Facile synthesis of N-(arylsulfonyl)-4-ethoxy-5-oxo-2,5-dihydro-1H-pyrolle- 2,3-dicarboxylates by one-pot three-component reaction

Article abstract of DOI:10.1016/j.cclet.2011.09.010

Three-component reaction of arylsulfonamides, dialkyl acetylenedicarboxylates, and ethyl chlorooxoacetate promoted by triphenylphosphine and triethylamine provides a sufficient route for the synthesis of dialkyl N-(arylsulfonyl)-4-ethoxy-5-oxo-2,5-dihydro

Full text of DOI:10.1016/j.cclet.2011.09.010

Available online at www.sciencedirect.com
Chinese Chemical Letters 23 (2012) 45–48
www.elsevier.com/locate/cclet
Facile synthesis of N-(arylsulfonyl)-4-ethoxy-5-oxo-2,5-dihydro-
1H-pyrolle-2,3-dicarboxylates by one-pot three-component reaction
a
b
Hossein Anaraki-Ardakani a, , Maziar Noei , Afrooz Tabarzad
*
a Department of Chemistry, Mahshahr Branch, Islamic Azad University, Mahshahr, Iran
b Department of Chemistry, Islamic Azad University, Yazd Branch, P.O. Box 89195-155, Yazd, Iran
Received 15 June 2011
Available online 8 November 2011
Abstract
Three-component reaction of arylsulfonamides, dialkyl acetylenedicarboxylates, and ethyl chlorooxoacetate promoted by
triphenylphosphine and triethylamine provides a sufficient route for the synthesis of dialkyl N-(arylsulfonyl)-4-ethoxy-5-oxo-2,5-
dihydro-1H-pyrolle-2,3-dicarboxylates in good yields.
# 2011 Hossein Anaraki-Ardakani. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: Arylsulfonamides; Dialkyl acetylenedicarboxylates; Triphenylphosphine; Multi-component reactions; 3-Pyrollin-2-ones
Five-membered ring lactams have successfully been used in routes to various alkaloids [1,2] and are suitable
precursors for unusual b-amino acids such as statine and its analogues [3,4]. There are also many examples of
pyrroline-containing natural products with pharmacological activities. Typical examples are the antitumor alkaloide
Jatropham and the platelet aggregation inhibitor PI-091[5]. N-Substituted 3-pyrrolines are important compounds
which exhibit neuritogenic activity [6] and serve as useful synthetic intermediates [7–9]. Despite their wide
applicability, available routes for the synthesis of 3-pyrrolin-2-ones are limited [10,11].
Sulfonamide-containing compounds have a high potential as pharmaceutical and agricultural agents due to their
diverse biological profiles. The ability to serve as amide surrogates, with unique physical properties, have made them
ideal functional groups for the development of novel peptidomimetics [12]. In addition, sulfonamides have served as
key functional groups in the development of novel nonpeptidal HIV protease inhibitors [13], matrix metalloproteinase
inhibitors, thrombin inhibitors and fibrinogen receptor antagonists [14].
Three-component addition reaction between triphenylphosphine, dialkyl acetylenedicarboxylates (DAAD’s) and
arylsulfonamides has been reported to produce sulfur-containing iminophosphoranes 4 (Scheme 1) [15–18].
Recently, we reported the reaction of dialkyl acetylenedicarboxylates, triphenylphosphine, with primary amines in
the presence of ethyl chlorooxoacetate for the synthesis of dialkyl N-aryl-4-ethoxy-5-oxo-2,5-dihydro-1H-pyrrole-
2,3-dicarboxylates [19]. We also reported one-pot synthesis of polysubstituted pyrrole derivatives by three-component
reaction between DAAD’s, aromatic amines, triphenylphosphine and arylglyoxals [20].
* Corresponding author.
E-mail address: hosseinanaraki@yahoo.com (H. Anaraki-Ardakani).
1001-8417/$ –see front matter # 2011 Hossein Anaraki-Ardakani. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
doi:10.1016/j.cclet.2011.09.010

