Synthesis of Poly-Substituted Quinolines via Friedländer Hetero-Annulation Reaction Using Silica-Supported P2O5 under Solvent-Free Conditions

Document Type : Research Article


1 Department of Chemistry, Faculty of Sciences, Persian Gulf University, Bushehr, I.R. IRAN

2 Department of Chemistry, Payame Noor University (PNU), Tehran, I.R. IRAN

3 Faculty of Chemistry, Bu-Ali Sina University, Hamedan, I.R. IRAN


A highly efficient, simple and green solvent-free protocol for the preparation of poly-substituted quinolines via Friedländer hetero-annulation reaction between 2-aminoaryl ketones and carbonyl compounds in the presence of silica-supported P2O5 (P2O5 / SiO2) is described. In this method, the title compounds are obtained in high to excellent yields and in short reaction times.  


Main Subjects

[1] Jones G., “Comprehensive Heterocyclic Chemistry II”, Katritzky, A.R., Rees, C.W. and Scriven, E.F.V. (Eds.), Pergamon: New York, Pyridines and Their Benzoderivatives Synthesis, 5 (1996).
[2] Yates F.S., “Comprehensive Heterocyclic Chemistry”, Boulton, A.J. and McKillop, A. (Eds.), Pergamon Press, New York, The Structure Reaction Synthesis and uses of Heterocyclic Compounds, 2 (1984).
[3] Jones  G.,  “The  Chemistry of  Heterocyclic Compounds”, Weissberger, A. and Taylor, E.C. (Eds.), John Wiley and Sons, Chichester, 32 (1977).
[4] Bilker O., Lindo V., Panico M., Etien, A.E., Paxton T., Dell A., Rogers M., Sinden R.E., Morris H.R., Identification of Xanthurenic Acid as the Putative Inducer of Malaria Development in the Mosquito, Nature, 392, p. 289 (1998).
[5] Aggarwal A.K., Jenekhe S.A., New Conjugated Polyanthrazolines Containing Thiophene Moieties in the Main Chain Macromolecules, 24,p. 6806 (1991).
[6] Jenekhe S.A., Lu L., Alam M.M., New Conjugated Polymers with Donor-Acceptor Architectures: Synthesis and Photophysics of Carbazole-Quinoline and Phenothiazine-Quinoline Copolymers and Oligomers Exhibiting Large iIntramolecular Charge Transfer,Macromolecules, 34,p.7315 (2001).
[7] Zhang  X.,  Shetty  A.S.,  Jenekhe  S.A., Electroluminescence of Multicomponent Conjugated Polymers. 1. Roles of Polymer/Polymer Interfaces in Emission Enhancement and Voltage-Tunable Multicolor Emission in Semiconducting Polymer/ Polymer Heterojunctions,Macromolecules, 33,p. 2069 (2000).
[18] Das B., Damodar K., Chowdhury N., Kumar R.A., Application of Heterogeneous Solid Acid Catalysts for Friedlander Synthesis of Quinolines, J. Mol. Catal. A: Chem., 274,p. 148 (2007). 
[9] Jiang B., Si Y.C., Zn(II)-Mediated  Alkynylation-Cyclization of O-Trifluoroacetyl Anilines: One-Pot Synthesis of 4-Trifluoromethyl-Substituted Quinoline Derivatives, J. Org. Chem., 67,p. 9449 (2002).
[10] Mansake R.H., Kulka M., The Skraup Synthesis of Quinolines, Org. React., 7, p. 59 (1953).
[11] Linderman R.J., Kirollos,S.K., Regioselective Synthesis of Trifluoromethyl Substituted Quinolines from Trifluoroacetyl Acetylenes Tetrahedron Lett., 31,p. 2689 (1990).
[12] Theclitou  M.E.,  Robinson  L.A.,  Novel  Facile Synthesis of 2,2,4 Substituted 1,2-Dihydroquinolines via a Modified Skraup Reaction, Tetrahedron Lett., 43, p. 3907 (2002).
[13] Friedländer P.,  Ueber  O-Amidobemaldehyd, Chem. Ber., 15, p. 2572 (1882).
[14] Cheng C.C., Yan S., The Friedlander Synthesis of Quinolines ,Org. React., 28, p. 37 (1982).
