Synthesis and structure of (R,S)-2-methyl-4-(4-nitrophenyl)-pyrano[3,2-c]chromen-5(4H)-one

Rosica P. Nikolova, Boris Shivachev, Bozhana Mikhova, Bistra Stamboliyska, Kristina Mladenovska, Ana P. Panovska, Emil Popovski


In this paper, the synthesis and structure of a novel pyrano[3,2-c]coumarin, which was obtained unexpectedly in a reaction of phosphoryl chloride and acenocoumarol, are presented. The chemical structure of the novel compound was elucidated by a detailed spectroscopic analysis based mainly on 1D and 2D NMR techniques. The structure was finally confirmed with a single-crystal X-ray analysis. The B3LYP/6-311+G** method correctly reproduces the bond lengths, bond angles, torsion angles, and other experimental spectroscopic data, which can be useful for investigating the characteristics of some structurally related molecules. Additionally, the title compound was obtained in high yields by performing a dehydratation reaction of acenocuomarol with acetic anhydride.  


acenocoumarol; pyrano[3,2-c]coumarin; crystal structure; DFT calcualations

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D. C. Mungra, M. P. Patel, D. P. Rajani, R. G. Patel, Synthesis and identification of b-aryloxyquinolines and their pyrano[3,2-c]chromene derivatives as a new class of antimicrobial and antituberculosis agents, Eur. J. .Med. Chem., 46, 4192–4200 (2011).

E. Melliou, P. Magiatis, S. Mitaku, A. L. Skaltsounis, E. Chinou, I. Chinou, Natural and synthetic 2,2-dimethylpyranocoumarins with antibacterial activity, J. Nat. Prod., 68, 78–82 (2005).

A. M. El-Agrody, M. S. Abd El-Latif, N. A. El- Hady, A. H. Fakery, A.H. Bedair, Heteroaromatization with 4-Hydroxycoumarin Part II: Synthesis of Some New Pyrano [2,3-d]pyrimidines, [1,2,4] triazolo[1,5-c]pyrimidines and Pyrimido[1,6- b]-[1,2,4]triazine Derivatives, Molecules, 6, 519– 527 (2001).

M.A. Al-Haiza, M.S. Mostafa, M.Y. El-Kady, Synthesis and Biological Evaluation of Some New Coumarin Derivatives, Molecules, 8, 275–286 (2003).

A.H. Bedair, N.A. El-Hady, M.S. Abd El-latif, A.M. Fakery, A.M. El-Agrody, 4-Hydroxycoumarin in heterocyclic synthesis. Part III. Synthesis of some new pyrano [2,3-d]pyrimidine, 2-substituted [1,2,4] triazolo[1,5-c]pyrimidine and pyrimido[1,6-b] [1,2,4]triazine derivatives, Farmaco, 55, 708–714 (2000).

I. Manolov; N. Danchev, Synthesis and pharmacological investigations of some 4-hydroxycoumarin derivatives, Archiv der Pharmazie, 336, 83–94 (2003).

I. Manolov, C. Maichle-Moessmer, I. Nicolova, N. Danchev, Synthesis and anticoagulant activities of substituted 2,4-diketochromans, biscoumarins, and chromanocoumarins, Archiv der Pharmazie (Weinheim, Germany), 339, 319–326 (2006).

L. Xie, Y. Takeuchi, L. Mark Cosentino, A.T. McPhail, K. H. Lee, Anti-AIDS agents. 42. Synthesis and anti-HIV activity of disubstituted (3′R,4′R)- 3′,4′-Di-O-(S)-camphanoyl-( + )-cis-khellactone Analogues, J. Med. Chem., 44, 664–671 (2001).

K. A. Nolan, H. Zhao, P. F. Faulder, D. A. Frenkel, D. J. Timson, D. Siegel, D, Ross, T. R. Burke, I. J. Stratford, R.A. Bryce, Coumarin-based inhibitors of human NAD(P)H:quinone oxidoreductase-1. Identification, structure-activity, off-target effects and in vitro human pancreatic cancer toxicity, J. Med. Chem., 50, 6316–6325, (2007).

Y. Jacquot, B. Refouvelet, L. Bermont, G. L. Adessi, G. Leclercq, A. Xicluna, Synthesis and cytotoxic activity of new 2,4-diaryl-4H,5H-pyrano[3,2-c] benzopyran-5-ones on MCF-7 cells, Pharmazie, 57, 233–237 (2002).

W. F. Fong, X. L. Shen, C. Globisch, M. Wiese, G. Y. Chen, G. Y. Zhu, Z. L. Yu, A. K. W. Tse, Y. J. Hu, Methoxylation of 30,40-aromatic side chains improves P-glycoprotein inhibitory and multidrug resistance reversal activities of 7,8-pyranocoumarin against cancer cells, Bioorg. Med. Chem., 16, 3694–3703 (2008).

PATENT; L. Zhu, H. Djaballah, Y. Li, C. C. Shelton, Sloan-kettering institute for cancer research; WO2010/75280; (2010).

C. R. Su, S. F. Yeh, C. M. Liu, A. G. Damu, T.H. Kuo, P. C. Chiang, K. F. Bastow, K. H. Lee, T. S. Wu, Anti-HBV and cytotoxic activities of pyranocoumarin derivatives, Bioorg. Med. Chem., 17, 6137–6143 (2009).

