Subject Areas : Journal of Physical Chemistry & Eleectrochemistry

Mohammad M Ghanbari ¹ , Mohammad A. Zare ²

1 - Department of Chemistry, Sarvestan Branch, Islamic Azad University, Sarvestan, Iran
2 - bDepartment of Chemistry, Marvdasht Branch, Islamic Azad University, Marvdasht, Iran

Received: 2013-07-15 Accepted : 2013-09-15 Published : 2015-12-01

Keywords:

References:

Journal of Physical Chemistry and Electrochemistry
Journal homepage: http://journals.miau.ac.ir/jpe
Journal of Physical Chemistry and Electrochemistry Vol.2 No.1(2013) 27-30
Islamic Azad University
Marvdasht Branch
*Correspondig Author
E-mail address: [e-mail]
1. Introduction
Fumarate was recently investigated to be used the various classes of compounds in pharmaceutical, medical [1], industrial [2] and polymer chemistry [3] which possess biologically significant properties such as anti-cancer [4], superior inhibitors of HIV [5] and an inhibitory effect on parasite-specific [6]. The Wittig reaction is unique of the significant methods for the synthesis of carbon–carbon double bond [7-9]. As part of our current studies on the development of new routes on the way to heterocyclic systems [10-12]. We now design an efficient reaction of dialkyl acetylenedicarboxylates 1 and 2-Pyrrolidin 2 in the presence of Ph3P, which constitutes a synthesis of yielding dialkyl (Z)- and (E)- 2-(2-Pyrrolidin-N-yl)-3-(triphenylphosphanylidene)succinate 3. Stabilized phosphoranes undergo a smooth intramolecular Wittig reaction in boiling toluene to synthesis functionalized dialkyl (E)-2-(4,5-Dihydro-3H-pyrrol-2-yl )fumarate
An Efficient One-pot Synthesis of Dialkyl fumarates Mediated by inyltriphenylphosphonium Salt in the Intramolecular Wittig Reaction
Mohammad M. Ghanbaria*, Zeinab Zareb, Marzieh Jamalia, Mohammad A. Zareb and Sina Matavos Aramyan a
aDepartment of Chemistry, Sarvestan Branch, Islamic Azad University, Sarvestan, Iran
bDepartment of Chemistry, Marvdasht Branch, Islamic Azad University, Marvdasht, Iran
Abstract
An efficient three-component reaction of dialkyl acetylendicarboxylates and 2-Pyrrolidin in the presence of triphenylphosphine produces dialkyl 2-(2-Pyrrolidin-N-yl)-3-(triphenylphosphanylidene)succinate. These phosphoranes undergo mild intramolecular Wittig reaction to produce dialkyl (E)-2-(4,5-dihydro-3H-pyrrol-2-yl)fumarate in excellent yields.
Keywords: Wittig reaction; Dialkyl fumarate; Ph3P; Acetylenic ester.
PPh3+CO2RCO2RR1a Me1b Et1c tBu+NHONOCO2RCO2RPh3PR3a Me3b Et3c tBuR4a Me4b Et4c tBu2NHHRO2Cr.tCH2Cl2Toluene24h refluxCO2R
Scheme 1. Synthesis of compounds 3 and 4.
4 in good yields (Scheme 1).
2. Results and discussion
The reaction of 2-Pyrrolidin 2 with dialkyl acetylenedicarboxylates 1 in the presence of Ph3P proceeded at room temperature in CH2Cl2, and was complete within a few hours. 1H and 13C NMR spectra of the crude products clearly indicated the formation of dialkyl 2-(2-pyrrolidin-N-yl)-3-(triphenylphosphanylidene)succinate 3 (Scheme 1). No other products than 3 could be detected. The structures of compounds 3a–3c were deduced from their IR, 1H and 13C NMR spectra. Any initial fragmentation involves loss from, or complete loss of the side chains and scission of the heterocyclic ring system.
