Triphenylphosphine-mediated reaction between dimethyl acetylenedicarboxylate and NH-acids derived from diaminobenzenes

Article abstract of DOI:10.1080/10426500500271550

Protonation of the 1:1 adduct produced in the reaction between triphenylphosphine and dimethyl acetylenedicarboxylate with ethyl 2-[(2-{[2-(ethyloxy)-2-oxoacetyl]amino}phenyl}amino]-2-oxoethanoate leads to a vinylphosphonium salt, which undergoes an inter

Full text of DOI:10.1080/10426500500271550

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Triphenylphosphine-Mediated
Reaction Between Dimethyl
Acetylenedicarboxylate
and NH-Acids Derived from
Diaminobenzenes
Issa Yavari a b & Leila Ahmadian-Razlighi c
a Chemistry Department, Science and Research
Campus, Islamic Azad University, Ponak, Tehran, Iran
b Chemistry Department, Tarbiat Modarres
University, Tehran, Iran
c Chemistry Department, Islamic Azad University,
Tehran North Branch, Tehran, Iran
Published online: 15 Aug 2006.
To cite this article: Issa Yavari & Leila Ahmadian-Razlighi (2006): Triphenylphosphine-
Mediated Reaction Between Dimethyl Acetylenedicarboxylate and NH-Acids Derived
from Diaminobenzenes, Phosphorus, Sulfur, and Silicon and the Related Elements,
181:4, 771-777
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Phosphorus, Sulfur, and Silicon, 181:771–777, 2006
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500500271550
Triphenylphosphine-Mediated Reaction Between
Dimethyl Acetylenedicarboxylate and NH-Acids Derived
from Diaminobenzenes
Issa Yavari
Chemistry Department, Science and Research Campus, Islamic Azad
University, Ponak, Tehran, Iran, and Chemistry Department, Tarbiat
Modarres University, Tehran, Iran
Leila Ahmadian-Razlighi
Chemistry Department, Islamic Azad University, Tehran North Branch,
Tehran, Iran
Protonation of the 1:1 adduct produced in the reaction between triphenylphos-
phine and dimethyl acetylenedicarboxylate with ethyl 2-[(2-{[2-(ethyloxy)-
2-oxoacetyl]amino}phenyl}amino]-2-oxoethanoate leads to
a
vinylphospho-
nium salt, which undergoes an intermolecular Wittig reaction to produce
dimethyl 4-(acetyloxy)-1-(2-{[2-(ethyloxy)-2-oxoacetyl]amino}phenyl)-5-oxo-2,
5-dihydro-1H-pyrrole-2,3-dicarboxylate. Using ethyl 2-[(3-{[2-(ethyloxy)-2-oxo-
acetyl]amino}phenyl)amino]-2-oxoethanoate or ethyl 2-[(4-[2-(ethyloxy)-2-oxo-
acetyl]amino}phenyl)amino]-2-oxoethanoate as an NH acid produces dimethyl 4-
(acetyloxy)-1-(3-{3-(ethyloxy)-4,5-bis[(methyloxy)carbonyl]-2-oxo-2,5-dihydro-1H-
pyrrol-1-yl}phenyl)-5-oxo-2,5-dihydro-1H-pyrrole-2,3-dicarboxylate or dimethyl
4-(ethyloxy)-1-(4-{3-(ethyloxy)-4,5-bis[(methyloxy)carbonyl]-2-oxo-2,5-dihydro-1H-
pyrrol-1-yl}-5-oxo-2,5-dihydro-1H-pyrrole-2,3-dicarboxylate.
Keywords Acetylenic ester; intramolecular Wittig rection; pyrrole derivatives;
triphenylphosphine
INTRODUCTION
Simple nitrogen-containing heterocycles receive considerable attention
in the literature as a consequence of their exciting biological proper-
ties and their role as pharmacophores of historical importance.1 Of
these heterocycles, the synthesis, reactions, and biological activities of
pyrrole-containing molecules stand as an area of research in heteroaro-
matic chemistry, and this structural motif appears in a large number
Received June 7, 2005; accepted June 7, 2005.
Address correspondence to Issa Yavari, Tarbiat Modarres University, Chemistry De-
partment, PO Box 14115-175, Tehran, Iran. E-mail: yavarisa@modares.ac.ir
771

