Synthesis of 5H-spiro[furan-2,2′-indene]-1′,3′,5-triones from tetrahydro-4-oxoindeno[1,2-b]pyrroles

Mohammad Piltan

doi:10.1515/hc-2017-0250

Article Open Access

Synthesis of 5H-spiro[furan-2,2′-indene]-1′,3′,5-triones from tetrahydro-4-oxoindeno[1,2-b]pyrroles

Mohammad Piltan

Published/Copyright: May 9, 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

A simple approach to assembling of functionalized spiro-butenolide-indenetriones from oxoindeno[1,2-b]pyrrole derivatives in the presence of H₂SO₄ is described. Simplicity of the procedure, short reaction time and excellent yields are important features of this protocol.

Keywords: amines; dialkyl acetylenedicarboxylates; 2(5H)-furanones; ninhydrin

Introduction

Five-membered oxygen-containing heterocycles have been referred to as privileged structural motifs owing to their wide distribution in pharmaceuticals and natural products [1], [2], [3], [4], [5]. In particular, 2(5H)-furanones have received increasing attention because of their biological and pharmacological activities, such as antitumor, antimicrobial, antiviral and anti-human immunodeficiency virus 1 (HIV-1) properties [6], [7], [8]. Furans are also present in agrochemical bioregulators, essential oils, cosmetics, dyes, photosensitizers and flavoring and fragrance compounds [9], [10]. The presence of a sterically constrained spiro structure in heterocyclic compounds also adds to the versatility of the properties of spiro compounds [11], [12]. In continuation of our work on the development of efficient protocols for the synthesis of heterocyclic compounds [13], [14], [15], [16], herein, a novel approach to the synthesis of spiro-2(5H)-furanone derivatives 2 is reported (Scheme 1). The products are unusual in that a different outcome could be expected based on the recent report of a closely related reaction [17].

Scheme 1

Results and discussion

Synthesis of indeno[1,2-b]pyrrole-2,3-dicarboxylate derivative 1a by the reaction of ninhydrin, methyl acetylenedicarboxylate and aniline has been reported by Yavari and co-workers [18], but conversion of the product 1a in the presence of concentrated sulfuric acid has not been studied. In this work, heating of compound 1a with a catalytic amount of sulfuric acid in acetic acid for 3 h furnished 5H-spiro[furan-2,2′-indene]-1′,3′,5-trione 2a. In order to show the generality and scope of this new protocol, additional products 2b–f were obtained, as summarized in Scheme 1. The structures of compounds 2a–f are in full agreement with their infrared (IR) spectroscopy, mass spectrometry (MS), proton nuclear magnetic resonance (¹H NMR), and carbon-13 nuclear magnetic resonance (¹³C NMR) data. A suggested mechanism is given in Scheme 2. The proposed sequence involves protonation of 1 in the first step and then is self-explanatory.

Scheme 2

Conclusions

A convenient and efficient methodology for synthesizing diverse 5H-spiro[furan-2,2′-indene]-1′,3′,5-triones with potential biological properties from commercially available materials was developed.

Experimental

IR spectra were recorded in KBr pellets on a Shimadzu 460 spectrometer. ¹H NMR (400 MHz) and ¹³C NMR (100 MHz) spectra were recorded on a Bruker Avance 400 spectrometer using CDCl₃ as solvent. Electron impact mass spectra were obtained at 70 eV on a Finnigan-MAT-8430 mass spectrometer. Elemental analyses for C, H and N were obtained on a Heraeus CHNO-Rapid analyzer. All commercially available chemicals and reagents were used without further purification.

General procedure for the preparation of compounds 2a–f

Concentrated H₂SO₄ (20 mol%) was added to a solution of dihydroxyindenopyrrole 1 (1 mmol) in acetic acid (5 mL). The mixture was heated in a water bath at 80°C for 3 h. After completion of the reaction as monitored by thin layer chromatography (TLC), eluting with a mixture of ethyl acetate and hexanes (1:4), the mixture was cooled to room temperature and then poured into 5 mL of water. The product was extracted with CH₂Cl₂ (2×5 mL). The extract was concentrated under reduced pressure and the viscous residue was purified by silica gel chromatography eluting with a mixture of ethyl acetate and hexanes (1:6).

