z)-β-Chlorovinyl aromatic ketones were prepared from the corre-
sponding acid chlorides and alkynes according the literature meth-
ods.23 All reactions were carried out in dried glassware, and moni-
tored by TLC. Yields refer to isolated yields of compounds. Melting
points were determined on a melting point apparatus in open capil-
laries and are uncorrected. 1H NMR spectra were recorded on a
Bruker 400 or 600 MHz spectrometer and 13C NMR spectra were re-
corded at 100 or 150 MHz. Unless otherwise stated CDCl3 and DMSO-
d6 were used as solvent. Chemical shifts (δ) are given in parts per mil-
lion (ppm) downfield relative to CDCl3 (1H NMR: CDCl3 at 7.26 ppm;
13C NMR: CDCl3 at 77.2 ppm) and DMSO-d6 (1H NMR: DMSO-d6 at
2.50 ppm; 13C NMR: DMSO-d6 at 39.5 ppm). Standard abbreviations
are used to report splitting patterns. Coupling constants are given in
hertz (Hz). High-resolution mass spectra were recorded on a Bruker
BIO TOF Q mass spectrometer.
13C NMR (100 MHz, CDCl3): δ = 177.3, 154.5, 140.6, 136.1, 132.1,
129.4, 128.7, 128.3, 127.4, 127.1, 123.5, 116.3, 112.9, 47.9, 30.8, 19.7,
13.4.
1-Butyl-2-(p-tolyl)quinolin-4(1H)-one (3ba)14j
Yellow solid; yield: 55.9 mg (96%); mp 85–87 °C.
1H NMR (600 MHz, CDCl3): δ = 8.51 (d, J = 7.7 Hz, 1 H), 7.68 (t, J = 7.2
Hz, 1 H), 7.55 (d, J = 8.5 Hz, 1 H), 7.38 (t, J = 6.6 Hz, 1 H), 7.33–7.27 (m,
4 H), 6.23 (s, 1 H), 4.03 (t, J = 7.8 Hz, 2 H), 2.44 (s, 3 H), 1.64 (br, 2 H),
1.17–1.14 (m, 2 H), 0.77 (t, J = 6.9 Hz, 3 H).
13C NMR (150 MHz, CDCl3): δ = 177.3, 154.8, 140.6, 139.4, 133.2,
132.1, 129.4, 128.2, 127.3, 126.9, 123.4, 116.4, 112.9, 47.9, 30.8, 21.4,
19.7, 13.5.
1-Butyl-2-[4-(tert-butyl)phenyl]quinolin-4(1H)-one (3ca)
Light yellow solid; yield: 64.6 mg (97%); mp 140–142 °C.
IR (KBr): 2956, 1624, 1597, 1484, 1421, 1179, 843, 763 cm–1
.
Intermediate (Z)-1-(2-Chlorophenyl)-3-phenyl-3-(phenylami-
1H NMR (400 MHz, CDCl3): δ = 8.51 (d, J = 8.0 Hz, 1 H), 7.70–7.65 (m, 1
H), 7.55–7.48 (m, 3 H), 7.38 (t, J = 7.4 Hz, 1 H), 7.32 (d, J = 7.2 Hz, 2 H),
6.24 (s, 1 H), 4.04 (t, J = 8.0 Hz, 2 H), 1.69–1.61 (m, 2 H), 1.38 (s, 9 H),
1.20–1.11 (m, 2 H), 0.73 (t, J = 7.2 Hz, 3 H).
no)prop-2-en-1-one (i-1)14j
A 10 mL Schlenk tube equipped with a magnetic stirring bar was
charged with (Z)-3-chloro-1-(2-chlorophenyl)-3-phenylprop-2-en-1-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

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D. Wang et al.
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13C NMR (100 MHz, CDCl3): δ = 177.4, 154.8, 152.6, 140.7, 133.1,
132.0, 128.1, 127.4, 127.0, 125.6, 123.4, 116.3, 112.9, 47.8, 34.8, 31.3,
30.7, 19.6, 13.3.
