Subscribe to RSS
Please copy the URL and add it into your RSS Feed Reader.
https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00000083.xml
Synlett 2020; 31(10): 965-971
DOI: 10.1055/s-0039-1690887
DOI: 10.1055/s-0039-1690887
letter
Highly Efficient Chemoselective Synthesis of Pyrrolo[2,3-c]pyrazole Bearing Oxindole via Sequential Condensation–Michael Addition–Intramolecular Cyclization Reactions
We gratefully acknowledge financial support from the Research Council of Shahid Beheshti University and the Iran National Science Foundation (INSF).Further Information
Publication History
Received: 01 February 2020
Accepted after revision: 20 March 2020
Publication Date:
07 April 2020 (online)
Abstract
An efficient and highly chemoselective approach for the synthesis of novel scaffolds based on pyrrolo[2,3-c]pyrazole bearing oxindole is accomplished by the acid-promoted sequential reactions between benzoylacetonitriles, phenylhydrazine, and 3-phenacylideneoxindoles as readily available starting materials. This value structure is dexterously embraced with oxindole, pyrrole, and pyrazole heterocycles, which are famous for their enriched biological properties. Besides, this is an eco-friendly and atom-economy approach, and water is the only side product of the reaction. In this protocol, the requirement of column chromatography is completely avoided, and the products were isolated by recrystallization in crude reactions. These compounds due to their excellent fluorescence features and bioactive scaffolds may be attracted great interest in biomedical applications and clinical diagnostics in the future.
Supporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/s-0039-1690887.
- Supporting Information
- CIF File
-
References and Notes
- 1a Karrouchi K, Radi S, Ramli Y, Taoufik J, Mabkhot YN, Al-aizari FA. Molecules 2018; 23: 134
- 1b Raffa D, Migliara O, Maggio B, Plescia F, Cascioferro S, Cusimano MG, Tringali G, Cannizzaro C, Plescia F. Arch. Pharm. 2010; 343: 631
- 1c El-Sabbagh OI, Baraka MM, Ibrahim SM, Pannecouque C, Andrei G, Snoeck R, Balzarini J, Rashad AA. Eur. J. Med. Chem. 2009; 44: 3746
- 1d Ong EB. B, Watanabe N, Saito A, Futamura Y, El Galil KH. A, Koito A, Najimudin N, Osada H. J. Biol. Chem. 2011; 286: 14049
- 1e Arikawa Y, Nishida H, Kurasawa O, Hasuoka A, Hirase K, Inatomi N, Hori Y, Matsukawa J, Imanishi A, Kondo M. J. Med. Chem. 2012; 55: 4446
- 2a Raffa D, Maggio B, Raimondi MV, Cascioferro S, Plescia F, Cancemi G, Daidone G. Eur. J. Med. Chem. 2015; 97: 732
- 2b Abdel-Mohsen SA. Bull. Korean Chem. Soc. 2005; 26: 719
- 2c Ochiana SO, Pandarinath V, Wang Z, Kapoor R, Ondrechen MJ, Ruben L, Pollastri MP. Eur. J. Med. Chem. 2013; 62: 777
- 3a Nevagi RJ, Dighe SN, Dighe SN. Eur. J. Med. Chem. 2015; 97: 561
- 3b Stevens FC, Bloomquist WE, Borel AG, Cohen ML, Droste CA, Heiman ML, Kriauciunas A, Sall DJ, Tinsley FC, Jesudason CD. Bioorg. Med. Chem. Lett. 2007; 17: 6270
- 3c Estévez V, Villacampa M, Menéndez JC. Chem. Soc. Rev. 2014; 43: 4633
- 3d Gulevich AV, Dudnik AS, Chernyak N, Gevorgyan V. Chem. Rev. 2013; 113: 3084
- 3e Millemaggi A, Taylor RJ. Eur. J. Org. Chem. 2010; 4527
- 3f Gangarapu K, Thumma G, Manda S, Jallapally A, Jarapula R, Rekulapally S. Med. Chem. Res. 2017; 26: 819
- 4a Edeson SJ, Jiang J, Swanson S, Procopiou PA, Adams H, Meijer AJ, Harrity JP. Org. Biomol. Chem. 2014; 12: 3201
- 4b Jiang S, Guo H.-M, Yao S, Shi D.-Q, Xiao W.-J. J. Org. Chem. 2017; 82: 10433
- 4c Gupta AK, Ahamad S, Gupta E, Kant R, Mohanan K. Org. Biomol. Chem. 2015; 13: 9783
- 4d Hu J.-D, Cao C.-P, Lin W, Hu M.-H, Huang Z.-B, Shi D.-Q. J. Org. Chem. 2014; 79: 7935
