Synthesis Of Pharmacologically Active Hexahydroacridine-1,8 (2H, 5H)-diones using Nickel (II) Flouride Tetrahydrate as a New Heterogeneous Catalyst

Abstract

COMMUNICATION IN PHYSICAL SCIENCES 2020, 5(2): 83-98

Authors: Ibanga .O Isaac and Abdul Hameed

Received 23rd March 2020/ Accepted 19th April 2020 

There are several reactions used in synthesis of dihydropyrimidines, but one of the simplest and most economical method for the synthesis of pharmacologically active acridine-1,8 (2H,5H)-dione derivatives is the classical Hantzsch reaction. Nickel (II) fluoride tetrahydrate catalyzed efficient Hantzsch reaction via one-pot three– component condensation of aromatic aldehydes, 5,5-dimethyl-1,3-cyclohexanedione (dimedone), and ammonium acetate refluxing in water was described for the preparation of hexahydroacridine1,8 (2H,5H)-dione derivatives. The products obtained were characterized on the basis of their melting-points, 1H NMR, 13C NMR, UV, IR, EI-MS, and HR-MS. Diethyl malonate and ethyl methyl ketone were observed to serve only as solvent and not reagent as proposed in solvent free synthesis of dihydropyrimidines. The attractive features of this environmentally benign protocol are excellent yields, cost-effective, simplicity and easy work-up. The higher catalytic activity of NiF2.4H2O is due to its high acidity, thermal stability and water tolerance.

