A Route to Highly Functionalized Stereospecific trans -Aminated Aurones from 3-Bromoflavones with Aniline and N -Phenylurea via a Domino Aza-Michael Ring Opening and Cyclization Reactions

Article abstract of DOI:10.1055/s-0037-1610662

A facile cascade reaction is reported via aza-Michael addition, ring opening, and cyclization between 3-bromoflavone and aniline derivatives or N -phenylurea in the presence of KO t -Bu and CuI in DMF under mild reaction conditions. Products were obtained as stereospecific trans -aminated aurones in good to excellent yields (61-83%). Our protocol is operationally successful with ease, avoids the requirement of additives and ligands, and offers broad substrate scope.

Full text of DOI:10.1055/s-0037-1610662

SYNTHESIS
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
© Georg Thieme Verlag Stuttgart · New York
2018, 50, A–K
paper
A
en
I. Parveen, N. Ahmed
Paper
Synthesis
A Route to Highly Functionalized Stereospecific trans-Aminated
Aurones from 3-Bromoflavones with Aniline and N-Phenylurea via
a Domino Aza-Michael Ring Opening and Cyclization Reactions
Iram Parveen
R1
NH2
Naseem Ahmed*
R7
R9
CuI (5 mol%)
KOtBu, DMF
CuI (5 mol%)
KOtBu, DMF
R2
O
O
O
25 °C, 20–30 min
R8
25 °C, 20–30 min
Department of Chemistry, Indian Institute of Technology
Roorkee, Roorkee 247 667, India
nasemfcy@iitr.ac.in
R6
or
R8
R7
O
HN
R6
R1
O
O
R8
R7
NH
R6
O
Br
O
H
N
NH2
R9
R5
R9
R2
Br
O
O
O
R4
34 examples
R3
R1, R2 = H, Cl; R3, R5 = H, OMe
good to excellent yields
less reaction time
broad substrate scope
gram-scale synthesis
R4 = H, Cl, Me, OMe; R6 = H, F, Cl, OMe, NO2
R7 = H, NO2; R8, R9 = H, Me
Received: 18.08.2018
Accepted after revision: 11.09.2018
Published online: 10.10.2018
and cyclizations of 2-hydroxyaryl phenylethynyl ketones17
are also known. Moreover, Patrick’s group described Au(I)18
and Xiaoquan et al. reported silver nanoparticles with
phosphine ligand19 stimulate the cyclization of 2-(1-hy-
droxyprop-2-ynyl)phenols. Chao-Jun and co-authors have
also successfully developed alkynylation/cyclization of ter-
minal alkynes with salicylaldehydes by using Cy3P-silver
complex.20 However, they have some drawbacks in the cy-
clization strategies such as harsh reaction condition, long
reaction time, expensive catalyst loading, etc. In 2014, Su
and co-workers and others synthesized Z-aurones of (2-
halogenphenyl)(3-phenyloxiran-2-yl)21 via intramolecular
tandem reaction. In 2015, Hartinger and co-workers22 syn-
thesized 1′-(alkylamino)aurones from tosylated flavone
without any catalyst and base, but this method is applicable
only when an excess amount of primary alkyl amine was
used and a mixture of E/Z-isomers was obtained after a long
reaction time (18 h). Therefore, we report herein a facile
method of isomerization-type reaction of flavones to au-
rones with Cu(I)-catalyzed cascade aza-Michael addition,
ring opening, and oxidative cyclization reactions in one-pot
under basic reaction condition, which afforded the regio-
specific and stereospecific trans-aminated aurone deriva-
tives in good to excellent yields (61–83%).
DOI: 10.1055/s-0037-1610662; Art ID: ss-2018-n0451-op
Abstract A facile cascade reaction is reported via aza-Michael addi-
tion, ring opening, and cyclization between 3-bromoflavone and aniline
derivatives or N-phenylurea in the presence of KOt-Bu and CuI in DMF
under mild reaction conditions. Products were obtained as stereospe-
cific trans-aminated aurones in good to excellent yields (61–83%). Our
protocol is operationally successful with ease, avoids the requirement of
additives and ligands, and offers broad substrate scope.
Key words domino reaction, aza-Michael addition, oxidative cycliza-
tion, ring opening, stereospecific trans-aminated aurones
Aurones [2-benzylidenebenzofuran-3(2H)-ones] are
one of the most interesting classes of flavonoids, which are
prevalent in the core structure of several naturally occur-
ring and biologically active alkaloids, drugs candidates, and
natural products1 and provide a bright yellow color to the
plant in which they occur.2 Along with their physiological
properties and effects on nature, they have shown thera-
peutic properties such as antiparasitic,3 antibacterial, insect
antifeedant,4 inhibition of cyclin-dependent kinases,5 anti-
fungal agents,6 inhibitor of iodothyronine deiodinase,7
probes of β-amyloid plaques,8 histone deacetylase inhibi-
tors,9 anti-inflammatory, and antimicrobial.10
Due to their enormous biological advantages, a number
of new strategies have been adopted for their synthesis. To-
ward this end, huge efforts have been devoted for the syn-
thesis of substituted aurones from chalcone dihalides11 and
by the reaction of benzaldehydes with benzofuran-3(2H)-
ones catalyzed by acid12 or base,13 or alumina.14 Other ap-
proaches like oxidative cyclization of 2′-hydroxychalcones
by thallium(III) nitrate15 or Hg(OAc)216 as an oxidative agent
Following the previous literature,22 the model reaction
was commenced between 3-bromoflavone (1a) and aniline
(1b) at 25 °C and also under reflux condition in THF with-
out using base and catalyst, which gave no product (Table 1,
entry 1). On the other hand, 35% yield of product was ob-
served when the reaction was carried out in DMF using
KOt-Bu base at 25 °C (entry 2). Further, the yield was slight-
ly enhanced to 45% after raising the temperature from 25 to
40 °C (entry 3). We further increased the temperature from
40 to 80 °C, however, this failed to improve the yield (entry
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–K

B
I. Parveen, N. Ahmed
Paper
Synthesis
4). Unexpectedly, the product 2a was obtained in low yield
(15%) when copper iodide was used with KOt-Bu at 80 °C
(entry 5). Serendipitously, the reduction of temperature of
entry 5 from 80 to 25 °C, led to the formation of the desired
product in excellent yield (83%) (entry 6). We also increased
the ratio of KOt-Bu from 3 to 5 equivalents, but failed to get
a better yield of the desired product. Conversely, the reac-
tion generated excess heat, which charred the reactants
(entry 7). Also, use of 1 to 2 equivalents of KOt-Bu afforded
only 30% product yield and the rest starting material re-
mained unreacted (entries 8, 19). Similarly, other catalysts
like copper bromide and copper chloride were tried; these
gave products in a yield of 69% (entry 9) and 55% (entry 10),
respectively.
Table 1 Optimization of Reaction Conditionsa
R3
R4
C
O
B
R5
A
R3
R4
Br
R1
A
R5
R8
O
C
1a
O
base, catalyst
solvent, temp
B
HN
R7
R2
D
NH2
O
R6
R9
R7
R9
2a–y
D
R8
R6
1b
Inorganic bases such as Na2CO3, K2CO3, and Cs2CO3 were
also used in the reaction at 25 °C (Table 1, entries 11–13)
and at 80 °C (entries 14–16) but no desired product was ob-
tained. Next, this reaction was examined with organic bases
like Et3N and DBU but again no product was obtained (en-
tries 17 and 18). When DMSO was used as a solvent, it was
found to be less effective than the DMF (entry 20). The
structural determination of products was confirmed on the
basis of crystal structure and spectral analysis (see Sup-
porting Information).
Having optimized reaction conditions in hand, we next
focused on the substrate scope of this protocol to show the
generality of this methodology (Scheme 1). The influence of
substituents on the aryl ring C of 3-bromoflavone and sub-
stituted aniline was screened. 3-Bromoflavone substituted
with chloro, methyl, methoxy, dimethoxy, and trimethoxy
on aryl ring were treated with substituted anilines with
electron-withdrawing groups, electron-releasing groups,
and both electron-withdrawing and -releasing groups on
the same ring under optimized conditions. The desire prod-
ucts 2a–y were obtained within 20–30 minutes at 25 °C in
good to excellent yield in all cases. The functional groups
including chloro, methyl, methoxy, dimethoxy, and trime-
thoxy were compatible with electron-withdrawing group,
which seem to be more efficient, and gave expected prod-
ucts in higher yields of 73–83% (2a, 2b, 2f, 2g, 2h, 2m, 2n,
2q, 2r, 2v, 2w, and 2y). Besides, multi-substituted anilines
such as 2-nitro-4-methylaniline with electron-withdrawing
group gave a similar yield of 75% (2j). Subsequently, unsub-
stituted anilines afforded good yields in the range of 64–
72% (2c, 2i, 2o, 2s, 2x). In addition, anilines with electron-
releasing group afforded the desired product in moderate
yield of 61–71% (2d, 2e, 2l, 2k, 2p, 2t, and 2u).
