Regioselective α-arylation of coumarins and 2-pyridones with phenylhydrazines under transition-metal-free conditions

Article abstract of DOI:10.1039/c5ra20954d

A facile regioselective metal-free direct α-arylation of coumarins and 2-pyridones is achieved by the reaction of coumarins and 2-pyridones with phenylhydrazine in good yields. The reaction proceeds at room temperature under mild conditions using inexpensive reagents and without the need for step intensive activating groups. The methodology is operationally simple, practically viable and also allows the coupling of similar nitrogen heterocycle aza-coumarins without prerequisite N-protection.

Full text of DOI:10.1039/c5ra20954d

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Regioselective α‐arylation of coumarins and 2‐pyridones with
phenylhydrazines under transition‐metal‐free condition
Parul Chauhan,a Makthala Ravi,a Shikha Singh,a Prashant Prajapati,b Prem. P. Yadav*a
Received 00th January 20xx,
Accepted 00th January 20xx
A facile regioselective metal‐free direct α‐arylation of coumarins and 2‐pyridones is achieved by the reaction of coumarins
and 2‐pyridones with phenylhydrazine in good yields. The reaction proceeds at room temperature under mild conditions
using inexpensive reagents and without the need of step intensive activating groups. The methodology is operationally
simple, practically viable and also allows the coupling of similar nitrogen heterocycle aza‐coumarin without prerequisite N‐
protection.
DOI: 10.1039/x0xx00000x
www.rsc.org/
The metal‐free direct C‐H arylation processes have started to 2‐pyridones are difficult due to regioselectivity bias of β‐
emerge as
a
straightforward, atom‐economical and arylation of coumarins and γ‐arylation of 2‐pyridones, which is
environment‐friendly research.1 These methods are an expected in Heck‐type reaction.12 Radical mediated C‐H
alternative to metal‐catalyzed processes, which are associated arylation methods proved as a convenient method because of
with limitations such as step and cost intensive procedures the inherent reactivity of heterocycles towards aryl radical
along with the use of toxic, sensitive and environmentally species. The
α‐regioselectivity in case of coumarins/aza‐
hazardous metals and ligands.2 In recent past, radical C‐H coumarins and 2‐pyridones towards aryl radical is due to the
functionalization of innately reactive heterocycles has re‐ formation of resonance stabilized benzylic radical13 and allylic
emerged as avenue for selective, early or late stage radical14 intermediates respectively. Herein, we report a
functionalization of pharmaceutically important precursors K2CO3/air promoted regioselective method for direct α‐
and products.3 Radical‐mediated metal‐free C‐H arylations arylation of biologically prominent heterocycles such as
have been achieved substantially utilizing a variety of aryl coumarins, 2‐pyridones and aza‐coumarins
without
coupling partners4 and among the notable radical‐mediated prerequisite N‐protection under metal and ligand‐free
aryl coupling partners, base‐mediated arylhydrazine derived condition.
aryl radicals have emerged as powerful synthetic intermediate
towards the direct C‐H arylation under oxidative conditions
X = H, SO2Na, SO2Cl
H
with limited substrate scope.5 However, the utility of these
intermediates with robust control of regioselectivity in
oxidative C‐H arylation reactions of biologically prominent and
synthetically useful motifs is highly challenging and valuable.
3‐Arylcoumarins and 3‐aryl‐2‐pyridones are important
scaffolds present in many natural products and bioactive
compounds.6 In particular, α‐arylated coumarin derivatives
have been shown to be potent, selective monoamine oxidase
B inhibitors,7 active in neurological disorders8 and inhibitors of
HIV‐1 replication (Figure 2).9 Furthermore, 3‐arylcoumarins are
X
β
H
α
K2CO3
Air, rt.
H
NHNH2
H
O
β
O
O
H
β
α
(re
f 16, 17)
N2BF4
α
Jafarpour et al.
O
O
O
H
β
H
1. Transition-metal-free
2. Exclusively α−arylation
3. Good Yields at rt
α
O
O
4. No N-H protection
Kanai et al. (ref 18)
B(OH)2
H
H
Pd (mol %)
Mn (Equiv)
K2CO3
Air, rt.
γ
α
H
H
NHNH2
γ
α
Oxidant, >70ο
C
H
N
R
O
γ
α
N
R
O
N
O
Maiti et al. (ref 20)
R
Miura et al.
(ref 21)
R= H, CH3
Literarure reports
also important class of fluorophores and found
their
Present W ork
R = CH3
application as fluorescent labels in complex biological
systems.10 On the other hand, the 3‐aryl‐2‐pyridones, which is
key pharmacophore of pharmaceutically important molecules
such as Perampanel, and PD180970 (figure 1).11 Despite the
importance of 3‐aryl coumarins and 3‐aryl‐2‐pyridones as
biologically active scaffolds, the α‐arylation of coumarins and
Scheme 1 Strategic approaches for the synthesis of 3‐Arylcoumarins and 3‐Aryl‐2‐
pyridones.
Mostly the α‐arylation of coumarins was achieved either
from suitable phenyl substituted precursors15 or require
prefunctionalization at α‐position such as in palladium‐
catalyzed Suzuki coupling of 3‐halo coumarin with arylboronic
acid16 and palladium‐catalyzed decarboxylative coupling of
coumarin‐3‐carboxylic acid with haloarenes.17 The most
notable methodologies for regioselective α‐arylation were
a. Division of Medicinal and Process Chemistry, CSIR‐Central Drug Research
Institute, Lucknow‐226031, India. Fax: +91‐522‐2623405/2623938; Tel: :+91‐522‐
2612411‐18, Ext. 4761/4762; E‐mail: pp_yadav@cdri.res.in:
ppy_cdri@yahoo.co.in
b. National Institute of Pharmaceutical Education and Research, Raebareli‐229010,
India.
c.
†
Electronic Supplementary Information (ESI) available: Experimental
procedures, data and NMR spectra of all the final compounds. See
DOI: 10.1039/b000000x/
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Journal Name
desulfitative coupling of coumarins with arenesulfonyl were found to give better yield than K2CO3/air system (Table 1,
chloride,18 dehydrogenative cross‐coupling of coumarins with entries 7‐11 versus entry
1). In the absence of K2CO3 no
arenes via two‐fold C‐H activation under Palladium catalyst19 product was observed (Table 1, entry 12), which clearly
and recently Kanai and co‐workers reported porphyrin‐ indicated that the base is essential for this reaction. Different
mediated Meerwein arylation of coumarins which suffer from solvents other than DMSO were also screened such as DMF
some disadvantages such as synthesis and solubility of organic (dimethylformamide), DMA (dimethylacetamide), NMP (N‐
electron mediators and use of unstable and explosive methylpyrrolidone) and MeOH (methanol) but all of them
arylcoupling partners (arenediazonium salts).13 In recent years, produced lower yield of product 3u (Table 1, entries
1
and 13‐
only
a few reports are available for metal‐catalyzed 16). To check the essentiality of air as an oxidant in this
regioselective α‐arylation of N‐protected 2‐pyridones (i) transformation, we performed the reaction with degassed
Suzuki‐coupling of 5‐halouracil with arylboronic acid by Wnuk DMSO under N2 atmosphere. The yield of product 3u
group,20 (ii) iron‐catalyzed regioselective direct α‐arylation of decreased to 24%, which clearly indicated that oxygen is
N‐alkyl‐2‐pyridones with aryl boronic acid using K2S2O8 as an crucial for the reaction (Table 1, entry 17). In the presence of
oxidant and K2CO3 as base at 70°C by Maiti group,21 and O2 (ballon) similar yield of product 3u was observed (Table 1,
manganese‐mediated α‐selective direct arylation of N‐alkyl‐2‐ entry 18).
pyridone with arylboronic acid under N2 condition at 90°C by
Table 1 Optimization of the reaction conditionsa
Miura group.14 Although all the above methodologies have
been utilized effectively for α‐arylation of coumarins and 2‐
pyridones, but are limited by the prefunctionalization, use of
transition‐metals (Cu or Ag was used in equivalents), use of
ligands, high temperatures and low yields (Schema 1). Thus,
the development of an efficient transition‐metal‐free
Entry
1
2
3
4
5
6
7
8
Base (3 equiv)
K2CO3
Na2CO3
Ag2CO3
Cs2CO3
NaOEt
KtOBt
PIDA
Solvent
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMF
Yieldb (%)
methodology towards regioselective α‐arylation of coumarins
and 2‐pyridones is highly desirable.
