An eco-benign and high speed protocol for the synthesis of 2-aroyl-3,5-diarylfuran derivatives using Teflon-supported iodine

Article abstract of DOI:10.1007/s00706-017-2061-2

Abstract: A new, practical, and convenient approach has been established for the expeditious synthesis of bioactive 2-aroyl-3,5-diarylfurans in excellent yields using a iodine-impregnated Teflon by a microwave-promoted process. The products are isolated w

Full text of DOI:10.1007/s00706-017-2061-2

Monatsh Chem
DOI 10.1007/s00706-017-2061-2
ORIGINAL PAPER
An eco-benign and high speed protocol for the synthesis of 2-
aroyl-3,5-diarylfuran derivatives using Teflon-supported iodine
Arash Mouradzadegun1,2 Mohammad Reza Ganjali2,3 Fatemeh Abadast1
Fatemeh Rahimi1
•
•
•
Received: 5 July 2017 / Accepted: 17 September 2017
Ó Springer-Verlag GmbH Austria 2017
Abstract A new, practical, and convenient approach has
been established for the expeditious synthesis of bioactive
2-aroyl-3,5-diarylfurans in excellent yields using a iodine-
impregnated Teflon by a microwave-promoted process.
The products are isolated without tedious aqueous work-up
in high purity. The microwave accelerated the reaction and
renders the whole synthesis into a truly eco-friendly
protocol.
Keywords 2-Aroyl-3,5-diarylfurans Á Heterocycles Á
Iodine-impregnated Teflon Á Green chemistry Á
Microwave-assisted synthesis
Introduction
Furan derivatives are a widespread sub-unit in numerous
natural products which exhibit a wide range of biological
activities and appear as key structural units in many
important pharmaceuticals and other materials [1–6].
Among them, 2-aroylfuran derivatives have attracted
tremendous attention due to their unique position in
medicinal chemistry which has tuberculostatic activities
[7–10]. Moreover, these molecules have found used as key
intermediates toward two enantiomers of frontalin [3], a
bark beetle pheromone that has useful control activities
against harmful insect infestations [11–15].
Graphical abstract
.
In view of different biological and chemical applications
of such type of molecules, the development of suit-
able synthetic methodologies for their generation has been
a topic of great interest in recent times. Generally,
2-aroylfuran derivatives are synthesized by the reaction of
pyrylium salts with O-nucleophiles in the presence of a
base and iodine [16]. However, this reaction has several
drawbacks, such as the need for extended reaction times
(e.g., 18 h for pyrylium salt 1a), poor yields (53% for 1a),
and complicated and often laborious workup and purifica-
tion steps. Therefore, a need still exists for further
development of versatile reaction conditions in synthesis of
these molecules.
Electronic supplementary material The online version of this
article (doi:10.1007/s00706-017-2061-2) contains supplementary
material, which is available to authorized users.
& Arash Mouradzadegun
arash_m@scu.ac.ir
1
Department of Chemistry, Faculty of Science, Shahid
Chamran University of Ahvaz, Ahvaz, Iran
2
Center of Excellence in Electrochemistry, University of
Tehran, Tehran, Iran
Recently, Teflon-supported materials were used as an
efficient catalyst and reactant for the preparation and
application of different reactions [17–19]. These materials
could exhibit high activity and stability in the reaction
3
Biosensor Research Center, Endocrinology & Metabolism
Molecular-Cellular Sciences Institute, Tehran University of
Medical Sciences, Tehran, Iran
123

