Triphenylphosphine-mediated synthesis of the E/Z isomers of methyl 6-(1,2-di(methoxycarbonyl))-8-(ethyl carbamoylformyl)-2-oxo-2H-chromene-4- carboxylate

Article abstract of DOI:10.1080/10426500500272301

Triphenylphosphine-mediated reaction of dimethyl acetylenedicarboxylate with ethyl (2-hydroxyphenylcarbamoyl)formate in boiling toluene produces a mixture of methyl 8-(ethyl carbamylformyl)-2-oxo-2H-chromene-4-carboxylate and the E/Z isomers of methyl 6-(

Full text of DOI:10.1080/10426500500272301

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Triphenylphosphine-
Mediated Synthesis of the E/
Z Isomers of Methyl 6-(1,2-
Di(methoxycarbonyl))-8-(ethyl
Carbamoylformyl)-2-oxo-2H-
chromene-4-carboxylate
Issa Yavari a b & Fakhrossadat Feiz-Javadian a 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 Campus , Tehran, Iran
Published online: 01 Feb 2007.
To cite this article: Issa Yavari & Fakhrossadat Feiz-Javadian (2006)
Triphenylphosphine-Mediated Synthesis of the E/Z Isomers of Methyl 6-(1,2-
Di(methoxycarbonyl))-8-(ethyl Carbamoylformyl)-2-oxo-2H-chromene-4-carboxylate,
Phosphorus, Sulfur, and Silicon and the Related Elements, 181:5, 1011-1016, DOI:
10.1080/10426500500272301
To link to this article: http://dx.doi.org/10.1080/10426500500272301
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Phosphorus, Sulfur, and Silicon, 181:1011–1016, 2006
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500500272301
Triphenylphosphine-Mediated Synthesis of the E/Z
Isomers of Methyl 6-(1,2-Di(methoxycarbonyl))-8-(ethyl
Carbamoylformyl)-2-oxo-2H-chromene-4-carboxylate
Issa Yavari
Chemistry Department, Science and Research Campus, Islamic Azad
University, Ponak, Tehran, Iran, and Chemistry Department, Tarbiat
Modarres University, Tehran, Iran
Fakhrossadat Feiz-Javadian
Chemistry Department, Islamic Azad University, Tehran North
Campus, Tehran, Iran, and Chemistry Department, Science and
Research Campus, Islamic Azad University, Ponak, Tehran, Iran
Triphenylphosphine-mediated reaction of dimethyl acetylenedicarboxylate with
ethyl (2-hydroxyphenylcarbamoyl)formate in boiling toluene produces a mixture
of methyl 8-(ethyl carbamylformyl)-2-oxo-2H-chromene-4-carboxylate and the E/Z
isomers of methyl 6-(1,2-di(methoxycarbonyl)-8-(ethyl carbamoylformyl)-2-oxo-2H-
chromene-4-carboxylate in moderate yields.
Keywords 2-oxo-2H-chromene; acetylenic ester; aromatic substitution; triphenylphos-
phine
INTRODUCTION
2-Oxo-2H-chromenes (coumarines) and their derivatives have stim-
ulated interesting research in organic chemistry and medicine due
to their antibiotic,1 anticoagulant,2,3 and antiinflamatory4 properties.
Also a considerable number of natural or synthetic derivatives of
coumarine have found pharmaceutical applications.5,6 Thus, the syn-
thesis of this heterocyclic nucleus is of interest. Coumarines have
been synthesized by several methods.7,8 Recently, we reported9 a new
method for the synthesis of 3-pyrrolin-2-ones 2 by an intramolecu-
lar Wittig reaction10 of phosphorane 1 (Scheme 1). In order to pre-
pare 3-pyrrolin-2-ones with a hydroxyl group in the ortho position of
Received April 26, 2005; accepted April 26, 2005.
Address correspondence to Issa Yavari, Chemistry Department, Tarbiat Modarres
University, PO Box 14115-175, Tehran, Iran. E-mail: yavarisa@modares.ac.ir
1011

1012
I. Yavari and F. Feiz-Javadian
the aromatic moiety, such as 3, we attempted the reaction of ethyl
(2-hydroxyphenylcarbamoyl)formate (4) with dimethyl acetylendicar-
boxylate (DMAD) in the presence of triphenylphosphine in boiling
toluene. The reaction proceeded spontaneously, but instead of 3, a
mixture of 5 and the E/Z isomers of 6 were obtained in moderate
yields (Scheme 1). The reaction of tertiary phosphorus nucleophiles
with DMAD and phenol have been discussed with emphesis upon the
synthesis of phosphorus heterocycles.11
SCHEME 1
RESULTS AND DISCUSSION
The reaction of 4 with DMAD in the presence of triphenylphos-
phine was carried out in toluene at a reflux temperature for 8 h.
The solvent was removed, and the yellow solid was separated by
preparative TLC to afford methyl 8-(ethyl carbamylformyl)-2-oxo-2H-
chromene-4-carboxylate (5) and the E/Z isomers of methyl 6-(1,2-
di(methoxycarbonyl)-8-(ethyl carbamoylformyl)-2-oxo-2H-chromene-4-
carboxylate (6). The structures of compounds 5 and 6 were assigned
on the basis of their elemental analyses and their IR,1H NMR, 13C

