Login Register Cart 0
Generic placeholder image

Current Organocatalysis

Editor-in-Chief

ISSN (Print): 2213-3372
ISSN (Online): 2213-3380

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Transition Metal-free Approach for the Synthesis of 2-substituted Quinazolin-4(3H)-one via Anhydrous Magnesium Perchlorate

Author(s): Shweta Mishra, Debashree Das, Adarsh Sahu, Shailendra Patil, Ram Kishor Agarwal and Asmita Gajbhiye*

Volume 7, Issue 2, 2020

Page: [118 - 123] Pages: 6

DOI: 10.2174/2213337207666200220101535

Abstract

Background: A convenient and efficient methodology for the synthesis of quinazolin- 4(3H)-ones from simple and readily available 2-amino benzamides and aromatic aldehydes in ethanol using Magnesium perchlorate are being reported in the present study. Good to excellent isolated yields (68-95%) of the corresponding 2-substituted quinazolinones were obtained under mild reaction conditions with excellent functional group tolerance. The affordability of the catalyst, the wide availability of the starting materials, transition metal free synthesis and the simplicity of the procedure renders the present methodology useful in organic synthesis.

Objective: A maneuver methodology developed for the synthesis of quinazolin-4(3H)-ones via using Magnesium perchlorate from 2-amino benzamides and aromatic aldehydes in ethanol.

Methods: 10% mol anhydrous Magnesium perchlorate in presence of ethanol give to simply rapid formation of Quinazolin-4(3H)-ones from 1 mole of 2-amino benzamides and 1 mole of aromatic aldehydes.

Results: Screening results of Anti-leishmanial showed that out of the synthesized series of 12 compounds, compounds 3c, 3d, 3g, 3h and 3i showed significant antileishmanial activities (L. donavani) with IC50 values 8.39, 9.37, 9.43, 7.1 and 8.7 μM.

Conclusion: In summary, we have developed convenient synthesis of quinazolin-4(3H)-one, from simple and easily available precursor employing anhydrous Mg(ClO4)2 under green conditions.

Keywords: Magnesium perchlorate, Quinazoline-4(3H)-ones, catalyst, nitrogen-containing heterocyclic, green synthesis, leishmanasis.

