Acrylamide in Rauhut-Currier reaction; intramolecular isomerization of activated alkenes for quinolone synthesis

Article abstract of DOI:10.1016/j.tet.2017.08.002

Acrylamides are fundamental Michael acceptors which have been used profoundly in synthetic, medicinal and polymer chemistry. However, due to their lower reactivity they have been least used in Morita-Baylis-Hillman (MBH) reaction and have been out of its vinylogus version Rauhut Currier (RC) reaction. Herein, use of acrylamide in RC reaction is being presented. Intramolecular RC reaction followed by [1,3]-H shift led to the synthesis of quinolone moiety. DABCO catalyzed IRC reaction of acrylamide at 80 °C in presence of water, was found to work on a number of precursors. En route chemo selective, gram scale method for ambiphilic, versatile precursor 2-amino chalcone is also reported. Chemoselective and economical conversion of 2-nitro chalcone to 2-aryl quinoline has also been developed.

Full text of DOI:10.1016/j.tet.2017.08.002

Accepted Manuscript
Acrylamide in Rauhut-Currier reaction; intramolecular isomerization of activated
alkenes for quinolone synthesis
Kishor Chandra Bharadwaj
PII:
S0040-4020(17)30816-5
10.1016/j.tet.2017.08.002
TET 28896
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 14 June 2017
Revised Date: 12 July 2017
Accepted Date: 3 August 2017
Please cite this article as: Bharadwaj KC, Acrylamide in Rauhut-Currier reaction; intramolecular
isomerization of activated alkenes for quinolone synthesis, Tetrahedron (2017), doi: 10.1016/
j.tet.2017.08.002.
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to
our customers we are providing this early version of the manuscript. The manuscript will undergo
copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please
note that during the production process errors may be discovered which could affect the content, and all
legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT
Graphical Abstract
Acrylamide in Rauhut-Currier reaction;
Intramolecular isomerization of activated
alkenes for quinolone synthesis
Leave this area blank for abstract info.
Kishor Chandra Bharadwaj
Department of Chemistry, Institute of Science, Banaras Hindu University, Varanasi, India-221005
Ar
O
DMF-Water (2:1)
DABCO (1eq.)
R1
O
O
Ar
80 oC
R1
NH
H
N
O
IRC
H

1
ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
Acrylamide in Rauhut-Currier reaction; Intramolecular isomerization of activated
alkenes for quinolone synthesis
Kishor Chandra Bharadwaja, 
a Department of Chemistry, Institute of Science, Banaras Hindu University, Varanasi 221005, India
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
Acrylamides are fundamental Michael acceptors which have been used profoundly in synthetic,
medicinal and polymer chemistry. However, due to their lower reactivity they have been least
used in Morita-Baylis-Hillman (MBH) reaction and have been out of its vinylogus version
Rauhut Currier (RC) reaction. Herein, use of acrylamide in RC reaction is being presented.
Intramolecular RC reaction followed by [1,3]-H shift led to the synthesis of quinolone moiety.
Available online
o
DABCO catalyzed IRC reaction of acrylamide at 80 C in presence of water, was found to work
Keywords:
Acrylamide
Intramolecular Rauhut Currier
2-amino chalcone
2-aryl quinoline
Quinolone
on a number of precursors. En route chemo selective, gram scale method for ambiphilic,
versatile precursor 2-amino chalcone is also reported. Chemoselective and economical
conversion of 2-nitro chalcone to 2-phenyl quionline has also been developed
2009 Elsevier Ltd. All rights reserved.
EWG
1. Introduction
Rauhut-Currier (RC)1 reaction, also known as vinylogus
Morita-Baylis-Hillman (MBH)2 reaction, is a mild and atom
economy method of C-C bond formation. Initiated by a
nucleophile, the reaction involves coupling of two Michael
acceptors where one serves as a source of enolate, while other
acts as an electrophile (Figure 1). With the advent of
organocatalysis the reaction has seen steep growth in its
popularity in last decade.3,4 Simultaneously its intramolecular
version (IRC), after the reports5 of Moore, Krishche and Roush,
has become an important tool for synthesis of carbo and
heterocyclic frameworks. Reaction has been extended to alkyne
and allene derived Michael acceptors.6 Further its efficiency has
been demonstrated by its application as a key step in synthesis of
complex natural products.3a,7 Although IRC is an efficient
method for construction of cyclic framework, the reaction largely
makes use of more reactive Michael acceptors such as enone8 and
acrylate,9 as a source of initial enolate. Use of other Michael
acceptors such as thioenoate, nitro styrene and others has been
limited.10 Furthermore, reaction is often associated with issues of
low reactivity and chemo selectivity.1b,c
Nu
O
O
EWG
R2
R1
Nu
Enolate
RC
MBH
O
OH
R2
EWG
R1
EWG
Fig. 1 MBH Vs RC reaction, the vinylogus shift.
acrylamide derived MBH reactions.14,15 In fact their
sluggishness has been the reason for development of
organometallic approaches for synthesis of acrylamide derived
MBH adducts.16 Comparatively other activated alkenes such as
enone, acrylate and acrylonitrile have been the mainstay in MBH
chemistry for decades.2 Thus within the domain of MBH
reactions, acrylamides have far inferior reactivity as compared to
other popular acryl units. Subsequently RC reaction which
involves the shift of reactivity to vinylogus position of
Acrylamides are fundamental activated alkene units and have
found applications in the field of synthetic,11 medicinal12 and
polymer chemistry.13 However, their reduced affinity as Michael
acceptor has largely diminished their role in MBH reaction. The
susceptibility of MBH reactions towards steric and electronic
parameters have led to only a few successful reports of
———
 Corresponding author. Tel.: ++91 542 670 2482; fax: + 91 542 236 8127; e-mail: kishorbharadwaj@gmail.com

2
Tetrahedron
ACCEPTED MANUSCRIPT
O
O
O
O
R1
AcOH, EtOH
Fe, 70 oC, 1h
R1
Ar
O
Ar
Ph
Ph
NH2
NO2
NH2
N
Ph
NO2
1a
2
1
3a
2a
O
O
Cl
Scheme 1. Reduction of 2-Nitro Chalcone.
NH2
NH2
electrophile further makes them a challenging and uphill task
as compared to MBH reaction. Thus owing to their low reactivity
profile and vinylogus reaction centre at electrophile, acrylamides
have been out of domain of RC reactions. Very recently
tosyl/mesyl activated acrylamides, were used for IRC reaction.17
However in absence of additional electron withdrawing group
(Ts) the reaction was not successful.17a Herein, development of
acrylamide for IRC reaction is being reported. The IRC reaction
followed by [1,3]-H shift lead to the synthesis of Quinolin-2(1H)-
one skeleton. Quinolones are important and celebrated template
for their medicinal activities18 and have drawn worldwide
attention from synthetic chemist.19 En route chemo selective
synthesis of 2-amino chalcone and 2-aryl quionline derivatives
has also been explored.
NH2
Cl
2c, 89%
2b, 80%
2a, 82%
O
O
OMe
O
NH2
NH2
Cl
NH2
OMe
2d, 77%
2f, 76%
2e, 71%
O
O
O
NH2
NH2
OMe
NH2
Br
Br
2g, 82%
2i, 83%
2h, 86%
O
O
O
NH2
F
2. Results and Discussion
NH2
Me
NH2
2l
2j, 74%
2k, 65%
At the start of study, precursor 2a was required whose
acrylation would lead to the required template for IRC reaction
(vide infra). The simple looking molecule 2a has a unique
structural feature of being ambiphilic in nature. Having both a
nucleophilic (amine) and electrophilic (Michael acceptor)
functional groups within proximity of each other makes this
molecule a very important building block.20 The dual groups can
also be manipulated for the synthesis of other valuable
templates.20a,b,i The high bench stability of 2a further adds to its
synthetic utility. A straight forward approach to access the
synthon 2a was reduction of corresponding 2-nitro Chalcone 1a
(Scheme 1). However, initial attempts to synthesize 2a led to
average yield of reaction. Simultaneously certain issues such as
isomerization of double bond, low yields and tedious purification
(not disclosed earlier) came up which required attention. Here in,
an economical, gram scale method for synthesis of 2-amino
chalcone along with data and spectra, is also reported.
O
O
O
Cl
S
NH2
NH2
OMe
NH2
Cl
OMe
2m 68%
2o, 83%
2n, 70%
O
Cl
NH2
2p, 72%
Scheme 2. Synthesis of 2-amino chalcones 2.
Initial efforts to synthesize 2a lead to two major concerns.
First, during the course of reduction there was an isomerization
of double bond followed by imine formation leading to the
synthesis of quionline 3a. Consequently, that led to the reduction
in yield of reaction. Secondly, the precursor nitro chalcone 1a
and the required product 2a appeared overlapping on TLC and
required tedious column chromatography for purification. Easiest
solution to the purification problem was complete disappearance
of starting material 1a. However, extended reaction time or
forcing conditions for complete consumption of starting material
1a, lead to increased formation of side product 3a and other
impurities and thus reducing yield (vide infra) of 2a. Therefore, a
right balance between 1a, 2a and 3a was required which would
lead to complete consumption of precursor along with minimum
formation of side products. Importantly a cost efficient method
was also a desirable aspect. That would enable the reaction to be
carried out on gram scale for the scale up of versatile precursor.
Table 1 Standardization for synthesis of 2a.a
O
O
Ph
1a
Ph
NO2
NH2
2a
S.
No.
Solvent
HCl
Fe
(eq.)
4
Time
Temp
(oC)
80
Yieldb
(%)
48
(mL)
(h)
5
1
EtOH
EtOH
EtOH
AcOH
0.01
2
0.05
4
1
80
54
3
0.1
4
1
80
55
4
-
-
-
-
-
4
2
120
70
-
Initially carrying out reduction using iron powder in refluxing
ethanol in presence of catalytic HCl, led to the formation of
amine 2a in 48 % yield as yellow solid (Table 1, entry 1).
Increase in amount of HCl led to slight increment in yield (entry
2). However, further increase in HCL didn’t lead to any
significant change (entry 3). Change of source for acidic proton
5c
6c
7c
8c
AcOH-EtOH
AcOH-EtOH
AcOH-EtOH
AcOH-EtOH
4
1
65
4
2
70
57
8
1
70
79
12
1
70
82
o
a All reactions were carried out using 0.5 mmol of 1a in 1.0 mL of solvent.
b Isolated Yield.
was then investigated. Use of acetic acid at 120 C did not give
any product (entry 4).21a At this stage use of mixture of solvent
(acetic acid and ethanol)21b at 70 C was helpful and lead to
o
c 0.5 mL of each solvent was used
improved yield of 65 % (entry 5). However, starting material was
still observed on reaction mixture TLC which made isolation of

3
O
Naphthyl derived precursor 2l was liquid and could not be
ACCEPTED MANUSCRIPT
O
obtained in pure form. Therefore it was carried forward as such.
It is worth mentioning here that all the reactions were carried out
on 4 mmol scale (>1 g of substrate) for the gram scale synthesis
of these templates. After accomplishing the method for 2-amino
chalcone, the precursor 4a for IRC reaction was obtained by
acrylation of 2a (Scheme 3). With the required precursor in hand,
having dual Michael acceptor units, investigations for IRC
reaction were carried out. Initially carrying out reaction at rt in
presence of DABCO as promoter didn’t lead to product
formation (Table 2, entry 1). However, carrying out reaction at
elevated temperature of 80 oC led to the formation of 4a, in 79%
yield (entry 2). The formation of 4a could be explained via initial
IRC reaction followed by [1,3]-H shift to give the quinolone
moiety. With the protocol working, it was further optimized for
O
Ph
Cl
Ph
NH
NH2
2a
O
4a
Et3N, DCM, 86 %
Scheme 3. Synthesis of bis activated alkene precursor 4a.
product a difficult task. Longer reaction time led to decrease
in yield of reaction (entry 6). Quicker reduction of nitro group in
shorter reaction time was then investigated by using higher
loading of iron. Increase in the loading of iron powder to 8
equivalents further increased yield to 79% (entry 7). Finally, 12
equivalents of iron gave reduced product 2a in 82 % yield, along
with disappearance of nitro precursor 1a (entry 8). With the
optimum conditions in hand the reaction scope was then explored
on various other precursors (Scheme 2). Different substitution
pattern (ortho, meta and para) worked well for the chemo
selective reduction (2b-2g). Furthermore both electron donating
and withdrawing groups were found compatible for the reaction.