Entry
Base
(3 equiv)
Catalyst
(5 mol%)
Solvent
Temp (°C) Yield
(%)b
1c
2
–
–
THF
25
25
40
80
80
25
25
25
25
25
25
25
25
80
80
80
80
80
25
25
–
KOt-Bu
KOt-Bu
KOt-Bu
KOt-Bu
KOt-Bu
KOt-Bu
KOt-Bu
KOt-Bu
KOt-Bu
Na2CO3
K2CO3
Cs2CO3
Na2CO3
K2CO3
Cs2CO3
Et3N
–
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMSO
35
45
dec.
15
83
–
3
–
4
–
5
CuI
CuI
–
6d
7e
8
CuI
CuBr
CuCl
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
30
69
55
–
9
10
11
12
13
14
15
16
17
18f
19
20
–
–
–
–
–
–
DBU
–
KOt-Bu
KOt-Bu
40
61
a Reaction conditions, unless specified otherwise: 1a (0.5 mmol), 1b (0.75
mmol), catalyst (5 mol%), KOt-Bu (3 equiv), solvent (4 mL); stirred at r.t. for
20–30 min.
b Isolated yield.
c Reflux at 65 °C.
d KOt-Bu (1 equiv).
e KOt-Bu (5 equiv).
f CuI (1 mol%).
Further, to extend the scope of this methodology, reac-
tions with other 3-bromoflavones were examined. When
phenyl ring C was replaced with a heterocyclic ring like fu-
ran, the corresponding products 4a–h were obtained in
moderate to high yields (Scheme 2). In general, it was found
that aniline substituted with electron-withdrawing groups
such as NO2 at ortho- and para-positions and Cl at para-po-
sition (4a, 4b, and 4c) gave higher yields of 71–76% of the
desired products in comparison to unsubstituted amine 4d
(67%) and those with electron-releasing methyl group 4e
(60%). The structure of 4b was confirmed by single-crystal
analysis (see Supporting Information). The influence of Cl
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–K

C
I. Parveen, N. Ahmed
Paper
Synthesis
substituent on the aryl ring A with aniline under the opti-
mized conditions gave acceptable yields of the products 4f–
h (66–74%).
Substituted and unsubstituted chromones were also re-
acted with aliphatic and aromatic amines under the opti-
mal reaction conditions, which resulted in E-aminated
R3
R4
R3
NH2
R4
R5
R5
R8
R7
CuI (5 mol%)
O
O
O
KOtBu, DMF
HN
R7
R8
R9
25 °C, 20–30 min
R6
X
O
R6
R9
X = Br, I
O
O
O
O
HN
HN
HN
Cl
HN
NO2
O
O
O
O
2a (X = Br, 80%)
2b (X = Br, 77%)
2c (X = Br, 70%)
2d (X = Br, 68%)
(X = I, 81%)
OMe
OMe
OMe
O
O
O
O
HN
O
NO2
HN
O
OMe
HN
Cl
HN
F
O
O
2e (X = Br, 62%)
2f (X = Br, 83%)
(X = I, 84%)
2g (X = Br, 79%)
2h (X = Br, 78%)
OMe
OMe
OMe
OMe
O
O
O
O
HN
O
OMe
HN
O
HN
O
HN
O
2i (X = Br, 71%)
2j (X = Br, 75%)
2l (X = Br, 65%)
O2N
2k (X = Br, 69%)
O
O
O
O
HN
O
HN
O
OMe
HN
Cl
HN
O
NO2
O
2m (X = Br, 79%)
2n (X = Br, 74%)
2o (X = Br, 68%)
(X = I, 69%)
2p (X = Br, 61%)
MeO
OMe
MeO
OMe
MeO
OMe
MeO
OMe
O
O
O
O
HN
O
HN
O
NO2
HN
O
HN
Cl
O
(X = Br, 82%)
2q
2r (X = Br, 80%)
2s (X = Br, 72%)
2t (X = Br, 71%)
(X = I, 71%)
Cl
MeO
OMe
Cl
MeO
OMe
OMe
Cl
O
O
O
O
O
HN
HN
O
OMe
HN
Cl
HN
NO2
HN
2v (X = Br, 78%)
NO2
O
O
O
O
2u (X = Br, 68%)
2w (X = Br, 76%)
2x (X = Br, 64%)
2y (X = Br, 81%)
Scheme 1 Substrate scope with aniline and flavones. Reagents and conditions (unless specified otherwise): 1a (0.5 mmol), 2a (0.75 mmol), CuI (5
mol%), KOt-Bu (3 equiv), and DMF (4 mL); stirred at 25 °C for 20–30 min.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–K

D
I. Parveen, N. Ahmed
Paper
Synthesis
R1
aurones (Scheme 3). This suggests that 3-bromochromones
can react with both aliphatic and aromatic amines in a fac-
ile manner.
O
O
R1
R2
Br
O
O
O
standard
conditions
R
O
CuI (5 mol%)
O
R
R1–NH2
R2
HN
R6
KOtBu, DMF
NH R1
O
NH2
Br
25 °C, 20–30 min
O
R7
R7
O
(i) R = Ph, R1 = Me (5a 74%)
R1 = Et (5b 76%)
Me
R6
O
(ii)
R =
R =
R1
=
OMe
(5c 88%)
H
(iii)
O
Scheme 3 Reaction with aliphatic/aromatic amines with 3-bromo-
HN
NO2
chromones
O
4a (76%)
4b (75%)
Furthermore, to extend substrate scope N-phenylurea
was used, which was converted into aniline anion in situ
under basic condition,23 and gave good yields with Me,
OMe, dimethoxy, and without substituent (2c, 2o, 2i, and
2s) by reacting with substituted 3-bromoflavones (Scheme
4). The reactivity and product distribution between aniline
and N-phenylurea with 3-bromoflavones were also com-
pared, which showed that aniline reacts faster than N-
phenylurea affording the products (a and b) in yields of 47%
and 14% under condition A and 49% and 11%, respectively,
under condition B along with unreacted aniline (c) and (d)
in slightly different ratios (Scheme 5). This result also sug-
gests that the proton abstraction did not occur directly
from urea.
The domino synthesis of aminated aurone was conduct-
ed on a gram scale by carrying the reaction out on a 4 mmol
(1.31 g) scale under standard optimized conditions without
varying reaction parameters (Scheme 6). The reaction pro-
ceeded easily and afforded the aminated aurone 2f in 79%
yield.
O
O
O
O
HN
HN
Cl
O
O
4d (67%)
4c (72%)
Cl
O
O
O
O
HN
HN
NO2
Cl
O
O
4e (60%)
4f (74%)
Cl
Cl
O
O
O
O
HN
HN
Cl
Cl
Cl
O
O
4g (71%)
4h (66%)
Scheme 2 Substrate scope with heterocyclic ring of flavones. Reagents
and conditions (unless specified otherwise): 1a (0.5 mmol), 1b (0.75
mmol), CuI (5 mol%), KOt-Bu (3 equiv), and DMF (4 mL); stirred at 25 °C
for 20–30 min.
R3
R4
R3
O
R4
O
CuI (5 mol%)
H2N
NH
O
O
KOtBu, DMF
NH
25 °C, 20–30 min
O
Br
1c
MeO
OMe
OMe
O
O
O
O
NH
NH
NH
NH
O
O
O
O
2c (70%)
2s (72%)
2o (65%)
2i (71%)
Scheme 4 Substrate scope with N-phenylurea. Reagents and conditions (unless specified otherwise): 1a (0.5 mmol), 1c (1.0 mmol), CuI (10 mol%),
KOt-Bu (3 equiv), and DMF (4 mL); stirred at 25 °C for 20–30 min.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–K

E
I. Parveen, N. Ahmed
Paper
Synthesis
NH2
NH2
NH2
H
O
O
N
NH2
CuI (5 mol%)
O
O
KOtBu, DMF
O
R2
Br
HN
R1
HN
R1
25 °C, 20–30 min
R1
R2
R1
O
O
a
c
b
d
A) Condition R1 = Me, R2 = H; yield: a = 47%, b = 14%, c = 29%, d = 63%.