A. Mouradzadegun et al.
media and can be readily recovered and reused several
times without significant loss of activity.
Following these tests, the target reaction was carried out
at different power and temperatures of microwave reactor
under similar conditions. The experimental results per-
suaded us that among all tested systems, 90 °C (800 W) is
the most effective system for this transformation. It was
found that increasing the temperature did not improve the
reaction rate, while reducing the temperature led to lower
yields. Predictably, it was observed that in the absence of
solvent under microwave irradiation, reaction rate
increased enormously and desired product was obtained in
high yields (Table 2, entry 1).
Under this light, in continuation of our studies directed
towards the development of practical and eco-friendly
procedures for some important transformations [20–23],
and our new interest in the synthesis of biologically
important molecules [24–27], in the present work, we
report a simple and high performance approach towards the
synthesis of bioactive 2-aroylfuran derivatives via ring
transformation of readily accessible pyrylium salts assisted
by microwave irradiation.
To further examine the efficacy of this synthetic
opportunity, the process is illustrated with various tri-
arylpyrylium perchlorates contain electron-donating and
withdrawing groups in the para position of substituted
phenyl rings with sodium carbonate and iodine under the
optimized reaction conditions (Table 2).
Results and discussion
Pyrylium salts are one of the elegant precursors for the
synthesis of 2-aroylfuran compounds due to their easy
availability and high reactivity [28, 29]. Nucleophilic
addition of hydroxide ion in basic media to the a-position
of these salts affords red-colored anion of the pseudobase
2a. This anion was similarly, although more slowly, con-
verted to the furan 3a when oxidized with iodine [16]. In
reported experiments, this conversion is restricted only to
2,4,6-triphenylpyrylium perchlorate (Scheme 1).
The structure of products was settled from their physical
1
and spectroscopic (IR, H NMR, 13C NMR) data. As is
evident from Table 1, besides model compound (entry 1),
other substituted triarylpyrylium perchlorates also gave the
expected products in high yields and short reaction times.
However, no significant substituent effect was found in
case of substrates.
Due to the low rate and poor yield this conversion, also
the increasing importance of solvent-free and microwave
irradiation in green synthesis of heterocyclic compounds,
herein, we report our results for a solvent-free microwave
reaction protocol that leads to a facile preparation of
2-aroylfuran from the corresponding pyrylium salts.
Preliminary tests were carried out to survey the requisite
reaction conditions and establish the modifications required
for this methodology. Triphenylpyrylium perchlorate was
chosen as the model compound to identify and optimize the
reaction conditions. For this purpose, the conversion of
model compound to the corresponding 2-aroylfuran was
studied on various solid support materials and I2 quantity to
identify and optimize the ideal support. The best result was
obtained in the presence of sodium carbonate and other
attempts in the absence of solid phases were not successful
(Table 1).
In fact that excess iodine in reaction media complicates
workup of this conversion, suggested that we ought to
examine a new strategy in which the reaction of pyrylium
perchlorates investigated in the presence of iodine-im-
pregnated Teflon. For this purpose, we soak Teflon strips
into the acetone solution of iodine and then dried in air
(Fig. 1; see video in ESI). The development of such ‘‘dip-
sticks’’ is extremely attractive as instant qualitative infor-
mation without resorting to any additional equipment.
When we treated the model substrate triphenylpyrylium
perchlorate (1a) with the iodine-impregnated Teflon, we
obtained desired product 3a in excellent yield without
complicated and often laborious workup and purification
steps.
Encouraged by this observation, further experiments
were designed to survey this strategy in the same reaction.
In this regard, the model reaction was investigated in the
presence of various amounts of iodine-impregnated Teflon.
Scheme 1
123

An eco-benign and high speed protocol for the synthesis of 2-aroyl-3,5-diarylfuran…
Table 1 The conversion of model compound 1a (0.1 mmol) into the corresponding 2-aroylfuran derivative 3a in the presence of various solid
support materials and I2 quantity
Entry
Solid support
Amount of solid support/g
Amount of iodine/mmol
Time/min
Yield 3a/%
1
2
3
4
5
6
7
8
9
Basic Amberlite resin
Basic alumina
Na2CO3
1
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.3
0.2
20
20
5
42
34
76
23
75
75
69
75
71
1
1
–
–
20
5
Na2CO3
0.8
0.5
0.4
0.5
0.5
Na2CO3
5
Na2CO3
5
Na2CO3
5
Na2CO3
5
Table 2 The conversion of various triarylpyrylium salts 1 into the corresponding 2-aroylfuran derivatives 3 using sodium carbonate and iodine
under microwave irradiation
Entry
Ar1
Ar2
Prod.
Time/min
Yield of 3/% (I2)
Yield of 3/% (I2-impregnated Teflon)
1
2
3
4
5
6
Ph
Ph
3a
3b
3c
3d
3e
3f
5
6
5
8
5
4
75
69
80
65
72
85
98
96
97
91
94
97
Ph
p-MeO-Ph
Ph
p-MeO-Ph
p-MeO-Ph
Ph
p-Me-Ph
p-Cl-Ph
p-NO2-Ph
Ph
As shown in Table 3, the use of 5 mM of iodine is the best
(entry 2).
Excess amount of iodine supported on Teflon could
reuse for the next run. For this purpose, after completion of
each reaction, the Teflon was removed and dried in air,
then reused for the next run. The results illustrated in Fig. 2
showed that the iodine-impregnated Teflon can be reused
for up to five cycles with excellent yields.
To further examine the efficacy of this synthetic
opportunity, the process is illustrated with various tri-
arylpyrylium perchlorates contain electron-donating and
withdrawing groups in the para position of substituted
phenyl rings (Table 2).
This protocol therefore offers the possibility of consid-
erably decreasing the reaction time and improving the yield
in comparison with conventional conditions. In addition,
the Teflon-supported iodine is much less hazardous to use
Fig. 1 a Teflon strip, Teflon-supported iodine, b before the reaction,
c after the reaction
123