ESI-MS: m/z = 333 [M+], 334 [M + 1]+.
HRMS-ESI: m/z [M + Na]+ calcd for C23H27NONa: 356.1990; found:
1-Butyl-6-methoxy-2-phenylquinolin-4(1H)-one (3ia)14j
Yellow solid; yield: 43 mg (70%); mp 108–111 °C.
1H NMR (600 MHz, CDCl3): δ = 7.91 (s, 1 H), 7.50–7.49 (m, 4 H), 7.40–
7.39 (m, 2 H), 7.32 (d, J = 8.9 Hz, 1 H), 6.23 (s, 1 H), 4.02 (t, J = 7.8 Hz, 2
H), 3.96 (s, 3 H), 1.69–1.60 (m, 2 H), 1.17–1.11 (m, 2 H), 0.75 (t, J = 7.2
Hz, 3 H).
356.1952.
13C NMR (150 MHz, CDCl3): δ = 176.7, 156.1, 153.7, 136.1, 135.2,
129.4, 128.7, 128.6, 128.4, 122.9, 118.1, 111.9, 105.8, 55.9, 48.1, 31.0,
19.7, 13.4.
1-Butyl-2-(4-fluorophenyl)quinolin-4(1H)-one (3da)9h,14j
Yellow solid; yield: 36 mg (61%); mp 98–100 °C.
1H NMR (400 MHz, CDCl3): δ = 8.50 (d, J = 8.0 Hz, 1 H), 7.69 (t, J = 7.8
Hz, 1 H), 7.54 (d, J = 8.7 Hz, 1 H), 7.43–7.16 (m, 5 H), 6.20 (s, 1 H), 4.01
(t, J = 8.0 Hz, 2 H), 1.68–1.61 (m, 2 H), 1.22–1.13 (m, 2 H), 0.78 (t, J =
7.3 Hz, 3 H).
1-Butyl-6-chloro-2-phenylquinolin-4(1H)-one (3ja)14j
Yellow solid; yield: 36 mg (58%); mp 87–89 °C.
1H NMR (400 MHz, CDCl3): δ = 8.46 (s, 1 H), 7.61 (d, J = 8.0 Hz, 1 H),
7.51–7.47 (m, 4 H), 7.40–7.38 (m, 2 H), 6.22 (s, 1 H), 4.00 (t, J = 8.0 Hz,
2 H), 1.67–1.59 (m, 2 H), 1.19–1.10 (m, 2 H), 0.76 (t, J = 7.2 Hz, 3 H).
13C NMR (150 MHz, CDCl3): δ = 176.1, 154.8, 139.0, 135.7, 132.4,
129.8, 129.6, 128.8, 128.4, 128.3, 126.3, 118.2, 113.1, 48.2, 30.7, 19.6,
13.4.
13C NMR (CDCl3, 100 MHz): δ = 177.3, 163.2 (d, 1JC,F = 249 Hz), 153.5,
4
3
140.6, 132.3, 132.1 (d, JC,F = 3.0 Hz), 130.3 (d, JC,F = 8.0 Hz), 127.4,
2
127.1, 123.7, 116.2, 115.9 (d, JC,F = 22.0 Hz), 113.1, 47.9, 30.8, 19.7,
13.4.
1-Butyl-2-(2-chlorophenyl)quinolin-4(1H)-one (3ea)9h,14j
White solid; yield: 52.9 mg (85%); mp 141–143 °C.