46
H. Anaraki-Ardakani et al. / Chinese Chemical Letters 23 (2012) 45–48
CO2R
H
N
PPh3
CO2R
O
S
O
PPh3
H2N
Ar
+
+
S
Ar
O
O
CO2R
CO2R
2
1
3
4
Scheme 1. Synthesis of sulfur-containing iminophosphoranes by reaction of PPh3-DAAD zwitterion with arylsulfonamides.
OEt
PPh3
O
1
Et3N, - Et3NHCl
-Ph3PO
O
CO2R
OEt
+
CO2R
RO2C
Cl
+
N
O
S
O
O
S
CO2R
3
Ar
NH2
5
Ar
O
O
2
6
R
Ar
Yield (%)
6
p-CH3-pheny
p-CH3-pheny
a
b
c
Me
88
80
85
Et
Me
Et
phenyl
d
e
phenyl
80
60
p-CH3-pheny
t-Bu
Scheme 2. Three-component reaction between arylsulfonamides, DAAD’s, triphenylphosphine and ethyl chlorooxoacetate.
Here we report an extention of this route for the synthesis of dialkyl N-(arylsulfonyl)-4-ethoxy-5-oxo-2,5-dihydro-
1H-pyrolle-2,3-dicarboxylates by three-component reaction of arylsulfonamides, DAAD’s, triphenyl-phosphine and
ethyl chlorooxoacetate in the presence of triethylamine (Scheme 2).
1. Results and discussion
The structures of compounds 6a–e were deduced from their elemental analyses and their IR, 1H NMR, 13C NMR
spectra. For example, the mass spectrum of 6a displayed the molecular-ion peak at m/z 397. The 500 MHz 1H NMR
spectrum of 6a exhibited three sharp signals at d 2.43, 3.79 and 3.81 for three methyl group’s protons. A triplet at 1.37
(J = 7 Hz) and a quartet at 4.60 were observed for ethyl protons. The proton of methine group of pyrroline ring
resonated as a singlet at 5.30. The aromatic protons were observed at 7.33 and 7.97 (d, J = 8.2 Hz). The 13C NMR
spectrum of compound 6a showed 15 distinct resonances in agreement with the proposed structure. The structural
assignments made on the basis of the NMR spectra of compound 6a were supported by its IR spectrum. The carbonyl
groups exhibited strong absorption bands at 1745 and 1679 cmÀ1
.
It is rational to assume compounds 6a–e are produced from the initial production of ylide 4 from three-component
reaction of arylsulfonamides 2, DAAD (3) and triphenylphosphine, which then reacted with ethyl chlorooxoacetate 5
to produce oxamate 7 that underwent intramolecular Wittig reaction to produce products 6 (Scheme 3).
CO2R
CO2R
O
Ph3P
O
OEt
H
N
PPh3
CO2R
Cl
EtO
OEt
O
CO2R
-Ph3PO
O
S
O
Ar
N
N
O
O
O
CO2R
Et3N, - Et3NHCl
S
CO2R
S
Ar
O
4
O
O
Ar
6
7
Scheme 3. Suggested mechanism for formation of 3-pyrollin-2-one 6.

