Studies on phosphonium ylides XXV: The behavior of active phosphacumulene and stabilized alkylidenephosphoranes towards 5-(4H)-oxazolones

Article abstract of DOI:10.1080/10426500802111090

The reaction of 2-phenyl-5-(4H)-oxazolone 1 and its 4-benzylidene derivative 2 with oxovinylidenetriphenylphosphorane 3 afforded 2-phenylfuro [3,2-d] [1,3]oxazol-5-(6H)-one 6 and 2,7-diphenyl-5H-pyrano[3,2-d][1,3]oxazol-5- one 7 along with triphenylphosph

Full text of DOI:10.1080/10426500802111090

This article was downloaded by: [University of Stellenbosch]
On: 05 September 2013, At: 00:07
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954
Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH,
UK
Phosphorus, Sulfur, and Silicon
and the Related Elements
Publication details, including instructions for
authors and subscription information:
http://www.tandfonline.com/loi/gpss20
Studies on Phosphonium
Ylides XXV: The Behavior
of Active Phosphacumulene
and Stabilized
Alkylidenephosphoranes
Towards 5-(4H)-Oxazolones
Leila S. Boulos a , Mona H. N. Arsanious a & Ewies F.
Ewies a
a National Research Centre, Dokki, Cairo, Egypt
Published online: 04 Feb 2009.
To cite this article: Leila S. Boulos , Mona H. N. Arsanious & Ewies F.
Ewies (2009) Studies on Phosphonium Ylides XXV: The Behavior of Active
Phosphacumulene and Stabilized Alkylidenephosphoranes Towards 5-(4H)-Oxazolones,
Phosphorus, Sulfur, and Silicon and the Related Elements, 184:2, 275-290, DOI:
10.1080/10426500802111090
To link to this article: http://dx.doi.org/10.1080/10426500802111090
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the
information (the “Content”) contained in the publications on our platform.
However, Taylor & Francis, our agents, and our licensors make no
representations or warranties whatsoever as to the accuracy, completeness,
or suitability for any purpose of the Content. Any opinions and views
expressed in this publication are the opinions and views of the authors, and
are not the views of or endorsed by Taylor & Francis. The accuracy of the

Content should not be relied upon and should be independently verified with
primary sources of information. Taylor and Francis shall not be liable for any
losses, actions, claims, proceedings, demands, costs, expenses, damages,
and other liabilities whatsoever or howsoever caused arising directly or
indirectly in connection with, in relation to or arising out of the use of the
Content.
This article may be used for research, teaching, and private study purposes.
Any substantial or systematic reproduction, redistribution, reselling, loan,
sub-licensing, systematic supply, or distribution in any form to anyone is
expressly forbidden. Terms & Conditions of access and use can be found at
http://www.tandfonline.com/page/terms-and-conditions

Phosphorus, Sulfur, and Silicon, 184:275–290, 2009
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500802111090
Studies on Phosphonium Ylides XXV: The Behavior of
Active Phosphacumulene and Stabilized
Alkylidenephosphoranes Towards 5-(4H)-Oxazolones
Leila S. Boulos, Mona H. N. Arsanious, and Ewies F. Ewies
National Research Centre, Dokki, Cairo, Egypt
The reaction of 2-phenyl-5-(4H)-oxazolone
1
and its 4-benzylidene deriva-
afforded 2-phenylfuro [3,2-
tive with oxovinylidenetriphenylphosphorane
2
3
d] [1,3]oxazol-5-(6H)-one 6 and 2,7-diphenyl-5H-pyrano[3,2-d][1,3]oxazol-5-one 7
along with triphenylphosphine. Alternatively, when 2-phenyl-5-(4H)-oxazolone 1
reacts with phosphorus ylides 4a–f the corresponding new phosphorane, the cyclic
and/or the olefinic adducts were obtained. Moreover, oxazolone reacts with N-
(triphenylphosphoranylidene)aniline 5 to give the new imino product 14 together
with triphenylphosphine oxide. Possible reaction mechanisms are considered and
the structural assignments are based on analytical and spectroscopic results. Bio-
logical evaluations of the new products are also studied.
Keywords 5-(4H)-Oxazolones; oxovinylidenetriphenylphosphorane; N-(triphenylpho-
sphoranylidene) aniline; ylides
INTRODUCTION
Oxazolones constitute a class of small heterocycles, which are impor-
tant intermediates in the synthesis of several small molecules, includ-
ing amino acids, peptides, antimicrobial or antitumor compounds,1,2
and heterocyclic precursors,3,4 as well as biosensor coupling and/or pho-
tosensitive composition devices for proteins.5
Some oxazolones have shown a wide range of pharmaceutical
properties.6 As part of our continuous interest in organophosphorus
chemistry,7–11 the present study deals with the reaction of active phos-
phacumulene ylides, namely 2-oxovinylidenetriphenylphosphorane 3
with 5-(4H)-oxazolone 1 and its 4-benzylidene derivative 2, and a com-
parison of the reactivity of the active phosphacumulene 3 with the
Received 12 February 2008; accepted 8 April 2008.
Address correspondence to Dr. Leila Sadek Boulos, Department of Organometallic and
Organometalloid Chemistry, National Research Centre, El Tahrir Street, Dokki, Cairo
12622, Egypt. E-mail: leilagoubran@yahoo.com
275