A. Mouradzadegun et al.
at 400 and 100 MHz, respectively, in CDCl3 with tetram-
ethylsilane as an internal standard. Micro-SYNTH
labstation, complete with glass door, dual magnetron sys-
tem with pyramid-shaped diffuser, 1000 W delivered
power, exhaust system, magnetic stirrer, ‘‘quality pressure’’
sensor for flammable organic solvents, and ATCFO fiber
optic system for automatic temperature control.
Table 3 The conversion of model compound 1a into the corre-
sponding 2-aroylfuran derivative 3a in the presence of various amount
of iodine-impregnated Teflon
Entry
Amount of I2-impregnated
Teflon (mM)
Yield 1a/%
1
2
3
4
10
5
98
98
96
95
3
General procedure for the synthesis
of triarylpyrylium perchlorates
2
All triarylpyrylium perchlorates were synthesized from the
corresponding aldehydes and ketones by the method pre-
viously described [28, 29]. Briefly, the corresponding
benzaldehyde (0.1 mol) and acetophenone (0.2 mol) were
stirred at room temperature, 6 cm3 sulfuric acid was added
dropwise during 30 min. The mixture was stirred at 100 °C
for 60 min. Then, 200 cm3 ethanol and 10 cm3 perchloric
acid (70%) was added. The mixture was excluded to form a
precipitate for 24 h. The precipitates recrystallized from
acetic acid.
General procedure for the synthesis of 2-aroyl-3,5-
diarylfuran derivatives in solvent conditions
Fig. 2 Reusability of iodine-impregnated Teflon
A
mixture
of
2,4,6-triarylpyrylium
perchlorate
because the iodine residues are retained on the Teflon, and
are not extracted into the reaction media. These aspects
point to this being an atom-efficient process that produces
less waste than would otherwise have arisen from the use
of excess reagents.
(2.52 mmol) in 50 cm3 acetone and 5 cm3 aqueous sodium
carbonate (1 M) was stirred for 2 h. Iodine (2 g,
7.88 mmol) was added and stirring was continued at reflux
temperature. The reactions were monitored by TLC using
ether/n-hexane (1:4) as eluent. After completion of the
reaction, the solvent was evaporated under vacuum,
residual was adsorbed on silica and mounted on a silica
column and eluted with a 20:80 mixture of ether:n-hexane.
The upper band is collected, solvent removed, and
recrystallized in EtOH.
Conclusion
In summary, iodine-containing Teflon was successfully
used in a high-yielding and clean conversion of a range of
triarylpyrylium perchlorates into 2-aroylfuran derivatives.
Because of its operational simplicity, this effective syn-
thetic route minimizes environmental impact in many
ways, including ease of manipulation and workup, better
control of hazardous iodine, and shorter reaction times. We
expect that this green and practical protocol will be useful
in academic research and in pharmaceutical development.
General procedure for the synthesis of 2-aroyl-3,5-
diarylfuran derivatives under microwave
irradiation
The 2,4,6-triarylpyrylium perchlorate (0.1 mmol) was
added to 0.5 g of wet sodium carbonate in a mortar (this
ratio was optimized under our experimental condition),
after homogenizing 0.3 mmol of iodine gradually added in
portion and the mixtures were grinded for further homog-
enization, then irradiated at 90 °C (800 W) for the
appropriate time. The reactions were monitored by TLC
using ether/n-hexane (1:4) as eluent. After completion of
the reaction, the residual was adsorbed on silica and
mounted on a silica column and eluted with a 20:80 mix-
ture of ether:n-hexane. The upper band is collected, solvent
removed, and recrystallized in EtOH.
Experimental
Chemicals were purchased from Fluka, Merck, and Aldrich
chemical companies. Monitoring of the reactions was
accomplished by TLC. IR spectra were obtained on a
1
Bomen MB:102 FT-IR spectrophotometer. H NMR and
13C NMR spectra were recorded on a Bruker spectrometer
123

