Chemoselective synthesis of new stable phosphorus ylides from the reaction between triphenylphosphine and activated acetylenic esters in the presence of heterocyclic biological bases

Article abstract of DOI:10.1080/10426501003776921

A facile and chemoselective one-pot synthesis of novel stable phosphorus ylides has been developed from the reaction between triphenylphosphine and dialkyl acetylenedicarbocxylates in the presence of (heterocyclic) biological bases such as purine, theophy

Full text of DOI:10.1080/10426501003776921

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Phosphorus, Sulfur, and Silicon and the
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Chemoselective Synthesis of New
Stable Phosphorus Ylides from the
Reaction Between Triphenylphosphine
and Activated Acetylenic Esters in the
Presence of Heterocyclic Biological Bases
Sayyed Mostafa Habibi-Khorassani a , Malek Taher Maghsoodlou a ,
Nourallah Hazeri a , Khatereh Bagherpour a , Mohsen Rostamizadeh a
& Hamed Najafi b
a Department of Chemistry , The University of Sistan and
Baluchestan , Zahedan, Iran
b The University of Iranshahr , Iranshahr, Iran
Published online: 13 Jan 2011.
To cite this article: Sayyed Mostafa Habibi-Khorassani , Malek Taher Maghsoodlou , Nourallah Hazeri ,
Khatereh Bagherpour , Mohsen Rostamizadeh & Hamed Najafi (2010) Chemoselective Synthesis of New
Stable Phosphorus Ylides from the Reaction Between Triphenylphosphine and Activated Acetylenic
Esters in the Presence of Heterocyclic Biological Bases, Phosphorus, Sulfur, and Silicon and the
Related Elements, 186:1, 21-30, DOI: 10.1080/10426501003776921
To link to this article: http://dx.doi.org/10.1080/10426501003776921
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Phosphorus, Sulfur, and Silicon, 186:21–30, 2011
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426501003776921
CHEMOSELECTIVE SYNTHESIS OF NEW STABLE
PHOSPHORUS YLIDES FROM THE REACTION BETWEEN
TRIPHENYLPHOSPHINE AND ACTIVATED ACETYLENIC
ESTERS IN THE PRESENCE OF HETEROCYCLIC
BIOLOGICAL BASES
Sayyed Mostafa Habibi-Khorassani,1 Malek Taher
Maghsoodlou,1 Nourallah Hazeri,1 Khatereh Bagherpour,1
Mohsen Rostamizadeh,1 and Hamed Najafi2
1Department of Chemistry, The University of Sistan and Baluchestan,
Zahedan, Iran
2The University of Iranshahr, Iranshahr, Iran
GRAPHICAL ABSTRACT
CO2R
Z
(Ph)3P
ROOC
+
C
Z-H
+
C
COOR
PPh3
RO2C
H
O
O
O
H3C
N
N
CH3
N
N
N
N
N
,
Z :
R :
,
,
N
N
N
N
O
N
S
O
N
H
N
H
CH3
Me , Et , t-Bu
Abstract A facile and chemoselective one-pot synthesis of novel stable phosphorus ylides
has been developed from the reaction between triphenylphosphine and dialkyl acetylenedi-
carbocxylates in the presence of (heterocyclic) biological bases such as purine, theophylline,
6-azauracil, and 6-aza-2-thiothymine at ambient temperature.
Keywords 6-Aza-2-thiothymine; 6-azauracil; purine; stable phosphorus ylides; theophylline
Received 13 December 2009; accepted 15 March 2010.
We gratefully acknowledge support of this work by the Research Council of the University of Sistan &
Baluchestan.
Address correspondence to Malek Taher Maghsoodlou, Department of Chemistry, The University of Sistan
and Baluchestan, P. O. Box 98135-674, Zahedan, Iran. E-mail: mt maghsoodlou@yahoo.com
21

22
S. M. HABIBI-KHORASSANI ET AL.
INTRODUCTION
Purine and pyrimidine ring systems form the backbone of many important biolog-
ical molecules, such as nucleic acids, cofactors, and various toxins. The ability of these
molecules to interact with proteins has been extensively exploited in the preparation of
inhibitors that work specifically against certain conditions, such as Gleevec (cancer) or
aronixil (atherosclerosis), for example. The privileged nature of the purine/pyrimidine
structure in terms of their shape and hydrogen-bonding characteristics make them ideal
starting points in the search for new chemical entities of biological significance.1
The synthesis and chemistry of purine has attracted considerable attention due to
its pharmaceutical and biological properties. Some purine derivatives such as theophylline
have long been used as anti-inflammatory drugs.2–4 Phosphorus ylides are reactive systems,
which take part in many reactions of value in organic synthesis.5–15 Several methods have
been developed for the preparation of phosphorus ylides. These ylides are usually prepared
by treatment of a phosphonium salt with a base, and phosphonium salts are usually obtained
from the phosphine and an alkyl halide.5,9,10,12,13 In recent years, there have been some
reports about the synthesis of stable phosphorus ylides.16–29 In this article, we describe an
efficient synthetic route to new stable phosphorus ylides.
