Synthesis of aurones under neutral conditions using a deep eutectic solvent

Article abstract of DOI:10.1016/j.tet.2013.08.060

Aurones are an interesting, but little studied member of the flavanoid family of natural products. Of the various methods available for their synthesis, the simplest involves the condensation of a coumaranone with an aldehyde. This reaction can be perform

Full text of DOI:10.1016/j.tet.2013.08.060

Accepted Manuscript
Synthesis of aurones under neutral conditions using a deep eutectic solvent
Ian Hawkins, Scott T. Handy
PII:
S0040-4020(13)01347-1
10.1016/j.tet.2013.08.060
TET 24749
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 5 July 2013
Revised Date: 20 August 2013
Accepted Date: 21 August 2013
Please cite this article as: Hawkins I, Handy ST, Synthesis of aurones under neutral conditions using a
deep eutectic solvent, Tetrahedron (2013), doi: 10.1016/j.tet.2013.08.060.
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Synthesis of aurones under neutral
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conditions using a deep eutectic solvent
Ian Hawkins and Scott T. Handy
Department of Chemistry, Middle Tennessee State University, Murfreesboro, TN 37132

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Tetrahedron
journal homepage: www.elsevier.com
Synthesis of aurones under neutral conditions using a deep eutectic solvent
Ian Hawkins and Scott T. Handy
Department of Chemistry, Middle Tennessee State University, Murfreesboro, TN 37132
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
Aurones are an interesting, but little studied member of the flavanoid family of natural products.
Of the various methods available for their synthesis, the simplest involves the condensation of a
coumaranone with an aldehyde. This reaction can be performed under acidic or basic
conditions. We have recently discovered an effectively neutral set of conditions that employ the
deep eutectic solvent comprised of choline chloride and urea as both solvent and catalyst.
Modest to good yields can be achieved for a range of aldehydes, thereby facilitating further
study of aurones from both a biological as well as a spectroscopic perspective.
Available online
Keywords:
condensation
green chemistry
ionic liquid
auronrs
2009 Elsevier Ltd. All rights reserved.
choline chloride
———
Corresponding author. Tel.: +0-615-217-3271; fax: +0-615-898-5182; e-mail: shandy@mtsu.edu

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1. Introduction
in turn can be formed several ways, including Friedel-Crafts
acylation of phenol derivatives.11 The compound is then
hydrolyzed to ketone 1 and then cyclization takes place forming
the coumaranone derivative 2. (Scheme 1)
1.1. Aurones
Aurones are a family of natural compounds that are found in
plants and are part of a larger family of natural products known
as flavonoids.1-3 This family consists of flavones, isoflavones,
chalcones, and aurones and are mainly secondary metabolites of
plants found in fruits and flowers. (Fig. 1) Aurones in particular
have been found to be involved in the coloring of fruits and
flowers.4 While flavones and chalcones have been well studied
over the years for various therapeutic effects, aurones have not
been as well studied. In early studies, aurones have been found to
be possibly beneficial in anti-cancer therapies,5 in the treatment
of malaria,6 and in microbial infections.7 Aurones have shown
higher activities in these assays when compared with the
corresponding flavones and chalcones. These early studies show
promise in the use of aurones in many different medical
applications.2,3
Scheme 1. Coumaranone Synthesis
An alternate approach is based upon the biosynthetic pathway
and follows the same procedure of oxidation followed by
cyclization of the aurone.12,13 (Scheme 2) Chalcones can also be
brominated first and then cyclization occurs in a KOH/EtOH
solvent.14 Also the use of thallium (III) nitrate in oxidative
rearrangement of chalcones15 and the use of gold catalyzed
cyclization of 2-(1-hydroxyprop-2-ynyl)phenols have been
reported recently.16
Scheme 2. Biosynthetic Pathway
Returning to the condensation approach, the reaction between
coumaranone and an aldehyde involves the use of acid or base
catalyzed conditions. Among the many possible variations, one
of the milder is the use of neutral alumina to mediate the
condensation.12 Here we report the acid- and base-free synthesis
of aurones by the condensation of coumaranone with
arylaldehydes using the deep eutectic solvent of choline chloride
and urea.