The reaction was then successfully carried out for hetero aryl
(2m) and multi substituted (2n, 2o) amino chalcones. Variation
on the other aryl group was equally acceptable (2p).
o
better results. Further increase of temperature to 130 C led to
reduction of yield (entry 3). Other solvents such as dioxane,
acetonitrile, t-BuOH lead to reduced yield (entries 4-6). Similarly
use of other catalyst such as TPP, DMAP, DBU (entries 7-9) in
DMF, gave inferior results. While DMAP led to reduced yield of
product (entry 8), no product formation was observed with TPP
and DBU (entries 7 and 9). This suggested superiority of
DABCO as an economical and commercially viable catalyst for
acrylamides in MBH and RC reactions. At this stage, use of
water as a co solvent gave 5a in better yield of 89 % in shorter
reaction time (18h, entry 10).22 This could be due to faster proton
transfer from acrylamide and elimination of catalyst. Decrease in
dilution did lead to further reduction of time but gave product in
reduced yield (entry 11). Use of 1 equivalent of DABCO was
found to be compatible to give similar results (entry 12). Further
reduction in catalyst loading led to longer reaction time and
lower yield (entry 13).
Table 2. Development of IRC reactiona
Ph
O
O
Ph
conditions
NH
N
O
4a
H
O
5a
With the optimized conditions in hand (entry 12) exploration
of protocol on other substrates was taken (Scheme 4). The
reaction was found to work on a variety of substrates having
different electron withdrawing and electron donating groups.
Electron donating group substituted precursors were found to
give slightly higher yields (5e-5g). Furthermore various
substitution patterns such as ortho, meta and para worked
equally well (5b-5g). Fluoro substituted quinolone was
synthesized in 83% yield (5k). Reaction scope was extendable
for quinolone having biaryl (naphthyl, 5l) heteroaryl (thiophene,
5m) moieties. Multi substituted quinolone (dichloro, dimethoxy
5n and 5o respectively) on aryl ring were also synthesized in
event free manner. Variation on other aryl ring also led to smooth
conversion to 5p.
Ph
IRC
O
O
[1,3]-H shift
N
H
S.
No
Catalyst (eq.)
Solvent
Temp
(oC)
rt
Time
(h)
12
28
20
28
36
36
24
48
18
18
12
20
26
Yield
(%)b
-
1
DABCO (2)
DABCO (2)
DABCO (2)
DABCO (2)
DABCO (2)
DABCO (2)
TPP (2)
DMF
2
DMF
80
79
67
73
71
74
-
3
DMF
130
80
4
Dioxane
MeCN
t-BuOH
DMF
After the successful demonstration of acrylamide derived IRC
reaction, the attention was then turned to 2-aryl quionline 3. As
mentioned earlier during the course of investigations for
reduction, 2-aryl quionline 3a, formation via Friedlander23
pathway was observed. Quionline skeleton has been one of the
most privileged frameworks for its medicinal24 and synthetic
values.23a,25 Recently 2-aryl quionline has gained attention as they
have been useful from C-H activation26 perspective. Thus their
synthesis from cheaper and stable precursors is an important and
desirable aspect. With a view to achieve synthesis of 2-aryl
quionline, reductive conditions which would lead to facile
isomerization of double bond were investigated. Increase in the
reaction temperature during the reduction was studied. Carrying
5
80
6
80
7
80
8
DMAP (2)
DBU (2)
DMF
80
15
-
9
DMF
80
10c
DABCO (2)
DMF, water
DMF, water
DMF, water
DMF, water
80
89
70
91
81
11c,,d DABCO (2)
80
12c
DABCO (1)
80
13c
DABCO (0.5)
80
o
a All reactions were carried out using 0.5 mmol of 3a in 1.5 mL of solvent.
b Isolated Yield.
out reduction of 1a in AcOH, at 120 C using 12 equivalents of
iron led to the formation of 2-phenyl quionline (3a) in 80 % yield
(Scheme 5). The reaction was then explored on different
precursor with varying substitution pattern such as ortho, meta
and para substitutions,
c DMF-water in 2:1 ratio was used.
d 0.75 mL of solvent was used

4
Tetrahedron
Ar
O
O
ACCEPTED MANUSCRIPT
R1
R1
R1
O
DMF-Water (2:1)
DABCO (1eq.)
Ar
AcOH, 120 o
Fe
C
Ar
R1
N
Ar
NH
NO2
80 o
C
3
1
N
O
4
O
H
5
Cl
Cl
Cl
Cl
N
N
3b, 2h, 88%
3a, 2h, 80 %
O
O
O
O
O
O
O
O
N
N
H
N
H
H
N
N
N
H
5a, 20h, 91%
5c, 14h, 81%
5b, 12h, 79%
3d, 3h, 92%
5d, 14h, 80%
3c, 6h, 77%
OMe
OMe
Br
Br
MeO
MeO
N
N
O
O
O
O
O
O
O
3f, 6h, 76%
3e, 4h, 86%
Me
Br
N
H
N
H
Cl
N
H
O
N
H
5e, 24h, 87%
5f, 24h, 92%
5g, 24h, 91%
5h, 16h, 76%
N
N
F
Br
3g, 5h. 85%
S
3h, 5h, 64%
Me
Scheme 5. Synthesis of 2-Aryl Quinoline.
O
O
MBH reaction. Use of Michael acceptor as electrophile opens
up new avenues for the development of methodologies in the
domain of MBH and RC reaction of acrylamides. Non-
conventional and other electrophiles1a can also be explored for
trapping of acrylamide generated enolate in MBH and RC
reactions. Moreover, cheaper and chemo selective routes for
synthesis of 2-amino chalcones 2 and 2-aryl quionline 3 have
been also developed. The two precursors have been bench mark
for the development of other successful methodologies and
synthons. The present methods for their synthesis would be
useful for synthetic and medicinal chemist.
O
O
O
O
O
O
N
H
N
H
N
H
N
H
5i, 16h, 75%
5k, 9h, 83%
5j, 24h, 86%
5l, 21h, 85%
OMe
Cl
MeO
S
Cl
O
O
O
O
O
O
O
O
4. Experimental
Cl
General Remarks
N
H
N
H
N
N
H
H
All the reactions were carried out using dry solvents and under
5n, 7h, 78%
5m, 21h, 72%
5p, 6h, 82%
5o, 24h, 87%
inert
atmosphere
until
unless
mentioned.
Column
chromatography was performed using silica gel mesh 100-200.
TLC Aluminum Sheets Silica Gel 60 F254 was used for TLC.
Melting Points were recorded on a Perfit (India) capillary melting
point apparatus and were uncorrected. Infrared spectra were
recorded on a Perkin Elmer FT-IR spectrometer Spectrum Two.
1H NMR and 13C NMR were recorded on a Jeol 500 MHz and
125 MHz spectrometer respectively. HRMS spectra were
recorded on Bruker Daltonics MicroTOF-Q-II with electron
spray ionization (ESI).
Scheme 4. IRC reaction for synthesis of various quinolones.
electron donating and withdrawing groups and hetero aryl
moieties. The reaction was found to work well on all the
substrates explored. It is worth mentioning here that previous
methods of reduction of 1 to 3 made use of sulphur or selenium,
palladium, In, SmI2, and others.27
3. Conclusions
Representative procedures and data
Synthetic methodology leading to successful usage of
acrylamide as a source of enolate for IRC reaction has been
carried out. Reaction was found to be progressive under heating
conditions while use of water as a co-solvent gave better results.
DABCO was a superior catalyst as compared to others. So far
carbonyl group in the form of aldehydes along with ketone
(occasionally) has been used for coupling with acrylamide in
(E)-3-(2-aminophenyl)-1-phenylprop-2-en-1-one (2a);
suspension of 1a (1.012 g, 4mmol) and Fe powder (2.688 g, 48
A
mmol) in AcOH and EtOH (4.0 mL each) was heated for 1 h at
o
70 C with vigorous stirring. Reaction mixture was then cooled,
filtered and washed with DCM. The filtrate obtained was
concentrated and the residue was purified by column

5
1
chromatography (EtOAc/Hexane, 1:4) to obtain 0.731 g of 2a as
yellow solid in 82% yield.
cm_1; H NMR (500 MHz, CDCl ): δ 3.90 (s, 3H), 4.07 (bs,
ACCEPTED MANUSCRIPT
3
2H), 6.71 (d, J = 7.5 Hz, 1H), 6.77 (app t, J = 7.5 Hz, 1H), 6.99
(d, J = 8.0 Hz, 1H), 7.04 (app t, J = 7.5 Hz, 1H), 7.17 (d appt, J =
7.5, 1.5 Hz, 1H), 7.33 (d, J = 16.0 Hz, 1H), 7.45-7.49 (m, 2H),
7.65 (dd, J = 7.5, 1.5 Hz, 1H), 7.82 (d, J = 15.5 Hz, 1H); 13C
NMR (125 MHz, CDCl3): δ 55.8, 111.7, 116.7, 118.9, 120.6,
120.9, 127.1, 128.45, 128.55, 130.5, 131.4, 133.0, 138.5, 146.1,
158.2, 192.7.
N-(2-((E)-3-oxo-3-phenylprop-1-enyl)phenyl)acrylamide
(4a); To a stirring solution of 2a (0.223 g, 1 mmol) in DCM (3.0
o
mL) at 0 C was added Et3N (0.18 mL, 1.3 mmol) followed by
acryloyl chloride (0.1 mL, 1.2 mmol) and the reaction was
allowed to stir at rt for 1 h. DCM was added to the reaction
mixture and organic phase was washed with water. Organic
fraction was collected, dried over Na2SO4, filtered and
concentrated. The residue obtained was purified by column
chromatography (EtOAc/Hexane, 3:7) to obtain 4a as light
yellow solid 0.238 g in 86% yield.
(E)-3-(2-aminophenyl)-1-(3-methoxyphenyl)prop-2-en-1-
one (2f); Yield: 76 % yellow solid; mp: 118-120 oC; IR (KBr): ν
1252, 1574, 3351 cm_1; H NMR (500 MHz, CDCl3): δ 3.89 (s,
1
3H), 4.07 (bs, 2H), 6.73 (d, J = 8.5 Hz, 1H), 6.80 (app t, J = 7.5
Hz, 1H), 7.13 (dd, J = 8.0, 2.5 Hz, 1H), 7.21 (app t, J = 7.5 Hz,
1H), 7.41 (app t, J = 7.5 Hz, 1H), 7.47 (d, J = 15.0 Hz, 1H), 7.53
(d, J = 7.5 Hz, 1H), 7.55 (app t, J = 2.0 Hz, 1H), 7.61 (d, J = 8.0
Hz, 1H), 7.99 (d, J = 15.5 Hz, 1H); 13C NMR (125 MHz, CDCl3):
δ 55.6, 112.9, 116.9, 119.0, 119.3, 120.3, 121.1, 121.9, 128.2,
129.6, 131.8, 139.8, 140.2, 146.3, 160.0, 190.1.
3-Methyl-4-(2-oxo-2-phenyl-ethyl)-1H-quinolin-2-one (5a);
To a solution of 4a (0.139 g, 0.5 mmol) in DMF (1.0 mL) and
water (0.5 mL) was added DABCO (0.056 g, 0.5 mmol) and the
o
reaction was heated for 20 h at 80 C. Thereafter volatiles were
removed under reduced pressure and the residue obtained was
purified by column chromatography (EtOAc/Hexane, 1:1 to
EtOAc) to obtain 0.126 g of 5a as white solid in 91 % yield.
(E)-3-(2-aminophenyl)-1-(4-methoxyphenyl)prop-2-en-1-
one (2g); Yield: 82 % yellow solid; mp: 124-126 oC; IR (KBr): ν
1217, 1582, 1652, 3342, 3406 cm_1; 1H NMR (500 MHz, CDCl3):
δ 3.89 (s, 3H), 4.07 (bs, 2H), 6.72 (d, J = 8.0 Hz, 1H), 6.79 (app
t, J = 7.5 Hz, 1H), 6.96-6.99 (m, 2H), 7.19 (d appt, J = 7.5, 1.5
Hz, 1H), 7.48-7.53 (m, 2H), 7.97 (d, J = 15.0 Hz, 1H), 8.03-8.05
(m, 2H); 13C NMR (125 MHz, CDCl3): δ 55.6, 113.9, 116.8,
118.9, 120.6, 121.8, 128.2, 130.8, 131.3, 135.5, 139.3, 146.2,
163.5, 188.6.