276
L. S. Boulos et al.
O
O
C
C
O
C
C
O
C
R1
R2
Ph
C Ph
Ph
C
H
N
N
1, R1=R2=H
2
C=C=O
Ph3P
3
Ph3P=C R1R2
4
a, R1= H;
b, R1= H;
c, R1= H;
d, R1= H;
e, R1= H;
f, R1+R2=
R2= COOC2H5
R2= COOCH3
R2= CH-CHO
R2= CN
R2= COCH3
9-fluorenylidene
Ph3P=N-Ph
5
FIGURE 1
reactivity of stabilized phosphorus ylides (4a–4f) and iminophospho-
rane (5) towards the above mentioned oxazolone 1 and 2 (Figure 1).
RESULTS AND DISCUSSION
We have found that 2-phenyl-5-(4H)-oxazolone 1 reacts with 1 mol
equivalent of 2-oxovinylidenetriphenylphosphorane 3 in dry tetrahe-
drofuran, at room temperature for 9 h to give colorless crystalline
product assigned structure 6. Triphenylphosphine was also isolated
from the reaction medium and identified (Scheme 1).
Structural support for 2-phenylfuro [3,2-d][1,3]oxazol-5-(6H)-one 6
was based upon correct elemental and spectroscopic data (IR, 1H,

Studies on Phosphonium Ylides XXV
277
H
C
N
C
CH2
N
CH
C
C=C=O
Ph3P
N
C
HC PPh3
C
O
Ph
Ph
3
O
OH
O
C
C
O
Ph
1
O
O
B
-TPP
N
C
C
CH2
C
C
O
Ph
O
O
6
SCHEME 1
13C NMR, and mass spectrum). Elemental analyses and molecular
weight determination (MS) of compound 6 support the molecular for-
mula C11H7NO3; accordingly, ms: m/z = 201(M+, 100). Its IR spectrum,
in KBr, exhibits an intense band at 1726 cm−1for the lacton car-
bonyl band. 1H NMR of compound 6 showed a singlet at 3.66 ppm
for the methylene protons (s, 2H, CH2). The aromatic protons ap-
peared as multiplet at 7.84–7.43 ppm (5H). 13C NMR of product 6
exhibits signals at 173.44 ppm (C O, lacton), 165.46 (C N), 134.75,
127.0 ppm (C C), 40.60 (CH2), 129.43, 128.22, 127.33, 126.30 (C-
CH, Ar). A possible explanation for the course of the reaction of 2-
oxovinylidenetriphenylphosphorane 3 with 1 is shown in Scheme 1.
Formation of product 6 can be explained in terms of protonation with
the hydrogen proton of compound 1 on the carbon-ion center of the
accumulated ylide 3 to give the intermediate B. Since triphenylphos-
phine is a good leaving group,12,13 Hoffmann elimination14 of triph-
enylphosphine afforded the final product 6. In addition, we stud-
ied the behavior of 4-benzylidene-2-phenyl-5-(4H)-oxazolone 2 with
2-oxovinylidenetriphenylphosphorane 3. Treatment of 2 with 1 mol
equivalent of 3 in tetrahedrofuran leads to the formation of the new
cyclic product 7. Triphenylphosphine was also isolated from the reac-
tion medium (Scheme 2). The structure of product 7 is deduced from
1
its elemental analysis, IR, H, 13C NMR, and mass spectral data (cf.
experimental, Scheme 2).14
Ph
C
Ph
C
PPh3
N
C
C
C
CHPh
N
C
C
C
CH
C
-TPP
N
C
C
C
CH
C
C=C=O
Ph3P
O
3
Ph
O
O
O
Ph
O
2
O
Ph
O
O
7
SCHEME 2

278
L. S. Boulos et al.
Furthermore, the reaction of 2-phenyl-5-(4H)-oxazolone 1 with
resonance stabilized ylidenetriphenylphosphoranes 4a–4f and
iminophosphorane 5 has also been investigated (Figure 1). 2-Phenyl-5-
(4H)-oxazolone 1 reacted with 1 mol equivalent of carbethoxymethylen-
etriphenynphosphorane 4a, in refluxing toluene for 6 h, to give two
crystalline compounds that were assigned structures 8a and 9a.
Triphenylphosphine oxide was also isolated from the reaction mixture
and identified (Scheme 3). The first product was obtained as yellow
crystals in 45% yield and was formulated as the known15 ethyl(2-
phenyl-1,3-oxazol-5-yl)acetate 8a based on elemental analysis, IR, 1H,
13C NMR, and mass spectral data (cf. Experimental).
N
C
CH2
Ph3P=CHCOOR
+
C
O
Ph
O
4a, R= C2H5
b,R= CH3
1
- TPPO
N
C
CH
N
CH2
C
N
C
CH2
C
O
OH
C
CH2COOR
C
Ph
Ph
O
O
Ph
CH COOR
O
C
COOR
PPh3
PPh3
8a , R= C2H5
b, R= CH3
9a, R= C2H5
b, R= CH3
SCHEME 3
The structure of the other isolated compound 9a (colorless crys-
talline compound m.p. 120◦C, yield 40%) was deduced from its
elemental analysis, IR, 1H, 13C, 31P NMR, and mass spectral data.
Elemental and mass spectroscopic analysis for compound 9a corre-
sponded to an empirical formula C31H28NO4P. Its IR spectrum (in
KBr) revealed the presence of strong absorption bands at 1733 (C O,
ester), 1644, 1590cm−1 (C P), 1439, 969cm−1(P-C, Phenyl), 3293cm−1
(OH).1H NMR spectrum of compound 9a showed signals at 0.82
(t, 3H, J = 8Hz, CH3), 3.84 (q, 2H, J = 8Hz, CH2), 2.21 (s, 1H, OH,
exchangeable with D2O), 7.32–7.96 (m, 20H, Ar). Moreover, the struc-
ture of product 9a is identified mainly from its 1H NMR which reveals
the presence of doublet of doublets for the unsymmetrical methylene

