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Current Microwave Chemistry

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ISSN (Print): 2213-3356
ISSN (Online): 2213-3364

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Research Article

Microwave-assisted Synthesis of 3-amino-2-phenylquinazolin-4(3H)-one (QH) and 4-oxo-2-phenylquinazoline-3(4H)-carbothioamide (QTh)

Author(s): Ranjan Kumar Das, Debdulal Sharma, Subrata Paul and Devashish Sengupta*

Volume 10, Issue 1, 2023

Published on: 06 July, 2023

Page: [53 - 59] Pages: 7

DOI: 10.2174/2213335610666230516165046

open access plus

Abstract

Background: Microwave synthesis has developed as a powerful tool for the cost-effective and greener synthesis of organic molecules, including quinazolines. Irradiation with microwave leads to the excitation of molecules and equitable distribution of thermal energy in a much shorter time than conventional synthesis. This results in shorter reaction time and, more often than not, higher efficiency.

Objective: The primary objective of the work presented in this article was to prepare hydrazine hydrate or thiourea derivative of quinazolines through microwave synthesis as small-molecule scaffolds for further need-based functionalisation, isolation, and characterisation. We, herein, report the synthesis of two quinazolinone derivatives of thiourea and hydrazine, 3-amino-2-phenylquinazolin-4(3H)-one (QH) and 4-oxo-2-phenylquinazoline-3(4H)-carbothioamide (QTh), respectively.

Method: A multi-step synthetic strategy starting from anthranilic acid was employed to synthesise the small molecule quinazolinones 3-amino-2-phenylquinazolin-4(3H)-one (QH) and 4-oxo-2- phenylquinazoline-3(4H)-carbothioamide (QTh). The compounds were synthesised by reacting hydrazine and thiourea with 2-benzamidobenzoyl chloride in DMF under microwave irradiation (800 W at 135 °C for 4 min) in the presence of potassium carbonate. The acid chloride was prepared by chlorination of 2-benzamidobenzoic acid, which in turn was synthesised from anthranilic acid by benzoylation. This method is an efficient alternative approach to synthesising quinazolinones from benzoxazin-4-ones.

Results: We have successfully synthesised, isolated, and characterised the quinazolinone derivative QH (yield: 81%) and QTh (yield: 85%). The structures of the compounds were established through spectroscopic techniques. Theoretical optimisation of the structures was also achieved using DFT. The HOMOLUMO difference for QH and QTh was calculated to be 4.60 and 4.47 eV, respectively.

Conclusion: The reported protocol is advantageous over conventional methods of quinazoline synthesis from benzoxazin-4-ones. The time required for the reaction is much less (4 min) as compared to the usual requirements of reflux (> 4 h); the higher energy gap of QH indicates greater stability than that of QTh.

Keywords: 3-amino-2-phenylquinazolin-4(3H)-one (QH), 4-oxo-2-phenylquinazoline-3(4H)-carbothioamide (QTh), HOMOLUMO, DMF, microwave irradiation. Small-molecule quinazolinone scaffolds, microwave synthesis, hydrazine hydrate, thiourea, DFT, Gaussian.