2-phenylquinoline (3a); To a solution of 1a (0.126 g, 0.5
mmol) in AcOH (1.0 mL) was added Fe powder (0.336 g, 6.0
o
mmol) and the reaction was heated at 120 C for 2h. Reaction
mixture was then cooled, filtered and washed with DCM. The
filtrate obtained was concentrated. The residue was purified by
column chromatography (EtOAc/Hexane, 1:19) to obtain 0.082 g
of 3a as white solid in 80% yield.
(E)-3-(2-aminophenyl)-1-phenylprop-2-en-1-one
(2a);
(E)-3-(2-aminophenyl)-1-(3-bromophenyl)prop-2-en-1-one
o
Yield: 82 % yellow solid; mp: 114-116 C; IR (KBr): ν 1214,
o
(2h); Yield: 86 % yellow solid; mp: 132-134 C; IR (KBr): ν
1
1344, 1590, 1650, 3350 cm_1; H NMR (500 MHz, CDCl3): δ
1
1206, 1342, 1580, 1658, 3392, 3402 cm_1; H NMR (500 MHz,
4.08 (s, 2H), 6.72 (d, J = 8.0 Hz, 1H), 6.79 (app t, J = 7.5 Hz,
1H), 7.20 (app t, J = 7.5 Hz, 1H), 7.47-7.54 (m, 4H), 7.58 (app t,
J = 7.5 Hz, 1H), 7.98-8.03 (m, 3H); 13C NMR (125 MHz,
CDCl3): δ 116.9, 119.0, 120.3, 121.8, 128.2, 128.5, 128.7, 131.7,
132.8, 138.4, 140.2, 146.3, 190.3.
CDCl3): δ 4.09 (bs, 2H), 6.73 (d, J = 8.5 Hz, 1H), 6.80 (app t, J =
7.5 Hz, 1H), 7.22 (app t, J = 7.5 Hz, 1H), 7.38 (app t, J = 8.0 Hz,
1H), 7.41 (d, J = 15.5 Hz, 1H), 7.53 (d, J = 8.0 Hz, 1H), 7.70 (d,
J = 8.0 Hz, 1H), 7.94 (d, J = 7.5 Hz, 1H), 8.01 (d, J = 15.5 Hz,
1H), 8.14 (s, 1H); 13C NMR (125 MHz, CDCl3): δ 117.0, 119.0,
120.0, 121.0, 123.0, 127.0 128.2, 130.3, 131.5, 132.1, 135.6,
140.2, 141.0, 146.5, 188.8.
(E)-3-(2-aminophenyl)-1-(2-chlorophenyl)prop-2-en-1-one
o
(2b); Yield: 80 % yellow solid; mp: 92-94 C; IR (KBr): ν 743,
1
1579, 1661, 3403 cm_1; H NMR (500 MHz, CDCl3): δ 4.00 (bs,
(E)-3-(2-aminophenyl)-1-(4-bromophenyl)prop-2-en-1-one
2H), 6.70 (d, J = 8.0 Hz, 1H), 6.78 (app t, J = 7.5 Hz, 1H), 7.08
(d, J = 15.5 Hz, 1H), 7.19 (d appt, J = 7.5, 1.5 Hz, 1H), 7.35 (d
appt, J = 7.5, 1.5 Hz, 1H), 7.41 (d appt, J = 8.0, 1.5 Hz, 1H),
7.44-7.45 (m, 2H), 7.49 (dd, J = 7.5, 1.5 Hz, 1H), 7.69 (d, J =
16.0 Hz, 1H); 13C NMR (125 MHz, CDCl3): δ 117.0, 119.1,
119.9, 125.9, 127.0, 128.5, 129.6, 130.4, 131.3, 131.5, 132.1,
139.4, 141.4, 146.3, 193.5.
o
(2i); Yield: 83 % red solid; mp: 124-126 C; IR (KBr): ν 1591,
1
1660, 3345 cm_1; H NMR (500 MHz, CDCl3): δ 4.09 (bs 2H),
6.73 (d, J = 8.5 Hz, 1H), 6.79 (app t, J = 7.5 Hz, 1H), 7.21 (app t,
J = 7.5 Hz, 1H), 7.42 (d, J = 15.5 Hz, 1H), 7.52 (d, J = 7.5 Hz,
1H), 7.62-7.64 (m, 2H), 7.87-7.89 (m, 2H), 8.00 (d, J = 15.0 Hz,
1H); 13C NMR (125 MHz, CDCl3): δ 117.0, 119.0, 120.1, 121.1,
127.9, 128.2, 130.0, 132.0, 137.1, 140.7, 146.4, 189.2.
(E)-3-(2-aminophenyl)-1-(3-chlorophenyl)prop-2-en-1-one
(E)-3-(2-aminophenyl)-1-p-tolylprop-2-en-1-one
(2j);
o
(2c); Yield: 89 % yellow solid; mp: 134-136 C; IR (KBr): ν
o
Yield: 74 % yellow solid; mp: 130-132 C; IR (KBr): ν 1180,
1339, 1580, 1655, 3343, 3404 cm_1; 1H NMR (500 MHz, CDCl3):
δ 2.44 (s, 3H), 4.06 (bs, 2H), 6.73 (d, J = 8.0 Hz, 1H), 6.80 (app
t, J = 7.5 Hz, 1H), 7.20 (app t, J = 7.5 Hz, 1H), 7.29-7.31 (m,
2H), 7.49 (d, J = 15.5 Hz, 1H), 7.53 (d, J = 7.5 Hz, 1H), 7.94-
7.95 (m, 2H), 7.98 (d, J = 15.5 Hz, 1H); 13C NMR (125 MHz,
CDCl3): δ 21.7, 116.8, 118.9, 120.4, 121.9, 128.2, 128.7, 129.4,
131.6, 135.8, 139.7, 143.6, 146.3, 189.8.
1
1340, 1567, 3392 cm_1; H NMR (500 MHz, CDCl3): δ 4.09 (bs,
2H), 6.73 (d, J = 8.5 Hz, 1H), 6.80 (app t, J = 7.5 Hz, 1H), 7.21
(app t, J = 7.5 Hz, 1H), 7.40-7.45 (m, 2H), 7.52-7.55 (m, 2H),
7.89 (d, J = 7.5 Hz, 1H), 7.98-8.02 (m, 2H); 13C NMR (125 MHz,
CDCl3): δ 117.0, 119.1, 120.1, 121.1, 126.6, 128.3, 128.6, 130.0,
132.1, 132.7, 135.0, 140.0, 141.0, 146.5, 188.9.
(E)-3-(2-aminophenyl)-1-(4-chlorophenyl)prop-2-en-1-one
o
(2d); Yield: 77 % yellow solid; mp: 124-126 C; IR (KBr): ν
(E)-3-(2-aminophenyl)-1-(4-fluorophenyl)prop-2-en-1-one
1
1343, 1512, 1670, 3413 cm_1; H NMR (500 MHz, CDCl3): δ
o
(2k); Yield: 65 % yellow solid; mp: 138-140 C; IR (KBr): ν
4.09 (bs, 2H), 6.73 (d, J = 8.5 Hz, 1H), 6.80 (app t, J = 7.5 Hz,
1H), 7.21 (app t, J = 7.5 Hz, 1H), 7.42-7.47 (m, 3H), 7.52 (d, J =
7.5 Hz, 1H), 7.95-8.01 (m, 3H); 13C NMR (125 MHz, CDCl3): δ
117.0, 119.0, 120.1, 121.1, 128.2, 129.0, 129.9, 132.0, 136.7,
139.2, 140.7, 146.4, 189.0.
1
1155, 1211, 1598, 1661, 3340, 3401 cm_1; H NMR (500 MHz,
CDCl3): δ 4.08 (bs, 2H), 6.73 (d, J = 8.0 Hz, 1H), 6.80 (app t, J =
7.5 Hz, 1H), 7.14-7.18 (m, 2H), 7.21 (app t, J = 8.0 Hz, 1H), 7.45
(d, J = 15.0 Hz, 1H), 7.52 (d, J = 8.5 Hz, 1H), 7.99 (d, J = 15.5
Hz, 1H), 8.04-8.07 (m, 2H); 13C NMR (125 MHz, CDCl3): δ
115.7, 115.9, 116.9, 119.0, 120.2, 121.3, 128.2, 131.06, 131.13,
131.9, 134.7, 140.4, 146.4, 164.6, 166.7, 188.7.
(E)-3-(2-aminophenyl)-1-(2-methoxyphenyl)prop-2-en-1-
one (2e); Yield: 71 % red liquid; IR (neat): ν 1599, 1654, 3361

6
Tetrahedron
(E)-3-(2-aminophenyl)-1-(thiophen-2-yl)prop-2-en-1-one
13C NMR (125 MHz, CDCl ): δ 122.6, 125.7, 126.0, 126.5,
ACCEPTED MANUSCRIPT
3
(2m); Yield: 68 % light brown solid; mp: 132-134 oC; IR (KBr):
126.9, 127.5, 128.4, 128.5, 129.9, 131.0, 132.6, 134.7, 137.0,
ν 1579, 1651, 3405 cm_1; H NMR (500 MHz, CDCl3): δ 4.09
139.5, 141.1, 164.5, 188.9.
1
(bs, 2H), 6.73 (d, J = 8.0 Hz, 1H), 6.80 (app t, J = 7.5 Hz, 1H),
7.17-7.22 (m, 2H), 7.36 (d, J = 15.5 Hz, 1H), 7.52 (d, J = 7.5 Hz,
1H), 7.675 (d, J = 5.0 Hz, 1H), 7.855 (d, J = 4.0 Hz, 1H), 8.01 (d,
J = 15.5 Hz, 1H); 13C NMR (125 MHz, CDCl3): δ 116.9, 119.0,
120.1, 121.5, 128.2, 128.3, 131.7, 131.8, 133.8, 139.4, 145.8,
146.4, 182.1.
N-(2-((E)-3-(4-chlorophenyl)-3-oxoprop-1-
o
enyl)phenyl)acrylamide (4d); white solid; mp: 172-174 C; IR
1
(KBr): ν 1600, 1663, 3273 cm_1; H NMR (500 MHz, CDCl3): δ
5.80 (d, J = 10.0 Hz, 1H), 6.33-6.38 (m, 1H), 6.47 (d, J = 16.5
Hz, 1H), 7.23-7.26 (m, 1H), 7.40-7.46 (m, 4H), 7.68 (d, J = 8.0
Hz, 1H), 7.73 (s, 1H), 7.86 (bs, 1H), 7.91-7.97 (m, 3H); 13C
NMR (125 MHz, CDCl3): δ 123.7, 125.2, 126.1, 127.3, 127.9,
128.7, 129.1, 130.0, 130.7, 131.4, 136.1, 136.4, 139.7, 139.9,
164.2, 189.0.
(E)-3-(2-aminophenyl)-1-(2,4-dichlorophenyl)prop-2-en-1-
one (2n); Yield: 70 % orange solid; mp: 116-118 oC; IR (KBr): ν
1
1583, 1662, 3332, 3405 cm_1; H NMR (500 MHz, CDCl3): δ
4.01 (bs, 2H), 6.71 (d, J = 8.0 Hz, 1H), 6.79 (app t, J = 7.5 Hz,
1H), 7.07 (d, J = 16.0 Hz, 1H), 7.21 (app t, J = 7.5 Hz, 1H), 7.35
(dd, J = 8.0, 1.5 Hz, 1H), 7.44-7.47 (m, 2H), 7.48 (d, J = 1.5 Hz,
1H), 7.71 (d, J = 15.5 Hz, 1H); 13C NMR (125 MHz, CDCl3): δ
117.0, 119.2, 119.8, 125.4, 127.4, 128.5, 130.3, 130.7, 132.3,
132.4, 137.0, 137.8, 141.6, 146.4, 192.2.
