A view of an unusual route for certain phosphorus ylide

Article abstract of DOI:10.14233/ajchem.2014.18098

An abnormal route for the synthesis of (5-(2-(2-cyanophenyl)hydrazono)-2,3-bis (methoxycarbonyl)-4-phenylcyclopent-2-enyl)triphenyl phosphonium (5) has been patented. The synthesis of compound (5) was performed by the reaction of 2-(2-(1,3-dioxo-1-phenylp

Full text of DOI:10.14233/ajchem.2014.18098

Asian Journal of Chemistry; Vol. 26, No. 23 (2014), 8239-8242
ASIAN JOURNAL OF CHEMISTRY
http://dx.doi.org/10.14233/ajchem.2014.18098
A View of an Unusual Route for Certain Phosphorus Ylide
KHADIJAH M. AL-ZAYDI
Department of Chemistry, Science Faculty for Girls, King Abdulaziz University, Jeddah, P.O. Box 50918, Jeddah 21533, Kingdom of Saudi
Arabia
Corresponding author: Tel.: +966 50 567 8718; E-mail: alzaydi_kh@yahoo.com; kalzaydi@kau.edu.sa
Received: 29 May 2014;
Accepted: 12 August 2014;
Published online: 15 November 2014;
AJC-16333
An abnormal route for the synthesis of (5-(2-(2-cyanophenyl)hydrazono)-2,3-bis(methoxycarbonyl)-4-phenylcyclopent-2-enyl)triphenyl
phosphonium (5) has been patented. The synthesis of compound (5) was performed by the reaction of 2-(2-(1,3-dioxo-1-phenylpropan-
2-ylidene)hydrazinyl)benzonitrile with dimethylacetylene dicarboxylate in dichloromethane at room temperature for 2 h in order to yield
a cyclic intermediate. The subsequent addition of triphenylphosphine afforded the desired product as interesting crystals suitable for
X-ray crystallographic analysis. The synthesized compound was characterized based on (FT-IR, NMR, elemental analysis and single
crystal X-ray diffraction studies). A possible mechanism for the synthesis was also reported.
Keywords: Phosphorus ylide.
2-ylidene)hydrazinyl)benzonitrile (2) with dimethyl-acetylene-
INTRODUCTION
dicarboxylate (3) in dichloromethane at room temperature
Phosphorus ylides are reactive systems which occur in a
significant number of valuable reactions of organic synthesis1-17
gives the intermediate (A) (Scheme-I). The subsequent addition
of triphenylphosphine resulted in two products20.
.
The development of simple synthetic routes for widely used
organic compounds from readily available reagents is one of
the major tasks in organic chemistry. Cyclopentene derivatives
are currently a matter of interest since many have been found
to be of benefit in inhibiting and treating tumors18.
Compound (5-(2-(2-aryl)hydrazono)-2,3-bis(methoxy-
carbonyl)-4-phenylcyclo-pent-2-enyl)triphenylphosphonium
(1) (Fig. 1) is an intermediate for the production of cyclo-
pentene derivatives.
After separation and identification of the obtained products
by spectral data and elemental analyses, one of the products
was identified as compound 4 (40 %), whereas the other one
was identified as compound 5 (60 %), (Scheme-I)20. Whereas,
it was found that one pot addition of reactants 2, 3 and triphenyl-
phosphine in dichloromethane as solvent at room temperature
lead to the direct formation of compound (4) (Scheme-I)24,25
.
EXPERIMENTAL
Literature survey shows that the major synthetic approach
that was used previously to prepare phosphorus ylides is based
on the treatment of the phosphonium salt (prepared via the
reaction of the phosphine with alkyl halide) with base2-4.
Furthermore, these compounds are generally prepared via the
Michael addition of phosphorus nucleophiles to activated
olefins19.
All melting points were measured on Gallenkamp electro-
thermal melting point apparatus and are uncorrected. IR spectra
were recorded on KBr disks using a Nicolet Magna 520 FTIR
spectrophotometer. 1H NMR and 13C NMR spectra was recorded
on a Bruker DPX400 spectrometer at 400 MHz with DMSO-
d6 as solvent and TMS as internal standards; chemical shifts
are reported in δ units (ppm). Mass spectra were measured on
a Shimadzu GCMS-QP1000 Ex mass spectrometer at 70 eV.
Elemental analysis was measured by means of a Perkin Elmer
2400 CHN elemental analyzer flow chart. X-ray crystallo-
graphy was carried out on a Kappa CCD Enraf Nonius FR
590 diffractometer, National Research Center, Dokki, Cairo,
Egypt.
It should be mentioned that (5-(2-(2-aryl)hydrazono)-2,3-
bis(methoxy carbonyl)-4-phenylcyclopent-2-enyl)triphenyl-
phosphonium derivatives have been previously synthesized
and isolated with difficulty from a mixture of products20-23
.
Therefore, there is a necessity to synthesize this compound in
pure form using a more straight forward method. It has been
reported that the reaction of 2-(2-(1,3-dioxo-1-phenylpropan-

