KF/Al2O3: As a Solid Phase and Recyclable Basic Catalyst for Synthesis Mono and Bis Pyrimidine Derivatives

Document Type : Research Article


1 Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman 76175493, Iran.

2 Department of Chemistry, Faculty of Sciences, Najafabad Branch, Islamic Azad University, Najafabad, I.R. IRAN


KF/Al2O3 as a green and efficient catalyst has been used for the synthesis of mono and bis pyrimidine derivatives via three-component reaction of amidines, malononitrile, and aldehydes in EtOH at reflux. The great advantage of this catalyst is the ease of handling. KF/Al2O3 can be used and removed by filtration, avoid cumbersome aqueous workups and decrease solvent waste handling issues. The additional benefit is achieved by taking advantage of the strongly basic nature of KF/Al2O3, which allows replacing organic bases in the reaction. A number of advantages are with this method such as no special handing necessity of catalyst, easy monitoring of reaction process, convenient workup procedure and high yields in short reaction times.


Main Subjects

[1] Blass B.E., KF/Al2O3 Mediated Organic Synthesis, Tetrahedron, 58: 9301-9320 (2002).
[4] Kumar H.M.S., Reddy B.V.S., Reddy E.J., Yadav J.S., Microwave-assisted Eco-friendly Synthesis of
2-Alkylated Hydroquinones in Dry Media
, Green Chem., 1: 141-142 (1999)
[7] Boruah M., Konwar D., KF/Al2O3: Solid-supported Reagent Used in 1,3-Dipolar Cycloaddition Reaction of Nitrile Oxide, Synth. Commun., 42: 3261-3268 (2012).
[8] Kharbangar I., Rohman R., Mecadon H., Myrboh B., KF-Al2O3 as an Efficient and Recyclable Basic Catalyst for the Synthesis of 4H-Pyran-3-carboxylates and 5-Acetyl-4H-pyrans, International Journal of Organic Chemistry, 2: 282-286 (2012).
[9] Dard B.A., Zaheerb Z., Fatemaa S., Jadav S., Farooqui, M., KF-Al2O3 Catalyzed Domino One-pot, Three-component Synthesis of 3,5-Disubstituted-1,2,4-oxadiazoles Under Microwave-Assisted Solvent Free Conditions and Their Biological Activity, International Journal of Pharmaceutical Research & Allied Sciences, 4: 93-99 (2015).
[10] Wang X.S., Zhou J.X., Zeng Z.S., Li Y.L., Shi D.Q., Tua S.J., One-pot Synthesis of Pyrano[3,2-c]pyran Derivatives Catalyzed by KF/Al2O3, Arkivoc, xi:107-113 (2006).
[11] Movassagh B., Soleiman-Beigi M., Nazari M., A Facile KF/Al2O3-mediated, One-pot Synthesis of Symmetrical Trithiocarbonates from Alkyl Halides and Carbon Disulfide, Chem. Lett., 37: 22-23 (2008).
[15] Zhu J., Bienayme H., "Multicomponent Reactions", Wiley-VCH, Weinheim (2005).
[16] Tietze L.F., Domino Reactions in Organic Synthesis, Chem. Rev., 96: 115-136 (1996).
[17] Tietze L.F., Beifuss U., Sequential Transformations in Organic Chemistry: A Synthesis Strategy with a Future, Angew. Chem. Int. Ed. Engl., 32: 131-163 (1993).
[18] Mohammadi Ziarani G., Mousavi S., Lashgari N., Badiei A., Shakiba M., Application of Sulfonic Acid Functionalized Nanoporous Silica (SBA-Pr-SO3H) in the Green One-pot Synthesis of Polyhydroacridine Libraries, Iran. J. Chem. Chem. Eng. (IJCCE), 32: 9-16 (2013).
[20] Shaabani A., Bazgir A., Arab Ameri S., Sharifi Kiasaraie M., Samadi S., Comparison of Catalytic Effect of Alkali and Alkaline Earth Metals Hydrogen Sulfate: As the Promoter for an Efficient Synthesis of 3,4-Dihydropyrimidin-2(1H)-ones under Solvent-Free Conditions, Iran. J. Chem. Chem. Eng. (IJCCE), 24: 67-71 (2005).
