Efficient Synthesis of 7,8-Dihydro-6H-benzo[c]chromen-6-one Derivatives by Base-Mediated Chemoselective Annulation of Alkylidene Malononitriles with α,β-Unsaturated Coumarins

Abstract

An efficient and chemoselective synthesis of biologically valuable 7,8-dihydro-6H-benzo[c]chromen-6-ones is described. In this method, neither a metal catalyst nor expensive starting materials are needed, and the products can be purified by simple filtration and washing with EtOH. Readily available starting materials, green and mild conditions, synthetically useful yields, and operational simplicity are some highlighted advantages of this unprecedented transformation.

Key words

alkylidenemalononitriles - coumarins - benzochromenones - 6π-electrocyclic ring closure - hydride shift

Publication History

Received: 03 December 2020

Accepted after revision: 04 January 2021

Article published online:
22 January 2021

• References and Notes

• 1a Garazd L, Garazd MM. Chem. Nat. Compd. 2016; 52: 1
• 1b Mao Z, Sun W, Fu L, Luo H, Lai D, Zhou L. Molecules 2014; 19: 5088
• 1c Raistrick H, Stilkings CE, Thomas R. Biochem. J. 1953; 55: 421
• 1d Pero RW, Harvan D, Blois MC. Tetrahedron Lett. 1973; 14: 945
• 1e Lv H.-N, Tu P.-F, Jiang Y. Mini Rev. Med. Chem. 2014; 14: 603
• 2 Koch K, Podlech J, Pfeiffer E, Metzler M. J. Org. Chem. 2005; 70: 3275
• 3 Meng X, Mao Z, Lou J, Xu L, Zhong L, Peng Y, Zhou L, Wang M. Molecules 2012; 17: 11303
• 4 Zhang M, Deng Y, Zhang H.-B, Su X.-L, Chen HL, Yu T, Guo P. Chem. Pharm. Bull. 2008; 56: 192
• 5 Asami Y, Ogura T, Otake N, Nishimura T, Xinsheng Y, Sakurai T, Nagasawa H, Sakuda S, Tatsuta K. J. Nat. Prod. 2003; 66: 729
• 6 Takahashi K, Tomita F. J. Antibiot. 1983; 36: 1531
• 7a Strelitz F, Flon H, Asheshov IN. J. Bacteriol. 1955; 69: 280
• 7b Weiss U, Yoshihira K, Highet RJ, White RJ, Wei TT. J. Antibiot. 1982; 35: 1194
• 8 Sehgal SN, Czerkawski H, Kudelski A, Pandev K, Saucier R, Vézina C. J. Antibiot. 1983; 36: 355
• 9a Edwards JP, West SJ, Marschke KB, Mais DE, Gottardis M, Jones TK. J. Med. Chem. 1998; 41: 303
• 9b Hamann LG, Higuchi RI, Zhi L, Edwards JP, Wang X.-N, Marschke KB, Kong JW, Farmer LJ, Jones TK. J. Med. Chem. 1998; 41: 623
• 9c Coghlan MJ, Kym PR, Elmore SW, Wang AX, Luly JR, Wilcox D, Stashko M, Lin C.-W, Miner J, Tyree C, Nakane M, Jacobson P, Lane BC. J. Med. Chem. 2001; 44: 2879
• 10 Zhang Y, Tian Y, Xiang P, Huang N, Wang J, Xu J.-H, Zhang M. Org. Biomol. Chem. 2016; 14: 9874
• 11 Huang L, Weix DJ. Org. Lett. 2016; 18: 5432
• 12 Dao PD. Q, Ho SL, Lim H.-J, Cho CS. J. Org. Chem. 2018; 83: 4140
• 13 Inamoto K, Kadokawa J, Kondo Y. Org. Lett. 2013; 15: 3962
• 14a Dong Y, Yu J.-T, Sun S, Cheng J. Chem. Commun. 2020; 56: 6688
• 14b Pottie IR, Nandaluru PR, Benoit WL, Miller DO, Dawe LN, Bodwell GJ. J. Org. Chem. 2011; 76: 9015
• 14c Luo Z, Gao Z.-H, Song Z.-Y, Han Y.-F, Ye S. Org. Biomol. Chem. 2019; 17: 4212
• 15 Dai J.-J, Xu W.-T, Wu Y.-D, Zhang W.-M, Gong Y, He X.-P, Zhang X.-Q, Xu H.-J. J. Org. Chem. 2015; 80: 911
• 16 Dong Y, Yu J.-T, Sun S, Cheng J. Chem Commun. 2020; 56: 6688
• 17 Luo S, Luo F.-X, Zhang X.-S, Shi Z.-J. Angew. Chem. Int. Ed. 2013; 52: 10598
• 18a Cuia H.-L, Chen Y.-C. Chem. Commun. 2009; 4479
