European Journal of Chemistry

A three step one-pot regioselective synthesis of highly substituted pyrazolo[1,5-a]pyrimidines assisted by KHSO4 in aqueous media under ultrasound irradiation


Main Article Content

Shunan Kaping
Philippe Helissey
Jai Narain Vishwakarma


A simple and efficient synthesis of substituted pyrazolo[1,5-a]pyrimidine derivatives has been developed by the use of ultrasound. 5-Methyl-4-phenyl-1H-pyrazol-3-amine required for the synthesis of pyrazolo[1,5-a]pyrimidine derivatives has been easily obtained by the reaction of 3-(dimethylamino)-2-phenylacrylonitrile (formed from readily available 2-phenylacetonitrile) with hydrazine hydrate in refluxing ethanol. The 5-aminopyrazole was then reacted with various formylated active proton compounds in presence of KHSO4 in aqueous medium under ultrasound irradiation to give the desired products. The chemical structures of the newly synthesized compounds were confirmed by IR, 1H NMR, 13C NMR and Mass spectral data. X-ray crystallographic study of a selected compound 6-(4-chlorophenyl)-2-methyl-3-phenylpyrazolo[1,5-a]pyrimidin-7-amine (7c) was performed to ascertain the regioselectivity of the reaction. Crystal data for compound 7c: Triclinic, space group P-1 (no. 2), a = 8.0198(3) Å, b = 14.0341(6) Å, c = 14.2099(6) Å, α = 87.672(2)°, β = 83.902(2)°, γ = 89.120(2)°, = 1588.87(11) Å3, Z = 4, T = 293(2) K, μ(MoKα) = 0.248 mm-1, Dcalc = 1.400 g/cm3, 12918 reflections measured (4.012° ≤ 2Θ ≤ 49°), 5152 unique (Rint = 0.0411, Rsigma = 0.0429) which were used in all calculations. The final R1 was 0.0486 (I > 2σ(I)) and wR2 was 0.1320 (all data).

icon graph This Abstract was viewed 1633 times | icon graph Article PDF downloaded 639 times icon graph Article CIF FILE downloaded 0 times

How to Cite
Kaping, S.; Helissey, P.; Vishwakarma, J. N. A Three Step One-Pot Regioselective Synthesis of Highly Substituted pyrazolo[1,5-a]pyrimidines Assisted by KHSO4 in Aqueous Media under Ultrasound Irradiation. Eur. J. Chem. 2020, 11, 179-186.

Article Details

Crossref - Scopus - Google - European PMC

[1]. Baluja, S.; Kachhadia, N.; Solanki, A. Open J. Org. Chem. 2013, 1, 1-5.

[2]. Buriol, L.; Munchen, T. S.; Frizzo, C. P.; Marzari, M. R. B.; Zanatta, N. Bonacorso, H. G.; Martins, M. A. P. Ultrason. Sonochem. 2013, 20, 1139-1143.

[3]. Cravotto, G.; Cintas, P. Chem. Soc. Rev. 2006, 35, 180-196.

[4]. Puri, S.; Kaur, B.; Parmar, A.; Kumar, H. Curr. Org. Chem. 2013, 17, 1790-1828.

[5]. Bretanha, L. C.; Teixeira, V. E.; Ritter, M.; Siqueira, G. M.; Cunico, W.; Pereira, C. M. P.; Freitag, R. A. Ultrason. Sonochem. 2011, 18, 704-707.

[6]. Mason, T. J.; Cobley, A. G.; Graves, J. E.; Morgan, D. Ultrason. Sonochem. 2011, 18, 226-230.

[7]. Bruni, F.; Selleri, S.; Constanzo, A.; Guerrilli, G.; Casilli, M. L.; Giusti, L. J. Heterocycl. Chem. 1995, 32, 291-298.

[8]. Maeba, I.; Nishiyama, Y.; Kanazawa, S.; Sato, A. Heterocycles 1995, 41, 507-513.

[9]. Bellec, Ch.; Lhommet, G. J. Heterocycl. Chem. 1995, 32, 1793-1800.

[10]. Howard, A. S. Comprehensive Heterocyclic Chemistry II, Vol. 8, Pergamon Press, Oxford, 249, 1995.

[11]. Barret, D. Heterocycles 1997, 45, 1839-1855.

[12]. Damont, A.; Medran-Navarrete, V.; Cacheux, F.; Kuhnast, B.; Pottier, G.; Bernards, N.; Marguet, F.; Puech, F.; Boisgard, R.; Dolle, F. J. Med. Chem. 2015, 58, 7449-7464.

