One-pot synthesis of 3,4-diaryl-substituted 2(5 H)-furanone and its commercial application

Article abstract of DOI:10.1080/00397911.2011.577923

One-pot synthesis of 3,4-diaryl substituted 2(5H)-furanones was established and its commercial application has been demonstrated by accomplishing total synthesis of rofecoxib, under mild reaction conditions, with good yields and purity.

Full text of DOI:10.1080/00397911.2011.577923

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One-Pot Synthesis of 3,4-Diaryl-
Substituted 2(5H)-Furanone and Its
Commercial Application
Anil Argade a b , Jigar Desai a , Pravin Thombare a , Kiran Shah a
, Sanjay Gite a , Vijay Prajapati a , Bipin Pandey a , Mukul Jain a ,
Pankaj Patel a & Rajesh Bahekar a
a Zydus Research Centre, Ahmedabad, India
b Department of Chemistry, Faculty of Science, M. S. University of
Baroda, Vadodara, India
Accepted author version posted online: 10 Jan 2012.Version of
record first published: 17 Aug 2012.
To cite this article: Anil Argade, Jigar Desai, Pravin Thombare, Kiran Shah, Sanjay Gite, Vijay
Prajapati, Bipin Pandey, Mukul Jain, Pankaj Patel & Rajesh Bahekar (2012): One-Pot Synthesis of 3,4-
Diaryl-Substituted 2(5H)-Furanone and Its Commercial Application, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 42:21, 3140-3149
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Synthetic Communications1, 42: 3140–3149, 2012
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2011.577923
ONE-POT SYNTHESIS OF 3,4-DIARYL-SUBSTITUTED
2(5H)-FURANONE AND ITS COMMERCIAL
APPLICATION
Anil Argade,1,2 Jigar Desai,1 Pravin Thombare,1 Kiran Shah,1
Sanjay Gite,1 Vijay Prajapati,1 Bipin Pandey,1 Mukul Jain,1
Pankaj Patel,1 and Rajesh Bahekar1
1Zydus Research Centre, Ahmedabad, India
2Department of Chemistry, Faculty of Science, M. S. University of Baroda,
Vadodara, India
GRAPHICAL ABSTRACT
Abstract One-pot synthesis of 3,4-diaryl substituted 2(5H)-furanones was established and
its commercial application has been demonstrated by accomplishing total synthesis of
rofecoxib, under mild reaction conditions, with good yields and purity.
Keywords Diethylphosphono phenyl acetic acid; furanone; Horner–Wadsworth–
Emmons reaction; phenacyl bromides; rofecoxib
INTRODUCTION
2(5H)-Furanones (butenolides) constitute an important class of oxygen hetero-
cycles, found in several natural products and drugs with diverse biological activities
such as antifungal, antibacterial, antiulcer, antitumor, insecticidal, cytotoxic, anti-
microbial, and anti-inflammatory activities.[1–3] Rofecoxib (1) is one of the well-
established bioactive drugs containing the 2(5H)-furanone ring system as an active
pharmacophore.[4] It is a cyclooxygenase-2 (COX-2) inhibitor and exhibits
anti-inflammatory, analgesic, and antipyretic activities.[5]
Knowing the pharmacological implication of furanone’s ring system, various
synthetic routes have been documented for the preparation of mono- and disubsti-
tuted 2(5H)-furanone derivatives,[6] and overall, synthesis of 3,4-diaryl=4-aryl-
derivatives of 2(5H)-furanone is more challenging than that for the corresponding
three- or five-substituted analogs.[7,8] The majority of literature methods reported
Received January 20, 2011.
ZRC Communication No. 327 (part of A. Argade’s PhD work).