1.2. Deep Eutectics
Deep eutectic solvents are solvents composed of two or more
materials where the melting point is drastically reduced
compared to that of the original two components.17 The choline
chloride/urea (CC/U) deep eutectic solvent is quite interesting
and has been more extensively studied for several reasons. First,
the two components are inexpensive, readily available in large
quantities, and non-toxic. Further, it can be seen as a much less
expensive alternative to room temperature ionic liquids. To date,
deep eutectic solvents have been most extensively explored in
areas such as metal extraction and electroplating.18 The use of a
mixture of choline chloride and urea forms a very inexpensive
solvent and a wide range of solutes have high solubilities in this
mixture. Abbott et. al. have looked specifically at choline
chloride and urea mixtures and determined that it is one of the
few deep eutectic solvents that have freezing points below
ambient temperatures.19,20 This makes it a useful solvent for
ambient temperature reactions. Abbott et. al. also established that
a molar ratio of urea to choline chloride of 2:1 results in the
optimal eutectic with a freezing point of 12°C. Despite their
promising attributes, deep eutectic solvents remain largely
unexplored as reaction solvents in Organic synthesis.21, 17
Figure 1. Some Flavonoid Sub-classes
Aurones are synthesized in plants by oxidation, cyclization,
and rearrangement of chalcones by an enzyme called aureusidin
synthase.8,9,10 In the lab, however, several methods have been
employed. One of the older methods involves the condensation
of an aldehyde with a coumaranone. The coumaranone fragment
2. Results and Discussion
Intrigued by the potential to employ the choline chloride/urea
deep eutectic as a solvent in Organic synthesis, we explored a
number of simple condensation reactions, including that of
coumaranone with aldehydes. (Table 1) Gratifiyingly, the
reaction proceeded cleanly in a relatively short time to afford the
anticipated aurone products. Neither any additional acid or base
was required, so the reactions proceed under effectively neutral
conditions. The mild nature of these reaction conditions could

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certainly be of use in synthesizing aurones with more sensitive
functionality such as the furan-containing aurone (Scheme 3).
When this reaction was attempted using even the mild neutral
alumina conditions of Varma, a very low 16% yield of the aurone
was formed, while in CC/U a modest 66% yield was isolated,
with no need for chromatography. In addition, the simplicity of
the reaction conditions renders the method quite user friendly:
simply mixing the coumaranone, and aryl aldehydes in the
urea/choline chloride solvent overnight at 80°C followed by an
extractive work-up affords the desired products. This reaction is
easily accomplished for most of the aryl aldehydes overnight and
because the coumaranone is heat labile the aldehyde is the only
other material potentially remaining. Product isolation can be
readily accomplished by simple partitioning between methylene
chloride and water. Most of the reactions required no further
purification. This procedure makes it easy to make numerous
aurones in a short amount of time with little effort. The choline
chloride/urea solvent is inexpensive and presents a wonderful
alternative to standard ionic liquid catalyzed reactions. This
condensation reaction displays the possible future utility of deep
eutectic solvents as catalysts and solvents.
reaction via hydrogen-bonding activation of the aldehyde. Urea
is known to be a weak organocatalyst, with its activity largely
diminished due to intermolecular hydrogen-bonding.23 Still, the
very high concentrations of urea present in the deep eutectic can
likely overcome this weakness and result in effective catalysis.
The stronger hydrogen-bonding capabilities and preorganized
nature of urea compared to glycerol account for the difference in
activity of the two deep eutectic solvents observed in this study.
Further applications and confirmation of this hypothesis are
underway and will be reported in due course.
