Iron-catalyzed regioselective direct arylation at the C-3 position of N-alkyl-2-pyridone

Article abstract of DOI:10.1021/jo502362k

A number of pharmaceutical compounds possess an arylated 2-pyridone moiety. The existing reports using expensive starting materials and/or superstoichiometric metal salts have prompted us to explore a possible user-friendly method for their synthesis. In this report, we demonstrate an easy-to-handle reaction condition with an iron catalyst for the exclusive generation of C-3-arylated pyridone via C-H functionalization.

Full text of DOI:10.1021/jo502362k

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Article
Iron catalysed regioselective direct arylation
at C-3 position of N-alkyl-2-pyridone
Atanu Modak, Sujoy Rana, and Debabrata Maiti
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/jo502362k • Publication Date (Web): 25 Nov 2014
Downloaded from http://pubs.acs.org on November 29, 2014
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Iron catalysed regioselective direct arylation at C-3 position of N-
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alkyl-2-pyridone
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Atanu Modak, Sujoy Rana and Debabrata Maiti*
Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai, 400076,
India
*Email: dmaiti@chem.iitb.ac.in
TABLE OF CONTENTS
H
O
Ar
O
ArB(OH)2, [Fe]
regioselective
direct arylation
N
N
R'
R'
R' = H, alkyl
ABSTRACT
A number of pharmaceutical compounds possess arylated-2-pyridone moiety. The
existing reports using expensive starting materials and/or superstoichiometric metal salts have
prompted us to explore the possible user-friendly method for their synthesis. In this report, we
have demonstrated an easy-to-handle reaction condition with iron catalyst for the exclusive
generation of C3-arylated pyridone via C-H functionalization.
INTRODUCTION
Functionalization of pyridone core has drawn serious attention in recent years primarily due
to its presence as building block in a number of pharmaceutical compounds (Figure 1).1
A
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regioselective direct C–H functionalization protocol for the synthesis of pyridine derivatives is
preferred over the conventional coupling reaction (e.g. Suzuki coupling) as it avoids the use of a
pre-functionalized substrate.2 Recently, direct olefination and arylation at electron rich C-5
position of 2-pyridone were achieved through palladium catalyst.3, 4 Hiyama group reported
direct alkylation and alkenylation at electrophilic C-6 position of 2-pyridone by using nickel
catalyst in combination with Lewis acid.5 Miura and coworkers developed a copper mediated
selective C-6 dehydrogenative heteroarylation protocol for 1-(2-pyridyl)-2-pyridone.6 By
blocking C-5 position, C-3 was alkenylated and arylated with structurally biased substrates.4,7
Very recently Zografos and coworkers reported a palladium catalyzed selective C-3 arylation of
N-protected pyridone, but scope of the method was limited to only 4-hydoxy-pyridone moiety.8
Hirano and Miura reported alternative pathways for C-3 alkylation and arylation of 2-pyridone
through homolytic radical aromatic substitution (HAS).9 Although the alkylation at C-3 position
was achieved with catalytic amount of nickel,9a the C-3 arylation required superstoichiometric
amount of manganese salt with boronic acid as the coupling partner.9b
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Iron catalyzed direct arylation of heterocycles and quinones has recently been reported by
Komeyama’s group by using arylboronic acids.10 We have also independently reported similar
arylation reactions involving heterocycles and quinones.11 Unfortunately, when our reaction
condition was applied to N-methyl-2-pyridone, only 7% arylated pyridone was obtained.
Notably, Wunk has recently reported two examples of Pd catalyzed C3-arylated pyridone
starting from 3-bromopyridone (Scheme 1).12 In this work, we demonstrate an easy-to-handle
reaction condition for the generation of C3-arylated pyridine exclusively. Notable features of the
present methodology include the use of easily available pyridone precursors in combination with
iron catalyst under mild reaction protocols.
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RESULTS AND DISCUSSION
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Figure 1. Drug molecules with 3-aryl-2-pyridone motifs
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Initial studies with N-methyl-2-pyridone and phenylboronic acid in the presence of
Fe(NO3)3/K2S2O8 in TFT:H2O (1:1) (TFT = α,α,α-trifluorotoluene) at 70 ºC led to the formation
of only one pyridone-arylated product (isolated yield, 9%).13
Scheme 1. Pathways for C-3 arylation of N-alkyl-2-pyridone
ArB(OH)2, Pd cat.
ArB(OH)2,
Suzuki coupling
stoichometric Mn salt
X = Br,I
Ref. 9b
H
O
X
Ar
O
N
N
O
N
HetAr-H, Pd cat.
R' = H; X = Br
R'
R'
R'
ArB(OH)2, Fe cat.
this work
Ref. 12
Table 1. C-3 arylation of N-methyl-2-pyridone
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entry
solvent
additive metal catalyst time (h) yielda (%)
5
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9
1
2
TFT:H2O (1:1)
TFT:H2O (1:1)
DCE:H2O (1:1)
DCE:H2O(1:1)
DCE:H2O(1:1)
DCE:H2O (1:1)
DCE:H2O(1:1)
DCE:H2O(1:1)
DCE:H2O(1:1)
DCE:H2O(1:1)
DCE:H2O(1:1)
TFA
-
Fe(NO3)3
Fe(NO3)3
Fe(NO3)3
Fe(NO3)3
Fe(NO3)3
Fe(NO3)3
-
24
24
24
24
24
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3
-
14
40
0*
40
22
0
4
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
5
6
7
8
AgNO3
9
Pd(OAc)2
Cu(OAc)2
Ni(acac)2
<1
13
20
10
11
*without K2S2O8; aGC yield.
By NMR and X-ray crystallography (vide infra), we confirmed that arylation was occurring
at the C-3 position exclusively.14 These promising initial results had prompted us to explore the
reaction with different solvent combinations, iron sources, ligands, additives and bases.15 A 40%
GC yield (isolated, 38%) of C-3 arylated product (Table 1, entry 6) was obtained with
Fe(NO3)3.9H2O/K2S2O8. The yield of C-3 arylated product, however failed to improve further
inspite of our best efforts. Starting materials mostly remained unreacted and homo-coupling of
arylboronic acid was obtained as the side product.
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The aforesaid optimized reaction protocol was then extended for the reaction of 4-methyl
phenylboronic acid (Table 2). Various N-alkylated pyridones gave desired arylated product in
44-54% yield (1-3). By varying the N-protecting group from alkyl to allyl, we obtained the C-3
arylated product 4 in 47% yield. In case of N-phenethyl-2-pyridone, C3-arylation decreased to
24% (5) and N-(4-cyanophenyl)-2-pyridone failed to increase the C3-arylation (6) as well.
Although N-acyl-2-pyridone did not deliver any C3-arylation product (7), 2-pyridone moiety
(without N-protection) afforded 34% yield of C-3 arylated product (8) selectively.
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Table 2. C-3 arylation with various N-alkyl-2-pyridones
Me
B(OH)2
Fe(NO3)3. 9H2O (10 mol%)
K2S2O8 (4 eq.), K2CO3 (1.5 eq.)
+
N
O
DCE:H2O (1:1) (2 mL), air
12 h, 70 °C
R1
N
O
Me
0.75 mmol
R1
0.25 mmol
isolated
Me
Me
Me
Me
N
O
N
O
N
O
N
O
Me
Me
(X-ray)
Me
2, 49%
3, 44%
4, 47%
1, 54%
Me
Me
Me
Me
N
O
N
O
N
O
N
O
H
Me
O
(without N-protection)
8, 34%
Ph
7, 0%
6, 19%
5, 24%
CN
Subsequently, the scope of the selective C-3 arylation on N-alkyl-2-pyridone with different
arylboronic acids was investigated (Table 3). Electron rich 4-methoxyarylboronic acid provided
the desired C-3 arylated product in 47% yield (10). Halo-aryl moieties were introduced at the C-
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3 position (11-13 and 19), with the intension of further functionalization. Electron poor boronic
acids also afforded arylation exclusively at the C-3 position of pyridone (13 and 14).
Additionally, sterically constrained ortho-tolylboronic acid gave the arylated pyridone 16.
Interestingly, a dibenzofuran moiety can also be coupled at the C-3 position of pyridone using
dibenzofuran-4-boronic acid as heterocyclic partner (17). Electron-withdrawing arylboronic
acids encompassing 4-NO2, 4-COMe and 4-CO2Me groups yielded very little C–C coupled
product with N-methyl-2-pyridone. Nevertheless, 3-(methoxycarbonyl) phenylboronic acid gave
the desired product in 9% yield (15).