1-Butyl-5-chloro-2-phenylquinolin-4(1H)-one (3ka)
1H NMR (600 MHz, CDCl3): δ = 8.53 (d, J = 7.9 Hz, 1 H), 7.71 (t, J = 7.9
Hz, 1 H), 7.55–7.52 (m, 2 H), 7.47 (t, J = 7.2 Hz, 1 H), 7.44–7.40 (m, 3
H), 6.19 (s, 1 H), 4.14–4.07 (m, 1 H), 3.78–3.73 (m, 1 H), 1.79–1.71 (m,
1 H), 1.56–1.49 (m, 1 H), 1.22–1.11 (m, 2 H), 0.75 (t, J = 7.3 Hz, 3 H).
13C NMR (150 MHz, CDCl3): δ = 177.6, 151.2, 140.4, 134.8, 132.9,
132.3, 131.0, 130.6, 129.9, 127.4, 127.2, 127.1, 123.6, 116.2, 112.8,
47.7, 30.4, 19.7, 13.4.
Yellow solid; yield: 49 mg (83%); mp 164–166 °C.
IR (KBr): 2958, 2929, 1624, 1590, 1465, 1397, 1066 cm–1
.
1H NMR (600 MHz, CDCl3): δ = 7.52–7.49 (m, 4 H), 7.44 (d, J = 8.0 Hz, 1
H), 7.41–7.37 (m, 2 H), 7.35 (d, J = 7.6 Hz, 1 H), 6.21 (s, 1 H), 3.98 (t, J =
8.0 Hz, 2 H), 1.64–1.59 (m, 2 H), 1.16–1.08 (m, 2 H), 0.74 (t, J = 7.4 Hz,
3 H).
13C NMR (150 MHz, CDCl3): δ = 176.9, 153.4, 143.2, 135.6, 134.9,
131.1, 129.5, 128.8, 128.3, 126.6, 124.0, 115.4, 115.1, 48.7, 30.4, 19.6,
13.4.
1-Butyl-2-(3-methoxyphenyl)quinolin-4(1H)-one (3fa)14j
Yellow solid; yield: 44.8 mg (73%); mp 97–99 °C.
ESI-MS: m/z = 311 [M+], 312 [M + 1]+.
HRMS-ESI: m/z [M + Na]+ calcd for C19H18ClNONa: 334.0975; found:
1H NMR (400 MHz, CDCl3): δ = 8.52 (d, J = 8.0 Hz, 1 H), 7.69 (t, J = 7.7
Hz, 1 H), 7.54 (d, J = 8.7 Hz, 1 H), 7.40 (t, J = 7.8 Hz, 2 H), 7.04–6.92 (m,
3 H), 6.25 (s, 1 H), 4.03 (t, J = 8.0 Hz, 2 H), 3.86 (s, 3 H), 1.72–1.64 (m, 2
H), 1.21–1.15 (m, 2 H), 0.79 (t, J = 7.2 Hz, 3 H).
13C NMR (150 MHz, CDCl3): δ = 177.4, 159.6, 154.4, 140.6, 137.2,
132.2, 129.9, 127.4, 127.1, 123.6, 120.6, 116.3, 114.9, 114.0, 112.6,
55.5, 48.0, 30.9, 19.7, 13.5.
334.0987.
1-Butyl-2-phenyl-1,8-naphthyridin-4(1H)-one (3oa)
Yellow solid; yield: 51.7 mg (93%); mp 112–113 °C.
IR (KBr): 3056, 2960, 1639, 1592, 1489, 1412, 1257, 708 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.76–8.73 (m, 2 H), 7.57–7.46 (m, 3 H),
7.46–7.37 (m, 2 H), 7.46–7.38 (m, 2 H), 7.34 (dd, J = 7.7, 4.6 Hz, 1 H),
6.26 (s, 1 H), 4.29 (t, J = 7.2 Hz, 2 H), 1.79–1.36 (m, 2 H), 1.31–0.95 (m,
2 H), 0.71 (t, J = 7.4 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 177.6, 155.4, 152.1, 150.6, 135.7,
135.6, 129.5, 128.6, 128.3, 121.6, 119.6, 113.5, 46.5, 31.5, 19.7, 13.4.
1,2-Dibutylquinolin-4(1H)-one (3ga)14j
Yellow solid; yield: 38 mg (74%); mp 91–9 °C.
