Ultrasonochemical synthesis of 2,3-dihydrofuranediones in aqueous medium

Leila Zare Fekri; Mohammad Nikpassand; Leila Imani-Darestani

doi:10.1515/hc-2017-0172

Article Open Access

Ultrasonochemical synthesis of 2,3-dihydrofuranediones in aqueous medium

Leila Zare Fekri , Mohammad Nikpassand and Leila Imani-Darestani

Published/Copyright: May 4, 2018

Published by

Become an author with De Gruyter Brill

Submit Manuscript Author Information Explore this Subject

From the journal Heterocyclic Communications Volume 24 Issue 3

Abstract

2,3-Dihydrofuranediones were prepared by an efficient one-pot multicomponent Knoevnagel-like condensation between pyrazolecarbaldehydes or indole-3-carbaldehyde, ethyl pyruvate and bromine, followed by an intramolecular cyclization in aqueous medium.

Keywords: 2,3-dihydrofuranedione; aqueous media; ethyl pyruvate; ultrasound irradiation; water

Introduction

Furanones are constituents of many bioactive molecules [1], [2], [3], [4], [5], [6], [7], [8], [9]. Furan derivatives can be synthesized by the cyclization of γ-hydroxyalkynones [10], cycloisomerization of allenic hydroxyketones [11], domino reaction of α,β-acetylenic γ-hydroxy nitriles with arenecarboxylic acids [12], silver triflate-catalyzed intramolecular addition of a hydroxyl or carboxylic group to olefins [13], cyclization of alkynes bearing a carboxylic acid in the presence of commercially available Au₂O₃ [14], DBU-mediated tandem Michael addition/5-exo-dig-cycloisomerization of enynes and keto-methylenes [15], palladium-catalyzed isomerization of acetylenic aldehydes followed by base-promoted deacetylation [16] and copper-catalyzed oxidative [3+2] cycloaddition of alkenes with anhydrides in the presence of oxygen [17]. Furanediones can be prepared from alkyne precursors [18]. One of the most common preparative methods for the synthesis of furane-2,3-diones is the reaction of 1,3-dicarbonyl compounds with oxalyl chloride [19].

To the best of our knowledge, this paper is the first report of the multicomponent synthesis of pyrazolyl or indolyl-substituted 2,3-dihydrofuranediones using aryl aldehydes, ethyl pyruvate and bromine under ultrasonic irradiation in water. The importance of ultrasonic-assisted organic synthesis has been widely reported [20], [21] and reviewed [22]. Overall, ultrasonic irradiation conducted in water is both economical and environmentally friendly [23].

Results and discussion

In continuation of our efforts to develop pharmaceutical heterocyclic compounds [24], [25], [26], [27], [28], herewith we report a simple, one-pot multicomponent method for the construction of 2,3-dihydrofuranediones 3a–g in water as a solvent starting from 4-pyrazolecarbaldehydes 1 or indole-3-carbaldehyde (1g), ethyl pyruvate (2) and bromine (Scheme 1). This reaction is enhanced by the use of microwave irradiation.

Scheme 1

Synthesis of 2,3-dihydrofuranediones under ultrasonic irradiation.

In order to optimize the preparation of products 3a–g, several commonly available solvents including ethyl acetate, water, ethanol, hexanes, chloroform and N,N-dimethylformamide were studied for comparison. The effect of temperature, the use of ultrasonic heating and conventional heating were also studied. In the initial experiments, a mixture of pyrazolecarbaldehyde (1a, 1 mmol), ethyl pyruvate (2, 1 mmol), bromine (1 mmol) and NaOH (0.5 g) were allowed to react in various solvents (10 mL) under ultrasonic irradiation with a frequency of 45 kHz. Among the solvents indicated above, the reaction conducted in water furnished product 3a in the highest yield of 92% after 30 min of irradiation. The use of other solvents provided compound 3a in yields ranging from 53% (hexanes) to 78% (ethanol) after the irradiation time greater than 45 min. The reaction was best conducted at room temperature. The yield 3a decreased to 56% at 0°C after the reaction time of 120 min, and the increase of the temperature to 60°C resulted in the yield of 91% after 30 min. Stirring of the mixture of substrates at room temperature for 120 min without microwave-assisted heating resulted in the yield of 3a of 63%. Conducting the reaction under classical reflux conditions without assistance from ultrasound was also less efficient and furnished product 3a in an 80% yield after 90 min. Under the optimized ultrasound-assisted reaction conducted in water at room temperature for 30 min, the remaining products 3b–g were obtained in yields ranging from 83% to 90%. We are currently studying the mechanism of this efficient reaction.