RESULTS AND DISCUSSION
The reaction between triphenylphosphine, electron-deficient acetylenic esters such
as dialkyl acetylenedicarbocxylates 1, and biological bases 3 such as purine, theophylline,
6-azauracil, and 6-aza-2-thiothymine led to the corresponding stable phosphorus ylides
(Figure 1). On the basis of the mechanism proposed in Figure 1, it is obvious that the reaction
between acetylenic esters and Ph3P produces the carbene–ylide intermediate 2, which is suf-
ficiently stabilized by resonance.26,27 Thus, compounds 4a–k are apparently obtained from
the initial addition of triphenylphosphine as a good nucleophile28 to acetylenic esters as a
OR
O
Ph3P
ROOC
C-COOR
2
+
Z-H
PPh3 +
ROOC
COOR
H
Z
Ph3P
1
3
COOR
4a-k
Z
Yield (%)
Yield (%)
4
a
R
4
Z
R
O
Me
Et
f
Me
t-Bu
90
92
88
90
95
N
N
N
N
g
h
b
N
N
N
O
t-Bu
N
H
O
N
O
c
Me
Et
i
j
Me
Et
90
93
85
88
H C
3
CH
N
N
3
N
d
e
N
O
S
k
N
H
t-Bu
t-Bu
90
95
CH
3
Figure 1 Synthesis of stable phosphorus ylides 4a–k.

SYNTHESIS OF NEW STABLE PHOSPHORUS YLIDES
23
Michael acceptor,29 and concomitant protonation of the carbene–ylide intermediate 2 by the
heterocyclic biological bases 3. Then the positively charged ion is attacked by the nitrogen
of the conjugated base of 3 to form succinic esters containing several functional groups 4.
The 1H and 13C NMR spectra of the crude products clearly indicated the formation of
phosphorus ylides 4. No product other than 4 could be detected by NMR spectroscopy. The
structures of compounds 4a–k were characterized on the basis of elemental analyses, IR,
mass, 1H NMR, and 13C NMR spectra. The 1H NMR spectrum of 4b showed two singlet
at δ = 1.01, 1.54 for tert-butyl groups and a doublet at δ = 5.22 (J = 16.6) arising from
methine proton (CH C P group). The aromatic protons of triphenylphosphine appeared
as a multiplet at δ = 7.26–7.69 and three singlets at δ = 8.56, 8.98, and 9.02 for aromatic
protons of purine. As can be seen in the Experimental section, the 13C NMR spectrum of
4b displayed 23 distinct resonances, which are in a good agreement with only one isomer,
presumably, because of the tert-butyl groups. Compounds 4e, 4h, and 4k are similar to
that of 4b. The 1H, 13C, and 31P NMR spectra of compounds 4a, 4c, 4d, 4f, 4g, 4i, and 4j
showed a mixture of two rotational isomers (Figure 2). Assignment of E-4(a, c, d, f, g, i,
j) and Z-4(a, c, d, f, g, i, j) isomers as the major or minor form in phosphorus ylides have
been previously reported in the literature.30–32 The 1H NMR spectrum of 4a exhibited two
singlets at 3.23 and 3.74 ppm arising from two methoxy groups in the Z isomer and two
singlets at 3.68 and 3.74 ppm for two methoxy groups in the E isomer. The shift at 3.23
ppm of the methoxy group in the Z isomer is shielded due to the anisotropic effect of a
phenyl group of triphenylphosphine. This effect confirms why the Z-4a and E-4a isomers
could appear as the major and minor forms, respectively, with respect to the experimental
abundance percentage of both isomers (see the Experimental section). Also, signals for
methine protons appeared as two doublets at δ = 5.37 (J = 16.7 Hz) and δ = 5.41 (J =
16.7 Hz), respectively, for the E and Z isomers. The carbonyl region of these compounds
4a–k exhibited absorption bands for each compound in their IR spectra. Of special interest
is the ester absorption at 1614–1755 cm−1. Conjugation with the negative charge of the ylide
moiety with the adjacent carbonyl group accounts for the reduction of the wave numbers
of the carbonyl absorption bands. This phenomenon confirms why the equilibrium could
appear between the E and Z isomers; this will be effective in the methodological study of
synthesis of these compounds. The ylide moiety of these compounds is strongly conjugated
with the adjacent carbonyl group, and rotation around the partial double bond E-4(a, c,
d, f, g, i, j) and Z-4(a, c, d, f, g, i, j) isomers is slow on the NMR time scale at ambient
temperature (Figure 2).
In continuation of our investigations, we found that from the reaction between triph-
enylphosphine, acetylenic esters, purine, or theophylline, a mixture of two products was ob-
tained with different portions in the presence of acetone, ethyl acetate, and dichloromethane
OR
O
O
Ph3P
Ph3P
OR
RO2CHC
Z
RO2CHC
Z
E-4(a, c, d, f, g, i, j)
Z-4(a, c, d, f, g, i, j)
Minor
Major
Figure 2 Equilibrium could appear between E and Z isomer.

24
S. M. HABIBI-KHORASSANI ET AL.
CH3
N
O
N
N
O
H
N
H3C
O
N
O
Ph3P
N
CH3
H
N
N
RO2C
CO2R
CO2R
CO2R
CH3
4c-e
Acetonitril or Diethyl Ether
r.t.
+
or
Ph3P
+
or
N
N
N
N
N
H
N
N
N
Ph3P
RO2C
H
CO2R
r.t.