B) Condition R1 = Me, R2 = H; yield: a = 49%, b = 11%, c = 25%, d = 62%.
Scheme 5 Reactivity measurement between nucleophiles.
OMe
R2
O
O
O
R1
Z
OMe
Br
O
R1
4 mmol (1.31 g)
NH2
O
R1 = H, R2 = H, Br
OH
O
CuI (5 mol%)
NH
NO2
CuI ( 5 mol%)
E
KOtBu (3 equiv)
DMF, 25 °C
20–30 min
HN
NO2
KOtBu (3 equiv)
DMF, rt, 1 h
NH2
O
R2
79% yield (1.22 g)
5d
(yield 90–92%)
NO2
NO2
6 mmol (0.828 g)
Scheme 8 Synthesis of β-aminated 2′-hydroxychalcone
Scheme 6 Synthesis of 2f on gram scale
O
NH2
generate the intermediate A. Intermediate A after ring
opening gets transformed to aza-Micheal adduct B. Adduct
B in the presence of KOt-Bu reacts with CuI to generate the
copper(I) complex C. Through the oxidative addition of Br
group, copper(I) complex C switches into copper(III) com-
plex D. Finally, copper(III) complex D undergoes reductive
elimination to afford the desired product 2c in the trans-
aminated form and regenerates CuI for the next catalytic
cycle.24 This tentative mechanism is also supported by the
literature.24c
HN
NH
O
CuI (5 mol%)
no reaction
KOtBu (3 equiv)
Br
DMF, rt, 1–3 h
O
N
NH2
Scheme 7 Reactions with benzamide, piperazine, and 2-aminopyridine
In summary, we have developed a facile and one-pot
cascade via aza-Michael addition, ring opening and cycliza-
tion reactions between 3-bromoflavones and anilines/N-
phenylurea for the competent and practical synthesis of
stereospecific E-aminated aurones. Our method has advan-
tages such as less reaction time, simple experimental pro-
cedure, and moderate to high yields. In this reaction, a six-
membered ring is converted into a five-membered ring,
which has enormous synthetic application in natural prod-
ucts.
We tried other nucleophiles such as benzamide, pipera-
zine, and 2-aminopyridine, but the reaction failed to give
the desired product (Scheme 7).
In order to establish the reaction mechanism, the reac-
tion with flavones (without 3-substituted bromo- or iodo-
flavones) was performed, which gave excellent yields of
products; for example, 5d (90–92%) within 1 hour. Thus,
the cascade aza-Michael and ring opening took place, how-
ever, for cyclization it needs 3-bromo or 3-iodo group
(Scheme 8).
Based on our observations, a tentative mechanism for
the cascade reaction of 3-bromoflavone and aniline or N-
phenylurea under the action of base and copper iodide to
All the required chemicals were purchased from Merck and Himedia.
TLC was performed on 0.25 mm silica gel plates (60 F254) using UV
light as the visualizing agent. Silica gel (100–200 mesh) was used for
column chromatography. Melting points were determined on a capil-
lary point apparatus equipped with a digital thermometer and are
uncorrected. NMR spectra were recorded on Jeol resonance ECX400
MHz and Bruker spectrospin DPX 500 MHz spectrometer, and chemi-
cal shifts are reported in δ units, parts per million (ppm), relative to
residual CHCl3 (δ = 7.26) in the deuterated solvent or with TMS (δ =
0.00) as the internal standard. 13C NMR spectra were referenced to
produce
stereospecifically
(E)-2-[phenyl(phenylami-
no)methylene]benzofuran-3(2H)-one is proposed as shown
in Scheme 9.22 Initially N-phenylurea gets converted into
aniline23 and CuI coordinates with oxygen to enhance the
electrophilic character of the double bond, and then the nu-
cleophile, created via KOt-Bu, attacks at the double bond to
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–K

F
I. Parveen, N. Ahmed
Paper
Synthesis
KOtBu
OH
1b
NH
NH2
Br
KOtBu
NH2
NH
O
O
O
Michael
addition
O
HN
O
CuI
Br
B
Br
A
KOtBu
CuI
CuI
O
1a
CuI
KI + t-BuOH
Cu
O
O
Br
oxidative
addition
reductive
elimination
Cu
H
O
Br
E
CuBr
CuI
KI
NH
O
N
O
HN
O
KBr
2c
D
C
Scheme 9 Proposed mechanism
CDCl3 (δ = 77.0274, the middle peak). Coupling constants were ex-
pressed in Hz. Standard abbreviations are used to explain the multi-
plicities. High-resolution mass spectra were recorded with a micro
TOF-Q analyzer spectrometer by using the electro-spray mode. IR
spectra of the compounds were recorded on a Thermo Nicolet FT-IR
spectrophotometer and are expressed as wavenumber (cm–1).
13C NMR (100 MHz, CDCl3): δ = 180.7, 162.5, 143.9, 138.1, 133.7,
133.7, 130.5, 129.9, 129.7, 129.2, 129.0, 128.8, 123.9, 123.5, 123.5,
122.3, 112.8.
HRMS (ESI+): m/z [M + Na]+ calcd for C21H14ClNO2Na: 370.0611;
found: 370.0615.
(E)-2-[Phenyl(phenylamino)methylene]benzofuran-3(2H)-one
(2c)
trans-Aminated Aurones; General Procedure
A round-bottom flask with a magnetic bar was charged with the ap-
propriate 3-bromoflavone (1 mmol), KOt-Bu (3 mmol, 3 equiv), DMF
(4 mL), the corresponding aniline (1.5 mmol) or N-phenylurea (2
mmol) with CuI (5 mol%). The reaction mixture was stirred at r.t. until
the complete consumption of the starting material (TLC monitoring
with 10% hexane and EtOAc). The reaction mixture was poured into
crushed ice, the precipitate formed was collected by suction filtration
and purified by column chromatography to give the required product
2a–5d, respectively, in excellent yield.
Yield: 219 mg (70%); yellow solid; mp 132–134 °C.
IR (KBr): 3448, 1644, 1591, 1202, 618 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 11.42 (s, 1 H), 7.87 (d, J = 7.8 Hz, 1 H),
7.55–7.42 (m, 6 H), 7.21 (d, J = 8.4 Hz, 1 H), 7.17 (t, J = 7.4 Hz, 1 H),
7.14–7.10 (m, 2 H), 6.99–6.96 (m, 1 H), 6.78 (d, J = 8.1 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 179.9, 162.1, 145.4, 139.2, 133.6,
133.4, 130.4, 130.2, 130.0, 128.9, 128.7, 128.5, 124.1, 123.5, 122.7,
122.2, 112.8.
HRMS (ESI+): m/z [M+ Na]+ calcd for C21H15NO2Na: 336.1000; found:
336.1003.
(E)-2-{[(4-Nitrophenyl)amino](phenyl)methylene}benzofuran-
3(2H)-one (2a)
Yield: 286 mg (80%); yellow solid; mp 159–161 °C.
(E)-2-{[(3,5-Dimethylphenyl)amino](phenyl)methylene}benzofu-
ran-3(2H)-one (2d)
IR (KBr): 3444, 1644, 1591, 1201, 618 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 11.21 (s, 1 H), 8.00 (d, J = 8.9 Hz, 2 H),
7.87 (d, J = 7.7 Hz, 1 H), 7.60–7.51 (m, 6 H), 7.25–7.20 (m, 2 H), 6.77
(d, J = 9.0 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 182.3, 163.4, 146.2, 142.5, 140.5,
135.0, 134.9, 131.0, 129.6, 129.5, 129.2, 125.0, 123.8, 123.3, 122.7,
120.1, 113.0.
Yield: 231 mg (68%); yellow solid; mp 177–179 °C.
IR (KBr): 3434, 1665, 1591, 1202, 620 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 11.37 (s, 1 H), 7.86 (d, J = 7.7 Hz, 1 H),
7.55–7.42 (m, 6 H), 7.20 (d, J = 8.4 Hz, 1 H), 7.16 (t, J = 7.5 Hz, 1 H),
6.61 (s, 1 H), 6.38 (s, 2 H), 2.11 (s, 6 H).