References 

• Abdelhamid, A. A., Mohamed, S. K., Maharramov, A. M., Khalilov, A. N.n Allahverdiev, M. A. (2014). Facile and efficient synthesis of acridinediones from primary amino alcohols via three-component condensation reactions assisted by microwave irradiation. Journal of Saudi Chemical Society, 18, pp. 474 - 478.
• Abdolmohammadi, S. Karimpour, S. (2016). Rapid and mild synthesis of quinazolinones and chromenodpyrimidinones using nanocrystalline copper (I) iodide under solventfree conditions. Chinese Chemical Letters, 27, pp. 114 - 118.
• Alagarsamy, V., Pathak, U. S., Pandaya, S. N. Sriram, D. De Clercq, . (2000). Anti-HIV and anti-bacterial activities of some disubstitutedquinazolones and their bio-isoster disubstituted thieno pyrimidones. Indian Journal of Pharmaceutical Sciences, 62, pp. 433-437.
• Ali, I., Isaac, I. O., Ahmed, F., Aslam, F., Ali, S., Imran, M., Alharthy, R. D., Shah, M. R., Malik, M. I. Hameed, A. (2019). AcridineThiosemicarbazones-Stabilized Silver Nanoparticles as a Selective Sensor for Copper (II)-Ion in Tap Water. Chemistry Select, 4, pp. 8757-8763.
• Aly, M. M., Mohamed, . A., l-Bayouki, K. M., Basyouni, W. M. Abbas, S. . (2010). Synthesis of some new 4(3H)-quinazolinone-2carboxaldehyde thiosemicarbazones and their metal complexes and a study on their anticonvulsant, analgesic, cytotoxic and antimicrobial activities. European Journal of Medicinal Chemistry, 45, pp. 3365 - 3373.
• Aswin, K., Logaiya, K., Sudhan, P. N. Mansoor, S. S. (2012). An efficient one-pot synthesis of 1,4-dihydropyridine derivatives through Hantsch reaction catalyzed by melamine trisulfonic acid. Journal of. Taibah University of Science and Technology. 6, pp. 1 - 9.
• Banothu, J., Basavou, S., Bavantula, R. Crooks, P. A. (2014). Synthesis of fused thiazolo3,2-a pyrimidinones: N-aryl-2-chloroacetamides as doubly electrophilic building blocks. Tetrahedron Letters, 55, pp. 224 - 226.
  Dahiya, R., Kumar, A. adav, R. (2008). Synthesis and biological activity of peptide derivatives of iodoquinazolinones/nitroimidazoles. Molecules, 13, pp. 958 - 976.
• Dutta, A. K., Gogoi, P., Saikia, S., and Borah, R. (2017).N,N-Disulfo-1,1,3,3-tetramethyl guanin ium Carboxylate Ionic Liquids as Reusable Homogeneous Catalysts for Multicomponent Synthesis of Tetrahydrobenzo xanthene and Tetrahydrobenzo Acridine Derivatives. Journal of Molecular Liquids, 225, pp. 585 - 591.
• Ghorab, M. M., Abdel-Gawad, S. M., M. S. A. lGaby M. S. A. (2000). Synthesis and evaluation of some new fluorinated hydroquinazoline derivatives as antifungal agents. IL Farmaco. 55, pp. 249-255.
• Gndz, M. G., Isli, F., l-Khouly, A., ldrm, S., Fincan, G. S. O., Simsek, R., Safak, C., Saroglu, ., ldrm, S. O. Butcher, R .J. (2014). Microwave-assisted synthesis and myorelaxant activity of 9-indolyl-1,8acridinedione -derivatives. European Journal of Medicinal Chemistry, 75, 258266.
• Hashim, J., Arshad, N., Khan, I., Nisar, S., Ali, B. Choudhary, M. I. (2014). Preparation of dihydrotetrazolo1,5-a pyrimidine derivatives from Biginelli 3,4-dihydropyrimidine-2-thiones. Tetrahedron, 70, pp. 8582 - 8587.
• Isaac, I. O., al-Rashida, M., Rahman, S. U., Alharty, R. D., Asari, A., Hameed, A., Khan, K. M. Iqbal, J. (2019). Acridine-based (thio)semicarbazones and hydrazones: Synthesis, in vitro urease inhibition, molecular docking and in-silico ADM evaluation. Bioorganic Chemistry, 82, pp. 6 - 16.
• Isaac, I. O., Munir, I., Al-Rashida, M., Ali, S. A., Shafiq, Z., Islam, M. Ludwig, R., Ayub, K., Khan, K. M. Hameed, A. (2018). Novel acridine-based thiosemicarbazones as turn-on chemosensors for selective recognition of fluoride anion: a spectroscopic and theoretical study. Royal Society Open Sci.http://dx.doi.org/10.1098/rsos.180646.
• Kidwai, M., Saxena, S., Khan, M. K. R. Thukral, S. S. (2005). Synthesis of 4-aryl-7,7- dimethyl1,2,3,4,5,6,7,8-octahydroquinazoline2one/thione-5-one derivatives and evaluation as antibacterials. European Journal of Medicinal Chemistry, 40, pp. 816-819.
• Kumar, A. Raput, C. S. (2009). Synthesis antiinflammatory activity of newer quinazolin-4-one derivatives. European Journal of Medicinal Chemistry, 44, pp. 83 - 90.
• Kumar, A., Sharma, S., Tripathi, V. D., Maurya, R. A., Srivastava, S. P., Bhatia, G., Tamrakar, A. K., Srivastava, A .K. (2010). Design and synthesis of 2,4-disubstituted polyhydroquinolines as prospective antihyperglycemic and lipid modulating agents. Bioorganic and Medicinal Chemistry, 18, pp. 4138 - 4148.
• Ladani, N. K., Mungra, D. C., Patel, M. P., Patel, R. G. (2011). Microwave assisted synthesis of novel Hantzsch 1,4-dihydropyridines, acridine1,8-diones and polyhydroquinolines bearing the tetrazolo1,5-aquinoline moiety and their antimicrobial activity assess. Chinese Chemical Letters, 22, pp.1407 - 1410.
• Mansoor, S. S., Aswin, K., Logaiya, K. Sudhan, S. P. N. (2014). Aqua-mediated synthesis of acridinediones with reusable silica-supported sulfuric acid as an efficient catalyst. Journal of Taibah University of Science and Technology, 8, pp.265 - 275.
  Mansoor, S. S., Aswin, K., Logaiya, K. Sudhan, S. P. N. (2016). Bismuth nitrate as an efficient recyclable catalyst for the one-pot multi component synthesis of 1,4-dihydropyridine derivative through unsymmetrical Hantzsch reaction. Journal of Saudi Chemical Society. 20, pp. S100 - S108.
• Nasresfahani, Z. Kassaee, M. Z. (2015). Mesoporous silica nanoparticles in an efficient, solvent-free green synthesis of acridinediones. Catalysis Communications, 60, pp. 100 - 104.
• Ramesh, K. B. Pasha, M. A. (2014). Study on One-pot Four-component Synthesis of 9-aryhexahydro-acridine- 1,8-diones Using SiO-I as a New Heterogeneous Catalyst and their Anticancer Activity. Bioorganic and Medicinal Chemistry Letters, 24, pp.3907 - 3913.
• Satheeshkumar, R., Sayin, K., Kaminsky, W. Prasad, K. J. R. (2017). Synthesis, spectral analysis and quantum chemical studies on molecular geometry, chemical reactivity of 7Chloro-9-(2-chlorophenyl)-2,3-dihydroacridin4(1H)-one and 7-chloro-9-(2-flourophenyl)2,3- dihydroacridin-4 (1H)-one. Journal of Molecular Structure., 112 8, pp.279 - 289.
• J. Zhang, K. (2012). Synthesis of Nsubstituted acridinediones and polyhydro- quinoline derivatives in refluxing water. Molecules. 17: 5339 - 5345.