1H NMR (400 MHz, CDCl3): δ = 8.46 (d, J = 8.0 Hz, 1 H), 7.64 (t, J = 7.8
Hz, 1 H), 7.49 (d, J = 8.7 Hz, 1 H), 7.34 (t, J = 7.4 Hz, 1 H), 6.27 (s, 1 H),
4.13 (t, J = 8.0 Hz, 2 H), 2.69 (t, J = 7.7 Hz, 2 H), 1.82–1.65 (m, 4 H),
1.54–1.44 (m, 4 H), 1.06–0.96 (m, 6 H).
ESI-MS: m/z = 278 [M+], 279 [M + 1]+.
13C NMR (150 MHz, CDCl3): δ = 177.7, 154.6, 140.8, 132.0, 126.9,
HRMS-ESI: m/z [M + H]+ calcd for C18H19N2O: 279.1497; found:
126.8, 123.2, 115.6, 110.9, 46.0, 33.6, 31.0, 30.9, 22.5, 20.0, 13.8, 13.7.
279.1493.
1-Butyl-6-methyl-2-phenylquinolin-4(1H)-one (3ha)14j
1-Methyl-2-phenylquinolin-4(1H)-one (3ab)14j,30a
Light yellow solid; yield: 57.6 mg (99%); mp 110–112 °C.
White solid; yield: 36.7 mg (78%); mp 61–63 °C.
1H NMR (400 MHz, CDCl3): δ = 8.31 (s, 1 H), 7.54–7.42 (m, 5 H), 7.42–
7.35 (m, 2 H), 6.21 (s, 1 H), 4.00 (t, J = 8.0 Hz, 2 H), 2.48 (s, 3 H), 1.67–
1.60 (m, 2 H), 1.19–1.10 (m, 2 H), 0.75 (t, J = 7.3 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 177.2, 154.2, 138.7, 136.2, 133.6,
133.4, 129.3, 128.7, 128.3, 127.3, 126.3, 116.2, 112.6, 47.9, 30.8, 20.8,
19.7, 13.4.
1H NMR (400 MHz, CDCl3): δ = 8.50 (d, J = 7.0 Hz, 1 H), 7.71–7.69 (m, 1
H), 7.56–7.41 (m, 7 H), 6.29 (s, 1 H), 3.60 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 177.5, 154.7, 141.9, 135.9, 132.3,
129.6, 128.8, 128.6, 126.9, 126.7, 123.6, 116.0, 112.7, 37.3.
1,2-Diphenylquinolin-4(1H)-one (3ac)14j,15b
White solid; yield: 38 mg (64%); mp 279–281 °C.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

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D. Wang et al.
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1H NMR (600 MHz, CDCl3): δ = 8.51 (d, J = 7.9 Hz, 1 H), 7.46 (t, J = 7.5
Hz, 1 H), 7.37–7.31 (m, 4 H), 7.19–7.15 (m, 7 H), 6.91 (d, J = 8.6 Hz, 1
H), 6.44 (s, 1 H).
1H NMR (600 MHz, DMSO-d6): δ = 11.96 (s, 1 H), 8.07 (d, J = 8.0 Hz, 1
H), 7.63–7.54 (m, 4 H), 7.52 (t, J = 7.1 Hz, 1 H), 7.46 (t, J = 7.4 Hz, 1 H),
7.30 (t, J = 7.4 Hz, 1 H), 5.98 (s, 1 H).
13C NMR (150 MHz, CDCl3): δ = 177.9, 154.0, 142.6, 139.1, 135.7,
131.9, 130.0, 129.6, 129.2, 129.0, 128.6, 127.9, 126.2, 126.1, 123.8,
118.1, 112.5.
13C NMR (150 MHz, DMSO-d6): δ = 176.8, 148.2, 140.1, 133.9, 132.0,
131.7, 131.5, 131.1, 129.8, 129.0, 127.6, 124.8, 123.4, 118.5, 109.8.
