Citation: CHEN Chen, RUAN Hongli, LÜ Le, SONG Zhixi, LÜ Chengwei, AN Yue. Synthesis of Pyridazine Derivatives by Base-Catalyzed Three-Component Reaction of Aldehyde, Malononitrile and Phthalhydrazide[J]. Chinese Journal of Applied Chemistry, ;2020, 37(5): 502-511. doi: 10.11944/j.issn.1000-0518.2020.05.190311 shu

Synthesis of Pyridazine Derivatives by Base-Catalyzed Three-Component Reaction of Aldehyde, Malononitrile and Phthalhydrazide

College of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian, Liaoning 116029, China

Corresponding author: LÜ Chengwei, chengweilv@126.com
Received Date: 19 November 2019
Revised Date: 6 January 2020
Accepted Date: 20 February 2020

Fund Project: the Department of Science and Technology of Liaoning Province 2019-ZD-0470the Department of Science and Technology of Liaoning Province 2019-MS-215Supported by the Department of Science and Technology of Liaoning Province(No.2019-MS-215, No.2019-ZD-0470)

Figures(3)

Catalytic amount of organic base triethylamine (Et₃N) or inorganic base dipotassium hydrogen phosphate (K₂HPO₄·3H₂O) is proved to effectively promote the three components reaction of aromatic aldehyde, malononitrile and phthalhydrazide under conventional heating conditions. As expected, introduction of water is favorable to the reaction. A series of 1H-pyrazole [1, 2-b]pyridazine-5, 10-diones derivatives was synthesized in the yield of 39%~97%. Both catalysts are soluble in water, and introduction of water also facilitate the separation of the catalyst after reaction. This approach also has advantages of mild reaction conditions, green environmental protection, simple operation and convenient post-treatment.
- trimethylamine,
- dipotassium hydrogen phosphate trihydrate,
- base catalytic,
- multi-component reactions,
- phthalazines derivatives
1. [1]
  Soheilizad M, Adib M, Sajjadifar S. One-Pot and Solvent-Free Synthesis of Aliphatic and Aromatic 1H-Indazolo[2, 1-b]phthalazinetriones Catalyzed by Boron Sulfonic Acid[J]. Monatsh Chem, 2014,145(8):1353-1356. doi: 10.1007/s00706-014-1194-9
2. [2]
  Sinkkonen J, Ovcharenko V, Zelenin K N. ¹H and ¹³C NMR Study of 1-Hydrazino-2, 3-Dihydro-1H-Pyrazolo[1, 2-a]pyridazine-5, 8-Diones and -1H-Pyrazolo[1, 2-b]phthalazine-5, 10-Diones and Their Ring-Chain Tautomerism[J]. Eur J Org Chem, 2002,2002(13):2046-2053. doi: 10.1002/1099-0690(200207)2002:13<2046::AID-EJOC2046>3.0.CO;2-C
3. [3]
  Grasso S, De Sarro G, De Sarro A. Synthesis and Anticonvulsant Activity of Novel and Potent 6, 7-Methylenedioxyphthalazin-1(2H)-Ones[J]. J Med Chem, 2000,43(15):2851-2859. doi: 10.1021/jm001002x
4. [4]
  EL-Sakka S, Soliman A H, Imam A. Synthesis, Antimicrobial Activity and Electron Impactof Mass Spectra of Phthalazine-1, 4-Dione Derivatives[J]. Afinidad, 2009,66(540):167-172.
5. [5]
  Ryu C K, Park R E, Ma M Y. Synthesis and Antifungal Activity of 6-Arylamino-Phthalazine-5, 8-Diones and 6, 7-Bis(Arylthio)-Phthalazine-5, 8-Diones[J]. Bioorg Med Chem Lett, 2007,17(9):2577-2580. doi: 10.1016/j.bmcl.2007.02.003
6. [6]
  Li J, Zhao Y F, Yuan X Y. Synthesis and Anticancer Activities of Novel 1, 4-Disubstituted Phthalazines[J]. Molecules, 2006,11(7):574-582. doi: 10.3390/11070574
7. [7]