To the best of our knowledge, this one-pot multicomponent synthesis of 2,3-dihydrofuranediones is a novel methodology. The procedure presented here not only furnishes the desired products in good yields, but also problems associated with the use of conventional solvents such as cost, handling, safety and pollution are avoided. Aqueous medium for these reactions provides an environmentally safe protocol. Water is the cheapest, most abundant and non-toxic chemical in nature.

Conclusion

A one-pot three-component synthesis of 2,3-dihydrofuranediones from 4-pyrazolecarbaldehydes or indole-3-carbaldehyde, ethyl pyruvate and bromine under ultrasonic irradiation was developed for the first time. The simplicity of the process, easy workup, inexpensive materials and the use of aqueous medium are the notable features.

Experimental

Melting points were measured on an Electrothermal 9100 apparatus. Infrared spectra were recorded in KBr pellets on a Shimadzu Fourier transform infrared (FTIR) 8600 spectrophotometer. proton nuclear magnetic resonance (¹H NMR) (400 MHz) and carbon-13 nuclear magnetic resonance (¹³C NMR) (100 MHz) spectra were taken in dimethyl sulfoxide-d₆ (DMSO-d₆) on a Bruker 400 DRX Avance instrument. Elemental analyses were done on a Carlo-Erba EA1110CNNO-S analyzer. An ultrasound apparatus Astra 3D operating at 45 KHz frequency, input power with heating, 305 W, from TECNO-GAZ was used.

General procedure for the preparation of 3a–g under ultrasonic irradiation

A mixture of aldehyde (1a–g, 1.0 mmol), ethyl pyruvate (2, 1.0 mmol) and aqueous NaOH (5%, 10 mL) were placed in a Pyrex-glass open vessel and microwave irradiated at room temperature for 10 min. Then, bromine (1.0 mmol) was added and the mixture was irradiated for an additional 20 min. The progress of the reaction was monitored by thin-layer chromatography (TLC) eluting with ethyl acetate/petroleum ether (1:2). After completion of the reaction, the mixture was filtered and the residue was subjected to silica gel chromatography eluting with ethyl acetate/petroleum ether (1:4).

4-Bromo-dihydro-5-(5-(4-methoxyphenyl)-1-phenyl-1H-pyrazol-3-yl)furane-2,3-dione (3a)

White solid; yield 92%; mp 283–285°C; IR: 1284, 1490, 1596, 1726, 2960 cm⁻¹; ¹H NMR: δ_H 3.94 (s, 3H, OCH₃), 4.08 (s, 1H, CHBr), 4.10 (s, 1H, CHO), 6.55 (dd, J=6 Hz and 2 Hz, 2H), 7.51 (m, 2H), 7.59 (s, 2H), 7.71 (m, 2H), 7.92 (dd, J=6 Hz and 2 Hz, 1H), 8.19 (d, J=2 Hz, 1H); ¹³C NMR: δ_C 62.4, 71.2, 95.8, 110.4, 118.4, 122.6, 124.7, 126.7, 128.9, 131.6, 132.5, 135.8, 138.9, 145.3, 164.8, 193.6. Anal. Calcd for C₂₀H₁₅BrN₂O₄: C, 56.22; H, 3.54; N, 6.56. Found: C, 56.24; H, 3.55; N, 6.54.