Entry
1
Ar
Yield (time)
68% (12 h)
2,3,4-
Trimethoxybenzaldehyde
2
3,4,5-
73% (48 h)
Trimethoxybenzaldehyde
3
4
3,4-Dimethoxybenzaldehyde
3-Nitrobenzaldehyde
4-Nitrobenzaldehyde
4-Cyanobenzaldehyde
4-Bromobenzaldehyde
Thiophene-2-carboxaldehyde
Pyrrole-2-carboxaldehyde
Pyridine-4-carboxaldehyde
4-Phenylbenzaldehyde
trans-Cinnamaldehyde
2-Furyl
66% (12 h)
40% (12 h)
59% (48 h)
67% (12 h)
58% (48 h)
66% (12 h)
60% (12 h)
54% (36 h)
61% (12 h)
78% (12 h)
66% (12 hr)
5
Scheme 3. Furan Aurone Syntheses.
6
7
In principle, the aurone products could form as E or Z
isomers. In practice, all existing reports note that the product is
mostly, or exclusively formed as the thermodynamically more
stable Z isomer. That has been our assumption in the present
work and is supported by comparison of melting point and
spectroscopic data for those aurones previously reported in the
literature. Spectroscopic trends further support this assignment
as analysis of 13C NMR data for aurones by Pelter and co-
workers has noted that the Z isomer of aurones affords an olefinic
signal around 111 ppm, while the E isomer affords an olefinic
signal roughly 9-10 ppm higher.22 In all cases, our spectra have
signals in the 110 ppm region.
8
9
10
11
12
13
Table 1. Aurone Synthesis Results
It is also worth noting that there were issues with purification.
Crude yields following extraction of the aurone from the DES
were all near quantitative, but in some cases contained unreacted
aldehyde. Purification via chromatography was not satisfactory
as the recovery was quite poor. Fortunately, simple trituration or
recrystallization from methanol was sufficient to afford pure
samples of the desired products.
3. Conclusion
Aurones are an interesting, but little studied member of the
flavanoid family of natural products. Of the various methods
available for their synthesis, the simplest involves the
condensation of a coumaranone with an aldehyde. This reaction
can be performed under acidic or basic conditions. We have
recently discovered an effectively neutral set of conditions that
employ the deep eutectic solvent comprised of choline chloride
and urea as both solvent and catalyst. Modest to good yields can
be achieved for a range of aldehydes, thereby facilitating further
study of aurones from both a biological as well as a spectroscopic
perspective. The results of these studies will be reported in due
course.
One hypothesis of how this DES promotes the reaction is via
hydrogen-bonding activation of the aldehyde. Support of this
hypothesis comes from a test reaction in an alternative deep
eutectic solvent: choline chloride/glycerol. Under the same
reaction conditions (time and temperature), a much slower
reaction occurs, affording roughly 40% conversion of the p-
anisaldehyde to the aurone product after 12 hours (compared to
96% in choline chloride/urea). For this reason, we propose that
the choline chloride/urea deep eutectic solvent catalyzes the
1
All H NMR spectra were collected using a JEOL 500 MHz
spectrometer, and the chemical shifts are reported in δ (ppm)
relative to TMS. 13C NMR spectra were also collected using a
JEOL 500 MHz spectrometer and are reported in δ (ppm) relative
4. Experimental section
4.1. General

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to the CHCl3 signal. Infrared spectra were taken neat using a
1H), 7.38 (d, J=8 Hz, 1H), 7.62 (t, J=8 Hz, 1H), 7.69 (t, J=8.55
Hz, 1H), 7.80 (d, J=8.6 Hz, 1H), 8.13 (d, J=7.45 Hz, 1H), 8.22 (d,
J=8 Hz, 1H), 8.79 (s, 1H); 13C NMR (500 MHz, CDCl3):
Varian 800 FT-IR with a Pike MIRacle ATR. Microwave
reactions were performed using a CEM Discover microwave
reactor. All solid products were recrystallized from methanol.
δ
=109.62, 113.11, 121.07, 123.95, 124.04, 124.88, 125.52,
129.79, 133.91, 136.71, 137.55, 147.86, 148.59, 166.23, 184.52.
4.2. General procedure for generation of Choline Chloride/Urea
solvent
HRMS: M+, found 267.24077. C15H9NO4 requires 267.2408.