[15] Gladiali S., Chelucci G., Mudadu M.S., Gastaut M.A., Thummel R.P., Friedländer Ssynthesis of Chiral Alkyl-Substituted 1,10-Phenanthrolines, J. Org. Chem., 66,p. 400 (2001).
[16] Narasimhulu  M.,  Reddy  T.S.,  Mahesh  K.C., Prabhakar P., Rao C.B., Venkateswarlu Y., Silica Supported Perchloric Acid: A Mild and Highly Efficient Heterogeneous Catalyst for the Synthesis of Poly-Substituted Quinolines via Friedlander Hetero-Annulation, J. Mol. Catal. A: Chem., 266,p. 114 (2007).
[17] Desai U.V.,  Mitragotri S.D.,  Thopate T.S.,  Pore D.M., Wadgaonkar P.P., A Highly Efficient Synthesis of Trisubstituted Quinolines Using Sodium Hydrogensulfate on Silica Gel as a Reusable Catalyst, ARKIVOC, xv, 198 (2006).
[18] Das B., Damodar K., Chowdhury N., Kumar R.A., Application of Heterogeneous Solid Acid Catalysts for Friedlander Synthesis of Quinolines, J. Mol. Catal. A: Chem., 274,p. 148 (2007).
[19] Shaabani A., Soleimani E., Badri, Z., Triflouroacetic Acid as an Efficient Catalyst for the Synthesis of Quinoline,  Synth. Commun., 37, p. 631 (2007).
[20] Muscia G.C., Bollini M., Carnevale J.P., Bruno A.M., Asis S.E., Microwave-Assisted Friedländer Synthesis of Quinolines Derivatives as Potential Antiparasitic Agents, Tetrahedron Lett., 47,p. 8811 (2006).
[21] Shaabani A.,  Rahmati A.,  Badri Z.,  Sulfonated Cellulose and Starch: New Biodegradable and Renewable Solid Acid Catalysts for Efficient Synthesis of Quinolines, Catal. Commun., 13 (2008).
[22] Yadav J.S., Rao P.P., Sreenu D., Rao R.S., Kumar V.N., Nagaiah K., Prasad A.R., Sulfamic Acid: an Efficient, Cost-Effective and Recyclable Solid Acid Catalyst for the Friedlander Quinoline Synthesis, Tetrahedron Lett., 46,p. 7249 (2005).
[23] Zolfigol  M.A.,  Salehi  P.,  Ghaderi  A.,  Shiri  M., A Catalytic and Green Procedure for Friedlander Quinoline Synthesis in Aqueous Media, Catal. Commun., 1214 (2007).
[24] De S.K., Gibbs R.A., A Mild and Efficient One-Step Synthesis of Quinolines, Tetrahedron Lett., 46, p. 1647 (2005).
[25] Zolfigol M.A.,  Salehi P.,  Ghaderi A.,  Shir, M., Tanbakouchian Z., An Eeco-Friendly Procedure for the Synthesis of Polysubstituted Quinolines Under Aqueous Media, J. Mol. Catal. A: Chem., 259,p. 253 (2006).
[26] Atechian S.,  Nock N.,  Norcross R.D.,  Ratni H., Thomas A.W., Verron J., Masciadri R., New Vistas in Quinoline Synthesis, Tetrahedron, 63,p. 2811 (2007).
[27] Arcadi A., Chiarini M., Giuseppe S.D., Marinelli F., A New Green Approach to the Friedlander Synthesis of Quinolines, Synlett, 203 (2003).
[28] Yadav J.S., Reddy B.V.S., Sreedhar P., Srinivasa R.R., Nagaiah K., Silver Phosphotungstate: A Novel and Recyclable Heteropoly Acid for Friedländer Quinoline Synthesis, Synthesis, 2381 (2004).
[29] Yadav J.S., Reddy B.V.S., Premalatha K., Bi(OTf)3-Catalyzed Friedlander Hetero-Annulation: A Rapid Synthesis of 2,3,4-Trisubstituted Quinolines, Synlett, 963 (2004).
[30] Bose D.S., Kumar R.K., An Efficient, High Yielding Protocol for the Synthesis of Functionalized Quinolines via the Tandem Addition/Annulation Reaction of O-Aminoaryl Ketones with A-Methylene Ketones,  Tetrahedron Lett., 47,p. 813 (2006).
[31] Zolfigol M.A., Salehi P., Ghaderi A., Shiri M., Iodine Catalyzed Friedlander Quinoline Synthesis Under Solvent-Free Conditions, J. Chin. Chem. Soc., 54,p. 267 (2007).
[32] Varala R.,  Enugala R.,  Adapa S.R.,  Efficient and Rapid Friedlander Synthesis of Functionalized Quinolines Catalyzed by Neodymium(III) Nitrate Hexahydrate, Synthesis, 3825 (2006).