N-(2-((E)-3-(2-methoxyphenyl)-3-oxoprop-1-
enyl)phenyl)acrylamide (4e); light yellow solid; mp: 134-136
1
oC; IR (KBr): ν 1604, 1658, 3215 cm_1; H NMR (500 MHz,
CDCl3): δ 3.88 (s, 3H), 5.78 (d, J = 10.0 Hz, 1H), 6.33-6.38 (m,
1H), 6.45 (d, J = 17.0 Hz, 1H), 6.98 (d, J = 8.5 Hz, 1H), 7.01
(app t, J = 7.0 Hz, 1H), 7.20 (app t, J = 7.0 Hz, 1H), 7.36-7.41
(m, 2H), 7.47 (app t, J = 7.5 Hz, 1H), 7.60-7.64 (m, 2H), 7.79
(bs, 1H), 7.84 (d, J = 16.0 Hz, 1H), 7.97 (bs, 1H); 13C NMR (125
MHz, CDCl3): δ 55.9, 111.8, 121.0, 124.6, 125.6, 127.5, 127.8,
128.4, 128.9, 129.4, 130.77, 130.79, 131.0, 133.6, 136.3, 137.2,
158.5, 164.0, 192.2
(E)-3-(2-aminophenyl)-1-(3,4-dimethoxyphenyl)prop-2-en-
1-one (2o); Yield: 83 % orange solid; mp: 140-142 oC; IR (KBr):
1
ν 1160, 1256, 1570, 1649, 3419, cm_1; H NMR (500 MHz,
CDCl3): δ 3.96 (s, 3H), 3.97 (s, 3H), 4.09 (bs, 2H), 6.73 (d, J =
8.0 Hz, 1H), 6.80 (app t, J = 7.5 Hz, 1H), 6.92 (d, J = 8.5 Hz,
1H), 7.20 (app t, J = 7.5 Hz, 1H), 7.48-7.53 (m, 2H), 7.62 (d, J =
1.5 Hz, 1H), 7.68 (dd, J = 8.0, 2.0 Hz, 1H), 7.97 (d, J = 15.5 Hz,
1H); 13C NMR (125 MHz, CDCl3): δ 56.10, 56.14, 110.1, 110.8,
116.8, 118.9, 120.6, 121.7, 123.0, 128.1, 131.47, 131.51, 139.4,
146.2, 149.3, 153.3, 188.5.
N-(2-((E)-3-(3-methoxyphenyl)-3-oxoprop-1-
enyl)phenyl)acrylamide (4f); light yellow solid; mp: 144-146
1
oC; IR (KBr): ν 1598, 1661, 3264 cm_1; H NMR (500 MHz,
CDCl3): δ 3.85 (s, 3H), 5.81 (d, J = 10.0 Hz, 1H), 6.35-6.40 (m,
1H), 6.49 (d, J = 17.0 Hz, 1H), 7.13 (dd, J = 8.0, 2.0 Hz, 1H),
7.23-7.26 (m, 1H), 7.39 (app t, J = 7.5 Hz, 1H), 7.43-7.50 (m,
3H), 7.57 (d, J = 8.0 Hz, 1H), 7.68-7.76 (m, 2H), 7.88-8.00 (m,
2H); 13C NMR (125 MHz, CDCl3): δ 55.4, 112.8, 119.8, 121.2,
123.9, 125.2, 125.8, 127.2, 128.0, 128.5, 129.7, 130.9, 131.1,
136.6, 139.2, 139.7, 159.9, 164.3, 190.1.
(E)-3-(2-amino-5-chlorophenyl)-1-phenylprop-2-en-1-one
o
(2p); Yield: 72 % yellow solid; mp: 138-140 C; IR (KBr): ν
1
1216, 1587, 1655, 3347 cm_1; H NMR (500 MHz, CDCl3): δ
4.09 (bs, 2H), 6.66 (d, J = 9.0 Hz, 1H), 7.14 (dd, J = 9.0, 2.0 Hz,
1H), 7.45-7.52 (m, 4H), 7.59 (app t, J = 7.5 Hz, 1H), 7.89 (d, J =
15.5 Hz, 1H), 8.02-8.04 (m, 2H); 13C NMR (125 MHz, CDCl3): δ
118.1, 121.5, 122.7, 123.7, 127.2, 128.6, 128.8, 131.3, 133.1,
138.1, 138.5, 144.8, 189.9.
N-(2-((E)-3-(4-methoxyphenyl)-3-oxoprop-1-
enyl)phenyl)acrylamide (4g); light yellow solid; mp: 186-188
1
oC; IR (KBr): ν 1593, 1663, 3033, 3231 cm_1; H NMR (500
N-(2-((E)-3-oxo-3-phenylprop-1-enyl)phenyl)acrylamide
MHz, CDCl3): δ 3.89 (s, 3H), 5.74 (d, J = 9.5 Hz, 1H), 6.42 (d, J
= 16.5 Hz, 1H), 6.53-6.58 (m, 1H), 6.97-6.99 (m, 2H), 7.25 (app
t, J = 6.0 Hz, 1H), 7.40 (app t, J = 7.0 Hz, 1H), 7.53 (d, J = 15.5
Hz, 1H), 7.69 (d, J = 6.0 Hz, 1H), 7.77 (d, J = 7.5 Hz, 1H), 7.99-
8.05 (m, 3H), 9.52 (s, 1H); 13C NMR (125 MHz, CDCl3): δ 55.0,
113.4, 122.6, 125.3, 125.8, 126.4, 126.7, 128.6, 130.1, 130.3,
(4a); light yellow solid; mp: 156-158 oC; IR (KBr): ν 1600, 1660,
1
3287 cm_1; H NMR (500 MHz, CDCl3): δ 5.80 (d, J = 10.0 Hz,
1H), 6.37 (dd, J = 16.0, 10.0 Hz, 1H), 6.48 (d, J = 16.0 Hz, 1H),
7.24 (app t, J = 7.5 Hz, 1H), 7.43 (app t, J = 7.5 Hz, 1H), 7.47-
7.50 (m, 3H), 7.58 (app t, J = 7.5 Hz, 1H), 7.69 (d, J = 8.0 Hz,
1H), 7.76 (bs, 1H), 7.92-7.99 (m, 4H); 13C NMR (125 MHz,
CDCl3): δ 124.1, 125.2, 125.9, 127.2, 128.0, 128.5, 128.6, 128.7,
130.8, 131.1, 132.2, 136.5, 137.8, 139.5, 164.2, 190.3.
1
130.8, 136.6, 139.0, 163.0, 164.2, 187.9; H NMR (500 MHz,
DMSO-d6): 3.87 (s, 3H), 5.81 (d, J = 10.5 Hz, 1H), 6.29 (dd, J =
17.5, 1.5 Hz, 1H), 6.57 (dd, J = 17.5, 10.5 Hz, 1H), 7.08-7.09 (m,
2H), 7.32 (app t, J = 7.5 Hz, 1H), 7.45 (app t, J = 7.5 Hz, 1H),
7.51 (d, J = 7.5 Hz, 1H), 7.84 (d, J = 15.5 Hz, 1H), 7.89 (d, J =
15.5 Hz, 1H), 8.11 (d, J = 8.0 Hz, 1H), 8.15-8.17 (m, 2H), 10.10
(s, 1H); 13C NMR (125 MHz, DMSO-d6): 55.6, 114.1, 122.8,
126.0, 126.6, 127.2, 129.4, 130.4, 130.5, 130.9, 131.4, 137.1,
138.7, 163.3, 163.8, 187.5.
N-(2-((E)-3-(2-chlorophenyl)-3-oxoprop-1-
enyl)phenyl)acrylamide (4b); light yellow solid; mp: 134-136
1
oC; IR (KBr): ν 1622, 1659, 3027, 3216 cm_1; H NMR (500
MHz, CDCl3) : δ 5.77 (d, J = 10.0 Hz, 1H), 6.28 (dd, J = 16.5,
10.0 Hz, 1H), 6.41 (d, J = 17.0 Hz, 1H), 7.08 (d, J = 16.0 Hz,
1H), 7.22 (app t, J = 7.5 Hz, 1H), 7.33 (app t, J = 7.5 Hz, 1H),
7.38-7.44 (m, 3H), 7.48 (d, J = 7.5 Hz, 1H), 7.61-7.68 (m, 3H),
7.77 (bs, 1H); 13C NMR (125 MHz, CDCl3): δ 125.3, 126.2,
127.0, 127.4, 127.9, 128.0, 128.4, 129.8, 130.4, 130.7, 131.3,
131.8, 136.3, 138.8, 140.9, 164.2, 193.3.
N-(2-((E)-3-(3-bromophenyl)-3-oxoprop-1-
enyl)phenyl)acrylamide (4h); light yellow solid; mp: 158-160
1
oC; IR (KBr): ν 1598, 1659, 3275 cm_1; H NMR (500 MHz,
CDCl3): δ 5.81 (d, J = 9.5 Hz, 1H), 6.34-6.39 (m, 1H), 6.48 (d, J
= 16.5 Hz, 1H), 7.26 (s, 1H), 7.34-7.45 (m, 3H), 7.69-7.73 (m,
3H), 7.80-7.90 (m, 2H), 7.96 (d, J = 15.5 Hz, 1H), 8.08 (s, 1H);
13C NMR (125 MHz, CDCl3): δ 123.1, 123.5, 125.3, 126.1,
127.1, 127.3, 127.9, 128.7, 130.4, 130.7, 131.5, 131.6, 136.0,
136.5, 139.6, 140.2, 164.2, 188.8.
N-(2-((E)-3-(3-chlorophenyl)-3-oxoprop-1-
enyl)phenyl)acrylamide (4c); light yellow solid; mp: 170-172
1
oC; IR (KBr): ν 1600, 1660, 3281 cm_1; H NMR (500 MHz,
CDCl3): δ 5.75 (dd, J = 10.0, 2.0 Hz, 1H), 6.44 (dd, J = 16.0, 1.5
Hz, 1H), 6.51 (dd, J = 16.0, 10.0 Hz, 1H), 7.24 (app t, J = 7.5 Hz,
1H), 7.40-7.46 (m, 3H), 7.55 (d, J = 7.5 Hz, 1H), 7.70 (d, J = 7.5
Hz, 1H), 7.75 (d, J = 7.5 Hz, 1H), 7.89 (d, J = 7.5 Hz, 1H), 7.97
(app t, J = 1.5 Hz, 1H), 8.03 (d, J = 15.5 Hz, 1H), 9.22 (bs, 1H);
N-(2-((E)-3-(4-bromophenyl)-3-oxoprop-1-
enyl)phenyl)acrylamide (4i); light yellow solid; mp: 170-172
1
oC; IR (KBr): ν 1599, 1663, 3265 cm_1; H NMR (500 MHz,

7
CDCl ): δ 5.81 (d, J = 10.0 Hz, 1H), 6.33-6.38 (m, 1H), 6.47 (d, J
= 17.0 Hz, 1H), 7.18-7.26 (m, 1H), 7.40-7.45 (m, 2H), 7.61-7.62
126.4, 127.1, 127.2, 127.4, 128.3, 128.4, 130.2, 130.5, 130.8,
131.5, 132.4, 136.4, 137.0, 137.3, 141.4, 164.3, 192.2.
ACCEPTED MANUSCRIPT
3
(m, 2H), 7.67-7.70 (m, 2H), 7.83-7.85 (m, 3H), 7.95 (d, J = 15.0
Hz, 1H); 13C NMR (125 MHz, CDCl3): δ 123.7, 125.2, 126.1,
127.3, 128.4, 128.7, 130.1, 130.7, 131.4, 132.1, 136.3, 136.4,
136.5, 139.9, 189.1; 1H NMR (500 MHz, DMSO-d6): δ 5.81 (dd,
J = 10.5, 1.5 Hz, 1H), 6.29 (dd, J = 17.0, 1.5 Hz, 1H), 6.56 (dd, J
= 17.0, 10.5 Hz, 1H), 7.32 (app t, J = 7.5 Hz, 1H), 7.47 (app t, J
= 7.5 Hz, 1H), 7.51 (d, J = 7.5 Hz, 1H), 7.77-7.79 (m, 2H), 7.87
(s, 2H), 8.09-8.10 (m, 2H), 8.13 (d, J = 8.0 Hz, 1H), 10.13 (s,
1H); 13C NMR (125 MHz, DMSO-d6): 122.3, 126.0, 126.6,
127.3, 129.1, 130.6, 131.0, 131.3, 131.9, 136.5, 137.3, 140.1,
163.8, 188.4.
