Effective and Rapid Synthesis of Pyrido[2,3-d:6,5-d′]Dipyrimidines Catalyzed by a Mesoporous Recoverable Silica-Based Nanomaterial


A simple, rapid and effective protocol for the synthesis pyrido[2,3-d:6,5-d′]dipyrimidines has been developed via the one-pot multi-component reaction of arylaldehydes, 2-thiobarbituric acid and NH4OAc using nano-[SiO2-R-NMe2SO3H][Cl] as a mesoporous nanaocatalyst in solvent-free conditions. The remarkable features of this protocol include superiority relative to the reported methods in terms of two or more of these items: the reaction times, yields, the reaction temperature and conditions.

Effective and rapid synthesis of pyrido[2,3-d:6,5-d′]dipyrimidines catalyzed by a mesoporous recoverable silica-based nanomaterial.

This is a preview of subscription content, log in to check access.


  1. 1.

    C.M. Hussain, A.K. Mishra (2018) Nanotechnology in Environmental Science, John Wiley & Sons. 1

  2. 2.

    Kazemi M, Shiri L (2018) Recoverable Bromine-Containing Nano-Catalysts in Organic Synthesis. Mini-Rev Org Chem 15:86–104

    CAS  Article  Google Scholar 

  3. 3.

    Safajoo N, Mirjalili BBF, Bamoniri A (2019) Fe3O4@nano-cellulose/Cu(ii): a bio-based and magnetically recoverable nano-catalyst for the synthesis of 4H-pyrimido[2,1-b]benzothiazole derivatives. RSC Adv 9:1278–1283

    CAS  Article  Google Scholar 

  4. 4.

    N. Fattahi, A. Ramazani, H. Ahankar, P.A. Asiabi, V. Kinzhybalo, Silicon, in press https://doi.org/10.1007/s12633-018-9954-5

  5. 5.

    Gawande M (2014). Org Chem: Curr Res 3:1000–1037

    Google Scholar 

  6. 6.

    Bodaghifard MA, Hamidinasab M, Ahadi N (2018) Recent Advances in the Preparation and Application of Organic– inorganic Hybrid Magnetic Nanocatalysts on Multicomponent Reactions. Curr Org Chem 22:234–267

    CAS  Article  Google Scholar 

  7. 7.

    Schmies H, Bergmann A, Drnec J, Wang G, Teschner D, Kühl S, Sandbeck DJ, Cherevko S, Gocyla M, Shviro M (2018) Unravelling Degradation Pathways of Oxide-Supported Pt Fuel Cell Nanocatalysts under In Situ Operating Conditions. Adv Energy Mater 8:1701663

    Article  Google Scholar 

  8. 8.

    Zare A, Merajoddin M, Moosavi-Zare AR, Zarei M, Beyzavi MH, Zolfigol MA (2016) Design and characterization of nano-silica-bonded 3-n-propyl-1-sulfonic acid imidazolium chloride {nano-SB-[PSIM]Cl} as a novel, heterogeneous and reusable catalyst for the condensation of arylaldehydes with β-naphthol and alkyl carbamates. Res Chem Intermed 42:2365–2378

    CAS  Article  Google Scholar 

  9. 9.

    Dezfoolinezhad E, Ghodrati K, Badri R, Silicon, in press, https://doi.org/10.1007/s12633-018-9977-y

  10. 10.

    Zare A, Sadeghi-Takallo M, Karami M, Kohzadian A (2019) Synthesis, characterization and application of nano-N,N,N′,N′-tetramethyl-N-(silica-n-propyl)-N′-sulfo-ethane-1,2-diaminium chloride as a highly efficient catalyst for the preparation of N,N′-alkylidene bisamides. Res Chem Intermed 45:2999–3018

    CAS  Article  Google Scholar 

  11. 11.

    Zhao G, Tong R (2019) A solvent-free catalytic protocol for the Achmatowicz rearrangement. Green Chem 21:64–68

    CAS  Article  Google Scholar 

  12. 12.

    Dong Z, Zhang X-W, Li W, Li Z-M, Wang W-Y, Zhang Y, Liu W, Liu W-B (2019) Synthesis ofN-Fused Polycyclic Indoles via Ligand-Free Palladium-Catalyzed Annulation/Acyl Migration Reaction. Org Lett 21:1082–1086

    CAS  Article  Google Scholar 

  13. 13.

    Jadhav AM, Balwe SG, Kim JS, Lim KT, Jeong YT (2019) Indium(III)chloride catalyzed synthesis of novel 1H-pyrazolo[1,2-b]phthalazine-5,10-diones and 1H-pyrazolo[1,2-a]pyridazine-5,8-diones under solvent-free condition. Tetrahedron Lett 60:560–565

    CAS  Article  Google Scholar 

  14. 14.