Triphenylphosphine-Mediated Synthesis
1013
NMR, and mass spectral data. The mass spectra of these compounds
display molecular ion peaks at appropriate m/z values. Any initial frag-
mentation involved the loss of ester moieties and the scission of the
heterocyclic ring.
1
The H NMR spectrum of 5 exhibited signals for methyl (δ = 1.47
ppm), methoxy (δ = 4.04 ppm), and methylene (δ = 4.48 ppm) protons
together with characteristic multiplets (δ = 7.01–8.70 ppm) for the aro-
matic protons. The amidic proton signal appears at δ = 9.50 ppm. The
13C NMR spectrum of 5 showed 15 distinct resonances in agreement
with the proposed structure. Partial assignments of these resonances
1
are given in the Experimental section. The H and 13C NMR spectra
of 6 are fairly similar to those of 5 except for the side chain and the
protons of the aromatic ring, which exhibit characteristic signals with
appropriate chemical shifts (see the Experimental section). The struc-
tural assignments of compounds 5 and 6 made on the basis of their 1H
and 13C NMR spectra were supported by their IR spectra. The carbonyl
region of these compounds displayed characteristic absorption bands.
The assignment of configuration of the carbon–carbon double bound in
6 is based on the chemical shift of the olefinic proton.12
A plausible mechanism for the formation of coumarine derivative 5
is shown in Scheme 2. On the basis of the well-established chemistry of
trivalent phosphorus nucleophiles,13,14 it is reasonable to assume that
compound 5 results from the initial addition of triphenylphosphine to
DMAD and subsequent protonation of the reactive 1:1 adduct by 3. Then
the positively charged ion 8 is attacked by the conjugate base of 4. The
product is presumably produced by the intramolecular lactonization of
the vinyl substituted phenol 12. Similar pathways may be proposed
for the formation of compound 6. The E/Z isomers of 6 are presum-
ably formed via further vinylation of 5 by the electrophilic substitution
reaction with 8.
We have found a simple reaction for the synthesis of methyl 8-(ethyl
carbamylformyl)-2-oxo-2H-chromene-4-carboxylate (5) and the E/Z iso-
mers of methyl 6-(1,2-di(methoxycarbonyl)-8-(ethyl carbamoylformyl)-
2-oxo-2H-chromene-4-carboxylate (6) in moderate yields. The one-pot
nature of the procedure makes it an acceptable method for preparation
of substituted coumarines.
EXPERIMENTAL
Ethyl (2-hydroxyphenylcarbamoyl)formate (4) was prepared using 2-
aminophenol and ethyl chloro-oxalate. Triphenylphosphine and DMAD
were obtained from Fluka and were used without further purifica-
tion. Melting points were measured on Electrothermal 9100 apparatus.

1014
I. Yavari and F. Feiz-Javadian
SCHEME 2
Elemental analyses for C and H were performed using a Heraus CHN-
O-Rapid analyzer. The NMR spectra were recorded at 300 (1H) and 75.5
(13C) MHz on a Bruker 300-AVANCE FT-NMR instrument with CDCl3
as a solvent. Chemical shifts (δ) are reported relative to TMS as the in-
ternal standard. IR spectra were recorded on a Bomem MB-100 IR spec-
trometer. Mass spectra were recorded on a Finnigan-Matt 8430 mass
spectrometer operating at an ionization potential of 70 eV. Preparative
TLC was performed on glass plates prepared with silica gel. Column
chromatography was performed using 230–400 mesh Merck silica gel,
and mixtures of n-hexane and EtOAc were used as an eluent.
Preparation of Compounds 5 and 6
To a magnetically stirred solution of 4 (1.05 g, 5 mmol) and triph-
enylphosphine (1.31 g, 5 mmol) in toluene (35 mL) a mixture of DMAD
(1.42 g, 10 mmol) in toluene (5 mL) at room temperature was added
dropwise. The mixture was refluxed for 8 h. The solvent was removed
under reduced pressure and the residue was purified by TLC using
n-hexane and EtOAc as an eluent. The light yellow crystals of 5 were
separated from the E/Z mixture of 6. The isomeric mixture of 6 was
separated by preparative TLC.