Methyl 1′,3′,5-trioxo-4-(phenylamino)-1′,3′-dihydro-5H-spiro[furan-2,2′-indene]-3-carboxylate (2a)

Yellow oil; yield 0.32 g (88%); IR: 3356, 1786, 1725, 1693 cm⁻¹; ¹H NMR: δ 3.45 (3H, s, OCH₃), 6.78 (1 H, br s, NH), 7.23–8.14 (9H, m, CH); ¹³C NMR: δ 52.3, 109.1, 120.2, 123.1, 124.5, 126.8, 129.2, 137.4, 139.8, 141.6, 145.3, 165.5, 170.1, 193.3; EI-MS: m/z 363 (M⁺, 9), 227 (23), 105 (100), 99 (54), 77 (90), 59 (61%). Anal. Calcd for C₂₀H₁₃NO₆: C, 66.12; H, 3.61; N, 3.86. Found: C, 66.28; H, 3.50; N, 3.81.

Ethyl 1′,3′,5-trioxo-4-(phenylamino)-1′,3′-dihydro-5H-spiro[furan-2,2′-indene]-3-carboxylate (2b)

Yellow oil; yield 0.33 g (87%); IR: 3353, 1782, 1726, 1695 cm⁻¹; ¹H NMR: δ 1.14 (3H, t, ³J=6.8 Hz, CH₃), 4.11 (2H, q, ³J=6.8 Hz, CH₂O), 6.69 (1 H, br s, NH), 7.21–8.14 (9H, m, CH); ¹³C NMR: δ 14.2, 61.2, 109.3, 120.3, 123.3, 124.6, 126.8, 129.1, 137.6, 139.5, 141.3, 145.2, 165.7, 170.2, 193.6; EI-MS: m/z 377 (M⁺, 11), 227 (25), 105 (100), 104 (48), 92 (70), 77 (78%). Anal. Calcd for C₂₁H₁₅NO₆: C, 66.84; H, 4.01; N, 3.71. Found: C, 66.62; H, 3.94; N, 3.66.

Methyl 4-(benzylamino)-1′,3′,5-trioxo-1′,3′-dihydro-5Hspiro[furan-2,2′-indene]-3-carboxylate (2c)

Yellow oil; yield 0.35 g (94%); IR: 3355, 1785, 1724, 1695 cm⁻¹; ¹H NMR: δ 3.43 (3H, s, MeO), 5.05 (2H, d, ³J=6.4 Hz, CH₂N), 6.75 (1H, br s, NH), 7.27–8.10 (9H, m, CH); ¹³C NMR: δ 48.6, 52.2, 109.5, 120.3, 124.7, 128.1, 128.3, 129.3, 137.1, 138.0, 141.2, 148.7, 166.8, 170.2, 193.6; EI-MS: m/z 337 (M⁺, 12), 233 (31), 227 (21), 120 (13), 105 (100), 104 (65), 91 (71), 59 (88%). Anal. Calcd for C₂₁H₁₅NO₆: C, 66.84; H, 4.01; N, 3.71. Found: C, 66.74; H, 3.95; N, 3.65.

Ethyl 4-(benzylamino)-1′,3′,5-trioxo-1′,3′-dihydro-5H-spiro[furan-2,2′-indene]-3-carboxylate (2d)

Yellow oil; yield 0.36 g (92%); IR: 3351, 1785, 1728, 1691 cm⁻¹; ¹H NMR: δ 1.28 (3H, t, ³J=6.8 Hz, Me), 4.12 (2H, q, ³J=6.8 Hz, Me), 5.03 (2H, d, ³J=6.2 Hz, CH₂N), 6.70 (1 H, br s, NH), 7.33–8.14 (9H, m, CH); ¹³C NMR: δ 14.2, 48.7, 62.1, 109.5, 120.8, 124.8, 128.2, 128.3, 129.5, 137.4, 138.2, 141.4, 148.6, 166.8, 170.2, 193.2; EI-MS: m/z 391 (M⁺, 11), 247 (21), 227 (16), 105 (100), 104 (38), 91 (64), 73 (87%). Anal. Calcd for C₂₂H₁₇NO₆: C, 67.51; H, 4.38; N, 3.58. Found: C, 67.32; H, 4.31; N, 3.52.