• 18b Ji D.-S, Luo Y.-C, Hu X.-Q, Xu P.-F. Org. Lett. 2020; 22: 1028
• 18c Alizadeh A, Hosseini SY, Sedighian H, Bayat F, Zhu Z, Dusek M. Tetrahedron 2015; 71: 7885
• 19a Heber D, Ivanov IC, Karagiosov SK. J. Heterocycl. Chem. 1995; 32: 505
• 19b Bochkov AY, Akchurin IO, Dyachenko OA, Traven VF. Chem. Commun. 2013; 49: 11653
• 19c Patel AA, Lad HB, Pandya KR, Patel CV, Brahmbhatt DI. Med. Chem. Res. 2013; 22: 4745
• 19d Bera R, Dhananjaya G, Nath S, Kumar R, Mukkanti K, Pal M. Tetrahedron 2009; 65: 1300
• 19e Heber D. Arch. Pharm (Weinheim, Ger.) 1987; 320: 577
• 19f Alizadeh A, Farajpour B, Mohammadi SS, Sedghi M, Naderi-Manesh H, Janiak C, Knedel T.-O. ChemistrySelect 2020; 5: 9362
• 19g Alizadeh A, Farajpour B, Amir Ashjaee Asalemi K, Taghipour S. ChemistrySelect 2020; 5: 9834
• 19h Alizadeh A, Amir Ashjei Asalemi K, Farajpour B, Halvagar MR. J. Iran. Chem. Soc. 2020; 17:  3393
• 20a Soltau M, Göwert M, Margaretha P. Org. Lett. 2005; 7: 5159
• 20b Chen J, Li Y, Xiao Z, He H, Gao S. Org. Lett. 2020; 22: 1485
• 20c Darwish OS, Granum KA, Tan Q, Hsung RP. Tetrahedron Lett. 2001; 42: 3283
• 21 7,8-Dihydro-6H-benzo[c]chromen-6-ones 3a–i; General Procedure Et₃N (0.5 mmol) was added to a mixture of the appropriate alkylidene malononitrile derivative 1 (0.5 mmol) and 4-chloro-3-(3-oxo-3-phenylprop-1-en-1-yl)-2H-chromen-2-one 2 (0.5 mmol) in anhyd EtOH (1 mL), and the mixture was stirred at 80 °C for 10 h until the reaction was complete (TLC). The resulting solid was isolated by simple filtration and washed twice with 96% EtOH. 6-Oxo-7-(2-oxo-2-phenylethyl)-9-phenyl-6H-benzo[c]chromene-8,8(7H)-dicarbonitrile (3a) White powder; yield: 0.34 g (77%); mp 284–286 °C. IR (KBr): 2229 (C≡N), 1732 (C=O), 1687 (COO), 1600, 1580, and 1500 (Ar), 1159, and 1085 (C–O) cm^–1. ¹H NMR (500 MHz, CDCl₃): δ = 3.25 (dd, ² J _HH = 16.0 Hz, ³ J _HH = 6.5 Hz, 1 H, CH¹), 3.83 (dd, ² J _HH = 16.0 Hz, ³ J _HH = 5.7 Hz, 1 H, CH¹), 4.77 (t, ³ J _HH = 6.0 Hz, 1 H, CH⁷), 7.27 (d, ³ J _HH = 8.3 Hz, 2 H, 2CH _ortho of Ph), 7.37 (t, ³ J _HH = 7.5 Hz, 1 H, CH² of coumarin), 7.43 (d, ³ J _HH = 8.4 Hz, 1 H, CH⁴ of coumarin), 7.45 (t, ³ J _HH = 7.6 Hz, 2 H, 2CH _meta of Ph), 7.54–7.57 (m, 3 H, 3CH of Ph), 7.63 (s, 1 H, CH¹⁰), 7.63 (t, ³ J _HH = 7.6 Hz, 1 H, CH³ of coumarin), 7.64 (t, ³ J _HH = 7.9 Hz, 1 H, CH _para of Ph), 7.73 (d, ³J_HH = 8.0 Hz, 1 H, CH¹ of coumarin), 7.92 (d, ³ J _HH = 7.7 Hz, 2 H, 2CH _ortho of Ph). ¹³C NMR (125 MHz, CDCl₃): δ = 37.3 (CH⁸), 37.3 (CH⁷), 37.8 (CH₂), 112.6 (CN), 113.4 (CN), 116.0 (C^10b), 116.8 (C^6a), 117.7 (CH⁴ of coumarin), 121.8 (CH¹⁰), 123.4 (CH² of coumarin), 124.8 (CH¹ of coumarin), 127.0 (2CH _meta of Ph), 128.3 (2CH _meta of Ph), 128.7 (2CH _ortho of Ph), 129.2 (2CH _ortho of Ph), 130.9 (CH _para of Ph), 132.6 (CH³ of coumarin), 133.6 (CH _para of Ph), 135.2 (C⁹), 136.1 (C of Ph), 137.8 (C of Ph), 139.8 (C^10a), 153.5 (C^4a), 159.4 (CO of coumarin), 194.9 (CO). MS (EI, 70 eV): m/z (%) = 442 (M⁺, 20), 416 (28), 297 (26), 105 (100), 77 (24). Anal. Calcd for C₂₉H₁₈N₂O₃ (442.46): C, 78.72; H, 4.10, N, 6.33. Found: C, 78.73; H, 4.12, N, 6.32.
• 22 CCDC 1955482 contains the supplementary crystallographic data for compound 3c. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures.