p-Toluenesulfonic acid monohydrate and trityl chloride as two efficient organic catalysts for the synthesis of 4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidine-6-carboxamides

Document Type : Original Article


Department of Chemistry, Payame Noor University, Tehran, Iran


In this work, facile and efficient procedures were described for the synthesis of 4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidine-6-carboxamides via three-component reaction of aryl aldehyde, acetoacetanilide and 3-amino-1,2,4-triazole. The reactions were performed using p-toluenesulfonic acid monohydrate in refluxing EtOH or trityl chloride under solvent-free conditions at 80 ºC. Comparison of the results shows that both organic catalysts are effective for the synthesis of these fused heterocyclic compounds. Some advantages of these methods are short reaction times, good to excellent yields and easy to operate. Additionally, all products were obtained through simple filtration and no need for column chromatography or tedious work-up, which is an important factor to reduce environmental pollutions.


[1] T. A. Paul, J. L. Irvin, E. P. Kathryn, Green Chemistry Education: Changing the Course of Chemistry, Oxford University Press, Oxford (2009).
[2] B. S. Takale, R. R. Thakore, F. Y. Kong, B. H. Lipshutz, Green Chem. 21 (2019) 6258.
[3] A. Maleki, F. Hassanzadeh-Afruzi, S. Bahrami, J. Of Applied Chemistry 55 (1399) 173. In Persian.
[4] A. I. Ayad, C. B. Marín, E. Colaco, C. Lefevre, C. Méthivier, A.O. Driss, J. Landoulsi, E. Guénin, Green Chem. 21 (2019) 6646.
[5] S. H. Banitaba, M. A. Daeizade, M. Taghdiri, J. Of Applied Chemistry 54 (1399) 167. In Persian.
[6] S. Zhu, Y. Zhang, J. Luo, F. Wang, X. Cao, S. Huang, Green Chem. 22 (2020) 657.
[7] S. Ramezanpour, A. Maleki, J. Of Applied Chemistry 55 (1399) 275. In Persian.
[8] S. Zangade, P. Patil, Curr. Org. Chem. 23 (2019) 2295.
[9] M. Nikpassand, L.Z. Fekri, J. Of Applied Chemistry 51 (1398) 325. In Persian.
[10] A. Hassankhani, Iran. Chem. Commun. 7 (2019) 248.
[11] Md. N. Khan, D. K. Parmar, H. B. Bhatt, Asian J. Green Chem. 3 (2019) 470.
[12] Z. Lasemi, B. Sadeghi, J. Of Applied Chemistry 55 (1399) 149. In Persian.
[13] D. W. C. MacMillan, Nature 455 (2008) 304.
[14] I. R. Shaikh, J. Catal. (2014) 402860.
[15] M. G. Dekamin, S. Sagheb-Asl, M. R. Naimi-Jamal, Tetrahedron Lett. 50 (2009) 4063.
[16] K. Oukoloff, B. Lucero, K. R. Francisco, K. R. Brunden, C. Ballatore, Eur. J. Med. Chem. 165 (2019) 332.
[17] L. C. S. Pinheiro, L. M. Feitosa, M. O. Gandi, F. F. Silveira, N. Boechat, Molecules 24 (2019) 4095.
[18] R. M. Gol, T. T. Khatri, V. M. Barot, Chem. Heterocycl. Compd. 55 (2019) 246.
[19] G. Ruisi, L. Canfora, G. Bruno, A. Rotondo, T. F. Mastropietro, E. A. Debbia, M. A. Girasolo, B. Megna, J. Organometal. Chem. 695 (2010) 546.
[20] Q. Renyu, L. Yuchao, W. M. W. W. Kandegama, C. Qiong, Y. Guangfu, Mini-Rev. Med. Chem. 18 (2018) 781.
[21] P. K. Singh, S. Choudhary, A. Kashyap, H. Verma, S. Kapil, M. Kummar, M. Arora, O. Silakari, Bioorg. Chem. 88 (2019) 102919.
[22] B. Adrom, N. Hazeri, M. Lashkari, M. T. Maghsodlou, J. Chem. Res. 40 (2016) 458.
[23] A. Shaabani, M. Seyyedhamzeh, N. Ganji, M. H. Sangachin, M. Armaghan, Mol. Divers. 19 (2015) 709.
[24] E. A. Muravyova, S. M. Desenko, R. V. Rudenko, S. V. Shishkina, O. V. Shishkin, Y. V. Sen’ko, E. V. Vashchenko, V. A. Chebanov, Tetrahedron 67 (2011) 9389.
[25] V. L. Gein, T. M. Zamaraeva, M. I. Vakhrin, Russ. J. Gen. Chem. 84 (2014) 82.
[26] J. Liu, M. Lei, L. Hu, Green Chem. 14 (2012) 840.
[27] L. –Y. Zeng, F. Li, C. Cai, J. Heterocyclic Chem. 49 (2012) 237.
[28] V. L. Gein, T. M. Zamaraeva, A. A. Kurbatova, E. V. Voronina, M. I. Vakhrin, Pharm. Chem. J. 44 (2010) 366.
[29] N. G. Boekell, D. J. Cerone, M. M. Boucher, P. K. Quach, W. B. N. Tentchou, C. G. Reavis, I. I. Okoh, J. O. A. Reid, H. E. Berg, B. A. Chang, C. S. Brindle, SynOpen 1 (2017) 97.