13C NMR (100 MHz, CDCl3): δ = 179.8, 162.0, 145.1, 139.0, 138.5,
133.4, 133.2, 130.3, 130.2, 130.0, 128.5, 125.8, 124.2, 123.3, 122.0,
120.3, 115.0, 112.7, 21.2.
HRMS (ESI+): m/z [M + Na]+ calcd for C21H14N2O4Na: 381.0852; found:
381.0855.
HRMS (ESI+): m/z [M + Na]+ calcd for C23H19NO2Na: 364.1313; found:
364.1318.
(E)-2-{[(4-Chlorophenyl)amino](phenyl)methylene}benzofuran-
3(2H)-one (2b)
Yield: 267 mg (77%); yellow solid; mp 189–191 °C.
(E)-2-{[(4-Methoxyphenyl)amino](phenyl)methylene}benzofu-
ran-3(2H)-one (2e)
IR (KBr): 3444, 1644, 1591, 1202, 618 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 11.26 (s, 1 H), 7.82 (d, J = 7.7 Hz, 1 H),
7.51–7.41 (m, 6 H), 7.19–7.13 (m, 2 H), 7.05 (d, J = 8.6 Hz, 2 H), 6.66
(d, J = 8.6 Hz, 2 H).
Yield: 212 mg (62%); yellow solid; mp 159–161 °C.
IR (KBr): 3467, 1644, 1580, 1205, 618 cm–1
.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–K

G
I. Parveen, N. Ahmed
Paper
Synthesis
1H NMR (500 MHz, CDCl3): δ = 11.48 (s, 1 H), 7.90 (d, J = 7.7 Hz, 1 H),
7.55–7.50 (m, 3 H), 7.47–7.44 (m, 2 H), 7.24 (d, J = 8.4 Hz, 1 H), 7.20 (t,
J = 7.4 Hz, 1 H), 6.78 (d, J = 8.9 Hz, 2 H), 6.71 (d, J = 8.9 Hz, 2 H), 3.75 (s,
3 H).
13C NMR (100 MHz, CDCl3): δ = 179.4, 161.8, 156.6, 145.9, 133.2,
133.0, 132.1, 130.2, 130.0, 128.5, 128.4, 124.5, 124.3, 123.3, 122.0,
114.2, 112.7, 55.4.
IR (KBr): 3387, 1665, 1598, 1201, 618 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 11.37 (s, 1 H), 7.87 (d, J = 7.7 Hz, 1 H),
7.53–7.48 (m, 3 H), 7.23 (d, J = 8.4 Hz, 1 H), 7.20–7.13 (m, 3 H), 6.99 (t,
J = 7.4 Hz, 1 H), 6.95 (d, J = 8.6 Hz, 2 H), 6.82 (d, J = 8.0 Hz, 2 H), 3.86 (s,
3 H).
13C NMR (100 MHz, CDCl3): δ = 179.8, 162.0, 161.2, 145.0, 139.7,
133.7, 133.2, 131.8, 129.0, 124.3, 124.0, 123.5, 122.7, 122.1, 122.0,
114.2, 112.8, 55.4.
HRMS (ESI+): m/z [M + Na]+ calcd for C22H17NO3Na: 366.1106; found:
366.1111.
HRMS (ESI+): m/z [M + Na]+ calcd for C22H17NO3Na: 366.1106; found:
366.1146.
(E)-2-{(4-Methoxyphenyl)[(4-nitrophenyl)amino]methylene}ben-
zofuran-3(2H)-one (2f)
(E)-2-{(4-Methoxyphenyl)[(4-methyl-2-nitrophenyl)amino]meth-
ylene}benzofuran-3(2H)-one (2j)
Yield: 322 mg (83%); yellow solid; mp 217–219 °C.
IR (KBr): 3444, 1644, 1591, 1202, 618 cm–1
.
Yield: 301 mg (75%); yellow solid; mp 156–158 °C.
1H NMR (400 MHz, CDCl3): δ = 11.16 (s, 1 H), 8.02 (d, J = 9.0 Hz, 2 H),
7.86 (d, J = 7.7 Hz, 1 H), 7.59–7.54 (m, 3 H), 7.26–7.24 (m, 1 H), 7.21 (t,
J = 7.4 Hz, 1 H), 7.01 (d, J = 8.6 Hz, 2 H), 6.80 (d, J = 9.0 Hz, 2 H), 3.89 (s,
3 H).
13C NMR (100 MHz, CDCl3): δ = 182.1, 163.3, 161.8, 146.7, 142.5,
140.7, 135.0, 134.8, 131.6, 125.1, 123.9, 123.5, 122.8, 121.4, 120.3,
114.7, 113.0, 55.6.
IR (KBr): 3327, 1688, 1591, 1208, 615 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 11.82 (s, 1 H), 7.86 (d, J = 7.4 Hz, 2 H),
7.55–7.51 (m, 1 H), 7.49 (d, J = 8.5 Hz, 2 H), 7.22–7.16 (m, 2 H), 6.96–
6.92 (m, 3 H), 6.52 (d, J = 8.5 Hz, 1 H), 3.84 (s, 3 H), 2.26 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 181.9, 163.3, 161.3, 139.4, 138.8,
135.9, 134.6, 134.6, 134.4, 132.2, 131.7, 125.9, 124.1, 124.0, 123.7,
122.6, 122.4, 114.5, 112.8, 55.5, 20.5.
HRMS (ESI+): m/z [M + Na]+ calcd for C22H16N2O5Na: 411.0957; found:
411.0961.
HRMS (ESI+): m/z [M + Na]+ calcd for C23H18N2O5Na: 425.1113; found:
425.1143.
(E)-2-{[(4-Chlorophenyl)amino](4-methoxyphenyl)methy-
lene}benzofuran-3(2H)-one (2g)
(E)-2-{[(3,5-Dimethylphenyl)amino](4-methoxyphenyl)methy-
lene}benzofuran-3(2H)-one (2k)
Yield: 294 mg (78%); yellow solid; mp 115–117 °C.
Yield: 255 mg (69%); yellow solid; mp 146–148 °C.
IR (KBr): 3320, 1644, 1601, 1202, 695 cm–1
.
IR (KBr): 3385, 1669, 1597, 1202, 614 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 11.30 (s, 1 H), 7.85 (d, J = 7.7 Hz, 1 H),
7.52–7.47 (m, 3 H), 7.22 (d, J = 8.4 Hz, 1 H), 7.17 (t, J = 7.4 Hz, 1 H),
7.10 (d, J = 8.6 Hz, 2 H), 6.94 (d, J = 8.6 Hz, 2 H), 6.72 (d, J = 8.6 Hz, 2 H),
3.85 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 180.3, 162.2, 161.4, 144.3, 138.4,
133.8, 133.6, 131.8, 129.2, 129.1, 124.1, 123.7, 123.4, 122.3, 121.6,
114.3, 112.8, 55.5.
1H NMR (400 MHz, CDCl3): δ = 11.36 (s, 1 H), 7.85 (d, J = 7.7 Hz, 1 H),
7.51–7.46 (m, 3 H), 7.22 (d, J = 8.4 Hz, 1 H), 7.18–7.14 (m, 1 H), 6.94
(d, J = 8.8 Hz, 2 H), 6.62 (s, 1 H), 6.43 (s, 2 H), 3.85 (s, 3 H), 2.13 (s, 6 H).
13C NMR (100 MHz, CDCl3): δ = 179.4, 161.8, 161.2, 145.3, 139.4,
138.6, 133.6, 133.1, 131.8, 125.8, 124.4, 123.4, 122.3, 121.9, 120.5,
114.1, 112.8, 55.5, 21.3.
HRMS (ESI+): m/z [M + Na]+ calcd for C24H21NO3Na: 394.1419; found:
394.1431.
HRMS (ESI+): m/z [M + Na]+ calcd for C22H16ClNO3Na: 400.0716;
found: 400.0736.
(E)-2-{(4-Methoxyphenyl)[(4-methoxyphenyl)amino]methy-
lene}benzofuran-3(2H)-one (2l)
(E)-2-{[(4-Fluorophenyl)amino](4-methoxyphenyl)methy-
lene}benzofuran-3(2H)-one (2h)
Yield: 242 mg (65%); yellow solid; mp 145–146 °C.