Studies on Phosphonium Ylides XXV
279
protons at 4.805, 4.801–4.791, 4.787 ppm with (JHH = 1.2 Hz, JHP
=
4.2 Hz). This is due to the mutual coupling of the unsymmetrical
methylene protons and the long range coupling with the phosphorus
atom.16 13C NMR of ethyl(5-hydroxy-2-phenyl-4,5-dihydro-1,3-oxazol-
5-yl)(triphenyl-λ5-phosphoranylidene) acetate 9a indicates signals at
166.91 ppm (d, 2J = 13.25 Hz, COOC2H5), 163.34 ppm (C N), 125.31
cp
ppm (d,1J = 93.2 Hz, P C)17 96.30 (d,2J = 15 Hz, C-OH), 68.53 ppm
cp
cp
(d,3J = 8.5 Hz, CH2), 57.78 ppm (ethoxy –CH2), 13.43 ppm (ethoxy
cp
–CH3). The 31P NMR shift recorded for adduct 9a was 18.50. The molec-
ular weight determination (MS) of 9a supports the molecular formula.
Similarly, carbmethoxymethylenetriphenylphosphorane 4b reacted
with 1 to give two products, 8b and 9b, along with triphenylphosphine
oxide. The structures of 8b and 9b were deduced from their analysis, IR,
1H, 13C NMR, and mass spectral data (cf. Scheme 3 and Experimental).
Formation of adducts 9a and 9b can be explained in terms of initial
attack of the ylidic carbon in 4 on the carbonyl carbon of lacton C(5) O
followed by migration of the α-proton of the first formed phosphonium
betain to the electron rich center (Scheme 3).
The forgoing results confirm the assigned structure 9 and rule out
the alternative open-chain structure A since the methylene protons
in its 1H NMR appeared as singlet at 4.82 ppm as previously reported
(Scheme 4).15,18−20
N
C
CH2
C
Ph3P=CHCOOC2H5
+
O
Ph
O
4a
1
- TPPO
O
N
C
CH
C
Ph3P
C
C CH2 NHCOPh
CH2COOC2H5
COOC2H5
Ph
O
8a
A
SCHEME 4

280
L. S. Boulos et al.
The reaction of 2-phenyl-5-(4H)-oxazolone 1 with formylmethylenet-
riphenylphosphorane 4c was also investigated. We have found that the
reaction of 1 with one mol equivalent of 4c, in dry toluene, proceeds at
reflux temperature to give a chromatographically pure compound for-
mulated as (5-hydroxy-2-phenyl-4,5-dihydro-1,3-oxazol-5-yl)triphenyl-
λ5-phosph- oranylidene)acetaldehyde 10 (Scheme 5). The structure of
product 10 is deduced from its elemental analysis, IR, 1H, 13C, 31P
NMR, and mass spectral data (cf. Experimental). Triphenylphosphine
N
C
CH2
C
N
C
CH2
C
O
Ph
OH
CHO
O
CH CHO
Ph
O
C
PPh3
PPh3
10
+ 4c
N
C
CH2
C
O
Ph
O
1
+ 4e
+ 4f
N
C
CH
C
N
C
CH2
N
CH2
C
OH
C
C
Ph
O
C
Ph
O
Ph
CHCOCH3
CN
O
11
13
PPh3
N
C
CH
C
Ph
CH2COCH3
O
12
SCHEME 5

Studies on Phosphonium Ylides XXV
281
N
C
CH2
C
-TPPO
N
C
CH2
C
Ph3P=N-Ph
+
O
Ph
O
N
Ph
Ph
5
O
1
14
SCHEME 6
and/or triphenylphosphine oxide are neither isolated nor detected in
the reaction medium.
Moreover, the reaction products of 1 with cyanomethylenetriph-
enylphosphorane 4d, 1-triphenylphosphoranylidene-2-propanone 4e,
and fluorenylidenetriphenylphosphorane 4f were assigned structures
11, 12, and 13, respectively on the basis of spectroscopic arguments
(cf. Scheme 5, Experimental section).
The reaction of 1 with N-(triphenylphosphoranylidene) aniline 5 was
also investigated.
We found that 2-phenyl-5-(4H)-oxazolone 1 reacts with 1 mol equiva-
lent of N-(triphenylphosphoranylidene) aniline 5 in refluxing toluene to
give the corresponding imino derivative 14 (Scheme 6). Triphenylphos-
phine oxide is also isolated from the reaction medium. Structure elu-
cidation of compound 14 is based on analytical and spectral data (cf.
Experimental).
CONCLUSION
Based on the results of the present investigation, it could be inferred
that phosphacumulene and stabilized phosphorus ylides behave dif-
ferently towards 2-phenyl-5-(4H)-oxazolones 1, 2. While the reaction of
active phosphacumulene ylide 3 with oxazolones 1,2 resulted in the for-
mation of the cyclic 2-phenylfuro[3,2-d][1,3]oxazol-5-(6H)-one 6 and 2,7-
diphenyl-5H-pyrano[3,2-d][1,3]oxazol-5-one 7, a different behavior was
observed in the reaction of 1 with stabilized ylides 4 and the iminophos-
phorane 5, depending on the stability of the addition products. More-
over, we have found that 2-phenyl-5(4H)-oxazolone1 reacted with
ethyl(triphenylphosphoranylidene)acetate 4a to give ethyl(5-hydroxy-
2-phenyl-4,5-dihydro-1,3-oxazol-5-yl(triphenyl-λ5-phosphoranyli dene)
acetate 9a and not the open chain phosphorane adduct A as previously
reported.15,18–20