Address correspondence to Rajesh Bahekar, Zydus Research Centre, Sarkhej-Bavla N.H. 8A
Moraiya, Ahmedabad 382210, India. E-mail: rajeshbahekar@zyduscadila.com
3140

3,4-DIARYL-SUBSTITUTED 2(5H)-FURANONES
3141
for the synthesis of substituted 2(5H)-furanones involve transition-metal-catalyzed
coupling, palladium-catalyzed coupling reactions (Stille or Suzuki coupling, Suzuki–
Miyaura cross-coupling) or use of expensive catalysts such as Grubbs catalyst.[7–10]
Considering the biological importance and synthetic challenges of 3,4-diaryl-
substituted 2(5H)-furanone derivatives, in the present communication, a one-pot,
high-yielding synthesis of 3,4-diaryl-substituted 2(5H)-furanones, involving a intra-
molecular Horner–Wadsworth–Emmons-type cyclization reaction under mild
conditions, has been reported. The generality of an efficient transformation has
been demonstrated via several examples. Mechanistically, an involvement of the
key intermediate has also been established based on precedence and experimental
design. Furthermore, the commercial application of this one-pot synthesis has been
demonstrated by accomplishing the total synthesis of rofecoxib.
In the past two decades, several methods have been disclosed for the synthesis
of rofecoxib.[5,11–15] In the original patent published by Merck, rofecoxib was synthe-
sized in three steps, starting from 4-(methylthio)acetophenone, using a cycloconden-
sation strategy.[11] In another approach, a Suzuki coupling strategy was employed
for the introduction of the second aryl group, while regioselective synthesis of rofe-
coxib was carried out using ruthenium-catalyzed lactonization of diarylacety-
lene.[12,13] A significant amount of undesired by-product formation is one of the
major drawbacks of this process. Desmond et al.[11] and Ducharme et al.[12] disclosed
multistep syntheses of rofecoxib, which involve conversion of phenyl acetic acid to
its corresponding 3-phenyl-4-(methylthio)phenyl-2-(5H)-furanone via intermediate
keto ester and 4-methylthio-phenylboric acid formation, which upon oxidation gives
the final product. This particular synthetic strategy involves expensive reagents and
multistep operations. Black et al.[14] disclosed a multistep synthesis of rofecoxib that
involves Friedel–Crafts acylation of thioanisole. Atkinson et al.[15] reported synthesis
of 2(5H)-furanone derivatives using expensive catalysts (palladium (PdCl2) or
rhodium [Rh6(CO)16)], with poor yield and purity.
Earlier, an efficient method for the synthesis of 4-aryl-substituted 2(5H)-
furanones starting from diethylphosphono acetic acid and phenacyl bromides, using
strong base diazabicycloundec-7-ene (DBU), has been reported.[16] However, this
method was for the synthesis of only mono-substituted 2(5H)-furanones. In continu-
ation, herein we extend the scope of intramolecular Horner–Wadsworth–
Emmons-type cyclization reaction under very mild conditions for efficient and
one-pot synthesis of 3,4-diaryl substituted 2(5H)-furanones.
As shown in Scheme 1 (method A), one-pot synthesis of 4-[4-(methylsulfonyl)
phenyl]-3-phenyl-2(5H)-furanone (rofecoxib, 1) was carried out by reacting

3142
A. ARGADE ET AL.
Scheme 1. Synthesis of rofecoxib [method A (new method) and method B (lit. method[5b])].
2-bromo-1-(4-methanesulfonyl-phenyl)-ethanone (2) and (dialkoxy-phosphonyl)-
phenyl-acetic acid (3a) in the presence of triethylamine (TEA) in dimethylforma-
maide (DMF) at room temperature. Typically, using this one-pot synthesis protocol,
rofecoxib can be prepared in 2 h, in good yield (90%), and the crude product
obtained after filtration was sufficiently pure (99% purity).
Previously, Therien et al.[5b] reported a two-step synthesis of rofecoxib by
reacting compound 2 with phenyl acetic acid (3b) in the presence of triethylamine
(TEA) to get ester intermediate (in situ), followed by 1,8-diazabiyclo[5.4.0]undec-7-
ene (DBU)–assisted cyclization (Scheme 1; method B). Despite using a strong
base (DBU), the overall yield was 54%, and the pure rofecoxib was obtained after
chromatographic purification. One of the plausible explanations for getting poor
yields (method B) could be the less acidity of the a-proton in the phenyl acetic acid
derivative.