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Table 3. C-3 arylation of N-alkyl-2-pyridones with arylboronic acids
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Fe(NO3)3. 9H2O (10 mol%)
K2S2O8 (4 eq.), K2CO3 (1.5 eq.)
B(OH)2
R2
+
DCE:H2O (1:1) (2 mL), air
12 h, 70 °C
N
O
N
O
R2
0.75 mmol
R1
0.25 mmol
isolated
R1
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Cl
I
F
OMe
N
O
N
O
N
O
N
O
N
O
(X-ray)
Me
Me
Me
Me
Me
13, 39%
9, 38%
10, 47%
11, 24%
12, 26%
CF3
CO2Me
Me
O
O
N
Me
N
O
N
O
N
O
Me
Me
Me
17, 24%
15, 9%
16, 35%
14, 22%
Me
Br
N
O
N
O
N
O
N
O
N
O
Me
Me
Me
Me
21, 31%
19, 26% 20, 45%
22, 30%
18, 32%
The applicability of the present method with different functionalized N-methyl pyridone entity
was also tested (Table 4). The C-6 (23-25) and C-5 (26-28) substituted N-methyl-2-pyridones
were successfully arylated. Notably, various chloro substituted pyridones could be employed for
C-3 arylation (24, 26 and 28). Expectedly, methylquinolin-2(1H)-one moieties was arylated at
the desired C-3 position (30-31).
Table 4 C-3 arylation of substituted N-methyl-2-pyridones
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Furthermore, a 10 mmol scale reaction under reflux conditions afforded the product in
35% yield (Scheme 2; also see Table 3, entry 9). Anti-inflammatory agent 1-methyl-3-
phenylpiperidin-2-one (32) was successfully prepared after hydrogenation of 9 (Scheme 2).15
We have also synthesized 3-(2-methoxyphenyl)quinolin-2(1H)-one (33, Scheme 2), which can
be further utilized as the precursor in generating pharmaceutically relevant benzofuro[2,3-
b]quinoline moiety through successive cyclization reaction.16
Scheme 2. Large scale reaction and application in pharmaceutically relevant scaffolds
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cyclization
2-OMePhB(OH)2
O
this work
N
O
Me
N
O
O
N
H
H
(without N-protection)
33, 26%
Table 5. Radical scavenger experiments
Entry
Radical Scavenger
No Scavenger
Isolated Yield (%)
1
2
40%
5%
TEMPO (1 equiv)
In order to derive mechanistic insights, the standardized reaction was tested in the presence
of TEMPO (2,2,6,6-tetramethylpiperidinyloxy) as the radical scavenger. With stoichiometric
amount of TEMPO, yield of the desired arylated product was reduced to 5%, implying the
involvement of radical intermediate under the present reaction conditions. However, when we
tested a reaction with Bu3SnPh in place of arylboronic acid, we failed to detect any arylated
pyridone product.
Scheme 3. Proposed mechanism for C-3 arylation of 2-pyridone
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Based on the literature reports as well as our experimental observations, it is proposed that
.
-
K2S2O8 thermally17 or in presence of iron (II)10a,18 decomposes to sulphate radical (SO4 ) which
reacts with arylbronic acid to give aryl radical.19 Subsequently, aryl radical reacts selectively at
the C-3 position of 2-pyridone moiety.9,20 This is likely since C-3 atom possesses a large
coefficient of HOMO and LUMO and leading to a resonance stabilized radical adduct A.9
Iron(III)21 or sulphate radical accepts one electron from A (Scheme 5) to make a cationic species
B,10c, 21-22 which facilitates the regaining of aromaticity, resulting in the desired C-3 arylated N-
protected-2-pyridone compound.9 Under aerobic condition (or in the presence of sulphate
radical/persulphate dianion), Fe(II) oxidizes to Fe(III). Therefore, iron may function both as a
Lewis acid19d and an electron transfer site.
The present iron catalyzed method is compatible with electron rich arylboronic acid. Such an
observation is complementary to the findings by Hirano and Miura’s C-3 arylation of N-
protected-2-pyridone with superstoichiometric managanese.9b The manganese promoted
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reaction gave better yields with electron poor arylboronic acids (44-58%) compared to the
electron rich analogues (28%). Additionally, the present iron catalyzed protocol can be
employed to unprotected 2-pyridone moiety.
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CONCLUSION
A direct C-3 arylation of unbiased N-alkyl-2-pyridone moiety with environmentally benign
and abundant iron catalyst has been developed. A radical mechanism has been proposed based
on preliminary studies. This Fe-catalyzed method is expected to be applicable in synthetic
chemistry due to its simplicity and easy to handle procedure.
EXPERIMENTAL SECTION
General Procedure A for Iron Catalyzed Direct Arylation of N-protected 2-pyridone
with Arylboronic acid. In clean oven-dried screw cap reaction tube charged with magnetic stir-
bar, pyridone (0.25 mmol), arylboronic acid (0.75 mmol), K2S2O8 (1 mmol, 270 mg),
K2CO3(0.375 mmol, 52 mg) and Fe(NO3)3.9H2O (0.025 mmol, 10 mg) were taken. 1mL DCE
and 1 mL H2O were added to it. Then the reaction tube was placed on a preheated oil bath at
70˚C. The reaction mixture was stirred at that temperature for 12 h. After cooling the reaction
mixture, 2 (N) HCl solution was added dropwise added to neutralize the reaction mixture. After
that 5 mL of ethyl acetate was added to the reaction mixture and another 5 mL of ethyl acetate
was used for washing the reaction tube. The organic portion was separated by separating funnel
and dried over anhyd. Na2SO4. Then, the organic solution was concentrated in rotary evaporator
and the desired product was purified through neutral aluminium oxide using petroleum ether-
ethyl acetate mixture as eluent.
1-Methyl-3-p-tolylpyridin-2(1H)-one (1). The title compound was purified by column
chromatography (neutral alumina, ethyl acetate/ petroleum ether (8:92 v/v) to get 1 (27 mg, 54%)
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as crystalline solid. m.p 130-133°C; H NMR (400 MHz, CDCl3) δ 2.37 (s, 3H), 3.60 (s, 3H),
5
6
7
8
6.23 (t, J = 6.8 Hz, 1H), 7.20 (d, J = 7.6 Hz, 2H), 7.28 (dd, J = 6.8, 2.1 Hz, 1H), 7.46 (dd, J =
7.0, 2.1 Hz, 1H), 7.59 (d, J = 7.6 Hz, 2H); 13C{1H}NMR (101 MHz, CDCl3) δ 21.4, 38.4, 106.1,
128.6, 129.0, 131.7, 134.1, 137.3, 137.4, 137.6, 162.2; HRMS (ESI-QTOF) m/z: [M+K]+
calcd.for C13H13KNO: 238.0629, found: 238.0625.
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1-Ethyl-3-p-tolylpyridin-2(1H)-one (2).
The title compound was purified by column
chromatography (neutral alumina, ethyl acetate/ petroleum ether (8:92 v/v) to get 2 (26 mg, 49%)
1
as white solid. m.p 81-84°C; H NMR (400 MHz, CDCl3) δ 1.39 (t, J = 7.2 Hz, 3H), 2.36 (s,
3H), 3.04 (q, J = 7.2 Hz, 2H), 6.24 (t, J = 6.8 Hz, 1H), 7.20 (d, J = 6.8 Hz, 2H), 7.27 (dd, 6.9, 2.1
Hz, 1H), 7.44 (dd, J = 6.9, 2.1 Hz, 1H), 7.59 (d, J = 6.8 Hz, 2H); 13C{1H}NMR (101 MHz,
CDCl3) δ 14.8, 21.4, 45.6, 106.2, 128.7, 128.9, 131.9, 134.2, 136.1, 137.1, 137.5, 161.4; HRMS
(ESI-QTOF) m/z: [M+Na]+: calcd.for C14H15NNaO: 236.1046, found: 236.1046.