    Abadi SSADM, Abdollahi-Alibeik M (2018). Silicon 10:1667–1678

    Article  Google Scholar 

  15. 15.

    Tamaddon F, Azadi D (2018) Nicotinium methane sulfonate (NMS): A bio-renewable protic ionic liquid and bi-functional catalyst for synthesis of 2-amino-3-cyano pyridines. J. Mol. Liq 249:789–794

    CAS  Article  Google Scholar 

  16. 16.

    Tripathi BP, Mishra A, Rai P, Pandey YK, Srivastava M, Yadav S, Singh J, Singh J (2017) A green and clean pathway: one pot, multicomponent, and visible light assisted synthesis of pyrano[2,3-c]pyrazoles under catalyst-free and solvent-free conditions. New J Chem 41:11148–11154

    Article  Google Scholar 

  17. 17.

    Shahid A, Ahmed NS, Saleh TS, Al-Thabaiti SA, Basahel SN, Schwieger W, Mokhtar M (2017) Solvent-Free Biginelli Reactions Catalyzed by Hierarchical Zeolite Utilizing a Ball Mill Technique: A Green Sustainable Process. Catalysts 7:84

    Article  Google Scholar 

  18. 18.

    M. Karami, A. Zare, Z. Naturforsch. (2018) 73b, 289–293

  19. 19.

    Z. Hosseinzadeh, A. Ramazani, H. Ahankar, K. Ślepokura, T. Lis, Silicon, in press, https://doi.org/10.1007/s12633-018-0034-7

  20. 20.

    Mohsenimehr M, Mamaghani M, Shirini F, Sheykhan M, Moghaddam FA (2014) One-pot synthesis of novel pyrido[2,3-d]pyrimidines using HAp-encapsulated-γ-Fe2O3 supported sulfonic acid nanocatalyst under solvent-free conditions. Chin Chem Lett 25:1387–1391

    CAS  Article  Google Scholar 

  21. 21.

    Yang L, Shi D, Chen S, Chai H, Huang D, Zhang Q, Li J (2012) Microwave-assisted synthesis of 2,3-dihydropyrido[2,3-d]pyrimidin-4(1H)-ones catalyzed by DBU in aqueous medium. Green Chem 14:945–951

    CAS  Article  Google Scholar 

  22. 22.

    Cordeu L, Cubedo E, Bandrés E, Rebollo A, Sáenz X, Chozas H, Domínguez MV, Echeverría M, Mendivil B, Sanmartin C (2007) Biological profile of new apoptotic agents based on 2,4-pyrido[2,3-d]pyrimidine derivatives. Bioorg Med Chem 15:1659–1669

    CAS  Article  Google Scholar 

  23. 23.

    Youssif S, El-Bahaie S, Nabih E (1999). J. Chem. Res., Synop 2:112–113

    Article  Google Scholar 

  24. 24.

    Trumpp-Kallmeyer S, Rubin JR, Humblet C, Hamby JM, Showalter HDH (1998). J. Med. Chem 41:1752–1763

    CAS  Article  Google Scholar 

  25. 25.

    Kovacs JA, Allegra C, Swan J, Drake J, Parrillo J, Chabner B, Masur H (1988) Potent antipneumocystis and antitoxoplasma activities of piritrexim, a lipid-soluble antifolate. Antimicrob Agents Chemother 32:430–433

    CAS  Article  Google Scholar 

  26. 26.

    Smaill JB, Palmer BD, Rewcastle GW, Denny WA, McNamara DJ, Dobrusin EM, Bridges AJ, Zhou H, Showalter HH, Winters RT, Leopold WR, Fry DW, Nelson JM, Slintak V, Elliot WL, Roberts BJ, Vincent PW, Patmore SJ (1999). J. Med. Chem 42:1803–1815

    CAS  Article  Google Scholar 

  27. 27.

    Furukawa K, Hasegawa T (1996). Chem. Abstr 124:289568c

    Google Scholar 

  28. 28.

    Kolla V, Deyanov A, Nazmetdinov FY, Kashina Z, Drovosekova L (1993) Investigation of the anti-inflammatory and analgesic activity of 2-substituted 1-aryl-6-carboxy(carbethoxy)-7-methyl-4-oxo-1, 4-dihydropyrido[2,3-d]pyrimidines. Pharm Chem J 27:635–636

    Article  Google Scholar 

  29. 29.

    Rosowsky A, Mota CE, Queener SF (1995). J. Heterocycl. Chem 32:335–340

    CAS  Article  Google Scholar 

  30. 30.

    Ellingboe JW (1996). N.J. Princeton, Chem. Abstr 124:176134q

    Google Scholar 

  31. 31.

    Donkor IO, Klein CL, Liang L, Zhu N, Bradley E, Clark AM (1995). J. Pharm. Sci 84:661–664

    CAS  Article  Google Scholar 

  32. 32.

