DBU Catalysis: An Efficient Synthetic Strategy for 5,7-disubstituted-1,2,4- triazolo[1,5-a]pyrimidines

Author(s): Yogesh K. Pandey, Anu Mishra, Pratibha Rai, Jaya Singh, Jagdamba Singh*, Ramendra K. Singh*

Journal Name: Current Organic Synthesis

Volume 17 , Issue 1 , 2020

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Graphical Abstract:


Aims and Objectives: An efficient and facile DBU catalysed synthesis of highly significant motif 5,7-disubstituted-1,2,4-triazolo[1,5-a]pyrimidines under solvent-free condition has been reported.

Materials and Methods: To a round bottom flask, 1.0 mmol of chalcone (1), 1.5 mmol of 3-amino-1,2,4- triazole (2) and 30 mol% of DBU were added at 70 °C and stirred in solvent-free condition. After the completion of the reaction (monitored by TLC), water (10 ml) was added. The aqueous layer was extracted with ethyl acetate (3 ×10 ml). The combined organic layers were dried over anhydrous Na2SO4. The combined organic layers were evaporated under reduced pressure and the resulting crude product was purified by column chromatography by using ethyl acetate and hexane as eluent.

Results: Reaction using chalcone and 3-amino-1,2,4-triazole as model substrates were carried out under different reaction conditions and it was observed that 30 mol% of DBU under the solvent-free condition at 70 °C was the optimum temperature for the proposed synthesis.

Conclusion: Use of DBU (an organocatalyst) as a base, operational simplicity, high yield of products and short reaction time are some of the significant advantages associated with the proposed strategy.

Keywords: Solvent-free, 1, 8-Diazabicyclo[5.4.0]undec-7-ene (DBU), green synthesis, 1, 2, 4-triazolo[1, 5-a]pyrimidines, chalcone, ethyl acetate.