« Previous Next »
Graphical Abstract

[1]
Gomtsyan, A. Heterocycles in drugs and drug discovery. Chem. Heterocycl. Compd., 2012, 48(1), 7-10.
[http://dx.doi.org/10.1007/s10593-012-0960-z]
[2]
Dua, R.; Shrivastava, S.; Sonwane, S.K.; Srivastava, S.K. Pharmacological significance of synthetic heterocycles scaffold: a review. Adv. Biol. Res. (Faisalabad), 2011, 5(3), 120-144.
[3]
Pozharskii, A.F. Soldatenkov; A.T.; Katritzky, A.R. Heterocycles in Agriculture; Heterocycles in Life and Society: An Introduction to Heterocyclic Chemistry, Biochemistry and Applications, 2nd ed; John Wiley & Sons, 2011.
[4]
Dash, B.; Dash, S.; Laloo, D.; Medhi, C. Design, synthesis and preliminary pharmacological screening (antimicrobial, analgesic and anti-inflammatory activity) of some novel quinazoline derivatives. J. Appl. Pharm. Sci., 2017, 7(06), 083-096.
[5]
Abbas, S.Y.; El-Bayouki, K.A.; Basyouni, W.M.; Mostafa, E.A. New series of 4 (3H)-quinazolinone derivatives: syntheses and evaluation of antitumor and antiviral activities. Med. Chem. Res., 2018, 27(2), 571-582.
[http://dx.doi.org/10.1007/s00044-017-2083-7]
[6]
Murugan, V.; Thomas, C.C.; Sarma, G.R.; Kumar, E.P.; Suresh, B. Synthesis of 2-substituted quinazolin-4 (3H)-ones as a new class of anticancer agents. Indian J. Pharm. Sci., 2003, 65(4), 386-389.
[7]
Zhang, L.; Chen, Q.; Li, X.Q.; Wu, S.Q.; Wan, J.L.; Ouyang, G.P. Synthesis and Antibacterial Activity of 2-substitued-(3-pyridyl)-quinazolinone Derivatives. J. Heterocycl. Chem., 2018, 55(3), 743-749.
[http://dx.doi.org/10.1002/jhet.3099]
[8]
Pandeya, S.N.; Sriram, D.; Nath, G.; De Clercq, E. Synthesis, antibacterial, antifungal and anti-HIV evaluation of Schiff and Mannich bases of isatin derivatives with 3-amino-2-methylmercapto quinazolin-4(3H)-one. Pharm. Acta Helv., 1999, 74(1), 11-17.
[http://dx.doi.org/10.1016/S0031-6865(99)00010-2] [PMID: 10748620]
[9]
Zhu, S.; Wang, J.; Chandrashekar, G.; Smith, E.; Liu, X.; Zhang, Y. Synthesis and evaluation of 4-quinazolinone compounds as potential antimalarial agents. Eur. J. Med. Chem., 2010, 45(9), 3864-3869.
[http://dx.doi.org/10.1016/j.ejmech.2010.05.040] [PMID: 20538379]
[10]
Aibibuli, Z.; Wang, Y.; Tu, H.; Huang, X.; Zhang, A. Facile synthesis and herbicidal evaluation of 4H-3,1-benzoxazin-4-ones and 3H-quinazolin-4-ones with 2-phenoxymethyl substituents. Molecules, 2012, 17(3), 3181-3201.
[http://dx.doi.org/10.3390/molecules17033181] [PMID: 22418925]
[11]
Khan, I.; Ibrar, A.; Abbas, N.; Saeed, A. Recent advances in the structural library of functionalized quinazoline and quinazolinone scaffolds: synthetic approaches and multifarious applications. Eur. J. Med. Chem., 2014, 76, 193-244.
[http://dx.doi.org/10.1016/j.ejmech.2014.02.005] [PMID: 24583357]
[12]
Khan, I.; Zaib, S.; Batool, S.; Abbas, N.; Ashraf, Z.; Iqbal, J.; Saeed, A. Quinazolines and quinazolinones as ubiquitous structural fragments in medicinal chemistry: An update on the development of synthetic methods and pharmacological diversification. Bioorg. Med. Chem., 2016, 24(11), 2361-2381.
[http://dx.doi.org/10.1016/j.bmc.2016.03.031] [PMID: 27112448]
[13]
He, L.; Li, H.; Chen, J.; Wu, X.F. Recent advances in 4 (3 H)-quinazolinone syntheses. RSC Advances, 2014, 4(24), 12065-12077.
[http://dx.doi.org/10.1039/C4RA00351A]
[14]
Rohokale, R.S.; Kshirsagar, U.A. Advanced synthetic strategies for constructing quinazolinone scaffolds. Synthesis, 2016, 48(09), 1253-1268.
[http://dx.doi.org/10.1055/s-0035-1560413]
[15]