772
I. Yavari and L. Ahmadian-Razlighi
of pharmaceutical agents and natural products.2 Accordingly, many
strategies have been developed for the preparation of pyrroles.2,3 Five-
membered ring lactams have been used in routes to various alkaloids4
and are suitable precursors for γ -amino acids such as statine and its
analogues.5 There are many examples of pyrroline-containing natural
products with interesting pharmacological activates. Typical examples
are the platelet aggregation inhibitor PI-091 and the antitumor al-
kaloide Jatropham.6,7 As part of our current studies on the develop-
ment of new routes to heterocyclic systems,8 we now report that the
reaction of dimethyl acetylenedicarboxylate (DMAD) with ethyl 2-[2-
{[2-(ethyloxy)-2-oxoacety)]amino}phenyl}amino]-2-oxoethanoate (1) in
the presence of triphenylphosphine leads to dimethyl 4-(acetyloxy)-
1-(2-{[2-(ethyloxy)-2-oxoacetyl]amino}-phenyl)-5-oxo-2,5-dihydro-1 H-
pyrrole-2,3-dicarboxylate (2) in a 72% yield (Scheme 1). Attempts to
construct another 5-oxo-2,5-dihydro-1 H-pyrrole moiety by reacting 2
with DMAD and triphenylphosphine were unsuccessful.
SCHEME 1
RESULTS AND DISCUSSION
The reaction of DMAD with 1 in the presence of triphenylphosphine
proceeded spontaneously room temperature in CH2Cl2 and was finished
1
within 24 h. H and 13C NMR spectra of the crude products clearly
indicated the formation of 2. Any product other than 2 could not be
detected by NMR spectroscopy.
Reactions are known in which an unsaturated heterocyclic com-
pound is produced from a phosphorane connected with a carbonyl group
by a chain containing a heteroatom.8−10 Thus, the 2,5-dihydropyrrole
derivative 2 may be regarded as the product of an intramolecular Wit-
tig reaction.10 Such an addition-cyclization product apparently results
from an initial addition of triphenylphosphine to DMAD and the sub-
sequent protonation of the 1:1 adduct 3 by 1 (Scheme 2). Then the posi-
tively charged ion 4 is attacked by the nitrogen atom of the conjugated

Triphenylphosphine-Mediated Reaction
773
base of the NH-acid to form the phosphorane 6, which is converted to
the 2,5-dihydropyrrole derivative 2.
SCHEME 2
The structure of 2 was deduced from its elemental analyses and its
1
IR, H, and 13C NMR spectra. The mass spectrum of this compound
confirms its molecular weight. Initial fragmentation involves the loss
from or the complete loss of the side chains and the scission of the
heterocyclic ring system.
1
The H NMR spectrum of 2 exhibits three sharp lines for methoxy
(δ = 3.61 and 3.84 ppm) and methine (δ = 5.31 ppm) protons. The aryl
moiety shows characteristic signals in the appropriate region of the
spectrum. The 13C NMR spectrum of 2 shows 18 sharp signals in agree-
ment with the proposed structure.
When the reaction between DMAD and triphenylphosphine
was carried out in the presence of ethyl 2-[(3-{[2-(ethyloxy)-2-
oxoacetyl]-amino}phenyl)amino]-2-oxoethanoate (7) or ethyl 2-[(4-
{[2-(ethyloxy)-2-oxoacetyl]amino}phenyl)amino]-2-oxoethanoate
(9)
as an NH-acid, the corresponding dimethyl 4-(acetyloxy)-1-(3-3-
(ethyloxy)-4,5-bis[(methyloxy)carbonyl]-2-oxo-2,5-dihydro-1H-pyrrol-
1-yl}phenyl)-5-oxo-2,5-dihydro-1H-pyrrole-2,3-dicarboxylate (8) or
dimethyl 4-(ethyloxy)-1-(4-{3-(ethyloxy)-4,5-bis[(methyloxy) carbonyl]-
2-oxo-2,5- dihydro-lH pyrrol-l-yl}-5-oxo-2,5-dihydro-lH-pyrrole-2,3-
dicarboxylate (10) was obtained in good yield (see Scheme 3).
1
The H and 13C NMR spectra of 8 and 10 are similar to those of
2. The proposed structures for these compounds were confirmed by
their elemental analyses and IR spectra. The mass spectra of these
isomeric structures are fairly similar and confirm their molecular
weights.