1-Propyl-3-p-tolylpyridin-2(1H)-one (3). The title compound was purified by column
chromatography (neutral alumina, ethyl acetate/ petroleum ether (8:92 v/v) to get 3 (25 mg, 44%)
as brown oily liquid. 1H NMR (400 MHz, CDCl3) δ 0.97 (t, J = 7.4 Hz, 3H), 1.82 (q, J = 7.4 Hz,
2H), 2.36 (s, 3H), 3.87 – 4.05 (m, 2H), 6.22 (t, J = 6.8 Hz, 1H), 7.20 (d, J = 7.9 Hz, 2H), 7.25
(dd, J = 7.2, 2.6 Hz, 1H), 7.45 (dd, J = 6.9, 2.1 Hz, 1H), 7.59 (d, J = 7.9 Hz, 2H); 13C{1H}NMR
(101 MHz, CDCl3) δ 11.4, 21.4, 22.6, 52.3, 105.9, 128.7, 128.9, 131.9, 134.2, 136.7, 137.1,
137.5, 161.6. HRMS (ESI-QTOF) m/z: [M+Na]+: calcd.for C15H17NNaO: 250.1202, found:
250.1203.
1-Allyl-3-p-tolylpyridin-2(1H)-one (4).
The title compound was purified by column
chromatography (neutral alumina, ethyl acetate/ petroleum ether (8:92 v/v) to get 4 (26 mg, 47%)
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as brown oily liquid. H NMR (400 MHz, CDCl3) δ 2.37 (s, 3H), 4.63 (dt, J = 5.9, 1.5 Hz, 2H),
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5.20 – 5.32 (m, 2H), 6.00 (m, 1H), 6.26 (t, J = 6.8 Hz, 1H), 7.20 (d, J = 8.0 Hz, 2H), 7.25 (dd, J
= 7.1, 2.1 Hz, 1H), 7.46 (dd, J = 6.9, 2.1 Hz, 1H), 7.59 (d, J = 8.0 Hz, 2H); 13C{1H}NMR (101
MHz, CDCl3) δ 21.4, 51.9,106.2, 118.7, 128.7, 129.0, 132.1, 132.9, 134.1, 136.1, 137.3, 137.7,
161.5; HRMS (ESI-QTOF) m/z: [M+K]+: calcd.for C15H15KNO: 264.0785, found: 264.0783.
1-Phenethyl-3-p-tolylpyridin-2(1H)-one (5). The title compound was purified by column
chromatography (neutral alumina, ethyl acetate/ petroleum ether (8:92 v/v) to get 5 (17 mg, 24%)
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as oily liquid. H NMR (400 MHz, CDCl3) δ 2.38 (s, 3H), 3.10 (t, J = 7.3 Hz, 2H), 4.20 (t, J =
7.2 Hz, 2H), 6.12 (t, J = 6.8 Hz, 1H), 6.97 (dd, J = 6.7, 2.1 Hz, 1H), 7.15 – 7.35 (m, 7H), 7.45
(dd, J = 7.0, 2.1 Hz, 1H), 7.61 (d, J = 8.0, 2H); 13C{1H}NMR (101 MHz, CDCl3) δ 21.4, 35.3,
53.0, 105.8, 126.8, 128.7, 128.8, 129.0, 129.2, 132.0, 134.1, 136.9, 137.4, 137.7, 138.4, 161.6;
HRMS (ESI-QTOF) m/z: [M+Na]+: calcd.for C20H19NNaO: 312.1359, found: 312.1359.
4-(2-Oxo-3-p-tolylpyridin-1(2H)-yl)benzonitrile (6). The title compound was purified by
column chromatography (neutral alumina, ethyl acetate/ petroleum ether (8:92 v/v) to get 6 (13
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mg, 19%) as cryatalline solid. H NMR (400 MHz, CDCl3) δ 2.37 (s, 3H), 6.40 (t, J = 6.9 Hz,
1H), 7.18 – 7.24 (m, 2H), 7.30 (dd, J = 6.9, 2.0 Hz, 1H), 7.47 – 7.66 (m, 5H), 7.72 – 7.87 (m,
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2H); C{1H}NMR (101 MHz, CDCl3) δ 21.5, 107.1, 112.5, 118.2, 128.0, 128.7, 129.1, 133.3,
133.3, 133.4, 135.7, 137.9, 138.3, 145.1, 161.3; HRMS (ESI-QTOF) m/z: [M+Na]+: calcd.for
C19H14N2NaO: 309.0998, found: 309.1000.
3-p-Tolylpyridin-2(1H)-one (8). The title compound was purified by column chromatography
(Silica gel mesh 60-180, ethyl acetate/petroleum ether (50:50 v/v) to get 8 (16 mg, 34%) as
brown solid. 1H NMR (400 MHz, CDCl3) δ 2.38 (s, 3H), 6.39 (t, J = 6.7 Hz, 1H), 7.23 (d, J = 7.8
Hz, 2H), 7.37 (dd, J = 6.4, 2.0 Hz, 1H), 7.58 (dd, J = 8.5, 6.4 Hz, 3H); 13C{1H}NMR (101 MHz,
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CDCl3) δ 21.5, 107.9, 128.6, 129.2, 131.7, 133.5, 133.7, 138.0, 139.9, 163.9; HRMS (ESI-
QTOF) m/z: [M+Na]+: calcd.for C12H11NNaO: 208.0733, found 208.0732.
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1-Methyl-3-phenylpyridin-2(1H)-one (9). The title compound was purified by column
chromatography (neutral alumina, ethyl acetate/ petroleum ether (8:92 v/v) to get 7 (17 mg, 38%)
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as cryatalline solid. m.p 128-131°C; H NMR (400 MHz, CDCl3) δ 3.62 (s, 3H), 6.26 (t, J = 6.8
Hz, 1H), 7.30 – 7.35 (m, 2H), 7.38 – 7.43 (m, 2H), 7.49 (dd, J = 7.0, 2.1 Hz, 1H), 7.65 – 7.75 (m,
2H); C{1H}NMR (101 MHz, CDCl3) δ 38.4, 106.0, 127.8, 128.3, 128.8, 131.8, 137.0, 137.6,
13
137.8, 162.1; HRMS (ESI-QTOF) m/z: [M+H]+: calcd.for C12H11NO: 186.0919, found:
186.0915.
3-(4-Methoxyphenyl)-1-methylpyridin-2(1H)-one (10). The title compound was purified by
column chromatography (neutral alumina, ethyl acetate/ petroleum ether (10:90 v/v) to get 8 (25
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mg, 47%) as cryatalline solid. H NMR (400 MHz, CDCl3) δ 3.61 (s, 3H), 3.84 (s, 3H), 6.24 (t, J
= 6.8 Hz, 1H), 6.90 – 6.97 (m, 2H), 7.27 (dd, J = 6.6, 2.2 Hz, 1H), 7.45 (dd, J = 7.0, 2.1 Hz, 1H),
7.62 – 7.72 (m, 2H); 13C{1H}NMR (101 MHz, CDCl3) δ 38.7, 55.5, 106.1, 113.7, 129.5, 130.0,
131.4, 136. 9, 137.0, 159.4, 162.3; HRMS (ESI-QTOF) m/z: [M+Na]+: calcd.for C13H13NNaO2:
238.0838, found: 238.0834.
3-(4-Chlorophenyl)-1-methylpyridin-2(1H)-one (11). The title compound was purified by
column chromatography (neutral alumina, ethyl acetate/ petroleum ether (12:88 v/v) to get 9 (13
1
mg, 24%) as white solid. m.p 139-143°C; H NMR (400 MHz, CDCl3) δ 3.61 (s, 3H), 6.25 (t, J
= 6.9 Hz, 1H), 7.28 – 7.40 (m, 3H), 7.47 (dd, J = 7.0, 2.1 Hz, 1H), 7.64 (d, J = 8.4 Hz, 2H);
13C{1H}NMR (101 MHz, CDCl3) δ 38.5, 106.1, 128.4, 130.1, 130.5, 133.7, 135.4, 137.8, 137.9,
161.9. HRMS (ESI-QTOF) m/z: [M+K]+: calcd.for C12H10ClKNO: 258.0082, found: 258.0082.
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3-(4-Iodophenyl)-1-methylpyridin-2(1H)-one (12). The title compound was purified by column
chromatography (neutral alumina, ethyl acetate/ petroleum ether (12:88 v/v) to get 10 (20 mg,
26%) as yellowish-white solid. m.p 144-147°C; 1H NMR (400 MHz, CDCl3) δ 3.59 (s, 3H),
6.23 (t, J = 6.8 Hz, 1H), 7.31 (dd, J = 6.7, 2.1 Hz, 1H), 7.38 – 7.50 (m, 3H), 7.70 (d, J = 8.4 Hz,
2H); 13C{1H}NMR (101 MHz, CDCl3) δ 38.4, 93.6, 106.0, 130. 4, 130.6, 136.4, 137.3, 137.7,
138.0, 161.7; HRMS (ESI-QTOF) m/z: [M+Na]+: calcd.for C12H10INNaO: 333.9699, found:
333.9698.