Triphenylphosphine-Mediated Synthesis
1015
Methyl 8-(Ethyl Carbamylformyl)-2-Oxo-2H-Chromene-
4-Carboxylate (5)
◦
Light yellow crystals; yield: 0.27 g (18%), m.p. 216–218 C. IR (KBr):
3386 (NH), 1745 and 1725 (C O), 1271 (C O) cm−1. 1H NMR (300 MHz,
CDCl3): δ = 1.47 (t, 3 H, 3 J = 7.2 Hz, CH3), 4.04 (s, 3 H, OCH3 ), 4.48
HH
(q, 2 H, 3 J = 7.2 Hz, OCH2), 7.01 (s, 1 H, CH), 7.39 (t, 1 H, J = 8.2
HH
HH
Hz, CH), 8.09 (dd, 1H , 3 J = 8.2 Hz and 4 J = 2.0 Hz, CH), 8.70 (dd,
HH
HH
1 H, 3 J = 8.2 Hz and 4 J = 2.0 Hz, CH), 9.50 (s, 1H, NH ) ppm. 13
C
HH
HH
NMR (75 MHz, CDCl3):δ = 14.4 (CH3), 53.8 (OCH3), 64.4 (OCH2), 116.2
(C), 119.8 (CH), 123.2 (CH), 123.3 (C), 123.4 CH), 125.3 (CH), 143.1 (C),
144.0 (C), 154.7 (C O), 158.5 (C O), 160.4 (C O), 164.3 (C O) ppm.
MS (EI, 70 eV): m/z = 319 (M+, 7), 304 (32), 290 (65), 260 (43), 246
(57), 228 (11), 105 (100). Anal. calcd. for C15H13NO7 (319.3): C, 56.43;
H, 4.10; N, 4.39. Found: C, 56.58; H, 4.08; N, 4.41%.
Methyl (Z)-6-(1,2-Di(methoxycarbonyl)-8-(ethyl
Carbamoylformyl)-2-oxo-2H-chromene-4-carboxylate (Z-6)
Yellow crystals; yield: 0.64 g (28%), m.p. 132–134◦C, IR (KBr): 3383
(NH), 1735, 1731, and 1720 (C O), 1271 and 1197 (C O) cm−1
.
1H
3
NMR (300.1 MHz, CDCl3): δ = 1.44 (t, 3 H, J = 7.2 Hz, CH3), 3.80
HH
(s, 3 H, OCH3), 3.98 (s, 3 H, OCH3), 4.01 (s, 3 H, OCH3), 4.46 (q, 2 H,
3 J = 7.2 Hz, OCH2) , 6.44 (s, 1 H, CH), 7.09 (s, 1 H, CH), 8.33 (d, 1
HH
H, 4 J = 2.1 Hz, CH), 8.92 (d, 1 H, 4 J = 2.1 Hz, CH), 9.56 (s, 1H,
HH
HH
NH ) ppm. 13C NMR (75 MHz, CDCl3): δ = 14.4 (CH3), 52.6 (OCH3),
53.3 (OCH3), 53.9 (OCH3), 64.5 (OCH2), 116.5 (C), 119.2 (CH), 120.8
(C), 121.0 (CH), 121.9 (CH), 126.0 (CH), 130.5 (C), 142.0 (C), 144.8 (C),
147.1 (C), 154.8 (C O), 157.7 (C O), 160.2 (C O), 163.7 (C O), 165.4
(C O), 168.0 (C O) ppm. MS (EI, 70 eV): m/z = 461 (M+, 4), 446 (53),
432 (31), 402 (52), 319 (28), 290 (46), 260 (49), 246 (63), 228 (31), 105
(100). Anal. calcd for C21H19NO11 (461.3): C, 54.67; H, 4.15; N, 3.04.
Found: C, 54.90; H, 4.12; N, 3.08%.
Methyl (E)-6-(1,2-Di(methoxycarbonyl)-8-(ethyl
Carbamoylformyl)-2-oxo-2H-chromene-4-carboxylate (E-6)
Yellow crystals; yield: 0.96 g (42%), m.p. 138–140◦C. IR (KBr): 3383
(NH), 1734, 1728, and 1722 (C O), 1225, 1221, and 1218 (C O) cm−1
.
3
1H NMR (300.1 MHz, CDCl3 ): δ = 1.45 (t, 3 H, J = 7.2 Hz, CH3),
HH
3.68 (s, 3 H, OCH3), 3.83 (s, 3 H, OCH3), 3.85 (s, 3 H, OCH3), 4.48 (q,
2 H, 3 J = 7.2 Hz, OCH2), 7.05 (s, 1 H, CH), 7.15 (s, 1 H, CH), 8.05
HH
4
4
(d, 1 H, J = 2.1 Hz, CH), 8.68 (d, 1 H, J = 2.1 Hz, CH), 9.59 (s,
HH
HH

1016
I. Yavari and F. Feiz-Javadian
1H, NH) ppm. 13C NMR (75 MHz, CDCl3): δ = 14.5 (CH3), 52.5 (OCH3),
53.6 (OCH3), 53.7 (OCH3), 64.4 (OCH2), 115.7 (C), 120.3 (CH), 123.8
(C), 124.0 (CH), 125.0 (C), 130.4 (CH), 131.0 (C), 142.6 (C), 143.1 (C),
147.1 (C), 154.6 (C O), 158.2 (C O), 160.3 (C O), 164.0 (C O), 165.4
(C O), 166.3 (C O) ppm. MS (EI, 70 eV): m/z = 461 (M+, 3), 446 (48),
432 (39), 402 (48), 319 (21), 290 (43), 260 (38), 246 (53), 228 (20), 105
(100). Anal. calcd for C21H19NO11 (461.3): C, 54.67; H, 4.15; N, 3.04.
Found: C, 54.86; H, 4.10; N, 3.10%.
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