4.8. (Z)-2-(4-nitrobenzylidene) benzofuran-3(2H)-one (Table 1,
entry 5)27
Choline chloride (7 g, 0.050 mol) and urea (6 g, 0.10 mol)
were combined in a vial and heated with shaking overnight at 80
°C on a JKEM orbital shaker at 150 rpm.
The crude solid product required further purification on silica
column with 50% CH2Cl2/Hexanes. mp = 165-170 °C.
IR
4.3. General procedure for Condensation of Coumaranone and
aryl aldehydes
ν=1711, 1603, 1517, 1476, 1458, 1343, 1322, 1299, 1204, 1188,
1130, 1111, 1097, 1033, 889, 860, 760, 688, 647 cm-1; 11H NMR
(500 MHz, CDCl3): δ=6.85 (s, 1H), 7.26 (t, J=7.45Hz, 1H), 7.35
To coumaranone (1mmol) was added the aryl aldehyde
(1mmol) and 2 mL of Choline Chloride/Urea solvent in a 5 mL
sealed vial. The reaction was stirred at 80 °C for the specified
time (Table 1). The reaction mixture was then diluted with water
(10 mL) and extracted with methylene chloride (3 x 10 mL). The
organic layer was then concentrated in vacuo to afford the
product. In most cases, this product was spectroscopically pure,
except where noted.
(d, J=8.05Hz, 1H), 7.69 (t, J=8.65 Hz, 1H), 7.82 (d, J=6.85 Hz,
3
1H), 8.04 (d, J=9.15 Hz, 2H), 8.28 (d, J=8.6 Hz, 2H); C NMR
(500 MHz, CDCl3):
δ=109.35, 113.01, 102.97, 123.85 (2C),
124.22, 125.06, 131.61 (2C), 137.29, 138.60, 148.37, 166.30,
184.94, 206.98. HRMS: M+, found 267.2408. C15H9NO4 requires
267.2408.
4.9. (Z)-4-((3-oxobenzofuran-2(3H)-ylidene)methyl)benzonitrile
(Table 1, entry 6)27
4.4. (Z)-2-(2,3,4-trimethoxybenzylidene)benzofuran-3(2H)-one
(Table 1, entry 1)23
mp = 181-184 °C. IR ν= 1703, 1650, 1602, 1475, 1461, 1302,
1190, 1130, 1108, 885, 833, 755, 734, 699, 664, 645, 626 cm-1;
mp = 115-120 °C. IR ν=1702, 1645, 1589, 1496, 1464, 1285,
1H NMR (500 MHz, CDCl3):
δ=6.79 (s, 1H), 7.24 (t, J=6.85 Hz,
1204, 1191, 1131, 1092, 1008, 910, 885, 802, 759, 732, 696 cm-1;
1H NMR (500 MHz, CDCl3):
δ= 3.86 (s, 3H), 3.90 (s, 3H), 3.94
1H), 7.32 (d, J=8.6 Hz, 1H), 7.65-7.70 (m, 3H), 7.79 (d, J=7.45,
1H), 7.97 (d, J=8.55 Hz, 2H); 13C NMR (500 MHz, CDCl3):
(s, 3H), 6.77 (d, J=9.15 Hz , 1H), 7.17 (t, J=7.45 Hz, 1H), 7.24-
7.28 (m, 2H), 7.58 (t, J=1.15 Hz 1H), 7.77 (d, J=6.3 Hz, 1H),
δ
=110.09, 112.65, 113.10, 118.65, 121.20, 124.17, 125.04,
8.06 (d, J=8.6 Hz, 1H); 13C NMR (500 MHz, CDCl3):
δ=56.13,
131.61 (2H), 132.56 (2H), 136.83, 137.64, 148.21, 166.34,
184.65. HRMS: M+, found 247.25303. C16H9NO2 requires
247.25300.