Compound 3 undergoes intramolecular Wittig reaction in boiling toluene to produce the Dialkyl (E)-2-(4,5-dihydro-3H-pyrrol-2-yl )fumarate derivative 4, which undergoes electrocyclic ring opening to produce 4. The 1H and 13C NMR spectra of the crude product 4a–4c clearly indicated the formation of (E) isomers. The structures of compounds 4a–4c were deduced from their elemental analyses and IR, 1H, and 13C NMR spectra. Although we have not yet established the mechanism of the thermal conversion of 3 to 4 in an experimental manner, a possible explanation is indicated in Scheme 2 on the basis of the well-established chemistry of the Wittig reaction. It is reasonable to assume that compound 4 results from an initial intramolecular Wittig reaction of phosphorane 3 and a subsequent electrocyclic ring opening reaction of the cyclobutene derivative 4.
The 1H and 13C NMR spectra of the ylides 3a–3c are consisted with the presence of two diastereoisomers. The ylide moiety of these compounds is strongly conjugated with the adjacent carbonyl group and rotation about the partial double bond in the (E)-3 and (Z)-3 geometrical isomers (Scheme 3) is slow on the NMR time scale at ambient temperature [13-14].
(Z)-3; Minor
(E)-3; Major
3. Experimental
Acetylenic esters 1 and Ph3P were obtained from Fluka and were used without further purification. 2-Pyrrolidin 2 were prepared by known methods [15]. Melting points were measured on an Electrothermal 9001; apparatus. The experimental data were in good agreement with the calculated values. 1H and 13C NMR spectra (CDCl3) were measured with
PPh3+1CO2RPh3PCO2RCO2RPh3PCO2R+NOCO2RPPh3CO2RNONOPh3PCO2RCO2R4Electrocyclicring openingNCO2RRO2C+ 2
Scheme 2. A plausible mechanism for the formation of compounds 3 and 4.
NOCO2RPPh3OORNOCO2RPPh3ORO
Scheme 3. (E)- and (Z)-stereoisomers of compound 3.
28 M.M. Ghanbari et al. / Journal of Physical Chemistry and Electrochemistry Vol.2 No.1 (2013) 27-30
a Bruker DRX-400 Avance spectrometer. IR spectra were recorded on a Shimadzu IR-460 spectrometer. Chromatography columns were prepared from Aldrich silica gel 70-230 mesh.
General procedure for the preparation of phosphorus ylides 3
To a stirred solution of 2 mmol of 1 and 2 mmol of 2 in 5 mL of CH2Cl2 was added drop wise a solution of 0.52 g of Ph3P (2 mmol) in 2 of CH2Cl2 at room temperature over 10 min. After 12 h stirring at r.t., the product was filtered and washed with cold ether.
Dimethyl 2-(2-pyrrolidin-N-yl)-3-(triphenylphosphanylidene)succinate (3a)
White powder; mp: 216-219°C; yield: 0.74 g (76%); IR (KBr) (νmax/cm−1): 1743 (C=O), 1437 (C=C). Major isomer (E)-3a (58%); 1H NMR (400 MHz, CDCl3): δ=2.04 (2 H, m, CH2), 2.23 (2 H, t, CH2-C=O), 2.39 (2 H, t, CH2-N), 3.10 (3 H, s, MeO), 3.72 (3 H, s, MeO), 4.70 (1 H, d, 3JPC=18.8 Hz, CH), 7.47–7.65 (15 H, m, 3 C6H5); 13C NMR (100 MHz, CDCl3): δ=18.1 (CH2), 35.1 (CH2-C=O), 37.6 (CH2-N), 44.6 (d, 1JPC=156 Hz, P=C), 49.0 (d, 2JPC=17 Hz, P=C-CH), 49.3 (MeO), 50.4 (MeO), 125.7-133.6 (18 C, C6H5), 171.5 (d, 3JPC=10 Hz, C=O), 172 (d, 2JPC=16 Hz, C=O), 173.9 (CH2C=O); 31PNMR (162 MHz, CDCl3): δ=23.93 (Ph3P+-C). Minor isomer (Z)-3a (42%); 1H NMR (400 MHz, CDCl3): δ=2.02 (2 H, m, CH2), 2.22 (2 H, t, CH2-C=O), 2.37 (2 H, t, CH2-N), 3.52 (3H, s, MeO), 3.70 (3H, s, MeO), 4.68 (1 H, d, 3JPC=17.5 Hz, CH), 7.47–7.65 (15 H, m, 3 C6H5); 13C NMR (100 MHz, CDCl3): δ=18.0 (CH2), 35.0 (CH2 -C=O), 37.5 (CH2-N), 42.5 (d, 1JPC=140 Hz, P=C), 48.3 (MeO), 50.2 (MeO), 50.5 (d, 2JPC=13 Hz, P=C-CH), 125.7-133.6 (18 C Arom), 171 (d, 2JPC=16 Hz, C=O), 171.5(d, 3JPC=11.5 Hz, C=O), 173.09 (CH2-C=O); 31PNMR(162 MHz, CDCl3): 24.43 (Ph3P+-C).