282
L. S. Boulos et al.
BIOLOGICAL EVALUATION OF THE TESTED COMPOUNDS
Materials
Adult worms of Schistosoma mansoni (Egyptian strain) are obtained
by infecting Syrian golden hamsters (Mesocricetus auratus) by percuta-
neous infection of 350 cercariae/animal, freshly shed from an infected
Biomphalaria alexandrina snail.21 The animal experiments have been
carried out according to the internationally valid guidelines in an in-
stitution complying with biological ethics (Theodor Bilharz Research
Institute).22 Worms are obtained by porto-mesenteric perfusion, 45
days post-infection using citrated saline (7.5 g Na citrate + 8.59Na
chloride/l).
The worms are washed in a small sterilized sieve three times by phos-
phate buffer (pH 7.4) then 3 other times by RPMI-1640 medium with
L glutamine containing antibiotics (300 µg streptomycin, 300 units
penicillin, and 160 µg gentamycin) + 20% foetal calf serum, inside a
sterilization laminar flow. Then the worms are poured into a small Petri
dish. Compound samples are kept at −20◦C in the dark.
Chemicals
The tested compounds are organophosphorus and olefinic compounds
derived from the reaction of oxazolone derivatives and organophospho-
rus reagents; they were prepared as mentioned in the text.
It is well known that organophosphorus compounds are the most
important group of pesticides due to their rapid metabolism.23 On
the other hand, oxazolone derivatives have a wide range of pharma-
ceutical and biological purposes,6 and they also possess insecticidal
properties.24 Therefore, this work aims to prepare some oxazolone
derivatives and test them for antischistosomal activity in vitro on
Schistosoma mansoni worms. The organophosphorus and olefinic com-
pounds were tested in 10 µg/mL for in vitro bioactivity on viable Schis-
tosoma mansoni mature worms in culture medium (RPMI 1640). Three
replicates were used for each compound and three pairs of worms, males
and females equally represented, were placed in each vial containing
the medium and the compound. The worms were considered dead when
they did not show motility for 1 min. Viability ratio of worms was de-
termined by calculating the number of dead worms relative to the total
number of worms. The results were compared with negative (DMSO)
and positive (praziquantel) controls. Praziquantel (PZQ) is the main-
stay of schistosomiasis control programs worldwide; in other words an

Studies on Phosphonium Ylides XXV
283
enormous investment in terms of money, manpower, and training rests
on the efficacy of a single synthetic compound.
The results revealed that 2,7-diphenyl-5H-pyrano[3,2-d][1,3] oxazol-
5-one 7 possessed in vitro antischistosomal activity (100% mortality).
Compounds showed various degrees of lethal effect 8.3–41.7% mor-
tality) on worms at 10 µg/ml of the compounds after 4 days of expo-
sure (Table I). 2,7-Diphenyl-5H-pyrano[3,2-d][1,3]oxazol-5-one 7 was
further subjected to determination of its IC50 and IC90 values (Table
II). The results clarified that 2,7-diphenyl-5H-pyrano[3,2-d][1,3]oxazol-
5-one 7, which possesses the strongest antischistosomal activity (IC50
values equal to or less than 10µg/ml) (Table II), and 2,7-diphenyl-
5H-pyrano[3,2-d][1,3]oxazol-5-one 7 were considered promising bioac-
tive compounds and deserving of further investigation. Therefore, the
present study is a trial to throw light on some new chemotherapeutic
antischistosomal drugs.
EXPERIMENTAL
Melting points were measured by means of electrothermal apparatus.
Phosphoranes 4a–4f and 5-(4H)-oxazolone 1, 2 were prepared.25−29,30,31
The IR spectra were measured in KBr pellets with a Perkin-Elmer
1
infrared spectrophotometer model 157.The H and 13C NMR spectra
were recoded in CDCl3 with a varian spectrometer at 270 and 67.5
MHz using TMS as internal reference. The 31P NMR spectra were
taken with a Varian CFT-20 (vs. external 85% H3PO4 standard).The
mass spectra were recoded at 70 eV with a Kratos MS equipment or
Varian MAT 311 A spectrometer. Elemental analyses were preformed
using the Elmentar Varu EL Germany Instrument. Their values agreed
favorably with the calculated ones.
Reaction of Phosphacumulene Ylide (3)
with 2-Phenyl-5-(4H)-Oxazolone (1)
A mixture of 3 (0.30 g, 0.001 mol) and 1 (0.16 g, 0.001 mol) in 30 cm3
THF was stirred at room temperature 10 h. The volatile materials were
evaporated under reduced pressure. The residue was subjected to silica
gel column chromatography to give 6 2-phenylfuro[3,2-d][1,3]oxazol-5-
(6H)-one (6, C11H7NO3).
Eluent: petroleum ether/acetone (90/10, v/v) product 6 was separated
as yellow crystals, yield 75% and m.p. 120◦C. IR (KBr): v = 1726 (C O,
lacton), 1630 (C N)cm−1; 1H NMR (270 MHz, CDCl3): δ = 3.66 (s, 2H,
CH2), 7.43–7.84 ppm (m, 5H, Ar); 13C NMR (270 MHz, CDCl3): δ =