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3-(4-Fluorophenyl)-1-methylpyridin-2(1H)-one (13). The title compound was purified by
column chromatography (neutral alumina, ethyl acetate/ petroleum ether (14:86 v/v) to get 11
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(20 mg, 39%) as brown oily liquid. H NMR (400 MHz, CDCl3) δ 3.61 (s, 3H), 6.25 (t, J = 6.8
Hz, 1H), 7.01 – 7.13 (m, 2H), 7.31 (dd, J = 6.7, 2.1 Hz, 1H), 7.46 (dd, J = 7.0, 2.1 Hz, 1H), 7.63
– 7.72 (m, 2H); 13C{1H}NMR (101 MHz, CDCl3) δ 38.5, 106.1, 115.2 (d, J = 21.4 Hz), 130.5,
130.6, 130.8, 133.0, 137.7, 162.1, 162.6 (d, J = 245 Hz); 19F NMR (376 MHz, CDCl3, proton
coupled) δ -114.51 (tt, J = 8.7, 5.5 Hz); 19F NMR (376 MHz, CDCl3, proton decoupled) δ -
114.51; HRMS (ESI-QTOF) m/z: [M+Na]+: calcd.for C12H10FNNaO: 226.0639, found:
226.0635.
1-Methyl-3-(3-(trifluoromethyl)phenyl)pyridin-2(1H)-one (14). The title compound was
purified by column chromatography (neutral alumina, ethyl acetate/ petroleum ether (16:84 v/v)
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to get 12 (14 mg, 22%) as brown oily liquid. H NMR (400 MHz, CDCl3) δ 3.64 (s, 3H), 6.29
(t, J = 6.9 Hz, 1H), 7.37 (dd, J = 6.7, 2.1 Hz, 1H), 7.47 – 7.61 (m, 3H), 7.91 (d, J= 7.7 Hz, 1H),
7.96 (s, 1H); 13C{1H}NMR (101 MHz, CDCl3) δ 38.5, 106.1, 123.1, 124.5, 124.6, 125.6, 125.6,
128.7, 130.3, 132.1, 137.7, 138. 3, 138.4, 161. 9; 19F NMR (376 MHz, CDCl3, proton coupled) δ
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-62.52 (t, J = 11.3 Hz); 19F{1H}NMR (376 MHz, CDCl3, proton decoupled) δ -62.52; HRMS
(ESI-QTOF) m/z: [M+K]+: calcd.for C13H10F3KNO: 292.0346, found:292.0345.
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Methyl 3-(1-methyl-2-oxo-1,2-dihydropyridin-3-yl)benzoate (15). The title compound was
purified by column chromatography (neutral alumina, ethyl acetate/ petroleum ether (17:83 v/v)
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to get 15 (5 mg, 9%) as brown oily liquid. H NMR (400 MHz, CDCl3) δ 8.31 (t, J = 1.6 Hz,
1H), 8.08 – 7.89 (m, 2H), 7.55 (dd, J = 7.0, 2.0 Hz, 1H), 7.47 (t, J = 7.8 Hz, 1H), 7.34 (dd, J =
6.7, 2.0 Hz, 1H), 6.28 (t, J = 6.9 Hz, 1H), 3.92 (s, 3H), 3.62 (d, J = 7.2 Hz, 3H); HRMS (ESI-
QTOF) m/z: [M+Na]+: calcd.for C14H13NNaO3: 266.0788, found:266.0789.
1-Methyl-3-o-tolylpyridin-2(1H)-one (16). The title compound was purified by column
chromatography (neutral alumina, ethyl acetate/ petroleum ether (8:92 v/v) to get 13 (17 mg,
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35%) as brown oily liquid. H NMR (400 MHz, CDCl3) δ 2.25 (s, 3H), 3.63 (s, 3H), 6.25 (t, J =
6.8 Hz, 1H), 7.14 – 7.39 (m, 6H); C{1H}NMR (101 MHz, CDCl3) δ 20.1, 38.3, 105.6, 125.8,
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128.0, 130.1, 130.2, 133.6, 137.1, 137.8, 139.1, 161.9; HRMS (ESI-QTOF) m/z: [M+K]+: calcd.
for C13H13KNO: 238.0629, found:238.0627.
3-(Dibenzo[b,d]furan-4-yl)-1-methylpyridin-2(1H)-one (17). The title compound was purified
by column chromatography (neutral alumina, ethyl acetate/ petroleum ether (10:90 v/v) to get 14
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(17 mg, 24%) as white solid. m.p 88-92°C; H NMR (400 MHz, CDCl3) δ 3.66 (s, 3H), 6.36 (t,
J = 6.8 Hz, 1H), 7.34 (td, J = 7.5, 1.0 Hz, 1H), 7.37 – 7.51 (m, 3H), 7.55 (dt, J = 8.3, 0.8 Hz,
1H), 7.87 – 8.01 (m, 4H); C{1H}NMR (101 MHz, CDCl3) δ 38.6, 106.0, 111.9, 120.3, 120.8,
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121.4, 122.8, 124. 6, 124.7, 126.8, 127.2, 128.7, 129.6, 138.2, 140. 2, 153.9, 156.1, 161.9;
HRMS (ESI-QTOF) m/z: [M+Na]+: calcd. for C18H13NNaO2: 298.0838, found: 298.0835.
3-Phenyl-1-propylpyridin-2(1H)-one (18). The title compound was purified by column
chromatography (neutral alumina, ethyl acetate/ petroleum ether (8:92 v/v) to get 15 (17 mg,
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32%) as oily liquid. H NMR (400 MHz, CDCl3) δ 0.98 (t, J = 7.4 Hz, 3H), 1.75 – 1.91 (m, 2H),
3.96 (t, J = 8.0 Hz, 2H), 6.24 (t, J = 6.8 Hz, 1H), 7.25 – 7.34 (m, 2H), 7.36 – 7.42 (m, 2H), 7.47
(dd, J = 6.9, 2.1 Hz, 1H), 7.63 – 7.76 (m, 2H). 13C{1H}NMR (101 MHz, CDCl3) δ 11.4, 22.6,
52.3, 105. 9, 127.7, 128.2, 128.8, 131.9, 137.0, 137.1, 137.6, 161.5. HRMS (ESI-QTOF) m/z:
[M+H]+: calcd. for C14H15NO: 214.1232, found: 214.1238.
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3-(3-Bromophenyl)-1-propylpyridin-2(1H)-one (19). The title compound was purified by
column chromatography (neutral alumina, ethyl acetate/ petroleum ether (12:88 v/v) to get 16
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(19 mg, 26%) as oily liquid. H NMR (400 MHz, CDCl3) δ 0.99 (t, J = 7.4 Hz, 3H), 1.83 (h, J =
7.4 Hz, 2H), 3.90 – 4.05 (m, 2H), 6.26 (t, J = 6.9 Hz, 1H), 7.20 – 7.38 (m, 2H), 7.42 – 7.52 (m,
2H), 7.64 (ddd, J = 7.8, 1.7, 1.0 Hz, 1H), 7.87 (t, J = 1.8 Hz, 1H); C{1H}NMR (101 MHz,
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CDCl3) δ 11.4, 22.7, 52.5, 105.9, 122.3, 127.5, 129.7, 130.4, 130.7, 131.7, 137.6, 138.0, 139.1,
161.3; HRMS (ESI-QTOF) m/z: [M+Na]+: calcd. for C14H14BrNNaO: 314.0151, found:
314.0151.