N-(2-((E)-3-(3,4-dimethoxyphenyl)-3-oxoprop-1-
enyl)phenyl)acrylamide (4o); yellow solid; mp: 136-138 oC; IR
1
(KBr): ν 1603, 1663, 3270 cm_1; H NMR (500 MHz, CDCl3): δ
3.85 (s, 3H), 3.91 (s, 3H), 5.78-5.80 (m, 1H), 6.43-6.51 (m, 2H),
6.84 (d, J = 8.0 Hz, 1H), 7.21 (app t, J = 7.5 Hz, 1H), 7.38-7.43
(m, 2H), 7.47 (s, 1H), 7.55 (dd, J = 8.5, 1.5 Hz, 1H), 7.64 (d, J =
8.0 Hz, 1H), 7.97-8.00 (m, 2H), 8.32 (bs, 1H); 13C NMR (125
MHz, CDCl3): δ 55.8, 56.0, 109.9, 110.6, 123.3, 125.0, 125.6,
127.1, 128.2, 130.76, 130.81, 131.0, 136.6, 139.0, 149.1, 153.4,
1
164.4, 188.3; H NMR (500 MHz, DMSO-d6): 3.86 (s, 3H), 3.87
(s, 3H), 5.81 (dd, J = 10.5, 1.0 Hz, 1H), 6.28 (dd, J = 17.0, 1.5
Hz, 1H), 6.56 (dd, J = 17.0, 10.5 Hz, 1H), 7.10 (d, J = 8.5 Hz,
1H), 7.32 (app t, J = 7.5 Hz, 1H), 7.46 (app t, J = 7.5 Hz, 1H),
7.50 (d, J = 7.5 Hz, 1H), 7.61 (d, J = 1.5 Hz, 1H), 7.84 (d, J =
15.5 Hz, 1H), 7.88-7.91 (m, 2H), 8.12 (d, J = 8.0 Hz, 1H), 10.10
(s, 1H); 13C NMR (125 MHz, DMSO-d6): 55.6, 55.8, 110.8,
110.9, 122.7, 123.4, 125.9, 126.6, 127.2, 127.3, 129.5, 130.47,
130.53, 131.4, 137.1, 138.6, 148.8, 153.3, 163.8, 187.5.
N-(2-((E)-3-oxo-3-p-tolylprop-1-enyl)phenyl)acrylamide
o
(4j); light yellow solid; mp: 158-160 C; IR (KBr): ν 1595,
1
1660, 3285 cm_1; H NMR (500 MHz, CDCl3): δ 2.43 (s, 3H),
5.81 (d, J = 10.0 Hz, 1H), 6.37 (dd, J = 16.0, 10.0 Hz, 1H), 6.48
(d, J = 16.0 Hz, 1H), 7.24 (app t, J = 7.5 Hz, 1H), 7.27-7.29 (m,
2H), 7.43 (app t, J = 7.5 Hz, 1H), 7.49 (d, J = 15.0 Hz, 1H), 7.68
(d, J = 7.5 Hz, 1H), 7.72 (bs, 1H), 7.89-7.91 (m, 2H), 7.95-7.98
(m, 2H); 13C NMR (125 MHz, CDCl3): δ 21.8, 124.3, 125.0,
125.8, 127.2, 127.9, 128.5, 128.8, 129.5, 130.9, 131.0, 135.2,
136.4, 139.0, 144.2, 164.2, 189.8.
N-(4-chloro-2-((E)-3-oxo-3-phenylprop-1-
enyl)phenyl)acrylamide (4p); light yellow solid; mp: 194-196
1
oC; IR (KBr): ν 1609, 1664, 3272 cm_1; H NMR (500 MHz,
N-(2-((E)-3-(4-fluorophenyl)-3-oxoprop-1-
DMSO-d6): δ 5.82 (dd, J = 10.0, 1.0 Hz, 1H), 6.30 (d, J = 17.0
Hz, 1H), 6.56 (dd, J = 17.0, 10.0 Hz, 1H), 7.51 (dd, J = 8.5, 2.5
Hz, 1H), 7.55-7.59 (m, 3H), 7.68 (app t, J = 7.5 Hz, 1H), 7.80 (d,
J = 16.0 Hz, 1H), 8.10 (d, J = 16.0 Hz, 1H), 8.19-8.21 (m, 2H),
8.27 (d, J = 2.0 Hz, 1H), 10.17 (s, 1H); 13C NMR (125 MHz,
DMSO-d6): δ 124.0, 126.7, 127.6, 128.1, 128.7, 128.8, 130.3,
130.9, 131.1, 133.3, 136.0, 137.3, 138.0, 163.9, 189.1.
enyl)phenyl)acrylamide (4k); light yellow solid; mp: 174-176
oC; IR (KBr): ν 1210, 1603, 1662, 3267 cm_1; H NMR (500
1
MHz, DMSO-d6): δ 5.81 (dd, J = 10.0, 1.0 Hz, 1H), 6.29 (dd, J =
17.0, 1.5 Hz, 1H), 6.56 (dd, J = 17.0, 10.0 Hz, 1H), 7.32 (app t, J
= 7.5 Hz, 1H), 7.38-7.42 (m, 2H), 7.47 (app t, J = 7.5 Hz, 1H),
7.51 (d, J = 7.5 Hz, 1H), 7.85-7.92 (m, 2H), 8.13 (d, J = 7.5 Hz,
1H), 8.24-8.27 (m, 2H), 10.13 (s, 1H); 13C NMR (125 MHz,
DMSO-d6): δ 115.8, 115.9, 122.5, 126.0, 126.6, 127.3, 129.1,
130.9, 131.3, 131.5, 131.6, 134.2, 137.3, 139.8, 163.8, 164.1,
166.1, 187.9.
3-Methyl-4-(2-oxo-2-phenyl-ethyl)-1H-quinolin-2-one (5a);
Reaction time: 20 h; Yield: 91% white solid; mp: 292-294 oC; IR
1
(KBr): ν 1674, 2923 cm_1; H NMR (500 MHz, DMSO-d6): δ
2.03 (s, 3H), 4.84 (s, 2H), 7.09 (app t, J = 7.5 Hz, 1H), 7.32 (d, J
= 8.0 Hz, 1H), 7.42 (app t, J = 7.5 Hz, 1H), 7.52 (d, J = 8.0 Hz,
1H), 7.59-7.62 (m, 2H), 7.72 (app t, J = 7.0 Hz, 1H), 8.15-8.17
(m, 2H), 11.78 (s, 1H); 13C NMR (125 MHz, DMSO-d6): δ 12.9,
38.9, 115.2, 119.8, 121.7, 124.6, 128.4, 128.9, 129.0, 129.1,
133.7, 136.3, 137.1, 140.7, 161.8, 196.2; HRMS (ESI):
calculated for C18H15NO2: 278.1181 (M+H)+, found: 278.1214
(M+H)+.
N-(2-((E)-3-(naphthalen-1-yl)-3-oxoprop-1-
enyl)phenyl)acrylamide (4l); light yellow solid; mp: 140-142
1
oC; IR (KBr): ν 1638, 1657, 3236 cm_1; H NMR (500 MHz,
CDCl3): δ 5.72 (d, J = 9.5 Hz, 1H), 6.21 (dd, J = 17.0, 10.0 Hz,
1H), 6.37 (d, J = 17.0 Hz, 1H), 7.21 (app t, J = 7.5 Hz, 1H), 7.25
(d, J = 16.0 Hz, 1H), 7.38 (app t, J = 7.5 Hz, 1H), 7.48 (app t, J =
7.5 Hz, 1H), 7.51-7.54 (m, 2H), 7.63-7.64 (m, 2H), 7.75-7.80 (m,
3H), 7.88-7.90 (m, 1H), 7.97 (d, J = 8.5 Hz, 1H), 8.33-8.35 (m,
1H); 13C NMR (125 MHz, CDCl3): δ 124.6, 125.4, 125.6, 126.1,
126.6, 127.2, 127.6, 127.8, 128.3, 128.5, 128.6, 130.5, 130.6,
131.2, 132.1, 133.9, 136.3, 136.6, 140.5, 164.2, 195.1.
4-[2-(2-Chloro-phenyl)-2-oxo-ethyl]-3-methyl-1H-quinolin-
2-one (5b); Reaction time: 12 h; Yield: 79% white solid; mp:
o
1
236-238 C; IR (KBr): ν 1660, 1691, 2927 cm_1; H NMR (500
MHz, DMSO-d6): δ 2.08 (s, 3H), 4.71 (s, 2H), 7.15 (app t, J = 7.5
Hz, 1H), 7.32 (d, J = 8.5 Hz, 1H), 7.44 (app t, J = 7.5 Hz, 1H),
7.51 (app t, J = 7.5 Hz, 1H), 7.55-7.60 (m, 2H), 7.66 (d, J = 8.0
Hz, 1H), 7.94 (d, J = 7.5 Hz, 1H), 11.82 (s, 1H); 13C NMR (125
MHz, DMSO-d6): δ 12.9, 42.8, 115.2, 119.5, 121.7, 124.5, 127.4,
129.2, 129.4, 129.5, 130.5, 132.5, 137.2, 138.3, 139.2, 161.7,
198.4; HRMS (ESI): calculated for C18H14ClNO2: 312.0791
(M+H)+, found: 312.0790 (M+H)+.
N-(2-((E)-3-oxo-3-(thiophen-2-yl)prop-1-
enyl)phenyl)acrylamide (4m); white solid; mp: 146-148 oC; IR
1
(KBr): ν 1595, 1660, 3288 cm_1; H NMR (500 MHz, CDCl3): δ
5.78 (d, J = 11.0 Hz, 1H), 6.39-6.49 (m, 2H), 7.14 (app t, J = 4.5
Hz, 1H), 7.22 (app t, J = 7.5 Hz, 1H), 7.31 (d, J = 15.5 Hz, 1H),
7.42 (app t, J = 7.5 Hz, 1H), 7.64-7.66 (m, 2H), 7.795 (d, J = 4.0
Hz, 1H), 7.94 (bs, 1H), 8.02 (d, J = 15.0 Hz, 1H), 8.16 (bs, 1H);
13C NMR (125 MHz, CDCl3): δ 123.8, 125.1, 125.8, 127.2,
127.7, 128.5, 130.9, 131.2, 132.3, 134.5, 136.6, 139.0, 145.2,
164.3, 182.0.
4-[2-(3-Chloro-phenyl)-2-oxo-ethyl]-3-methyl-1H-quinolin-
2-one (5c); Reaction time: 14 h; Yield: 81% white solid; mp:
o
1
294-296 C; IR (KBr): ν 1661, 1686, 2859 cm_1; H NMR (500
MHz, DMSO-d6): δ 2.03 (s, 3H), 4.87 (s, 2H), 7.09 (app t, J = 7.5
Hz, 1H), 7.32 (d, J = 8.0 Hz, 1H), 7.41 (app t, J = 7.5 Hz, 1H),
7.55 (d, J = 8.0 Hz, 1H), 7.63 (app t, J = 8.0 Hz, 1H), 7.79 (d, J =
7.5 Hz, 1H), 8.09 (d, J = 8.0 Hz, 1H), 8.20 (s, 1H), 11.81 (s, 1H);
13C NMR (125 MHz, DMSO-d6): δ 12.8, 39.1, 115.2, 119.7,
121.6, 124.6, 126.9, 128.2, 129.0, 129.2, 130.8, 133.3, 133.8,
137.1, 138.1, 140.3, 161.8, 195.2; HRMS (ESI): calculated for
C18H14ClNO2: 312.0791 (M+H)+, found: 312.0791 (M+H)+.
N-(2-((E)-3-(2,4-dichlorophenyl)-3-oxoprop-1-
enyl)phenyl)acrylamide (4n); light yellow solid; mp: 132-134
1
oC; IR (KBr): ν 1627, 1658, 3262 cm_1; H NMR (500 MHz,
CDCl3): δ 5.81 (d, J = 10.0 Hz, 1H), 6.29 (dd, J = 16.5, 10.0 Hz,
1H), 6.43 (d, J = 17.0 Hz, 1H), 7.09 (d, J = 15.5 Hz, 1H), 7.25
(app t, J = 7.5 Hz, 1H), 7.32 (dd, J = 8.5, 1.5 Hz, 1H), 7.42 (app
t, J = 7.5 Hz, 1H), 7.45-7.46 (m, 2H), 7.51 (bs, 1H), 7.63-7.68
(m, 2H), 7.74 (bs, 1H); 13C NMR (125 MHz, CDCl3): δ 125.7,

8
Tetrahedron
4-[2-(4-Chloro-phenyl)-2-oxo-ethyl]-3-methyl-1H-
115.2, 119.7, 121.6, 124.5, 127.8, 129.0, 129.1, 130.3, 131.9,
ACCEPTED MANUSCRIPT
quinolin-2-one (5d); Reaction time: 14 h; Yield: 80% white
135.3, 137.1, 140.3, 161.8, 195.4; HRMS (ESI): calculated
solid; mp: 274-276 C; IR (KBr): ν 1652, 1683, 2849 cm_1; H
NMR (500 MHz, DMSO-d6): δ 2.03 (s, 3H), 4.84 (s, 2H), 7.08
(app t, J = 7.5 Hz, 1H), 7.32 (d, J = 8.0 Hz, 1H), 7.41 (app t, J =
7.5 Hz, 1H), 7.52 (d, J = 8.0 Hz, 1H), 7.67-7.68 (m, 2H), 8.16-
8.18 (m, 2H), 11.80 (s, 1H) ; 13C NMR (125 MHz, DMSO-d6): δ
12.8, 38.9, 115.2, 119.7, 121.6, 124.5, 128.9, 129.0, 129.2, 130.3,
135.0, 137.1, 138.6, 140.4, 161.8, 195.2; HRMS (ESI):
calculated for C18H14ClNO2: 312.0791 (M+H)+, found: 312.0775
(M+H)+.