CH2Cl2
4a-b
CH3
N
O
N
O
N
N
H3C
O
N
N
N
N
N
N
N
N
N
N
H3C
N
N
+
O
CO2R
PPh3
or
H
H
+
CH3 H
RO2C
CO2R
PPh3
CO2R
PPh3
H
CO2R
PPh3
RO2C
RO2C
RO2C
4c-e
4a-b
5
6
Figure 3 Synthesis of stable phosphorus ylide from purine and theophylline in different solvents.
solvents, respectively; our efforts to separate them was were unsuccessful by chromatog-
raphy, whereas they (purine or theophylline) produce only one product (4a–b or 4c–e) in
ether and acetonitrile solvents, respectively (Figure 3).
NMR spectroscopy was employed to distinguish 4 from the products 5 and 6. For example,
for the ylide containing a purine, the chemical shift of the 13C NMR spectra for the carbon
atom between two nitrogen atoms in the place of fused rings changes from 154.8 ppm (in
the uncoordinated purine) to 151.6 ppm in product. This can be seen as a whole for bases
with fused rings.33 The structural assignments made for stable phosphorus ylides 4a–e on
the basis of the 1H, 13C, and 31P NMR spectra were supported by their IR spectra.
CONCLUSIONS
In summary, we have demonstrated a one-pot, simple, and effective procedure for the
preparation of stable phosphorus ylides from the reaction between triphenylphosphine and
dialkyl acetylenedicarbocxylates in the presence of biological bases such as purine, theo-
phylline, 6- azauracil, and 6-aza-2-thiothymine at ambient temperature. The present method
carries the advantage that, not only is the reaction performed under neutral conditions, but
the substances can be mixed without any activation or modifications.12–23,31
EXPERIMENTAL
Dialkyl acetylenedicarboxylate, purine, theophylline, 6-azauracil, 6-aza-2-
thiothymine, and triphenylphosphine were purchased from Fluka (Buchs, Switzerland)
and were used without further purification. Melting points and IR spectra were measured

SYNTHESIS OF NEW STABLE PHOSPHORUS YLIDES
25
on an Electrothermal 9100 apparatus and a Shimadzu IR-460 spectrometer, respectively.
1
Also, the H, 13C, and 31P NMR spectra were obtained from a Bruker DRX-500 Avance
instrument using CDCl3 as applied solvent at 500.1, 125.8, and 202.4 MHz, respectively.
In addition, the mass spectra were recorded on a Shimadzu GC/MS QP 1100 EX mass
spectrometer operating at an ionization potential of 70 eV. Elemental analyses for C, H,
and N were performed using a Heraeus CHN-O-Rapid analyzer.
General Procedure for the Synthesis of Stable Phosphorus Ylides
To a magnetically stirred solution of triphenylphosphine (0.262 g, 1 mmol) and N H
acid (1 mmol) indiethyl ether (10mL), a mixtureof dialkyl acetylenedicarboxylate (1mmol)
in diethyl ether (2 mL) was added dropwise at −5◦C over 10 min. The reaction mixture was
then allowed to warm up to room temperature and stirred for 10 h. The solvent was then
removed under reduced pressure, and the generated precipitate was filtered and washed
with cold diethyl ether.
Dimethyl 2-(purine-1-yl)-3-triphenylphosphoranylidene)-butanedioate
(4a). Mp 160–162◦C, yield 90%; IR (KBr) (vmax, cm−1): 1752 and 1630 (C O).; MS,
(m/z,%): 524(M+, 8), 466 (42), 262 (85), 183 (100), 120 (76), 108 (42). Anal. Calcd. For
C29H25N4O4P (524): C, 66.41; H, 4.77; N, 10.68%. Found: C, 66.85; H, 4.73; N, 10.4%.
Major isomer 4a-(Z) (55%): 1H NMR (500.1 MHz, CDCl3): δ 3.23 and 3.74 (6H, 2s,
2OCH3), 5.41 (1H, d, 3JPH = 16.7 Hz, P C CH), 7.43–7.60 (15H, m, 3C6H5), 8.58, 8.93
and 9.04 (3H, s, N C H). 13C NMR (125.8 MHz, CDCl3): δ 43.4 (d, 1JPC = 127.5 Hz,
P C), 49.6 and 53.0 (2s, 2OCH3), 56.7 (d, 2JPC = 17.2 Hz, P C CH), 125.7 (d, 1JPC
=
3
91.6 Hz, Cipso), 129.0 (d, JPC = 12.3 Hz, Cmeta), 129.3 (C5H4N4), 132.5 (Cpara), 133.4
3
2
(d, JPC = 9.9 Hz, Cortho), 146.1, 147.1, 151.6 and 155.1 (C5H4N4), 165.5 (d, JPC
=
15.9 Hz, P C C), 171.0 (d, 3JPC = 12.4, C O). 31P NMR (202.4 MHz, CDCl3): δ 23.21
(Ph3P+ C).
Minor isomer 4a-(E) (45%): 1H NMR (500.1 MHz, CDCl3): δ 3.68 and 3.74 (6H, 2s,
2OCH3), 5.37 (1H, d, 3JPH = 16.7 Hz, P C CH), 7.43–7.60 (15H, m, 3C6H5), 8.62, 8.71
and 9.06 (3H, s, N C H). 13C NMR (125.8 MHz, CDCl3): δ 43.2 (d, 1JPC = 131.0 Hz,
2
1
P C), 52.3 and 53.1 (2OCH3), 56.5 (d, JPC = 16.7 Hz, P C CH), 125.1 (d, JPC
=
3
92.7 Hz, Cipso), 128.5 (d, JPC = 11.2 Hz, Cmeta), 129.2 (C5H4N4), 132.5 (Cpara), 132.5
2
2
(d, JPC = 10.2 Hz, Cortho), 146.6, 147.3, 150.7 and 154.3 (C5H4N4), 170.8 (d, JPC
=
15.7 Hz, P C C), 170.5 (d, JPC = 12.2 Hz, C O). 31P NMR (202.4 MHz, CDCl3): δ
3
24.40 (Ph3P+ C).