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[1]
Dutta, A.; Sarma, D. Recent advances in the synthesis of Quinazoline analogues as Anti-TB agents. Tuberculosis , 2020, 124, 101986.
[http://dx.doi.org/10.1016/j.tube.2020.101986] [PMID: 32942187]
[2]
Bhat, M.; Belagali, S.L.; Mamatha, S.V.; Sagar, B.K.; Sekhar, E.V. Importance of quinazoline and quinazolinone derivatives in medicinal chemistry. Stud. Nat. Prod. Chem., 2021, 71, 185-219.
[3]
Wahan, S.K.; Sharma, B.; Chawla, P.A. Medicinal perspective of quinazolinone derivatives: Recent developments and STRUCTURE–ACTIVITY relationship studies. J. Heterocycl. Chem., 2022, 59(2), 239-257.
[http://dx.doi.org/10.1002/jhet.4382]
[4]
Le, Y.; Gan, Y.; Fu, Y.; Liu, J.; Li, W.; Zou, X.; Zhou, Z.; Wang, Z.; Ouyang, G.; Yan, L. Design, synthesis and in vitro biological evaluation of quinazolinone derivatives as EGFR inhibitors for antitumor treatment. J. Enzyme Inhib. Med. Chem., 2020, 35(1), 555-564.
[http://dx.doi.org/10.1080/14756366.2020.1715389] [PMID: 31967481]
[5]
Li, W.; Chen, S.Y.; Hu, W.N.; Zhu, M.; Liu, J.M.; Fu, Y.H.; Wang, Z.C.; OuYang, G.P. Design, synthesis, and biological evaluation of quinazoline derivatives containing piperazine moieties as antitumor agents. J. Chem. Res., 2020, 44(9-10), 536-542.
[http://dx.doi.org/10.1177/1747519820910384]
[6]
Asif, M. Chemical characteristics, synthetic methods, and biological potential of quinazoline and quinazolinone derivatives. Int. J. Med. Chem., 2014, 2014, 395637.
[http://dx.doi.org/10.1155/2014/395637] [PMID: 25692041]
[7]
Mravljak, J.; Slavec, L.; Hrast, M.; Sova, M. Synthesis and evaluation of antioxidant properties of 2-substituted quinazolin-4(3H)-ones. Molecules, 2021, 26(21), 6585.
[http://dx.doi.org/10.3390/molecules26216585] [PMID: 34770996]
[8]
Heba, E.H. Synthesis of quinazoline and quinazolinone derivatives In Quinazolinone and Quinazoline Derivatives; intechopen. , 2020.
[9]
El-Azab, A.S.; Al-Omar, M.A.; Abdel-Aziz, A.A.M.; Abdel-Aziz, N.I.; El-Sayed, M.A.A.; Aleisa, A.M.; Sayed-Ahmed, M.M.; Abdel-Hamide, S.G. Design, synthesis and biological evaluation of novel quinazoline derivatives as potential antitumor agents: Molecular docking study. Eur. J. Med. Chem., 2010, 45(9), 4188-4198.
[http://dx.doi.org/10.1016/j.ejmech.2010.06.013] [PMID: 20599299]
[10]
Bhatia, P.; Sharma, V.; Alam, O.; Manaithiya, A.; Alam, P. Kahksha; Alam, M.T.; Imran, M. Novel quinazoline-based EGFR kinase inhibitors: A review focussing on SAR and molecular docking studies (2015-2019). Eur. J. Med. Chem., 2020, 204, 112640.
[http://dx.doi.org/10.1016/j.ejmech.2020.112640] [PMID: 32739648]
[11]
Misra, A.; Kishore, D.; Verma, V.P.; Dubey, S.; Chander, S.; Gupta, N.; Bhagyawant, S.; Dwivedi, J.; Alothman, Z.A.; Wabaidur, S.M.; Sharma, S. Synthesis, biological evaluation and molecular docking of pyrimidine and quinazoline derivatives of 1,5-benzodiazepine as potential anticancer agents. J. King Saud Univ. Sci., 2020, 32(2), 1486-1495.
[http://dx.doi.org/10.1016/j.jksus.2019.12.002]
[12]
Kazemi, S.S.; Keivanloo, A.; Nasr-Isfahani, H.; Bamoniri, A. Synthesis of novel 1,5-disubstituted pyrrolo[1,2-a]quinazolines and their evaluation for anti-bacterial and anti-oxidant activities. RSC Advances, 2016, 6(95), 92663-92669.
[http://dx.doi.org/10.1039/C6RA21219K]
[13]
Saravanan, G.; Alagarsamy, V.; Prakash, C.R. Synthesis and evaluation of antioxidant activities of novel quinazoline derivatives. Int. J. Pharm. Pharm. Sci., 2010, 2(4), 83-86.
[14]