I. Manolov, C. Maichle-Moessmer, N. Danchev, Synthesis, structure, toxicological and pharmacological investigations of 4-hydroxycoumarin derivatives, Eur. J. Med. Chem., 41, 882–890 (2006).

PATENT: S. B. Levy, M. N. Alekshun, B. L. Podlogar, K. Ohemeng, A. K. Verma, T. Warchol, B. Bhatia, US2003/229065; (2003).

Y. Liu, J. Zhu, J. Qian, B. Jiang, Z. Xu, Gold(III)- catalyzed tandem conjugate addition/annulation of 4-hydroxycoumarins with α,β-unsaturated ketones, J. Org. Chem., 76, 9096−9101 (2011).

W. Ma, X. Wang, F. Yan, L. Wu, Y. Wang, Reusable melamine trisulfonic acid-catalyzed three-component synthesis of 7-alkyl-6H,7H-naphtho[1′,2′:5,6] pyrano[3,2-c]chromen-6-ones, Monatsh Chem., 142, 163–167 (2011).

S. Maiti, S.K. Panja, C. Bandyopadhyay, Synthesis of 6,8-diarylimino-7H-pyrano[3,2-c:5,6-c’]dicoumarins; chemoselective hydrolysis of the ether-and imino-functions, J. Chem. Res., 35, 84–86 (2011).

H. R. Shaterian, M. Honarmand, Task-specific ionic liquid as the recyclable catalyst for the rapid and green synthesis of dihydropyrano[3,2-c]chromene derivatives, Syn. Comm., 41, 3573–3581 (2011).

R. Ghorbani-Vaghei, Z. Toghraei-Semiromi, R. Karimi-Nami, One-pot synthesis of 4h-chromene and dihydropyrano[3,2-c]chromene derivatives in hydroalcoholic media, J. Braz. Chem. Soc., 22, 905–909 (2011).

A. T. Khan, M. Lal, S. Ali, Md. M. Khan, One-pot three-component reaction for the synthesis of pyran annulated heterocyclic compounds using DMAP as a catalyst, Tetrahedron Lett., 52, 5327–5332 (2011).

Agilent (2010) CrysAlis PRO (version Agilent Technologies Ltd, England.

G. M. Sheldrick, A short history of SHELX, Acta Cryst. A, 64, 112–122 (2008).

M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone, B. Mennucci, G. A. Petersson, H. Nakatsuji, M. Caricato, X. Li, H. P. Hratchian, A. F. Izmaylov, J. Bloino, G. Zheng, J. L. Sonnenberg, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, T. Vreven, J. A. Montgomery, Jr., J. E. Peralta, F. Ogliaro, M. Bearpark, J. J. Heyd, E. Brothers, K. N. Kudin, V. N. Staroverov, R. Kobayashi, J. Normand, K. Raghavachari, A. Rendell, J. C. Burant, S. S. Iyengar, J. Tomasi, M. Cossi, N. Rega, J. M. Millam, M. Klene, J. E. Knox, J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski, R. L. Martin, K. Morokuma, V. G. Zakrzewski, G. A. Voth, P. Salvador, J. J. Dannenberg, S. Dapprich, A. D. Daniels, Ö. Farkas, J. B. Foresman, J. V. Ortiz, J. Cioslowski, D. J. Fox, Gaussian 09, Revision A1, Gaussian Inc., Wallingford CT, 2009.

A. D. Becke, Density ‒ functional thermochemistry. III. The role of exact exchange, J. Chem. Phys., 98, 5648–5652 (1993).

C. Lee, W. Yang, G. R. Parr, Development of the Colle-Salvetti conelation energy formula into a functional of the electron density, Phys. Rev., B37, 785–791 (1988).

J. P. Merrick, D. Moran, L. Radom, An Evaluation of Harmonic Vibrational Frequency Scale Factors, J. Phys. Chem., A 111, 11683–11700 (2007).

R. Ditchfield, Self-consistent Perturbation Theory of Diamagnetism. I. A Gauge-Invariant LCAO (Linear Combination of Atomic Orbitals) Method for NMR Chemical Shifts Mol. Phys., 27, 789–807 (1974).

B. Stamboliyska, V. Janevska, B. Shivachev, R. P. Nikolova, G. Stojkovic, B. Mikhova, E. Popovski, Experimental and theoretical investigation of the structure and nucleophilic properties of 4-aminocoumarin, ARKIVOC, (x), 62–76 (2010).

R. Sarma, M. M. Sarmah, K. C. Lekhok, D. Prajapati, Organic Reactions in Water: An Efficient Synthesis of Pyranocoumarin Derivatives, Synlett., 19, 2847–2852 (2010).

S. Tu, H. Jiang, F. Fang, Y. Feng, S. Zhu, T. Li, X. Zhang, D. Shi, Synthesis of 2-amino-3-ethoxycarbonyl- 4-aryl-4H,5H-pyrano-[3,2-c]benzopyran- 5-one. J. Chem. Res., 6, 396–398 (2004).

Z. He, X. Lin, Y. Zhu, Y. Wang, DDQ-Mediated Tandem Synthesis of Functionalized Pyranocoumarins from 4-Hydroxycoumarins and 1,3-Diarylallylic Compounds. Heterocycles, 81, 965–976 (2010).

Spectral Database for Organic Compounds, www.



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