284
L. S. Boulos et al.
TABLE I In Vitro Evaluation of Compounds for Schistosomicidal
Activity at 10 µg/mL
1st. day No.
of worms (12)
2nd Day No.
of worms (12)
3rd day No.
of worms (12)
4th Day No.
of worms (12)
Code Number
of compound
Dead Mortality% Dead Mortality% Dead Mortality% Dead Mortality%
0
0
0
0
7
66.7
12
100*
0
0
0
0
0
0
0
0
2
0
16.7
5
4
41.7
33.3
0
0
0
0
0
0
0
0
0
1
0
8.3
0
3
1
25
8.3
0
0
0
0
0
0
0
0
2
1
16.7
8.3
4
5
33.3
41.7
0
0
0
0
1
8.3
1
8.3
PZQ (+ve) control
12
0
100
0
12
0
100
0
12
0
12
0
12
0
100
0
DMSO (-ve) control

Studies on Phosphonium Ylides XXV
285
TABLE II In Vitro Antischistosomal Effect
(IC50 & IC90) of Compound 7 Compared to
PZQ
Code Number of compound
IC50
6.62
IC90
9,02
PZQ(+ve) control
0.4
0.64
173.44 (C O, lacton), 165.46 (C N), 134,0 127.0 (C C), 40.60 (CH2),
129.43, 128.2, 127.3, 126.3 (C-CH, Ar); MS (EI): m/z (%) 201 (M+,
100). Triphenylphosphine was also separated and identified (mix. m.p.,
ms).
Reaction of Phosphacumulene Ylide (3)
with 4-Benzylidene-2-phenyl-5-oxazolone (2)
A mixture of 3 (0.30 g, 0.001 mol) and 2 (0.25 g, 0.001 mol) in 30 cm3 THF
was stirred at room temperature for 12 h. The volatile materials were
evaporated under reduced pressure. The residue was subjected to sil-
ica gel column chromatography to give 7 2,7-diphenyl-5H-pyrano[3,2-
d][1,3]oxazol-5-one (7, C18H11NO3).
Eluent: petroleum ether/acetone (85/15, v/v) product 7 was sepa-
rated as pale yellow crystals, yield 80% m.p. 150◦C. IR (KBr): v = 1720
1
(C O, lacton), 1651 (C N); H NMR (270 MHz, CDCl3): δ = 6.32 (s,
1H, C CH), 7.44–7.70 (m, 10H, Ar) ppm; 13C NMR (270 MHz, CDCl3):
δ = 174.55 (C O, lacton), 165.81 (C N), 133.36, 126.53 (C C), 132.08,
121.9 (C CH), 128.92–125.03 (C-CH, Ar); MS (EI): m/z (%) 289(M+,
99). Triphenylphosphine was also separated and identified (mix. m.p.,
ms).
General Procedures for the Reaction of Phosphonium Ylides
(4a) and (4b) with Oxazolone (1)
A mixture of 0.001 mol 4a and 4b and 0.001mol oxazolone 1 in 30 cm3
dry toluene was refluxed for 6 h. The volatile materials were evaporated
under reduced pressure. The residue was subjected to silica gel column
chromatography to give products 8a, 9a, 8b, and 9b.