Thus, introduction of diethyl phosphate group at the a-position in phenyl
acetic acid (method A) resulted in an increased acidity of a-hydrogen, which makes
reaction more facile and together led to a one-pot synthesis of 3,4-diaryl-substituted
2(5H)-furanones, even in the presence of a mild base such as TEA.
Further to confirm that one-pot intramolecular Horner–Wadsworth–Emmons-
type cyclization reaction proceed via highly reactive phosphonate ester intermediate
formation, synthesis of rofecoxib was attempted via an alternate route (Scheme 2).
Scheme 2. Two-step synthesis of rofecoxib.

3,4-DIARYL-SUBSTITUTED 2(5H)-FURANONES
3143
Figure 1. Proposed reaction mechanism for the one-pot synthesis of rofecoxib.
Compounds 2 and 3a were reacted in the presence of dichloromethane (DCM) in
DMF at 0 ꢀC to isolate intermediate phosphonate ester 4 (HPLC purity 98.20%;
yield: 92%). Incubation of compound 4, in TEA and DMF at 30 ꢀC, leads to the for-
mation of rofecoxib (1) via intramolecular cyclization (HPLC purity 98.83%; yield:
95%). Thus, formation and isolation of intermediate phosphonate ester (4), under
mild reaction condition (Scheme 2) confirms that the one-pot intramolecular
Horner–Wadsworth–Emmons-type cyclization reaction in Scheme 1, actually pro-
ceeds via highly reactive phosphonate ester intermediate formation.
As shown in Fig. 1, the one-pot synthesis of rofecoxib (Scheme 1) begins with
the nucleophilic substitution reaction to give intermediate phosphonate ester. After
phosphonate formation, it is postulated that this one-pot reaction proceeds via an
intramolecular Horner–Wadsworth–Emmons-type cyclization pathway, which
involves deprotonation of the phosphonate ester to get phosphonate carbanion.
Intramolecular nucleophilic addition of this carbanion to ketone gives oxapho-
sphetane (via C-C bond rotation and betaine formation) and finally, elimination
of the phosphonate group leads to the formation of the desired alkene (rofecoxib).
Overall, an electron-withdrawing group (EWG; phenyl ring) at the a-position to
the phosphonate group is essential for the final elimination of the phosphonate
group.
Finally, to broaden the commercial application and scope of this one-pot reaction
with respect to diversified aryl substitutions, eight derivatives of 3,4-diaryl-substituted
2(5H)-furanones were prepared as depicted in Scheme 3 and Table 1. Two sets of com-
pounds were prepared either by introducing electron-donating groups (EDG), such as
Scheme 3. General scheme for the synthesis of 3,4-diaryl-substituted 2(5H)-furanones.

3144
A. ARGADE ET AL.
Table 1. Reactivity comparison of various substituents at 3,4-positions of 2(5H)-
furanones (1a–h)
Compounds
R1
R2
Time (h)a
Purity (%)b
Yield (%)
1a
1b
1c
1d
1e
1f
4-Me-Ph-
4-OMe-Ph-
4-F-Ph-
4-NO2-Ph-
Ph-
Ph-
Ph-
Ph-
Ph-
2
2
2
2
4
4
1
1
97.61
97.33
98.01
97.96
97.15
98.09
97.99
97.08
90.02
91.11
90.07
91.5
4-Me-Ph-
4-OMe-Ph-
4-F-Ph-
90.96
90.03
91.01
91.18
Ph-
Ph-
1g
1h
Ph-
4-NO2-Ph-
aReaction completion time monitored with TLC.
bPurity of compounds analyzed by HPLC at kmax 220 nm using column ODS C-18,
150 cm ꢁ 4.6 mm ꢁ 4 mm on AGILENT 1100.
methyl and methoxy groups at the para-position of either of the phenyl rings (com-
pounds 1a, 1b, 1e and 1f), or electron-withdrawing groups (EWG), such as fluoro
and nitro groups at the para-position of either of the phenyl rings (compounds 1c,
1d, 1g and 1h), and all the eight compounds were isolated with purity >97% and yield
>90% (Table 1). However, it was interesting to observe that compounds 1e and 1f
(EDG at R2 position) took relatively longer reaction time (4 h) than compounds 1g
and 1h (EWG at R2 position, with 1 h reaction time). Similar substitutions at R1 showed
no difference the reactivity (reaction time same as rofecoxib, 2 h), which confirms
that an increase in the electronegativity at the a-position to the phosphonate group
facilitates one-pot intramolecular Horner–Wadsworth–Emmons-type cyclization
reaction and overall elimination of the phosphonate group as the rate-limiting step.