H. Anaraki-Ardakani et al. / Chinese Chemical Letters 23 (2012) 45–48
47
2. Experimental
Melting points were determined with an electrothermal 9100 apparatus. Elemental analyses were performed using a
Heraeus CHN-O-Rapid analyzer. Mass spectra were recorded on a FINNIGAN-MAT 8430 mass spectrometer
operating at an ionization potential of 70 eV. IR spectra were recorded on a Shimadzu IR-470 spectrometer. 1H and 13
C
NMR spectra were recorded on Bruker DRX-500 Avance spectrometer at solution in CDCl3 using TMS as internal
standard. The chemicals used in this work purchased from Fluka (Buchs, Switzerland) and were used without further
purification.
2.1. General procedure
To a magnetically stirred solution of PPh3 (1 mmol) and arylsulfonamides derivative (1 mmol) in CH2Cl2 (10 mL)
was added dropwise a mixture of DAAD (1 mmol) in CH2Cl2 (3 mL) at room temperature over 2 min. The reaction
mixture was then stirred for one more min. triethylamine (1 mmol) and ethyl chlorooxoacetate (1 mmol) was added
and the reaction mixture was stirred for more 24 h. Solvent was evaporated and the residue was purified by column
chromatography on SiO2 using EtOAc-hexane (1:4) mixture as eluent.
Dimethyl 4-ethoxy-2,5-dihydro-5-oxo-1-tosyl-1H-pyrrole-2,3-dicarboxylate (6a): Viscous oil, IR (KBr) (nmax
,
cmÀ1): 1745 (2 C O), 1679 (C O, amide). Anal. Calcd. (%) for C17H19NO8S: C, 51.38; H, 4.82; N, 3.52. Found: C,
51.42; H, 4.79; N, 3.54. 1H NMR (500 MHz, CDCl3): d 1.37 (t, 3H, 3JHH = 7 Hz, CH3), 2.43 (s, 3H, CH3), 3.79 and
3.81 (2s, 6H, 2 OCH3), 4.60 (m, 2H, OCH2), 5.30 (s, 1H, CH), 7.33 and 7.97 (2d, 4H, 3JHH = 8.2 Hz, aromatic). 13
C
NMR (125.8 MHz, CDCl3): d 15.91 and 22.17 (2 CH3), 52.76 and 53.86 (2 OCH3), 59.46 (OCH2), 69.30 (CH), 115.80,
126.84, 129.17, 131.32, 134.61 and 146.46 (aromatic and olefinic carbons), 161.97, 162.785, 168.05 (3 C O). MS, m/z
(%) = 397(M+, 16).
Diethyl 4-ethoxy-2,5-dihydro-5-oxo-1-tosyl-1H-pyrrole-2,3-dicarboxylate (6b): Viscous oil, IR (KBr) (nmax
,
cmÀ1): 1723 (2 C O, ester), 1641 (C O, amide). Anal. Calcd. (%) for C19H23NO8S: C, 53.64; H, 5.45; N, 3.29.
Found: C, 53.79; H, 5.52; N, 3.34 1H NMR (500 MHz, CDCl3): d 1.01, 1.14 and 1.25 (t, 9H, 3JHH = 7 Hz, 3ÂCH3),
3
2.36 (s, 3H, CH3), 3.96, 4.12 and 4.22 (m, 6H, 3ÂOCH2), 5.35 (s, 1H, CH), 7.26 and 7.91 (2d, 4H, JHH = 8.2 Hz,
aromatic). 13C NMR (125.8 MHz, CDCl3): d 14.24, 14.52, 15.71 and 22.15 (4 CH3), 59.86, 61.76 and 64.84 (3 OCH2),
68.59 (CH), 113.12, 126.88, 129.18, 130.17, 133.60 and 146.66 (aromatic and olefinic carbons), 161.42, 163.51,
168.22 (3 C O). MS, m/z (%) = 425 [M+, 22].
Dimethyl-1-benzenesulfonyl-4-ethoxy-5-oxo-2,5-dihydro-1H-pyrrole-2,3-dicarboxylate (6c): Viscous oil, IR
(KBr) (nmax, cmÀ1): 1722, 1703 (2 C O, ester), Anal. Calcd. (%) for C16H17NO8S: C, 50.13; H, 4.47; N, 3.65.
Found: C, 50.23; H, 4.52; N, 3.52. 1H NMR (500 MHz, CDCl3): d 1.23 (t, 3H, 3JHH = 7 Hz, CH3), 3.70, 3.75 (s, 6H,
2ÂOCH3), 4.23 (q, 2H, 3JHH = 7 Hz, OCH2), 5.24 (s, 1H, CH), 7.46 (t, 2H, 3JHH = 7.7 Hz, 2CH of Ph), 7.58 (t, 1H,
3JHH = 7.5 Hz, CH of Ph), 8.02 (d, 2H, 3JHH = 7.6 Hz, 2CH of Ph). 13C NMR (125.8 MHz, CDCl3): d 14.50 (CH3),
52.81, 53.88, 59.50 (2 OCH3 and OCH2), 69.38 (CH), 115.90, 129.06, 129.53, 135.18, 137.96 and 152.32 (aromatic
and olefinic carbons), 161.95, 162.81, 167.98 (3 C O). MS, m/z (%) = 383 [M+, 11].
Diethyl-1-benzenesulfonyl-4-ethoxy-5-oxo-2,5-dihydro-1H-pyrrole-2,3-dicarboxylate (6d): Viscous oil, IR (KBr)
(nmax, cmÀ1): 1730, 1699 (2 C O, ester), Anal. Calcd. (%) for C18H21NO8S: C, 52.55; H, 5.14; N, 3.40. Found: C,
52.74; H, 5.23; N, 3.67, 1H NMR (500 MHz, CDCl3): d 1.29 (m, 9H, 3ÂCH3), 4.19, 4.26 and 4.56 (m, 6H, 3ÂOCH2),
3
3
5.28 (s, 1H, CH), 7.52 (t, 2H, JHH = 7.7 Hz, 2CH of Ph), 7.64 (t, 1H, JHH = 7.5 Hz, CH of Ph), 8.03 (d, 2H,
3JHH = 7.6 Hz, 2CH of Ph). 13C NMR (125.8 MHz, CDCl3): d 14.34, 14.41 and 15.82 (3 CH3), 59.75, 61.92 and 63.18
(3 OCH2), 69.32 (CH), 116.32, 129.08, 129.44, 135.06, 137.72 and 152.16 (aromatic and olefinic carbons), 161.35,
162.89, 167.39 (3 C O). MS, m/z (%) = 411 [M+, 10].
Di-tert-butyl 4-ethoxy-2,5-dihydro-5-oxo-1-tosyl-1H-pyrrole-2,3-dicarboxylate (6e): Viscous oil, IR (KBr) (nmax
,
cmÀ1): 1730, 1699 (2 C O, ester), Anal. Calcd. (%) for C23H31NO8S: C, 57.36; H, 6.49; N, 2.91. Found: C, 57.22; H,
1
6.70; N, 2.81, H NMR (500 MHz, CDCl3): d 1.23 (t, 3H, JHH = 7 Hz, CH3), 1.34 (s, 9H, C(CH3)3), 1.40 (s, 9H,
3
3
C(CH3)3), 2.43 (s, 3H, CH3), 4.32 (q, 3H, JHH = 7.1 Hz, OCH2), 5.23 (s, 1H, CH), 7.33 and 7.97 (d, 4H,
3JHH = 8.1 Hz, aromatic). 13C NMR (125.8 MHz, CDCl3): d 13.79, 21.70 (2CH3), 27.52, 27.96 (2C(CH3)3), 65.83
(OCH2), 64.37. (CH), 82.21, 83.18 (2C (CH3)3), 115.12, 126.40, 128.73,129.72, 134.49 and 153.64 (aromatic and
olefinic carbons), 162.21, 164.01, 166.92 (3 C O). MS, m/z (%) = 481 [M+, 16].