1-Propyl-3-(m-tolyl)pyridin-2(1H)-one (20). The title compound was purified by column
chromatography (neutral alumina, ethyl acetate/ petroleum ether (8:92 v/v) to get 17 (26 mg,
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45%) as oily liquid. H NMR (400 MHz, CDCl3) δ 0.97 (t, J = 7.4 Hz, 3H), 1.82 (q, J = 7.4 Hz,
2H), 2.38 (s, 3H), 3.89 – 4.02 (m, 2H), 6.23 (t, J = 6.8 Hz, 1H), 7.09 – 7.19 (m, 1H), 7.22 – 7.35
(m, 2H), 7.39 – 7.50 (m, 2H), 7.54 (s 1H). 13C{1H}NMR (101 MHz, CDCl3) δ 11.3, 21.6, 22.6,
52.3, 105.9, 125.8, 128.1, 128.5, 129.5, 132.0, 136.9, 137.0, 137.5, 137.6, 161.5. HRMS (ESI-
QTOF) m/z: [M+Na]+: calcd. for C15H17NNaO: 250.1202, found: 250.1202.
3-([1,1'-biphenyl]-4-yl)-1-propylpyridin-2(1H)-one (21). The title compound was purified by
column chromatography (neutral alumina, ethyl acetate/ petroleum ether (8:92 v/v) to get 18 (22
mg, 31%) as white solid. m.p 131-134°C; 1H NMR (400 MHz, CDCl3) δ 1.00 (t, J = 7.4 Hz, 3H),
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1.85 (q, J = 7.4 Hz, 2H), 3.90 – 4.05 (m, 2H), 6.26 (t, J = 6.8 Hz, 1H), 7.29 (dd, J = 6.8, 2.1 Hz,
1H), 7.32 – 7.38 (m, 1H), 7.40 – 7.49 (m, 2H), 7.54 (dd, J = 7.0, 2.1 Hz, 1H), 7.58 – 7.68 (m,
4H), 7.74 – 7.86 (m, 2H); 13C{1H}NMR (101 MHz, CDCl3) δ 11.4, 22.6, 52.4, 105.9, 127.0,
127.3, 127.4, 128.9, 129.2, 131.4, 136.1, 137.0, 137.4, 140.5, 141.1, 161.6; HRMS (ESI-QTOF)
m/z: [M+Na]+: calcd. for C20H19NNaO: 312.1359, found: 312.1360.
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1-Allyl-3-phenylpyridin-2(1H)-one (22). The title compound was purified by column
chromatography (neutral alumina, ethyl acetate/ petroleum ether (8:92 v/v) to get 19 (16 mg,
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30%) as oily brown liquid. H NMR (400 MHz, CDCl3) δ 4.63 (dt, J = 5.9 Hz, 2H), 5.21 – 5.30
(m, 2H), 6.00 (ddt, J = 17.2, 10.3, 5.9 Hz, 1H), 6.27 (t, J = 6.8 Hz, 1H), 7.24 – 7.36 (m, 2H),
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7.36 – 7.42 (m, 2H), 7.48(dd, J = 7.0, 2.1 Hz, 1H), 7.63 – 7.72 (m, 2H); C{1H}NMR (101
MHz, CDCl3) δ 51.9, 106.2, 118.7, 127.8, 128.2, 128.8, 132.0, 132.7, 136.4, 137.0, 137.7, 161.4;
HRMS (ESI-QTOF) m/z: [M+Na]+: calcd. for C14H13NNaO: 234.0889, found: 234.0882.
1,6-Dimethyl-3-p-tolylpyridin-2(1H)-one (23). The title compound was purified by column
chromatography (neutral alumina, ethyl acetate/ petroleum ether (8:92 v/v) to get 20 (17 mg,
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32%) as solid. m.p 134-137°C; H NMR (400 MHz, CDCl3) δ 2.36 (d, J = 2.2 Hz, 6H), 3.58 (s,
3H), 6.11 (d, J = 7.1 Hz, 1H), 7.19 (d, J = 8.2 Hz, 2H), 7.35 (d, J = 7.2 Hz, 1H), 7.57 (d, J = 8.2
Hz, 2H); 13C{1H}NMR (101 MHz, CDCl3) δ 21.3, 21.3, 31.8, 106.6, 128.1, 128.5, 128.9, 134.6,
136.6, 137.1, 145.3, 162.8. HRMS (ESI-QTOF) m/z: [M+K]+: calcd. for C14H15KNO: 252.0785,
found:252.0786.
6-Chloro-1-methyl-3-p-tolylpyridin-2(1H)-one (24). The title compound was purified by column
chromatography (neutral alumina, ethyl acetate/ petroleum ether (14:86 v/v) to get 21 (29 mg,
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50%) as white solid. m.p 118-120°C; H NMR (400 MHz, CDCl3) δ 2.37 (s, 3H), 3.75 (s, 3H),
6.39 (d, J = 7.6 Hz, 1H), 7.21 (d, J = 7.9 Hz, 2H), 7.37 (d, J = 7.6 Hz, 1H), 7.54 (d, J = 7.9 Hz,
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2H); C{1H}NMR (101 MHz, CDCl3) δ 21.4, 34.0, 106.8, 128.5, 129.1, 129.4, 133.6, 136.4,
136.5, 137.9, 162.3; HRMS (ESI-QTOF) m/z: [M+Na]+: calcd. for C13H12ClNNaO: 256.0500,
found:256.0501.
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4-(1-Methyl-6-oxo-5-(p-tolyl)-1,6-dihydropyridin-2-yl)benzonitrile (25). The title compound
was purified by column chromatography (neutral alumina, ethyl acetate/ petroleum ether (30:70
v/v) to get 26 (16 mg, 20%) as white solid. m.p >200°C; 1H NMR (400 MHz, CDCl3) δ 2.38 (s,
3H), 3.43 (s, 3H), 6.18 (d, J = 7.2 Hz, 1H), 7.23 (d, J = 8.0 Hz, 2H), 7.48 – 7.55 (m, 3H), 7.63(d,
J = 8.1 Hz, 2H), 7.77 – 7.81 (m, 2H); 13C{1H}NMR (101 MHz, CDCl3) δ 21.5, 35.3, 108.3,
113.4, 118.2, 128.7, 129.1, 129.5, 131.1, 132.8, 133.9, 136.1, 138.0, 140.1, 146.7, 162.5; HRMS
(ESI-QTOF) m/z: [M+Na]+: calcd. for C20H16N2NaO: 323.1160, found: 323.1161.
5-Chloro-1-methyl-3-p-tolylpyridin-2(1H)-one (26). The title compound was purified by column
chromatography (neutral alumina, ethyl acetate/ petroleum ether (14:86 v/v) to get 22 (16 mg,
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28%) as white solid. H NMR (400 MHz, CDCl3) δ 2.37 (s, 3H), 3.59 (s, 3H), 7.21 (d, J = 7.6
Hz, 2H), 7.33 (d, J = 2.9 Hz, 1H), 7.43 (d, J = 2.9 Hz, 1H), 7.57 (d, J = 7.6 Hz, 2H);
13C{1H}NMR (101 MHz, CDCl3) δ 21.5, 38.6, 112.3, 128.6, 129.2, 132.6, 132.9, 134.5, 137.9,
138.5, 160.8; HRMS (ESI-QTOF) m/z: [M+Na]+: calcd. for C13H12ClNNaO: 256.0500,
found:256.0497.
1-Methyl-3-p-tolyl-5-(trifluoromethyl)pyridin-2(1H)-one (27). The title compound was purified
by column chromatography (neutral alumina, ethyl acetate/ petroleum ether (16:84 v/v) to get 23
(23 mg, 35%) as white solid. m.p 142 -144°C; 1H NMR (400 MHz, CDCl3) δ 2.38 (s, 3H), 3.64
(s, 3H), 7.17 – 7.31 (m, 2H), 7.53 – 7.62 (m, 3H), 7.68 (dq, J = 2.5, 1.3 Hz, 1H); 13C{1H}NMR
(101 MHz, CDCl3) δ 21.5, 38.9, 109.7 (q, J = 34.8 Hz), 123.7 (q, J = 269.7 Hz), 128.6, 129.2,
132.5, 132.8, 136.3, 136.3, 138.7, 161.7; 19F{1H}NMR (376 MHz, CDCl3, proton decoupled) δ -
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62.25; HRMS (ESI-QTOF) m/z: [M+Na]+: calcd. for C14H12F3NNaO: 290.0763, found:
290.0761.