(a)Anastas, P.T.; Warner, J.C. Green Chem: Theory and Practice; Oxford University Press: New York, 1998.
(b)Bihani, M.P.; Bora, P.; Bez, G.; Askari, H. Amberlyst A21 Catalyzed Chromatography-Free Method for Multicomponent Synthesis of Dihydropyrano[2,3-c]pyrazoles in Ethanol. ACS Sustain. Chem.& Eng., 2013, 1, 440-447.Available at.
(c)Cue, B.W.; Zhang, J. Green process chemistry in the pharmaceutical industry. Green Chem. Lett. Rev., 2009, 2, 193-211.Available at.
(d)Sanderson, K. Chemistry: It’s not easy being green. Nature, 2011, 469(7328), 18-20.Available at.
[http://dx.doi.org/10.1038/469018a] [PMID: 21209638]
(e)Sheldon, R.A. Green chemistry and resource efficiency: Towards a green economy. Green Chem., 2016, 18, 3180-3183.Available at.
(a)Himaja, M. Green technique solvent free synthesis and its advantage. IJRAP, 2011, 2, 1079-1086.
(b)Anastas, P.; Eghbali, N. Green chemistry: Principles and practice. Chem. Soc. Rev., 2010, 39(1), 301-312.Available at.
[http://dx.doi.org/10.1039/B918763B] [PMID: 20023854]
(c)Dicks, A.P. Solvent-free reactivity in the undergraduate organic laboratory. Green Chem. Lett. Rev., 2009, 2(2), 87-100.Available at.
(d)Horváth, I.T. Green chemistry. Acc. Chem. Res., 2002, 35(9), 685-685.Available at.
[http://dx.doi.org/10.1021/ar020160a] [PMID: 12234197]
(a)Babu, N. S.; Reddy, S. M. Impact of solvents leading to environmental pollution. J. Chem. Pharm. Sci, , 2014, 49-52.
(b)Welton, T. Solvents and sustainable chemistry. Proc. R. Soc., 2015, 451Available at.
Awol, A. Transition metal oxides nanoparticles catalysis for sustainable organic synthesis under solvent free conditions. Saudi J. Biomed. Res., 2017, 2, 10-18.
(a)Ghonchepour, E.; Islami, M.R.; Mostafavi, H.; Tikdari, A.M.; Sheikhshoaie, I. Transition metal-free and base-mediated transformation arylation of unactivated benzene with aryl halides in presence of N,N′-bis(salicylidene)ethylenediamine as organocatalyst. Catal. Commun., 2018, 107, 87-91.Available at.
(b)Zhong, J.; Guan, Z.; He, Y.H. A novel organocatalyst for direct asymmetric Michael additions of cyclohexanone to nitroolefins. Catal. Commun., 2013, 32, 18-22.Available at.
(c)Chandrasekhar, S.; Reddy, N.R.; Sultana, S.S.; Narsihmulu, Ch.; Reddy, K.V. l-Proline catalysed asymmetric aldol reactions in PEG-400 as recyclable medium and transfer aldol reactions. Tetrahedron, 2006, 62, 338-345.Available at.
Shaikh, I.R. Organocatalysis: Key trends in green synthetic chemistry, challenges, scope towards heterogenization, and importance from research and industrial point of view. J. Catal., 2014, 2014, 1-35.Available at.
(a)Arya, A.K.; Kumar, M. Base catalyzed multicomponent synthesis of spiroheterocycles with fused heterosystems. Mol. Divers., 2011, 15(3), 781-789.Available at.
[http://dx.doi.org/10.1007/s11030-011-9309-2] [PMID: 21424596]
(b)Mishra, S.; Ghosh, R. K2CO3-Mediated, One-Pot, Multicomponent Synthesis of Medicinally Potent Pyridine and Chromeno[2,3-b]pyridine Scaffolds. Synth. Commun., 2012, 42, 2229-2244.Available at.
(a)Singh, H.; Sindhu, J.; Khurana, J.M. Synthesis of biologically as well as industrially important 1,4,5-trisubstituted-1,2,3-triazoles using a highly efficient, green and recyclable DBU–H2O catalytic system. RSC Advances, 2013, 3, 22360-22366.Available at.
(b)Khurana, J.M.; Nand, B.; Saluja, P. DBU: a highly efficient catalyst for one-pot synthesis of substituted 3,4- dihydropyrano[3,2-c]chromenes, dihydropyrano[4,3-b]pyranes, 2-amino-4Hbenzo[h]chromenes and 2-amino-4H benzo[g]chromenes in aqueous medium. Tetrahedron, 2010, 66, 5637-5641.Available at.
(a)Nieczypor, P.; Mol, J.C.; Bespalova, N.B.; Bubnov, Y.N. Synthesis of Nitrogen-Containing Spiro Compounds from Lactams by Allylboration and Subsequent Ring-Closing Metathesis. Eur. J. Org. Chem., 2004, 812-819.Available at.
(b)Naito, T. Development of new synthetic reactions for nitrogen-containing compounds and their application. Chem. Pharm. Bull. (Tokyo), 2008, 56(10), 1367-1383.Available at.