2-(3-Methoxyphenyl)quinolin-4(1H)-one (3fd)14d
2-Phenylquinolin-4(1H)-one (3ad)9d,15a,30b
Yellow solid; yield: 41.2 mg (82%); mp 242–244 °C.
Light yellow solid; yield: 33 mg (75%); mp 256–258 °C.
1H NMR (600 MHz, DMSO-d6): δ = 11.70 (s, 1 H), 8.11 (d, J = 8.0 Hz, 1
H), 7.78 (d, J = 8.3 Hz, 1 H), 7.69 (t, J = 7.6 Hz, 1 H), 7.52 (t, J = 7.9 Hz, 1
H), 7.41–7.34 (m, 3 H), 7.16 (d, J = 8.0 Hz, 1 H), 6.37 (s, 1 H), 3.88 (s, 3
H).
1H NMR (600 MHz, DMSO-d6): δ = 11.79 (br, 1 H), 8.07 (d, J = 7.8 Hz, 1
H), 7.79–7.77 (m, 2 H), 7.74 (d, J = 8.3 Hz, 1 H), 7.65–7.61 (m, 1 H),
7.56–7.49 (m, 3 H), 7.30 (t, J = 7.2 Hz, 1 H), 6.33 (s, 1 H).
13C NMR (150 MHz, DMSO-d6): δ = 176.8, 150.3, 140.6, 134.1, 131.9,
130.5, 129.0, 127.4, 124.7, 124.6, 123.4, 118.9, 107.2.
13C NMR (150 MHz, CDCl3): δ = 182.2, 164.8, 155.0, 145.7, 140.8,
137.1, 130.1, 128.6, 128.4, 125.0, 124.7, 124.0, 118.1, 117.9, 112.7,
60.6.
N-Hydroxy-2-phenylquinolin-4(1H)-one (3ae)30c
6-Methyl-2-phenylquinolin-4(1H)-one (3hd)9d,30b
Light yellow solid; yield: 16.2 mg (34%); mp 226–228 °C.
Yellow solid, yield: 39 mg (83%); mp 290–292 °C.
1H NMR (400 MHz, DMSO-d6): δ = 11.67 (s, 1 H), 7.91–7.83 (m, 3 H),
7.69–7.51 (m, 5 H), 6.31 (s, 1 H), 2.43 (s, 3 H).
1H NMR (400 MHz, DMSO-d6): δ = 12.10 (br, 1 H), 8.12 (d, J = 7.9 Hz, 1
H), 7.95–7.89 (m, 3 H), 7.66 (t, J = 7.5 Hz, 1 H), 7.56 (br, 3 H), 7.33 (t, J =
7.4 Hz, 1 H), 6.41 (s, 1 H).
13C NMR (151 MHz, DMSO-d6): δ = 176.5, 150.4, 141.1, 134.4, 131.5,
13C NMR (150 MHz, DMSO-d6): δ = 176.8, 149.6, 138.6, 134.3, 133.2,
130.3, 128.9, 127.5, 124.8, 124.6, 123.2, 119.4, 107.0.
132.5, 130.4, 129.0, 127.4, 124.8, 124.0, 118.6, 107.0, 20.8.
2-(p-Tolyl)quinolin-4(1H)-one (3bd)30d
6-Chloro-2-phenylquinolin-4(1H)-one (3jd)30e,f
Light yellow solid; yield: 26.8 mg (57%); mp 287–289 °C.
Light yellow solid; yield: 20.4 mg (40%); mp 348–350 °C.
1H NMR (400 MHz, DMSO-d6): δ = 11.65 (s, 1 H), 8.10 (d, J = 7.6 Hz, 1
H), 7.79–7.73 (m, 3 H), 7.69–7.65 (m, 1 H), 7.40 (d, J = 8.0 Hz, 2 H),
7.34 (t, J = 7.4 Hz, 1 H), 6.33 (d, J = 1.4 Hz, 1 H), 2.41 (s, 3 H).