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5-Chloro-1-methyl-3-phenylpyridin-2(1H)-one (28). The title compound was purified by
column chromatography (neutral alumina, ethyl acetate/ petroleum ether (6:94 v/v) to get 24 (16
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mg, 29%) as white solid. m.p 133 -137°C; H NMR (400 MHz, CDCl3) δ 3.59 (s, 3H), 7.34 –
7.43 (m, 4H), 7.45 (d, J = 2.8 Hz, 1H), 7.61 – 7.70 (m, 2H); 13C{1H}NMR (101 MHz, CDCl3) δ
38.6, 112.3, 128.4, 128.5, 128.8, 132.6, 134.9, 135.7, 138.4, 160.7; HRMS (ESI-QTOF) m/z:
[M+H]+: calcd. for C12H10ClNO: 220.0529, found: 220.0532.
1-Methyl-3-(p-tolyl)quinolin-2(1H)-one (30). The title compound was purified by column
chromatography (neutral alumina, ethyl acetate/ petroleum ether (16:84 v/v) to get 27 (21 mg,
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34%) as viscous liquid. H NMR (400 MHz, CDCl3) δ 2.40 (s, 3H), 3.79 (s, 3H), 7.20 – 7.29 (m,
3H), 7.35 – 7.39 (m, 1H), 7.55 (ddd, J = 8.7, 7.2, 1.6 Hz, 1H), 7.58 – 7.63 (m, 3H), 7.78 (s, 1H);
13C{1H}NMR (101 MHz, CDCl3) δ 21.5, 30.1, 114.1, 121.0, 122.3, 128.9, 129.0, 129.0, 130.3,
132.6, 134.1, 136.5, 138.1, 139.7, 161.8;
C17H15NNaO: 272.1046, found: 272.1047.
HRMS (ESI-QTOF) m/z: [M+Na]+: calcd. for
3-(2-Methoxyphenyl)-1-methylquinolin-2(1H)-one (31). The title compound was purified by
column chromatography (neutral alumina, ethyl acetate/ petroleum ether (18:82 v/v) to get 29
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(14 mg, 21%) as brown oily liquid. H NMR (400 MHz, CDCl3) δ 3.79 (s, 3H), 3.81 (s, 3H),
6.95 – 7.07 (m, 2H), 7.24 (td, J = 7.5, 1.0 Hz, 1H), 7.30 – 7.42 (m, 3H), 7.52 – 7.60 (m, 2H),
7.73 (s, 1H); 13C{1H}NMR (101 MHz, CDCl3) δ 30.2, 56.0, 111.4, 114.2, 120.7, 120.8, 122.2,
126.4, 128.9, 129.7, 130.3, 131.1, 131.2, 138.5, 140.0, 157.5, 161.6; HRMS (ESI-QTOF) m/z:
[M+Na]+: calcd. for C17H15NNaO2: 288.0995, found: 288.0992.
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3-(2-Methoxyphenyl)quinolin-2(1H)-one (33). The title compound was purified by column
chromatography (silica gel 60-120-mesh, ethyl acetate/ petroleum ether (50:50 v/v) to get 33 (16
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mg, 26%) as white solid. H NMR (500 MHz, CDCl3) δ 3.82 (s, 3H), 7.03 (dd, J = 8.3, 1.0 Hz,
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1H), 7.06 (td, J = 7.5, 1.1 Hz, 1H), 7.19 (ddd, J = 8.1, 7.3, 1.1 Hz, 1H), 7.29 – 7.33 (m, 1H), 7.40
(ddd, J = 8.3, 7.5, 1.7 Hz, 1H), 7.42 – 7.47 (m, 2H), 7.56 (dd, J = 7.8, 1.3 Hz, 1H), 7.84 (s, 1H),
11.52 (s, 1H); 13C{1H}NMR (101 MHz, CDCl3) δ 56.0, 111.5, 115.8, 120.3, 120.8, 122.6, 125.7,
127.9, 130.2, 131.0, 131.4, 138.3, 140.3, 157.6, 163.0; HRMS (ESI-QTOF) m/z: [M+Na]+:
calcd. for C16H13NNaO2: 274.0838, found 244.0840.
Produre for Large Scale Synthesis of 1-Methyl-3-phenylpyridin-2(1H)-one (8): In a 250 mL
round-bottom flask, 10.8 gm (40 mmol) K2S2O8; 2.07 gm (15 mmol) K2CO3; 3.66 gm (30 mmol)
phenylboronic acid; 0.403 gm (1 mmol) Fe(NO3)3.9H2O and 1.180 gm ( 10 mmol) N-methyl-2-
pyridone were taken, then 40 mL H2O and 40 mL DCE were added to it. The total reaction
mixture was set with reflux condenser on a preheated 70˚C oil-bath and stirred for 12 h. After
cooling the reaction mixture, 2 (N) HCl solution was drop wise added to neutralize the reaction
mixture. After that 50 mL of ethyl acetate was added to the reaction mixture and another 25 mL
of ethyl acetate was used for washing the round bottom flask. Organic portion was separated by
separating funnel and dried over anhyd. Na2SO4. Then, the organic solution was concentrated in
rotary evaporator and desired product was purified through neutral alumina using ethyl
acetate/petroleum ether (8:92 v/v) mixture as eluent. Isolated yield 0.641gm (34%).
1-Methyl-3-phenylpiperidin-2-one (32). In a clean oven-dried screw cap reaction tube charged
with magnetic stir-bar, 1-methyl-3-phenyl-2-pyridone (9) (0.25 mmol), Palladium in charcoal
(10 mol%) were taken. Then the reaction tube was closed tightly. The reaction tube was
evacuated and filled with H2 gas. 2mL H2 purged EtOH was added to it and stirred at room
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temperature for 24 h.23 After 24 h the reaction mixture was filtered through celite and washed
with 20 ml EtOAc. Total organic solution was concentrated and afforded 1-methyl-3-
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phenylpiperidin-2-one in 99% yield. H NMR (400 MHz, CDCl3) δ 1.71 – 1.84 (m, 1H), 1.84 –
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1.99 (m, 1H), 2.08 – 2.24 (m, 1H), 3.02 (s, 3H), 3.29 – 3.38 (m, 1H), 3.37 – 3.50 (m, 1H), 3.59 –
3.72 (m, 1H), 7.15 – 7.24 (m, 3H), 7.26 – 7.33 (m, 2H); 13C{1H}NMR (101 MHz, CDCl3) δ
21.0, 30.7, 35.2, 48.7, 50.5, 126.7, 128.4, 128.6, 141.9, 170.9; HRMS (ESI-QTOF) m/z:
[M+Na]+:calcd.for C12H15NNaO: 212.1046, found: 212.1050.
General Procedure B for synthesis of N-alkyl-2-pyridone from corresponding 2-hydroxy
pyridine24. 2-Hydroxy-pyridine (5 mmol), alkyl iodide (1.5 equiv., 7.5 mmol) and K2CO3 (1.5
equiv., 7.5 mmol, 1.035 g) were taken in a 50 mL round bottom flask. Then 20 mL MeOH was
added to it and set for overnight reflux in a condenser set up at 65˚C. After the reaction the
reaction mixture was dried in rota-vap and the residue was diluted with 20 mL ethyl acetate.
Organic part was washed with 10 mL brine solution and concentrated in rotary evaporator.
Desired N-protected-2-pyridone was isolated through neutral aluminium oxide using petrolium
ether-ethyl acetate mixture as eluent.
1-Ethylpyridin-2(1H)-one. The title compound was prepared following general procedure B and
was purified by column chromatography (neutral alumina, ethyl acetate) to get as brown oily
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liquid. H NMR (400 MHz, CDCl3) δ 1.26 – 1.45 (m, 3H), 3.92 – 4.10 (m, 2H), 6.18 (t, J = 6.7
Hz, 1H), 6.57 (d, J = 9.1 Hz, 1H), 7.20 – 7.40 (m, 2H); 13C{1H}NMR (101 MHz, CDCl3) δ 14.8,
45.0, 106.3, 121.2, 137.1, 139.5, 162.7. HRMS (ESI-QTOF) m/z: [M+Na]+: calcd. for
C7H9NNaO: 146.0576, found: 146.0577.