60.96, 61.96, 107.61, 112.86, 119.21, 121.92, 123.31, 124.63,
127.37, 136.52, 142.27, 146.61, 153.92, 155.62, 165.57, 184.38.
HRMS: M+, found 312.32203. C18H14O5 requires 312.32204.
4.10. (Z)-2-(4-bromobenzylidene)benzofuran-3(2H)-one (Table
1, entry 7)28
4.5. (Z)-2-(3,4,5-trimethoxybenzylidene)benzofuran-3(2H)-one
(Table 1, entry 2)24
The crude solid product required further purification on silica
column with 50% CH2Cl2/Hexanes. mp = 152-158 °C. IR ν=
1714, 1655, 1601, 1487, 1474, 1460, 1298, 1205, 1186, 1128,
The crude solid product required further purification on a
silica column with 50% CH2Cl2/Hexanes followed by a wash
with 10% EtOAc/Hexanes. mp = 175-178 °C. IR ν=1708, 1647,
1602, 1581, 1505, 1460, 1336, 1296, 1244, 1189, 1151, 1125,
1098, 1005, 879, 758, 668, 640 cm-1; 1H NMR (500 MHz,
1
1112, 1099, 1071, 1008, 884, 821, 756, 697, 653, 626 cm-1; H
NMR (500 MHz, CDCl3): δ=6.81 (s, 1H), 7.24 (t, J=7.45 Hz,
1H), 7.34 (d, J=8 Hz, 1H), 7.58 (d, J=8.6 Hz, 2H), 7.67 (t, J=8.6
Hz, 1H), 7.78 (d, J=8.6 Hz, 2H), 7.81 (d, J=8.6 Hz, 1H); 13C
CDCl3):
7.23 (d, J=8 Hz, 1H), 7.57 (t, J=6.9 Hz, 1H), 7.73 (d, J=6.85 Hz,
1H); 13C NMR (500 MHz, CDCl3):
=56.15 (2C), 60.97, 108.85
δ=6.74 (s, 1H), 7.10 (s, 2H), 7.15 (t, J=7.45 Hz, 1H),
NMR (500 MHz, CDCl3):
124.21, 124.66, 131.03, 132.07 (2C), 132.61 (2C), 136.99,
146.99, 165.99, 184.58.
δ
=111.47, 112.87, 121.39, 123.57,
HRMS: M+, found 300.15356.
δ
(2C), 112.82, 113.30, 121.65, 123.48, 124.63, 127.62, 136.71,
140.08, 146.34, 153.27 (2C), 165.84, 184.48. HRMS: M+, found
312.32207. C18H14O5 requires 312.32204.
C15H9BrO2 requires 300.15359.
4.11. (E)-2-(thiophen-2-ylmethylene)benzofuran-3(2H)-one
(Table 1, entry 8)29
4.6. (Z)-2-(3,4-dimethoxybenzylidene)benzofuran-3(2H)-one
(Table 1, entry 3)25
mp = 92-96 °C. IR ν=1698, 1684, 1645, 1593, 1504, 1475,
1458, 1417, 1391, 1328, 1295, 1232. 1185, 1124, 1095, 992, 881,
846, 756, 710, 695, 625 cm-1; 1H NMR (500 MHz, CDCl3):
mp = 123-130 °C. IR ν=1705, 1595, 1522, 1463, 1296, 1269,
1248, 1202, 1153, 1124, 1019, 885, 758, 731, 645 cm-1; 1H NMR
δ
=7.17 (t, J=4cHz, 1H), 7.20 (s, 1H), 7.24 (t, J=7.45cHz, 1H),
(500 MHz, CDCl3): δ= 3.86 (s, 3H), 3.89 (s, 3H), 6.78 (s, 1H),
7.27 (s, 1H), 7.36 (d, J=8.55 Hz, 1H), 7.57 (d, J=3.45 Hz, 1H),
7.63 (d, J=5.15Hz, 1H), 7.66 (t, J=8.55Hz, 1H), 7.81 (d,
6.86 (d, J=8.6 Hz, 1H), 7.13 (t, J=7.4 Hz, 1H), 7.23 (d, J=8.6 Hz,
1H), 7.41 (d, J=10.3 Hz, 1H), 7.45 (d, J=1.7 Hz, 1H), 7.56 (t,
J=8.55 Hz, 1H), 7.72 (d, J=7.45 Hz, 1H); 13C NMR (500 MHz,
J=7.45Hz, 1H); 13C NMR (500 MHz, CDCl3):
δ
=107.12, 112.92,
122.25, 123.52, 124.58, 128.09, 131.54, 133.17, 135.55, 136.71,
CDCl3): δ=111.13, 112.79, 113.67 (2C), 121.81, 123.30, 124.54,
145.33, 165.65, 183.85.