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H. Anaraki-Ardakani et al. / Chinese Chemical Letters 23 (2012) 45–48
3. Conclusion
In conclusion here we report the reaction between dialkyl acetylenedicarboxylates, arylsulfonamides and ethyl
chlorooxoacetate promoted by triphenylphosphine and triethylamine, to produce functionalized 3-pyrrolin-2-one
derivatives in high yields. The present method carries the advantage that not only is the reaction performed under
simple conditions but also that the substances can be mixed without any activation or modification.
Acknowledgments
We gratefully acknowledge the financial support from the Research Council of Islamic Azad University, Mahshahr
Branch.
References
[1] G. Casiraghi, P. Spanu, G. Rassu, et al. J. Org. Chem. 59 (1994) 2906.
[2] D. Griffart-Brunet, N. Langlois, Tetrahedron Lett. 35 (1994) 119.
[3] P. Jouin, D. Castro, B. Nisato, J. Chem. Soc. Perkin Trans. 1 (1987) 1177.
[4] D.W. Ma, J.Y. Ma, W.L. Ding, et al. Tetrahedron Asymm. 7 (1996) 2365.
[5] N. Iwasawa, K. Maeyama, J. Org. Chem. 62 (1997) 1918.
[6] H. Kakeya, C. Onozawa, M. Sato, et al. J. Med. Chem. 40 (1997) 391, and references therein.
[7] B.A. Kulkarani, A. Ganesan, Angew. Chem. Int. Ed. Engl. 36 (1997) 2454.
[8] S. Bienz, C. Busacca, A.I. Mayers, J. Am. Chem. Soc. 111 (1989) 1905.
[9] B. Tarnchompoo, C. Thebtaranonth, Y. Thebtaranonth, Tetrahedron Lett. 28 (1987) 6675.
[10] J. Barluenga, F. Palacios, S. Fustero, et al. Synthesis (1981) 200.
[11] J.T. Baker, S. Sifniades, J. Org. Chem. 44 (1979) 2798.
[12] W.J. Moree, G.A. van der Marel, R.M.J. Liskamp, Tetrahedron Lett. 32 (1991) 409.
[13] J.L. Radkiewicz, M.A. McAllister, E. Goldstein, et al. J. Org. Chem. 63 (1998) 1419.
[14] D.K. Jones-Hertzog, W.L. Jorgensen, J. Med. Chem. 40 (1997) 1539.
[15] I. Yavari, N. Zabarjad-Shiraz, H.R. Bijanzadeh, Phosphorus Sulfur Silicon 179 (2004) 1381.
[16] L.W. Ye, J. Zhou, Y. Tang, Chem. Soc. Rev. 37 (2008) 1140.
[17] I. Yavari, N. Zabarjad-Shiraz, H.R. Bijanzadeh, Phosphorus Sulfur Silicon 176 (2001) 141.
[18] A. Shaabani, A. Rahmati, S. Naderi, Monatshefte fur Chemie 138 (2007) 553.
[19] M. Anary-Abbasinejad, H. Anaraki-Ardakani, A. Dehghan, et al. J. Chem. Res. (2007) 574.
[20] M. Anary-Abbasinejad, K. Charkhati, H. Anaraki-Ardakani, Synlett (2009) 1115.