85
30
35
60
55
30
35
20c
30
‐
N
OH
O
O
O
O
N
O
O
O
O
O
O
O
O
O
Vipirinin, HIV-1 Vpr Inhibitor
Lead for Alzheimer's disease
therapy
Inhibitor of HIV-1
Replication
TBHP
K2S2O8
DTBP
I2
Cl
NC
9
Me
F
O
N
10
11
12
13
14
15
16
17
18
Me
Cl
N
N
O
N
N
N
Me
H
‐
‐
Me
O
O
-
MAO-B inhibitor
Perampanel
PD180970
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
35
30
20
43
24d
84e
Figure 1 3‐arylcoumarin and 3‐aryl‐2‐pyridone based bioactive molecules.
DMA
NMP
MeOH
DMSO
DMSO
As part of our continuous efforts for the development of
efficient C‐H arylation and coupling processes for biologically
important motifs,5c,22 we pursued the synthetic challenge to
a Reaction condition: 1c (1.0 mmol), 2h (1.2 mmol), K2CO3 (3.0 mmol), DMSO (15
mL) at rt. b Isolated yield. c 70% aq. TBHP was used. d Under nitrogen atmosphere.
e Under O2 atmosphere.
identify
a practically viable metal‐free regioselective α‐
arylation of coumarin and 2‐pyridone with phenylhydrazines.
We initially investigated the α‐arylation of 7‐hydroxy coumarin
1c with 4‐methoxy phenylhydrazine 2i in the presence of
K2CO3 in DMSO (dimethyl sulfoxide) at room temperature
under air for 4 hours. To our delight, the reaction yielded only
After optimization results in hand, we turned our attention
towards the scope of the substrate in metal‐free regioselective
α‐arylation of coumarins with various phenylhydrazines. The
phenylhydrazines having electron‐withdrawing groups such as
4‐F, 4‐Cl, 4‐Br, 3F (Table 2, product 3a
donating groups such as 4‐Me, 3,4‐diMe, 4‐OMe (Table 2,
product 3g 3i) respectively on the aromatic ring, afforded the
α‐arylated products in good to excellent yields. However, 4‐
cyano substituted phenylhydrazine produced the α‐arylated
product in 20% yield (Table 2, product 3e). Electron donating
groups (such as OMe, Me) at C‐4 of phenylhydrazine reduce
the reaction time (Table 2, products 3g & 3i), however 4‐CN
function in the phenylhydrazine afforded only 20% yield in 24
h (Table 2, product 3e) and further no product was observed in
α‐arylated product 3u with 85% yield (Table 1, entry
C‐4 arylated product was observed.
1) and no
‐3d) and electron‐
Encouraged by above promising results in hand, further a
set of experiments was performed to optimize the reaction
conditions with various bases and oxidants (Table 1). We
screened different bases such as Na2CO3, Ag2CO3, Cs2CO3,
NaOEt and KtOBt (Table 1, entries 2‐6) and none of them were
found to be better than K2CO3. The efficiency of other oxidants
‐
such
as
(diacetoxyiodo)benzene
(PIDA),
tert‐butyl
hydroperoxide (TBHP), K2S2O8, di‐tert‐butyl peroxide (DTBP)
and molecular iodine were checked, however, none of them
2 | J. Name., 2012, 00, 1‐3
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the case of 4‐nitrophenylhydrazine even after prolonged (4‐6 h) (Table 2, products 3o‐3u) as compared to C‐7 methoxy
reaction time.
(14‐20 h) (Table 2, products 3v & 3w) and C‐6 methyl (6‐10 h)
(Table 2, products (Table 2, products 3j‐3n) substituted
coumarins. Notably, the nitro group at 6‐position of coumarin
did not furnish the α‐arylated product (Table 2, product 3x).
The C‐6 halogen (Cl and Br) containing coumarins with C‐4
electron‐donating (methyl and methoxy) phenylhydrazines
afforded α‐arylated product 67% and 52% respectively (Table
2, product 3y and 3z), however the substrates possessing
electron withdrawing groups (Cl and Br) both on C‐6 of
coumarins and C‐4 of arylhydrazines, drastically affect the
reaction outcome where no product was observed. To check
the feasibility of regioselective arylation on aza‐coumarins, we
tested the reaction of unprotected 2‐hydroxyqyinolines with
phenylhydrazines under optimized condition. Pleasingly, the
reaction proceeded smoothly without N‐protection and
afforded regioselectively α‐arylated products in moderate
yields (Table 2, products 3za and 3zb).
Table 2 Scope of regioselective α‐arylation of coumarin and aza‐coumarina
Scheme 2 Synthesis of 3‐(7‐chloroquinolin‐4‐yl)‐7‐hydroxy‐2H‐chromen‐2‐one.
Subsequently, the compatibility of present methodology
was further tested with heteroaromatic hydrazine, since the
heteroaromatic substitutions on bioactive molecules impart
desirable pharmacological and pharmacokinetic properties. To
achieve the unique substitution at α‐position, we attempted
the reaction of 4‐hydrazinoquinoline with 7‐hydroxycoumarin
under the optimized condition. To our delight, the reaction
afforded the compound
4 α‐(7‐chloroquinolin‐4‐yl)‐7‐hydroxy‐
2H‐chromen‐2‐one, a unique hybrid of quinoline and coumarin
in 51% yield (Scheme 2).
Table 3 Scope of regioselective α‐arylation of 2‐pyridonea
NHNH2.HCl
R1
H
γ
H
α
K2CO3 (3 equiv), DMSO
rt, air, 8 h-18 h
H
γ
α
N
R
O
R1
N
R
O
2
5
6
R = H, CH3
R = H, CH3
Br
F
Cl
N
H
O
N
H
O
N
H
O
N
O
H
6ab, 12 h, 76%
6d
, 16 h, 68%
6b, 8 h, 78%
Me
6c, 14 h, 82%
Br
Cl
a Reaction condition: 1 (1.0 mmol), 2 (1.2 mmol), K2CO3 (3.0 mmol), DMSO (15
mL) at rt. Isolated yields are given . b Phenylhydrazine was used as free base.
N
O
N
O
N
O
N
O
H
Me
Me
Me
6f, 10 h, 72%
Further, the scope of the methodology was investigated
with respect to coumarins. The coumarin moiety bearing
electron‐donating groups such as methyl, methoxy and
hydroxyl at the C‐6 or C‐7 position afforded their
corresponding α‐arylated products in moderate to good yields
(Table 2, products 3j‐3w), however the reaction time in case of
hydroxyl substituted coumarins at C‐7 was considerably less
6e, 18 h, 71%
6g
, 12 h, 77%
6h, 15 h, 74%
Br
Me
OMe
N
O
N
O
N
O
H
Me
Me
6c, No C-5 Arylation
6i, 14 h, 73%
6j
, 16 h, 76%
a Reaction condition: 5 (1.0 mmol), 2 (1.2 mmol), K2CO3 (3.0 mmol), DMSO (15
mL) at rt. Isolated yields are given .b Phenylhydrazine was used as free base.
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Successful installation of α‐arylation in aza‐coumarins
Conclusions
inspired us to expand the applicability of the method towards
metal‐free regioselective arylation of the 2‐pyridone moiety.
