Login Register Cart 0
Generic placeholder image

Current Organic Synthesis

Editor-in-Chief

ISSN (Print): 1570-1794
ISSN (Online): 1875-6271

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

Synthesis of Dihydropyrimidinones (DHPMs) and Hexahydro Xanthene Catalyzed by 1,4-Diazabicyclo [2.2.2] Octane Triflate Under Solvent-Free Condition

Author(s): Deepa, Geeta D. Yadav, Mohd J. Aalam, Pooja Chaudhary and Surendra Singh*

Volume 16, Issue 5, 2019

Page: [776 - 786] Pages: 11

DOI: 10.2174/1570179415666181113154232

Price: $65

Abstract

Objective: DABCO salts were evaluated as catalysts for the Biginelli reaction between 4- methoxybenzaldehyde, urea and ethyl acetoacetate under solvent-free conditions. 1,4-Diazabicyclo [2.2.2] octane triflate was found to be a simple, inexpensive, highly efficient catalyst for Biginelli reaction for a variety aromatic aldehyde with urea and ethyl acetoacetate at 80°C afforded corresponding 3,4-dihydropyrimidinones in 50-99% yields after 30-120 minutes. 1,3-Cyclohexadione was used in place of ethyl acetoacetate in the absence of urea this methodology is giving hexahydro xanthene derivatives in good to excellent yields after 3-4 hours.

Methods: DABCO salt 4 (5 mol%), 4-methoxybenzaldehyde (0.73 mmol) and urea (0.73 mmol) were stirred for 10 minutes at 80°C, then ethyl acetoacetate (1.5 equiv.) was added and reaction mixture was stirred at 80°C for specified time. The resulting solution was stirred continuously and progress of the reaction was followed by TLC. The crude reaction mixture was purified by flash column chromatography on silica gel (hexane/ethyl acetate (1:2)) to give pure desired product.

Results: Reaction conditions of the Biginelli reaction were optimized using 4-methoxybenzaldehyde (0.73 mmol), urea (0.73 mmol), and ethyl acetoacetate (5 equiv.) as model substrates catalyzed by 1,4-Diazabicyclo [2.2.2] octane triflate (5 mol%) in a different solvents, screening of different catalysts and different temperatures. Neat condition was found to be the best for the Biginelli condensation and corresponding 3,4- dihydropyrimidinones was obtained in good to excellent yields. When the reaction was carried out with benzaldehyde derivatives and cyclohexane-1,3-dione in place of ethyl acetoacetate in the absence of urea, solely corresponding hexahydro xanthene derivatives were obtained in 61-91% yields.

Conclusion: In conclusion, we have applied salts of 1,4-Diaza-bicyclo [2.2.2] octane as catalysts in the Biginelli condensation and corresponding 3,4-dihydropyrimidinones were obtained in 50- 99% yields under solvent free conditions. This methodology is having advantages like simple work-up; low loading of catalyst and reaction was performed at moderate temperature under solvent-free conditions.

Keywords: Dabco salts, Biginelli reaction, benzaldehyde derivative, cyclohexane-1, 3-dione, xanthene, catalysts.