4-Bromo-dihydro-5-(5-(4-hydroxyphenyl)-1-phenyl-1H-pyrazol-3-yl)furane-2,3-dione (3b)

White solid; yield 90%; mp 263–265°C; IR: 1282, 1465, 1600, 1728, 2960, 3068, 3419 cm⁻¹; ¹H NMR: δ_H 4.08 (s, 1H, CHBr), 4.09 (s, 1H, CHO), 7.53 (m, 5H), 7.71 (m, 4H), 8.26 (s, 1H); ¹³C NMR: δ_C 71.8, 97.2, 110.6, 118.2, 125.8, 128.7, 128.8, 130.9, 132.4, 132.5, 135.1, 141.2, 148.3, 164.6, 199.8. Anal. Calcd for C₁₉H₁₃BrN₂O₄: C, 55.23; H, 3.17; N, 6.78. Found: C, 55.22; H, 3.17; N, 6.81.

4-Bromo-dihydro-5-(5-(3-nitrophenyl)-1-phenyl-1H-pyrazol-3-yl)furane-2,3-dione (3c)

White solid; yield 85%; mp 274–276°C; IR: 1282, 1344, 1521, 1596, 1631, 2960 cm⁻¹; ¹H NMR: δ_H 4.09 (s, 1H, CHBr), 4.10 (s, 1H, CHO), 7.36 (m, 1H), 7.51 (m, 2H), 7.62 (m, 2H), 7.72 (m, 2H), 8.06 (s, 1H), 8.25 (s, 1H), 8.38 (s, 1H); ¹³C NMR: δ_C 71.8, 94.9, 118.9, 120.2, 122.4, 123.1, 127.4, 128.8, 129.1, 129.3, 129.6, 130.9, 132.7, 133.2, 133.3, 163.4, 191.2. Anal. Calcd for C₁₉H₁₂BrN₃O₅: C, 51.60; H, 2.74; N, 9.50. Found: C, 51.62; H, 2.77; N, 9.49.

4-Bromo-5-(5-(4-chlorophenyl)-1-phenyl-1H-pyrazol-3-yl)dihydrofurane-2,3-dione (3d)

White solid; yield 87%; mp 221–223°C, IR: 1282, 1492, 1595, 1726, 2923 cm⁻¹; ¹H NMR: δ_H 4.14 (s, 2H, CHBr and CHO), 7.42 (d, J=6 Hz, 2H), 7.57 (m, 5H), 7.92 (d, J=6 Hz, 2H), 7.98 (s, 1H); ¹³C NMR: δ_C 71.9, 93.9, 119.4, 119.8, 127.8, 127.9, 128.6, 128.9, 129.2, 131.6, 133.7, 137.4, 148.3, 168.4, 197.8. Anal. Calcd for C₁₉H₁₂BrClN₂O₃: C, 52.87; H, 2.80; N, 6.49. Found: C, 52.86; H, 2.82; N, 6.46.

4-Bromo-dihydro-5-(1,5-diphenyl-1H-pyrazol-3-yl)furane-2,3-dione (3e)

White solid; yield 90%; mp 124–126°C; IR: 1280, 1514, 1596, 1726, 2960, 3066 cm⁻¹; ¹H NMR: δ_H 4.09 (s, 1H, CHBr), 4.22 (s, 1H, CH-O), 7.44 (m, 3H), 7.54 (m, 2H), 7.60 (d, J=7 Hz, 1H), 7.73 (m, 3H), 8.00 (m, 1H), 8.03 (s, 1H); ¹³C NMR: δ_C 71.8, 94.4, 118.8, 126.9, 127.7, 128.3, 128.8, 129.5, 130.9, 131.7, 132.3, 139.5, 150, 165.3, 197.4. Anal. Calcd for C₁₉H₁₃BrN₂O₃C: C, 57.45; H, 3.30; N, 7.05. Found: C, 57.42; H, 3.32; N, 7.04.

