Dodecatungstophosphoric acid (H3PW12O40), samarium and ruthenium (III) chloride catalyzed synthesis of unsaturated 2-phenyl-5(4H)-oxazolone derivatives under solvent-free conditions

Article abstract of DOI:10.3390/molecules13123246

We have found that dodecatungstophosphoric acid (H₃PW ₁₂O₄₀), samarium or ruthenium(III) chloride act as efficient catalysts for the synthesis of unsaturated 2-phenyl-5(4H)oxazolone derivatives under solvent-free condition

Full text of DOI:10.3390/molecules13123246

Molecules 2008, 13, 3246-3252; DOI: 10.3390/molecules13123246
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molecules
ISSN 1420-3049
www.mdpi.com/journal/molecules
Article
Dodecatungstophosphoric Acid (H3PW12O40), Samarium and
Ruthenium (ІІІ) Chloride Catalyzed Synthesis of Unsaturated
2-Phenyl-5(4H)-oxazolone Derivatives under Solvent-free
Conditions
Ahmad Momeni Tikdari 1,*, Samieh Fozooni 1 and Hooshang Hamidian 2
1
Department of Chemistry, Shahid Bahonar University of Kerman, Kerman, 76135-133, Iran
2
Department of Chemistry, Payame Noor University (PNU), Kerman, Iran
* Author to whom correspondence should be addressed; E-mail: amomeni_uk@yahoo.com.
Received: 5 November 2008; in revised form: 27 November 2008 / Accepted: 16 December 2008 /
Published: 18 December 2008
Abstract: We have found that dodecatungstophosphoric acid (H3PW12O40), samarium or
ruthenium(III) chloride act as efficient catalysts for the synthesis of unsaturated 2-phenyl-
5(4H)oxazolone derivatives under solvent-free conditions. The key features of the reported
protocols are short reaction times, high yields of products under ambient conditions and
simple workups.
Keywords: 2-Phenyl-5(4H)-oxazolone; Microwave irradiation; Samarium; Ruthenium(III)
chloride; Dodecatungstophosphoric acid.
Introduction
Heterocyclic compounds have acquired more importance in recent years due to their
pharmacological activities [1, 2] and nitrogen-, sulphur- and oxygen-containing five/six member
heterocyclic compounds have achieved enormous significance in the field of Medicinal Chemistry.
Oxazole plays a very pivotal role in the manufacture of various biologically active drugs with
analgesic, anti-inflammatory, anti-depressant, anti-cancer, anti-microbial, anti-diabetic and antiobesity
properties [3-5].

Molecules 2008, 13
3247
2-Phenyl-5(4H)-oxazolones are important intermediates in the synthesis of several molecules
including amino acids, peptides, antimicrobial or antitumor compounds and heterocyclic precursors, as
well as in biosensor coupling and photosensitive composition devices for proteins [6-11].
A number of methods are available for the synthesis of azalactones, including the use of acetic
anhydride and sodium acetate, lead acetate, polyphosphoric acid, sulphur trioxide/dimethylformamide
complex, perchloric acid and carbodiimides [12-15]. Recently, synthesis of oxazolones using
anhydrous zinc chloride or bismuth (III) acetate as catalysts has been reported [15-19].
Microwave irradiation is a nonconventional energy source whose popularity and synthetic utility in
Organic Chemistry has increased considerably in recent years. The rapid heating induced by such
radiation avoids harsh classical conditions and the decomposition of the reagents, leading to the
formation of products under mild reaction conditions, thus typically increasing the yields. The
elimination of toxic organic solvents and use of catalysts is one of the most important goals in Green
Chemistry. Coupling of these two techniques, that is, organic reactions using catalyst with microwave
irradiation has been a field that has shown excellent results leading to the development of many
reaction procedures, which are environmental friendly, thus falling within the domain of Green
Chemistry [20, 21].
We report herein that dodecatungstophosphoric acid (H3PW12O40), Sm or RuCl3 act as efficient
heterogeneous catalysts for the synthesis of 2-phenyl-5(4H)-oxazolone derivatives. In recent years, the
use of solid acids as heterogeneous catalysts has received considerable attention in different areas of
organic synthesis. Heteropolyacids (HPAs) are attractive, because of their flexibility in modifying the
acid strength, environmental compatibility, no toxicity and experimental simplicity. The use of HPA as
a catalyst makes the process convenient and environmentally benign [22-24].
There have been extensive efforts to utilize the potential of the HPAs in synthetic Organic
Chemistry such as deprotection of t-butyldimethylsilanes, regioselective aerobic oxygenation of
nitrobenzene to 2-nitrophenol and oxidation of aliphatic, benzylic and allylic alcohols using dimethyl
sulfoxides as oxygen transfer agents. Heteropolyacids, due to their unique physicochemical properties
are widely used in variety of acid catalyzed reactions, such as esterification, hydration and
dehydration, de-esterification, polymerization, condensation in homogenous and heterogenous systems
[25-27].
The direct use of metallic samarium in organic transformations has attracted the attention of many
organic chemists. In most cases, the reactions promoted by samarium were carried out in THF, and
metallic samarium had to be activated or pretreated by various methods so as to ensure the reactions
proceed smoothly. Only a few reports could be found in the literature concerning organic reactions
promoted efficiently by metallic samarium without activation or pretreatment. We now report a novel
and facile synthesis of 2-phenyl-5(4H)oxazolone compounds promoted by metallic samarium [28, 29].
Ruthenium(III) trichloride has been widely used to catalyze oxidations, reductions or
polymerizations of organic compounds. Ruthenium compounds are advantageous as they can be used
both in acidic as well as in alkaline medium [30, 31].