- 4e Sharma N, Peddinti RK. J. Org. Chem. 2017; 82: 918
- 4f Sun J, Xie Y.-J, Yan C.-G. J. Org. Chem. 2013; 78: 8354
- 4g Vivekanand T, Vinoth P, Agieshkumar B, Sampath N, Sudalai A, Menéndez JC, Sridharan V. Green Chem. 2015; 17: 3415
- 4h Shanthi G, Perumal PT. Tetrahedron Lett. 2009; 50: 3959
- 4i Sharma N, Peddinti RK. J. Org. Chem. 2017; 82: 9360
- 4j Vivekanand T, Vachan B, Karuppasamy M, Muthukrishnan I, Maheswari CU, Nagarajan S, Bhuvanesh N, Sridharan V. J. Org. Chem. 2019; 84: 4009
- 4k Jiang Y.-H, Yan C.-G. Synthesis 2016; 48: 3057
- 4l Dai L, Shu P, Wang Z, Li Q, Yu Q, Shi Y, Rong L. Synthesis 2017; 49: 637
- 5 Zollinger H. Color Chemistry: Syntheses, Properties, and Applications of Organic Dyes and Pigments. Wiley-VCH; Weinheim: 2003
- 6a Rabindranath A, Zhu Y, Heim I, Tieke B. Macromolecules 2006; 39: 8250
- 6b Zhu Y, Heim I, Tieke B. Macromol. Chem. Phys. 2006; 207: 2206
- 6c Cao D, Liu Q, Zeng W, Han S, Peng J, Liu S. J. Polym. Sci., Part A: Polym. Chem. 2006; 44: 2395
- 7a Zhang X, Richter LJ, DeLongchamp DM, Kline RJ, Hammond MR, McCulloch I, Heeney M, Ashraf RS, Smith JN, Anthopoulos TD. J. Am. Chem. Soc. 2011; 133: 15073
- 7b Wang B, He N, Li B, Jiang S, Qu Y, Qu S, Hua J. Austr. J. Chem. 2012; 65: 387
- 8 Schutting S, Borisov SM, Klimant I. Anal. Chem. 2013; 85: 3271
- 9a Burchak ON, Mugherli L, Ostuni M, Lacapere JJ, Balakirev MY. J. Am. Chem. Soc. 2011; 133: 10058
- 9b Javanbakht S, Shaabani A. ACS Appl. Bio Mater. 2020; 3: 156
- 10a Shaabani A, Nazeri MT, Afshari R. Mol. Diversity 2019; 23: 751
- 10b Shaabani A, Seyyedhamzeh M, Maleki A, Behnam M, Rezazadeh F. Tetrahedron Lett. 2009; 50: 2911
- 10c Shaabani A, Maleki A, Mofakham H, Moghimi-Rad J. J. Org. Chem. 2008; 73: 3925
- 10d Ghandi M, Nazeri MT, Kubicki M. Tetrahedron 2013; 69: 4979
- 11 Nazeri MT, Javanbakht S, Shaabani A, Khavasi HR. ChemistrySelect 2019; 4: 14271
- 12a Alizadeh A, Mokhtari J. Tetrahedron 2011; 67: 3519
- 12b Li M.-Y, Xu H.-W, Fan W, Ye Q, Wang X, Jiang B, Wang S.-L, Tu S.-J. Tetrahedron 2014; 70: 1004
- 13 3-{1,3,5-Triphenyl-1,6-dihydropyrrolo[2,3-c]pyrazol-4-yl}indolin-2-one (5a); Typical Procedure Benzoylacetonitrile (1a, 0.25 mmol) and phenylhydrazine (2a, 0.25 mmol) were mixed in neat conditions and heated at 120 °C for 2.0 h. After completion of the reaction, the reaction mixture was cooled to room temperature. Then, 3-(2-aryl-2-oxoethylidene)indolin-2-one (4a, 0.25 mmol) PTSA·H2O (0.05 mmol) and EtOH (2.5 mL) were added to the reaction mixture. Afterwards, the mixture was stirred for 6 h under reflux conditions. Upon the completion of the reaction (monitored by TLC), the reaction mixture was cooled to room temperature. The precipitate was collected by filtration and washed with cold ethanol to give the pure product 5a (93 mg, yield 80%).
- 14 3-{1,3,5-Triphenyl-1,6-dihydropyrrolo[2,3-c]pyrazol-4-yl}indolin-2-one (5a) White powder (92 mg, 80%); mp 214–216 °C. Anal. Calcd (%) for C31H22N4O: C, 79.81; H, 4.75. Found: C, 79.73; H, 4.70. IR (ATR): νmax = 3146 (NH), 1708 (CO), 1467 (C=C) cm–1. 1H NMR (300 MHz, CDCl3): δ (mixture of tautomers) = 4.91 (s, 0.85 H, H3), 5.16 (s, 0.15 H, H3), 6.71 (s, 1 H, HAr), 6.88–6.96 (m, 2 H, HAr), 7.08–7.28 (m, 10 H, HAr), 7.39–7.52 (m, 5 H, HAr), 7.69–7.76 (m, 5 H, HAr), 8.10–8.23 (br s, 1 H, NH), 8.49 (br s, 1 H, NH). 13C NMR (125 MHz, CDCl3): δ (mixture of tautomers) = 179.8 (CO), 146.1, 141.6, 141.6, 141.2, 139.3, 133.4, 132.2, 130.2, 129.7, 129.2, 128.7, 128.4, 128.3, 128.2, 127.8, 127.6, 125.5, 124.5, 122.6, 118.6, 115.4, 110.0 (CAr), 44.9 (C3). MS (EI, 70 eV): m/z = 466 (100) [M+], 437 (25), 334 (47), 231 (23), 104 (29), 77 (91).