Thus, the flexibility in the usage of different starting materials (substituted phenacyl
bromides (2a–e) and diethylphosphono phenyl acetic acids (3a, c–f; Scheme 3) broaden
the scope of this one-pot reaction toward the synthesis of 3,4-diaryl substituted
2(5H)-furanones.
In summary, this novel one-pot synthetic procedure overcomes numerous
drawbacks of earlier reported procedures and possesses several advantages: (a) It
involves operational simplicity and fewer steps, thereby the time cycle required for
the synthesis of substituted 3,4-diaryl substituted 2(5H)-furanones has been drasti-
cally reduced, which makes the process commercially viable. (b) It involves
high-yielding solution-phase chemistry, flexibility in the usage of substituted starting
materials, and mild reaction conditions, which facilitate its commercial scalability
and overall cost-effectiveness.
CONCLUSION
In conclusion, we demonstrated a novel and highly efficient one-pot synthesis
of 3,4-diaryl-substituted 2(5H)-furanones, accomplished with the total synthesis of
rofecoxib (1), which overcomes several drawbacks and operational difficulties of
earlier reported procedures and establishes sufficient evidence to confirm our obser-
vations that this proposed one-pot reaction proceeds via intramolecular Horner–
Wadsworth–Emmons-type cyclization pathway.

3,4-DIARYL-SUBSTITUTED 2(5H)-FURANONES
3145
EXPERIMENTAL
Melting points were recorded on open glass capillaries, using a scientific
melting-point apparatus and are uncorrected. Infrared (IR) spectra were recorded
on a Shimadzu Fourier transform (FT)–IR 8300 spectrophotometer (Vmax in cmꢂ1
,
1
using KBr pellets). The H and 13C NMR spectra were recorded on a Brucker
Avance-400 spectrometer (400 and 100 MHz respectively). The chemical shifts (d)
are reported in parts per million (ppm) relative to tetramethylsilane (TMS), either
in acetone-d6, CDCl3, or dimethylsulfoxide (DMSO-d6) solution. Signal multiplici-
ties are represented by s (singlet), d (doublet), dd (doublet of doublet), t (triplet),
q (quartet), bs (broad singlet), and m (multiplet). Mass spectra (ESI-MS) were
obtained on Shimadzu LC-MS 2010-A spectrometer. Elemental analyses were car-
ried out using a Perkin-Elmer 2400 CHN analyzer, and values within limit of
ꢃ0.4% of the theoretical values were taken into consideration. High-performance
liquid chromatographic (HPLC) analysis were carried out at kmax 220 nm using col-
umn ODS C-18, 150 cm ꢁ 4.6 mm ꢁ 4 mm on an Agilent 1100 series instrument. All
the chemicals used for the synthesis were purchased from Aldrich Company Limited,
Dorset (UK).
Preparation of 4-(4-(Methylsulfonyl)phenyl)-3-phenylfuran-2(5H)-
one (1)
2-(Diethoxyphosphino)-2-phenylacetic acid (5 g, 18.3 mmol; 3a) was added to a
mixture of 2-bromo-1-(4-(methylsulfonyl)phenyl)ethanone (5.09 g, 18.3 mmol; 2) in
DMF (50 mL) under a nitrogen atmosphere. The reaction mixture was cooled to
0ꢀC, and TEA (7.94 mL, 55.0 mmol) was added. Further, the mixture was stirred
at 30ꢀC for 2 h and quenched in ice-cold water (200 mL). The precipitated compound
was filtered, washed with acetone, and dried under reduced pressure to afford the
title compound as a yellow solid (4.5 g, 92%), mp 203–204 ꢀC, lit mp 204.7 ꢀC[5b]
HPLC purity: 98.83%; IR (KBr, cmꢂ1): 3481, 3018, 1745, 1747, 1446, 1340; ESI
1
(m=z) 315.06 (M þ H); H NMR (acetone-d6): d ¼ 3.15 (s, 3H), 5.37 (s, 2H), 7.32
(m, 2H), 7.42 (m, 3H), 7.68 (d, 2H, J ¼ 8.46 Hz), 7.96 (d, 2H, J ¼ 8.47 Hz); 13C
(DMSO-d6): d ¼ 43.1, 70.9, 126.9, 127.4, 128.7, 128.8, 128.9, 129.1, 129.8, 135.8,
142.0, 156.0, 172.4 ppm. Elemental analyses found (calcd.): C, 64.95 (64.92); H,
4.49 (4.52); O, 20.36 (20.37); S, 10.20 (10.18).