Molecules 2008, 13
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Results and Discussion
In the past, the synthesis of unsaturated 2-phenyl-5(4H)-oxazolones have been accomplished by the
classical Erlenmeyer reaction, involving condensation of hippuric acid, aldehydes or ketones in
presence of acetic anhydride and sodium acetate under refluxing conditions. This procedure requires
long reaction times and the yields are moderate. We report here three solvent-free procedures for the
synthesis of unsaturated 2-phenyl-5(4H)-oxazolones 3a-j from appropriate aldehydes or ketones (1)
with hippuric acid (2) under microwave irradiation in the presence of three different catalysts, namely
dodecatungstophosphoric acid, samarium and ruthenium(ΙΙΙ) chloride. Then we contemplated a
comparison between dodecatungstophosphoric acid, samarium and ruthenium(ΙΙΙ) chloride, which
have not been employed for the synthesis of 2-phenyl-5(4H)-oxazolones, in terms of the yield and rate
of the reaction.
A reaction mixture consisting of hippuric acid, aldehydes or ketones, in the presence of acetic
anhydride and corresponding catalysts, was exposed to microwaves for a suitable time (Table 1). The
mixture turned solid at room temperature and led to the isolation of 2-phenyl-5(4H)-oxazolone
derivatives (Scheme 1). It was evidently observed that the yield and rate of the reaction were high in
all the cases. Dodecatungstophosphoric acid, samarium and ruthenium(III) chloride appeared to be
efficient catalysts. The comparisons between these catalysts are shown in Table 1.
Scheme1. Synthesis of 5(4H)-oxazolones in the presence of H3PW12O40, Sm, RuCl3.
R
1
O
C
O
C
O
R
2
Ac2O/catalyst
MW,300W
+
R
R
Ph
NH
CH2
COOH
2
1
N
O
Ph
(1)
(2)
Catalysts: H3PW12O40, Sm, RuCl3
(3)
1a) Benzaldehyde
1f) 4-(N,N-Dimethylamino)benzaldehyde
1g) 4-Methylbenzaldehyde
1b) 4-Chlorobenzaldehyde
1c) 2,4-Dichlorobenzaldehyde 1h) Furfural
1d) 3-Nitrobenzaldehyde
1i) Thiophenecarboxaldehyde
1j) Cyclohexanone
1e) 4-Methoxybenzaldehyde
It was observed that the reaction proceeds faster in the case of dodecatungstophosphoric acid, but
the products were obtained in high yields in the case of samarium. The structures of the products were
confirmed by IR, 1H-NMR and mass spectroscopy (Table 2).
In conclusion, we have reported novel, simple, efficient and modified methods for synthesis of
unsaturated 2-phenyl-5(4H)-oxazolone derivatives. The reaction is catalyzed by dodecatungsto-
phosphoric acid (H3PW12O40), samarium and ruthenium(III) chloride, which are environmentally
benign.