Diethyl 2-(2-pyrrolidin-N-yl)-3-(triphenylphosphanylidene) succinate (3b)
Yellow powder; mp: 210-213°C; yield: 0.76 g (74%); IR (KBr) (νmax/cm−1): 1747 (C=O), 1493 (C=C). Major isomer (E)-3b (68%); 1H NMR (400 MHz, CDCl3): δ=0.5 (3 H, t, 3JHH =7.0 Hz, Me), 1.28 (3 H, t, 3JHH=7.0 Hz, Me), 2.06 (2 H, m, CH2), 2.33 (2 H, t, CH2 -C=O), 2.37 (2 H, t, CH2-N), 3.92 (2 H, q, CH2O), 4.52 (2 H, q, CH2O), 5.43 (1 H, d, 3JPC=16.5 Hz, CH), 7.33–7.72 (15 H, m, 3 C6H5); 13C NMR (100 MHz, CDCl3): δ=13.8 (Me), 14.5 (Me), 18.3 (CH2), 35.2 (CH2-C=O), 37.5 (CH2-N), 37.7 (d, 1JPC=132 Hz, P=C), 57.6 (CH2O), 63.0 (d, 2JPC=18.0 Hz, CH), 61.2 (CH2O), 128.7-143.5 (18 C Arom), 169.9 (d,3JPC=14 Hz, C=O), 170.1 (d, 2JPC=16 Hz, C=O), 173.9 (CH2C=O). Minor isomer (Z)-3b (32%); 1H NMR (400 MHz, CDCl3): δ=0.39 (3 H, t, 3JHH =7.0 Hz, Me), 1.37 (3 H, t, 3JHH=7.0 Hz, Me), 2.08 (2 H, m, CH2), 2.33 (2 H, t, CH2-C=O), 2.39 (2 H, t, CH2-N), 3.92 (2 H, q, CH2O), 4.05 (2 H, q, CH2O), 5.31 (1 H, d, 3JPC=15.5 Hz, CH), 7.33–7.72 (15 H, m, 3 C6H5); 13C NMR (100 MHz, CDCl3): δ=13.8 (Me), 14.3 (Me), 18.2 (CH2), 35.1 (CH2-C=O), 37.6 (CH2-N), 36.7 (d, 1JPC=130 Hz, P=C), 57.6 (CH2O), 60.0 (d, 2JPC=17.0 Hz , CH), 60.3 (CH2O), 128.7-143.5 (18 C Arom), 168.9 (d,3JPC=14 Hz, C=O), 170.4 (d, 2JPC=16 Hz , C=O), 174.9 (CH2C=O).