Preparation of 2-(4-(Methylsulfonyl)phenyl)-2-oxoethyl
2-(Diethoxyphosphoryl)-2-phenylacetate (4)
Compound 3a (5 g, 18.3 mmol) was added to a mixture of compound 2 (5.09 g,
18.3 mmol) in DCM (50 mL) under a nitrogen atmosphere. The reaction mixture was
cooled to 0ꢀC, and TEA (3.97 mL, 27.5 mmol) was added to the reaction mixture at
0 ꢀC and stirred for 1h. The reaction mixture was quenched in water (100 mL) and
extracted with ethyl acetate (100 mL ꢁ 3), the organic layer was dried over sodium
sulfate (15 g), and the solvent was removed under reduced pressure to afford the
intermediate compound 4, as a thick oil (7.9 g, 92%). HPLC purity: 98.20%; IR
(KBr, cmꢂ1): 3018, 2410, 1747, 1761, 1321, 1153; ESI (m=z) 469.19 (MþH);

3146
A. ARGADE ET AL.
1H NMR (acetone-d6): d 1.16 (t, 3H, J ¼ 7.02 Hz), 1.28 (t, 3H, J ¼ 7.05 Hz), 3.07 (s,
3H), 3.95 (m, 1H), 4.06 (m, 3H), 4.39–4.47 (d, 1H, J ¼ 23.64 Hz), 5.36 (d, 2H,
J ¼ 4.02 Hz), 7.35 (d, 3H, J ¼ 6.21 Hz), 7.52 (d, 2H, J ¼ 6.93 Hz), 8.04 (s, 4H); 13C
NMR (DMSO-d6): d ¼ 14.2, 40.6, 41.1, 62.3, 75.7, 126.5 127.2, 128.9, 129.6, 135.0,
142.3, 196.6 ppm. Elemental analyses found (calcd.): C, 53.84 (53.87); H, 5.38
(5.41); O, 27.32 (27.35); P, 6.61 (6.59); S, 6.85 (6.88).
Preparation of 4-(4-(Methylsulfonyl)phenyl)-3-phenylfuran-2(5H)-
one (1)
Compound 4 (5 g, 10.7 mmol) was dissolved in DMF (50 mL) under a nitrogen
atmosphere. The reaction mixture was cooled to 0ꢀC, and TEA (4.45 mL, 32.1 mmol)
was added. Further, the mixture was stirred at 30ꢀC for 2 h and quenched in ice-cold
water (200 mL). The precipitated compound was filtered, washed with acetone, and
dried under reduced pressure to afford the title compound 1 as a yellow solid (3.2 g,
95%), mp 203–204 ꢀC. HPLC Purity: 98.83%. Spectral data of compound 1 were
found to be identical as obtained using Scheme 1.
Preparation of Compounds 1a–h
A mixture of compound 2 (18.3 mmol; 2a–e) and compound 3 (18.3 mmol; 3a,
c–f) in DMF (5 vol.) was stirred at 0 ꢀC, and TEA (3.97 mL, 36.6 mmol) was added.
Further, the mixture was stirred at 30 ꢀC for 1–4 h (monitored by thin-layer chroma-
togrpahy, TLC). The reaction mixture was quenched in ice-cold water (10 vol.). The
precipitated compound was filtered, washed with acetone, and dried under reduced
pressure to afford the title compounds 1a–h.