To the best of our knowledge, this is the first metal‐free report
for α‐C‐H arylation of 2‐pyridone. Gratifyingly the reaction of
2‐pyridones with phenylhydrazines afforded exclusively α‐
arylated products in good to excellent yields (Table 3, product
6a‐6j). It was noteworthy that the reaction proceeded with or
without N‐H protection of 2‐pyridones at room temperature
and also compatible with both electron withdrawing and
electron donating substitutions on phenylhydrazine.
In conclusion, we have achieved a transition‐metal‐free
regioselective α‐arylation of coumarins, 2‐pyridones and aza‐
coumarin via base/air‐promoted denitrogenative coupling of
phenylhydrazines in moderate to good yields. High functional
group tolerability with excellent regioselectivity and room
temperature reaction condition are salient features of the
present strategy.
Experimental
To gain insight into the mechanism, we performed control
experiment for radical trapping. The reaction of 2,2,6,6‐
General Information
tetramethylpiperidine‐1‐oxyl
phenylhydrazine 2e afforded
tetramethylpiperidin‐1‐yl)oxy)benzonitrile
Scheme 3)
(TEMPO)
with
4‐cyano
4‐((2,2,6,6‐
1
adduct
All glass apparatus were oven dried prior to use. H NMR and
13C NMR spectra were recorded on Bruker Avance‐400 using
CDCl3 and DMSO‐d6 as solvent and tetramethylsilane as
internal reference. Splitting patterns are described as singlet
(s), doublet (d), triplet (t), multiplet (m) and broad (br). IR
spectra were recorded on a FT‐IR spectrophotometer and
melting points were determined on melting point apparatus
and are uncorrected. Electrospray ionization mass
spectrometry (ESI‐MS) was obtained on Thermo LCQ
Advantage Max Spectrometer and HRMS was recorded on
Agilent 6520 Q‐TOF. Reactions were monitored on silica gel
TLC plates (coated with TLC grade silica gel, obtained from
Merck). Detecting agents used (for TLC) were: iodine vapors
and/or spraying with an aq. solution of vanillin in 10% sulfuric
acid followed by heating at 100°C. Column chromatography
was performed over silica gel (230‐400 Mesh) by using Smart
flash EPCLC AI‐700X YAMAZEN with minimal amount of
solvent. All chemicals and reagents were obtained from Aldrich
, Lancaster, Alfa Aesar and were used without further
purification.
7
in 64% yield
(
.
Scheme 3 Radical trapping experiment with TEMPO.
Based on our experiment, previous literature reports14,20 23‐
,
and our previous work,5c a possible mechanism has been
proposed in Scheme 3. Initially, the treatment of
27
phenylhydrazine
Phenylhydrazine [
hydrochloride
], which further undergoes oxidation in the
24,27 by removal of
with
base
afforded
A
presence of Base/O2 to form aryl radical [
N2 and then aryl radical addition to coumarin/aza‐coumarin (
and 2‐pyridone (
) afforded benzylic radical13 intermediates [
and allylic radical14 intermediate [
B]
1
C
)
]
4
D
] respectively, which were
stabilized by resonance. Upon further oxidation,26
intermediates [ ] and [ ] leads to α‐arylated product of
) and pyridone ( ) (Scheme 4).
C
D
General Experimental Procedures
coumarin, aza‐coumarin (
3
5
Representative procedure for the synthesis of product 3a
A
solution of coumarin 1a (146 mg, 1.0 mmol),
NHNH2
Base
NHNH2.HCl
phenylhydrazine 2a (215 mg, 1.2 mmol) and potassium
carbonate (408 mg, 3.0 mmol) in dimethyl sulphoxide (15 mL)
was stirred at room temperature for 15 hours. Next, the
reaction was diluted with water (80 mL) and the aqueous layer
was extracted with ethyl acetate (3×20 mL). The organic layer
was further dried over sodium sulphate (anhydrous) and
concentrated under reduced pressure to give crude product,
which upon purification by column chromatography over silica
gel (gradient elution with Hexane: ethyl acetate, 9:1 to 7:3)
afforded the desired product 179 mg (70%) of 3a as white
solid. The remaining reactions were carried out following this
procedure for products 3b‐3zb.
A
2
Base/O2
N2
H
O2
B
Fast
X
O
X
O
X
C
O
3
1
X = O, NH
Coumarin, Aza-Coumarin
O2
B
Fast
N
R
O
N
R
O
R = H, CH3
N
R
O
4
5
D
Pyridone
Scheme 4 Plausible mechanism.
Representative procedure for the synthesis of product 6b
A
solution of 2‐pyridone 5a (95 mg, 1.0 mmol),
phenylhydrazine 2b (215 mg, 1.2 mmol) and potassium
carbonate (408 mg, 3.0 mmol) in dimethyl sulphoxide (15 mL)
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was stirred at room temperature for 8 hours. Next, the Yield 55% as white solid: mp 152‐154°C; FT‐IR (KBr, cm‐1) 3019,
reaction was diluted with water (80 mL) and the aqueous layer 1610, 1215, 1069; 1H NMR (400 MHz, CDCl3) δ 7.08‐7.13 (m,
was extracted with ethyl acetate (3×20 mL). The organic layer 1H), 7.29‐7.33 (m, 1H), 7.37‐7.44 (m, 2H), 7.45‐7.51 (m, 2H),
was further dried over sodium sulphate (anhydrous) and 7.53‐7.57 (m, 2H), 7.84 (s, 1H); 13C NMR (100 MHz, CDCl3) δ
concentrated under reduced pressure to give crude product, 115.81 (d, J = 22.85 Hz, CH), 115.89 (d, J = 21.04 Hz, CH),
which was further purified by column chromatography over 116.54 (CH), 119.42 (C), 124.19 (d, J = 2.86 Hz, CH), 124.65
silica gel to afford the desired product 160 mg (78%) of 6b as (CH), 127.06 (C), 128.08 (CH), 130.03 (d, J = 8.37 Hz, CH),
white solid. The remaining reactions were carried out 131.82 (CH), 136.74 (d, J = 8.28 Hz, C), 140.40 (CH), 153.62 (C),
following this procedure for products 6a and 6c—6j.
160.20 (C), 163.90 (d, J = 244.27 Hz, C‐F); ESI‐MS (m/z) 241
(M+H)+; HRMS (ESI) calculated for C15H10FO2 (M+H)+ 241.0665
found 241.0659.
Representative for the synthesis of product 7
4‐(2‐oxo‐2H‐chromen‐3‐yl)benzonitrile (3e).30
A solution of phenylhydrazine 2e (169 mg, 1.0 mmol), 4‐
((2,2,6,6‐tetramethylpiperidin‐1‐yl)oxy)benzonitrile (234 mg,
1.5 mmol) and potassium carbonate (408 mg, 3.0 mmol) in
dimethyl sulphoxide (20 mL) was stirred at room temperature
for 5 hours. Next, the reaction was diluted with water (100 mL)
and the aqueous layer was extracted with ethyl acetate (3×20
mL). The organic layer was further dried over sodium sulphate
(anhydrous) and concentrated under reduced pressure to give
crude product, which was further purified by column
chromatography over silica gel to afford the desired product
Yield 20% as white solid: mp 152‐154oC; FT‐IR (KBr, cm‐1) 3019,
2230, 1614, 1215, 1068; 1H NMR (300 MHz, CDCl3) δ 7.31‐7.41
(m, 2H), 7.57‐7.62 (m, 2H), 7.72‐7.76 (m, 2H), 7.83‐7.87 (m,
2H), 7.89 (s, 1H); 13C NMR (75 MHz, CDCl3) δ 112.46 (C), 116.68
(CH), 118.51 (C), 119.19 (C), 124.85 (CH), 126.47 (C), 128.29
(CH), 129.20 (2×CH), 132.22 (2×CH), 132.41 (CH), 139.18 (C),
141.31 (CH), 153.82 (C), 159.87 (C); ESI‐MS (m/z) 248 (M+H)+;
HRMS (ESI) calculated for C16H10NO2 (M+H)+ 248.0712 found
248.0687.