« Previous Next »
Graphical Abstract

[1]
Verma, S.; Jain, S.L.; Sain, B. PEG-embedded KBr3: A recyclable catalyst for multicomponent coupling reaction for the efficient synthesis of functionalized piperidines. J. Org. Chem., 2011, 7, 1334-1341.
[2]
Veisi, H.; Maleki, A.; Jahangard, S. Electrogenerated base promoted synthesis of 3-methyl-4-aryl-2,4,5,7-tetrahydropyrazolo[3,4-b]pyridin-6-ones via multicomponent reactions of 5-methylpyrazol-3-amine, aldehydes, and meldrum’s acid. Tetrahedron Lett., 2015, 56, 1882-1886.
[3]
Yarim, M.; Sarac, S.; Kilic, F.S.; Erol, K. Synthesis and in vitro calcium antagonist activity of 4-aryl-7,7-dimethyl/1,7,7-trimethyl-1,2,3,4,5,6,7,8-octaquinazoline-2,5-dione derivatives. Farmaco, 2003, 58, 17-24.
[4]
Aron, Z.D.; Overman, L.E. The tethered Biginelli condensation in natural product synthesis. Chem. Commun., 2004, 2004, 253-265.
[5]
Haggarty, S.J.; Mayer, T.U.; Miyamoto, D.T.; Fathi, R.; King, R.W.; Mitchison, T.J.; Schreiber, S.L. Dissecting cellular processes using small molecules: identification of colchicine-like, taxol-like and other small molecules that perturb mitosis. Chem. Biol., 2000, 7, 275-286.
[6]
Ram, V.J.; Haque, N.P.; Guru, Y. Chemotherapeutic agents XXV: synthesis and leishmanicidal activity of carbazolylpyrimidines. Eur. J. Med. Chem., 1992, 27, 851-855.
[7]
Amir, M.; Javed, S.A.; Kumar, H. Pyrimidine as anti-inflammatory agent: A review. Int. J. Pharma Sci., 2007, 69, 337-343.
[8]
Sondhi, S.M.; Jain, S.; Dwivedi, A.D.; Shukla, R.; Raghubir, R. Synthesis of condensed pyrimidines and their evaluation for anti-inflammatory and analgesic activities. Ind. J. Chem. B, 2008, 47, 136-143.
[9]
Vega, S.; Alonso, J.; Diaz, J.A.; Junquera, F. Synthesis of 3-Substituted-4-phenyl-2-thioxo-1,2,3,4,5,6,7,8-octahydrobenzo[4,5]-thieno[2,3-d]-pyrimidi-nes. J. Heterocycl. Chem., 1990, 27, 269-273.
[10]
Smith, P.A.S.; Kan, R.O. Cyclization of isothiocyanates as a route to phthalic and homophthalic acid derivatives. J. Org. Chem., 1964, 29, 2261-2265.
[11]
a)Rovnyak, G.C.; Kimball, S.D.; Beyere, B.; Cucinotta, G.J.; DiMarco, D.; Gougoutas, J.; Hedberg, A.; Malley, M.; McCarthy, J.P. Calcium entry blockers and activators: Conformational and structural determinants of dihydropyrimidine calcium channel modulators. J. Med. Chem., 1995, 38, 119-129.
b)Hannah, D.R.; Stevens, M.F.G. Structural studies on bioactive compounds. Part 38.1 Reactions of 5-aminoimidazole-4-carboxamide: Synthesis of imidazo[1,5-a]quinazoline-3- carboxamides. J. Chem. Res., 2003, 2003(7), 398-401.
[12]
Suresh, Sandhu. J.S. Past, present and future of the Biginelli reaction: a critical perspective. ARKIVOC, 2012, 2012(i), 66-133.
[13]
Kappe, C.O. 100 Years of Biginelli dihydropyrimidine synthesis. Tetrahedron, 1993, 49, 6937-6963.
[14]
Biginelli, P. Aldehyde-urea derivatives of aceto- and oxaloacetic acids. Gazz. Chim. Ital., 1893, 23, 360-413.
[15]
Folkers, K.; Harwood, H.; Johnson, J.T.B. Researches on pyrimidines. CXXX. Synthesis of 2-keto-l, 2,3,4-tetrahydropyrimidines. J. Am. Chem. Soc., 1932, 54, 3751-3758.
[16]
Hu, E.H.; Sidler, D.R.; Dolling, U.H. Unprecedented catalytic three component one-pot condensation reaction: An efficient synthesis of 5-alkoxycarbonyl4-aryl-3,4-dihydropyrimidin-2(1H)-ones. J. Org. Chem., 1998, 63, 3454-3457.