3-Phenyl-4-(p-tolyl)furan-2(5H)-one (1a). Yellow solid (yield 90.02%), mp.
212–213 ꢀC; HPLC purity: 97.61%; IR (KBr, cmꢂ1): 3481, 3018, 1745, 1742, 1446,
1
1375; ESI (m=z) 251.29 (MþH); H NMR (acetone-d6): d ¼ 2.34 (s, 3H), 5.37 (s,
2H), 7.23 (m, 2H), 7.34 (m, 3H), 7.42 (d, 2H, J ¼ 8.46 Hz), 7.68 (d, 2H, J ¼ 8.47 Hz);
13C (DMSO-d6): d ¼ 25.3, 70.9, 126.9, 127.4, 128.7, 128.8, 128.9, 129.1, 129.8, 135.8,
142.0, 156.0, 172.4 ppm. Elemental analyses found (calcd.): C, 81.58 (81.56); H, 5.64
(5.62); O, 12.78 (12.80).
4-(4-Methoxyphenyl)-3-phenylfuran-2(5H)-one (1b). Yellow solid (yield ¼
91.11%), mp 188–189 ꢀC. HPLC purity: 97.33%; IR (KBr, cmꢂ1): 3478, 3015, 1755,
1738, 1450, 1375; ESI (m=z) 267.29 (MþH); 1H NMR (acetone-d6): d ¼ 3.83 (s, 3H),
5.37 (s, 2H), 7.23 (m, 2H), 7.32 (m, 3H), 7.42 (d, 2H, J ¼ 8.46 Hz), 7.62 (d, 2H,
J ¼ 8.47 Hz); 13C (DMSO-d6): d ¼ 57.8, 70.9, 116.9, 117.4, 128.7, 128.8, 128.9,
129.1, 129.8, 135.8, 142.0, 156.0, 172.4 ppm. Elemental analyses found (calcd.): C,
76.68 (76.65); H, 5.30 (5.32); O, 18.02 (18.04).
4-(4-Fluorophenyl)-3-phenylfuran-2(5H)-one (1c). Yellow solid (yield ¼
90.07%), mp 223–224 ꢀC. HPLC purity: 98.01%; IR (KBr, cmꢂ1): 3484, 3010,
1
1745, 1742, 1446, 1342; ESI (m=z) 255.26 (MþH); H NMR (acetone-d6): d ¼ 5.37
(s, 2H), 7.23 (m, 2H), 7.32 (m, 3H), 7.44 (d, 2H, J ¼ 8.46 Hz), 7.64 (d, 2H,
J ¼ 8.47 Hz); 13C (DMSO-d6): d ¼ 70.9, 115.9, 116.4, 128.7, 128.8, 128.9, 129.1,

3,4-DIARYL-SUBSTITUTED 2(5H)-FURANONES
3147
129.8, 135.8, 142.0, 162.0, 172.4 ppm. Elemental analyses found (calcd.): C, 75.58
(75.56); H, 4.36 (4.38); F, 7.47 (7.49), O, 12.59 (12.57).
4-(4-Nitrophenyl)-3-phenylfuran-2(5H)-one (1d). Yellow solid (yield ¼
91.50%), mp 238–239 ꢀC. HPLC purity: 97.96%; IR (KBr, cmꢂ1): 3488, 3014,
1
1745, 1742, 1446, 1342; ESI (m=z) 282.26 (MþH); H NMR (acetone-d6): d ¼ 5.37
(s, 2H), 7.23 (m, 2H), 7.32 (m, 3H), 7.64 (d, 2H, J ¼ 8.46 Hz), 7.86 (d, 2H,
J ¼ 8.47 Hz); 13C (DMSO-d6): d ¼ 70.9, 116.9, 117.4, 124.7, 124.8, 128.9, 129.1,
129.8, 135.8, 142.0, 156.0, 172.4 ppm. Elemental analyses found (calcd.): C, 68.32
(68.34); H, 3.94 (3.92); N, 4.98 (4.96); O, 22.75 (22.77).