286
L. S. Boulos et al.
Ethyl (2-Phenyl-1,3-oxazol-5-yl)Acetate (8a, C13H13NO3)15
Eluent: petroleum ether/acetone (95/5, v/v) product 8a was separated
as yellow crystals, yield 45% m.p. 46◦C. IR (KBr): v = 1740 (COOC2H5);
1H NMR (270 MHz, CDCl3): δ = 1.2 (t, J = 8Hz, 3H, CH3), 3.7 (s, 2H,
CH2), 4.2 (q, J = 8Hz, 2H, CH2), 7.06 CH (s, 1H, H-4), 7.2–8.2 (m, 5H,
Aryl H); MS (EI): m/z (%) 231(M+, 100).
Ethyl(5-hydroxy-2-phenyl-4,5-dihydro-1,3-oxazol-5-
yl)(triphenyl-λ5-phosphoranylidene) Acetate (9a,
C31H28NO4P)
Eluent: petroleum ether/acetone (85/15, v/v) product 9a was sepa-
rated as colorless crystals, yield 40% m.p. 120◦C. IR (KBr): v = 1733
(C O, ester), 1644, 1590 cm−1(C P); 1439, 969 cm−1(P-C, phenyl),
3293 cm−1(OH); 1H NMR (270 MHz, CDCl3): δ = 0.82 (t, 3H, J =
8Hz, 3H, CH3), 3.84 (q, J = 8Hz, CH2), 2.21 (s, 1H, OH, exchange-
able with D2O), 7.32–7.96 (m, 20H, Ar). Doublet of doublets at 4.805,
4.801–4.791, 4.787 with JHH = 1.2 Hz, JHP = 4.2 Hz) for the unsym-
2
metrical methylene protons. 13C NMR of 9a δ = 166.91ppm (d, J
=
cp
1
13.25 Hz, COOC2H5), 163.34 (C N), 125.31 (d, J = 93.2 Hz, P C)
cp
[15], 96.30 (d, 2J = 15 Hz, C-OH), 68.53 ppm (d, 3J = 8.5 Hz,
cp
cp
CH2), 57.78 (ethoxy-CH2), 13.43 ppm (ethoxy-CH3), MS m/z ( M+, rel.
int. %):509(M+, 10), 479(M+-C2H5, 20), 463(M+-OC2H5), 347([Ph3P C-
COOC2H5]+,25), 105([C6H5CO]+,45), 77([C6H5]+, 100);31P NMR 18.5
ppm.
Methyl (2-Phenyl-1,3-oxazol-5-yl)Acetate (8b, C12H11NO3)
Eluent: petroleum ether/acetone (95/5, v/v) product 8b was separated
as yellow crystals, yield 42% m.p. 47◦C. IR (KBr): v = 1735 cm−1(C O,
1
ester); H NMR (270 MHz, CDCl3): δ = 3.32(s, 3H, COOCH3), 3.75(s,
2H, CH2), 7.2–8.15 (m, 5H, aryl H); MS (EI):m/z (%) 217 (M+, 100).
Triphenylphosphine oxide was also isolated and identified (mix. m.p.;
ms).
Methyl(5-hydroxy-2-phenyl-4,5-dihydro-1,3-oxazol-5-
yl)(triphenyl-λ5-phosphoranylidene) Acetate (9b,
C30H26NO4P)
Eluent: petroleum ether/acetone (80/20, v/v) product 9b was sep-
arated as colorless crystals, yield 45% m.p. 108◦C. IR (KBr):v = 1740
(C O, ester), 1640, 1595 cm−1(C P), 1430, 970 cm−1(C-P, phenyl), 3300
cm−1 (OH);1H NMR (270 MHz, CDCl3): δ = 3.32 (s, 3H, COOCH3), 2.01
(s, 1H, OH), 7.32–7.69 (m, 20H, Ar), dd centered at 4.80 and 4.79 ppm
(CH2,JHH = 1.2 Hz, JHP = 4.2 Hz, unsymmetrical methylene protons);

Studies on Phosphonium Ylides XXV
287
13C NMR of 9b δ = 165.80 ppm (d, 2J = 13.7 Hz, C O), 164.53 (C N),
cp
1
2
124.53 (d, J = 100 Hz, P C), 89.43 ppm (d, J = 15.6 Hz), 64.35
cp
cp
3
ppm (d, J = 8.5 Hz, CH2), 52.21 (COOCH3), 133.19, 132.07, 132.03,
cp
130.9, 128.7, 128.6, 128.17, 127.14 (Ar-C-H); 31P NMR δ = 18.9 ppm, MS
m/z ( M+, rel.int. %):497(M+, 10), 482 (M+-CH3, 20), 466(M+-OCH3),
333([Ph3P C-COOCH3]+,25), 105([C6H5CO]+,45), 77([C6H5]+, 100).
Reaction of Formylmethylenetriphenyphosphorane (4c)
with 2-Phenyl-5-(4H)-oxazolone (1)
A mixture of 4c (0.30 g, 0.001 mol) and 1 (0.16 g, 0.001 mol) in 50 cm3 dry
toluene was refluxed for 10 h. The volatile materials were evaporated
under reduced pressure. The residue was subjected to silica gel column
chromatography to give 10.
(5-Hydroxy-2-phenyl-4,5-dihydro-1,3-oxazol-5-yl)(triphenyl-λ5-
phosphoranylidene) Acetaldehyde (10, C29H24NO3P)
Eluent: petroleum ether/acetone (93/7, v/v) product 10 was separated
as pale yellow crystals, yield 75% m.p. 116◦C. IR (KBr): v = 1690 (C O,
aldehyde), 1630 (C N) cm−1, 3300 (OH), 1582 cm−1(C P), 1430, 968
1
cm−1(C-P, phenyl), 2925 (C-H, aldehyde); H NMR (270 MHz, CDCl3):
δ = 2.15 (s, 1H, OH, exchangeable with D2O), 8.20 (d, 1H, 3JHP = 6.8 Hz
CHO), doublet of doublets centered at 4.20, 4.31 for the unsymmetrical
4
methylene protons with JHH = 1.8 Hz, JHP = 4.65Hz, 7.20–7.81 (m,
20H, Ar); 31P NMR of 10 δ = 19.05 ppm; MS (EI): m/z(%) 469 (M+, 12),
440 (M+-CHO, 35), 162 (M+- [Ph3P C-CHO]., 40),105([C6H5CO]+,90),
77([C6H5]+, 100).
Triphenylphosphine and/or triphenylphosphine oxide are neither
isolated nor detected in the reaction medium.
Reaction of Cyanomethylenetriphenyphosphorane (4d)
with 2-Phenyl-5-(4H )-oxazolone (1)
A mixture of 4d (0.30 g, 0.001 mol) and 1 (0.16 g, 0.001 mol) in 50
cm3 dry toluene was refluxed for 10 h. The volatile materials were
evaporated under reduced pressure. The residue was subjected to silica
gel column chromatography to give 11.