[17]
Lu, J.; Bai, Y.; Wang, Z.; Yang, B.; Ma, H. One-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones using lanthanum chloride as a catalyst. Tetrahedron Lett., 2000, 41, 9075-9078.
[18]
Bose, D.S.; Fatima, L.; Mereyala, H.B. Green chemistry approaches to the synthesis of 5-alkoxycarbonyl-4-aryl-3,4- dihydropyrimidin-2(1H)-ones by a three-component coupling of one-pot condensation reaction: Comparison of ethanol, water, and solvent-free Conditions. J. Org. Chem., 2003, 68, 587-590.
[19]
Ranu, B.C.; Hajra, A.; Jana, U. Indium(III) chloride-catalyzed one-pot synthesis of dihydropyrimidinones by a Three-Component Coupling of 1,3-dicarbonyl compounds, aldehydes, and urea: An improved procedure for the Biginelli reaction. J. Org. Chem., 2000, 65, 6270-6272.
[20]
Ramalinga, K.; Vijayalakshmi, P.; Kaimala, T.N.B. Bismuth (III)-catalyzed synthesis of dihydropyrimidinones: improved protocol conditions for the Biginelli reaction. Synlett, 2001, 863-865.
[21]
Paraskar, A.S.; Dewkar, G.K.; Sudalai, A. Cu(OTf)2: a reusable catalyst for high-yield synthesis of 3,4-dihydropyrimidin-2(1H)-ones. Tetrahedron Lett., 2003, 44, 3305-3308.
[22]
Fu, N.Y.; Yuan, Y.F.; Cao, Z.; Wang, S.W.; Wang, J.T.; Peppe, C. Indium (III) bromide-catalyzed preparation of dihydropyrimidinones: Improved protocol conditions for the Biginelli reaction. Tetrahedron, 2002, 58, 4801-4807.
[23]
Yadav, J.S.; Reddy, B.V.S.; Srinivas, R.; Venugopal, C.; Ramalingam, T. LiClO4-Catalyzed one-pot Synthesis of dihydropyrimidinones: An improved protocol for Biginelli reaction. Synthesis, 2001, 9, 1341-1345.
[24]
Maiti, G.; Kundua, P.; Guin, C. One-pot synthesis of dihydropyrimidinones catalysed by lithium bromide: An improved procedure for the Biginelli reaction. Tetrahedron Lett., 2003, 44, 2757-2758.
[25]
Lu, J.; Ma, H. Iron (III) Catalyzed synthesis of dihydropyrimidinones. improved condition for Biginelli reaction. Synlett, 2000, 63-64.
[26]
Cepance, I.; Litvic, M.; Bartolincic, A.; Lovric, M. Ferric chloride/tetraethyl orthosilicate as an efficient system for synthesis of dihydropyrimidinones by Biginelli reaction. Tetrahedron, 2005, 61, 4275-4280.
[27]
Kuraitheerthakumaran, A.; Pazhamalai, S.; Popalakrishnan, M. Microwave-assisted multicomponent reaction for the synthesis of 3,4-dihydropyrimidin-2(1H)-ones and their corresponding 2(1H)-thiones using lanthanum oxide as a catalyst under solvent-free conditions. Arab. J. Chem., 2016, 9, S461-S465.
[28]
Song, X.; Cai, S.Y.; Li, L.Y.; Ming, S.X.; Xiang, Q. Synthesis of 4-Aryl-3-4-dihydropyrimidinones using microwave-assisted solventless Biginelli Reaction. Chin. J. Chem., 2002, 20, 385-389.
[29]
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, 3864-3868.
[30]
Arfan, A.; Paquin, L.; Bazureau, J.P. Acidic task-specific ionic liquid as catalyst of microwave-assisted solvent-free Biginelli reaction. Russ. J. Org. Chem., 2007, 43, 1058-1064.
[31]
Chavan, S.S.; Sharma, Y.O.; Degani, M.S. Cost-effective ionic liquid for environmentally friendly synthesis of 3,4-dihydropyrimidin-2(1H)- ones. Green Chem. Lett. Rev., 2009, 2, 175-179.
[32]