1-Propylpyridin-2(1H)-one. The title compound was prepared following general procedure B
and was purified by column chromatography (neutral alumina, ethyl acetate) to get as brown oily
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liquid. H NMR (400 MHz, CDCl3) δ 0.96 (t, J = 8 Hz, 3H), 1.81-1.76 (m, 2H), 3.90 (t, J = 6
Hz, 2H), 6.15 (t, J = 6 Hz, 1H), 6.57 (d, J = 7 Hz, 1H), 7.25-7.31(m, 2H). 13C{1H}NMR (101
MHz, CDCl3) δ 11.3, 22.7, 51.6, 106.0, 121.3, 137.8, 139.4, 162.9. HRMS (ESI-QTOF) m/z:
[M+Na]+: calcd. for C8H11NNaO: 160.0733, found: 160.0732.
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1-Allylpyridin-2(1H)-one. The title compound was prepared following general procedure B and
was purified by column chromatography (neutral alumina, ethyl acetate) to get as brown oily
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liquid. H NMR (400 MHz, CDCl3) δ 4.54 (dt, J = 5.8, 1.5 Hz, 2H), 5.15 (dq, J = 17.1, 1.5 Hz,
1H), 5.23 (dq, J = 10.3, 1.3 Hz, 1H), 5.93 (ddt, J = 17.1, 10.2, 5.8 Hz, 1H), 6.15 (td, J = 6.7, 1.4
Hz, 1H), 6.56 (ddd, J = 9.2, 1.3, 0.7 Hz, 1H), 7.23 (ddd, J = 6.8, 2.1, 0.7 Hz, 1H), 7.30 (ddd, J =
9.0, 6.6, 2.1 Hz, 1H); 13C{1H}NMR (101 MHz, CDCl3) δ 51.1, 106.2, 118.5, 121.2, 132.6,
137.2, 139.6, 162.5. HRMS (ESI-QTOF) m/z: [M+Na]+: calcd. for C8H9NNaO: 158.0576,
found: 158.0578.
1-Phenethylpyridin-2(1H)-one. The title compound was prepared following general procedure B
and was purified by column chromatography (neutral alumina, ethyl acetate) to get as crystalline
solid. m.p 106-108°C; 1H NMR (400 MHz, CDCl3) δ 2.06 (t, J = 7.1 Hz, 2H), 4.14 (t, J = 7.1 Hz,
2H), 5.99 (td, J = 6.7, 1.4 Hz, 1H), 6.59 (ddd, J = 9.2, 1.4, 0.7 Hz, 1H), 6.88 (ddd, J = 6.8, 2.1,
0.7 Hz, 1H), 7.10 – 7.19 (m, 2H), 7.18 – 7.34 (m, 4H); 13C{1H}NMR (101 MHz, CDCl3) δ 35.2,
52.3, 105.7, 121.2, 126.9, 128.8, 129.2, 138.1, 138.2, 139.7, 162.8; HRMS (ESI-QTOF) m/z:
[M+Na]+: calcd. for C13H13NNaO: 222.0889, found: 222.0889.
4-(2-Oxopyridin-1(2H)-yl)benzonitrile. The title compound was prepared following general
procedure B and was purified by column chromatography (neutral alumina, ethyl acetate) to get
1
as white solid. H NMR (400 MHz, CDCl3) δ 6.30 (td, J = 6.8, 1.3 Hz, 1H), 6.67 (ddd, J = 9.4,
1.3, 0.8 Hz, 1H), 7.30 (ddd, J = 6.9, 2.1, 0.8 Hz, 1H), 7.43 (ddd, J = 9.3, 6.6, 2.1 Hz, 1H), 7.52 –
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7.59 (m, 2H), 7.78 – 7.83 (m, 2H); 13C{1H}NMR (101 MHz, CDCl3) δ 106.9, 112.6, 118.1,
122.5, 127.8, 133.5, 136.9, 140.5, 144.6, 162.0; HRMS (ESI-QTOF) m/z: [M+H]+: calcd. for
C12H9N2O: 197.0709, found: 197.0707.
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1,6-Dimethylpyridin-2(1H)-one. The title compound was prepared following general procedure
B and was purified by column chromatography (neutral alumina, ethyl acetate) to get as yellow
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oily liquid. H NMR (400 MHz, CDCl3) δ 2.33 (s, 3H), 3.51 (s, 3H), 5.96 – 6.09 (m, 1H), 6.43
(ddd, J = 9.1, 1.5, 0.7 Hz, 1H), 7.19 (dd, J = 9.1, 6.8 Hz, 1H); 13C{1H}NMR (101 MHz, CDCl3)
δ 21.1, 31.3, 106.7, 117.4, 138.8, 146.5, 164.1; HRMS (ESI-QTOF) m/z: [M+H]+: calcd. for
C7H10NO: 124.0757, found: 124.0755.
6-Chloro-1-methylpyridin-2(1H)-one. The title compound was prepared following general
procedure B and was purified by column chromatography (neutral alumina, ethyl acetate) to get
as white crystalline solid. m.p 59-60°C; 1H NMR (400 MHz, CDCl3) δ 3.70 (s, 3H), 6.32 (dd, J =
13
7.2, 1.3 Hz, 1H), 6.52 (dd, J = 9.2, 1.2 Hz, 1H), 7.15 – 7.32 (m, 1H); C{1H}NMR (101 MHz,
CDCl3) δ 33.4, 106.8, 118.4, 138.4, 138.7, 163.5. HRMS (ESI-QTOF) m/z: [M+H]+: calcd. for
C6H7ClNO: 144.0211, found: 144.0210.
5-Chloro-1-methylpyridin-2(1H)-one. The title compound was prepared following general
procedure B and was purified by column chromatography (neutral alumina, ethyl acetate) to get
1
as white solid. m.p 60-62°C; H NMR (400 MHz, CDCl3) δ 3.50 (s, 3H), 6.52 (dt, J = 9.6, 1.3
Hz, 1H), 7.20 – 7.44 (m, 2H); 13C{1H}NMR (101 MHz, CDCl3) δ 38.0, 112.3, 121.2, 132.9,
142.6, 161.7. HRMS (ESI-QTOF) m/z: [M+H]+: calcd. for C6H7ClNO: 144.0211, found:
144.0209.
1-Methyl-5-(trifluoromethyl)pyridin-2(1H)-one. The title compound was prepared following
general procedure B and was purified by column chromatography (neutral alumina, ethyl
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acetate) to get as white crystalline solid. m.p 78-82°C; H NMR (400 MHz, CDCl3) δ 3.58 (s,
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3H), 6.62 (dt, J = 9.5, 0.8 Hz, 1H), 7.45 (dd, J = 9.6, 2.7 Hz, 1H), 7.69 (dt, J = 3.1, 1.3 Hz, 1H);
13C{1H}NMR (101 MHz, CDCl3) δ 38.3, 109.7 (q, J =35 Hz), 123.5 (q, J =271 Hz), 135.4,
138.1, 162.5. 19F NMR (376 MHz, CDCl3, proton decoupled) δ -62.34. HRMS (ESI-QTOF)
m/z: [M+H]+: calcd. for C7H7F3NO: 178.0474, found: 178.0475.
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3-Chloro-1-methylpyridin-2(1H)-one. The title compound was prepared following general
procedure B and was purified by column chromatography (neutral alumina, ethyl acetate) to get
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as brown oily liquid. H NMR (400 MHz, CDCl3) δ 3.62 (s, 3H), 6.16 (dd, J = 7.3, 6.8 Hz, 1H),
7.33(dd, J = 6.8, 1.9 Hz, 1H), 7.54 (dd, J = 7.3, 1.9 Hz, 1H); 13C{1H}NMR (101 MHz, CDCl3) δ
38.6, 105.3, 126.1, 137.1, 137.8, 159.4. HRMS (ESI-QTOF) m/z: [M+H]+: calcd. for
C6H7ClNO: 144.0211, found: 144.0211.