  Franklin E C. Heterocyclic Nitrogen Compounds.I.Pentacyclic Compounds[J]. Chem Rev, 1935,16(3):305-361. doi: 10.1021/cr60055a001
8. [8]
  Bergstrom F W. Heterocyclic Nitrogen Compounds.Part IIA.Hexacyclic Compounds:Pyridine, Quinoline, and Isoquinoline[J]. Chem Rev, 1944,35(2):77-277. doi: 10.1021/cr60111a001
9. [9]
  Lichtenthaler F W. Unsaturated O- and N-heterocycles from Carbohydrate Feedstocks[J]. Acc Chem Res, 2002,35(9):728-737. doi: 10.1021/ar010071i
10. [10]
  Litvinov V P. Multicomponent Cascade Heterocyclisation as a Promising Route to Targeted Synthesis of Polyfunctional Pyridines[J]. Russ Chem Rev, 2003,72(1):69-85. doi: 10.1070/RC2003v072n01ABEH000764
11. [11]
  Wu H, Chen X M, Wan Y. Synthesis and Luminescence of 7-Amino-2H-Indazolo[2, 1-b]phthalazine-1, 6, 11(13H)-Triones Catalyzed by Silica Sulfuric Acid[J]. Lett Org Chem, 2009,6(3):219-223.
12. [12]
  Tayebee R, Abdizadeh M F, Maleki B. Heteropolyacid-Based Ionic Liquid[Simp]₃PW₁₂O₄₀ Nanoparticle as a Productive Catalyst for the One-Pot Synthesis of 2H-Indazolo[2, 1-b]phthalazine-Triones under Solvent-Free Conditions[J]. J Mol Liq, 2017,241:447-455. doi: 10.1016/j.molliq.2017.06.033
13. [13]
  Mirhosseini-Eshkevari B, Ghasemzadeh M A, Safaei-Ghomi J. An Efficient and Green One-Pot Synthesis of Indazolo[1, 2-b]phthalazinetriones via Three-Component Reaction of Aldehydes, Dimedone, and Phthalhydrazide Using Fe₃O₄@SiO₂ Core-Shell Nanoparticles[J]. Res Chem Intermed, 2015,41(10):7703-7714. doi: 10.1007/s11164-014-1854-8
14. [14]
  Saha M, Phukan S, Jamatia R. Solvent Free, Ni-Nanoparticle Catalyzed Greener Synthesis and Photophysical Studies of Novel 2H-Indazolo[2, 1-b]phthalazine-Trione Derivatives[J]. RSC Adv, 2013,3(6):1714-1721. doi: 10.1039/C2RA22396A
15. [15]
  Shaterian H R, Ghashang M, Feyzi M. Silica Sulfuric Acid as an Efficient Catalyst for the Preparation of 2H-Indazolo[2, 1-b]phthalazine-Triones[[J]. Appl Catal A-Gen, 2008,345(2):128-133. doi: 10.1016/j.apcata.2008.04.032
16. [16]
  Ghahremanzadeh R, Shakibaei G I, Bazgir A. An Efficient One-Pot Synthesis of 1H-Pyrazolo[1, 2-b]phthalazine-5, 10-Dione Derivatives[J]. Synlett, 2008(8):1129-1132.
17. [17]
  Raghuvanshi D S, Singh K N. A Highly Efficient Green Synthesis of 1H-Pyrazolo[1, 2-b]phthalazine-5, 10-Dione Derivatives and Their Photophysical Studies[J]. Tetrahedron Lett, 2011,52(43):5702-5705. doi: 10.1016/j.tetlet.2011.08.111
18. [18]
  Sabour F H, Nasr-Esfahani M, Mohammadpoor-Baltork I. A Convenient Approach for the Synthesis of Various Derivatives of Pyrazolo[1, 2-b]phthalazinediones in the Presence of an Efficient Supported Basic Ionic Liquid at Ambient Temperature and Solvent-Free Media[J]. J Iran Chem Soc, 2018,15(3):671-683. doi: 10.1007/s13738-017-1267-x
19. [19]
  Piltan M. Preparation of 1H-Pyrazolo[1, 2-b]phthalazine-5, 10-Diones Using ZrO₂ Nanoparticles as a Catalyst under Solvent-Free Conditions[J]. Heterocycl Commun, 2017,23(5):401-403.
20. [20]
  Tayebee R, Maleki B. A New Simple Method for the Preparation of PbO Nanoparticles and Implementation of an Efficient and Reusable Catalytic System for the Synthesis of 1H-Pyrazolo[1, 2-b]phthalazine-5, 10-Diones[J]. J Iran Chem Soc, 2017,14(6):1179-1188. doi: 10.1007/s13738-017-1068-2