Li, M.; Guo, W.S.; Wen, L.R.; Li, Y.F.; Yang, H.Z. One-pot synthesis of Biginelli and Hantzsch products catalyzed by non-toxic ionic liquid (BMImSac) and structural determination of two products. J. Mol. Catal. A: Chem., 2006, 258, 133-138.
[33]
Chen, X.; Peng, Y. Chloroferrate(III) Ionic Liquid: Efficient and Recyclable Catalyst for Solvent-free Synthesis of 3,4-Dihydropyrimidin-2(1H)-ones. Catal. Lett., 2008, 122, 310-313.
[34]
Shaterian, H.R.; Aghakhanizadeh, M. Bronsted reusable acidic ionic liquids catalyzed Biginelli reaction under solvent free condition. Phosphorus Sulfur and Silicon, 2013, 188, 1064-1070.
[35]
Roy, S.R.; Jadhavar, P.S.; Seth, K.; Sharma, K.K.; Chakraborti, A.K. Organocatalytic application of ionic liquids: [bmim][MeSO4] as a recyclable organocatalyst in the multicomponent reaction for the preparation of dihydropyrimidinones and –thiones. Synthesis, 2011, 14, 2261-2267.
[36]
Zare, A.; Nasouri, Z. A green approach for the synthesis of 3,4-dihydropyrimidin-2-(1H)-ones (and -thiones) using N,N-diethyl-N-sulfoethanaminium hydrogen sulfate. J. Mol. Liq., 2016, 216, 364-369.
[37]
Dondoni, A.; Massi, A. Parallel synthesis of dihydropyrimidinones using Yb(III)-resin and polymer-supported scavengers under solvent-free conditions. A green chemistry approach to the Biginelli reaction. Tetrahedron Lett., 2001, 42, 7975-7978.
[38]
Shirini, F.; Zolfigol, M.A. Albadi, Melamine trisulfonic acid (MTSA) as an efficient catalyst for the synthesis of triazolo[1,2-a]indazole-triones and some 2H-indazolo[2,1-b]phthalazinetriones. J. Chin. Chem. Lett., 2011, 22, 318-321.
[39]
Hankari, S.E.; Motos-Pérez, B.; Hesemann, P.; Bouhaouss, A.; Moreau, J.J.E. Periodic mesoporous organosilica from zwitterionic precursors. Chem. Commun., 2011, 47, 6704-6706.
[40]
Rafiee, E.; Jafari, H. A practical and green approach towards synthesis of dihydropyrimidinones: Using heteropoly acids as efficient catalysts. Bioorg. Med. Chem. Lett., 2006, 16, 2463-2466.
[41]
Choudhary, V.R.; Tillu, V.H.; Narkhede, V.S.; Borate, H.B.; Wakharkar, R.D. Microwave assisted solvent-free synthesis of dihydropyrimidinones by Biginelli reaction over Si-MCM-41 supported FeCl3 catalyst. Catal. Commun., 2003, 4, 449-453.
[42]
Tayebee, R.; Amini, M.M.; Ghadamgahi, M.; Armaghan, M.H. 5PW10V2O40/Pip-SBA-15: A novel reusable organic–inorganic hybrid material as potent Lewis acid catalyst for one-pot solvent-free synthesis of 3,4-dihydropyrimidinones. J. Mol. Catal. Chem., 2013, 366, 266-274.
[43]
Kolvari, E.; Koukabi, N.; Armandpour, O. A simple and efficient synthesis of 3,4-dihydropyrimidin-2-(1H)- ones via Biginelli reaction catalyzed by nanomagnetic-supported sulfonic acid. Tetrahedron, 2014, 70, 1383-1386.
[44]
Mondal, J.; Sen, T.; Bhaumik, A. Fe3O4@mesoporous SBA-15: A robust and magnetically recoverable catalyst for one-pot synthesis of 3,4-dihydro-pyrimidin-2(1H)-ones via the Biginelli reaction. Dalton Trans., 2012, 41, 6173-6181.
[45]
Abelman, M.M.; Smith, S.C.; James, D.R. Cyclic ketones and substituted -keto acids as alternative substrates for novel Biginelli-like scaffold syntheses. Tetrahedron Lett., 2003, 44, 4559-4562.
[46]
Hazarkhani, H.; Karimi, B. N-Bromosuccinimide as an almost neutral catalyst for efficient synthesis of dihydropyrimidinones under microwave irradiation. Synthesis, 2004, 8, 1239-1242.
[47]