Methyl 4-(ethylamino)-1′,3′,5-trioxo-1′,3′-dihydro-5H-spiro[furan-2,2′-indene]-3-carboxylate (2e)

Yellow oil; yield 0.29 g (91%); IR: 3353, 1784, 1723, 1687, 1642 cm⁻¹; ¹H NMR: δ 1.30 (3H, t, ³J=7.2 Hz, Me), 3.44 (3H, s, MeO), 3.86 (2H, q, ³J=7.2 Hz, CH₂N), 6.78 (1 H, br s, NH), 7.97–8.12 (4H, m, 4CH); ¹³C NMR: δ 16.6, 29.6, 51.8, 109.2, 120.3, 124.6, 137.3, 141.4, 148.7, 166.7, 170.1, 194.2; EI-MS: m/z 315 (M⁺, 8), 227 (18), 105 (100), 59 (92), 44 (66%). Anal. Calcd for C₁₆H₁₃NO₆: C, 60.95; H, 4.16; N, 4.44. Found: C, 61.71; H, 4.14; N, 4.37.

Ethyl 4-(ethylamino)-1′,3′,5-trioxo-1′,3′-dihydro-5H-spiro[furan-2,2′-indene]-3-carboxylate (2f)

Yellow oil; yield 0.29 g (89%); IR: 3355, 1783, 1720, 1692, 1649 (C=O) cm⁻¹; ¹H NMR: δ 0.89 (3H, t, ³J=7.2 Hz, Me), 1.29 (3H, t, ³J=6.8, Me), 3.86 (2H, q, ³J=7.2 Hz, CH₂N), 4.20 (2H, q, ³J=6.8 Hz, CH₂O), 6.78 (1 H, br s, NH), 7.96–8.10 (4H, m, CH); ¹³C NMR: δ 14.2, 16.5, 29.5, 61.4, 109.1, 120.0, 124.5, 137.2, 141.2, 148.2, 166.5, 170.0, 194.4; EI-MS: m/z 329 (M⁺, 11), 227 (19), 105 (100), 44 (70), 73 (92), 29 (50%). Anal. Calcd for C₁₇H₁₅NO₆: C, 62.00; H, 4.59; N, 4.25. Found: C, 61.87; H, 4.50; N, 4.20.

Acknowledgments

The author gratefully acknowledges financial support from the Research Council of Islamic Azad University, Sanandaj Branch.

References

[1] Aghahosseini, H.; Ramazani, A.; Ślepokura, K.; Lis, T. The first protection-free synthesis of magnetic bifunctional l-proline as a highly active and versatile artificial enzyme: synthesis of imidazole derivatives. J. Colloid Interface Sci.2018, 511, 222–232.10.1016/j.jcis.2017.10.020Search in Google Scholar PubMed

[2] Aghahosseini, H.; Ramazani, A.; Gouranlou, F.; Joo, S. W. Nanoreactors technology in green organic synthesis. Curr. Org. Synth.2017, 14, 810–864.10.2174/1570179413666161008200641Search in Google Scholar

[3] Padwa, A.; Dimitroff, M.; Waterson, A. G.; Wu, T. Diels−Alder reaction of 2-amino-substituted furans as a method for preparing substituted Anilines. J. Org. Chem.1997, 62, 4088–4096.10.1021/jo9702599Search in Google Scholar

[4] Kappe, O. C.; Murphree, S. S.; Padwa, A. Synthetic applications of furan Diels-Alder chemistry. Tetrahedron1997, 53, 14179–14233.10.1016/S0040-4020(97)00747-3Search in Google Scholar

[5] Mortensen, D. S.; Rodriguez, A. L.; Carlson, K. E.; Sun, J.; Katzenellenbogen, B. S.; Katzenellenbogen, J. A. Synthesis and biological evaluation of a novel series of furans:ligands selective for estrogen receptor α. J. Med. Chem.2001, 44, 3838–3848.10.1021/jm010211uSearch in Google Scholar PubMed

[6] Bandurraga, M. M.; Fenical, W.; Donovan, S. F.; Clardy, J. Pseudopterolide, an irregular diterpenoid with unusual cytotoxic properties from the Caribbean sea whip Pseudopterogorgia acerosa. J. Am. Chem. Soc.1982, 104, 6463–6465.10.1021/ja00387a059Search in Google Scholar