[21] Mohammadi Ziarani G., Aleali F., Lashgari N., Badiei, A., An Efficient Green Approach for the Synthesis of Structurally Diversified Spirooxindoles Using Sulfonic Acid Functionalized Nanoporous Silica (SBA-Pr-SO3H), Iran. J. Chem. Chem. Eng. (IJCCE), 35: 17-23 (2016).
[24] Mehta P.D., Sengar N.P.S., Pathak A.K., 2-Azetidinone: A New Profile of Various Pharmacological Activities, Eur. J. Med. Chem., 45: 5541-5560 (2010).
[26] Shabani M., Yousefi M., Abdouss M., Aziznejad F., Shahrozvand H., Kinetics and Mechanism of the Substitution Reaction of Amine in (bis(Acetyle Acetonato) Ethylenediimine) (Diamine)Cobalt(III) Perchlorate with N3-, Br- and NCS-, Iran. J. Chem. Chem. Eng. (IJCCE), 30: 49-54 (2011).
[28] Iqbal P.F., Parveen H., Bhat A.R., Hayat F., Azam A., Synthesis, Characterization, Antiamoebic Activity and Toxicity of Novel Bisdioxazole Derivatives, Eur. J. Med. Chem., 44: 4747-4751 (2009).
[29] Cox R.A., Macromolecular Structure and Properties of Ribonucleic Acids, Quart. Rev. Chem. Soc., 22: 499-526 (1968).
[30] Agarwal O.P., "Organic Chemistry; Reaction and Reagent", Krishna Prakashan Media, New Delhi (2006).
[31] Jain M.K., Sharnevsas S.C., "Modern Organic Chemistry", Jalandhar-Delhi (2008).
[32] Mitsuya H., "Anti-HIV Nucleosides: Past, Present and Future", Chapman and Hall, New York (1997).
[33] Kompis I., Wick A., Synthese Von 4-Halogensubstituierten Analogen Von Trimethoprim, Helv. Chim. Acta, 60: 3025-3034 (1977).
[35] Cannito A., Pemmsin M., Lnu-Due C., Hoguet F., Gaultier C., Narcisse J., Synthesis and Pharmacological Activities of Some 3-Substituted Thienopyrimidin-4-one-2-thiones, Eur. J. Med. Chem., 25: 635-639 (1990).
[36] Smith P.A.S., Kan R.O., Cyclization of Isothiocyanates as a Route to Phthalic and Homophthalic Acid Derivatives, J. Org. Chem., 29: 2261-2265 (1964).
[37] Polak A., Scholer H.J., Mode of Action of 5-Fluorocytosine and Mechanisms of Resistance, Chemotherapy, 21: 113-130 (1975).
[38] So H.L., Ibrahim M.E.D., Design and Synthesis of New Anticancer Pyrimidines with Multiple-kinase Inhibitory Effect, Bioorg. Med. Chem., 18: 3860-3874 (2010).
[40] Kapupara P.P., Dholakia S.P., Patel V.P., Suhagia B.N., Design, Synthesis and Pharmacological Screening
of 4-Amino-5-pyrimidinecarbonitriles as Potential Anti-inflammatory Agents
, J. Chem. Pharm. Res., 2: 287-294 (2010).
[41] Deshmukh M.B., Anbhule P.V., Jadhav S.D., Jagtap S.S., Patil D.R., Salunkhe S.M., Sankpa S.A., A Novel and Environmental Friendly, One-step Synthesis of 2,6-Diamino-4-phenyl pyrimidine-5-carbonitrile Using Potassium Carbonate in Water, Indian J. Chem., 47B: 792-795 (2008).
[45] Zare A., Hasaninejad A., Moosavi-Zare A.R., Beyzavi M.H., Khalafi-Nezhad A., Pishahang N., Parsaee Z., Mahdavinasab P., Hayati N., KF/Al2O3 as a Highly Efficient Reagent for the Synthesis of N-Aryl Derivatives of Pyrimidine and Purine Nucleobases, Arkivoc, xvi: 178-188 (2008).
[47] Abaszadeh M., Seifi M., Asadipour A., Ultrasound Promotes One-pot Synthesis of 1,4-Dihydropyridine and Imidazo[1,2-a]quinolone Derivatives, Catalyzed by ZnO Nanoparticles, Res. Chem. Intermed., 41: 5229-5238 (2015).