Zhu, Y.L.; Huang, S.L.; Pan, Y.J. Highly chemoselective multicomponent Biginelli-type condensations of cycloalkanones, urea or thiourea and aldehydes. Eur. J. Org. Chem., 2005, 2354-2367.
[48]
Sabitha, G.; Reddy, G.S.K.K.; Reddy, C.S.; Yadav, J.S. One-pot synthesis of dihydropyrimidinones using iodotrimethylsilane. facile and new improved protocolfor the Biginelli reaction at room temperature. Synlett, 2003, 2003, 858-860.
[49]
Kappe, C.O.; Falsone, S.F. Polyphosphate ester-mediated synthesis of dihydropyrimidines. improved conditions for the Biginelli reaction. Synlett, 1998, 1998, 718-720.
[50]
Yang, Z.; Fan, M.; Mu, R.; Liu, W.; Liang, Y. A facile synthesis of highly functionalized dihydrofurans based on 1,4-diazabicyclo[2.2.2]octane (DABCO) catalyzed reaction of halides with enones. Tetrahedron, 2005, 61, 9140-9146.
[51]
Marra, A.; Vecchi, A.; Chiappe, C.; Melai, B.; Dondoni, A. Validation of the copper(I)-catalyzed azide-alkyne coupling in ionic liquids. synthesis of a triazole-Linked C-disaccharide as a case study. J. Org. Chem., 2008, 73, 2458-2461.
[52]
a)Sharma, Y.O.; Degani, M.S. CO2 absorbing cost-effective ionic liquid for synthesis of commercially important alpha cyanoacrylic acids: A safe process for activation of cyanoacetic acid. Green Chem., 2009, 11, 526-530.
b)Ranu, B.C.; Jana, R. Ionic liquid as catalyst and reaction medium – a simple, efficient and green procedure for knoevenagel condensation of aliphatic and aromatic carbonyl compounds using a task-specific basic ionic liquid. Eur. J. Org. Chem., 2006, 3767-3770.
c)Zhu, A.; Jiang, T.; Wang, D.; Han, B.; Liu, L.; Huang, J.; Zhang, J.; Sun, D. Direct aldol reactions catalyzed by 1,1,3,3-tetramethylguanidine lactate without solvent. Green Chem., 2005, 7, 514-517.
(d)Xu, D.Z.; Liu, Y.; Shi, S.; Wang, Y. A simple, efficient and green procedure for Knoevenagel condensation catalyzed by [C4dabco][BF4] ionic liquid in water. Green Chem., 2010, 12, 514-517.
[53]
Jiang, T.; Gao, H.; Han, B.; Zhao, G.; Chang, Y.; Wu, W.; Gao, L.; Yang, G. Ionic liquid catalyzed Henry reactions. Tetrahedron Lett., 2004, 45, 2699-2701.
[54]
Dixit, A.; Yadav, G.D.; Chauhan, M.S.; Singh, S. Salts of 1-(chloromethyl)-DABCO: A highly efficient organocatalyst for the alcoholysis of epoxides. Curr. Catal., 2016, 5, 203-211.
[55]
Yadav, G.D. Deepa, Singh, S. 1,4-diazabicyclo[2.2.2]octane trifluoroacetate: A highly efficient organocatalyst for the cyanosilylation of carbonyl compounds under solvent free condition. Chem. Select, 2017, 2, 483-4835.
[56]
Kappe, C.O. A Reexamination of the mechanism of the Biginelli dihydropyrimidine synthesis. support for an N-acyliminium ion intermediate. J. Org. Chem., 1997, 62, 7201-7204.
[57]
CrysAlisPro, Agilent Technologies, Version 1.171.36.32 (release 02-08-2013 CrysAlis171 .NET)
[58]
Sheldrick, G.M. A short history of SHELX. Acta Crystallogr. Sect A, 2008, 64, 112-122.
[59]
Amini, M.M.; Shaabani, A.; Bazgir, A. Tangstophosphoric acid (H3PW12O40): An efficient and eco-friendly catalyst for the one-pot synthesis of dihydopyrimidin-2(1H)-ones. Catal. Commun., 2006, 7, 843-847.
[60]
Khorshidi, A.; Tabatabaeian, K.; Azizi, H.; Hashjin, M.A.; Gilandeh, E.A. Efficient one-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones catalyzed by a new heterogeneous catalyst based on co-functionalized Na+-montmorillonite. RSC Advances, 2017, 7, 17732-17740.