8240 Al-Zaydi
Asian J. Chem.
MeOOC
COOMe
Ph
1H, J = 14.4 Hz, cyclopentane H), 3.70 (s, 3H, OCH3), 3.77
(s, 3H, OCH3), 6.16-7.92 (m, 24H, Ar-H), 11.22 (s, 1H, NH,
D2O exchangeable). 13C NMR (DMSO-d6, 100 MHz): δ 45.3,
49.0, 50.6, 50.81, 100.3, 111.5, 113.0, 117.6, 117.6, 121.6,
123.6, 124.3, 126.9, 128.5, 128.6, 132.8, 133.5, 136.5, 142.2,
147.8, 150.5, 116.5 (CN), 165.1, 171.2 (C=O); MS: 650 (M+);
Anal. Calcd. for C40H33N3O4P (650.68): C, 73.83; H, 5.11; N,
6.46. Found: C, 73.92; H, 5.08; N, 6.40 %.
Ph3P
HN
N
Ar
Fig. 1. Intermediate that is used for the production of cyclopentene derivatives
O
O
C
O
RESULTS AND DISCUSSION
COOMe
COOMe
H
COOMe
Ph
Ph
Ph P
3
As an extension of our studies, compound 4 was synthe-
sized according to the previously mentioned method24, and
the structure of 4 was confirmed by X-ray diffraction analysis
(Table-1 for crystal's data) of a suitable crystal, Fig. 226. The
proposed reaction mechanism is described in Scheme-II24.
N
N
+
N
NH
CH Cl , R.T.
2
2
NC
NC
COOMe
3
4
2
TABLE-1
CRYSTAL DATA AND STRUCTURE REFINEMENT FOR 4
CH Cl , R.T.
2
2
Then addn. of Ph P
3
A
O
Empirical formula
Formula weight
Temperature
C21H17N3O5
391.383
298 K
MeOOC
Ph3P
COOMe
Wavelength
Crystal system
Space group
0.71073 Å
Prismatic
C2/c
COOMe
P
h
Ph
+
N
N
COOMe
N
HN
NC
Unit cell dimensions
a = 10.1935 (6) Å
b = 16.9076 (11) Å
c = 23.211 (2) Å
3957.4 (5) Å3
8
α = 90.00°
β = 98.402 (3)°
γ = 90.00°
NC
Volume
4
5
Z
Scheme-I: Normal route for formation of compounds (4) and (5)
Density (calculated)
Absorption coefficient
∆/σmax
1.314 Mg/m3
0.10 mm-1
0.039
Synthesis of dimethyl 6-benzoyl-2-(2-cyanophenyl)-
2,3-dihydropyridazine-3,4-dicarboxylate (4): Dimethyl-
acetylenedicarboxylate (3) (0.14 g, 10 mmol) in 10 mL dichlo-
roethane was added to a stirred solution of triphenylphosphine
(0.26 g, 10 mmol) and 2-(2-(1,3-dioxo-1-phenylpropan-2-
ylidene)hydrazinyl)benzonitrile (2) (0.28 g, 10 mmol) in
10 mL dichloroethane, then the reaction mixture was left at
room temperature overnight. The solvent was removed and
the residue cooled to deposit a solid, m.p. 205-206 ºC; IR (KBr,
νmax, cm-1): 2221 (C=N), 1746, 1717 (2C=O ester) and 1673
(C=O ketone); 1H NMR (DMSO-d6, 400 MHz): δ 3.67, 3.76
(s, 3H, 2OCH3), 6.61-7.32 (m, 9H, Ar-H) and 7.80 (s, 1H,
pyridazine H-5); MS: 403 (M+); Anal. Calcd. for C22H17N3O5
(403.39): C, 65.50; H, 4.25; N, 10.42; Found: C, 65.92; H,
4.08; N, 10.42 %.
Synthesis of (5-(2-(2-cyanophenyl)hydrazono)-2,3-
bis(methoxycarbonyl)-4-phenylcyclopent-2-enyl)tri-
phenylphosphonium (5): A mixture of (0.28 g, 10 mmol) of
2-(2-(1,3-dioxo-1-phenylpropan-2-ylidene)hydrazinyl)-
benzonitrile (3) and (0.14 g, 10 mmol) dimethylacetylenedi-
carboxylate (4) in 25 mL CH2Cl2 was stirred for 2 h at room
temperature. Then, triphenylphosphine (0.26 g, 10 mmol) was
added and stirring was maintained at room temperature
overnight. After evaporating to dryness under vacuum, the
resulting solid product was collected by filtration, washed with
ethanol, dried and recrystallized from ethanol to give
compound 6 as orange crystals: yield (0.59 g, 91 %). m.p.
175-176 ºC; IR (KBr, νmax, cm-1): 3416 (NH), 2229 (C=N),
1746 (C=O, ester); 1H NMR (DMSO-d6, 400 MHz): δ 2.75 (d,
0.25eÅ-3
-0.25eÅ-3
∆ρmax
∆ρmin
Theta range for data
collection
2.910-18.499°.
Index ranges
-9 < = h < = 9, -15 < = k <
= 15, -20 < = l < = 20
2778
Reflections collected
Independent reflections 1073 [R(int) = 0.029]
Completeness to
θ = 18.49°
99.5 %
Absorption correction
Refinement method
Multi-scan
Full-matrix least-squares
on F2
Data/restraints/parameters 1073/0/271
Goodness-of-fit on F2
1.001
R1 = 0.033, wR2 = 0.068
R1 = 0.063, wR2 = 0.153
Not determined
Final R indices [I > 3σ(I)]
R indices (all data)
Absolute structure
parameter
Efforts have been directed towards the development of
convenient synthetic approaches for the construction of some
heterocyclic compounds22,27. The method for the synthesis of
(5-(2-(2-cyanophenyl)hydrazono)-2,3-bis(methoxycar-bonyl)-
4-phenylcyclopent-2-enyl)triphenyl phosphonium (5) was
modified. In this case, the reaction of 2-(2-(1,3-dioxo-1-phenyl-
propan-2-ylidene)hydrazinyl)benzonitrile (2) with dimethyl-
acetylene dicarboxylate (3) in dichloromethane was performed
at room temperature for 2 h in order to yield a cyclic intermediate.