4-Bromo-5-(5-(2-chlorophenyl)-1-phenyl-1H-pyrazol-3-yl)-dihydrofurane-2,3-dione (3f)

White solid; yield 89%; mp 233–235°C; IR: 1099, 1237, 1593, 1670, 1726 cm⁻¹; ¹H NMR: δ_H 4.08 (s, 1H, CHBr), 4.10 (s, 1H, CHO), 7.25 (m, 2H), 7.51 (m, 4H), 7.67 (m, 1H), 7.73 (dd, J=6 Hz and 3 Hz, 1H), 7.97 (m, 1H), 8.01 (s, 1H); ¹³C NMR: δ_C 70.7, 93.6, 118.4, 123.4, 123.9, 128.0, 128.8, 128.9, 129.3, 129.8, 130.8, 133.6, 136.9, 139.0, 139.4, 151.7, 154.6, 197.2. Anal. Calcd for C₁₉H₁₂BrClN₂O₃: C, 52.87; H, 2.80; N, 6.49. Found: C, 52.89; H, 2.78; N, 6.48.

4-Bromo-dihydro-5-(1H-indol-3-yl)furane-2,3-dione (3g)

White solid; yield 83%; mp 246–248°C, IR: 1095, 1234, 1435, 1589, 1733 cm⁻¹; ¹H NMR: δ_H 4.07 (s, 1H, CHBr), 4.09 (s, 1H, CHO), 7.45 (d, J=3 Hz, 1H), 7.53 (dd, J=7 Hz and 3 Hz, 1H), 7.59 (d, J=7 Hz, 1H), 7.66 (d, J=7 Hz, 1H), 7.73 (dd, J=7 Hz and 3 Hz, 1H), 8.31 (s, 1H, NH); ¹³C NMR: δ_C 71.0, 93.7, 118.9, 127.8, 129.9, 135.4, 136.8, 138.9, 142.3, 151.6, 153.7, 197.1. Anal. Calcd for C₁₂H₈BrNO₃: C, 49.01; H, 2.74; N, 4.76. Found: C, 49.02; H, 24.72; N, 4.78.

Acknowledgments

Financial support from the Research Council of Payame Noor University and Islamic Azad University of Rasht branch is sincerely acknowledged.

References

[1] Schobert, R.; Schlenk, A. Tetramic and tetronic acids: an update on new derivatives and biological aspects. Bioorg. Med. Chem. 2008, 16, 4203–4221.10.1016/j.bmc.2008.02.069Search in Google Scholar PubMed

[2] El-Gendy, K. S.; Aly, N. M.; Mahmoud, F. H.; Kenawy, A. A.; EI-Sebae, K. H. The role of vitamin C as antioxidant in protection of oxidative stress induced by imidacloprid. Food. Chem. Toxicol.2010, 48, 215–221.10.1016/j.fct.2009.10.003Search in Google Scholar PubMed

[3] Mittra, A.; Yamashita, M.; Kawasaki, I.; Murai, H.; Yoshioka, T.; Ohta, S. A useful oxidation procedure for the preparation of 3-alkanoyltetronic acids. Synlett1997, 8, 909–910.10.1055/s-1997-960Search in Google Scholar

[4] Schobert, R.; Jagusch, C. Solution-phase and solid-phase syntheses of enzyme inhibitor RK-682 and antibiotic agglomerins. J. Org. Chem. 2005, 70, 6129–6132.10.1021/jo050797iSearch in Google Scholar PubMed

[5] Gein, V. L.; Gein, L. F.; Sheptukha, M. A.; Voronina, E. V. Synthesis and antimicrobiogical activity of 4-acyl-3-hydroxyspiro-[2,5-dihydrofuran-5,2′-indan]-2,1′,3′-triones. Pharm. Chem. J.2005, 39, 537–538.10.1007/s11094-006-0016-8Search in Google Scholar

[6] Schobert, R.; Dietrich, M.; Mullen, G.; Urbina-Gonzalez, J. M. Phosphorus ylide based functionalizations of tetronic and tetramic acids. Synthesis2006, 22, 3902–3914.10.1055/s-2006-950310Search in Google Scholar