Yield: 285 mg (79%); yellow solid; mp 155–157 °C.
IR (KBr): 3387, 1665, 1591, 1208, 616 cm–1
.
IR (KBr): 3444, 1644, 1591, 1202, 712 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 11.39 (s, 1 H), 7.86 (d, J = 7.7 Hz, 1 H),
7.49–7.46 (m, 3 H), 7.22 (d, J = 8.4 Hz, 1 H), 7.16 (t, J = 7.5 Hz, 1 H),
6.92 (d, J = 8.8 Hz, 2 H), 6.77 (d, J = 9.0 Hz, 2 H), 6.69 (d, J = 9.0 Hz, 2 H),
3.84 (s, 3 H), 3.73 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 179.1, 161.6, 161.2, 156.5, 146.1,
133.3, 132.9, 132.4, 131.9, 124.6, 124.5, 123.3, 122.0, 121.9, 114.3,
114.1, 112.7, 55.5, 55.4.
1H NMR (400 MHz, CDCl3): δ = 11.43 (s, 1 H), 7.87 (d, J = 7.7 Hz, 1 H),
7.52 (d, J = 7.8 Hz, 1 H), 7.48 (d, J = 8.4 Hz, 2 H), 7.23 (d, J = 8.4 Hz, 1 H),
7.18 (t, J = 7.5 Hz, 1 H), 6.94 (d, J = 8.6 Hz, 2 H), 6.88–6.84 ( m, 2 H),
6.81–6.78 (m, 2 H), 3.86 (s, 3 H).
13C NMR (100 MHz. CDCl3): δ = 179.8, 162.03, 161.2, 159.5 (J1= 243
Hz), 145.3, 135.7 (4J = 3.61 Hz), 133.4, 131.9, 124.5 (3J = 8.4 Hz), 124.2,
123.5, 122.2, 121.7, 115.8 (2J = 22.7 Hz), 114.2, 113.7, 112.8, 55.4.
HRMS (ESI+): m/z [M + Na]+ calcd for C23H19NO4Na: 396.1212; found:
396.1236.
HRMS (ESI+): m/z [M + Na]+ calcd for C22H16FNO3Na: 384.1012; found:
384.1022.
(E)-2-{[(4-Nitrophenyl)amino](p-tolyl)methylene}benzofuran-
3(2H)-one (2m)
(E)-2-[(4-Methoxyphenyl)(phenylamino)methylene]benzofuran-
3(2H)-one (2i)
Yield: 293 mg (79%); yellow solid; mp 217–218 °C.
Yield: 243 mg (71%); yellow solid; mp 179–181 °C.
IR (KBr): 3387, 1665, 1559, 1208, 616 cm–1
.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–K

H
I. Parveen, N. Ahmed
Paper
Synthesis
1H NMR (400 MHz, CDCl3): δ = 11.24 (s, 1 H), 8.01 (d, J = 8.7 Hz, 2 H),
7.86 (d, J = 7.7 Hz, 1 H), 7.57 (t, J = 7.8 Hz, 1 H), 7.49 (d, J = 7.8 Hz, 2 H),
7.31 (d, J = 7.8 Hz, 2 H), 7.25–7.19 (m, 2 H), 6.78 (d, J = 8.8 Hz, 2 H),
2.45 (s, 3 H).
1H NMR (500 MHz, CDCl3): δ = 11.18 (s, 1 H), 8.04 (d, J = 8.4 Hz, 2 H),
7.88 (d, J = 7.7 Hz, 1 H), 7.60 (t, J = 7.7 Hz, 1 H), 7.27–7.23 (m, 3 H),
7.11 (s, 1 H), 7.00 (d, J = 8.3 Hz, 1 H), 6.83 (d, J = 8.7 Hz, 2 H), 3.99 (s, 3
H), 3.84 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 182.2, 163.3, 146.4, 142.5, 141.7,
141.1, 135.0, 134.8, 130.0, 129.7, 126.5, 125.1, 123.9, 123.4, 122.8,
120.3, 113.0, 21.7.
13C NMR (125 MHz, CDCl3): δ = 182.0, 163.2, 151.4, 149.4, 146.6,
142.4, 140.6, 135.0, 134.7, 125.0, 123.8, 123.4, 123.4, 122.7, 121.5,
120.1, 112.9, 112.4, 111.4, 56.1, 56.0.
HRMS (ESI+): m/z [M + H]+ calcd for C22H16N2O4Na: 395.1008; found:
HRMS (ESI+): m/z [M + Na]+ calcd for C23H18N2O6Na: 441.1063; found:
395.1046.
441.1126.
(E)-2-{[(4-Chlorophenyl)amino](p-tolyl)methylene}benzofuran-
3(2H)-one (2n)
(E)-2-{[(4-Chlorophenyl)amino](3,4-dimethoxyphenyl)methy-
lene}benzofuran-3(2H)-one (2r)
Yield: 267 mg (74%); yellow solid; mp 183–184 °C.
Yield: 325 mg (80%); yellow solid; mp 165–167 °C.
IR (KBr): 3352, 1689, 1596, 1221, 618 cm–1
.
IR (KBr): 3438, 1689, 1596, 1202, 618 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 11.32 (s, 1 H), 7.86 (d, J = 7.8 Hz, 1 H),
7.51 (t, J = 7.8 Hz, 1 H), 7.43 (d, J = 7.7 Hz, 2 H), 7.26–7.24 (m, 2 H),
7.22 (d, J = 8.5 Hz, 1 H), 7.18 (t, J = 7.4 Hz, 1 H), 7.10 (d, J = 8.2 Hz, 2 H),
6.72 (d, J = 8.2 Hz, 2 H), 2.42 (s, 3 H).
1H NMR (400 MHz, CDCl3): δ = 11.26 (s, 1 H), 7.86 (d, J = 7.7 Hz, 1 H),
7.52 (t, J = 7.8 Hz, 1 H), 7.24 (d, 8.4 Hz, 1 H), 7.21–7.18 (m, 2 H), 7.11
(d, J = 8.6 Hz, 2 H), 7.00 (s, 1 H), 6.94 (d, J = 8.4 Hz, 1 H), 6.74 (d, J = 8.7
Hz, 2 H), 3.94 (s, 3 H), 3.77 (s, 3 H).
13C NMR (100 MHz, CDCl3: δ = 180.4, 162.3, 144.7, 141.1, 139.3, 138.2,
133.7, 129.9, 129.6, 129.1, 126.7, 123.6, 123.5, 122.3, 121.2, 114.1,
112.9, 21.7.
13C NMR (100 MHz, CDCl3): δ = 180.3, 162.3, 150.9, 149.0, 144.1,
138.4, 133.8, 133.7, 129.2, 129.1, 124.1, 123.7, 123.6, 123.5, 122.3,
121.7, 112.8, 112.7, 111.1, 56.1, 56.0.
HRMS (ESI+): m/z [M + Na]+ calcd for C22H16ClNO2Na: 384.0767;
HRMS (ESI+): m/z [M + Na]+ calcd for C23H18ClNO4Na: 430.0822;
found: 384.0795.
found: 430.0842.
(E)-2-[(Phenylamino)(p-tolyl)methylene]benzofuran-3(2H)-one
(2o)
(E)-2-[(3,4-Dimethoxyphenyl)(phenylamino)methylene]benzofu-
ran-3(2H)-one (2s)
Yield: 222 mg (68%) as yellow solid; mp 183–184 °C.
Yield: 268 mg (72%); yellow solid; mp 127–129 °C.
IR (KBr): 3357, 1685, 1591, 1202, 618 cm–1
.
IR (KBr): 3438, 1688, 1593, 1204, 618 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 11.31 (s, 1 H), 7.85 (d, J = 7.8 Hz, 1 H),
7.50 (t, J = 7.8 Hz, 1 H), 7.42 (d, J = 7.7 Hz, 2 H), 7.25–7.20 (m, 4 H),
7.17 (t, J = 7.4 Hz, 1 H), 7.09 (d, J = 8.2 Hz, 2 H), 6.71 (d, J = 8.2 Hz, 2 H),
2.41 (s, 3 H).