1H NMR (600 MHz, DMSO-d6): δ = 11.91 (s, 1 H), 8.04 (d, J = 2.4 Hz, 1
H), 7.86–7.80 (m, 3 H), 7.75–7.73 (m, 1 H), 7.62–7.61 (m, 3 H), 6.40 (s,
1 H).
13C NMR (101 MHz, CDCl3): δ = 182.2, 155.1, 145.7, 145.6, 137.0,
13C NMR (150 MHz, DMSO-d6): δ = 175.7, 150.4, 139.1, 133.9, 132.0,
136.5, 134.8, 132.5, 130.1, 129.9, 128.4, 123.9, 112.2, 26.1.
130.7, 129.0, 127.9, 127.5, 125.9, 123.7, 121.2, 107.5.
2-[4-(tert-Butyl)phenyl]quinolin-4(1H)-one (3cd)
5-Chloro-2-phenylquinolin-4(1H)-one (3kd)
Light yellow solid; yield: 38.2 mg (69%); mp 297–299 °C.
Yellow solid; yield: 22.5 mg (47%); mp 296–298 °C.
IR (KBr): 3435, 2924, 1635, 1498, 1048, 668 cm–1
.
IR (KBr): 3439, 2923, 2852, 1634, 1605, 1591, 1548, 1506 cm–1
.
1H NMR (400 MHz, DMSO-d6): δ = 11.66 (s, 1 H), 8.10 (d, J = 8.0 Hz, 1
H), 7.76 (t, J = 7.5 Hz, 3 H), 7.67 (t, J = 7.5 Hz, 1 H), 7.62 (d, J = 8.2 Hz, 2
H), 7.34 (t, J = 7.5 Hz, 1 H), 6.33 (s, 1 H), 1.35 (s, 9 H).
1H NMR (600 MHz, DMSO-d6): δ = 11.85 (s, 1 H), 7.87–7.85 (m, 2 H),
7.81 (d, J = 8.3 Hz, 1 H), 7.58–7.54 (m, 4 H), 7.28 (d, J = 7.6 Hz, 1 H),
6.36 (s, 1 H).
13C NMR (151 MHz, CDCl3): δ = 182.2, 158.5, 155.2, 145.7, 136.9,
13C NMR (150 MHz, DMSO-d6): δ = 175.9, 149.3, 143.8, 133.8, 131.7,
136.7, 132.6, 132.3, 131.2, 131.1, 130.9, 130.1, 112.3, 39.9, 36.2.
131.3, 130.4, 128.9, 127.4, 125.7, 120.9, 118.9, 109.1.
ESI-MS: m/z = 277 [M+], 278 [M + 1]+.
ESI-MS: m/z = 255 [M+], 256 [M + 1]+.
HRMS-ESI: m/z [M + Na]+ calcd for C19H19NONa: 300.1364; found:
HRMS-ESI: m/z [M + Na]+ calcd for C15H10ClNONa: 278.0349; found:
300.1334.
278.0357.
2-(4-Fluorophenyl)quinolin-4(1H)-one (3dd)30d
2-Phenyl-4H-thiochromen-4-one (3ae)28b,c
Light yellow solid; yield: 31.1 mg (65%); mp 322–325 °C.
Yellow solid; yield: 21.9 mg (46%, Table 3, entry 1) and 45.2 mg (95%,
Table 3, entry 2); mp 125–126 °C.
1H NMR (400 MHz, CDCl3): δ = 8.55 (d, J = 7.9 Hz, 1 H), 7.70–7.60 (m, 4
1H NMR (400 MHz, DMSO-d6): δ = 11.73 (s, 1 H), 8.11 (d, J = 7.4 Hz, 1
H), 7.93–7.90 (m, 2 H), 7.77–7.75 (m, 1 H), 7.70–7.67 (m, 1 H), 7.47–
7.43 (m, 2 H), 7.37–7.33 (m, 1 H), 6.34 (s, 1 H).