3‐phenyl‐2H‐chromen‐2‐one (3f).28
165 mg (64%) of 7 as white solid.
Yield 64% as white solid: mp 135‐137°C; FT‐IR (KBr, cm‐1) 3019,
1613, 1215, 1069; 1H NMR (400 MHz, CDCl3) δ 7.28‐7.32 (m,
1H), 7.37‐7.48 (m, 4H), 7.51‐7.56 (m, 2H), 7.69‐7.72 (m, 2H),
7.82 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 116.49 (CH), 119.71
(C), 124.50 (CH), 127.91 (CH), 128.42 (C), 128.49 (2×CH),
128.55 (2×CH), 128.88 (CH), 131.41 (CH), 134.73 (C), 139.86
(CH), 153.56 (C), 160.60 (C); ESI‐MS (m/z) 223 (M+H)+; HRMS
(ESI) calculated for C15H11O2 (M+H)+ 223.0759 found 223.0763.
3‐(p‐tolyl)‐2H‐chromen‐2‐one (3g).28
Compound Characterization Data
3‐(4‐chlorophenyl)‐2H‐chromen‐2‐one (3a).28
Yield 70% as white solid: mp 180‐182°C; FT‐IR (KBr, cm‐1) 3019,
1618, 1210, 1076; 1H NMR (400 MHz, CDCl3) δ 7.29‐7.33 (m,
1H), 7.36‐7.39 (m, 1H), 7.41‐7.44 (m, 2H), 7.53‐7.57 (m, 2H),
7.66‐7.68 (m, 2H), 7.82 (s, 1H); 13C NMR (100 MHz, CDCl3) δ
116.54 (CH), 119.51 (C), 124.63 (CH), 127.20 (C), 127.98 (CH),
128.71 (2×CH), 129.85 (2×CH), 131.68 (CH), 133.10 (C), 134.96
(C), 139.91 (CH), 153.58 (C), 160.34 (C); ESI‐MS (m/z) 257
(M+H)+; HRMS (ESI) calculated for C15H10ClO2 (M+H)+ 257.0369,
found 257.0367.
Yield 68% as white solid: mp 150‐152°C; FT‐IR (KBr, cm‐1) 3019,
1
1618, 1210, 1076; H NMR (400 MHz, CDCl3) δ 2.41 (s, 3H),
7.27‐7.32 (m, 3H), 7.37 (d, J = 8.2 Hz, 1H), 7.51‐7.55 (m, 2H),
7.62 (d, J = 7.76 Hz, 2H), 7.79 (s, 1H); 13C NMR (100 MHz,
CDCl3) δ 21.30 (CH3) 116.44 (CH), 119.80 (C), 124.44 (CH),
127.80 (CH), 128.41 (C & 2×CH), 129.19 (2×CH), 131.19 (CH),
131.83 (C), 138.94 (C), 139.19 (CH), 153.46 (C), 160.69 (C); ESI‐
MS (m/z) 237 (M+H)+; HRMS (ESI) calculated for C16H13O2
(M+H)+ 237.0916 found 237.0897.
3‐(4‐bromophenyl)‐2H‐chromen‐2‐one (3b).28
Yield 59% as light yellow solid: mp 190‐192°C; FT‐IR (KBr, cm‐1)
3019, 1610, 1215, 1069; 1H NMR (400 MHz, CDCl3) δ 7.29‐7.33
(m, 1H), 7.36‐7.39 (m, 1H), 7.53‐7.62 (m, 6H), 7.82 (s, 1H); 13
C
NMR (100 MHz, CDCl3) δ 116.55 (CH), 119.50 (C), 123.21 (C),
124.65 (CH), 127.23 (C), 127.99 (CH), 130.12 (2×CH), 131.67
(2×CH), 131.72 (CH), 133.57 (C), 139.93 (CH), 153.58 (C),
160.27 (C); ESI‐MS (m/z) 301 (M+H)+; HRMS (ESI) calculated for
C15H10BrO2 (M+H)+ 300.9864 found 300.9862.
3‐(3,4‐dimethylphenyl)‐2H‐chromen‐2‐one (3h).
Yield 66% as light yellow solid: mp 110‐112°C; FT‐IR (KBr, cm‐1)
3019, 1609, 1215, 1069; 1H NMR (400 MHz, CDCl3) δ 2.31 (s,
3H), 2.33 (s, 3H), 7.21 (d, J = 7.80 Hz, 1H), 7.27‐7.31 (m, 1H),
7.35‐7.37 (m, 1H), 7.43‐7.46 (m, 1H), 7.48‐7.54 (m, 3H), 7.78 (s,
1H); 13C NMR (100 MHz, CDCl3) δ 19.61 (CH3), 19.89 (CH3),
116.42 (CH), 119.83 (C), 124.40 (CH), 125.99 (CH), 127.77 (CH),
128.50 (C), 129.61 (CH), 129.76 (CH), 131.11 (CH), 132.26 (C),
136.69 (C), 137.65 (C), 139.12 (CH), 153.44 (C), 160.72 (C); ESI‐
MS (m/z) 251 (M+H)+; HRMS (ESI) calculated for C17H15O2
(M+H)+ 251.1072 found 251.1069.
3‐(4‐fluorophenyl)‐2H‐chromen‐2‐one (3c).28
Yield 57% as white solid: mp 158‐160°C; FT‐IR (KBr, cm‐1) 3021,
1609, 1215, 1113; 1H NMR (400 MHz, CDCl3) δ 7.11‐7.17 (m,
2H) 7.29‐7.33 (m, 1H), 7.37‐7.39 (m, 1H), 7.52‐7.56 (m, 2H),
7.69‐7.72 (m, 2H), 7.79 (s, 1H); 13C NMR (100 MHz, CDCl3) δ
115.60 (d, J = 21.47 Hz, 2×CH), 116.49 (CH), 119.58 (C), 124.59
(CH), 127.32 (C), 127.91 (CH), 130.47 (d, J = 8.15 Hz, 2×CH),
130.71 (C), 131.52 (CH), 139.69 (CH), 153.51 (C), 160.55 (C),
164.33 (d, J = 247.39 Hz, C‐F); ESI‐MS (m/z) 241 (M+H)+; HRMS
(ESI) calculated for C15H10FO2 (M+H)+ 241.0665 found
241.0668.
3‐(4‐methoxyphenyl)‐2H‐chromen‐2‐one (3i).28
Yield 69% as white solid: mp 140‐142°C; FT‐IR (KBr, cm‐1) 3019,
1
1610, 1215, 1026; H NMR (400 MHz, CDCl3) δ 3.86 (s, 3H),
6.97‐6.99 (m, 2H), 7.27‐7.31 (m, 1H), 7.35‐7.37 (m, 1H), 7.49‐
7.54 (m, 2H), 7.66‐7.69 (m, 2H), 7.76 (s, 1H); 13C NMR (100
MHz, CDCl3) δ 55.38 (CH3), 113.94 (2×CH), 116.40 (CH), 119.87
3‐(3‐fluorophenyl)‐2H‐chromen‐2‐one (3d).29
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1‐3 | 5
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Journal Name
(C), 124.43 (CH), 127.10 (C), 127.70 (CH), 127.91 (C), 129.85 Yield 82% as light yellow solid: mp 252‐254°C; FT‐IR (KBr, cm‐1)
(2×CH), 131.01 (CH), 138.48 (CH), 153.33 (C), 160.19 (C), 3401, 3019, 1602, 1215, 1069; 1H NMR (400 MHz, DMSO‐d6) δ
160.80 (C); ESI‐MS (m/z) 253 (M+H)+; HRMS (ESI) calculated for 6.75 (d, J = 2.16 Hz , 1H), 6.82‐6.84 (dd, J = 8.48, 2.24 Hz, 1H),
C16H13O3 (M+H)+ 253.0865 found 253.0855.