HRMS: M+, found 228.27134.
125.20, 125.98, 136.51, 145.86, 148.98, 150.82, 165.70, 184.43.
HRMS: M+, found 282.29574. C17H14O4 requires 282.29576.
C13H8SO2 requires 228.27132.
4.12. (Z)-2-((1H-pyrrol-2-yl)methylene)benzofuran-3(2H)-one
(Table 1, entry 9)
4.7. (Z)-2-(3-nitrobenzylidene)benzofuran-3(2H)-one (Table 1,
entry 4)26
mp = 138-142 °C. IR ν=1687, 1635, 1594, 1477, 1458, 1430,
mp = 163-166 °C. IR ν= 1708, 1655, 1601, 1531, 1475, 1458,
1347, 1303, 1191, 1132, 1098, 885, 810, 757, 734, 699, 675 cm-1;
1319, 1300, 1195, 1143, 1125, 1100, 1039, 885, 868, 819, 756,
1
725, 696 cm-1; H NMR (500 MHz, CDCl3):
δ
= 6.72 (s, 1H),
1H NMR (500 MHz, CDCl3):
δ= 6.86 (s, 1H), 7.25 (t, J=7.75 Hz,

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2. Haudecoeur, R.; Boumendjel, A. Cur. Med. Chem. 2012, 19,
6.96 (s, 1H), 7.03 (s, 1H), 7.14 (s, 1H), 7.19-7.23 (m, 1H), 7.30
(d, J=8 Hz, 1H), 7.60-7.63 (m, 1H), 7.79 (d, J=1.15 Hz, 1H), 9.56
(bs, 1H); 13C NMR (500 MHz, CDCl3):
=105.16, 111.43,
112.58, 118.43, 122.62, 123.37, 124.23, 124.61, 126.10, 136.00,
143.70, 164.53, 183.00.
C13H9NO2 requires 211.22000.
2861-2875.
3. Zwergel, C.; Gaascht, F.; Valente, S.; Diedrich, M.; Bagrel, D.;
Kirsch, G. Nat. Prod. Commun. 2012, 7, 389-394.
4. Harborne, J.B.; Williams, C.A. Phytochem. 2000, 55, 481-504.
5. Lawrence, N.J.; Rennison, D.; McGowan, A.T.; Hadfield, J.A.
Bioorg. & Med. Chem. Let. 2003,13, 3759-3763.
6. Kayser, O.; Kiderlen, A.F.; Brun, R. Planta Medica. 2001, 67,
718-721.
δ
HRMS: M+, found 211.22002.
4.13. (Z)-2-(pyridine-4-ylmethylene)benzofuran-3(2H)-one
(Table 1, entry 10)30
7. Bandgar, B.P.; Patil, S.A.; Korbad, B.L.; Biradar, S.C.; Nile, S.N.;
Khobragade, C.N. Euro. J. of Med. Chem. 2010, 45, 3223-3227.
8. Nakayama, T.; Sato, T.; Fukui, Y.; Yonekura-Sakakibara, K.;
Hayashi, H.; Tanaka, Y.; Kusumi, T.; Nishino, T. FEBS Lett.,
2001, 499, 107-111.
mp = 89-93 °C.