[13]. Hassan, A. S.; Hafez, T. S.; Osman, S. A. Sci. Pharm. 2015, 83, 27-39.

[14]. George, C. F. P. Lancet 2001, 358, 1623-1626.

[15]. Wegner, F.; Deuther-Conrad, W.; Scheunemann, M.; Brust, P.; Fischer, S.; Hiller, A.; Diekers, M.; Strecker, K.; Wohlfarth, K.; Allgaier, C.; Steinbach, J.; Hoepping, A. Eur. J. Pharmacol. 2008, 580, 1-2.

[16]. Ahmetaj, S.; Velikanje, N.; Groselj, U.; Sterbal, I.; Prek, B.; Golobic, A.; Kocar, D.; Dahmann, G.; Stanovnik, B.; Svete, J. Mol. Divers. 2013, 17, 731-743.

[17]. Kalita, U.; Kaping, S.; Nellanant, J.; Helissey, P.; Vishwakarma, J. N. Heteroletters 2014, 4, 137-145.

[18]. Devi, A. S.; Kaping, S.; Vishwakarma, J. N. Mol. Divers. 2015, 19, 759-771.

[19]. Kaping, S.; Boiss, I.; Singha, L. I.; Helissey, P.; Vishwakarma, J. N. Mol. Divers. 2016, 20, 379-390.

[20]. Kaping, S.; Kalita, U.; Sunn, M.; Singha, L. I.; Vishwakarma, J. N. Monatsch. Chem. 2016, 147, 1257-1276.

[21]. Bourhis, L. J.; Dolomanov, O. V.; Gildea, R. J.; Howard, J. A. K.; Puschmann, H. Acta Cryst. A 2015, 71, 59-75.

[22]. Sheldrick, G. M. Acta Cryst. C 2015, 71, 3-8.

[23]. Dolomanov, O. V.; Bourhis, L. J.; Gildea, R. J.; Howard, J. A. K; Puschmann, H. J. Appl. Cryst. 2009, 42, 339-341.

[24]. Chanda, K.; Dutta, M. C.; Karim, E.; Vishwakarma, J. N. J. Indian Chem. Soc. 2004, 81, 791-793.

[25]. Chanda, K.; Dutta, M. C.; Vishwakarma, J. N. Ind. J. Chem. B 2004, 43, 2475-2477.

[26]. Elnagdi, M. H.; Erian, A. W. Bull. Chem. Soc. 1990, 63, 1854-1856.

[27]. Almazrao, S.; Elnagdi, M. H.; El-Din, A. M. S. J. Het. Chem. 2004, 41, 267-272.

[28]. Bellec, C.; Maitte, P. Can. J. Chem. 1981, 59, 2826-2832.

[29]. Gopalsamy, A.; Ciszewski, G.; Shi, M.; Berger, D.; Hu, Y.; Lee, F.; Feldberg, L.; Frommer, E.; Kim, S.; Collins, K.; Wojciechowicz, D.; Mallon, R. Biorg, Med. Chem. Lett. 2009, 19, 6890-6892.

[30]. Radl, S.; Blahovcova, M.; Tkadlecova, M.; Havlicek, J. Heterocycles 2010, 80, 1359-1379.

[31]. Etse, K. S.; Dassonneville, B.; Zaragoza, G.; Demonceau, A. Tetrahedron Lett. 2017, 58, 789-793.

[32]. Portilla, J.; Quiroga, J.; Cobo, J.; Low, J. N.; Glidewell, C. Acta. Cryst. C 2006, 62, 186-189.

Supporting Agencies

Department of Biotechnology, Government of India, New Delhi, India.

Dimensions - Altmetric - scite_ - PlumX

Downloads and views


Download data is not yet available.


Metrics Loading ...
License Terms

License Terms


Copyright © 2024 by Authors. This work is published and licensed by Atlanta Publishing House LLC, Atlanta, GA, USA. The full terms of this license are available at and incorporate the Creative Commons Attribution-Non Commercial (CC BY NC) (International, v4.0) License ( By accessing the work, you hereby accept the Terms. This is an open access article distributed under the terms and conditions of the CC BY NC License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited without any further permission from Atlanta Publishing House LLC (European Journal of Chemistry). No use, distribution, or reproduction is permitted which does not comply with these terms. Permissions for commercial use of this work beyond the scope of the License ( are administered by Atlanta Publishing House LLC (European Journal of Chemistry).