Di-tert-butyl 2-(2-pyrrolidin-N-yl)-3-(triphenylphosphanylidene)succinate (3c)
Withe powder; mp: 206-209°C; yield: 0.91 g (80%); IR (KBr) (νmax/cm−1): 1747 (C=O), 1492 (C=C). major isomer (E)-3c (74%); 1H NMR (400 MHz, CDC13): δ=1.03 (9 H, s, 3 Me), 1.54 (9 H, s, 3 Me), 2.17 (2 H, m, CH2), 2.35 (2 H, t, CH2-C=O), 2.47 (2 H, t, CH2-N), 5.41 (1 H, d, 3JPC=17 Hz, CH), 7.43–7.92 (15 H, m, 3 C6H5); 13C NMR (100 MHz, CDCl3): δ=19.3 (CH2), 27.1 (3 Me), 28.4 (3 Me), 34.7 (CH2-C=O), 38.5 (CH2-N), 38.7 (d, 1JPC=135 Hz, P=C), 64.0 (d, 2JPC=18.0 Hz, CH), 74.5 (CMe3), 74.8 (CMe3), 169.4 (d,2JPC=18 Hz, C=O), 170.5 (d, 2JPC=13 Hz, C=O), 172.7 (CH2C=O). Minor isomer (E)-3c (26%); 1H NMR (400 MHz, CDCl3): δ=1.04 (9 H, s, 3
M.M. Ghanbari et al./ Journal of Physical Chemistry and Electrochemistry Vol.2 No.1 (2013) 27-30 29
Me), 1.64 (9 H, s, 3 Me), 2.19 (2 H, m, CH2), 2.37 (2 H, t, CH2-C=O), 2.45 (2 H, t, CH2-N), 5.45 (1 H, d, 3JPC=17, CH), 7.43–7.92 (15 H, m, 3 C6H5); 13C NMR (100 MHz, CDCl3): δ=18.3 (CH2), 28.1 (3 Me), 29.4 (3 Me), 35.7 (CH2-C=O), 36.5 (CH2-N), 37.7 (d, 1JPC=132 Hz, P=C), 64.0 (d, 2JPC=16 Hz, CH), 73.6 (CMe3), 73.9 (CMe3), 169.6 (d,2JPC=18 Hz, C=O), 170.9 (d, 2JPC=13 Hz, C=O), 172.9 (CH2C=O).
General procedure for conversion of 3 to 4
A solution of 1 mmol of 3a-c in 20 mL of toluene was refluxed for 24 h. The solvent was removed under reduced pressure and the yellowish oil was separated from triphenylphosphine oxide using cold Et2O. The solvent was removed under reduced pressure and the residue was separated by silica column chromatography (Merck 230-400 mesh) using hexane/ethyl acetate as eluent.
Dimethyl (E)-2-(4,5-dihydro-3H-pyrrol-2-yl )fumarate (4a)
Yellow oil; yield: 0.16 g (79%); IR (KBr) (νmax/cm−1): 3478 (NH), 1493 (C=C), 1765 (C=O); 1H NMR (400 MHz, CDCl3): δ =1.66 (1 H, s, NH), 1.32 (2 H, m, CH2-CH2-NH), 2.18 (2 H, dt, CH2-CH), 2.47 (2 H, t, CH2-NH), 3.72 (1 H, t, CH-NH), 3.76 (3 H, s, MeO), 3.83 (3 H, s, MeO), 6.76 (1 H, s, C=CH); 13C NMR (100 MHz, CDCl3): δ=25.6 (CH2), 26.2 (CH2), 45.3 (CH2-NH), 50.2 (CH-NH), 52.7 (MeO), 53.9 (MeO), 127.5 (CH=C), 152 (C), 162.2 (C=O), 162.9 (C=O).