1H NMR (400 MHz, CDCl3): δ = 11.38 (s, 1 H), 7.87 (d, J = 7.7 Hz, 1 H),
7.51 (t, J = 7.7 Hz, 1 H), 7.24 (d, J = 8.3 Hz, 2 H), 7.20–7.14 (m, 4 H),
7.01–6.98 (m, 2 H), 6.93 (d, J = 8.4 Hz, 1 H), 6.83 (d, J = 8.1 Hz, 2 H),
3.93 (s, 3 H), 3.72 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 181.9, 163.3, 155.2, 139.3, 138.4,
135.9, 134.6, 134.4, 132.2, 131.7, 125.9, 124.0, 123.7, 122.6, 122.4,
114.5, 112.8, 20.5.
13C NMR (125 MHz, CDCl3): δ = 179.8, 162.0, 150.8, 148.9, 144.9,
139.6, 133.6, 133.2, 128.9, 124.2, 124.0, 123.7, 123.4, 122.6, 122.1,
122.0, 113.0, 112.7, 111.0, 56.0, 55.9.
HRMS (ESI+): m/z [M + Na]+ calcd for C22H17NO2Na: 350.1157; found:
HRMS (ESI+): m/z [M + Na]+ calcd for C23H19NO4Na: 396.1212; found:
350.1197.
396.1242.
(E)-2-{[(4-Methoxyphenyl)amino](p-tolyl)methylene}benzofu-
ran-3(2H)-one (2p)
(E)-2-{(3,4-Dimethoxyphenyl)[(3,5-dimethylphenyl)amino]meth-
ylene}benzofuran-3(2H)-one (2t)
Yield: 217 mg (61%); yellow solid; mp 161–162 °C.
Yield: 284 mg (71%); yellow solid; mp 167–169 °C.
IR (KBr): 3448, 1656, 1596, 1204, 616 cm–1
.
IR (KBr): 3440, 1688, 1591, 1202, 618 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 11.49 (s, 1 H), 7.86 (d, J = 7.8 Hz, 1 H),
7.47 (t, J = 7.8 Hz, 1 H), 7.40 (d, J = 7.8 Hz, 2 H), 7.21 (d, J = 7.7 Hz, 3 H),
7.16 (t, J = 7.5 Hz, 1 H), 6.76 (d, J = 8.9 Hz, 2 H), 6.68 (d, J = 8.9 Hz, 2 H),
3.72 (s, 3 H), 2.39 (s, 3 H).
1H NMR (400 MHz, CDCl3): δ = 11.35 (s, 1 H), 7.86 (d, J = 7.7 Hz, 1 H),
7.49 (t, J = 7.7 Hz, 1 H), 7.23–7.15 (m, 3 H), 7.02 (s, 1 H), 6.92 (d, J = 8.4
Hz, 1 H), 6.63 (s, 1 H), 6.44 (s, 2 H), 3.93 (s, 3 H), 3.75 (s, 3 H), 2.14 (s, 6
H).
13C NMR (100 MHz, CDCl3): δ = 179.1, 161.7, 156.6, 146.7, 140.7,
133.0, 132.2, 130.1, 129.4, 129.2, 127.0, 124.6, 124.4, 123.3, 122.1,
114.2, 112.8, 55.4, 21.7.
13C NMR (125 MHz, CDCl3): δ = 179.4, 161.8, 150.7, 148.8, 145.1,
139.4, 138.5, 133.5, 133.0, 125.8, 124.3, 123.7, 123.3, 122.0, 120.4,
115.0, 113.0, 112.7, 110.9, 56.0, 55.9, 21.3.
HRMS (ESI+): m/z [M + H]+ calcd for C23H19NO3Na: 380.1263; found:
HRMS (ESI+): m/z [M + Na]+ calcd for C25H23NO4Na: 424.1525; found:
380.1293.
424.1535.
(E)-2-{(3,4-Dimethoxyphenyl)[(4-nitrophenyl)amino]methy-
lene}benzofuran-3(2H)-one (2q)
(E)-2-{(3,4-Dimethoxyphenyl)[(4-methoxyphenyl)amino]methy-
lene}benzofuran-3(2H)-one (2u)
Yield: 342 mg (82%); yellow solid; mp 200–202 °C.
Yield: 274 mg (68%); yellow solid; mp 120–122 °C.
IR (KBr): 3436, 1685, 1591, 1202, 619 cm–1
.
IR (KBr): 3441, 1688, 1591, 1207, 618 cm–1
.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–K

I
I. Parveen, N. Ahmed
Paper
Synthesis
1H NMR (400 MHz, CDCl3): δ = 11.39 (s, 1 H), 7.86 (d, J = 7.7 Hz, 1 H),
7.48 (t, J = 7.8 Hz, 1 H), 7.22 (d, J = 8.4 Hz, 1 H), 7.20–7.15 (m, 2 H),
6.95 (s, 1 H), 6.90 (d, J = 8.4 Hz, 1 H), 6.78 (d, J = 8.9 Hz, 2 H), 6.69 (d,
J = 8.9 Hz, 2 H), 3.92 (s, 3 H), 3.73 (s, 3 H), 3.72 (s, 3 H).
1H NMR (400 MHz, CDCl3): δ = 11.48 (s, 1 H), 8.05 (d, J = 9.0 Hz, 1 H),
8.01 (d, J = 9.1 Hz, 2 H), 7.85 (d, J = 7.9 Hz, 1 H), 7.58–7.54 (m, 1 H),
7.22–7.19 (m, 2 H), 6.78 (s, 1 H), 6.73 (d, J = 9.1 Hz, 2 H), 4.00 (s, 3 H),
3.92 (s, 3 H), 3.82 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 179.1, 161.6, 156.6, 150.6, 148.8,
146.0, 133.2, 132.9, 132.4, 124.5, 124.4, 123.8, 123.3, 122.1, 122.0,
114.2, 113.0, 112.7, 110.9, 56.0, 55.9, 55.4.
13C NMR (100 MHz, CDCl3): δ = 181.9, 163.3, 153.7, 152.1, 145.5,
145.1, 142.8, 139.5, 135.0, 134.3, 126.4, 125.7, 125.3, 123.8, 123.4,
122.8, 119.1, 113.1, 109.3, 61.5, 61.4, 56.5.
HRMS (ESI+): m/z [M + Na]+ calcd for C24H21NO5Na: 426.1317; found:
HRMS (ESI+): m/z [M + Na]+ calcd for C24H20N2O7Na: 471.1168; found:
426.1339.
471.1176.
(E)-2-{(4-Chlorophenyl)[(4-nitrophenyl)amino]methylene}ben-
zofuran-3(2H)-one (2v)
(E)-2-{Furan-2-yl[(4-nitrophenyl)amino]methylene}benzofuran-
3(2H)-one (4a)
Yield: 305 mg (78%); yellow solid; mp 142–143 °C.
Yield: 264 mg (76%); yellow solid; mp 173–175 °C.
IR (KBr): 3444, 1689, 1591, 1202, 712 cm–1
.
IR (KBr): 3441, 1669, 1597, 1202, 710 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 11.07 (s, 1 H), 8.03 (d, J = 9.0 Hz, 2 H),
7.86 (d, J = 7.7 Hz, 1 H), 7.62–7.58 (m, 1 H), 7.55 (d, J = 8.4 Hz, 2 H),
7.49 (d, J = 8.4 Hz, 2 H), 7.25–7.21 (m, 2 H), 6.78 (d, J = 9.1 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 181.2, 163.3, 146.4, 142.5, 141.7,
141.1, 135.0, 130.0, 129.7, 129.3, 126.5, 125.0, 124.0, 123.4, 122.7,
120.2, 113.0.
1H NMR (400 MHz, CDCl3): δ = 10.46 (s, 1 H), 8.07 (d, J = 7.7 Hz, 2 H),
7.81 (d, J = 7.6 Hz, 1 H), 7.59 (t, J = 7.8 Hz, 1 H), 7.51 (br s, 1 H), 7.33–
7.28 (m, 2 H), 7.21 (t, J = 7.4 Hz, 1 H), 6.78 (d, J = 7.8 Hz, 2 H), 6.68–
6.67 (m, 1 H).
13C NMR (100 MHz, CDCl3): δ = 182.7, 163.2, 147.4, 145.4, 143.0,
142.7, 135.2, 134.2, 128.6, 125.1, 124.0, 123.4, 123.1, 120.0, 119.0,
113.2, 112.9.
HRMS (ESI+): m/z [M + Na]+ calcd for C21H13ClN2O4Na: 415.0462;
found: 415.0470.