774
I. Yavari and L. Ahmadian-Razlighi
SCHEME 3
In conclusion, the presented reaction gives a simple one-pot entry
into the synthesis of polyfunctionalized 5-oxo-2,5-dihydro-1H-pyrrole
derivatives of potential synthetic interest.
EXPERIMENTAL
Melting points were measured on an Electrothermal 9100 apparatus.
Elemental analyses for C, H, and N were performed using a Heraeus
CHN-O-Rapid analyzer. IR spectra were recorded on a Shimadzu IR-
460 spectrometer. Mass spectra were recorded on a FINNIGAN-MAT
8430 mass spectrometer operating at an ionization potential of 70 eV.
The NMR spectra were recorded at 300 (1H) and 75 (13C) MHz on a
Bruker Avance DPX-300 MHz NMR instrument with CDCl3 as a sol-
vent. Chemical shifts (δ) are reported relative to TMS as the internal
standard. The reagents and solvents used in this work were obtained
from Fluka and used without further purification.

Triphenylphosphine-Mediated Reaction
775
Preparation of 1,7, and 9 Examplified on Ethyl 2-[(2-{[2-(Ethyl-
oxy)-2-oxoacetyl]amino}phenyl}amino]-2-oxoethanoate (1):
Typical Procedure
To a stirred solution of 1,2-diaminobenzene (1.08 g, 10 mmol) in dry
diethyl ether (30 mL) was added, dropwise, a solution of ethyl oxalyl
chloride (3.0 g, 22 mmol) in 10 mL of dry diethyl ether at 10◦C over
10 min. The reaction mixture was allowed to stand at r.t. for 24 h. The
solvent was removed under reduced pressure and the viscous residue
was crystallized from ethanol to produce 1 as pale yellow crystals; m.p.
162–165◦C; yield: 2.7 g (87%). IR (KBr) (νmax/cm−1): 3305 (N H), 1720
and 1728 (C O). 1H NMR (300 MHz, CDCl3): δH = 1.44 (6 H, t, 3 J
=
HH
7.2 Hz, 2 CH3), 4.43 (4 H, q, 3 J = 7.2 Hz, 2 OCH2), 7.34–7.76 (4 H, m,
HH
C6H4), 9.32 (2 H, s, 2 NH) ppm. 13C NMR (75.5 MHz, CDCl3,): δC = 14.3
(2 CH3), 64.2 (2 OCH2), 125.3 (2 CH), 127.8 (2 CH), 129.2 (2 C), 155.4
(2 C O), 160.6 (2 C O) ppm.
Ethyl 2-[(3-{[2-(Ethyloxy)-2-Oxoacetyl]amino}phenyl)amino]-
2-oxoethanoate (7)
Pale yellow crystals; m.p. 121–123◦C; yield: 2.8 g (90%). IR (KBr)
1
(νmax/cm−1): 3301 (N H), 1718 and 1723 (C O). H NMR (300 MHz,
3
3
CDCl3): δH = 1.38 (6 H, t, J = 7 Hz, 2 CH3), 4.38 (4 H, q, J = 7
HH
HH
Hz, 2 OCH2) 7.34–7.53 (3 H, m, 3 H of C6H4), 8.03 (1 H, t, 4 J = 2
HH
Hz, H of C6H4), 9.09 (2 H, s, 2 NH) ppm. 13C NMR (75.5 MHz, CDCl3):
δC = 14.3 (2 CH3), 64.2 (2 OCH2), 111.6 (2 CH), 117.2 (CH), 130.4 (CH),
137.5 (2 C), 154.5 (2 C O), 161.1 (2 C O) ppm.
Ethyl 2-[(4-{[2-(Ethyloxy)-2-oxoacetyl]amino}phenyl)amino]-
2-oxoethanoate (9)
Pale yellow crystals; m.p. 203–205◦C; yield: 2.9 g (93%).
1
IR (KBr) (νmax/cm−1): 3304 (N H), 1714 and 1725 (C O). H NMR
(300 MHz, CHCl3): δH = 1.45 (6 H, t, 3 J = 7.2 Hz, 2 CH3), 4.45 (4 H,
HH
q, 3 J = 7.2 Hz, 2 OCH2), 7.69 (4 H, s, C6H4), 8.91 (2 H, s, 2 NH) ppm.
HH
13C NMR (75.5 MHz, CDCl3.): δC = 14.3 (2 CH3), 64.2 (2 OCH2), 120.9
(4 CH), 134.0 (2 C), 154.1 (2 C O), 161.3 (2 C O) ppm.
Preparation of 2, 8, and 10 Examplified on Dimethyl 4-(Acetyl-
oxy)-1-(2-{[2-ethyloxy)-2-oxoacetyl]amino}phenyl)-5-oxo-2,5-
dihydro-1H-pyrrole-2,3-dicarboxylate(2): Typical Procedure
To a stirred solution of 1 (0.6 g, 2 mmol) and triphenylphosphine (0.52 g,
2 mmol), in 10 mL of toluene was added, dropwise, a solution of DMAD
(0.28 g, 2 mmol) in 5 mL of toluene at 20◦C over 10 min. The reaction