7.49‐7.51 (m, 2H), 7.60 (d, J = 8.56 Hz, 1H), 7.72‐7.75 (m, 2H),
3‐(4‐chlorophenyl)‐6‐methyl‐2H‐chromen‐2‐one (3j).
8.19 (s, 1H), 10.65 (s, 1H); 13C NMR (DMSO‐d6) δ 102.21 (CH),
Yield 64% as white solid: mp 158‐160°C; FT‐IR (KBr, cm‐1) 3021, 112.35 (C), 113.96 (CH), 121.29 (C), 128.63 (2×CH), 130.46
1
1612, 1215, 1026; H NMR (400 MHz, CDCl3) δ 2.43 (s, 3H), (2×CH), 130.58 (CH), 133.13 (C), 134.39 (C), 141.85 (CH),
7.25‐7.27 (m, 1H), 7.33‐7.36 (m, 2H), 7.39‐7.43 (m, 2H), 7.64‐ 155.47 (C), 160.38 (C), 161.93 (C); ESI‐MS (m/z) 273 (M+H)+;
7.67 (m, 2H), 7.75 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 20.80 HRMS (ESI) calculated for C15H10ClO3 (M+H)+ 273.0318, found
(CH3), 116.25 (CH), 119.25 (C), 127.03 (C), 127.75 (CH), 128.68 273.0291.
(2×CH), 129.85 (2×CH), 132.75 (CH), 133.27 (C), 134.33 (C), 3‐(4‐fluorophenyl)‐7‐hydroxy‐2H‐chromen‐2‐one (3p).32
134.85 (C), 139.95 (CH), 151.73 (C), 160.57 (C); ESI‐MS (m/z) Yield 79% as light yellow solid: mp 245‐247°C; FT‐IR (KBr, cm‐1)
271 (M+H)+; HRMS (ESI) calculated for C16H12ClO2 (M+H)+ 3394, 3019, 1608, 1215, 1024; 1H NMR (400 MHz, DMSO‐d6) δ
271.0526 found 271.0518.
6.75 (d, J = 2.24 Hz , 1H), 6.81‐6.84 (dd, J = 8.52, 2.28 Hz, 1H),
7.25‐7.29 (m, 2H), 7.59 (d, J = 8.56 Hz , 1H), 7.72‐7.76 (m, 2H),
3‐(4‐fluorophenyl)‐6‐methyl‐2H‐chromen‐2‐one (3k).
Yield 53% as white solid: mp 158‐160°C; FT‐IR (KBr, cm‐1) 3019, 8.15 (s, 1H), 10.60 (s, 1H); 13C NMR (DMSO‐d6) δ 102.19 (CH),
1
1603, 1215, 1084; H NMR (400 MHz, CDCl3) δ 2.42 (s, 3H), 112.39 (C), 113.90 (CH), 115.60 (d, J = 21.31 Hz, 2×CH), 121.63
7.11‐7.15 (m, 2H), 7.25‐7.27 (m, 1H), 7.32‐7.35 (m, 2H), 7.67‐ (C), 130.45 (CH), 130.89 (d, J = 8.1 Hz, 2×CH), 131.92 (C),
7.71 (m, 2H), 7.73 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 20.80 141.54 (CH), 155.38 (C), 160.56 (C), 161.75 (C), 163.55 (d, J =
(CH3), 115.57 (d, J = 21.49 Hz, 2×CH), 116.22 (CH), 119.32 (C), 243.92 Hz, C‐F); ESI‐MS (m/z) 257 (M+H)+; HRMS (ESI)
127.19 (C), 127.67 (CH), 130.45 (d, J = 8.17 Hz, 2×CH), 130.87 calculated for C15H10FO3 (M+H)+ 257.0614 found 257.0593.
(C), 132.57 (CH), 134.28 (C), 139.70 (CH), 151.67 (C), 160.76 3‐(4‐bromophenyl)‐7‐hydroxy‐2H‐chromen‐2‐one (3q).33
(C), 164.29 (d, J = 247.4 Hz, C‐F); ESI‐MS (m/z) 255 (M+H)+; Yield 80% as light yellow solid: mp 228‐230oC; FT‐IR (KBr, cm‐1)
HRMS (ESI) calculated for C16H12FO2 (M+H)+ 255.0821 found 3410, 3019, 1602, 1215, 1084; 1H NMR (400 MHz, DMSO‐d6) δ
255.0823.
6.75 (d, J = 2.16 Hz , 1H), 6.81‐6.84 (dd, J = 8.48, 2.24 Hz, 1H),
6‐methyl‐3‐phenyl‐2H‐chromen‐2‐one (3l).28
7.59‐7.68 (m, 5H), 8.20 (s, 1H), 10.65 (s, 1H); 13C NMR (DMSO‐
Yield 57% as light brown solid: mp 140‐142°C; FT‐IR (KBr, cm‐1) d6) δ 102.22 (CH), 112.37 (C), 113.98 (CH), 121.35 (C), 121.75
3019, 1613, 1215, 1070; 1H NMR (400 MHz, CDCl3) δ 2.43 (s, (C), 130.60 (CH), 130.76 (2×CH), 131.57 (2×CH), 134.77 (C),
3H), 7.28 (s, 1H), 7.33‐7.35 (m, 2H), 7.38‐7.47 (m, 3H), 7.68‐ 141.86 (CH), 155.48 (C), 160.33 (C), 161.95 (C); ESI‐MS (m/z)
7.71 (m, 2H), 7.76 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 20.80 317 (M+H)+; HRMS (ESI) calculated for C15H10BrO3 (M+H)+
(CH3), 116.20 (CH), 119.45 (C), 127.69 (CH), 128.26 (C), 128.47 316.9813 found 316.9806.
(2×CH), 128.55 (2×CH), 128.78 (CH), 132.46 (CH), 134.17 (C), 7‐hydroxy‐3‐phenyl‐2H‐chromen‐2‐one (3r).19
134.90 (C), 139.89 (CH), 151.71 (C), 160.82 (C); ESI‐MS (m/z) Yield 78% as light yellow solid: mp 180‐182°C; FT‐IR (KBr, cm‐1)
237 (M+H)+; HRMS (ESI) calculated for C16H13O2 (M+H)+ 3400, 3019, 1611, 1215, 1069; 1H NMR (400 MHz, DMSO‐d6) δ
237.0916 found 237.0900.
6.76 (d, J = 2.12 Hz, 1H), 6.81‐6.84 (dd, J = 8.48, 2.28 Hz, 1H),
7.36‐7.46 (m, 3H), 7.60 (d, J = 8.52 Hz, 1H), 7.68‐7.70 (m, 2H),
3‐(4‐methoxyphenyl)‐6‐methyl‐2H‐chromen‐2‐one (3m).19
Yield 67% as white solid: mp 134‐136°C; FT‐IR (KBr, cm‐1) 3019, 8.15 (s, 1H), 10.59 (s, 1H); 13C NMR (DMSO‐d6) δ 102.19 (CH),
1
1611, 1215, 1069; H NMR (400 MHz, CDCl3) δ 2.38 (s, 3H), 112.47 (C), 113.86 (CH), 122.66 (C), 128.47 (CH), 128.63
3.82 (s, 3H), 6.92‐6.96 (m, 2H), 7.20‐7.23 (m, 1H), 7.27‐7.28 (m, (2×CH), 128.73 (2×CH), 130.46 (CH), 135.58 (C), 141.58 (CH),
2H), 7.62‐7.65 (m, 2H), 7.67 (s, 1H); 13C NMR (100 MHz, CDCl3) 155.40 (C), 160.54 (C), 161.72 (C); ESI‐MS (m/z) 239 (M+H)+;
δ 20.80 (CH3), 55.38 (CH3), 113.92 (2×CH), 116.11 (CH), 119.60 HRMS (ESI) calculated for C15H11O3 (M+H)+ 239.0708 found
(C), 127.26 (C), 127.50 (CH), 127.76 (C), 129.83 (2×CH), 132.07 239.0738.