HRMS (ESI+): m/z [M + Na]+ calcd for C19H12N2O5Na: 371.0644; found:
371.0651.
(E)-2-{(4-Chlorophenyl)[(4-chlorophenyl)amino]methylene}ben-
zofuran-3(2H)-one (2w)
(E)-2-{Furan-2-yl[(2-nitrophenyl)amino]methylene}benzofuran-
3(2H)-one (4b)
Yield: 289 mg (76%); yellow solid; mp 142–143 °C.
Yield: 261 mg (75%); yellow solid; mp 179–181 °C.
IR (KBr): 3443, 1687, 1591, 1202, 713 cm–1
.
IR (KBr): 3442, 1662, 1597, 1202, 711 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 11.14 (s, 1 H), 7.85 (d, J = 7.7 Hz, 1 H),
7.53 (t, J = 7.8 Hz, 1 H), 7.48 (d, J = 8.4 Hz, 2 H), 7.42 (d, J = 8.4 Hz, 2 H),
7.22–7.17 (m, 2 H), 7.11 (d, J = 8.7 Hz, 2 H), 6.71 (d, J = 8.6 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 181.0, 162.6, 142.3, 138.0, 136.8,
134.1, 133.8, 131.4, 129.5, 129.2, 128.3, 124.0, 123.9, 123.7, 123.6,
122.5, 112.8.
1H NMR (400 MHz, CDCl3): δ = 11.26 (s,1 H), 8.13 (d, J = 8.4 Hz, 1 H),
7.83 (d, J = 7.6 Hz, 1 H), 7.59 (t, J = 7.8 Hz, 1 H), 7.44 (br s, 1 H), 7.32–
7.26 (m, 3 H), 7.20 (t, J = 7.6 Hz, 1 H), 6.99 (t, J = 7.8 Hz, 1 H), 6.64–6.62
(m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 182.5, 163.5, 145.2, 144.9, 144.0,
138.5, 138.3, 135.7, 135.2, 133.9, 125.9, 125.5, 124.2, 123.5, 121.5,
121.3, 118.6, 118.3, 113.0.
HRMS (ESI+): m/z [M + Na]+ calcd for C21H13Cl2NO2Na: 404.0221;
found: 404.0233.
HRMS (ESI+): m/z [M + Na]+ calcd for C19H12N2O5Na: 371.0644; found:
371.0651.
(E)-2-{(4-Chlorophenyl)(phenylamino)methylene}benzofuran-
3(2H)-one (2x)
(E)-2-{[(4-Chlorophenyl)amino](furan-2-yl)methylene}benzofu-
ran-3(2H)-one (4c)
Yield: 222 mg (64%); yellow solid; mp 153–154 °C.
IR (KBr): 3444, 1644, 1591, 1202, 618 cm–1
.
Yield: 242 mg (72%); yellow solid; mp 185–187 °C.
1H NMR (400 MHz, CDCl3): δ = 11.27 (s, 1 H), 7.87 (d, J = 7.8 Hz, 1 H),
7.54–7.49 (m, 3 H), 7.41 (d, J = 8.1 Hz, 2 H), 7.23–7.19 (m, 2 H), 7.16 (t,
J = 7.7 Hz, 2 H), 7.01 (t, J = 7.3 Hz, 1 H), 6.80 (d, J = 7.9 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 181.0, 162.6, 142.3, 138.0, 136.7,
134.1, 133.8, 129.5, 129.3, 129.2, 128.2, 124.0, 123.9, 123.7, 123.6,
122.5, 112.8.
IR (KBr): 3448, 1669, 1597, 1202, 617 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 10.71 (s, 1 H), 7.83 (d, J = 7.6 Hz, 1 H),
7.57–7.53 (m, 1 H), 7.47 (br s, 1 H), 7.31–7.27 (m, 2 H), 7.22–7.18 (m,
3 H), 6.79 (d, J = 8.6 Hz, 2 H), 6.63–6.62 (m, 1 H).
13C NMR (100 MHz, CDCl3): δ = 181.1, 162.3, 145.1, 143.2, 139.5,
134.0, 133.1, 132.1, 129.3, 129.0, 124.0, 123.6, 123.0, 122.4, 119.0,
112.8, 112.7.
HRMS (ESI+): m/z [M + Na]+ calcd for C21H14ClNO2Na: 370.0611;
found: 370.0620.
HRMS (ESI+): m/z [M + Na]+ calcd for C19H12ClNO3Na: 360.0403;
found: 360.0412.
(E)-2-{[(4-Nitrophenyl)amino](3,4,5-trimethoxyphenyl)methy-
lene}benzofuran-3(2H)-one (2y)
(E)-2-[Furan-2-yl(phenylamino)methylene]benzofuran-3(2H)-one
(4d)
Yield: 362 mg (81%); yellow solid; mp 174–175 °C.
IR (KBr): 3448, 1669, 1591, 1202, 618 cm–1
.
Yield: 203 mg (67%); yellow semi-solid.
IR (KBr): 3448, 1669, 1597, 1202, 617 cm–1
.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–K

J
I. Parveen, N. Ahmed
Paper
Synthesis
1H NMR (400 MHz, CDCl3): δ = 10.88 (s, 1 H), 7.86 (d, J = 7.6 Hz, 1 H),
7.56 (t, J = 7.8 Hz, 1 H), 7.47 (br s, 1 H), 7.32 (d, J = 8.2 Hz, 1 H), 7.28–
7.26 (m, 2 H), 7.24–7.19 (m, 2 H), 7.08 (t, J = 7.3 Hz, 1 H), 6.89 (d, J =
8.1 Hz, 2 H), 6.63–6.62 (m, 1 H).
13C NMR (100 MHz, CDCl3): δ = 180.8, 162.0, 145.0, 143.4, 140.6,
133.8, 132.9, 132.8, 129.0, 124.2, 124.1, 123.5, 122.5, 121.9, 118.8,
112.7, 112.5.
1H NMR (400 MHz, CDCl3): δ = 11.03 (s, 1 H), 7.73 (s, 1 H), 7.54 (s, 1
H), 7.46 (s, 1 H), 7.43–7.42 (m, 1 H), 7.28 (t, J = 7.7 Hz, 2 H), 7.14 (t, J =
7.3 Hz, 1 H), 6.94 (d, J = 7.9 Hz, 2 H), 6.66–6.65 (m, 1 H).
13C NMR (100 MHz, CDCl3): δ = 177.4, 155.4, 145.6, 142.7, 139.9,
135.1, 133.2, 132.5, 129.1, 128.2, 126.6, 125.0, 122.7, 121.4, 120.5,
119.0, 112.9.
HRMS (ESI+): m/z [M + Na]+ calcd for C19H11Cl2NO3Na: 394.0014;
found: 394.0022.
HRMS (ESI+): m/z [M + Na]+ calcd for C19H13NO3Na: 326.0793; found:
326.0803.
(E)-2-[(Methylamino)(phenyl)methylene]benzofuran-3(2H)-one
(E)-2-[Furan-2-yl(p-tolylamino)methylene]benzofuran-3(2H)-one
(5a)
(4e)
Yield: 185 mg (71%); yellow solid; mp 122–124 °C.
Yield: 190 mg (60%); yellow solid; mp 164–166 °C.
1H NMR (500 MHz, CDCl3): δ = 9.93 (s, 1 H), 7.84 (d, J = 7.6 Hz, 1 H),
7.42–7.34 (m, 6 H), 7.16–7.11 (m, 2 H), 3.10 (s, 3 H).
IR (KBr): 3447, 1669, 1597, 1201, 615 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 10.89 (s, 1 H), 7.84 (d, J = 7.8 Hz, 1 H),
7.53 (t, J = 7.8 Hz, 1 H), 7.46 (br s, 1 H), 7.30 (d, J = 8.4 Hz, 1 H), 7.24–
7.23 (m, 1 H), 7.19 (t, J = 7.5 Hz, 1 H), 7.04 (d, J = 8.1 Hz, 2 H), 6.78 (d,
J = 8.1 Hz, 2 H), 6.61–6.60 (m, 1 H), 2.29 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 180.3, 161.8, 145.0, 143.4, 137.9,
134.0, 133.5, 133.4, 132.7, 129.6, 124.2, 123.4, 122.4, 122.0, 118.8,
112.7, 112.4, 21.0.