Di-tert-butyl 2-(purine-1-yl)-3-(triphenylphosphoranylidene)-butanedio-
ate (4b). Mp 153–155◦C. yield 92%; IR (KBr) (νmax, cm−1): 1742, 1628 (C O). MS, m/z
(%): 608 (M+,11), 507 (63), 407 (96), 262 (98), 183 (73), 108 (39), 57 (44). Anal. Calcd.
For C35H37N4O4P: C, 69.06; H, 6.13; N, 9.20%. Found: C, 69.10; H, 6.11; N, 9.14%.
Only isomer 4b-(Z) (92%): 1H NMR (500.1 MHz, CDCl3), δ 1.01 and 1.54 (18H, 2s,
2CMe3), 5.22 (1H, d, 3JPH = 16.6 Hz, P C CH), 7.27–7.69 (15H, m, 3C6H5), 8.56, 8.98
and 9.02 (3H, 3s, N C H). 13C NMR (125.8 MHz, CDCl3), δ 28.1 and 28.3 (2CMe3), 43.3
(d, 1JPC = 128.2 Hz, P C), 57.4 (d, 2JPC = 17.8 Hz, P C CH), 78.2 and 82.0 (2OCMe3),
1
3
126.9 (d, JPC = 91.8 Hz, Cipso), 128.8 (d, JPC = 12.3 Hz, Cmeta), 132.3 (Cpara), 133.5
2
2
(d, JPC = 9.9 Hz, Cortho), 147.4, 150.7, 151.5 and 152.6 (C5H4N4), 169.5 (d, JPC
=
12.5 Hz, P C C), 169.6 (d, JPC = 13.1 Hz, C O). 31P NMR (202.4 MHz, CDCl3): δ
3
22.83 (Ph3P+ C−).

26
S. M. HABIBI-KHORASSANI ET AL.
Dimethyl 2-(theophylline-1-yl)-3-(triphenylphosphoranylidene)-butane-
dioate (4c). Mp 157–159◦C. yield 90%; IR (KBr) (νmax, cm−1): 1755, 1707, 1663 and
1638 (C O). MS, m/z (%): 584 (M+,5), 262 (100), 183 (58), 180 (14), 108 (24), 77 (18).
Anal. Calcd. For C31H29N4O6P: C, 63.69; H, 5.00; N, 9.58%. Found: C, 63.66; H, 5.08;
N, 9.54%.
Major isomer 4c-(Z) (53%): 1H NMR (500.1 MHz, CDCl3): δ 3.18 and 3.61 (6H,
3
2s, 2CH3), 3.46 and 3.74 (6H, 2s, 2OCH3), 5.53 (1H, d, JPH = 17.6 Hz, P C CH),
7.40–7.71 (15H, m, 3C6H5), 8.28 (1H, s, N C H). 13C NMR (125.8 MHz, CDCl3): δ
27.5 and 29.6 (2CH3), 43.0 (d, 1JPC = 130.7 Hz, P C), 49.6 and 52.9 (2OCH3), 60.1 (d,
1
2JPC = 15.8 Hz, P C CH), 106.9 (C7H8N4O2), 125.9 (d, JPC = 88.7 Hz, Cipso), 129.0
3
2
(d, JPC = 12.0 Hz, Cmeta), 132.5 (Cpara), 133.4 (d, JPC = 8.8 Hz, Cortho), 139.9, 147.8,
151.7, 154.5 (C7H8N4O2), 170.3 (d, 2JPC = 12.6 Hz, P C C), 170.9 (d, 3JPC = 12.8 Hz,
C O). 31P NMR (202.4 MHz, CDCl3): δ 24.74 (Ph3P+ C).
Minor isomer 4c-(E) (47%): 1H NMR (500.1 MHz, CDCl3): δ 3.60 and 3.66 (6H,
3
2s, 2CH3), 3.56 and 3.64 (6H, 2s, 2OCH3), 5.50 (1H, d, JPH = 16.8 Hz, P C CH),
7.40–7.71 (15H, m, 3C6H5), 8.16 (1H, s, N C H). 13C NMR (125.8 MHz, CDCl3): δ
28.2 and 30.1 (2CH3), 38.1 (d, 1JPC = 127.1 Hz, P C), 50.4 and 52.8 (2OCH3), 60.1 (d,
2JPC = 15.8 Hz, P C CH), 107.0 (C7H8N4O2), 125.2 (d, JPC = 91.0 Hz, Cipso), 129.0
1
(d, 3JPC = 12.0 Hz, Cmeta), 132.5 (Cpara), 133.4 (d, 2JPC = 8.8 Hz, Cortho), 141.1, 148.63,
150.7, 155.5 (C7H8N4O2), 170.5 (d, 2JPC = 12.9 Hz, P C C), 170.9 (d, 3JPC = 13.0 Hz,
C O). 31P NMR (202.4 MHz, CDCl3): δ 25.80 (Ph3P+ C).