Niementowski, S. Syntheses of quinazoline compounds. J. Prakt. Chem., 1895, 51(1), 564-572.
[16]
Sugimori, T.; Okawa, T.; Eguchi, S.; Yashima, E.; Okamoto, Y. The first total synthesis of (−)-benzomalvin a via intramolecular Aza-Wittig reactions. Chem. Lett., 1997, 26(9), 869-870.
[http://dx.doi.org/10.1246/cl.1997.869]
[17]
Jafari, E.; Khajouei, M.R.; Hassanzadeh, F.; Hakimelahi, G.H.; Khodarahmi, G.A. Quinazolinone and quinazoline derivatives: recent structures with potent antimicrobial and cytotoxic activities. Res. Pharm. Sci., 2016, 11(1), 1-14.
[PMID: 27051427]
[18]
Wang, L.; Xia, J.; Qin, F.; Qian, C.; Sun, J. Yb (OTf) 3-catalyzed one-pot synthesis of quinazolin-4 (3H)-ones from anthranilic acid, amines and ortho esters (or formic acid) in solvent-free conditions. Synthesis, 2003, 2003(08), 1241-1247.
[http://dx.doi.org/10.1055/s-2003-39397]
[19]
Bakavoli, M.; Sabzevari, O.; Rahimizadeh, M. Microwave activated synthesis of 2-aryl-quinazolin-4 (3H) ones. Chin. Chem. Lett., 2007, 18(12), 1466-1468.
[http://dx.doi.org/10.1016/j.cclet.2007.10.023]
[20]
Zhou, J.; Fang, J. One-pot synthesis of quinazolinones via iridium-catalyzed hydrogen transfers. J. Org. Chem., 2011, 76(19), 7730-7736.
[http://dx.doi.org/10.1021/jo201054k] [PMID: 21851120]
[21]
McGowan, M.A.; McAvoy, C.Z.; Buchwald, S.L. Palladium-catalyzed N-monoarylation of amidines and a one-pot synthesis of quinazoline derivatives. Org. Lett., 2012, 14(14), 3800-3803.
[http://dx.doi.org/10.1021/ol301700y] [PMID: 22765354]
[22]
Sahu, A.; Mishra, S.; Sahu, P.; Gajbhiye, A.; Agrawal, R.K. Indium (III) chloride: an efficient catalyst for one-pot multicomponent synthesis of 2, 3-dihydroquinazoline-4 (1H)-ones. Curr. Organocatal., 2018, 5(2), 137-144.
[http://dx.doi.org/10.2174/2213337205666180614112318]
[23]
Wu, X.F.; He, L.; Neumann, H.; Beller, M. Palladium-catalyzed carbonylative synthesis of quinazolinones from 2-aminobenzamide and aryl bromides. Chemistry, 2013, 19(38), 12635-12638.
[http://dx.doi.org/10.1002/chem.201302182] [PMID: 24175339]
[24]
Maiden, T.M.M.; Harrity, J.P.A. Recent developments in transition metal catalysis for quinazolinone synthesis. Org. Biomol. Chem., 2016, 14(34), 8014-8025.
[http://dx.doi.org/10.1039/C6OB01402J] [PMID: 27477737]
[25]
Sahu, A.; Mishra, S.; Gajbhiye, A.; Agrawal, R.K. Magnesium perchlorate catalyzed phospha-michael addition of dialkyl phosphite to chalcone. Curr. Org. Synth., 2018, 15(7), 1020-1023.
[http://dx.doi.org/10.2174/2210315508666180103162452]
[26]
Bhagat, S.; Shah, P.; Garg, S.K.; Mishra, S.; Kaur, P.K.; Singh, S.; Chakraborti, A.K. α-Aminophosphonates as novel anti-leishmanial chemotypes: synthesis, biological evaluation, and CoMFA studies. MedChemComm, 2014, 5(5), 665-670.
[http://dx.doi.org/10.1039/C3MD00388D]
[27]
Huheey, J.E. Inorganic Chemistry: Principles of Structure and ReactiVity, 3rd ed; Harper & Row: Singapore, 1983.
[28]
Sahu, A.; Kumar, D.; Agrawal, R. K. Antileishmanial drug discovery: synthetic methods, chemical characteristics, and biological potential of quinazolines and its derivatives. Antiinflamm. Antiallergy. Agents Med. Chem., (Formerly Current Medicinal Chemistry- Anti-Inflammatory and Anti-Allergy Agents), 2017, 16(1), 3-32.
[29]
Gajbhiye, A.; Patil, S.; Mishra, S.; Das, D. In Vitro Experimental Pharmacology, 1st ed.; CBS Publishers & Distributors Pvt. Ltd.: Delhi, 2019.

Rights & Permissions Print Cite
Article Metrics
22
2
© 2024 Bentham Science Publishers | Privacy Policy