13C NMR (125 MHz, CDCl3): δ = 177.5, 160.9, 152.2, 140.5, 132.0,
129.4, 128.9, 126.8, 124.8, 122.9, 121.6, 115.0, 112.6, 30.5.
HRMS (ESI+): m/z [M + Na]+ calcd for C16H13NO2Na: 274.0844; found:
274.0849.
(E)-2-[(Ethylamino)(p-tolyl)methylene]benzofuran-3(2H)-one
(5b)
HRMS (ESI+): m/z [M + Na]+ calcd for C20H15NO3Na: 340.0950; found:
Yield: 212 mg (76%); yellow solid; mp 129–131 °C.
340.0955.
IR (KBr): 3449, 1669, 1597, 1202, 617 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 9.97 (s, 1 H), 7.86 (d, J = 7.6 Hz, 1 H),
7.44–7.37 (m, 5 H), 7.18–7.14 (m, 2 H), 3.31 (q, J = 7.1 Hz, 2 H), 2.48 (s,
3 H), 1.25 (t, J = 7.2 Hz, 3 H).
13C NMR (125 MHz, CDCl3): δ = 177.6, 160.9, 152.2, 140.6, 132.0,
129.4, 128.9, 126.9, 124.8, 122.9, 121.6, 115.0, 112.6, 39.4, 21.5, 16.2.
(E)-5,7-Dichloro-2-{furan-2-yl[(4-nitrophenyl)amino]methy-
lene}benzofuran-3(2H)-one (4f)
Yield: 307 mg (74%); yellow solid; mp 250–252 °C.
IR (KBr): 3448, 1668, 1597, 1202, 619 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 10.59 (s, 1 H), 8.13 (d, J = 8.7 Hz, 2 H),
7.71 (br s, 1 H), 7.58 (br s, 1 H), 7.52 (br s, 1 H), 7.49–7.48 (m, 1 H),
6.88 (d, J = 8.7 Hz, 2 H), 6.74–6.73 (m, 1 H).
HRMS (ESI+): m/z [M + Na]+ calcd for C18H17NO2Na: 302.1157; found:
302.1161.
13C NMR (100 MHz, CDCl3): δ = 182.2, 163.4, 146.4, 142.5, 141.7,
141.1, 135.0, 130.0, 129.7, 129.3, 126.5, 125.0, 124.0, 123.4, 122.8,
120.2, 113.0.
HRMS (ESI+): m/z [M + Na]+ calcd for C19H10Cl2N2O5Na: 438.9864;
found: 438.9887.
(E)-2-{[(4-Methoxyphenyl)amino]methylene}benzofuran-3(2H)-
one (5c)
Yield: 234 mg (88%); yellow solid; mp 112–114 °C.
1H NMR (500 MHz, CDCl3): δ = 10.90 (s, 1 H), 8.55–8.51 (m, 2 H), 8.29
(d, J = 7.9 Hz, 1 H), 7.55 (d, J = 8.9 Hz, 1 H), 6.73 (d, J = 8.4 Hz, 2 H), 6.62
(d, J = 8.3 Hz, 2 H), 4.62 (s, 1 H), 3.73 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 181.1, 163.8, 157.5, 152.8, 150.3,
144.7, 139.9, 129.5, 124.9, 118.8, 116.4, 114.8, 112.5, 55.7.
(E)-5,7-Dichloro-2-{[(4-chlorophenyl)amino](furan-2-yl)methy-
lene}benzofuran-3(2H)-one (4g)
Yield: 286 mg (71%); yellow solid; mp 199–201 °C.
HRMS (ESI+): m/z [M + Na]+ calcd for C16H13NO3Na: 290.0793; found:
290.0833.
IR (KBr): 3448, 1669, 1598, 1202, 619 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 10.84 (s, 1 H), 7.70 (br s, 1 H), 7.53 (br
s, 1 H), 7.47 (br s, 1 H), 7.43–7.42 (m, 1 H), 7.37 (d, J = 8.2 Hz, 2 H),
6.79 (d, J = 8.1 Hz, 2 H), 6.66–6.65 (m, 1 H).
(E)-2-Hydroxyphenyl)-3-[(4-nitrophenyl)amino]-3-phenylprop-2-
en-1-one (5d)
13C NMR (100 MHz, CDCl3): δ = 177.9, 155.7, 145.8, 142.5, 139.2,
134.3, 133.3, 132.9, 132.1, 128.4, 126.4, 124.0, 121.5, 120.8, 119.0,
118.0, 113.1.
HRMS (ESI+): m/z [M + Na]+ calcd for C19H10Cl3NO3Na: 427.9624;
found: 427.9634.
Yield: 334 mg (71%); yellow solid; mp 227–229 °C.
IR (KBr): 3449, 3100, 1669, 1597, 1202, 617 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 12.76 (s, 1 H), 12.39 (s, 1 H), 8.07 (d, J =
9.0 Hz, 2 H), 7.77 (d, J = 7.9 Hz, 1 H), 7.48–7.39 (m, 6 H), 7.02 (d, J = 8.3
Hz, 1 H), 6.90 (t, J = 7.2 Hz, 1 H), 6.84 (d, J = 8.9 Hz, 2 H), 6.24 (s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 193.7, 162.9, 158.5, 145.2, 143.5,
137.1, 135.5, 133.4, 129.7, 129.5, 128.5, 125.0, 121.8, 120.2, 118.9,
118.8, 99.1.
HRMS (ESI+): m/z [M + Na]+ calcd for C21H16N2O4Na: 383.1008; found:
383.1012.
(E)-5,7-Dichloro-2-[furan-2-yl(phenylamino)methylene]benzofu-
ran-3(2H)-one (4h)
Yield: 244 mg (66%); yellow solid; mp 142–144 °C.
IR (KBr): 3449, 1669, 1597, 1202, 617 cm–1
.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–K

K
I. Parveen, N. Ahmed
Paper
Synthesis
Funding Information
(8) Ono, M.; Maya, Y.; Haratake, M.; Ito, K.; Mori, H.; Nakayama, M.
Biochem. Biophys. Res. Commun. 2007, 361, 116.
(9) Zwick, V.; Chatzivasileiou, O. A.; Deschamps, N.; Roussaki, M.;
Simões-Pires, C. A.; Nurisso, A.; Denis, I.; Blanquart, C.;
Martinet, N.; Carrupt, A. P.; Detsi, A.; Cuendet, M. Bioorg. Med.
Chem. Lett. 2014, 24, 5497.
(10) Bandgar, P. B.; Patil, S. A.; Korbad, L. B.; Biradar, C. S.; Nile, S. N.;
Khobragade, C. N. Eur. J. Med. Chem. 2010, 45, 3223.
(11) (a) Emilewicz, T.; Kostanecki, S. Ber. Dtsch. Chem. Ges. 1898, 31,
696. (b) Donnelly, A. J.; Fox, M. J.; Sharma, T. C. Tetrahedron
1979, 35, 875. (c) Bose, G.; Mondal, E.; Khan, T. A.; Bordoloi, M. J.
Tetrahedron Lett. 2001, 42, 8907.
I.P. is thankful to UGC (Grant No: 6405-13-044), New Delhi for a fel-
lowship.
U
G
C
(6
4
0
5-13-0
4
4)
Acknowledgment
We sincerely thank Instrumentation centre IITR and Department of
Chemistry IITR for various facilities. The reviewers are highly appreci-
ated for their valuable suggestions to improve the manuscript.
(12) Cheng, H.; Zhang, L.; Liu, Y.; Chen, S.; Cheng, H.; Lu, X.; Zheng,
Z.; Zhou, G.-C. Eur. J. Med. Chem. 2010, 45, 5950.
Supporting Information
(13) Okombi, S.; Rival, D.; Bonnet, S.; Mariotte, A. M.; Perrier, E.;
Boumendjel, A. J. Med. Chem. 2006, 49, 329.
(14) Varma, S. R.; Varma, M. Tetrahedron Lett. 1992, 33, 5937.
(15) Thakkar, K.; Cushman, M. J. Org. Chem. 1995, 60, 6499.
(16) Patel, K. A.; Patel, H. N.; Patel, M. A.; Brahmbhatt, D. I. J. Hetero-
cycl. Chem. 2012, 49, 504.
Supporting information for this article is available online at
https://doi.org/10.1055/s-0037-1610662.
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–K