    Corre LL, Girard AL, Aubertin J, Radvanyi F, Lasselin CB, Jonquoy A, Mugniery E, Mallet LL, Busca P, Merrer YL (2010) Synthesis and biological evaluation of a triazole-based library of pyrido[2,3-d]pyrimidines as FGFR3 tyrosine kinase inhibitors. Org Biomol Chem 8:2164–2173

    Article  Google Scholar 

  33. 33.

    Rawal RK, Tripathi R, Katti SB, Pannecouque C, Clercq ED (2007) Synthesis and evaluation of 2-(2,6-dihalophenyl)-3-pyrimidinyl-1,3-thiazolidin-4-one analogues as anti-HIV-1 agents. Bioorg Med Chem 15:3134–3142

    CAS  Article  Google Scholar 

  34. 34.

    Deyanov A, Niyazov RK, Nazmetdinov FY, Syropyatov BY, Kolla V, Konshin M (1991) Synthesis and biological activity of amides and nitriles of 2-arylamino-5-carboxy(carbethoxy)-6-methylnicotinic acids and 1-aryl-6-carbethoxy-7-methyl-4-oxo-1,4-dihydropyrido[2,3-d]pyrimidines. Pharm Chem J 25:248–250

    Article  Google Scholar 

  35. 35.

    Pastor A, Alajarin R, Vaquero JJ, Alvarez-Builla J, de Casa-Juana MF, Sunkel C, Priego JG, Fonseca I, Sanz-Aparicio J (1994) Synthesis and Structure of New Pyrido[2,3-d]pyrimidine Derivatives with Calcium Channel Antagonist Activity. Tetrahedron. 50:8085–8098

    CAS  Article  Google Scholar 

  36. 36.

    El-Gazzar ABA, Hafez HN (2009) Synthesis of 4-substituted pyrido[2,3-d]pyrimidin-4(1H)-one as analgesic and anti-inflammatory agents. Bioorg Med Chem Lett 19:3392–3397

    CAS  Article  Google Scholar 

  37. 37.

    Gangjee A, Zhu Y, Queener SF (1998). J. Med. Chem 41:4533–4541

    CAS  Article  Google Scholar 

  38. 38.

    Zare A, Kohzadian A, Abshirini Z, Sajadikhah SS, Phipps J, Beyzavi MH (2019) Nano-2-(dimethylamino)-N-(silica-n-propyl)-N,N-dimethylethanaminium chloride as a novel basic catalyst for the efficient synthesis of pyrido[2,3-d:6,5-d′]dipyrimidines. New J Chem 43:2247–2257

    CAS  Article  Google Scholar 

  39. 39.

    Mamaghani M, Moslemi L, Badrian A (2018). Mod Org Chem Res 3:8

    Article  Google Scholar 

  40. 40.

    Naeimi H, Nejadshafiee V, Islami MR (2016) Iron (III)-doped, ionic liquid matrix-immobilized, mesoporous silica nanoparticles: Application as recyclable catalyst for synthesis of pyrimidines in water. Micropor Mesopor Mater 227:23–30

    CAS  Article  Google Scholar 

  41. 41.

    Naeimi H, Didar A, Mol J (2017). Struct. 1137:626–633

    CAS  Google Scholar 

  42. 42.

    Naeimi H, Didar A, Rashid Z, Zahraie Z (2017) Sonochemical synthesis of pyrido[2,3-d:6,5-d′]-dipyrimidines catalyzed by [HNMP]+[HSO4]− and their antimicrobial activity studies. J Antibiot 70:845–852

    CAS  Article  Google Scholar 

  43. 43.

    Naeimi H, Didar A (2017) Efficient sonochemical green reaction of aldehyde, thiobarbituric acid and ammonium acetate using magnetically recyclable nanocatalyst in water. Ultrason Sonochem 34:889–895

    CAS  Article  Google Scholar 

  44. 44.

    Naeimi H, Didar A, Rashid Z, Iran J (2017). Chem Soc 14:377–385

    CAS  Google Scholar 

Download references


The authors thank Research Council of Payame Noor University for the support of this work.

Author information



Corresponding authors

Correspondence to Alireza Kohzadian or Abdolkarim Zare.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material


(DOCX 3314 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Kohzadian, A., Zare, A. Effective and Rapid Synthesis of Pyrido[2,3-d:6,5-d′]Dipyrimidines Catalyzed by a Mesoporous Recoverable Silica-Based Nanomaterial. Silicon 12, 1407–1415 (2020). https://doi.org/10.1007/s12633-019-00235-0

Download citation


  • Pyrido[2,3-d:6,5-d′]dipyrimidines. Nano-[SiO2-R-NMe2SO3H][cl]. Mesoporous nanocatalyst. Multi-component reaction. Solvent-free