4-Phenyl-3-(p-tolyl)furan-2(5H)-one (1e). Yellow solid (yield ¼ 90.96%),
mp 217–218 ꢀC; HPLC purity: 97.15%; IR (KBr, cmꢂ1): 3481, 3018, 1745, 1742,
1446, 1375; ESI (m=z) 251.29 (MþH); 1H NMR (acetone-d6): d ¼ 2.34 (s, 3H),
5.37 (s, 2H), 7.23 (m, 2H), 7.34 (m, 3H), 7.42 (d, 2H, J ¼ 8.46 Hz), 7.68 (d, 2H,
J ¼ 8.47 Hz); 13C (DMSO-d6): d ¼ 24.3, 70.9, 126.9, 127.4, 128.7, 128.8, 128.9,
129.1, 129.8, 135.8, 142.0, 156.0, 172.4 ppm. Elemental analyses found (calcd.): C,
81.58 (81.56); H, 5.64 (5.62); O, 12.78 (12.80).
3-(4-Methoxyphenyl)-4-phenylfuran-2(5H)-one (1f). Yellow solid (yield ¼
90.03%), mp 192–193 ꢀC. HPLC purity: 98.09%; IR (KBr, cmꢂ1): 3484, 3018,
1
1745, 1742, 1448, 1375; ESI (m=z) 267.29 (MþH); H NMR (acetone-d6): d ¼ 3.83
(s, 3H), 5.37 (s, 2H), 7.23 (m, 2H), 7.32 (m, 3H), 7.42 (d, 2H, J ¼ 8.46 Hz), 7.62
(d, 2H, J ¼ 8.47 Hz); 13C (DMSO-d6): d ¼ 57.8, 70.9, 116.9, 117.4, 128.7, 128.8,
128.9, 129.1, 129.8, 135.8, 142.0, 156.0, 172.4 ppm. Elemental analyses found
(calcd.): C, 76.68 (76.65); H, 5.30 (5.32); O, 18.02 (18.04).
3-(4-Fluorophenyl)-4-phenylfuran-2(5H)-one (1g). Yellow solid (yield ¼
91.01%), mp 226–227 ꢀC. HPLC purity: 97.99%; IR (KBr, cmꢂ1): 3484, 3010,
1
1745, 1742, 1446, 1342; ESI (m=z) 255.26 (MþH); H NMR (acetone-d6): d ¼ 5.37
(s, 2H), 7.23 (m, 2H), 7.32 (m, 3H), 7.44 (d, 2H, J ¼ 8.46 Hz), 7.64 (d, 2H,
J ¼ 8.47 Hz); 13C (DMSO-d6): d ¼ 70.9, 115.9, 116.4, 128.7, 128.8, 128.9, 129.1,
129.8, 135.8, 142.0, 162.0, 172.4 ppm. Elemental analyses found (calcd.): C, 75.58
(75.56); H, 4.36 (4.38); F, 7.47 (7.49); O, 12.59 (12.57).
3-(4-Nitrophenyl)-4-phenylfuran-2(5H)-one (1h). Yellow solid (yield ¼
91.18%), mp 234–236 ꢀC. HPLC purity: 97.08%; IR (KBr, cmꢂ1): 3484, 3010,
1
1745, 1742, 1446, 1342; ESI (m=z) 282.26 (MþH); H NMR (acetone-d6): d ¼ 5.37
(s, 2H), 7.23 (m, 2H), 7.32 (m, 3H), 7.64 (d, 2H, J ¼ 8.46 Hz), 7.86 (d, 2H,
J ¼ 8.47 Hz); 13C (DMSO-d6): d ¼ 70.9, 116.9, 117.4, 124.7, 124.8, 128.9, 129.1,
129.8, 135.8, 142.0, 156.0, 172.4 ppm. Elemental analyses found (calcd.): C, 68.32
(68.34); H, 3.94 (3.92); N, 4.98 (4.96); O, 22.75 (22.77).
ACKNOWLEDGMENTS
We are grateful to the management of the Zydus Group for encouragement.
We thank the analytical department for providing analytical support.

3148
A. ARGADE ET AL.
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