[http://dx.doi.org/10.1248/cpb.56.1367] [PMID: 18827374]
(a)Fizer, M.; Slivka, M. Synthesis of [1,2,4]triazolo[1,5-a]pyrimidine (microreview). Chem. Heterocycl. Compd., 2016, 52, 155-157.Available at.
(b)Jiang, N.; Deng, X.Q.; Li, F.N.; Quan, Z.S. Synthesis of Novel 7-Substituted-5-phenyl-[1,2,4]triazolo[1,5-a] Pyrimidines with Anticonvulsant Activity. Iran. J. Pharm. Res., 2012, 11(3), 799-806.
[PMID: 24250507]
Olar, R.; Calu, L.; Badea, M.; Chifiriuc, M.C.; Bleotu, C.; Velescu, B.; Stoica, O.; Ionita, G.; Stanica, N.; Silvestro, L.; Dulea, C.; Uivarosi, V. Thermal behaviour of some biologically active species based on complexes with a triazolopyrimidine pharmacophore. J. Therm. Anal. Calorim., 2017, 127, 685-696.Available at.
Wang, H.; Lee, M.; Peng, Z.; Blázquez, B.; Lastochkin, E.; Kumarasiri, M.; Bouley, R.; Chang, M.; Mobashery, S. Synthesis and evaluation of 1,2,4-triazolo[1,5-a]pyrimidines as antibacterial agents against Enterococcus faecium. J. Med. Chem., 2015, 58(10), 4194-4203.Available at.
[http://dx.doi.org/10.1021/jm501831g] [PMID: 25923368]
Girasolo, M.A.; Di Salvo, C. Schillaci, D.; Barone, G.; Silvestri, A.; Ruisi, G. Synthesis, characterization, and in vitro antimicrobial activity of organotin (IV) complexes with triazolo-pyrimidine ligands containing exocyclic oxygen atoms. J. Organomet. Chem., 2005, 690, 4773-4783.Available at.
(a)Girasolo, M.A.; Schillaci, D.; Salvo, C.D.; Barone, G.; Silvestri, A.; Ruisi, G. Synthesis, spectroscopic characterization and in vitro antimicrobial activity of diorganotin(IV) dichloride adducts with [1,2,4]triazolo-[1,5-a]pyrimidine and 5,7-dimethyl-[1,2,4]triazolo- [1,5-a]pyrimidine. J. Organomet. Chem., 2006, 691, 693-701.Available at.
(b)Ruisi, G.; Canfora, L.; Bruno, G.; Rotondo, A.; Mastropietro, T.F.; Debbia, E.A.; Girasolo, M.A.; Megna, B. Triorganotin(IV) derivatives of 7-amino-2-(methylthio)[1,2,4]triazolo[1,5-a]pyrimidine- 6-carboxylic acid. Synthesis, spectroscopic characterization, in vitro antimicrobial activity and X-ray crystallography. J. Organomet. Chem., 2010, 695, 546-551.Available at.
Yu, W.; Goddard, C.; Clearfield, E.; Mills, C.; Xiao, T.; Guo, H.; Morrey, J.D.; Motter, N.E.; Zhao, K.; Block, T.M.; Cuconati, A.; Xu, X. Design, synthesis, and biological evaluation of triazolo-pyrimidine derivatives as novel inhibitors of hepatitis B virus surface antigen (HBsAg) secretion. J. Med. Chem., 2011, 54(16), 5660-5670.Available at.
[http://dx.doi.org/10.1021/jm200696v] [PMID: 21786803]
(a)Peng, H.; Kumaravel, G.; Yao, G.; Sha, L.; Wang, J.; Van Vlijmen, H.; Bohnert, T.; Huang, C.; Vu, C.B.; Ensinger, C.L.; Chang, H.; Engber, T.M.; Whalley, E.T.; Petter, R.C. Novel bicyclic piperazine derivatives of triazolotriazine and triazolopyrimidines as highly potent and selective adenosine A2A receptor antagonists. J. Med. Chem., 2004, 47(25), 6218-6229.Available at.
[http://dx.doi.org/10.1021/jm0494321] [PMID: 15566292]
(b)Bhatt, J.D.; Chudasama, C.J.; Patel, K.D. Pyrazole clubbed triazolo[1,5-a]pyrimidine hybrids as an anti-tubercular agents: Synthesis, in vitro screening and molecular docking study. Bioorg. Med. Chem., 2015, 23(24), 7711-7716.Available at.
[http://dx.doi.org/10.1016/j.bmc.2015.11.018] [PMID: 26631439]
(c)Zhang, N.; Ayral-Kaloustian, S.; Nguyen, T.; Afragola, J.; Hernandez, R.; Lucas, J.; Gibbons, J.; Beyer, C. Synthesis and SAR of [1,2,4]triazolo[1,5-a]pyrimidines, a class of anticancer agents with a unique mechanism of tubulin inhibition. J. Med. Chem., 2007, 50(2), 319-327.Available at.
[http://dx.doi.org/10.1021/jm060717i] [PMID: 17228873]
(d)Novinson, T.; Springer, R.H.; O’Brien, D.E.; Scholten, M.B.; Miller, J.P.; Robins, R.K. 2-(Alkylthio)-1,2,4-triazolo[1,5-a]pyrimidines as adenosine cyclic 3′,5′-monophosphate phosphodiesterase inhibitors with potential as new cardiovascular agents. J. Med. Chem., 1982, 25(4), 420-426.Available at.
[http://dx.doi.org/10.1021/jm00346a017] [PMID: 6279846]