[33] Clark J.H.,  Rhodes C.N.,  “Clean Synthesis Using Porous Inorganic Solid Catalysts and Supported Reagents”, 1st ed., Royal Society of Chemistry,UK (2000). 
[34] Kybett A.P., Sherrington D.C., “Supported Catalysts and Their Applications”, 1st ed., Royal Society of Chemistry, UK (2001).
[35] Zare A., Hasaninejad A., Beyzavi M.H., Moosavi Zare A.R., Khalafi-Nezhad A., Asadi F., Baramaki L., Jomhori-Angali S., Ghaleh-Golabi R., KF/Al2O3 as a Highly Efficient, Green, Heterogeneous, and Reusable Catalytic System for the Solvent-Free Synthesis of Carboacyclic Nucleosides via Michael Addition reaction, Synth. Commun., 39,p. 139 (2009).
[36] Zare  A.,  Hasaninejad A.,  Moosavi-Zare A.R., BeyzaviM.H., Khalafi-Nezhad A., PishahangN., ParsaeeZ., 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 (2008).
[37] Zare A., Hasaninejad A., Shekouhy M., Moosavi Zare A.R., A Green Solventless Protocol for the Synthesis of  N-Sulfonylimines in the Presence of Silica Sulfuric Acid as an Efficient, Heterogeneous and Reusable Catalyst, Org. Prep. Proced. Int., 40, p. 457 (2008).
[38] Khalafi-Nezhad  A.,  Zare  A.,  Parhami  A.,  Soltani Rad M.N., Nejabat G.R., Highly Regioselective
N-Alkylation of Benzotriazole Under Solvent-Free Conditions, J. Iran. Chem. Soc., 4,271 (2007).
[39] Hasaninejad A., Zare A., Sharghi H., Shekouhy M., Khalifeh R., Salimi Beni A., Moosavi Zare A.R.,
[39] Hasaninejad A., Zare A., Sharghi H., Shekouhy M., Khalifeh R., Salimi Beni A., Moosavi Zare A.R.,A Solvent-Free Protocol for Facile Condensation of Indoles with Carbonyl Compounds using Silica Chloride as a New, Highly Efficient, and Mild Catalyst, Can. J. Chem., 85, p. 416 (2007).
[40] Khalafi-Nezhad A., Parhami A., Soltani Rad M.N., Zolfigol M.A., Zare A., A Catalytic Method for Chemoselective Detritylation of 5'-Tritylated Nucleosides Under Mild and Heterogeneous Conditions Using Silica Sulfuric Acid as a Recyclable Catalyst, Tetrahedron Lett., 48, p. 5219 (2007).
[41] Alinezhad H., Tajbakhsh M., Soleimani R., Selective Oxidation of Benzylic and Allylic Acohols with NaOCl/Silica Gel System, J. Iran. Chem. Soc., 6, p. 288 (2009).
[42] Niknam K., Saberi D., Sadegheyan M., Deris A., Silica-Bonded S-Sulfonic Acid: an Efficient and Recyclable Solid Acid Catalyst for the Synthesis of 4,40- (arylmethylene) bis(1H-pyrazol-5-Ols), Tetrahedron Lett., 51, p. 692 (2010).
[43] Khalilzadeh  M.A.,  Hosseini  A.,  Tajbakhsh  M., Mohannazadeh F., LiAlH4/Silica Chloride as a New Chemoselective System for Reduction of Carbonyl Compounds and Phosphine Oxides, J. Iran. Chem. Soc., 5, p. 699 (2008).
[44] Zolfigol M.A., Salehi P., Shiria M., Rastegar T.F., Ghaderi A., Silica Sulfuric Acid as an Efficient Catalyst for the Friedländer Quinoline Synthesis from Simple Kketones and Ortho-Aminoaryl Ketones Under Microwave Irradiation, J. Iran. Chem. Soc., 5, p. 490 (2008).
[45] Niknam  K.,  Saberi  D.,  Nouri Sefat  M.,  Silica-Bonded S-Sulfonic Acid as a Recyclable Catalyst for Chemoselective Synthesis of 1,1-Diacetates, Tetrahedron Lett., 50, p. 4058 (2009).
[46] Mohammadpoor-Baltork  I.,  Moghadam  M., Tangestaninejad S., Mirkhani V., Zolfigol M.A., Hojati S.F., Silica Sulfuric Acid Catalyzed Synthesis of Benzoxazoles, Benzimidazoles and Oxazolo[4,5-b] Pyridines under Heterogeneous and Solvent-Free Conditions, J. Iran. Chem. Soc., 5, p. S65 (2008).