[7] Andrade, R.; Ayer, W. A.; Trifonov, L. S. The metabolites of trichoderma longibrachiatum. III. Two new tetronic acids: 5-hydroxyvertinolide and bislongiquinolide. Aust. J. Chem. 1997, 50, 255–258.10.1071/C96103Search in Google Scholar

[8] Shin, S. S.; Noh, M. S.; Byun, Y. J.; Choi, J. K.; Kim, J. Y.; Lim, K. M.; Ha, J. Y.; Kim, J. K.; Lee, C. H.; Chung, S. 2,2-Dimethyl-4,5-diaryl-3(2H)furanone derivatives as selective cyclo-oxygenase-2 inhibitors. Bioorg. Med. Chem. Lett. 2001, 11, 165–168.10.1002/chin.200115116Search in Google Scholar

[9] Kozminykh, V. O.; Igidov, N. M.; Kozminykh, E. N.; Aliev, Z. G. Reactions of 5-aryl-furan-2,3-diones with acylmethylenetriphenylphosphoranes-synthesis and biological-activity of 3(2H)-furanone derivatives. Pharmazie1993, 48, 99–106.Search in Google Scholar

[10] Egi, M.; Azechi, K.; Saneto, M.; Shimizu, K.; Akai, S. Cationic gold(I)-catalyzed intramolecular cyclization of γ-hydroxyalkynones into 3(2H)-furanones. J. Org. Chem. 2010, 75, 2123–2126.10.1021/jo100048jSearch in Google Scholar PubMed

[11] Poonoth, M.; Krause, N. Cycloisomerization of functionalized allenes: synthesis of 3(2H)-furanones in water. J. Org. Chem. 2011, 76, 1934–1936.10.1021/jo102416eSearch in Google Scholar PubMed

[12] Trofimov, B. A.; Shemyakina, O. A.; Mal’kina, A. G.; Ushakov, I. A.; Kazheva, O. N.; Alexandrov, G. G.; Dyachenko, O. A. A domino reaction of α, β-acetylenic γ-hydroxy nitriles with arenecarboxylic acids: an unexpected facile shortcut to 4-cyano-3(2H)-furanones. Org. Lett. 2010, 12, 3200–3203.10.1021/ol1011532Search in Google Scholar PubMed

[13] Yang, C.-G.; Reich, N. W.; Shi, Z.; He, C. Intramolecular additions of alcohols and carboxylic acids to inert olefins catalyzed by silver(I) triflate. Org. Lett. 2005, 7, 4553–4556.10.1021/ol051065fSearch in Google Scholar PubMed

[14] Toullec, P. Y.; Genin, E.; Antoniotti, S.; Genêt, J.-P.; Michelet, V. Au₂O₃ as a stable and efficient catalyst for the selective cycloisomerization of γ-acetylenic carboxylic acids to γ-alkylidene-γ-butyrolactones. Synlett2008, 5, 707–711.10.1055/s-2008-1032108Search in Google Scholar

[15] Reddy, C. R.; Reddy, M. D. A metal-free tandem C–C/C–O bond formation approach to diversely functionalized tetrasubstituted furans. J. Org. Chem.2014, 79, 106–116.10.1021/jo4023342Search in Google Scholar PubMed

[16] Reddy, C. R.; Krishna, G.; Reddy, M. D. Synthesis of substituted 3-furanoates from MBH-acetates of acetylenic aldehydes via tandem isomerization–deacetylation–cycloisomerization: access to Elliott’s alcohol. Org. Biomol. Chem. 2014, 12, 1664–1670.10.1039/c3ob42396dSearch in Google Scholar PubMed

[17] Huang, L.; Jiang, H.; Qi, C.; Liu, X. Copper-catalyzed intermolecular oxidative [3 + 2] cycloaddition between alkenes and anhydrides: a new synthetic approach to γ-lactones. J. Am. Chem. Soc. 2010, 132, 17652–17654.10.1021/ja108073kSearch in Google Scholar PubMed