(a)He, X.; Kassab, S.E.; Heinzl, G.; Xue, F. Base-catalyzed one-step synthesis of 5,7-disubstituted-1,2,4-triazolo[1,5-a]pyrimidines. Tetrahedron Lett., 2015, 56, 1034-1037.Available at.
(b)Shahi, M.N.; Perveen, N.; Khan, M.N.; Khakwani, S.; Khan, M.A. Triazolopyrimidines: Synthesis of Aryl-1,2,4-triazolo[1,5-a]pyrimidines by Doebner-Miller reaction and their antibacterial activity. Asian J. Chem., 2016, 28, 2665-2669.Available at.
(c)Hassaneen, H.M.E.; Farghaly, T.A.A. A simple, convenient, one-pot synthesis of Dihydro-azolopyrimidines, DFT Calculation, and NMR Determination by Using H-Ferrierite Zeolite as Catalyst; J. Heterocyclic Chem, 2014.
(d)Hassaneen, H.M.E. Chemistry of the enaminone of 1-acetylnaphthalene under microwave irradiation using chitosan as a green catalyst. Molecules, 2011, 16(1), 609-623.Available at.
[http://dx.doi.org/10.3390/molecules16010609] [PMID: 21242941]
(e)Saleh, T.S.; Al-Bogami, A.S. A simplified green chemistry approach to synthesis of Azolo[1,5-a]pyrimidine incorporated thiophene moiety. Heterocycles, 2016, 92, 2066-2077.Available at.
(f)Palaniraja, J.; Roopan, S.M. UV-light induced domino type reactions: synthesis and photophysical properties of unreported nitrogen ring junction quinazolines. RSC Advances, 2015, 5, 37415-37423.Available at.
(g)Ovchinnikova, I.G.; Valova, M.S.; Matochkina, E.G.; Kodess, M.I.; Tumashov, A.A.; Slepukhin, P.A.; Fedorova, O.V.; Rusinov, G.L.; Charushin, V.N. Unusual heterocyclization of chalcone podands with 3_amino_1,2,4_triazole. Russ. Chem. Bull., 2011, 60, 965-974.Available at.
(h)Souza, L.A.; Santos, J.M.; Mittersteiner, M.; Andrade, V.P.; Lobo, M.M.; Santos, F.B.; Bortoluzzi, A.J.; Bonacorso, H.G.; Martins, M.A.P.; Zanatta, N. Synthetic Versatility of β-Alkoxyvinyl Trichloromethyl Ketones for Obtaining [1,2,4]Triazolo[1,5-a]pyrimidines. Synthesis, 2018, 50, 3686-3695.Available at.
(i)Ovchinnikova, I.G.; Fedorova, O.V.; Rusinov, G.L.; Charushin, V.N. 7-(2-Ethoxyphenyl)dihydroazolopyrimidines in oxidation reactions with bromine. Chem. Heterocycl. Compd., 2018, 54, 892-901.
(j)Hassan, A.Y.; Sarg, M.T.; Bayoumi, A.H.; El‐Deeb, M.A. Synthesis and anticancer evaluation of some novel 5-Amino[1,2,4]Triazole derivatives. J. Heterocycl. Chem., 2018, 55, 1450-1478.Available at.
(k)Chernyshev, V.M.; Pyatakov, D.A.; Astakhov, A.V.; Sokolov, A.N. akhrutdinov A.N.F.; Rybakov V.B.; Chernyshev V.V. Partially hydrogenated 2-amino[1,2,4]triazolo[1,5-a]pyrimidines as synthons for the preparation of polycondensed heterocycles: Reaction with a-bromoketones. Tetrahedron, 2015, 71, 6259-6271.Available at.
(l)Rasputin, N.A.; Demina, N.S.; Irgashev, R.A.; Rusinov, G.L.; Chupakhin, O.N.; Charushin, V.N. Direct (het)arylation of [1,2,4]triazolo[1,5-a]pyri-midines: Both eliminative and oxidative pathways. Tetrahedron, 2017, 73, 5500-5508.Available at.
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(b)Rai, P.; Mishra, A.; Srivastava, M.; Yadav, S.; Tripathi, B.P.; Singh, J. Singh, J. An amino sugar promoted green protocol: A One-Pot, Meglumine- Catalyzed, multicomponent strategy for synthesis of Multifaceted Pyrroloacridin-1(2H)-one Derivatives. Chemistry Select,, 2017, 2, 2245-2250.Available at.
(c)Mishra, A.; Rai, P.; Srivastava, M.; Tripathi, B.P.; Yadav, S.; Singh, J. Singh, J. A peerless aproach: Organophotoredox/Cu(I) Catalyzed, regioselective, visible light facilitated, click synthesis of 1,2,3-Triazoles via Azide-Alkyne [3 + 2] Cycloaddition. Catal. Lett.,, 2017, 147, 2600-2611.Available at.
(d)Tripathi, B.P.; Mishra, A.; Rai, P.; Pandey, Y.K.; Srivastava, M.; Yadav, S.; Singh, J. Singh, J. A green and clean pathway: One pot, multicomponent, and visible light assisted synthesis of pyrano[2,3-c]pyrazoles under catalystfree and solvent-free conditions. New J. Chem.,, 2017, 4, 11148-11154.Available at.
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Year: 2020
Page: [73 - 80]
Pages: 8
DOI: 10.2174/1570179417666191216123339
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