Baltaş N. Synthesis of quinazolinone derivatives containing an acyl hydrazone skeleton as potent anti-urease agents enzyme kinetic studies and anti-oxidant properties. J. Chem. Res., 2022, 46(3)
[http://dx.doi.org/10.1177/17475198221096568]
[15]
Kaur, A.; Katoch, D.; Singh, B.; Arora, S. Seclusion of vasicine-and quinazoline alkaloid from bioactive fraction of Justicia adhathoda and its antioxidant, antimutagenic and anticancerous activities. J. Glob. Biosci, 2016, 5, 3836-3850.
[16]
Hashem, H.E. Synthesis of Quinazoline and Quinazolinone Derivatives. In: Quinazolinone and Quinazoline Derivatives; IntechOpen, 2020; p. 41.
[17]
Mhaske, S.B.; Argade, N.P. The chemistry of recently isolated naturally occurring quinazolinone alkaloids. Tetrahedron, 2006, 62(42), 9787-9826.
[http://dx.doi.org/10.1016/j.tet.2006.07.098]
[18]
Wiklund, P. Synthesis of heterocycles from anthranilic acid and its derivatives, Biovetenskaper och näringslära / Biosciences and Nutrition, 2004.
[19]
Vibhute, S.; Jamale, D.; Undare, S.; Valekar, N.; Kolekar, G.; Anbhule, P. An efficient, one-pot three components synthesis of [1,2,4] triazoloquinazolinone derivatives using anthranilic acid as green catalyst. Res. Chem. Intermed., 2017, 43(8), 4561-4574.
[http://dx.doi.org/10.1007/s11164-017-2896-5]
[20]
Mass, E.B.; Duarte, G.V.; Russowsky, D. The quinazoline-chalcone and quinazolinone-chalcone hybrids: A promising combination for biological activity. Mini Rev. Med. Chem., 2021, 21(2), 186-203.
[http://dx.doi.org/10.2174/1389557520666200730160325] [PMID: 32744973]
[21]
Varule, |S.J.; Bhawal, G.S.; Raka, K.C.; Rahane, R.D. Synthesis, method optimization, in-vitro antitumor activity of some new substituted quinazoline and quinazolin-4-one derivatives: Search for anticancer agent. J. Posit. Psychol., 2022, 6(7), 4833-4843.
[22]
Szewc, M. Radzikowska-Bűchner, E.; Wdowiak, P.; Kozak, J.; Kuszta, P.; Niezabitowska, E.; Matysiak, J.; Kubiński, K.; Masłyk, M. MSCs as tumor-specific vectors for the delivery of anticancer agents—a potential therapeutic strategy in cancer diseases: Perspectives for quinazoline derivatives. Int. J. Mol. Sci., 2022, 23(5), 2745.
[http://dx.doi.org/10.3390/ijms23052745] [PMID: 35269887]
[23]
Kang, J.; Zhong, Y.; Tian, W.; Li, J.; Li, X.; Zhai, L.; Hou, H.; Li, D. A novel anthraquinone quinazoline hybrid 7B blocks breast cancer metastasis and EMT via targeting EGFR and Rac1. Int. J. Oncol., 2021, 58(5), 19.
[http://dx.doi.org/10.3892/ijo.2021.5199] [PMID: 33760108]
[24]
Yu, P.; Cao, W.; Yang, S.; Wang, Y.; Xia, A.; Tan, X.; Wang, L. Design, synthesis and antitumor evaluation of novel quinazoline analogs in hepatocellular carcinoma cell. J. Mol. Struct., 2022, 1268, 133718.
[http://dx.doi.org/10.1016/j.molstruc.2022.133718]
[25]
Lv, J.; Song, W.; Li, X.; Gao, J.; Yuan, Z. Synthesis of a new phenyl chlormethine-quinazoline derivative, a potential anti-cancer agent, induced apoptosis in hepatocellular carcinoma through mediating Sirt1/Caspase 3 signaling pathway. Front. Pharmacol., 2020, 11, 911.
[http://dx.doi.org/10.3389/fphar.2020.00911] [PMID: 32670058]
[26]
Ha, H.A.; Chiang, J.H.; Tsai, F.J.; Bau, D.T.; Juan, Y.N.; Lo, Y.H.; Hour, M.J.; Yang, J.S.; Ha, H-A.; Chiang, J-H.; Tsai, F-J.; Bau, D-T.; Juan, Y-N.; Lo, Y-H.; Hour, M-J.; Yang, J-S. Novel quinazolinone MJ 33 induces AKT/mTOR mediated autophagy associated apoptosis in 5FU resistant colorectal cancer cells. Oncol. Rep., 2020, 45(2), 680-692.
[http://dx.doi.org/10.3892/or.2020.7882] [PMID: 33416156]