(CH), 134.08 (C), 138.53 (CH), 151.48 (C), 160.12 (C), 161.03 7‐hydroxy‐3‐(p‐tolyl)‐2H‐chromen‐2‐one (3s).34
(C); ESI‐MS (m/z) 267 (M+H)+; HRMS (ESI) calculated for Yield 88% as light yellow solid: mp 242‐244oC; FT‐IR (KBr, cm‐1)
C17H15O3 (M+H)+ 267.1021 found 267.1012.
3400, 3019, 1602, 1215, 1084; 1H NMR (400 MHz, DMSO‐d6) δ
2.34 (s, 3H), 6.74 (d, J = 2.24 Hz , 1H), 6.80‐6.83 (dd, J = 8.48,
6‐methyl‐3‐(p‐tolyl)‐2H‐chromen‐2‐one (3n).7b
Yield 67% as light yellow solid: mp 138‐140°C; FT‐IR (KBr, cm‐1) 2.28 Hz , 1H), 7.24 (d, J = 7.96 Hz , 2H), 7.58‐7.60 (dd, J = 8.52,
3019, 1621, 1215, 1112; 1H NMR (400 MHz, CDCl3) δ 2.39 (s, 2.08 Hz, 3H), 8.11 (s, 1H), 10.56 (s, 1H); 13C NMR (DMSO‐d6) δ
3H), 2.41 (s, 3H), 7.23‐7.25 (m, 3H), 7.30‐7.32 (m, 2H), 7.59 (d, 21.26 (CH3) 102.16 (CH), 112.51 (C), 113.81 (CH), 122.57 (C),
J = 8.16 Hz, 2H), 7.72 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 128.56 (2×CH), 129.21 (2×CH), 130.33 (CH), 132.65 (C), 137.90
20.79 (CH3), 21.29 (CH3), 116.14 (CH), 119.53 (C), 127.60 (CH), (C), 140.91 (CH), 155.27 (C), 160.58 (C), 161.56 (C); ESI‐MS
128.19 (C), 128.41 (2×CH), 129.16 (2×CH), 131.99 (C), 132.24 (m/z) 253 (M+H)+; HRMS (ESI) calculated for C16H13O3 (M+H)+
(CH), 134.09 (C), 138.82 (C), 139.22 (CH), 151.61 (C), 160.90 253.0865 found 253.0846.
(C); ESI‐MS (m/z) 251 (M+H)+; HRMS (ESI) calculated for 3‐(3,4‐dimethylphenyl)‐7‐hydroxy‐2H‐chromen‐2‐one (3t).
C17H15O2 (M+H)+ 251.1072 found 251.1073.
Yield 82% as light brown solid: mp 210‐212oC; FT‐IR (KBr, cm‐1)
3399, 3019, 1602, 1215, 1084; 1H NMR (400 MHz, DMSO‐d6) δ
2.25 (s, 3H), 2.26 (s, 3H), 6.74 (d, J = 2.12 Hz, 1H), 6.79‐6.82
3‐(4‐chlorophenyl)‐7‐hydroxy‐2H‐chromen‐2‐one (3o).31
6 | J. Name., 2012, 00, 1‐3
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(dd, J = 8.48, 2.24 Hz , 1H), 7.18 (d, J = 7.88 Hz, 1H), 7.41‐7.47 (M+H)+; HRMS (ESI) calculated for C16H12BrO3 (M + H)+
(m, 2H), 7.59 (d, J = 8.52 Hz, 1H), 8.09 (s, 1H), 10.56 (s, 1H); 13
C
330.9970 found 330.9971.
NMR (DMSO‐d6) δ 19.61 (CH3), 19.93 (CH3) 102.15 (CH), 112.53 3‐(4‐chlorophenyl)quinolin‐2(1H)‐one (3za).38
(C), 113.79 (CH), 122.69 (C), 126.12 (CH), 129.62 (CH), 129.71 Yield 65% as white solid: mp 252‐254°C; FT‐IR (KBr, cm‐1) 3410,
(CH), 130.28 (CH), 133.00 (C), 136.34 (C), 136.66 (C), 140.80 3019, 1656; 1H NMR (400 MHz, DMSO‐d6) δ 7.18‐7.22 (m, 1H),
(CH), 155.24 (C), 160.57 (C), 161.50 (C); ESI‐MS (m/z) 267 7.34 (d, J = 8.2 Hz, 1H), 7.48‐7.53 (m, 3H), 7.73 (d, J = 7.16 Hz,
(M+H)+; HRMS (ESI) calculated for C17H15O3 (M+H)+ 267.1021 1H), 7.80‐7.83 (m, 2H), 8.16 (s, 1H), 11.99 (s, 1H); 13C NMR
found 267.1018.
(100 MHz, DMSO‐d6) δ 115.20 (CH), 119.91 (C), 122.45 (CH),
128.40 (2×CH), 128.69 (CH), 130.54 (C), 130.90 (3×CH), 132.97
7‐hydroxy‐3‐(4‐methoxyphenyl)‐2H‐chromen‐2‐one (3u).35
Yield 85% as light brown solid: mp 220‐222oC; FT‐IR (KBr, cm‐1) (C), 135.50 (C), 138.36 (CH), 138.91 (C), 161.33 (C); ESI‐MS
3408, 3019, 1611, 1215, 1069; 1H NMR (400 MHz, DMSO‐d6) δ (m/z) 236 (M+H)+; HRMS (ESI) calculated for C15H11ClNO
3.79 (s, 3H), 6.74 (d, J = 2.16 Hz, 1H), 6.79‐6.82 (dd, J = 8.48, (M+H)+ 256.0529 found 256.0525.
2.28 Hz, 1H), 6.98‐7.01 (m, 2H), 7.59 (d, J = 8.56 Hz, 1H), 7.63‐ 4‐methyl‐3‐phenylquinolin‐2(1H)‐one (3zb).39
7.67 (m, 2H), 8.08 (s, 1H), 10.53 (s, 1H); 13C NMR (100 MHz, Yield 52% as white solid: mp 240‐242°C; FT‐IR (KBr, cm‐1) 3408,
DMSO‐d6) δ 55.65 (CH3) 102.15 (CH), 112.58 (C), 113.77 (CH), 3019, 1646; 1H NMR (400 MHz, DMSO‐d6) δ 2.25 (s, 3H), 7.19‐
114.08 (2×CH), 122.32 (C), 127.78 (C), 129.96 (2×CH), 130.17 7.25 (m, 3H), 7.33‐7.38 (m, 2H), 7.41‐7.45 (m, 2H), 7.49‐7.53
(CH), 140.19 (CH), 155.12 (C), 159.62 (C), 160.68 (C), 161.37 (m, 1H), 7.77‐7.79 (dd, J = 8.12, 0.96 Hz, 1H), 11.78 (s, 1H); 13C
(C); ESI‐MS (m/z) 269 (M+H)+; HRMS (ESI) calculated for NMR (100 MHz, DMSO‐d6) δ 17.02 (CH3), 115.60 (CH), 120.36
C16H13O4 (M+H)+ 269.0814 found 269.0773.
(C), 122.25 (CH), 125.70 (CH), 127.62 (CH), 128.29 (2×CH),
130.45 (CH), 130.74 (2×CH), 132.46 (C), 136.76 (C), 138.27 (C),
3‐(4‐chlorophenyl)‐7‐methoxy‐2H‐chromen‐2‐one (3v).33
Yield 58% as white solid: mp 158‐160°C; FT‐IR (KBr, cm‐1) 3020, 143.71 (C), 161.47 (C); ESI‐MS (m/z) 236 (M+H)+; HRMS (ESI)
1613, 1215, 1076; H NMR (400 MHz, CDCl3) δ 3.89 (s, 3H), calculated for C16H14NO (M+H)+ 236.1075 found 236.1068.