C18H14BrNO2: 358.0286 (M+2+H)+, found: 358.0268 (M+2+H)+.
o
1
3-Methyl-4-(2-oxo-2-p-tolyl-ethyl)-1H-quinolin-2-one (5j);
Reaction time: 24 h; Yield: 86% white solid; mp: 274-276 oC; IR
(KBr): ν 1651, 1678, 2850, 2922 cm_1; H NMR (500 MHz,
1
DMSO-d6): δ 2.04 (s, 3H), 2.42 (s, 3H), 4.76 (s, 2H), 7.08 (app t,
J = 8.0 Hz, 1H), 7.33 (d, J = 7.5 Hz, 1H), 7.39-7.42 (m, 3H), 7.50
(d, J = 8.0 Hz, 1H), 8.04-8.06 (m, 2H), 11.66 (s, 1H); 13C NMR
(125 MHz, DMSO-d6): δ 12.8, 21.2, 38.7, 115.2, 119.8, 121.6,
124.5, 128.4, 128.97, 129.01, 129.4, 133.9, 137.1, 140.8, 144.1,
161.8, 195.6; HRMS (ESI): calculated for C19H17NO2: 292.1338
(M+H)+, found: 292.1338 (M+H)+.
4-[2-(2-Methoxy-phenyl)-2-oxo-ethyl]-3-methyl-1H-
quinolin-2-one (5e); Reaction time: 24h; Yield: 87% white
solid; mp: 178-180 C; IR (KBr): ν 1665, 2842 cm_1; H NMR
(500 MHz, DMSO-d6): δ 2.04 (s, 3H), 3.98 (s, 3H), 4.66 (s, 2H),
7.06 (app t, J = 7.5 Hz, 1H), 7.12 (app t, J = 7.5 Hz, 1H), 7.25 (d,
J = 8.5 Hz, 1H), 7.31 (d, J = 8.0 Hz, 1H), 7.42 (app t, J = 7.5 Hz,
1H), 7.53 (d, J = 8.0 Hz, 1H), 7.57-7.61 (m, 2H), 11.76 (s, 1H);
13C NMR (125 MHz, DMSO-d6): δ 12.8, 43.6, 56.0, 112.6, 115.2,
119.7, 120.6, 121.6, 124.4, 127.7, 128.9, 129.5, 133.9, 137.1,
140.5, 158.2, 161.8, 197.7; HRMS (ESI): calculated for
C19H17NO3: 308.1287 (M+H)+, found: 308.1288 (M+H)+.
o
1
4-[2-(4-Fluoro-phenyl)-2-oxo-ethyl]-3-methyl-1H-quinolin-
2-one (5k); Reaction time: 9 h; Yield: 83% white solid; mp:
276-278 C; IR (KBr): ν 1655, 1685, 2883, 3432 cm_1; H NMR
(500 MHz, DMSO-d6): δ 2.03 (s, 3H), 4.83 (s, 2H), 7.09 (app t, J
= 7.5 Hz, 1H), 7.32 (d, J = 8.5 Hz, 1H), 7.40-7.45 (m, 3H), 7.52
(d, J = 8.5 Hz, 1H), 8.23-8.26 (m, 2H), 11.80 (s, 1H); 13C NMR
(125 MHz, DMSO-d6): δ 12.8, 38.9, 115.2, 115.8, 115.9 119.8,
121.6, 124.5, 129.0, 129.1, 131.36, 131.44, 133.1, 137.1, 140.5,
161.8, 164.3, 166.3, 194.7; HRMS (ESI): calculated for
C18H14FNO2: 296.1087 (M+H)+, found: 296.1072 (M+H)+.
o
1
4-[2-(3-Methoxy-phenyl)-2-oxo-ethyl]-3-methyl-1H-
quinolin-2-one (5f); Reaction time: 24h; Yield: 92% white
3-Methyl-4-(2-naphthalen-1-yl-2-oxo-ethyl)-1H-quinolin-2-
one (5l); Reaction time: 21 h; Yield: 85% white solid; mp: 248-
250 oC; IR (KBr): ν 1658, 2854, 2925 cm_1; 1H NMR (500 MHz,
DMSO-d6): δ 2.12 (s, 3H), 4.92 (s, 2H), 7.12 (app t, J = 7.5 Hz,
1H), 7.34 (d, J = 8.0 Hz, 1H), 7.43 (app t, J = 7.5 Hz, 1H), 7.58-
7.59 (m, 2H), 7.68-7.71 (m, 2H), 8.03-8.04 (m, 1H), 8.20 (d, J =
8.5 Hz, 1H), 8.37-8.39 (m, 1H), 8.49 (d, J = 7.0 Hz, 1H), 11.82
(s, 1H); 13C NMR (125 MHz, DMSO-d6): δ 12.9, 42.2, 115.2,
119.8, 121.7, 124.6, 124.9, 125.1, 126.5, 128.0, 128.60, 128.63,
129.0, 129.2, 129.4, 132.9, 133.5, 134.8, 137.2, 140.5, 161.8,
200.0; HRMS (ESI): calculated for C22H17NO2: 328.1338
(M+H)+, found: 328.1322 (M+H)+.
solid; mp: 240-242 C; IR (KBr): ν 1650, 2830 cm_1; H NMR
(500 MHz, DMSO-d6): δ 2.03 (s, 3H), 3.85 (s, 3H), 4.83 (s, 2H),
7.09 (app t, J = 7.5 Hz, 1H), 7.29 (dd, J = 8.0, 2.0 Hz, 1H), 7.31
(d, J = 8.0 Hz, 1H), 7.42 (app t, J = 7.5 Hz, 1H), 7.51-7.54 (m,
2H), 7.63 (app t, J = 1.5 Hz, 1H), 7.77 (d, J = 7.5 Hz, 1H), 11.79
(s, 1H); 13C NMR (125 MHz, DMSO-d6): δ 12.8, 39.1, 55.4,
112.9, 115.2, 119.7, 119.8, 120.7, 121.6, 124.5, 129.0, 129.1,
130.0, 137.1, 137.7, 140.6, 159.5, 161.8, 195.9; HRMS (ESI):
calculated for C19H17NO3: 308.1287 (M+H)+, found: 308.1287
(M+H)+.
o
1
4-[2-(4-Methoxy-phenyl)-2-oxo-ethyl]-3-methyl-1H-
quinolin-2-one (5g); Reaction time: 24h; Yield: 91% white
solid; mp: 256-258 oC; IR (KBr): ν 1168, 1650, 1670, 2924 cm_1;
1H NMR (500 MHz, DMSO-d6): δ 2.03 (s, 3H), 3.88 (s, 3H),
4.75 (s, 2H), 7.07-7.12 (m, 3H), 7.31 (d, J = 8.0 Hz, 1H), 7.41
(app t, J = 7.5 Hz, 1H), 7.50 (d, J = 7.5 Hz, 1H), 8.13-8.14 (m,
2H), 11.77 (s, 1H); 13C NMR (125 MHz, DMSO-d6): δ 12.8,
38.5, 55.6, 114.0, 115.1, 119.9, 121.6, 124.5, 128.9, 129.0, 129.3,
130.6, 137.1, 140.9, 161.8, 163.5, 194.4; HRMS (ESI):
calculated for C19H17NO3: 308.1287 (M+H)+, found: 308.1287
(M+H)+.
3-Methyl-4-(2-oxo-2-thiophen-2-yl-ethyl)-1H-quinolin-2-
one (5m); Reaction time: 21 h; Yield: 72% white solid; mp:
o
1
274-276 C; IR (KBr): ν 1653, 2854 cm_1; H NMR (500 MHz,
DMSO-d6): δ 2.07 (s, 3H), 4.79 (s, 2H), 7.11 (app t, J = 7.5 Hz,
1H), 7.32 (d, J = 8.0 Hz, 1H), 7.35 (app t, J = 4.0 Hz, 1H), 7.42
(app t, J = 7.5 Hz, 1H), 7.58 (d, J = 8.5 Hz, 1H), 8.08 (d, J = 5.0
Hz, 1H), 8.32 (d, J = 3.5 Hz, 1H), 11.80 (s, 1H); 13C NMR (125
MHz, DMSO-d6): δ 12.9, 39.0, 115.2, 119.7, 121.7, 124.5, 128.9,
129.1, 129.3, 134.2, 135.5, 137.1, 139.9, 143.2, 161.8, 189.1;
HRMS (ESI): calculated for C16H13NO2S: Exact Mass: 284.0745
(M+H)+, found: 284.0730 (M+H)+.
4-[2-(3-Bromo-phenyl)-2-oxo-ethyl]-3-methyl-1H-quinolin-
2-one (5h); Reaction time: 16 h; Yield: 76% white solid; mp:
4-[2-(2,4-Dichloro-phenyl)-2-oxo-ethyl]-3-methyl-1H-
292-294 C; IR (KBr): ν 1661, 1687, 2861 cm_1; H NMR (500
MHz, DMSO-d6): δ 2.03 (s, 3H), 4.87 (s, 2H), 7.09 (app t, J = 7.5
Hz, 1H), 7.32 (d, J = 8.0 Hz, 1H), 7.41 (app t, J = 7.5 Hz, 1H),
7.54-7.58 (m, 2H), 7.92 (d, J = 7.5 Hz, 1H), 8.13 (d, J = 7.5 Hz,
1H), 8.32 (s, 1H), 11.79 (s, 1H); 13C NMR (125 MHz, DMSO-
d6): δ 12.8, 39.1, 115.1, 119.7, 121.6, 122.2, 124.6, 127.2, 129.0,
129.2, 131.0, 136.2, 137.1, 138.3, 140.2, 161.8, 195.1; HRMS
(ESI): calculated for C18H14BrNO2: 358.0286 (M+2+H)+, found:
358.0249 (M+2+H)+.
o
1
quinolin-2-one (5n); Reaction time: 7 h; Yield: 78% white solid;
o
1
mp: 240-242 C; IR (KBr): ν 1661, 1709, 2855 cm_1; H NMR
(500 MHz, DMSO-d6): δ 2.07 (s, 3H), 4.72 (s, 2H), 7.14 (app t, J
= 7.5 Hz, 1H), 7.32 (d, J = 8.0 Hz, 1H), 7.43 (app t, J = 7.5 Hz,
1H), 7.62-7.66 (m, 2H), 7.78 (d, J = 1.5 Hz, 1H), 8.03 (d, J = 8.5
Hz, 1H), 11.82 (s, 1H); 13C NMR (125 MHz, DMSO-d6): δ 12.9,
42.7, 115.2, 119.5, 121.7, 124.6, 127.6, 129.2, 129.4, 130.2,
130.8, 131.1, 136.4, 136.9, 137.2, 139.1, 161.7, 197.4; HRMS
(ESI): calculated for C18H13Cl2NO2: 346.0402 (M+H)+, found:
346.0400 (M+H)+.