288
L. S. Boulos et al.
(5-Hydroxy-2-phenyl-4,5-dihydro-1,3-oxazol-5-yl)(triphenyl-λ5-
phosphoranylidene) acetonitrile (11, C29H23N2O2P)
Eluent: petroleum ether/acetone (75/25, v/v) product 11 was sepa-
rated as colorless crystals, yield 72% m.p. 170◦C. IR (KBr): ν 1625
(C N), 3300 (OH), 1580 (C P), 1435, 960 cm−1, (P-C, phenyl), 2210
(C≡N) cm−1; 1H NMR (270 MHz, CDCl3): δ = 6.75–7.48 (m, 20H, Aryl),
1.33 (s, 1H, OH, exchangeable with D2O), doublet of doublets centered
at 4.31–4.32 for the methylene protons with JHH = 1.8 Hz, 4JHp = 4.70
Hz; 31P NMR δ = 18.78 ppm, MS (EI): m/z (%) 463 (M+, 10), 435 (M+-
CN, 20), 162 (M+-[Ph3P C-CN, 30]., 105 ([C6H5CO]+,77), 77 ([C6H5]+,
100). Triphenylphosphine and/or triphenylphosphine oxide are neither
isolated nor detected in the reaction medium.
Reaction of 1-Triphenylphosphoranylidene-2-propanone (4e)
with 2-Phenyl-5(4H)-oxazolone (1)
A mixture of 4e (0.31 g, 0.001 mol) and 1 (0.16 g, 0.001 mol) in 50 cm3
dry toluene was refluxed for 8 h. The volatile materials were evaporated
under reduced pressure. The residue was subjected to silica gel column
chromatography to give 12.
1-(5-Hydroxy-2-phenyl-1,3-oxazol-4-yl)propan-2-one (12,
C12H11NO3)
Eluent: petroleum ether/acetone (80/20, v/v) product 12 was sepa-
rated as yellow crystals, yield 75% m.p. 103◦C. IR (KBr): ν 1671 (C O,
COCH3), 1602 (C C), 3340 (OH) cm−1. 1H NMR (270 MHz, CDCl3): δ =
1.42 (s, 3H, CH3), 2.29 (s, 2H, CH2), 9.17 (s, 1H, OH, exchangeable
with D2O), 7.01–8.01 (m, 5H, Aryl); MS (EI): m/z (%) 217 (M+, 25),
202(M+-CH3, 10), 173(M+-COCH3, 20), 144(M+-CH2COCH3, 30), 105
([C6H5CO]+,77), 77 ([C6H5]+, 100).
Triphenylphosphine was also isolated from the reaction medium and
identified (mix. m.p.; ms).
Reaction of Fluorenylidenetriphenylphosphorane (4F) with
2-Phenyl-5-(4H)-Oxazolone (1)
A mixture of 4f (0.42 g, 0.001 mol) and 1 (0.16 g, 0.001 mol) in 50 cm3 dry
toluene was refluxed for 12 h. The volatile materials were evaporated
under reduced pressure. The residue was subjected to silica gel column
chromatography to give 13.