[27]
Liang, D.; Su, Z.; Tian, W.; Li, J.; Li, Z.; Wang, C.; Li, D.; Hou, H. Synthesis and screening of novel anthraquinone−quinazoline multitarget hybrids as promising anticancer candidates. Future Med. Chem., 2020, 12(2), 111-126.
[http://dx.doi.org/10.4155/fmc-2019-0230] [PMID: 31718309]
[28]
Narang, R.; Narasimhan, B.; Sharma, S. A review on biological activities and chemical synthesis of hydrazide derivatives. Curr. Med. Chem., 2012, 19(4), 569-612.
[http://dx.doi.org/10.2174/092986712798918789] [PMID: 22204327]
[29]
Vainlavichyus, P.I.; Rochka, Y.S.M.; Syadyaryavichuyute, V.Y.; Denene, A.A.; Beganskene, A.B.; Krenyavichene, M.I.; Abramova, L.G. Synthesis, structure, and biological activity of hydrazine derivatives of (6-phenoxy-4-pyrimidinylthio) acetic acids. Pharm. Chem. J., 1991, 25(11), 822-825.
[http://dx.doi.org/10.1007/BF00767268]
[30]
Yonova, P.A.; Stoilkova, G.M. Synthesis and biological activity of urea and thiourea derivatives from 2-aminoheterocyclic compounds. J. Plant Growth Regul., 2004, 23(4), 280-291.
[http://dx.doi.org/10.1007/s00344-003-0054-3]
[31]
Kocyigit-Kaymakcioglu, B.; Celen, A.; Tabanca, N.; Ali, A.; Khan, S.; Khan, I.; Wedge, D. Synthesis and biological activity of substituted urea and thiourea derivatives containing 1,2,4-triazole moieties. Molecules, 2013, 18(3), 3562-3576.
[http://dx.doi.org/10.3390/molecules18033562] [PMID: 23519199]
[32]
Evranos-Aksöz, B. Yabanoğlu-Çiftçi, S.; Uçar, G.; Yelekçi, K.; Ertan, R. Synthesis of some novel hydrazone and 2-pyrazoline derivatives: Monoamine oxidase inhibitory activities and docking studies. Bioorg. Med. Chem. Lett., 2014, 24(15), 3278-3284.
[http://dx.doi.org/10.1016/j.bmcl.2014.06.015] [PMID: 24986657]
[33]
Awwad, A.R.; Fars, K.A. Biological activity of quinazolinones. In: Quinazolinone and Quinazoline Derivatives; Ali Gamal; A.K. IntechOpen, 2020.
[34]
Akazome, M.; Kondo, T.; Watanabe, Y. Transition-metal complex-catalyzed reductive N-heterocyclization: synthesis of 4(3H)-quinazolinone derivatives from N-(2-nitrobenzoyl)amides. J. Org. Chem., 1993, 58(2), 310-312.
[http://dx.doi.org/10.1021/jo00054a008]
[35]
Aly, M.M.; Mohamed, Y.A.; El-Bayouki, K.A.M.; Basyouni, W.M.; Abbas, S.Y. Synthesis of some new 4(3H)-quinazolinone-2-carboxaldehyde thiosemicarbazones and their metal complexes and a study on their anticonvulsant, analgesic, cytotoxic and antimicrobial activities – Part-1. Eur. J. Med. Chem., 2010, 45(8), 3365-3373.
[http://dx.doi.org/10.1016/j.ejmech.2010.04.020] [PMID: 20510483]
[36]
Rajasekhar, K.; Nizamuddin, N.; Surur, A.S.; Mekonnen, Y.T. Synthesis, characterization, antitubercular and antibacterial activity, and molecular docking of 2, 3-disubstituted quinazolinone derivatives. Res. Rep. Med. Chem., 2016, 6, 15-26.
[37]
Panicker, C.Y.; Varghese, H.T.; Ambujakshan, K.R.; Mathew, S.; Ganguli, S.; Nanda, A.K.; Van Alsenoy, C.; Mary, Y.S. Vibrational spectra and computational study of 3-amino-2-phenyl quinazolin-4(3H)-one. J. Mol. Struct., 2010, 963(2-3), 137-144.
[http://dx.doi.org/10.1016/j.molstruc.2009.10.026]
[38]
Lee, C.; Yang, W.; Parr, R.G. Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Phys. Rev. B Condens. Matter, 1988, 37(2), 785-789.
[http://dx.doi.org/10.1103/PhysRevB.37.785] [PMID: 9944570]
[39]
Becke, A.D. A new mixing of Hartree–Fock and local density‐functional theories. J. Chem. Phys., 1993, 98(2), 1372-1377.
[http://dx.doi.org/10.1063/1.464304]

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