H), 7.57–7.50 (m, 4 H), 7.24 (s, 1 H).
1
13C NMR (150 MHz, DMSO-d6): δ = 176.9, 163.3 (d, JC,F = 248 Hz),
13C NMR (150 MHz, CDCl3): δ = 180.9, 153.1, 137.7, 136.6, 131.6,
130.9, 130.9, 129.3, 128.6, 127.8, 127.0, 126.5, 123.5.
149.0, 140.4, 131.9, 130.6 (d, 4JC,F = 3 Hz), 129.9 (d, 3JC,F = 9 Hz), 124.8,
124.7, 123.3, 118.7, 116.0 (d, 2JC,F = 23 Hz), 107.4.
2-(p-Tolyl)-4H-thiochromen-4-one (3be)30g
2-(2-Chlorophenyl)quinolin-4(1H)-one (3ed)9d,14d
Yellow solid; yield: 39.3 mg (78%); mp 118–119 °C.
Yellow solid, yield: 35.7 mg (70%); mp 208–210 °C.
1H NMR (400 MHz, CDCl3): δ = 8.54 (d, J = 8.0 Hz, 1 H), 7.67–7.51 (m, 5
H), 7.30 (d, J = 8.0 Hz, 2 H), 7.23 (s, 1 H), 2.43 (s, 3 H).
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13C NMR (100 MHz, CDCl3): δ = 180.9, 153.1, 141.3, 137.7, 133.8,
13C NMR (150 MHz, CDCl3): δ = 180.7, 156.6, 137.8, 131.3, 131.0,
131.5, 131.0, 123.0, 128.6, 127.7, 126.8, 126.5, 122.9, 21.4.
128.6, 127.5, 126.2, 124.1, 37.2, 31.9, 22.0, 13.8.
2-[4-(tert-Butyl)phenyl]-4H-thiochromen-4-one (3ce)28c
6-Methyl-2-phenyl-4H-thiochromen-4-one (3he)30c
Yellow solid; yield: 47.6 mg (81%); mp 101–103 °C.
Light yellow solid; yield: 48.9 mg (97%); mp 150–152 °C.
1H NMR (600 MHz, CDCl3): δ = 8.46 (d, J = 8.0 Hz, 1 H), 7.56–7.53 (m, 3
1H NMR (400 MHz, CDCl3): δ = 8.35 (s, 1 H), 7.70–7.64 (m, 2 H), 7.55–
H), 7.52 (t, J = 6.7 Hz, 1 H), 7.47–7.43 (m, 3 H), 7.17 (s, 1 H), 1.28 (s, 9
7.42 (m, 5 H), 7.22 (s, 1 H), 2.48 (s, 3 H).
H).
13C NMR (150 MHz, CDCl3): δ = 180.9, 153.0, 138.1, 136.7, 134.7,
133.0, 130.8, 130.7, 129.3, 128.3, 127.0, 126.4, 123.3, 21.4.
13C NMR (151 MHz, CDCl3): δ = 179.9, 153.4, 152.0, 136.7, 132.6,
130.5, 129.9, 127.5, 126.6, 125.6, 125.4, 125.2, 121.8, 33.9, 30.1.
6-Chloro-2-phenyl-4H-thiochromen-4-one (3je)28a
2-(4-Methoxyphenyl)-4H-thiochromen-4-one (3me)28b,c
White solid; yield: 18 mg (33%); mp 189–191 °C.
Yellow solid; yield: 39.1 mg (73%); mp 125–127 °C.
1H NMR (400 MHz, CDCl3): δ = 8.53 (d, J = 7.9 Hz, 1 H), 7.68–7.58 (m, 4
1H NMR (400 MHz, CDCl3): δ = 8.53 (s, 1 H), 7.69 (d, J = 8.0 Hz, 2 H),
7.63–7.58 (m, 2 H), 7.53–7.52 (m, 3 H), 7.25 (s, 1 H).