Studies on Phosphonium Ylides XXV
289
5-(9H-Fluoren-9-yl)-2-phenyl-1,3-oxazole (13, C22H15NO)
Eluent: petroleum ether/acetone (95/5, v/v) product 13 was separated
as colorless crystals, yield 80% m.p. 105◦C. IR (KBr): ν 1630 (C N);
1H NMR (270 MHz, CDCl3): δ = 6.90 (s, 1H, CH), 5.35 ppm (s, 1H,
CH-fluorene), 7.25–7.90 (m, 13H, Aryl). MS (EI): m/z (%) 309 (M+,
30), 144(M+-[C13H9], 100).
Triphenylphosphine oxide was also separated and identified (mix.
m.p.; ms).
Reaction of N-(Triphenylphosphoranylidene)Aniline (5)
with 2-Phenyl-5-(4H)-oxazolone (1)
A mixture of 5 (0.35 g, 0.001 mol) and 1 (0.16 g, 0.001 mol) in 50 cm3 dry
toluene was refluxed for 5 h. The volatile materials were evaporated
under reduced pressure. The residue was subjected to silica gel column
chromatography to give 14.
N-(2-Phenyl-1,3-oxazol-5-(4H)-ylidene)Aniline (14, C15H12N2O)
Eluent: petroleum ether/acetone (90/10, v/v) product 15 was sep-
arated as colorless crystals, yield 55% m.p. 198–200◦C. IR (KBr): ν
1637.65 (C N-Ph), 1310 (C-O), 1682 (C N); 1H NMR (270 MHz,
CDCl3): δ = 4.34 (s, 2H, CH2), 7.24–7.82 (m, 10H, Aryl). 13C NMR (270
MHz, CDCl3), δ =168.31 (C N-Ph), 167.22 (C N, ring), 133.19-124.50
(Aryl), 45.08 (CH2); MS (EI): m/z (%) 236 (M+, 10), 159(M+-C6H5,
25), 105 ([C6H5CO]+, 80), 77 ([C6H5]+, 100).
Triphenylphosphine oxide was also separated and identified (mix.
m.p.; ms).
REFERENCES
[1] N. Lalitha, J. Annaparna, D. S. Iyengar, and U. T. Bhaleras, Arzneimittel-Forsch
(Drug Research), 41, 827(1991).
[2] C. Rao and N. Lalitha, Indian J. Chem., 33B, 3 (1994).
[3] P. D. Croce, R. Ferraccidi, and C. L. Rosa, J. Chem. Soc. Perkin Trans I, 2499 (1994).
[4] I. Arenal, M. Bernaba, E. F. Alvarez, M. L. Izquierdo, and S. Penades, J. Heterocycl.
Chem., 20, 607 (1983).
[5] S. Kojima, H. Ohkawa, T. Hirano, S. Maki, H. Niwa, M. Ohashi, S. Inouye, and F. I.
Tsuji, Tetrahedron Lett., 39, 5239 (1998).
[6] C. Cativiela, J. M. Fraile, J. J. Garcia, M. P. Lopez, J. A. Mayoral, and E. Pires,
Tetrahedron Asymmetry, 7, 2391 (1996).
[7] L. S. Boulos and H. A. Abdel-Malek, Indian. J. Heterocycl. Chem., 14, 254 (2005).
[8] L. S. Boulos, E.-S. M. A. Yakout, and M. H. N. Arsanious, Phosphorus, Sulfur, and
Silicon, 181, 1615 (2006).

290
L. S. Boulos et al.
[9] L. S. Boulos, K. E. Nahed, and M. H. N. Arsanious, Phosphorus, Sulfur, and Silicon,
181, 1467 (2006).
[10] M. H. N. Arsanious and L. S. Boulos, Monatsh. Chem., 137, 1177 (2006).
[11] L. S. Boulos, M. H. N. Arsanious, and E.-S. M. A. Yakout, Monatsh. Chem., 138, 979
(2007).
[12] E. Zibral Tetrahedron Lett., 5107 (1970).
[13] C. G. Krespan, J. Am. Chem. Soc. 83, 3434 (1961).
[14] H. J. Bestmann, G. Schmid, and D. Sandmeier, Angew. Chem., 88, 92 (1976); Angew.
Chem., Int. Ed. Engl., 5, 115 (1976).
[15] E. Erba, M. L. Gelmi, and D. Pocar, Chem. Ber., 121, 1519 (1988).
[16] P. Clerc and S. Simon, Spectral Data for Structure, Determination of Organic Com-
pounds (Springer-Verlag, Berlin, Heidelberg, New York, Tokyo, 1983).
[17] H. O. Kalinowski, S. Berger, and S. Braun, 13C NMR Spectroskopie (Georg Thieme
Verlag; Stuttgart, New York, 1984).
[18] F. Clerici, E. Folpini, M. L. Gelmi, and D. Pocar, Tetrahedron, 47, 8907 (1991).
[19] M. L. Gelmi and D. Pocar, Synthesis, 452 (1992).
[20] H. Behringer, K. Falkenberg, Ber. 96, 1428-1435(1963).
[21] Y. S. Liang, J. I. Bruce, and D. A. Boy, Laboratory Cultivation of Schistosome Vector
Snails and Maintenance of Schistosome life Cycles. Proceedings of the First Sino-
American Symposium, 1, 34–48 (1987).
[22] N. G. Nessim, S. I. Hassan, S. William, et al., Effect of the Broad Spectrum An-
thelminic Drug Flubendazole on Schistosoma Mansoni Experimentally Infected
Mice Arzneimittel-Forsch/Drug Res., 50(11), 1129 (2000).
[23] G. S. Gruzdyev, The Chemical Properties of Plants (MIR Publisher, Moscow, 1983),
p. 79.
[24] R. W. Addor, J. A. Furch, and D. G. Kuhn; US Patent 5,030,735, (1991),Chem.
Abstr.115: P183084r (1991).
[25] H. J. Bestmann and O. Kratzer, Chem. Ber., 95, 1894 (1962).
[26] F. Ramirez and S. Dershowitz, J. Org. Chem., 22, 41 (1957) .
[27] H. J. Bestmann and D. Sandmeier, Chem. Ber., 113, 274 (1980).
[28] W. Wiegrabe and H. Bock, Chem. Ber., 101, 1414 (1968).
[29] L. A. Pinck and G. E. Hilbert, J. Am. Chem. Soc., 69, 723 (1947).
[30] J. W. Cornfort, In H.T. Clarke, J. R. Johnson, R. Robinson, The Chemistry of Peni-
cillin (Princeton University Press, Princeton, 1949), p. 778.
[31] H. B. Gillespie and E. R. Snyderin, Org. Synth. (John Wiley, London, 1943), A. H.
Blatt, Ed. Coll., Vol. 2, p.489.