[47] Terauchi T., Machida S., Komba S., A New Method for Cleavage of Silicon-Carbon Linkers on Glass Plate Supports with Applications to Solid-Phase Syntheses on Silica Resins, Tetrahedron Lett., 51, p. 1497 (2010).
[48] Niknam  K.,  Saberi  D.,  Silica-Bonded  N-Propyl Sulfamic Acid as an Efficient Catalyst for the Formylation and Acetylation of Alcohols and Amines under Heterogeneous Conditions, Tetrahedron Lett., 50, p. 5210 (2009).
[49] Mohammadpoor-Baltork  I.,  Zolfigol  M.A., Abdollahi-Alibeik M., Novel and Chemoselective Dehydrogenation of 2-Substituted Imidazolines with Potassium Permanganate Supported on Silica Gel, Tetrahedron Lett., 45, p. 8687 (2004).
[50] Hasaninejad A., Zare A., Sharghi H., Niknam K., Shekouhy M., P2O5/SiO2 as an Eficient, Mild, and Heterogeneous Catalytic System for the Condensation of Indoles with Carbonyl Compounds under Solvent-Free Conditions ARKIVOC, xiv,39 (2007).
[51] Hasaninejad A., Zare A., Sharghi H., Shekouhy M., P2O5/SiO2  an  Efficient,  Ggreen and Heterogeneous Catalytic System for the Solvent-Free Synthesis of N-Sulfonyl Imines, ARKIVOC, xi,p. 64 (2008).
[52] Eshghi H., Gordi Z.,  P2O5/SiO2  as  an  Efficient Reagent for the Preparation of Z-Aldoximes under Solvent-Free Conditions, Phosphorus, Sulfur, and Silicon, 180, p. 1553 (2005).
[53] Mirjalili M., Zolfigol M., Bamoniri A., An Efficient Conversion of Aldehydes to Their Corresponding Acylals with P2O5/SiO2 under Mild Condition, Phosphorus, Sulfur, and Silicon, 179,p. 19 (2004).
[54] Eshghi H., Shafieyoon P., P2O5/SiO2 as an Efficient Reagent for Selective Deprotection of 1,1-Diacetates Under Solvent-Free Conditions, J. Chin. Chem. Soc., 52,p. 155 (2005).
[55] Hajipour A., Kooshki R.B., Ruoho A.E., Nitric Acid in the Presence of Supported P2O5 on Silica Gel: an Efficient and Novel Reagent for Oxidation of Sulfides to the Corresponding Sulfoxides, Tetrahedron Lett., 46, p. 5503 (2005).
[56] Mirjalili B., Zolfigol M., Bamoniri A., Amrollahi M., Hazar, A. An Efficient Procedure for Acetalization of Carbonyl Compounds with P2O5/SiO2, Phosphorus Sulfur, and Silicon, 179, p. 1397 (2004).
[57] Hajipour A.R.,  Ruoho A.E.,  Nitric  Acid  in  the Presence of P2O5 Supported on Silica Gel: a Useful Reagent for Nitration of Aromatic Compounds under Solvent-Free Conditions, Tetrahedron Lett., 46,p. 8307 (2005).
[58] Eshghi H.,  Rafei M.,  Karimi M.H.,  P2O5/SiO2 as an Efficient Reagent for Esterification of Phenols in Dry media, Synth. Commun., 31,p. 771 (2001).
[61] Hajipour A.R., Zarei A., Khazdooz L., Pourmousavi S.A., Mirjalili B.F., Ruoho A.E., Direct Sulfonylation of Aromatic Rings with Aryl or Alkyl Sulfonic Acid Using Supported P2O5/Al2O3, Phosphorus, Sulfur, and Silicon, 180,p. 2029 (2005).
[62] Eshghi H.,  Gordi Z.,  Microwave-Assisted Efficient One-Pot Synthesis of Nitriles from Aldehydes in the Presence of P2O5 /SiO2 in Solvent-Free Media, Phosphorus, Sulfur, and Silicon, 180,p. 619 (2005).
[63] Hasaninejad Niknam A.K., Zare A., Farsimadan E., Shekouhy M., Silphox [POCl3-n(SiO2)n] as a New, Efficient, and Heterogeneous Reagent for the Synthesis of Benzimidazole Derivatives Under Microwave Irradiation, Phosphorus, Sulfur, and Silicon, 184,p. 147 (2009).
[64] Khalafi-Nezhad A.,  Zare A.,  Parhami R.,  Soltani Rad M.N., Nejabat G.R., Microwave-Assisted N-Nitroarylation of Some Pyrimidine and Purine Nucleobases, Can. J. Chem., 84, p. 979 (2006).