H), 7.56–7.51 (m, 1 H), 7.20 (s, 1 H), 7.01 (d, J = 8.7 Hz, 2 H), 3.87 (s, 3
H).
13C NMR (100 MHz, CDCl3): δ = 180.9, 161.9, 152.7, 137.6, 131.5,
13C NMR (150 MHz, CDCl3): δ = 179.7, 153.3, 136.3, 135.8, 134.4,
132.1, 132.0, 131.1, 129.4, 128.3, 128.0, 127.0, 123.3.
130.9, 128.9, 128.6, 128.3, 127.6, 126.4, 122.2, 114.7, 55.5.
Funding Information
2-(4-Fluorophenyl)-4H-thiochromen-4-one (3de)28b,l
31300286We are grateful for the financial support from the Funda-
mental Research Funds for the Central Universities (2572015EB02)
and the National Natural Science Foundation of China (31400294 and
Yellow solid; yield: 24.6 mg (48%); mp 158–160 °C.
1H NMR (600 MHz, CDCl3): δ = 8.55 (d, J = 8.0 Hz, 1 H), 7.70–7.63 (m, 4
H), 7.56 (t, J = 7.3 Hz, 1 H), 7.22–7.17 (m, 3 H).
31300286).
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13C NMR (150 MHz, CDCl3): δ = 180.80, 164.3 (d, JC,F = 251 Hz),
1
151.81, 137.45, 132.7 (d, 4JC,F = 3 Hz), 131.74, 130.83, 129.0 (d, 3JC,F = 9
Hz), 128.66, 127.92, 126.48, 123.48, 116.5 (d, 2JC,F = 22.5 Hz).
Supporting Information
Supporting information for this article is available online at
2-(o-Tolyl)-4H-thiochromen-4-one (3pe)30h
https://doi.org/10.1055/s-0036-1588466.
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Yellow solid; yield: 43.4 mg (86%); mp 96–98 °C.
1H NMR (600 MHz, CDCl3): δ = 8.58 (d, J = 8.0 Hz, 1 H), 7.65–7.60 (m, 2
H), 7.56 (t, J = 6.6 Hz, 1 H), 7.39–7.27 (m, 4 H), 6.92 (s, 1 H), 2.39 (s, 3
H).
References
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19.9.
2-(4-Chlorophenyl)-4H-thiochromen-4-one (3qe)28c,30g,i
White solid; yield: 40.8 mg (75%); mp 166–168 °C.
1H NMR (600 MHz, CDCl3): δ = 8.53 (d, J = 8.0 Hz, 1 H), 7.66–7.60 (m, 4
H), 7.55 (t, J = 7.2 Hz, 1 H), 7.47 (d, J = 7.6 Hz, 2 H), 7.19 (s, 1 H).
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131.8, 130.8, 129.6, 128.7, 128.2, 128.0, 126.5, 123.6.
2-(2-Chlorophenyl)-4H-thiochromen-4-one (3ee)30g
White solid; yield: 51.7 mg (95%); mp 129–130 °C.
1H NMR (400 MHz, CDCl3): δ = 8.58 (d, J = 8.0 Hz, 1 H), 7.66–7.60 (m, 2
H), 7.58–7.54 (m, 1 H), 7.53–7.51 (m, 1 H), 7.46–7.35 (m, 3 H), 7.02 (s,
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2-Butyl-4H-thiochromen-4-one (3ge)28c
Yellow solid; yield: 30.1 mg (69%); mp 95–97 °C.
1H NMR (600 MHz, CDCl3): δ = 8.50 (d, J = 8.0 Hz, 1 H), 7.59–7.57 (m, 2
H), 7.53–7.48 (m, 1 H), 6.87 (s, 1 H), 2.68 (t, J = 7.6 Hz, 2 H), 1.75–1.70
(m, 2 H), 1.46–1.39 (m, 2 H), 0.96 (t, J = 7.3 Hz, 3 H).
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L