[61]
Fu, N.Y.; Yuan, Y.F.; Cao, Z.; Wang, S.W.; Wang, J.T.; Peppe, C. Indium(III) bromide-catalyzed preparation of dihydropyrimidinones: Improved protocol conditions for the Biginelli reaction. Tetrahedron, 2002, 58, 4801-4807.
[62]
Gholap, A.R.; Venkatesan, K.; Daniel, T.; Lahoti, R.J.; Srinivasan, K.V. Ionic liquid promoted novel and efficient one pot synthesis of 3,4-dihydropyrimidin-2-(1H)-ones at ambient temperature under ultrasound irradiation. Green Chem., 2004, 6, 147-150.
[63]
Stadler, A.; Kappe, C.O. Automated library generation using sequential microwave-assisted chemistry. application toward the Biginellli multicomponent condensation. J. Comb. Chem., 2001, 3, 624-630.
[64]
Lillo, V.J.; Saa, J.M. Towards enzyme-like, sustainable catalysis: switchable, highly efficient asymmetric synthesis of enantiopure Biginelli dihydropyrimidinones or hexahydropyrimidinones. Chem. Eur. J., 2016, 22, 17182-17186.
[65]
Nguyen, N.H.T.; Nguyen, P.P.T.; Nguyen, T.D.T.; Tran, M.N.T.; Huynh, T.N.T.; Tran, P.H. Au Nanorod: An efficient catalyst for one‐pot synthesis of 3,4‐dihydropyrimidin‐2(1H)‐ones via the multicomponent Biginelli reaction. ChemistrySelect, 2017, 2, 3932-3936.
[66]
Napoleon, A.A.; Khan, F.R.N. Potential anti-tubercular and in vitro anti-inflammatory agents: 9-substituted 1,8-dioxo-octahydroxanthenes through cascade/domino reaction by citric fruit juices. Med. Chem. Res., 2014, 23, 4749-4760.
[67]
Shirini, F.; Langarudi, M.S.N.; Seddighi, M.; Jolodar, O.G. Bi-SO3H functionalized ionic liquid based on DABCO as a mild and efficient catalyst for the synthesis of 1,8-dioxo-octahydro-xanthene and 5-arylmethylene-pyrimidine-2,4,6-trione derivatives. Res. Chem. Intermed., 2015, 41, 8483-8497.
[68]
Jin, T.S.; Qi, N.; Li, M.; Han, L.S. liu, L.B.; Li, T.S. One-pot synthesis of 9-aryl-1,8-dioxo-1,2,3,4,6,7,8- octahydroxanthenes catalyzed by p-Dodecylbenzene sulfonic acid in aqueous media. Asian J. Chem., 2007, 19, 3803-3809.
[69]
Thakur, A.; Sharma, A.; Sharma, A. Efficient synthesis of xanthenedione derivatives using cesium salt of phosphotungstic acid as a heterogeneous and reusable catalyst in water. Synth. Commun., 2016, 46, 1766-1771.
[70]
Kokkirala, S.; Sabbavarapu, N.M.; Yadavalli, V.D.N. β-cyclodextrin mediated synthesis of 1,8-dioxooctahydroxanthenes in water. Eur. J. Chem., 2011, 2, 272-275.
[71]
Li, P.; Ma, F.; Wang, P.; Zhang, Z. Highly efficient low melting mixture catalyzed synthesis of 1,8‐dioxo‐dodecahydroxanthene derivatives. Chin. J. Chem., 2013, 31, 757-763.
[72]
Amoozadeh, A.; Rahmani, S.; Bitaraf, M.; Abadi, F.B.; Tabrizian, E. Nano-zirconia as an excellent nano support for immobilization of sulfonic acid: A new, efficient and highly recyclable heterogeneous solid acid nanocatalyst for multicomponent reactions. New J. Chem., 2016, 40, 770-780.
[73]
Bhattacharjee, D.; Sutradhar, D.; Chandra, A.K.; Myrboth, B. L-proline as an efficient asymmetric induction catalyst in the synthesis of chromeno[2,3-d]pyrimidine-triones, xanthenes in water. Tetrahedron, 2017, 73, 3497-3504.

Rights & Permissions Print Cite
Article Metrics
41
3
© 2024 Bentham Science Publishers | Privacy Policy