4-[2-(4-Bromo-phenyl)-2-oxo-ethyl]-3-methyl-1H-quinolin-
2-one (5i); Reaction time: 16 h; Yield: 75 % white solid; mp:
4-[2-(3,4-Dimethoxy-phenyl)-2-oxo-ethyl]-3-methyl-1H-
quinolin-2-one (5o); Reaction time: 24 h; Yield: 87% white
solid; mp: 306-308 oC; IR (KBr): ν 1652, 1672, 2843, 3434 cm_1;
1H NMR (500 MHz, DMSO-d6): δ 2.03 (s, 3H), 3.84 (s, 3H),
3.88 (s, 3H), 4.78 (s, 2H), 7.09 (app t, J = 7.5 Hz, 1H), 7.15 (d, J
= 8.0 Hz, 1H), 7.31 (d, J = 8.0 Hz, 1H), 7.41 (app t, J = 7.5 Hz,
o
1
276-278 C; IR (KBr): ν 1658, 2854, 2925 cm_1; H NMR (500
MHz, DMSO-d6): δ 2.03 (s, 3H), 4.82 (s, 2H), 7.08 (app t, J = 7.5
Hz, 1H), 7.32 (d, J = 8.0 Hz, 1H), 7.41 (app t, J = 7.5 Hz, 1H),
7.52 (d, J = 8.0 Hz, 1H), 7.81-7.83 (m, 2H), 8.08-8.10 (m, 2H),
11.79 (s, 1H); 13C NMR (125 MHz, DMSO-d6): δ 12.8, 38.9,

9
1H), 7.50 (d, J = 8.5 Hz, 1H), 7.58 (s, 1H), 7.90 (dd, J = 8.5, 1.5
Hz, 1H), 11.78 (s, 1H); 13C NMR (125 MHz, DMSO-d6): δ 12.8,
38.5, 55.6, 55.9, 110.6, 111.0, 115.2, 119.9, 121.6, 123.0, 124.5,
129.0, 129.2, 137.1, 140.9, 148.6, 153.4, 161.8, 194.4; HRMS
(ESI): calculated for C20H19NO4: 338.1392 (M+H)+, found:
338.1383 (M+H)+.
δ 7.15 (app t, J = 4.0 Hz, 1H), 7.45-7.49 (m, 2H), 7.68 (d appt,
ACCEPTED MANUSCRIPT
J = 7.5, 1.5 Hz, 1H), 7.72 (d, J = 4.0 Hz, 1H), 7.76 (d, J = 8.0 Hz,
1H), 7.78 (d, J = 8.0 Hz, 1H), 8.08 (d, J = 8.5 Hz, 1H), 8.12 (d, J
= 8.5 Hz, 1H); 13C NMR (125 MHz, CDCl3): δ 117.7, 125.9,
126.2, 127.3, 127.5, 128.1, 128.6, 129.4, 129.9, 136.7, 145.5,
148.2, 152.4.
6-Chloro-3-methyl-4-(2-oxo-2-phenyl-ethyl)-1H-quinolin-
6-chloro-2-phenylquinoline (3h); Reaction time: 5 h; Yield:
64 % white solid; mp: 100-102 oC; 1H NMR (500 MHz, CDCl3):
δ 7.47 (app t, J = 7.5 Hz, 1H), 7.51-7.54 (m, 2H), 7.65 (dd, J =
9.0, 2.0 Hz, 1H), 7.80 (s, 1H), 7.88 (d, J = 8.5 Hz, 1H), 8.09-8.15
(m, 4H); 13C NMR (125 MHz, CDCl3): δ 119.9, 126.2, 127.6,
127.8, 129.0, 129.6, 130.6, 131.4, 132.0, 135.9, 139.3, 146.7,
157.6.
2-one (5p); Reaction time: 6 h; Yield: 82% white solid; mp: 304-
o
306 C; IR (KBr): ν 1656, 2914 cm_1; 1H NMR (500 MHz,
DMSO-d6): δ 2.02 (s, 3H), 4.87 (s, 2H), 7.33 (d, J = 9.0 Hz, 1H),
7.47 (dd, J = 8.5, 1.5 Hz, 1H), 7.59-7.62 (m, 2H), 7.67 (d, J = 1.5
Hz, 1H), 7.72 (app t, J = 7.5 Hz, 1H), 8.15-8.17 (m, 2H), 11.93
(s, 1H); 13C NMR (125 MHz, DMSO-d6): δ 12.9, 38.9, 117.0,
121.2, 124.0, 125.8, 128.4, 128.8, 128.9, 130.4, 133.6, 135.8,
136.3, 139.9, 161.5, 196.0; HRMS (ESI): calculated for
C18H14ClNO2: 312.0791 (M+H)+, found: 312.0075 (M+H)+.
Acknowledgments
KCB is thankful to SERB-DST, New Delhi for funding (CS-
27/2013), Prof. R. M. Singh BHU, for lab facilities and director
CBMR, for HRMS.
2-phenylquinoline (3a); Reaction time: 2 h; Yield: 80 %
o
1
white solid; mp: 76-78 C; H NMR (500 MHz, CDCl3): δ 7.46
(app t, J = 7.5 Hz, 1H), 7.50-7.54 (m, 3H), 7.72 (app t, J = 7.5
Hz, 1H), 7.82 (d, J = 8.0 Hz, 1H), 7.87 (d, J = 8.5 Hz, 1H), 8.15-
8.18 (m, 3H), 8.21 (d, J = 8.5 Hz, 1H); 13C NMR (125 MHz,
CDCl3): δ 119.1, 126.3, 127.3, 127.5, 127.6, 128.9, 129.4, 129.7,
129.8, 136.8, 139.8, 148.4, 157.4.
Supplementary Material
Copies of 1H and 13C NMR for compounds 2, 5 and 3 series is
being provided in supporting information.
2-(2-chlorophenyl)quionline (3b); Reaction time: 2 h; Yield:
o
1
88 % white solid; mp: 76-78 C; H NMR (500 MHz, CDCl3): δ
7.36-7.43 (m, 2H), 7.51 (dd, J = 8.0, 1.5 Hz, 1H), 7.58 (app t, J =
7.5 Hz, 1H), 7.70 (dd, J = 7.0, 2.0 Hz, 1H), 7.73-7.76 (m, 2H),
7.87 (d, J = 8.0 Hz, 1H), 8.18 (d, J = 8.5 Hz, 1H), 8.22 (d, J = 8.5
Hz, 1H); 13C NMR (125 MHz, CDCl3): δ 122.8, 126.8, 127.2,
127.3, 127.6, 129.75, 129.79, 129.9, 130.2, 131.8, 132.5, 135.7,
139.8, 148.2, 157.5.
References and notes
1. (a) Bharadwaj KC. RSC Adv. 2015; 5: 75923; (b) Xie P, Huang Y.
Eur. J. Org. Chem. 2013; 6213; (c) Aroyan CE, Dermenci A,
Miller SJ. Tetrahedron. 2009; 65: 4069.
2. (a) Basavaiah D, Reddy GC. Arkivoc. 2016; 172; (b) Bhowmik S,
Batra S. Curr. Org. Chem. 2014; 18: 3078; (c) Wei Y, Shi M.
Chem. Rev. 2013; 113: 6659; (d) Liu T.-Y., Xie M, Chen Y.-C.
Chem. Soc. Rev. 2012; 41: 4101.
3. (a) Jeon S, Han S. J. Am. Chem. Soc. 2017; 139: 6302; (b) Kang
T.-C., Wu L.-P., Yu Q.-W., Wu X.-Y. Chem. Eur. J. 2017; 23:
6509; (c) Frias M, Mas-Ballesté R, Arias S, Alvarado C, Alemán
J. J. Am. Chem. Soc. 2017; 139: 672; (d) Li S, Liu Y, Huang B,
Zhou T, Tao H, Xiao Y, Liu L, Zhang J. ACS Catal. 2017; 7:
2805; (e) Li Y, Liu T, Zhang H, Du Z, Chen C. Mol. Catal. 2017;
432: 292; (f) Yang S.-M., Reddy GM, Liu M.-H., Wang T.-P., Yu
J.-K., Lin W. J. Org. Chem. 2017; 82: 781.
2-(4-methoxyphenyl)quinoline (3c); Reaction time: 6 h;
o
1
Yield: 77 % white solid; mp: 116-118 C; H NMR (500 MHz,
CDCl3): δ 3.87 (s, 3H), 7.03-7.05 (m, 2H), 7.48 (app t, J = 7.5
Hz, 1H), 7.70 (d appt, J = 7.5, 1.0 Hz, 1H), 7.79 (d, J = 8.0 Hz,
1H), 7.82 (d, J = 8.5 Hz, 1H), 8.13-8.17 (m, 4H); 13C NMR (125
MHz, CDCl3): δ 55.5, 114.3, 118.6, 126.0, 127.0, 127.5, 129.0,
129.6, 132.4, 136.7, 148.4, 157.0, 160.9.
4. (a) Zhou W, Chen P, Tao M, Su X, Zhao Q, Zhang J. Chem.
Commun. 2016; 52: 7612; (b) Dong X, Liang L, Li E, Huang Y.
Angew. Chem. Int. Ed. 2015; 54: 1621; (c) Zhou R, Wang J, Yu J,
He Z. J. Org. Chem. 2013; 78: 10596; (d) Kumar R, Kumar T,
Mobin SM, Nambothiri INN. J. Org. Chem. 2013; 78: 5073; (e)
Hu C, Geng Z, Ma J, Huang Y, Chen R. Chem. Asian J. 2012; 7:
2032; (f) Zhao Q.-Y., Pei C.-K., Guan X.-Y., Shi M. Adv. Synth.
Catal. 2011; 353: 1973.
5. (a) Frank SA, Mergott DJ, Roush WR. J. Am. Chem. Soc. 2002;
124: 2404; (b) Wang L.-C., Luis AL, Agapiou K, Jang H.-Y.,
Krische MJ. J. Am. Chem. Soc. 2002; 124: 2402; (c) Erguden J.-
K., Moore HW. Org. Lett. 1999; 1: 375.
6. (a) Lee SY, Fujiwara Y, Nishiguchi A, Kalek M, Fu GC. J. Am.
Chem. Soc. 2015; 137: 4587; (b) MacKay JA, Landis ZC, Motika
SE, Kench MH. J. Org. Chem. 2012; 77: 7768; (c) Henry CE,
Kwon O. Org. Lett. 2007; 9: 3069; (d) Wang J.-C., Ng S.-S.,
Krische MJ. J. Am. Chem. Soc. 2003; 125: 3682.
7. (a) Han J.-c., Li F, Li C.-c. J. Am. Chem. Soc. 2014; 136: 13610;
(b) Kim HJ, Ruszczycky MW, Choi S.-h., Liu Y.-n., Liu H.-w.
Nature. 2011; 473: 109; (c) Dermenci A, Selig PS, Domaoal RA,
Spasov KA, Anderson KS, Miller SJ. Chem. Sci. 2011; 2: 1568;
(d) Winbush SM, Mergott DJ, Roush WR. J. Org. Chem. 2008;
73: 1818; (e) Stark LM, Pekari K, Sorensen EJ. Proc. Natl. Acad.
Sci. U.S.A. 2004; 101: 12064.
2-(3-bromophenyl)quionline (3d); Reaction time: 3 h; Yield:
o
1
92 % white solid; mp: 64-66 C; H NMR (500 MHz, CDCl3): δ
7.39 (app t, J = 8.0 Hz, 1H), 7.54 (app t, J = 7.5 Hz, 1H), 7.58 (d,
J = 8.5 Hz, 1H), 7.74 (d app t, J = 8.0, 1.0 Hz, 1H), 7.82-7.84
(m, 2H), 8.07 (d, J = 8.0 Hz, 1H), 8.17 (d, J = 8.5 Hz, 1H), 8.23
(d, J = 8.5 Hz, 1H), 8.36 (s, 1H); 13C NMR (125 MHz, CDCl3): δ
118.8, 123.2, 126.1, 126.7, 127.4, 127.6, 129.9, 130.0, 130.4,
130.7, 132.3, 137.1, 141.8, 148.3, 155.7.
2-(4-bromophenyl)quionline (3e); Reaction time: 4 h; Yield:
86 % white solid; mp: 112-114 oC; 1H NMR (500 MHz, CDCl3):
δ 7.54 (app t, J = 7.5 Hz, 1H), 7.64-7.66 (m, 2H), 7.73 (app t, J =
7.5 Hz, 1H), 7.82 (d, J = 2.0 Hz, 1H), 7.83 (d, J = 3.5 Hz, 1H),
8.04-8.06 (m, 2H), 8.15 (d, J = 8.0 Hz, 1H), 8.21 (d, J = 8.5 Hz,
1H); 13C NMR (125 MHz, CDCl3): δ 118.6, 124.0, 126.6, 127.3,
127.6, 129.2, 129.8, 129.9, 132.1, 137.0, 138.6, 148.3, 156.1.