1
6.86‐6.89 (m, 2H), 7.39‐7.45 (m, 3H), 7.63‐7.66 (m, 2H), 7.76 (s, 3‐(7‐chloroquinolin‐4‐yl)‐7‐hydroxy‐2H‐chromen‐2‐one (4).
1H); 13C NMR (100 MHz, CDCl3) δ 55.84 (CH3), 100.47 (CH), Yield 51% as light yellow solid: mp 225‐230°C; FT‐IR (KBr, cm‐1)
112.97 (CH), 113.18 (C), 123.58 (C), 128.63 (2×CH), 128.94 3409, 3019, 1644, 1215, 1069; 1H NMR (400 MHz, DMSO‐d6) δ
(CH), 129.69 (2×CH), 133.44 (C), 134.45 (C), 140.08 (CH), 6.85‐6.98 (m, 2H), 7.61‐7.66 (m, 3H), 7.97 (d, J = 9.12 Hz , 1H),
155.41 (C), 160.66 (C), 162.87 (C); ESI‐MS (m/z) 287 (M+H)+; 8.17 (d, J = 14.68 Hz, 2H), 9.01 (d, J = 3.84 Hz, 1H), 10.80 (brd,
HRMS (ESI) calculated for C16H12ClO3 (M+H)+ 287.0475 found 1H); 13C NMR (100 MHz, DMSO‐d6) δ 102.53 (CH), 111.97 (C),
287.0473.
114.06 (CH), 120.02 (C), 123.26 (CH), 125.47 (C), 127.76 (CH),
128.36 (CH), 128.64 (CH), 130.85 (CH), 134.60 (C), 142.71 (C),
7‐methoxy‐3‐(p‐tolyl)‐2H‐chromen‐2‐one (3w).19
Yield 51% as white solid: mp 105‐107°C; FT‐IR (KBr, cm‐1) 3019, 145.11 (CH), 148.74 (C), 152.01 (CH), 156.23 (C), 160.18 (C),
1618, 1215, 1069; H NMR (400 MHz, CDCl3) δ 2.42 (s, 3H), 162.45 (C); ESI‐MS (m/z) 324 (M+H)+; HRMS (ESI) calculated for
1
3.91 (s, 3H), 6.88‐6.90 (m, 2H), 7.26‐7.28 (m, 2H), 7.43‐7.46 C18H11ClNO3 (M+H)+ 324.0427 found 324.0429.
(m, 1H), 7.60‐7.62 (m, 2H), 7.76 (s, 1H); 13C NMR (100 MHz, 3‐phenylpyridin‐2(1H)‐one (6a).
CDCl3) δ 21.26 (CH3), 55.79 (CH3), 100.43 (CH), 112.73 (CH), Yield 76% as white solid: mp 197‐199°C; FT‐IR (KBr, cm‐1) 3402,
113.46 (C), 124.86 (C), 128.27 (2×CH), 128.73 (CH), 129.13 3019, 1641; 1H NMR (400 MHz, DMSO‐d6) δ 6.29 (t, J = 6.68 Hz,
(2×CH), 132.14 (C), 138.44 (C), 139.39 (CH), 155.23 (C), 161.00 1H), 7.28‐7.31 (m, 1H), 7.36‐7.39 (m, 3H), 7.62‐7.64 (dd, J =
(C), 162.49 (C); ESI‐MS (m/z) 267 (M+H)+; HRMS (ESI) 6.88, 2.0 Hz, 1H), 7.69‐7.72 (m, 2H), 11.77 (s, 1H); 13C NMR
calculated for C17H15O3 (M + H)+ 267.1021 found 267.1010.
(100 MHz, DMSO‐d6) δ 105.85 (CH), 127.66 (CH), 128.32
(2×CH), 128.58 (2×CH), 130.43 (C), 135.15 (CH), 137.27 (C),
6‐chloro‐3‐(p‐tolyl)‐2H‐chromen‐2‐one (3y).36
Yield 67% as white solid: mp 176‐178°C; FT‐IR (KBr, cm‐1) 3019, 139.16 (CH), 161.70 (C); ESI‐MS (m/z) 172 (M+H)+; HRMS (ESI)
1621, 1230, 1071; H NMR (400 MHz, CDCl3) δ 2.43 (s, 3H), calculated for C11H10NO (M+H)+ 172.0762 found 172.0756.
1
7.28‐7.34 (m, 3H), 7.47‐7.49 (dd, J = 8.76, 2.4 Hz, 1H), 7.54 (d, J 3‐(4‐chlorophenyl)pyridin‐2(1H)‐one (6b).
= 2.36 Hz, 1H), 7.62 (d, J = 8.12 Hz, 1H), 7.72 (s, 1H); 13C NMR Yield 78% as white solid: mp 182‐184°C; FT‐IR (KBr, cm‐1) 3409,
(100 MHz, CDCl3) δ 21.32 (CH3), 117.85 (CH), 120.83 (C), 3019, 1631; 1H NMR (400 MHz, DMSO‐d6) δ 6.29 (t, J = 6.72 Hz,
126.97 (CH), 128.42 (2×CH), 129.27 (2×CH), 129.50 (C), 129.67 1H), 7.39‐7.44 (m, 3H), 7.67‐7.69 (dd, J = 6.96, 2.08 Hz, 1H),
(C), 131.06 (CH), 131.35 (C), 137.72 (CH), 139.38. (C), 151.78 7.78 (d, J = 8.6 Hz, 2H), 11.84 (s, 1H); 13C NMR (100 MHz,
(C), 160.09 (C); ESI‐MS (m/z) 271 (M+H)+; HRMS (ESI) DMSO‐d6): δ 105.90 (CH), 128.31 (2×CH), 128.88 (C), 130.27
calculated for C16H12ClO3 (M + H)+ 271.0526 found 271.0522.
(2×CH), 132.27 (C), 135.61 (CH), 136.01 (C), 139.37 (CH),
6‐bromo‐3‐(4‐methoxyphenyl)‐2H‐chromen‐2‐one (3z).37
161.52 (C); ESI‐MS (m/z) 206 (M+H)+; HRMS (ESI) calculated for
Yield 52% as white solid: mp 197‐199°C; FT‐IR (KBr, cm‐1) 3019, C11H9ClNO (M+H)+ 206.0373 found 206.0369.
1
1615, 1228, 1067; H NMR (400 MHz, CDCl3) δ 3.89 (s, 3H), 3‐(4‐bromophenyl)pyridin‐2(1H)‐one (6c).
7.01 (d, J = 8.80 Hz, 2H), 7.28‐7.29 (brd, 1H), 7.59‐7.62 (dd, J = Yield 82% as light brown solid: mp 245‐247°C; FT‐IR (KBr, cm‐1)
8.71, 2.12 Hz, 1H), 7.68‐7.70 (m, 4H); 13C NMR (100 MHz, 3412, 3020, 1652; 1H NMR (400 MHz, DMSO‐d6) δ 6.29 (t, J =
CDCl3) δ 55.41 (CH3), 114.03 (2×CH), 116.98 (C), 118.12 (CH), 6.8 Hz, 1H), 7.39‐7.42 (dd, J = 6.4, 2.04 Hz, 1H), 7.54‐7.58 (m,
121.43 (C), 126.57 (C), 129.04 (C), 129.91 (C & 2×CH), 133.69 2H), 7.67‐7.73 (m, 3H), 11.84 (s, 1H): 13C NMR (100 MHz,
(CH), 136.83 (C), 152.11 (C), 160.47 (C); ESI‐MS (m/z) 331 DMSO‐d6) δ 106.00 (CH), 120.88 (C), 128.93 (C), 130.61 (2×CH),
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131.26 (2×CH), 135.63 (CH), 136.37 (C), 139.43 (CH), 161.49 (100 MHz, DMSO‐d6) δ 21.24 (CH3), 37.91 (CH3), 105.59 (CH),
(C), ESI‐MS (m/z) 250 (M+H)+; HRMS (ESI) calculated for 128.61 (2×CH), 128.90 (2×CH), 129.67 (C), 134.55 (C), 136.96
C11H9BrNO (M+H)+ 249.9868 found 249.9860.