1300, 1201, 1130, 828, 756, 734, 697, 675, 660 cm-1; H NMR
(500 MHz, CDCl3): =6.87 (s, 1H), 7.43 (t, J=7.45 Hz, 2H), 7.57
IR ν= 1647, 1599, 1474, 1464, 1416, 1378,
1
δ
9. Nakayama, T.; Yonekura-Sakakibara, K.; Sato, T.; Kikuchi, S.;
Fukui, Y.; Fukuchi-Mizutani, M.; Ueda, T.; Nakao, M.; Tanaka,
Y.; Kusumi, T.; Nishino, T. Science. 2000, 290, 1163-1166.
10. Nakayama, T. J Biosci and Bioengineering 2002, 94, 487-491.
11. Adams, C.J.; Main, L. Tetrahedron. 1992, 48, 9929-9938.
12. Varma, R.S.; Varma, M. Tetrahedron Lett. 1992, 33, 5937-5940.
13. Donnelly, D.J.; Donnelly, J.A.; Keegan, J.R. Tetrahedron, 1977,
33, 3285-3288.
(d, J=8.6 Hz, 1H), 7.71 (d, J=7.45 Hz, 1H), 7.75 (d, J=5.75 Hz,
2H), 8.20 (d, J=6.3 Hz, 1H), 8.79 (d, J=6.3 Hz, 1H); 13C NMR
(500 MHz, CDCl3):
δ=109.34, 118.24, 119.86 (2C), 124.07,
124.73, 125.86, 134.43, 150.78 (2C), 156.20, 160.59, 178.22.
HRMS: M+, found 223.23100. C14H9NO2 requires 223.23100.
4.14. (Z)-2-(biphenyl-4-ylmethylene)benzofuran-3(2H)-one
(Table 1, entry 11)31
14. Bose, G.; Modal, E.; Khan, A.T.; Bordoloi, M.J. Tetrahedron Lett.
2001, 42, 8907-8909.
15. Thakkar, K.; Cushman, M. Tetrahedron Lett. 1994, 35, 6441-
6444.
16. Harkat, H.; Blanc, A.; Weibel, J.; Pale, P. J. Org. Chem. 2008, 73,
1620-1623.
mp = 63-68 °C.
IR ν=1702, 1646, 1597, 1486, 1461, 1299,
1209, 1185, 1150, 1128, 1109, 1007, 886, 838, 755, 729, 696 cm-
1; H NMR (500MHz, CDCl3): δ= 6.95 (s, 1H), 7.24 (t, J=7.45
1
17. Russ, C.; Koenig, B. Green Chem. 2012, 14, 2969-2982.
18. Abbott, A.P.; Frisch, G.; Hartley, J.; Ryder, K.S. Green Chem.
2011, 13, 471-481. Zhang, Q.; Vigier, K. D. O.; Royer, S.;
Jerome, F. Chem. Soc. Rev. 2012, 41, 7108-7146. Francisco, M.;
van den Bruinhorst, A.; Kroon, M.C. Angew. Chem. Int. Ed.
2013, 52, 3074-3085
Hz, 2H), 7.35-7.71 (m, 8H), 7.82 (d, J=8.55 Hz, 1H), 8.01 (d,
J=8.05 Hz, 2H). 13C NMR (500MHz, CDCl3): δ=112.84, 112.96,
121.67, 123.50, 124.70, 127.08, 127.36, 127.40, 127.52, 127.92,
128.26, 128.77, 128.93, 131.28, 132.04, 136.90, 140.08, 142.52,
146.94, 166.08, 184.75. HRMS: M+, found 298.34095. C21H14O2
requires 298.34096.
19. Abbott, A.P.; Capper, G.; Davies, D.L.; Rasheed, R.K.;
Tambyrajah, V. Chem. Commun. 2003, 70-71.
4.15. (Z)-2-((E)-3-phenylallylidene)benzofuran-3(2H)-one
(Table 1, entry 12)
20. Abbott, A.P.; Boothby, D.; Capper, G.; Davies, D.L.; Rasheed,
R.K. J. Am. Chem. Soc. 2004, 126, 9142-9147.