[7] Hofnung, M.; Quillardet, P.; Michel, V.; Touati, E. Genotoxicity of 2-nitro-7-methoxy-naphtho[2,1-b]furan (R7000): a case study with some considerations on nitrofurantoin and nifuroxazide. Res. Microbiol.2002, 153, 427–434.10.1016/S0923-2508(02)01354-2Search in Google Scholar

[8] Kobayashi, J.; Ohizumi, Y.; Nakamura, H. Hippospongin, a novel furanosesterterpene possessing antispasmodic activity from the Okinawan marine sponge Hippospongia sp. Tetrahedron Lett. 1986, 27, 2113–2116.10.1016/S0040-4039(00)84462-7Search in Google Scholar

[9] Yang, Y.; Wong, H. N. C. Regiospecific synthesis of 3,4-disubstituted furans and 3-substituted furans using 3,4-bis(tri-n-butylstannyl)furan and 3-(tri-n-butylstannyl)furan. Tetrahedron1994, 50, 9583–9608.10.1016/S0040-4020(01)85528-9Search in Google Scholar

[10] Gabriele, B.; Salerno, G.; Lauria, E. A general and facile synthesis of substituted furans by palladium-catalyzed cycloisomerization of (Z)-2-en-4-yn-1-ols. J. Org. Chem.1999, 64, 7687–7692.10.1021/jo990847hSearch in Google Scholar

[11] Matloubi-Moghaddam, F.; Hojabri, L.; Taheri, S.; Pirani, P. A tandem aldol-diels-alder reaction accelerated in water: an approach to the catalyst-free one-pot synthesis of spiro thio-oxindoles. J. Iran. Chem. Soc.2010, 7, 781–790.10.1007/BF03246069Search in Google Scholar

[12] Patel, S. V.; Patel, M. P.; Patel, R. G. Synthesis and characterization of bromoquinazolinone substituted spiro[isobenzofuran-1,9′-xanthene]-3-ones. J. Iran. Chem. Soc.2005, 2, 220–225.10.1007/BF03245925Search in Google Scholar

[13] Piltan, M. Preparation of 1H-pyrazolo[1,2-b]phthalazine-5,10- dione derivatives by ZrO₂ nanoparticles as catalyst under solvent-free conditions. Heterocycl. Commun.2017, 23, 401–404.10.1515/hc-2017-0142Search in Google Scholar

[14] Sharafi, Z.; Piltan, M. Efficient assembly of quinoxaline derivatives from benzene-1,2-diamines, dialkyl acetylenedicarboxylates and ninhydrin. Heterocycl. Commun.2016, 22, 53–57.10.1515/hc-2015-0187Search in Google Scholar

[15] Moradi, L.; Piltan, M.; Abasi, G. One-pot synthesis of novel pyrrolo[1,2-a]quinoxaline-4(5H)-ones using benzene-1,2-diamine, acetylenedicarboxylates, and β-nitrostyrene derivatives. Helv. Chim. Acta2014, 97, 646–651.10.1002/hlca.201300209Search in Google Scholar

[16] Moradi, L.; Piltan, M.; Rostami, H. One-pot synthesis of novel pyrrolo-1,4-benzoxazines via a three-component reaction of 2-aminophenols, acetylenic esters and nitrostyrene derivatives. Chin. Chem. Lett.2014, 25, 123–126.10.1016/j.cclet.2013.10.009Search in Google Scholar

[17] Pathak, S.; Kundu, A.; Pramanik, A. Facile synthesis of substituted pyrrole-fused isocoumarins from ninhydrin. Tetrahedron Lett.2011, 52, 5180–5183.10.1016/j.tetlet.2011.07.133Search in Google Scholar

[18] Yavari, I.; Seyfi, S.; Nematpour, M.; Zinatossadat, H. Synthesis of functionalized tetrahydro-4-oxoindeno[1,2-b]pyrroles from ninhydrin, acetylenedicarboxylates, and primary amines. Helv. Chim. Acta2010, 93, 1413–1417.10.1002/hlca.200900408Search in Google Scholar

Received: 2017-12-5

Accepted: 2018-2-2

Published Online: 2018-5-9

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-2017-0250

Keywords for this article

amines; dialkyl acetylenedicarboxylates; 2(5H)-furanones; ninhydrin

Creative Commons

BY-NC-ND 3.0