Vol. 26, No. 23 (2014)
A View of an Unusual Route for Certain Phosphorus Ylide 8241
COOMe
COOMe
PPh3
Ph3P
+
MeOOC
COOMe
3
O
O
C
H
Ph
N
NH
Ar
2
H
C
O
O
Ph
Ph
Ph
COOMe
COOMe
P
O
Ph
O
COOMe
N
HN
Ph
Ph3P
COOMe
Ar
N
NH
Ar
-Ph3PO
Fig. 2. Ortep of dimethyl 6-benzoyl-2-(2-cyanophenyl)-2,3-dihydropyri-
dazine-3,4-dicarboxylate (4)
O
O
Afterwards, the addition of triphenylphos-phine to the reaction
mixture afforded compound 5 as the sole product (Scheme-
III).
The structure of compound 5 was confirmed by elemental
analysis, spectral data, and X-ray crystallography (Fig. 3)26.
Single crystal X-ray diffraction of compound 5 adds strong
COOMe
COOMe
Ph
COOMe
COOMe
Ph
Carbene Insertion
N
N
NH
Ar
N
Ar
Ar= C6H4CN-o
4
Scheme-II: Proposed mechanism for the formation of compound 4
O
COOMe
COOMe
CHO
O
O
C
Ph
COOMe
COOMe
C
COOMe
PhOC
HN
C
H
C
Ph
C
N
C
H
+
N
N
NH
Ar
HN
Ar
O
Ar
COOMe
unstable Intermediate
3
2
C
B
Then addn. of Ph3P
COOMe
O
MeOOC
Ph3P
COOMe
Ph
N
C
COOMe
OH
C
HN
Ar
Ph
Ph3P
N
HN
Ar
D
Ar=C6H4CN-o
5
Scheme-III: Proposed mechanism of the formation of compound 5

8242 Al-Zaydi
Asian J. Chem.
TABLE-2
CRYSTAL DATA AND STRUCTURE REFINEMENT FOR 5
evidence for the proposed structure (Table-2 for crystal's data).
Formation of compound 5 was assumed to proceed via cyclo-
addition of compounds 2 to 3, which gives the unstable four-
membered ring (B) that subsequently rearrange to give inter-
mediate (C). The nucleophilic attack of triphenylphosphine
to the aldehydic group in (C), followed by the addition and
finally deoxygenation of compound D yielded the new poly-
functional phosphacyclopentane 5 (Scheme-III). This synthesis
is superior to the former methods as it supplies a higher yield
and simplifies the separation process.
Empirical formula
Formula weight
Temperature
C40H30N3O4P
647.671
298 K
Wavelength
Crystal system
Space group
0.71073 Å
Prismatic
P21/c
Unit cell dimensions
a = 9.1133 (11) Å
b = 20.945 (3) Å
c = 17.994 (3) Å
3317.5 (8) Å3
4
α = 90.00°
β = 105.010 (2)°
γ = 90.00°
Conclusion
Volume
Z
Changing the mode of addition of reactants, resulted in
an efficient, facile pathway for the synthesis of an important
phosphourus ylide in pure form.
Density (calculated)
Absorption coefficient
∆/σmax
1.297 Mg/m3
0.13 mm-1
0.041
0.71e Å-3
-0.96e Å-3
2.910-19.980 °.
-8 < = h < = 8, -20 < =
k < = 20, -17 < = l < =
17
∆ρmax
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∆ρmin
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8620
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Fig. 3. Ortep of (5-(2-(2-cyanophenyl)hydrazono)-2,3-bis(methoxy-
carbonyl)-4-phenylcyclopent-2-enyl)triphenylphosphonium (5)