4-(1-Methyl-6-oxo-1,6-dihydropyridin-2-yl)benzonitrile. The titled compound was prepared by
C-C coupling of 6-Chloro-1-methylpyridin-2(1H)-one (1 mmol, 143 mg), and 4-cyano-
phenylboronic acid (1.5 mmol, 221 mg). The reaction was done in screw cap reaction tube with
K3PO4 (3 mmol, 690 mg), Pd(OAc)2 (0.03 mmol, 7 mg), X-Phos (0.03 mmol, 7 mg), THF (3
mL). Reaction was carried out in N2 atmosphere at 110°C for 24h. After the reaction, the mixture
was filtered through celite. Pure product was isolated by column chromatography (neutral
alumina, ethyl acetate) to get white solid. 1H NMR (400 MHz, CDCl3) δ 3.35 (s, 3H), 6.08 (dd, J
= 8, 2 Hz), 6.64 (dd, J = 8, 2 Hz 1H), 7.38-7.34 (m, 1H), 7.48-7.51 (m, 2H), 7.77-7.80 (m, 2H);
13C{1H}NMR (101 MHz, CDCl3) δ 34.6, 108.2, 113.6, 118.1, 120.4, 129.5, 132.8, 138.6, 139.9,
148.2, 163.6. HRMS (ESI): calcd. for C13H11N2O: 211.0866, found: 211.0865.
ASSOCIATED CONTENTS
Notes
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The authors declare no competing financial interest.
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ACKNOWLEDGMENTS
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This activity is supported by CSIR (P81102); India. Financial support received from CSIR-India
(fellowship to A.M. and S.R.) is gratefully acknowledged.
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Supporting Information
Figures giving 1H and 13C NMR and all compounds text giving details of the optimization. This
material is available free of charge via the Internet at http://pubs.acs.org.
REFERENCES
1. (a) Pierce, J. B.; Ariyan, Z. S.; Ovenden, G. S. J. Med. Chem. 1982, 25, 131-136; (b) Earl, R.
A.; Vollhardt, K. P. C. J. Org. Chem. 1984, 49, 4786-4800; (c) Mirkin, C. A.; Lu, K. L.;
Snead, T. E.; Geoffroy, G. L.; Rheingold, A. L. J. Am. Chem. Soc. 1990, 112, 2809-2810; (d)
Adam, W.; Hartung, J.; Okamoto, H.; Marquardt, S.; Nau, W. M.; Pischel, U.; Saha-Moller,
C. R.; Spehar, K. J. Org. Chem. 2002, 67, 6041-6049; (e) Surup, F.; Wagner, O.; Frieling, J.
V. Schleicher, M.; Oess, S.; Muller, P.; Grond, S.; J. Org. Chem. 2007, 72, 5085-5090; (f)
Fotiadou, A. D.; Zografos, A. L. Org. Lett. 2011, 13, 4592-4595.
2. (a) Conreaux, D.; Bossharth, E.; Monteiro, N.; Desbordes, P.; Vors, J.-P.; Balme, G. V.;
Org. Lett. 2006, 9, 271; (b) Chou, S.-S. P.; Chung, Y.-C.; Chen, P.-A.; Chiang, S.-L.; Wu,
C.-J. J. Org. Chem. 2011, 76, 692-695; (c) McElhinny, C. J.; Carroll, F. I.; Lewin, A. H.
Synthesis 2012, 44, 57-62.
3. Itahara, T.; Ouseto, F. Synthesis 1984, 488-489.
4. Chen, Y. Y.; Wang, F.; Jia, A. Q.; Li, X. W. Chem. Sci. 2012, 3, 3231-3236.
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5. (a) Nakao, Y.; Idei, H.; Kanyiva, K. S.; Hiyama, T. J. Am. Chem. Soc. 2009, 131, 15996-
15997; (b) Tamura, R.; Yamada, Y.; Nakao, Y.; Hiyama, T. Angew. Chem. Int. Ed. 2012, 51,
5679-5682.
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6. Odani, R.; Hirano, K.; Satoh, T.; Miura, M. Angew. Chem. Int. Ed. 2014, 53, 10784-10788.
7. (a) Cheng, D.; Gallagher, T. Org. Lett. 2009, 11, 2639-2641; (b) Min, M.; Kim, Y.; Hong, S.
Chem. Commun. 2013, 49, 196-198.
8. Anagnostaki, E. E.; Fotiadou, A.D.; Demertzidou, V.; Zografos, A. L. Chem. Commun. 2014,
50, 6879-6882.
9. (a) Nakatani, A.; Hirano, K.; Satoh, T.; Miura, M. Chem. Eu. J. 2013, 19, 7691-7695; (b)
Nakatani, A.; Hirano, K.; Satoh, T.; Miura, M. J. Org. Chem. 2014, 79, 1377–1385.
10. (a) Komeyama, K.; Kashihara, T.; Takaki, K. Tetrahedron Lett. 2013, 54, 1084-1086. (b)
Komeyama, K.; Nagao, Y.; Abe, M; Takaki, K. Bull. Chem. Soc. Jpn. 2014, 87, 301-313. (c)
Minisci, F.; Vismara, E.; Fontana, F.; Morini, G.; Serravalle, M.; Giordano, C.; J. Org.
Chem. 1986, 51, 4411-4416; (d) Fontana, F.; Minisci, F.; Nogueira Barbosa, M. C.;
Vismara, E. Tetrahedron 1990, 46, 2525-2538; (e) Harrowven, D. C.; Sutton, B. J.;. Gribble
Gordon W. a. J. J. A. in Prog. Heterocycl. Chem., Vol. Volume 16, Elsevier, 2005, pp. 27-53.
11. (a) Deb, A.; Manna, S.; Maji, A.; Dutta, U.; Maiti, D. Eur. J. Org. Chem. 2013, 24, 5251-
5256 ; (b) Deb, A.; Agasti, S.; Saboo, T.; Maiti, D. Adv. Syn. Cat. 2014, 356, 705-710.
12. Liang, Y.; Gloudeman, J.; Wnuk, S. F.; J. Org. Chem. 2014, 79, 4094–4013.
13. See Supporting Information for details.
14. Experimental details of the structure determination can be found in the Supporting
Information.
CCDC-947672 (entry 1) and
CCDC-947671 (entry 7) contain the
supplementary crystallographic data for this paper.These data can be obtained free of charge
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1
2
3
4
5
6
7
8
9
from
http://www.ccdc.cam.ac.uk/data_request/cif.
15. Merck and Co. Inc., U.S. Patents 3754088 (1973), 3814771 (1974), and 3830922 (1974).
The
Cambridge
Crystallographic
Data
Centre
via
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
16. (a) Kawase, Y.; Yamaguchi, S.; Maeda, O.; Hayashi, A.; Hayashi, I.; Tabata K.; Kondo, M.
J. Heterocycl. Chem. 1979, 16, 487-491; (b) Yang, C. L.; Tseng, C. H.; Chen, Y. L.; Lu, C.
M.; Kao, C. L.; Wu, M. H.; Tzeng, C. C. Eur. J. Med. Chem. 2010, 45, 602-607; (c) Kawase,
Y.; Yamaguchi, S.; Morita, M.; Uesugi, T. Bull. Chem. Soc. Jpn. 1980, 53, 1057-1060.
17. (a) Bartlett, P. D.; Cotman, J.D. J. Am. Chem. Soc., 1949, 71, 1419–1422. (b) Kolthoff, I. M.;
Miller, I. K. J. Am. Chem. Soc., 1951, 73, 3055–3059.
18. Wille, U. Org. Lett. 2000, 2, 3485-3488.
19.
(a) Riyajan, S.-A.; Sasithornsonti Y. J. Polym. Environ. 2013, 21, 472-478; (b) Manna,
S.; Maity, S.; Rana, S.; Agasti, S.; Maiti, D. Org. Lett. 2012, 14, 1736-1739; (c) Wang, J.;
Wang, S.; Wang, G.; Zhang, J.; Yu, X.-Q. Chem. Commun. 2012, 48, 11769-11771; (d) Seiple,
I. B.; Su, S.; Rodriguez, R. A.; Gianatassio, R.; Fujiwara, Y.; Sobel A. L.; Baran, P. S. J. Am.
Chem. Soc. 2010, 132, 13194-13196.
20. (a) Morales, O. G.; Mendez, F.; Miranda, L. D. Tetrahedron Lett. 2007, 48, 4515-4518. (b)
Osornio, Y. M.; Almanza, R. C.; Montano, V. J.; Miranda. L. D. Chem. Commun. 2013, 48,
2316-2318.
21. Eberhardt, M. K. J. Org. Chem. 1977, 42, 832–835.
22. Giordano, C.; Belli, A. J. Org. Chem. 1979, 44, 2314–2315.
23. Witherington J.; Elliott R.L. Process for preparing quinolin antibiotic intermediates
WO/2004/014859.
24. Chen, P.; Carroll, P. J.; Sieburth, S. M. Synthesis 2007, 2351.
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