The Effects of Different Catalysts, Substituted Aromatic Aldehydes on One-Pot Three-Component Biginelli Reaction

Author(s): Zong-liang Liu*, Ren-mei Zhang, Ye Liu, Yan Guo, Qing-guo Meng.

Journal Name: Current Organic Synthesis

Volume 16 , Issue 1 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Aim and Objective: The Biginelli reaction, first reported in 1893, is one great example of the important multicomponent reactions reported from 1893. Under the same conditions, the influence of the common catalysts on the yield of the Biginelli reaction was investigated.

Materials and Method: To a round-bottom flask equipped with a spherical condenser were added 1,3- dicarbonyl compound (1.0 eq), urea (1.45 eq), aromatic aldehyde (1.0 eq), catalyst and methanol. The mixture was heated at reflux for 16 h. After cooling off, the mixture was filtered and washed with cold methanol to give DHPMs. Reaction solution was further purified by recrystallization with petroleum ether and ethyl acetate. Six catalytic systems, different 1,3-dicarbonyl compounds and different substituted aromatic aldehydes with varied substitutions are described for the Biginelli reaction. An analysis was also performed to study the factors that affect the yield of the reaction.

Results: When 1,3-dicarbonyl compound was ethyl acetoacetate, the CuCl/ conc.H2SO4 system gave the highest yield (90.5%). While when acetoacetamide was used, the yields of DHPMs in presence of PTSA/conc. HCl, conc. HCl or FeCl3•6H2O were all over 90%. Nine DHPMs with different substituents were obtained.

Conclusion: The Lewis acid or mixed catalyst had no significant advantage over a single protonic acid as catalyst. Conc. HCl as the catalyst was found to be the most effective condition for the preparation of DHPMs. The aromatic aldehyde with weak electron-withdrawing substituent such as Br resulted in the best yield.

Keywords: Multicomponent reactions, Biginelli reaction, catalysts, synthetize, substituents, reaction conditions.