Diethyl
2-(theophylline-1-yl)-3-(triphenylphosphoranylidene)-butane-
dioate (4d). Mp 185–186◦C. yield 93%; IR (KBr) (νmax, cm−1): 1754, 1704, 1666 and
1637(C O). MS, m/z (%): 612 (M+, 6), 539 (4), 433 (100), 277 (4), 262 (95), 183 (40),
108 (22). Anal. Calcd. For C33H33N4O6P: C, 64.70; H, 5.43; N, 9.15%. Found: C, 64.77;
H, 5.41; N, 9.10%.
Major isomer 4d-(Z) (54%): 1H NMR (500.1 MHz, CDCl3): δ 0.53 and 1.29 (6H,
2OCH2CH3), 3.19 and 3.58 (6H, 2s, 2CH3), 3.80 and 4.28 (4H, m, 2OCH2CH3), 5.52 (1H,
d, JPH = 17.2 Hz, P C CH), 7.47–7.69 (15H, m, 3C6H5), 8.30 (1H, s, N C H). 13C
3
NMR (125.8 MHz, CDCl3) δ: 14.0 and 14.1 (2OCH2CH3), 27.5 and 29.6 (2CH3), 42.8 (d,
1JPC = 127.0 Hz, P C), 58.3 and 60.0 (2OCH2CH3), 61.7 (d, 2JPC = 17.7 Hz, P C CH),
1
3
107.0 (C7H8N4O2), 126.0 (d, JPC = 91.8 Hz, Cipso), 128.9 (d, JPC = 11.8 Hz, Cmeta),
132.0 (Cpara), 133.4 (d, 2JPC = 9.6 Hz, Cortho), 141.8, 147.7, 151.7 and 154.4 (C7H8N4O2),
2
3
165.1 (d, JPC = 12.6 Hz, P C C), 170.5 (d, JPC = 12.2 Hz, C O). 31P NMR (202.4
MHz, CDCl3): δ 23.56 (Ph3P+ C).
Minor isomer 4d-(E) (46%): 1H NMR (500.1 MHz, CDCl3): δ 1.26 and 1.31 (6H,
2OCH2CH3), 3.22and 3.58 (6H, 2s, 2CH3), 4.08 and 4.16 (4H, m, 2OCH2CH3), 5.46(1H,
d, JPH = 18.6 Hz, P C CH), 7.47–7.69 (15H, m, 3C6H5), 8.20 (1H, s, N C H). 13C
3
NMR (125.8 MHz, CDCl3): δ: 14.1 and 14.8 (2OCH2CH3), 28.2 and 30.1 (2CH3), 42.8 (d,
1JPC = 135.6 Hz, P C), 58.8 and 59.8 (2OCH2CH3), 61.8 (d, 2JPC = 17.2 Hz, P C CH),
1
3
106.7 (C7H8N4O2), 125.4 (d, JPC = 91.6 Hz, Cipso), 128.5 (d, JPC = 12.0 Hz, Cmeta),
132.1 (Cpara), 133.5 (d, 2JPC = 8.4 Hz, Cortho), 141.7, 148.4, 151.8 and 155.3 (C7H8N4O2),
2
3
169.7 (d, JPC = 12.0 Hz, P C C), 170.3 (d, JPC = 12.0 Hz, C O). 31P NMR (202.4
MHz, CDCl3): δ 24. 78 (Ph3P+ C).
Di-tert-butyl-2-(theophylline-1-yl)-3-(triphenylphosphoranylidene)-bu-
tanedioate (4e). Mp 136–137◦C. yield 95%; IR (KBr) (νmax, cm−1): 1746, 1703, 1655
and 1630 (C O). MS, m/z (%): 668 (M+, 8), 489 (4), 377 (8), 26 2 (100), 183 (38), 108
(93). Anal. Calcd. For C37H41N4O6P: C, 66.45; H, 6.18; N, 8.38%. Found: C, 66.40; H,
6.21; N, 8.34%.

SYNTHESIS OF NEW STABLE PHOSPHORUS YLIDES
27
Only isomer 4e-(Z) (95%): 1H NMR (500.1 MHz, CDCl3), δ 0.99 and 1.54 (18H, 2s,
2CMe3), 3.17 and 3.56 (6H, 2s, 2CH3), 5.40 (1H, d, 3JPH = 17.3 Hz, P C CH), 7.27–7.71
(15H, m, 3C6H5), 8.34 (1H, s, N C H). 13C NMR (125.8 MHz, CDCl3), δ 27.5 and 29.6
(2CH3), 28.1 and 28.2 (2CMe3), 43.0 (d, 1JPC = 127.1 Hz, P C), 60.7 (d, 2JPC = 17.5 Hz,
P C CH), 78.0 and 81.7 (2OCMe3), 106.7 (C7H8N4O2), 126.4 (d, 1JPC = 91.5 Hz, Cipso),
128.8 (d, 3JPC = 12.0 Hz, Cmeta), 132.3 (Cpara), 133.4 (d, 2JPC = 9.5 Hz, Cortho), 142.1 and
2
147.6 and 151.7 and 154.4 (C7H8N4O2), 169.2 (d, JPC = 12.3 Hz, P C C), 169.7 (d,
3JPC = 11.7 Hz, C O). 31P NMR (202. 4 MHz, CDCl3): δ 23.14 (Ph3P+ C).