Molecules 2008, 13
3249
Yields of the products, short reaction times, easing of work-up and preclusion of toxic solvents are
the striking features of the present protocol.
Table 1. Comparison of H3PW12O40, RuCl3 and Sm as catalysts for synthesis of 2-phenyl-
5(4H)-oxazolones in terms of yield and time.
Product Y(%)(t) a Y(%)(t)b Y(%)(t)c m.p.(◦C) m.p.(Lit)
3a
3b
3c
3d
3e
3f
87(2)
80(3)
73(4)
86(5)
82(5)
87(2)
87(2)
82(3)
80(3)
84(4)
71(3)
92(5)
87(7)
96(8)
93(7)
97(4)
95(4)
93(5)
87(5)
93(6)
82(4)
160-161 158 [13]
189-190 185 [14]
181-182 183 [14]
174-175 175-176 [15]
158-159 159 [16]
212-213 213-214 [15]
146-147 145-146 [18]
171-172 171[16]
83(2.5)
93(3)
87(3)
95(1.5)
92(1.5)
89(2)
3g
3h
3i
84(2)
89(2.5)
77(2)
178-179 180 [16]
138-139 137-138 [15]
3j
aYield(time/min) using H3PW12O40
b Yield(time/min) using RuCl3
c Yield(time/min) using Sm
Table 2. Spectral Data of Compounds 3a-j.
Product IR (KBr)/υ [cm-1] 1H-NMR (CDCl3)/δ[ppm]
MS/m/z (%)
3a
1790, 1650
7.24 (s, 1H, vinyl); 7.44-8.12 (m, 249 (M+, 15), 105
10H, ArH)
(100), 77 (70)
3b
1800,1650
7.44-8.12 (m, 10H, vinyl and ArH) 285 (M+2), 283 (M+,
15), 105 (100), 77
(70)
3c
1800, 1660
7.36-8.08 (m, 9H, vinyl and ArH)
319 (M+4, 2), 317
(M+2, 8), 318 (M+,
10), 105 (100), 77
(70)
3d
3e
3f
1800,1660
1790,1660
1810, 1660
1800, 1660
1790, 1660
7.42-8.29 (m, 10H, vinyl and ArH) 294 (M+, 15), 105
(100), 77 (70)
4.02 (s, 3H, CH3); 7.07 (s, 1H, 279 (M+, 10), 105
vinyl); 7.25-8.22 (m, 9H, ArH)
3.12 (s, 6H, CH3); 6.86-8.12 (m, 292 (M+, 10), 105
10H, vinyl and ArH) (100), 77 (70)
2.35 (s, 3H, CH3); 7.07 (s, 1H, 263 (M+, 10), 105
vinyl); 7.25-8.12 (m, 9H, ArH) (100), 77 (70)
6.66 (q, 1H, 2-furyl);7.17-8.28 (m, 239 (M+, 5), 105
8H, vinyl , furyl and ArH) (100), 77 (70)
(100), 77 (70)
3g
3h

Molecules 2008, 13
3250
Table 2. Cont.
3i
3j
1810, 1660
1780, 1650
6.89 (q, 1H, 2-thienyl);7.37-8.04 255 (M+, 5), 105
(m, 8H, vinyl, thienyl and ArH)
1.34-2.13 (m, 10H, cyclohexyl); 241 (M+, 10), 105
7.34-7.88 (m, 5H, ArH) (100), 77 (70)
(100), 77 (70 )
Experimental
General
Melting points were determined on a Gallenkamp melting point apparatus and are uncorrected.
Mass spectra were obtained on a Shimadzu QP 1100 EX. IR spectra were recorded with a Mattson
1000 FT-IR spectrophotometer. Nuclear magnetic resonance spectra were recorded on a Bruker DRX-
500 AVANCE spectrometer using tetramethylsilane (TMS) as an internal standard. All the reactions
were carried out in an unmodified domestic microwave oven BC380W having a maximum output of
900 W, operating at 2450 MHz.
General Procedure for Synthesis of 2-phenyl-5(4H)-oxazolone derivatives 3a-j
The appropriate aldehyde or ketone (1, 0.01 mol), hippuric acid (2, 0.01 mol), acetic anhydride (1
mL) and the appropriate catalyst (0.2 g) were introduced into a beaker and mixed. The paste thus
obtained was irradiated in a microwave oven at a power output of 300 W for an appropriate time
(Table 1) until the mixture had gone from white to a deep yellow, semi-solid mass. The mixture was
then cooled to room temperature and was washed with cold water, and then the crude product was
recrystallized from 96% ethanol (using active carbon for ruthenium chloride).
Acknowledgments
The authors appreciate the support of the Department of Chemistry, Shahid Bahonar University of
Kerman during this investigation.
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Sample Availability: Samples of the compounds are available from the authors.
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