21. Singh, B.; Lobo, H.; Shankarling, G. Cat. Lett. 2011, 141, 178-
182. Pawar, P.M.; Jarag, K.J.; Shankarling, G.S. Green Chem.
2011, 13, 2130-2134. Phadtare, S.B.; Shankarling, G.S. Green
Chem. 2010, 12, 458-462.
22. Pelter, A.; Ward, R.S.; Heller, RH.G. J. Chem. Soc. Perkin
Trans.1 1979, 328-329.
23. Schreiner, P.R. Chem. Soc. Rev. 2003, 32, 289-296.
24. Imafuku, K.; Honda, M.; Mcomie, J.F.W. Synthesis 1987, 199-
201.
mp = 57-64 °C. IR ν=1699, 1638, 1608, 1475, 1462, 1298,
1198, 1149, 1117, 970, 879, 753, 698, 669 cm-1; 1H NMR
(500MHz, CDCl3): δ=6.78 (d, J=11.45 Hz, 1H) 7.02 (d, J=16.05
Hz, 1H), 7.18 (t, J=7.45 Hz, 1H), 7.24-7.38 (m, 6H), 7.54 (d,
J=7.45 Hz, 1H), 7.62 (t, J=8.6 Hz, 1H), 7.76 (d, J=7.45 Hz, 1H);
13C NMR (500 MHz, CDCl3):
δ=112.58, 114.44, 120.79, 122.42,
123.34, 124.62, 127.55 (2H), 128.98 (2H), 129.46, 136.39,
136.80, 141.52, 147.46, 165.52, 183.91. HRMS: M+, found
248.28106. C17H12O2 requires 248.28108.
25. Morimoto, M.; Fukumoto, H.; Toki, H.A.; Komai, K. J. Ag. &
Food Chem. 2007, 55, 700-705.
26. Detsi, A.; Majdalani, M.; Kontogiorgis, C.A.; Hajipavlou-Litina,
D.; Kefalas, P. Bioorg.& Med. Chem. 2009, 17, 8073-8085.
27. Donnelly, J.A.; Emersosns, G.M. Tetrahedron 1990, 46, 7227-
7236.
4.16. (Z)-2-(furylmethylene)benzofuran-3(2H)-one
entry 13)
(Table 1,
28. Paronav, T.; Bognar, R.; Litkei, G. Tetrahedron 2984, 40, 2555-
2562.
29. Manjulatha, K.; Srinivas, S.; Mulakayala, N.; Rambabu, B.D.;
Prabhakar, M.;Arunasree, K.M.; Pal, M. Bioorg. & Med. Chem.
Lett. 2012, 22, 6160-6165.
30. Donnelly, D.J.; Donnelly, J.A.; Keegan ,J.R. Tetrahedron 1977,
33, 3289-3294.
31. Bobbitt, J.M.; Katritzk, A.R.; Kennewel, P.D.; Snarey, M. J.
Chem. Soc.B 1968, 550.
mp = 66-68 °C. IR ν=1730, 1650, 1610, 1480, 1300, 1190,
1105, 850, 760 cm-1; 1H NMR (500MHz, CDCl3): δ=6.56 (br s,
1H) 6.85 (s, 1H), 7.10 (d, J=3.45 Hz, 1H), 7.17 (t, J = 8.0 Hz,
1H), 7.27 (d, J = 8.6 Hz, 1H), 7.61-7.57 (m, 2H), 7.75 (d, J=8.6
Hz, 1H); 13C NMR (500 MHz, CDCl3):
δ=101.57, 112.81,
113.11, 117.24, 121.87, 123.39, 124.41, 136.62, 144.87, 145.34,
148.65, 165.59, 183.90. HRMS: M+, found 196.05241. C13H8O2
requires 196.05243
32. Jimenez, M.C.; Miranda, M.A.; Tormos, R.; Tetrahedron 1997,
53, 1472-14736.
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5. References and notes
1. Boumendjel, A. Cur. Med. Chem. 2003, 10, 2621-2630.