Dimethyl 2-(6-azauracil-1-yl)-3-(triphenylphosphoranylidene)-butane-
dioate (4f). Mp 170–171◦C, yield 88%; IR (KBr) (νmax, cm−1): 3449 (N H)1736, 1702,
1646 and 1618 (C O). MS, m/z (%): 517 (M+,11), 473 (3), 405 (3), 262 (100), 183 (53),
108 (29).). Anal. Calcd. For C27H24N3O6P: C, 62.67; H, 4.67; N, 8.12%. Found: C, 62.70;
H, 4.61; N, 8.18%.
1
Major isomer 4f-(Z) (60%): H NMR (500.1 MHz, CDCl3): δ 3.15 and 3.75 (6H,
3
2s, 2OCH3), 5.26 (1H, d, JPH = 16.5 Hz, P C CH), 7.27–7.69 (16H, m, 3C6H5 and
C3H3N3O2), 9.15(1H, s, NH). 13C NMR (125.8 MHz, CDCl3): δ 38.6 (d, 1JPC = 129.6 Hz,
2
1
P C), 49.2 and 52.9 (2OCH3), 62.8 (d, JPC = 16.0 Hz, P C CH), 126.4 (d, JPC
=
91.5 Hz, Cipso), 128.9 (d, 3JPC = 12.0 Hz, Cmeta), 132.4 (Cpara), 133.6 (d, 2JPC = 9.7 Hz,
2
Cortho), 147.6, 156.4 and 165.4 (C3H3N3O2), 170.8 (d, JPC = 13.2 Hz, P C C), 170.9
(d, 3JPC = 12.1 Hz, C O). 31P NMR (202.4 MHz, CDCl3): δ 23.03 (Ph3P+ C).
1
Minor isomer 4f-(E) (40%): H NMR (500.1 MHz, CDCl3): δ 3.56 and 3.70
3
(6H, 2s, 2OCH3), 5.31 (1H, d, JPH = 17.9, P C CH), 7.27–7.69 (16H, m, 3C6H5
and C3H3N3O2), 9.15(1H, s, NH). 13C NMR (125.8 MHz, CDCl3): δ 39.7 (d, JPC
=
1
2
138.1 Hz, P C), 50.4 and 52.3 (2OCH3), 62.2 (d, JPC = 16.0 Hz, P C CH), 125.7
1
3
(d, JPC = 91.5 Hz, Cipso), 128.5 (d, JPC = 12.1 Hz, Cmeta), 132.4 (Cpara), 133.6 (d,
2JPC = 9.1 Hz, Cortho), 148.7, 159.7 and 165.6 (C3H3N3O2), 169.9 (d, JPC = 12.9 Hz,
2
P C C), 171.1 (d, JPC = 17.3 Hz, C O). 31P NMR (202.4 MHz, CDCl3): δ 23.12
3
(Ph3P+ C).
Diethyl-2-(6-azauracil-1-yl)-3-(triphenylphosphoranylidene)-butane-
dioate (4g). Mp 165–166◦C. yield 90%; IR (KBr) (νmax, cm−1): 3273 (N H), 1730,
1702 and 1614 (C O). MS, m/z (%): 545 (M+,10), 409 (2), 380 (10), 283 (3), 262 (100),
183 (72), 113(5), 108 (28). Anal. Calcd. For C29H28N3O6P: C, 63.85; H, 5.17; N, 7.70%.
Found: C, 63.894; H, 5.20; N, 7.74%.
Major isomer 4g-(Z) (55%): 1H NMR (500.1 MHz, CDCl3): δ 0.44 and 1.29 (6H,
2OCH2CH3), 3.71 and 4.17 (4H, m, 2OCH2CH3), 5.31 (1H, d, 3JPH = 17.3 Hz, P C CH),
7.46–7.72 (16H, m, 3C6H5 and C3H3N3O2), 8.76(1H, s, NH). 13C NMR (125.8 MHz,
1
CDCl3): δ 14.1 and 14.8 (2OCH2CH3), 38.4 (d, JPC = 129.9 Hz, P C), 57.8 and 61.3
(2OCH2CH3), 62.9 (d, 2JPC = 16.4 Hz, P C CH), 126.7 (d, 1JPC = 91.4 Hz, Cipso), 128.5
3
2
(d, JPC = 12.1 Hz, Cmeta), 131.9 (Cpara), 133.6 (d, JPC = 9.0 Hz, Cortho), 147.4, 156.3
and 165.0 (C3H3N3O2), 169.3 (d, 2JPC = 12.7 Hz, P C C), 170.22 (d, 3JPC = 12.7 Hz,
C O). 31P NMR (202.4 MHz, CDCl3): δ 23.03 (Ph3P+ C).