776
I. Yavari and L. Ahmadian-Razlighi
mixture was refluxed for 8 h. The solvent was removed under re-
duced pressure and the viscous residue was purified by preparative
TLC on silica gel (Merck silica gel DC-Fertigplatten 60/Kieselgur F254
)
20 × 20 cm plates using CHCl3 and EtOAc (10:1) as an eluent. Zones
were detected by the quenching of indicator fluorescence upon expo-
sure to 366 nm of UV light. The product was obtained by the ex-
traction of the silica gel with CH2Cl2 to produce a yellow powder;
m.p. 120–123◦C; yield: 0.6 g (72%). IR (KBr) (νmax/cm−1): 1644 and
1717 (C O). 1H NMR (300 MHz, CHCl3): δH = 1.43 (3 H, t, 3 J = 7.1
HH
Hz, CH3), 1.49 (3 H, t, 3 J = 7.1 Hz, CH3), 3.61 (3 H, s, OCH3),
HH
3.84 (3H, s, OCH3), 4.42 (2 H, q, 3 J = 7.1 Hz, OCH2), 4.86 (2 H,
HH
q, 3 J = 7.1 Hz, OCH2), 5.31 (1 H, s, CH), 7.29–7.43 (3 H, m, 3
HH
H of C6H4), 8.20 (1 H, d, 3 J = 8.0 Hz, H of C6H4), 9.42 (1H, s,
HH
NH) ppm. 13C NMR (75.5 MHz, CDCl3): δC = 14.3 (CH3), 16.1 (CH3),
52.5 (OCH3) 53.8 (OCH3), 62.8 (OCH2), 63.9 (CH), 69.2 (OCH2), 113.9
(O C C), 124.9 (CH), 126.8 (CH), 126.9 (CH 127.4 (CH), 130.1 (C),
133.6 (C) 153.7 (O C C), 154.8 (C O), 160.7 (C O), 162.3 (C O), 164.3
(C O), 168.45 (C O) ppm. MS (El, 70 eV): m/z (%) = 436 (M+ + 1,
7), 326 (100), 298 (74), 230 (58), 57 (47), 41 (38). Anal. calcd. of
C20H22N2O9 (436.4): C, 55.04; H, 5.54; N, 6.42. Found: C, 55.26; H, 5.71;
N, 6.46%.
Dimethyl 4-Etyloxy-1-{3-[3-ethyloxy-4,5-bis(methyloxy-
carbonyl)-2-oxo-2,5-dihydro-1H-pyrrol-1-yl]phenyl}-5-oxo-2,5-
dihydro-1H-pyrrole-2,3-dicarboxylate (8)
Yellow powder; m.p. 111–114◦C; yield: 0.66 g (60%). IR (KBr)
1