(C), 137.75 (CH), 139.30 (CH), 161.36 (C), ESI‐MS (m/z) 200
3‐(4‐fluorophenyl)pyridin‐2(1H)‐one (6d).
(M+H)+; HRMS (ESI) calculated for C13H14NO (M+H)+ 200.1075
Yield 68% as white solid: mp 218‐220°C; FT‐IR (KBr, cm‐1) 3418, found 200.1067.
3019, 1632; 1H NMR (400 MHz, DMSO‐d6) δ 6.29 (t, J = 6.68 Hz, 3‐(4‐methoxyphenyl)‐1‐methylpyridin‐2(1H)‐one (6j).21
1H), 7.17‐7.22 (m, 2H), 7.37‐7.39 (dd, J = 6.4, 2.0 Hz, 1H), 7.63‐ Yield 76% as white solid: mp 110‐112°C; FT‐IR (KBr, cm‐1) 3020,
1
7.65 (dd, J = 6.92, 2.0 Hz, 1H), 7.75‐7.79 (m, 2H), 11.80 (s, 1H); 1657; H NMR (400 MHz, CDCl3) δ 3.45 (s, 3H), 3.68 (s, 3H),
13C NMR (100 MHz, DMSO‐d6) δ 105.88 (CH), 115.21 (d, J = 6.07 (t, J = 6.8 Hz, 1H), 6.76‐6.79 (m, 2H), 7.09‐7.12 (m, 1H),
21.03 Hz, 2×CH), 129.28 (C), 130.60 (d, J = 7.89 Hz, 2×CH), 7.28‐7.30 (dd, J = 6.96, 2.24 Hz, 1H), 7.49‐7.52 (m, 2H); 13C
133.57 (C), 135.21 (CH), 139.10 (CH), 161.65 (C), 163.11 (d, J = NMR (100 MHz, CDCl3) δ 38.20 (CH3), 55.32 (CH3), 105.90 (CH),
242.77 Hz, C‐F); ESI‐MS (m/z) 190 (M+H)+; HRMS (ESI) 113.56 (2×CH), 129.30 (C), 129.79 (2×CH), 131.23 (C), 136.66
calculated for C11H9FNO (M+H)+ 190.0668 found 190.0667.
(2×CH), 139.79 (CH), 159.25 (C), 162.09 (C); ESI‐MS (m/z) 216
3‐(p‐tolyl)pyridin‐2(1H)‐one (6e).21
(M+H)+; HRMS (ESI) calculated for C13H14NO2 (M+H)+ 216.1025
Yield 71% as light yellow solid: mp 191‐194°C; FT‐IR (KBr, cm‐1) found 216.1012.
3412, 3019, 1636; 1H NMR (400 MHz, DMSO‐d6) δ 2.31 (s, 3H), 4‐((2,2,6,6‐tetramethylpiperidin‐1‐yl)oxy)benzonitrile (7).40
) 6.27 (t, J = 6.76 Hz, 1H), 7.18 (d, J = 7.92 Hz, 2H), 7.34‐7.36 Yield 64% as white solid: mp 78‐81°C; FT‐IR (KBr, cm‐1) 3019,
(dd, J = 6.4, 2.08 Hz, 1H), 7.59‐7.63 (m,3H), 11.72 (s, 1H); 13C 2231, 1591; 1H NMR (400 MHz, CDCl3) δ 0.99 (s, 6H), 1.25 (s,
NMR (100 MHz, DMSO‐d6) δ 21.25 (CH3), 105.84 (CH), 128.42 6H), 1.44‐1.49 (m, 1H), 1.59‐1.66 (m, 5H), 7.28 (s, 2H), 7.54 (d,
(2×CH), 128.90 (2×CH), 130.36 (C), 134.36 (C), 134.77 (CH), J = 9.12 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 16.90 (CH2),
136.91 (C), 138.62 (CH), 161.75 (C); ESI‐MS (m/z) 186 (M+H)+; 20.46 (4×CH3), 32.31 (CH2), 39.69 (CH2), 60.76 (2×C), 103.21
HRMS (ESI) calculated for C12H12NO (M+H)+ 186.0919 found (C), 114.89 (2×CH), 119.61 (C), 133.52 (2×CH), 166.91 (C).
186.0913.
1‐methyl‐3‐phenylpyridin‐2(1H)‐one (6f).21
Yield 72% as white solid: mp 127‐129°C; FT‐IR (KBr, cm‐1) 3019,
1641; 1H NMR (400 MHz, CDCl3) δ 3.61 (s, 3H), 6.25 (t, J = 6.8
Hz, 1H), 7.29‐7.34 (m, 2H), 7.37‐7.41 (m, 2H), 7.47‐7.49 (dd, J =
6.88, 2.0 Hz, 1H), 7.67‐7.70 (m, 2H); 13C NMR (100 MHz, CDCl3)
δ 38.20 (CH3), 105.82 (CH), 127.65 (CH), 128.09 (2×CH), 128.61
(2×CH), 131.64 (C), 136.85 (C), 137.41 (CH), 137.59 (CH),
161.95 (C), ESI‐MS (m/z) 186 (M+H)+; HRMS (ESI) calculated for
C12H12NO (M+H)+ 186.0919 found 186.0907.
Acknowledgements
P.C., M.R. and S.S. are thankful to the Council of Scientific and
Industrial Research (CSIR), New Delhi, for Fellowship, Mr.
Anoop. K. Srivastava for providing technical support, SAIF‐CDRI
Lucknow for providing spectral and analytical data. This work
was supported by CSIR network project “THUNDER”
(BSC0102). This is CDRI communication no. (will be inserted
after acceptance).
1‐methyl‐3‐phenylpyridin‐2(1H)‐one (6g).21
Yield 77% as white solid: mp 135‐137°C; FT‐IR (KBr, cm‐1) 3019,
1646; 1H NMR (400 MHz, CDCl3) δ 3.61 (s, 3H), 6.25 (t, J = 6.84
Hz, 1H), 7.31‐7.33 (dd, J = 6.68, 2.0 Hz, 1H), 7.36 (d, J = 8.64 Hz,
2H), 7.46‐7.48 (dd, J = 7.0, 2.04 Hz, 1H), 7.65 (d, J = 8.64 Hz,
2H): 13C NMR (100 MHz, CDCl3) δ 38.25 (CH3), 105.84 (CH),
128.25 (2×CH), 129.89 (2×CH), 130.34 (C), 133.52 (C), 135.23
(CH), 137.57 (CH), 137.76 (C), 161.74 (C), ESI‐MS (m/z) 206
(M+H)+; HRMS (ESI) calculated for C12H11ClNO (M+H)+ 220.0529
found 220.0517.
Notes and references
1
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8 | J. Name., 2012, 00, 1‐3
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Regioselective α-arylation of coumarins and 2-pyridones with
phenylhydrazines under transition-metal-free condition
Parul Chauhan,a Makthala Ravi,a Shikha Singh,a Prashant Prajapati,b Prem. P. Yadav*a
A transition-metal-free regioselective α-arylation of coumarins and 2-pyridones have been
accomplished by the reaction of phenylhydrazines with coumarins or 2-pyridones. The reaction
conditions are mild (Base/air system) and atom economical with broad substrate scope.