Diethyl (E)-2-(4,5-dihydro-3H-pyrrol-2-yl 2,)fumarate (4b)
Yellow oil; yield: 0.17 g (73%); IR (KBr) (νmax/cm−1): 3338 (NH), 1495 (C=C), 1782 (C=O); 1H NMR (400 MHz, CDCl3): δ=1.38 (3H , t, Me), 1.41 (3 H , t, Me), 1.49 (2 H, m, CH2-CH2-NH), 1.67 (1 H, s, NH), 2.38 (2 H, dt, CH2-CH), 2.44 (2 H, t, CH2-NH), 3.74 (1 H, t, CH-NH), 4.31 (2 H, q, CH2O), 4.28 (2 H, q, CH2O), 6.77 (1 H, s, CH); 13C NMR (100 MHz, CDCl3): δ=15.2 (Me), 15.8 (Me), 25.9 (CH2), 27.5 (CH2), 46.2 (CH2-NH), 54.2 (CH-NH), 63.0 (CH2O), 65.3 (CH2O), 132.5 (CH=C), 162 (C), 169.2 (C=O), 172.9 (C=O).
Di-tert-butyl (E)-2-(4,5-dihydro-3H-pyrrol-2-yl)fumarate (4c)
Yellow oil; yield: 0.22 g (75%); IR (KBr) (νmax/cm−1): 3437 (NH), 1484 (C=C), 1772 (C=O); 1H NMR (400 MHz, CDCl3): δ=1.42 (9 H, s, 3 Me), 1.49 (9 H, s, 3 Me), 1.51 (2 H, m, CH2-CH2-NH), 1.87 (1 H, s, NH), 2.42 (2 H, dt, CH2-CH), 2.64 (2 H, t, CH2-NH), 3.63 (1 H, t, CH-NH), 6.97 (1 H, s, CH); 13C NMR (100 MHz, CDCl3): δ=26.9 (CH2), 27.2 (CH2), 27.9 (3 Me), 28.8 (3 Me), 48.5 (CH2-NH), 52.2 (CH-NH), 73.7 (CMe3), 74.2 (CMe3), 138.5 (CH=C), 142 (C), 170.2 (C=O), 171.9 (C=O).
References
[1] S. Patrizia, G. Silvana, S. Angela, D. Roberto. Bull Environ Contam Toxico., 86(2011) 428.
[2] W. Yanling, W. Xueye, L. Liming, P. Xinyu. J. Mol. Model., 15 (2009) 1043.
[3] E.G.Paul, O. Amit, G. Rakesh, N. Jean-Marc, D. Roland, B. Jan, R. Caroline, W. Nancy, C. Michael, M.T. Lesley. Breast Cancer Research and Treatment., 59 (2000) 55.
[4] A. Elise, B. Stéphane, C. Marie-Laure, N. Eric, R. Christine, M. James, G. Glenda, C. Patrick, L.S. Kruy, E. Didier, D. François. Retrovirology., (2008) 5.
[5] V. Marisol, S. Pablo, P.C. Beatriz, R. Jorge, G. Veronica, O.A. Claudio, O. Lucıa, A. Gabriela, C. Hugo, G. Mercedes, G.B. Alicia, G. Beatriz, G. Dinorah. J. Biol. Inorg. Chem., 13 (2008)723.
[6] B.E. Maryanoff, A. B. Reitz. Chem Rev., 89 (1989) 863.
[7] R.W. Hoffmann. Angew Chem Int. 2001, Ed 40, 1411.
[8] F. Volatron, O.Eisenstein. J Am Chem Soc., 10, (1987) 2.
[9] I.Yavari, M.M. Ghanbari, A.S. Shahvelayati and M. Ghazvini, Phosphorus, Sulfur, Silicon, Relat. Elem., 185 (2010) 2551.
[11] I. Yavari, M.M. Ghanbari, J. Azizian, F. Sheikholeslami, J. Chem. Res., (2011) 87.
[12] M.M.Ghanbari. Monatsh Chem., 142 (2011)749.
[13] K.B. Becker. Tetrahedron., 36 (1980) 1717.
[14] E.L Eliel, S.H Wilen, Stereochemistry of Organic Compounds., Wiley, New York,(1994)569–573.
[15] J. Safari, H. Naeimi, M.M Ghanbari, O. Sabzi-Fini, Russ. J. Org. Chem., 45 (2009) 477.
30 M.M. Ghanbari et al. / Journal of Physical Chemistry and Electrochemistry Vol.2 No.1 (2013) 27-30