Document Type : Original Article

Authors

Department of Chemistry, Payame Noor University, PO BOX 19395-4697 Tehran, Iran

10.22034/jaoc.2021.277050.1007

Abstract

< p>Benzopyranes and their derivatives are of interest due to their wide range of biological and medicinal properties. In this study, 2-amino-4H-pyran derivatives were obtained through a one-step multi-component reaction of aromatic aldehyde, malononitrile and dimedone in the presence of ninhydrin as a catalyst in water with high efficiency and short time.

Graphical Abstract

Ninhydrin as a novel and efficient catalyst for the synthesis of 2-amino-4H-Pyran derivatives in aqueous media using

Keywords

Main Subjects

Introduction

pyran derivatives are a large group of organic compounds that have important chemical properties and are of great biological and pharmacological importance. Benzopyran is a derivative of this group that is found in nature [1]. Benzopyranes are present in the structure of various plant species and their welded rings are flat and have anti-allergic, antimicrobial, anti-influenza, anti-tumor, anti-fungal, anti-cancer properties and are used in industry in pigments [3-7]. Because these compounds are found in small quantities in natural resources and are very difficult and expensive to extract, chemists are forced to synthesize these very valuable compounds [8]. Benzene pyran cations are present in the red, purple, and blue pigments of flower petals, known as anthocyanins and glycosides.

There are many studies on the synthesis of pyranes, but most of them have shortcomings such as high reaction time, problem purification methods, low efficiency and the use of toxic solvents. Therefore, the need to invent new methods under suitable conditions for the environment for the synthesis of pyran derivatives is of great importance [9-19].

Given our strong desire to develop highly suitable methods for the preparation of heterocyclic derivatives, in this report, we introduced ninhydrin catalyst as a suitable catalyst for the preparation of 2-amino-4H-pyran under reflux conditions (Scheme 1).

Result and Discussion

Because of our recent interest in developing useful method for synthesis of heterocyclic compounds having biological properties, in this study, we selected ninhydrin as a useful catalyst for the synthesis of 2-amino-4H-pyrans. The reaction of malononitrile, aldehydes and dimedone in the presence of ninhydrin as a catalyst in water as a solvent produced 2-amino-4H-pyranes with high efficiency.

It should be noted that the effect of substitution type on the aromatic ring has no noticeable effect on the reaction efficiency. These compounds were obtained with high efficiency in a short time. The results are shown in Table 1.

In other words, we accomplished effects of varied solvents for the preparation of 4a. This reaction was investigated in the presence of different solvents. For instance, chloroform, dichloromethane, water, Ethanol, and solvent-free were used. It is evident from data that, the best yields were achieved in water (Table 3).

To optimize the amount of catalyst, various amounts (0.01, 0.02, 0.03, 0.05, and 0.08 g) of ninhydrin were used. The results presented in the Table 3 revealed that 0.05 g of ninhydrin had the best efficiency.

After comparing the results for the synthesis of 4a with other methods, we found that the ninhydrin catalyst performed the reaction faster and with higher efficiency (Table 4).

The proposed mechanism for the preparation of 2-amino-4H-Pyransusing ninhydrin is shown in Scheme 2.

Conclusion

Due to the great interest in inventing new methods for the synthesis of heterocyclic compounds and the use of water as a solvent in chemical reactions, we reported here a facile and improved protocol for preparation of 4H-pyrans, from malononitrile, benzaldehydes, dimedon and ninhydrin as a catalyst in water at ambient conditions.

Among the advantages of this method in general can be mentioned the following:

  • Reaction in aqueous medium is a clean, non-toxic and environmentally friendly reaction. On the other hand, water is a cheap substance with the highest abundance compared to other solvents.
  • Separation of products is done by simple filtering with filter paper and the percentage of products lost during the purification process is very small.
  • The yield of the reactions was high and the compounds were easily obtained by crystallization in ethanol solvent.
  • The reaction is a single-phase three-component compression, so there is no need to separate the interface, thus saving time, energy and costs.