[1]
Medyouni, R.; Elgabsi, W.; Naouali, O.; Romerosa, A.; Sulaiman Al-Ayed, A.; Baklouti, L.; Hamdi, N. One-pot three-component Biginelli-type reaction to synthesize 3,4-dihydropyrimidine-2- (1H)-ones catalyzed by Co phthalocyanines: Synthesis, characterization, aggregation behavior and antibacterial activity. Spectrochim. Acta A Mol. Biomol. Spectrosc., 2016, 167, 165-174.
[2]
Kappe, C.O. Biologically active dihydropyrimidones of the Biginelli-type--a literature survey. Eur. J. Med. Chem., 2000, 35(12), 1043-1052.
[3]
Chiang, A.N.; Valderramos, J.C.; Balachandran, R.; Chovatiya, R.J.; Mead, B.P.; Schneider, C.; Bell, S.L.; Klein, M.G.; Huryn, D.M.; Chen, X.S.; Day, B.W.; Fidock, D.A.; Wipf, P.; Brodsky, J.L. Select pyrimidinones inhibit the propagation of the malarial parasite, Plasmodium falciparum. Bioorg. Med. Chem., 2009, 17(4), 1527-1533.
[4]
Raju, B.C.; Rao, R.N.; Suman, P.; Yogeeswari, P.; Sriram, D.; Shaik, T.B.; Kalivendi, S.V. Synthesis, structure-activity relationship of novel substituted 4H-chromen-1,2,3,4-tetrahydropyrimidine-5-carboxylates as potential anti-mycobacterial and anticancer agents. Bioorg. Med. Chem. Lett., 2011, 21(10), 2855-2859.
[5]
Matsuda, T.; Hirao, I. Antibacterial activity of 5-nitrofuran derivatives. Nippon Kagaku Zasshi, 1965, 86, 1195-1197.
[6]
Kappe, C.O. 100 years of the Biginelli dihydropyrimidine synthesis. Tetrahedron, 1993, 49(32), 6937-6963.
[7]
Godfraind, T.; Miller, R.; Wibo, M. Calcium antagonism and calcium entry blockade. Pharmacol. Rev., 1986, 38(4), 321-416.
[8]
Atwal, K.S.; Rovnyak, G.C.; O’Reilly, B.C.; Schwartz, J. Substituted 1,4-dihydropyrimidines. 3. Synthesis of selectively functionalized 2-hetero-1,4-dihydropyrimidines. J. Org. Chem., 1989, 54(25), 5898-5907.
[9]
Nagarajaiah, H.; Mukhopadhyay, A.; Moorthy, J.N. Biginelli reaction: An overview. Tetrahedron Lett., 2016, 57(47), 5135-5149.
[10]
Aron, Z.D.; Overman, L.E. Total synthesis and properties of the crambescidin core zwitterionic acid and crambescidin 359. J. Am. Chem. Soc., 2005, 127(10), 3380-3390.
[11]
Arnold, M.A.; Day, K.A.; Duron, S.G.; Gin, D.Y. Total synthesis of (+)-batzelladine A and (-)-batzelladine D via [4 + 2]-annulation of vinyl carbodiimides with N-alkyl imines. J. Am. Chem. Soc., 2006, 128(40), 13255-13260.
[12]
Makarieva, T.N.; Tabakmaher, K.M.; Guzii, A.G.; Denisenko, V.A.; Dmitrenok, P.S.; Shubina, L.K.; Kuzmich, A.S.; Lee, H.S.; Stonik, V.A. Monanchocidins B-E: polycyclic guanidine alkaloids with potent antileukemic activities from the sponge Monanchora pulchra. J. Nat. Prod., 2011, 74(9), 1952-1958.
[13]
Kappe, C.O. Recent advances in the Biginelli dihydropyrimidine synthesis. New tricks from an old dog. Acc. Chem. Res., 2000, 33(12), 879-888.
[14]
Dondoni, A.; Massi, A. Decoration of dihydropyrimidine and dihydropyridine scaffolds with sugars via Biginelli and Hantzsch multicomponent reactions: an efficient entry to a collection of artificial nucleosides. Mol. Divers., 2003, 6(3-4), 261-270.
[15]
Biggs-Houck, J.E.; Younai, A.; Shaw, J.T. Recent advances in multicomponent reactions for diversity-oriented synthesis. Curr. Opin. Chem. Biol., 2010, 14(3), 371-382.
[16]
Kolosov, M.A.; Orlov, V.D.; Beloborodov, D.A.; Dotsenko, V.V. A chemical placebo: NaCl as an effective, cheapest, non-acidic and greener catalyst for Biginelli-type 3,4-dihydropyrimidin-2(1H)-ones (-thiones) synthesis. Mol. Divers., 2009, 13(1), 5-25.
[17]
Panda, S.S.; Khanna, P.; Khanna, L. Biginelli Reaction: A green perspective. Curr. Org. Chem., 2012, 16(4), 507-520.
[18]
Dong, F.; Jun, L.; Xinli, Z.; Zhiwen, Y.; Zuliang, L. One-pot green procedure for Biginelli reaction catalyzed by novel task-specific room-temperature ionic liquids. J. Mol. Catal. A: Chem., 2007, 274(1-2), 208-211.