[18] Reddy, C. R.; Ranjan, R.; Kumaraswamy, P.; Reddy, M. D.; Gree, R. 1-Aryl propargylic alcohols as handy synthons for the construction of heterocycles and carbocycles. Curr. Org. Chem.2014, 18, 2603–2645.10.2174/138527281820141028104907Search in Google Scholar

[19] Lisovenko, N. Y.; Merkushev, A. A.; Nasibullina, E. R.; Slepukhin, P. A.; Rubtsov, A. E. First case of synthesis of furan-2,3-dione with trifluoroacyl substituent in position 4. Russ. J. Org. Chem. 2014, 50, 759–761.10.1134/S1070428014050261Search in Google Scholar

[20] Li, J. T.; Yin, Y.; Sun, M. X. An efficient one-pot synthesis of 2,3-epoxyl-1,3-diaryl-1-propanone directly from acetophenones and aromatic aldehydes under ultrasound irradiation. Ultrason. Sonochem. 2010, 17, 363–366.10.1016/j.ultsonch.2009.09.007Search in Google Scholar PubMed

[21] Shekouhy, M.; Hasaninejad, A. Ultrasound-promoted catalyst-free one-pot four component synthesis of 2H-indazolo[2,1-b]phthalazine-triones in neutral ionic liquid 1-butyl-3-methylimidazolium bromide. Ultrason. Sonochem. 2012, 19, 307.10.1016/j.ultsonch.2011.07.011Search in Google Scholar PubMed

[22] Cella, R.; Stefani, H. Ultrasound in heterocycles chemistry. Tetrahedron2009, 65, 2619–2641.10.1016/j.tet.2008.12.027Search in Google Scholar

[23] Simon, M. O.; Li, C. J. Green chemistry oriented organic synthesis in water. Chem. Soc. Rev. 2012, 41, 1415–1427.10.1039/C1CS15222JSearch in Google Scholar

[24] Zare, L.; Mahmoodi, N.O.; Yahyazadeh, A.; Mamaghani, M. Convenient ultrasound-promoted regioselective synthesis of fused 6-amino-3-methyl-4-aryl-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile. Synth. Commun. 2011, 41, 2323–2330.10.1080/00397911.2010.502990Search in Google Scholar

[25] Zare Fekri, L.; Nikpassand, M.; Hassanpour, K. Green aqueous synthesis of mono, bis and trisdihydropyridines using nano Fe₃O₄ under ultrasound irradiation. Curr. Org. Synth. 2015, 12, 76–79.10.2174/1570179411666140806005614Search in Google Scholar

[26] Zare Fekri, L.; Nikpassand, M. Ultrasound-promoted Friedel-Crafts acylation of arenes and cyclic anhydrides catalyzed by ionic liquid of [bmim]Br/AlCl₃. Russ. J. Gen. Chem. 2014, 84, 1825–1829.10.1134/S107036321409031XSearch in Google Scholar

[27] Zare Fekri, L.; Nikpassand, M.; Maleki, R. 1,4-Diazabicyclo [2.2.2] octanium diacetate: as an effective, new and reusable catalyst for the synthesis of benzo[d]imidazole. J. Mol. Liq. 2016, 222, 77–81.10.1016/j.molliq.2016.07.009Search in Google Scholar

[28] Zare, L.; Mahmoodi, N. O.; Yahyazadeh, A.; Nikpassand, M. Ultrasound-promoted regio and chemoselective synthesis of pyridazinones and phthalazinones catalyzed by ionic liquid [bmim]Br/AlCl₃. Ultrason. Sonochem. 2012, 19, 740–744.10.1016/j.ultsonch.2011.11.008Search in Google Scholar PubMed

Received: 2017-8-20

Accepted: 2018-3-5

Published Online: 2018-5-4

Published in Print: 2018-6-27

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Articles in the same Issue

https://doi.org/10.1515/hc-2017-0172

Keywords for this article

2,3-dihydrofuranedione; aqueous media; ethyl pyruvate; ultrasound irradiation; water

Creative Commons

BY-NC-ND 3.0