2-p-tolylquinoline (3f); Reaction time: 6 h; Yield: 76 % white
solid; mp: 74-76 oC; 1H NMR (500 MHz, CDCl3): δ 2.43 (s, 3H),
7.32-7.33 (m, 2H), 7.50 (app t, J = 8.0 Hz, 1H), 7.71 (app t, J =
7.5 Hz, 1H), 7.80 (d, J = 8.0 Hz, 1H), 7.85 (d, J = 8.5 Hz, 1H),
8.06-8.08 (m, 2H), 8.16 (d, J = 8.5 Hz, 1H), 8.18 (d, J = 8.5 Hz,
1H); 13C NMR (125 MHz, CDCl3): δ 21.4, 118.9, 126.1, 127.2,
127.5, 129.6, 129.7, 136.7, 137.0, 139.5, 148.4, 157.4.
8. (a) Krasley AT, Malachowski WP. Tetrahedron Lett. 2015; 56:
6073; (b) Zhao X, Gong J.-J., Yuan K, Sha F, Wu X.-Y.
Tetrahedron Lett. 2015; 56: 2526; (c) Zhang X.-N., Shi M. Eur. J.
Org. Chem. 2012; 6271; (d) Gong J.-J., Li T.-Z., Pan K, Wu X.-Y.
Chem. Commun. 2011; 47: 1491; (e) Aroyan CE, Dermenci A,
2-(thiophen-2-yl)quionline (3g); Reaction time: 5 h; Yield:
85 % white solid; mp: 124-126 oC; 1H NMR (500 MHz, CDCl3):

10
Tetrahedron
ACCEPTED MANUSCRIPT
Miller SJ. J. Org. Chem. 2010; 75: 5784; (f) Aroyan CE,
Miller SJ. J. Am. Chem. Soc. 2007; 129: 256.
Christoffers J. Eur. J. Org. Chem. 2008; 1811; (k) Barros AIRNA,
Silva AMS. Tetrahedron Lett. 2003; 44: 5893.
9. (a) Su X, Zhou W, Li Y, Zhang J. Angew. Chem. Int. Ed. 2015;
54: 6874; (b) Scanes RJH, Grossmann O, Grossmann A, Spring
DR. Org. Lett. 2015; 17: 2462; (c) Albrecht A, Skrzyńska A,
Przydacz A, Albrecht Ł. Synlett. 2015; 26: 2679; (d) Takizawa S,
Nguyen TM.-N., Grossmann A, Suzuki M, Enders D, Sasai H.
Tetrahedron. 2013; 69: 1202; (e) Takizawa S, Nguyen TM.-N.,
Grossmann A, Enders D, Sasai H. Angew. Chem. Int. Ed. 2012;
51: 5423.
10. (a) Bhunia A, Yetra SR, Gonnade RG, Biju AT. Org. Biomol.
Chem. 2016; 14: 5612; (b) Ross TM, Burke SJ, Malachowski WP,
Tetrahedron Lett. 2014; 55: 4616; (c) Wang X.-F., Peng L, An J,
Li C, Yang Q.-Q., Lu L.-Q., Gu F.-L., Xiao W.-J. Chem. Eur. J.
2011; 17: 6484; (d) Marqués-Lόpez E, Herrera RP, Marks T,
Jacobs WC, Könning D, Figueiredo RMd, Christmann M. Org.
Lett. 2009; 11: 4116; (e) Agapiou K, Krische MJ, Org. Lett. 2003;
5: 1737.
11. (a) Li C.-C., Yang S.-D. Org. Lett. 2015; 17: 2142; (b) Ji Y, Yan
H, Jiang Q. Eur. J. Org. Chem. 2015; 2051; (c) Kuhl N, Schröder
N, Glorius F. Org. Lett. 2013; 15: 3860; (d) Molander GA, Jean-
Gérard L. J. Org. Chem. 2009; 74: 5446.
12. (a) Li J, Zeng K.-W., Shi S.-P., Jiang Y, Tu P.-F. Fitoterapia.
2012; 83: 896; (b) Baell JB, Holloway GA. J. Med. Chem. 2010;
53: 2719; (c) Deng F, Tang N, Xu J, Shi Y.-H., Zhao M, Zhang J.-
S. J. Asian Nat. Prod. Res. 2008; 10: 531; (d) Surup F, Shojaei H,
Zezschwitz PV, Kunze B, Grond S. Bioorg. Med. Chem. 2008; 16:
1738; (e) Duong TN, Edrada R, Ebel R, Wray V, Frank W, Duong
AT, Lin WH, Proksch P. J. Nat. Prod. 2007; 70: 1640; (f) Janecki
T, Błaszczyk E, Studzian K, Janecka A, Krajewska U, Różalski
M. J. Med. Chem. 2005; 48: 3516.
21. (a) Basavaiah D, Reddy KR. Tetrahedron. 2010; 66: 1215; (b)
Bowman WR, Fletcher AJ, Pedersen JM, Lovell PJ, Elsegood
MRJ, López EH, McKee V, Potts GBS. Tetrahedron. 2007; 63:
191.
22. (a) Plata RE, Singleton DA. J. Am. Chem. Soc. 2015; 137: 3811;
(b) Dong L, Qin S, Su Z, Yang H, Hu C. Org. Biomol. Chem.
2010; 8: 3985.
23. (a) Prajapati SM, Patel KD, Vekariya RH, Panchal SN, Patel HD.
RSC Adv. 2014; 4: 24463; (b) Marco-Contelles J, Pérez-Mayoral E,
Samadi A, Carreiras MdC, Soriano E. Chem. Rev. 2009; 109:
2652.
24. (a) Afzal O, Kumar S, Haider MR, Ali MR, Kumar R, Jaggi M,
Bawa S. Eur. J. Med. Chem. 2015; 97: 871; (b) Kaur K, Jain M,
Reddy RP, Jain R. Eur. J. Med. Chem. 2010; 45: 3245.
25. (a) Liu G, Qian J, Hua J, Cai F, Li X, Liu L. Org. Biomol. Chem.
2016; 14: 1147; (b) Natarajan R, Unnikrishnan PA, Radhamani S,
Rappai JP, Prathapan S. Tetrahedron Lett. 2016; 57: 2981; (c)
Stopka T, Niggemann M. Chem. Commun. 2016; 52: 5761; (d)
Singh JB, Bharadwaj KC, Gupta T, Singh RM. RSC Adv. 2016; 6:
26993; (e) Borah A, Gogoi P. Eur. J. Org. Chem. 2016; 2200; (f)
Singh RM, Kumar R, Bharadwaj KC, Gupta T. Org. Chem. Front.
2016; 3: 1100; (g) Gupta T, Bharadwaj KC, Singh RM. Eur. J.
Org. Chem. 2016; 4981; (h) Zhu Y, Cai C. RSC Adv. 2014; 4:
52911.
26. (a) Dong J, Long Z, Song F, Wu N, Guo Q, Lan J, You J. Angew.
Chem. Int. Ed. 2013; 52: 580; (b) Yang L, Qian B, Huang H.
Chem. Eur. J. 2012; 18: 9511; (c) Zhang X.-S., Zhu Q.-L., Luo F.-
X., Chen G, Wang X, Shi Z.-J. Eur. J. Org. Chem. 2013; 6530.
27. (a) Umeda R, Kouno H, Kitagawa T, Okamoto T, Kawashima K,
Mashino T, Nishiyama Y. Heteroat. Chem. 2014; 25: 698; (b)
Xing R.-G., Li Y.-N., Liu Q, Han Y.-F., Wei X, Li J, Zhou B.
Synthesis. 2011; 2066; (c) Han R, Chen S, Lee SJ, Qi F, Wu X,
Kim BH. Heterocycles. 2006; 68: 1675; (d) Shi D, Rong L, Wang
J, Zhuang Q, Wang X, Tu S, Hu H. J. Chem. Res. Synop. 2003;
342; (e) Wang X, Zhang Y. Syn. Commun. 2002; 32: 3617.
13. (a) Nakahata M, Takashima Y, Harada A. Macromol. Rapid
Commun. 2016; 37: 86; (b) Ye Z, Feng M, Gou S, Liu M, Huang
Z, Liu T. J. Appl. Polym. Sci. 2013; 130: 2901; (c) Chen X, Hong
L. J. Am. Ceram. Soc. 2010; 93: 96.
14. (a) Bharadwaj KC. ChemistrySelect. 2017; 2: 5384; (b) Singh RM,
Bharadwaj KC, Tiwari DK. Beilstein J. Org. Chem. 2014; 10:
2975; (c) Guo W, Wu W, Fan N, Wu Z, Xia C. Synth. Commun.
2005; 35: 1239; (d) Faltin C, Fleming EM, Connon SJ. J. Org.
Chem. 2004; 69: 6496; (e) Yu C, Hu L. J. Org. Chem. 2002; 67:
219.
15. (a) Basavaiah D, Reddy GC, Lingaiah B, Naganaboina RT.
Tetrahedron. 2017; 73: 859; (b) Bharadwaj KC, Tiwari DK.
Tetrahedron. 2016; 72: 312; (c) Basavaiah D, Reddy GC,
Bharadwaj KC. Tetrahedron. 2014; 70: 7991; (d) Basavaiah D,
Reddy GC, Bharadwaj KC. Eur. J. Org. Chem. 2014; 1157.
16. (a) Kim ES, Lee HS, Kim JN. Tetrahedron Lett. 2009; 50: 6286;
(b) Pigge FC, Dhanya R, Hoefgen ER. Angew. Chem. Int. Ed.
2007; 46: 2887; (c) Youn SW, Park HS, Kim YH. Chem.
Commun. 2000; 2005.
17. During the communication of present manuscript, following
papers appeared (a) Zhang X.-Z., Gan K.-J., Liu X.-X., Deng Y.-
H., Wang F.-X., Yu K.-Y., Zhang J, Fan C.-A. Org. Lett. 2017;
19: 3207; (b) Kishi K, Arteaga FA, Takizawa S, Sasai H. Chem.
Commun. 2017; 53: 7724.
18. (a) Bisacchi GS. J. Med. Chem. 2015; 58: 4874; (b) Aldred KJ,
Kerns RJ, Osheroff N. Biochemistry. 2014; 53: 1565; (c)
Mugnaini C, Pasquini S, Corelli F. Curr. Med. Chem. 2009; 16:
1746; (d) Strahilevitz J, Jacoby GA, Hooper DC, Robicsek A.
Clin. Microbio. Rev. 2009; 22: 664.
19. (a) Wang D, Zhao J, Wang Y, Hu J, Li L, Miao L, Feng H,
Désaubry L, Yu P. Asian J. Org. Chem. 2016; 5: 1442; (b) Chen J,
Chen Z, Zhao H, Zou Y, Zhang X, Yan M. Org. Biomol. Chem.
2016; 14: 11148; (c) Gupta S, Ganguly B, Das S. RSC Adv. 2014;
4: 41148; (d) Aksenov AV, Smirnov AN, Aksenov NA,
Aksenova IV, Matheny JP, Rubin M. RSC Adv. 2015; 5: 8647; (e)
Manikandan R, Jeganmohan M. Org. Lett. 2014; 16: 3568.
20. (a) Hu Z, Dong J, Men Y, Li Y, Xu X. Chem. Commun. 2017; 53:
1739; (b) Hu Z, Yuan H, Men Y, Liu Q, Zhang J, Xu X. Angew.
Chem. Int. Ed. 2016; 55: 7077; (c) Jiang L, Xu R, Kang Z, Feng
Y, Sun F, Hu W. J. Org. Chem. 2014; 79: 8440; (d) Lu X.-M., Li
J, Cai Z.-J., Wang R, Wang S.-Y., Ji S.-J. Org. Biomol. Chem.
2014; 12: 9471; (e) Yang W, Du D.-M. Chem. Commun. 2013; 49:
8842; (f) Zhang H.-R., Dong Z.-W., Yang Y.-J., Wang P.-L. , Hui
X.-P., Org. Lett. 2013; 15: 4750; (g) Liao H.-H., Hsiao C.-C.,
Sugiono E, Rueping M. Chem. Commun. 2013; 49: 7953; (h) Jia
Z.-X., Luo Y.-C., Wang Y, Chen L, Xu P.-F., Wang B. Chem.
Eur. J. 2012; 18: 12958; (i) Tan HR, Ng HF, Chang J, Wang J,
Chem. Eur. J. 2012; 18: 3865; (j) Diedrich CL, Haase D, Saak W,