[19]
Singhal, S.; Joseph, J.K.; Jain, S.L.; Sain, B. Synthesis of 3,4-dihydropyrimidinones in the presence of water under solvent free conditions using conventional heating, microwave irradiation/ultrasound. Green Chem. Lett. Rev., 2010, 3(1), 23-26.
[20]
Yu, J.; Shi, F.; Gong, L.Z. Bronsted-acid-catalyzed asymmetric multicomponent reactions for the facile synthesis of highly enantioenriched structurally diverse nitrogenous heterocycles. Acc. Chem. Res., 2011, 44(11), 1156-1171.
[21]
Wang, R.; Liu, Z.Q. Solvent-free and catalyst-free Biginelli reaction to synthesize ferrocenoyl dihydropyrimidine and kinetic method to express radical-scavenging ability. J. Org. Chem., 2012, 77(8), 3952-3958.
[22]
Alvim, H.G.; Lima, T.B.; de Oliveira, A.L.; de Oliveira, H.C.; Silva, F.M.; Gozzo, F.C.; Souza, R.Y.; da Silva, W.A.; Neto, B.A. Facts, presumptions, and myths on the solvent-free and catalyst-free Biginelli reaction. What is catalysis for? J. Org. Chem., 2014, 79(8), 3383-3397.
[23]
Zhang, Z.; Zhang, L.; Duan, X.; Yan, X.; Yan, Y.; Liu, Q.; Liu, T.; Zhang, G. Iron-catalyzed four-member multicomponent reaction for assembly of (E)-6-arylvinyl-3,4-dihydropyrimidin-2(1H)-ones. Tetrahedron, 2015, 71(40), 7745-7751.
[24]
Lacotte, P.; Buisson, D.A.; Ambroise, Y. Synthesis, evaluation and absolute configuration assignment of novel dihydropyrimidin-2-ones as picomolar sodium iodide symporter inhibitors. Eur. J. Med. Chem., 2013, 62, 722-727.
[25]
Ma, Y.; Qian, C.; Wang, L.; Yang, M. Lanthanide triflate catalyzed Biginelli reaction. One-pot synthesis of dihydropyrimidinones under solvent-free conditions. J. Org. Chem., 2000, 65(12), 3864-3868.
[26]
Kamal, A.; Shaheer Malik, M.; Bajee, S.; Azeeza, S.; Faazil, S.; Ramakrishna, S.; Naidu, V.G.; Vishnuwardhan, M.V. Synthesis and biological evaluation of conformationally flexible as well as restricted dimers of monastrol and related dihydropyrimidones. Eur. J. Med. Chem., 2011, 46(8), 3274-3281.
[27]
Akhaja, T.N.; Raval, J.P. 1,3-Dihydro-2H-indol-2-ones derivatives: design, synthesis, in vitro antibacterial, antifungal and antitubercular study. Eur. J. Med. Chem., 2011, 46(11), 5573-5579.
[28]
Ismaili, L.; Nadaradjane, A.; Nicod, L.; Guyon, C.; Xicluna, A.; Robert, J.F.; Refouvelet, B. Synthesis and antioxidant activity evaluation of new hexahydropyrimido[5,4-c]quinoline-2,5-diones and 2-thioxohexahydropyrimido [5,4-c]quinoline-5-ones obtained by Biginelli reaction in two steps. Eur. J. Med. Chem., 2008, 43(6), 1270-1275.
[29]
Singh, O.M.; Devi, N.S. Application of beta-oxodithioesters in domino and multicomponent reactions: facile route to dihydropyrimidines and coumarins. J. Org. Chem., 2009, 74(8), 3141-3144.
[30]
Shen, Z.L.; Xu, X.P.; Ji, S.J. Bronsted base-catalyzed one-pot three-component Biginelli-type reaction: An efficient synthesis of 4,5,6-triaryl-3,4-dihydropyrimidin-2(1H)-one and mechanistic study. J. Org. Chem., 2010, 75(4), 1162-1167.
[31]
Srivastav, S.; Shukla, C.; Luhach, K.; Pandeya, S.N. Pyrimidine hydrazones as potent anticonvulsant. World J. Pharma. Res., 2016, 5(6), 2101-2108.
[32]
Peng, L.; Jian, H.; Zhan, Z. A general, efficient and green procedure for synthesis of dihydropyrimidine-5-carboxamides in low melting betaine hydrochloride/urea mixture. Chin. J. Chem., 2016, 34, 637-645.
[33]
Roozbeh, J.K.; Ahmad, R.M.; Behnam, D. Preparation and characterization of bentonite/PS-SO3H nanocomposites as an efficient acid catalyst for the Biginelli reaction. App. Clay Sci., 2012, 55, 1-9.


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 16
ISSUE: 1
Year: 2019
Page: [181 - 186]
Pages: 6
DOI: 10.2174/1570179416666181122100405
Price: $58

Article Metrics

PDF: 24
HTML: 3
EPUB: 1
PRC: 1