Minor isomer 4g-(E) (45%),1H NMR (500.1 MHz, CDCl3): δ 1.15 and 1.31(6H,
2OCH2CH3), 4.01 and 4.23 (4H, m, 2OCH2CH3), 5.21 (1H, d, 3JPH = 17.3 Hz, P C CH),
7.46–7.72 (16H, m, 3C6H5 and C3H3N3O2), 8.76(1H, s, NH). 13C NMR (125.8 MHz,
1
CDCl3): δ 13.8 and 14.0 (2OCH2CH3), 39.6 (d, JPC = 133.1 Hz, P C), 58.5 and 61.2
(2OCH2CH3), 62.3 (d, 2JPC = 17.2 Hz, P C CH), 126.0 (d, 1JPC = 91.5 Hz, Cipso), 128.7
(d, 3JPC = 12.1 Hz, Cmeta), 131.9 (Cpara), 132.1 (d, 2JPC = 9.8 Hz, Cortho), 147.5, 158.4 and
165.3 (C3H3N3O2), 170.3 (d, 2JPC = 11.3 Hz, P C C), 170.9 (d, 3JPC = 15.1 Hz, C O).
31P NMR (202.4 MHz, CDCl3): δ 23.38 (Ph3P+ C).

28
S. M. HABIBI-KHORASSANI ET AL.
Di-tert-butyl-2-(6-azauracil-1-yl)-3-(triphenylphosphoranylidene)-bu-
tanedioate (4h). Mp 186–188◦C. yield 95%; IR (KBr) (νmax, cm−1): 3180 (N H),
1750, 1714, 1681 and 1650 (C O). MS, m/z (%): 601 (M+,10), 262 (100), 183 (56), 108
(32), 57 (33). Anal. Calcd. For C33H36N3O6P: C, 65.88; H, 6.03; N, 6.98%. Found: C,
65.90; H, 6.01; N, 6.93%.
Only isomer 4h-(Z) (95%): 1H NMR (500.1 MHz, CDCl3), δ 0.93 and 1.54 (18H,
3
2s, 2CMe3), 5.00 (1H, d, JPH = 16.8 Hz, P C CH), 7.27–7.72 (16H, m, 3C6H5 and
C3H3N3O2), 9.15 (1H, s, NH). 13C NMR (125.8 MHz, CDCl3), δ 27.4 and 27.4 (2s,
2CMe3), 39.5 (d, 1JPC = 125.4 Hz, P C), 62.3 (d, 2JPC = 17.4 Hz, P C CH), 80.3 and
81.0 (2OCMe3), 126.6 (d, 1JPC = 91.3 Hz, Cipso), 128.0 (d, 3JPC = 12.0 Hz, Cmeta), 131.3
2
(Cpara), 133.9 (Cortho), 147.3, 148.8 and 157.0 (C3H3N3O2), 167.7 (d, JPC = 12.2 Hz,
3
P C C), 168.8 (d, JPC = 13.6 Hz, C O). 31P NMR (202.4 MHz, CDCl3): δ 22.46
(Ph3P+ C).
Dimethyl-2-(6-aza-2-thiothymine-1-yl)-3-(triphenylphosphoranylidene)-
butanedioate (4i). Mp 132–134◦C. yield 85%; IR (KBr) (νmax, cm−1): 3423 (N H),
1752, 1702 and 1628 (C O).MS, m/z (%): 547 (M+,11), 277 (12), 262 (100), 183 (100),
143 (13), 108 (35), 59 (23). Anal. Calcd. For C28H26N3O5PS: C, 61.42; H, 4.79; N, 7.67%.
Found: C, 61.40; H, 4.075; N, 7.70%.
1
Major isomer 4i-(Z) (70%): H NMR (500.1 MHz, CDCl3): δ 2.26 (3H, s, CH3),
3.15 and 3.81 (6H, 2s, 2OCH3), 6.05(1H, d, 3JPH = 19.1 Hz, P C CH), 7.30–7.69 (15H,
m, 3C6H5), 9.39(1H, s, N H). 13C NMR (125.8 MHz, CDCl3): δ 16.6 (s, CH3), 41.4 (d,
1JPC = 138.4 Hz, P C), 49.4 and 52.7 (2s, 2OCH3), 68.8 (d, 2JPC = 15.5 Hz, P C CH),
126.4 (d, 1JPC = 91.5 Hz, Cipso), 128.9 (d, 3JPC = 12.5 Hz, Cmeta), 132.2 (Cpara), 133.6 (d,
2
2JPC = 9.7 Hz, Cortho), 147.1, 152.6 (C4H5N3OS), 170.1 (d, JPC = 12.6 Hz, P C C),
172.3 (d, 3JPC = 16.8 Hz, C O). 173.3 (C4H5N3OS),. 31P NMR (202.4 MHz, CDCl3): δ
24.05 (Ph3P+ C).
Minor isomer 4i-(E) (30%),1H NMR (500.1 MHz, CDCl3): δ 2.29 (3H, s, CH3),
3.56 and 3.70 (6H, 2s, 2OCH3), 6.10 (1H, d, 3JPH = 18.6 Hz, P C CH), 7.30–7.69 (15H,
m, 3C6H5), 9.39 (1H, s, N H). 13C NMR (125.8 MHz, CDCl3): δ 16.1 (s, CH3), 40.1 (d,
2
1JPC = 130.8 Hz, P C), 50.5 and 53.4 (2OCH3), 67.9 (d, JPC = 15.8 Hz, P C CH),
125.7 (d, 1JPC = 91.7 Hz, Cipso), 128.6 (d, 3JPC = 13.5 Hz, Cmeta), 132.2 (Cpara), 132.0 (d,
2JPC = 7.3 Hz, Cortho), 148.2, 154.72, (C4H5N3OS), 169.9 (d, 2JPC = 16.6 Hz, P C C),
171.3 (d, 3JPC = 17.7 Hz, C O), 173.3 (s, C4H5N3OS),. 31P NMR (202.4 MHz, CDCl3):
δ 24.09 (Ph3P+ C).