(νmax/cm−1): 1651 and 1715 (C O). H NMR (300 MHz, CHCl3): δH
=
1.43 (6 H, t, 3 J = 7.2 Hz, 2 CH3), 3.68 (6 H, s, 2 OCH3), 3.82 (6 H, s, 2
HH
OCH3), 4.80 (4 H, q, 3 J = 7.2 Hz, 2 OCH2), 5.37 (2 H, s, 2 CH), 7.42–
HH
7.47 (3 H, m, 3 H of C6H4), 7.90 (1 H, t,4 J = 2 Hz, H of C6H4), ppm.
HH
13C NMR (75.5 MHz, CDCl3): δC = 16.1 (2 CH3), 52.5 (2 OCH3), 53.6
(2 OCH3), 61.2 (2 CH), 69.3 (2 OCH2), 112.2 (O C C), 114.9 (2 CH),
119.4 (CH), 130.4 (CH), 137.7(2 C), 154.5 (2 O C C), 162.0 (C O), 164.0
(C O), 168.4 (C O) ppm. MS (El, 70 eV): m/z (%) = 562 (M+ + 1, 7), 326
(100), 298 (74), 230 (58), 57 (47), 41 (38). Anal. calcd. for C26H28N2O12
(562.5): C, 55.51; H, 5.38; N, 4.98. Found: C, 55.68; H, 5.01; N, 5.02%.
Dimethyl 4-Ethoxy-1-{4-[3-ethoxy-4,5-bis(methoxycarbonyl)-
2-oxo-2,5-dihydro-1H-pyrrol-1-Yl]phenyl}-5-oxo-2,5-
dihydro-1H-pyrrole-2,3-dicarboxylate (10)
Yellow powder; m.p. 117–120◦C; yield: 0.7 g (63%). IR (KBr) (νmax/cm−1):
1
1648 and 1717 (C O). H NMR (300 MHz, CHCl3): δH = 1.42 (6 H, t,

Triphenylphosphine-Mediated Reaction
777
3 J = 7.2 Hz, 2 CH3), 3.65 (6 H, s, 2 OCH3), 3.88 (6 H, s. 2 OCH3), 4.81
HH
(4 H, q, 3 J = 7.2 Hz, 2 OCH2), 5.35 (2H, s, 2 CH) 7.62 (4 H, s, C6H4)
HH
ppm. 13C NMR (75.5 MHz, CDCl3): δC = 16.0 (2 CH3), 52.4 (2 OCH3),
53.5 (2 O CH3), 61.1 (2 CH), 62.2 (2 OCH2), 112.1 (2 O C C), 122.3
(4 CH), 134.6 (2 C), 154.6 (2 O C C), 162.4 (C O), 163.9 (C O), 168.4
(C O) ppm. MS (El, 70 eV): m/z (%) = 562 (M+ + 1, 7), 326 (100). 298
(74), 230 (58), 57 (47), 41 (38). Anal. Calcd. for C26H28N2O12 (562.5): C,
55.51; H, 5.38; N, 4.98. Found: C, 55.74; H, 5.05; N, 5.04%.
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