An eco-benign and high speed protocol for the synthesis of 2-aroyl-3,5-diarylfuran…
The preparation of Teflon-supported iodine
(ArC), 129.5, 130.9 (ArCq), 132.0 (ArC), 137.3 (ArCq),
138.1 (C-2), 145.6, 155.6, 160.3 (ArCq), 162.8 (C-5), 181.8
(C-1) ppm.
Iodine was absorbed into Teflon strip by immersing the
Teflon in a solution of the iodine (5 mM) in acetone. It was
allowed to stand for about 5 s, so the iodine could
impregnate the Teflon strip. A deep brown Teflon-sup-
ported iodine strip was obtained.
[3-(4-Chlorophenyl)-5-phenyl-2-furyl](phenyl)methanone
(3e, C23H15ClO2)
Yellow crystals; m.p.: 106–108 °C (from EtOH); IR (neat):
vꢀ = 1632 (CO) cm-1
;
1H NMR (400 MHz, CDCl3):
d = 6.96 (s, 1H, H1), 7.35–8.00 (m, 14H, Ar–H) ppm;
13C NMR (100 MHz, CDCl3): d = 109.5 (C-4), 124.9,
128.1, 128.3, 129.02 (ArC), 129.06 (C-3), 129.4 (ArCq),
129.7, 130.5, 130.6, 132.3 (ArC), 134.4 (ArCq), 136.4 (C-
2), 137.9, 145.9 (ArCq), 156.0 (C-5), 183.3 (C-1) ppm.
General procedure for the synthesis of 2-aroyl-3,5-
diarylfuran derivatives in the presence of Teflon-
supported iodine under microwave irradiation
2,4,6-Triarylpyrylium perchlorate (0.1 mmol) was added to
0.5 g of wet sodium carbonate in a mortar, after homoge-
nizing, the mixture was spread on the Teflon-supported
iodine sheet, then irradiated at 90 °C (800 W) for the
appropriate time. The reactions were monitored by TLC
using ether/n-hexane (1:4) as eluent. After completion of
the reaction, Teflon-supported iodine was removed and the
product was extracted by ether then recrystallized in EtOH.
[3-(4-Nitrophenyl)-5-phenyl-2-furyl](phenyl)methanone
(3f, C23H15NO4)
Yellow crystals; m.p.: 122–124 °C (from EtOH); IR (neat):
;
vꢀ = 1640 (CO), 1343, 1518 (NO2) cm-1 1H NMR
(400 MHz, CDCl3): d = 7.02 (s, 1H, H1), 7.46–8.28 (m,
14H, Ar–H) ppm; 13C NMR (100 MHz, CDCl3):
d = 109.3 (C-4), 123.4, 125.0, 128.3 (ArC), 128.7 (ArCq),
129.1 (ArC), 129.6 (C-2), 129.7, 130.1, 132.7 (ArC), 135.1,
137.4, 138.9, 147.5 (ArCq), 156.4 (C-5), 183.1 (C-1) ppm.
(3,5-Diphenyl-2-furyl)(phenyl)methanone (3a)
Yellow crystals; m.p.: 117–119 °C (from EtOH) (Ref. [16]
117–118 °C).
Acknowledgements This work was supported by the Research
Council at the University of Shahid Chamran.
[3-(4-Methoxyphenyl)-5-phenyl-2-furyl]-
(phenyl)methanone (3b, C24H18O3)
Yellow crystals; m.p.: 121–123 °C (from EtOH); IR (neat):
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vꢀ = 1638 (CO) cm-1
;
1H NMR (400 MHz, CDCl3):
d = 3.85 (s, 3H, OCH3), 6.90–6.95 (d, 2H, Ar–H), 6.98
(s, 1H, H1), 7.38–7.99 (m, 12H, Ar–H) ppm; 13C NMR
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;
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