Diethyl-2-(6-aza-2-thiothymine-1-yl)-3-(triphenylphosphoranylidene)-
butanedioate (4j). Mp 136–137◦C. yield 88%; IR (KBr) (νmax, cm−1): 3423 3419
(N H), 1740, 1698, 1616 and (C O). MS, m/z (%): 575 (M+,4), 491 (7), 277 (10), 262
(40), 183 (22), 108 (9). Anal. Calcd. For C30H30N3O5PS: C, 62.60; H, 5.25; N, 7.30%.
Found: C, 62.65; H, 5.21; N, 7.33%.
1
Major isomer 4j-(Z) (70%): H NMR (500.1 MHz, CDCl3): δ 0.47 and 1.25
(6H, 2OCH2CH3), 2.26 (3H, s, CH3), 3.65 and 4.07 (4H, m, 2OCH2CH3), 6.00 (1H,
3
d, JPH = 17.1 Hz, P C CH), 7.44–7.72 (15H, m, 3C6H5), 9.60 (1H, s, N H). 13C
NMR (125.8 MHz, CDCl3) δ: 13.9 and 14.1 (2OCH2CH3), 16.5 (s, CH3), 40.0 (d, 1JPC
=
130.4 Hz, P C), 57.9 and 61.5 (2OCH2CH3), 69.0 (d, 2JPC = 15.3 Hz, P C CH), 126.7
(d, 1JPC = 91.5 Hz, Cipso), 128.7 (d, 3JPC = 11.8 Hz, Cmeta), 132.2 (Cpara), 133.7 (d, 2JPC
=
9.4 Hz, Cortho), 147.0, 152.6 (C4H5N3OS), 169.4 (d, 2JPC = 11.5 Hz, P C C), 172.5 (d,
3JPC = 12.2 Hz, C O), 172.2 (C4H5N3OS). 31P NMR (202.45 MHz, CDCl3): δ 23.99
(Ph3P+ C).

SYNTHESIS OF NEW STABLE PHOSPHORUS YLIDES
29
Minor isomer 4j-(E) (30%),1H NMR (500.1 MHz, CDCl3): δ 1.16 and 1.29 (6H,
2OCH2CH3), 2.30 (3H, s, CH3), 3.77 and 4.16 (4H, m, 2OCH2CH3), 6.12 (1H, d, 3JPH
=
17.5 Hz, P C CH), 7.44–7.72 (15H, m, 3C6H5), 9.60 (1H, s, N H). 13C NMR (125.8
1
MHz, CDCl3): δ: 14.9 and 15.2 (2OCH2CH3), 16.4 (s, CH3), 41.3 (d, JPC = 138.5 Hz,
P C), 58.5 and 61.4 (2OCH2CH3), 67.9 (d, 2JPC = 16.2 Hz, P C CH), 126.0 (d, 1JPC
=
91.7 Hz, Cipso), 128.9 (d, 3JPC = 11.1 Hz, Cmeta), 132.1 (Cpara), 133.5 (d, 2JPC = 8.4 Hz,
Cortho), 146.8, 152.9 (C4H5N3OS), 169.4 (d, 2JPC = 12.0 Hz, P C C), 171.0 (d, 3JPC
=
17.7 Hz, C O), 173.2 (C4H5N3OS),. 31P NMR (202.4 MHz, CDCl3): δ 24. 31 (Ph3P+ C).
Di-tert-butyl-2-(6-aza-2-thiothymine-1-yl)-3-(triphenylphosphoranyli-
dene)-butanedioate (4k). Mp 162–163◦C. yield 90%; IR (KBr) (νmax, cm−1): 3420
(N-H), 1750, 1702 and 1653 (C O).MS, m/z (%): 631 (M+,45), 262 (48), 183 (45), 57
(43). Anal. Calcd. For C34H38N3O5PS: C, 64.64; H, 6.06; N, 6.65%. Found: C, 64.60; H,
6.01; N, 6.68%.
1
Only isomer 4k-(Z) (90%): H NMR (500.1 MHz, CDCl3), δ 0.94 and 1.54 (18H,
2s, 2CMe3), 2.39 (3H, s, CH3), 5.62 (1H, d, 3JPH = 17.2 Hz, P C CH), 7.45–7.72 (15H,
m, 3C6H5), 9.11 (1H, s, N H). 13C NMR (125.8 MHz, CDCl3), δ 16.9 (CH3), 28.0 and
28.2 (2CMe3), 39.5 (d, 1JPC = 131.7 Hz, P C), 69.5 (d, 2JPC = 18.0 Hz, P C CH), 77.3
1
3
and 81.2 (2OCMe3), 127.3 (d, JPC = 91.3 Hz, Cipso), 128.7 (d, JPC = 12.0 Hz, Cmeta),
132.1 (Cpara), 133.6 (d, 2JPC = 9.2 Hz, Cortho), 146.9, 152.4 and 172.0 (C4H5N3OS), 168.1
(d, JPC = 13.4 Hz, P C C), 168.1 (d, JPC = 13.8 Hz, C O). 31P NMR (202.4 MHz,
2
3
CDCl3): δ 23.64 (Ph3P+ C).
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