Acknowledgments

The   authors are grateful   to   Payame   Noor University for financial support

Orcid:

Bita Baghernejad: https://orcid.org/0000-0002-1733-0829

Mahsa Fiuzat: https://orcid.org/0000-0003-3492-7341  

References

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References
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[2] W.O. Foye, Principal di Chemico Farmaceutica; Piccin: Padova, Italy, 1991, 416. [Link], [Google Scholar]
[3] C.S. Konkoy, D.B. Fick, S.X. Cai, N.C. Lan, J.F.W. Keana, PCT Int. Appl. WO 0075123, 2000, Chem. Abstr., 2001, 134, 29313a. [Google Scholar]
[4] D.J. Macquarrie, Tetrahedron Lett., 1998, 39, 4125-4128. [crossref], [Google Scholar], [Publisher]
[5] R.A. Holton, A.D. Williams, R.M. Kennedy, J. Org. Chem., 1986, 51, 5480-5482. [crossref], [Google Scholar], [Publisher]
[6] A. Lubineau, J. Auge, Tetrahedron Lett., 1992, 33, 8073-8074. [crossref], [Google Scholar], [Publisher]
[7] R. Maggi, R. Ballini, G. Sartori, R. Sartorio, Tetrahedron Lett., 2004, 45, 2297-2299. [crossref], [Google Scholar], [Publisher]
[8] D. Armesto, W.M. Horspool, N. Martin, A. Ramos, C. Seaone, J. Org. Chem., 1989, 54, 3069-3073. [crossref], [Google Scholar], [Publisher]
[9] L. Bonsignore, G. Loy, D. Secci, Calignano, Eur. J. Med. Chem., 1993, 28, 517-520. [crossref], [Google Scholar], [Publisher]
[10] R. Bernetti, F. Mancini, C.C. Price, J. Org. Chem., 1962, 27, 2863-2865. [crossref], [Google Scholar], [Publisher]
[11] C. Wiener, C.H. Schroeder, B. D. West, K. P. Link, J. Org. Chem., 1962, 27, 3086-3088. [crossref], [Google Scholar], [Publisher]
[12] A.S. Prasad, J.S. Sandhu, J.N. Baruah, J. Heterocycl. Chem., 1984, 21, 1657-1659. [crossref], [Google Scholar], [Publisher]
[13] H. Junek, H. Aigner, Cehm. Ber., 1973, 106, 914-921. [crossref], [Google Scholar], [Publisher]
[14] I. Devi, B.S.D. Kumar, P.J. Bhuyan Tetrahedron Lett., 2003, 44, 8307-8310. [crossref], [Google Scholar], [Publisher]
[15] P. B. Hiremath, K. Kantharaju, Chem. Select., 2020, 5, 1896-1906. [crossref], [Google Scholar], [Publisher]
[16] S. Amirnejati, A. Nosrati, R. Peymanfar, Sh. Javanshir, Research. Chem. Int., 2020, 46, 3683-3701. [crossref], [Google Scholar], [Publisher]
[17] F. Auria-Luna, M.C. Gimeno, R.P. Herrera, Scientific. Report., 2020, 10, 11594. [crossref], [Google Scholar], [Publisher]
[18] M.A. Wanzheng, A. Ebadi; Jimenez, G. Rsc Adv., 2019, 9, 12801-12812. [crossref], [Google Scholar], [Publisher]
[19] Z.J. Karimi, B. Pooladian, Scientific. World. Journal, 2012, 10, 208796. [crossref], [Google Scholar], [Publisher]
[20] S.J. Gao, Y. Guo, C. Shi, D. Lu, Synth. Commun., 2002, 32, 2137-2141. [crossref], [Google Scholar], [Publisher]
[21] I. Devi, P.J. Bhuyan, Tetrahedron. Lett., 2004, 45, 8626-8631. [crossref], [Google Scholar], [Publisher]
[22] T. Sh. Jin, A.Q. Wang, F. Shi, L. Sh. Han, L. B. Liu, T. Sh. Li, Arkivoc, 2006, (Xiv), 78-91. [crossref], [Google Scholar], [Publisher]
[23] S. Balalaie, M. Bararjanian, A. M. Amini, B. Movassagh, Tetrahedron Lett., 2005, 35, 264-274. [crossref], [Google Scholar], [Publisher]
[24] R. Hekmatshoar, S. Majedi, Kh. Bakhtiari, Catal. Commun., 2007, 9, 308-312. [crossref], [Google Scholar], [Publisher]
[25] Sh. Gao, H. Ch. Tsai, Ch. Tseng, Ch-Fa. Yao, Tetrahedron., 2008, 64, 9143-9148. [crossref], [Google Scholar], [Publisher]
[26] M. Seifi, H. Sheibani, Catal Lett., 2008, 126, 275-282. [crossref], [Google Scholar], [Publisher]