21. [21]
  Sangani C B, Makwana J A, Duan Y T. Synthesis of 1H-Pyrazolo[1, 2-b]phthalazine-5, 10-Dione Derivatives:Assessment of Their Antimicrobial, Antituberculosis and Antioxidant Activity[J]. Res Chem Intermed, 2016,42(3):2101-2117. doi: 10.1007/s11164-015-2138-7
22. [22]
  Vafaee A, Davoodnia A, Pordel M. An Efficient and High-Yielding One-Pot Synthesis of 1H-Pyrazolo[1, 2-b]phthalazine-5, 10-Diones Catalyzed by Sodium Hydrogen Carbonate under Solvent-Free Conditions[J]. Orient J Chem, 2015,31(4):2153-2158. doi: 10.13005/ojc/310437
23. [23]
  Nabid M R, Rezaei S J T, Ghahremanzadeh R. Ultrasound-Assisted One-Pot, Three-Component Synthesis of 1H-Pyrazolo[1, 2-b]phthalazine- 5, 10-Diones[J]. Ultrason Sonochem, 2010,17(1):159-161.
24. [24]
  Saiprathima P, Srinivas K, Rao M M. "On water" Catalysis:An expeditious Approach for the Synthesis of Quaternary Centered 3-Hydroxy-3-(nitromethyl)indolin-2-one Derivatives[J]. Green Chem, 2015,17:2339-2343. doi: 10.1039/C4GC02203C
25. [25]
  Liu X, Zhang S B, Zhu H. Copper(I)-Catalyzed Tandem One-Pot Synthesis of 2-Arylthiobenzothiazoles and 2-Arylthiobenzoxazoles in Water[J]. J Org Chem, 2018,83(19):11703-11711. doi: 10.1021/acs.joc.8b01644
26. [26]
  Lv C W, Wang J J, Li F. Efficient Synthesis of 2-Amino-3-Cyano-4H-Pyran Derivatives via a Non-catalytic One-Pot Three-Component Reaction[J]. Res Chem Intermed, 2018,44(2):1035-1043. doi: 10.1007/s11164-017-3151-9
27. [27]
  Yu S J, Wu S, Zhao X M. Green and Efficient Synthesis of Acridine-1, 8-Diones and Hexahydroquinolines via a KH₂PO₄ Catalyzed Hantzsch-Type Reaction in Aqueous Ethanol[J]. Res Chem Intermed, 2016,43(5):3121-3130.
28. [28]
  RUAN Hongli, ZHANG Jingyuan, SUN Sai. N-Bromosuccinimide Mediated the Reaction of 2-Hydroxyaryl Aldehydes with Meldrum's Acid for Synthesis of Coumarin-3-carboxylic Acids[J]. Chinese J Org Chem, 2017,37(8):2139-2144.
29. [29]
  XIAO Di, ZHENG Wang, WEI Xiaoyu. Choline Chioride Promoted Synthesis of Coumarin-3-carboxylic Acids[J]. Chinese J Appl Chem, 2017,34(11):1295-1300. doi: 10.11944/j.issn.1000-0518.2017.11.170005
30. [30]
  Zhang X, Li K, Li H. Dipotassium Hydrogen Phosphate as Reducing Agent for the Efficient Reduction of Graphene Oxide Nanosheets[J]. J Colloid Interfaace Sci, 2013,409(11):1-7.
31. [31]
  Lv C W, Gao S, Xiao D. KH₂PO₄ Promoted Practical and Environmentally Friendly Preparation of Coumarin-3-carboxylic Acids under Solvent-Free Condition[J]. Heterocycles, 2016,92(9):1698-1705. doi: 10.3987/COM-16-13510
32. [32]
  Kidwai M, Chauhan R. A Rapid and an Efficient Route to the One-Pot, Multicomponent Synthesis of 1H-Pyrazolo[1, 2-b]phthalazine-5, 10-Dione Ring Systems[J]. J Heterocycl Chem, 2014,51(6):1689-1696. doi: 10.1002/jhet.1809
33. [33]
  Azarifar A, Nejat-Yami R, Azarifar D. Nano-ZnO:An Efficient and Reusable Catalyst for One-Pot Synthesis of 1H-pyrazolo[1, 2-b]phthalazine-5, 10-diones and Pyrazolo[1, 2-a] [1, 2, 4]triazole-1, 3-diones[J]. J Iran Chem Soc, 2013,10:297-306. doi: 10.1007/s13738-012-0159-3
34. [34]
  Nabid M R, Rezaei S J T, Ghahremanzadeh R. Ultrasound-Assisted One-Pot, Three-Component Synthesis of 1H-Pyrazolo[1, 2-b]phthalazine- 5, 10-Diones[J]. Ultrason Sonochem, 2010,17(1):159-161.
35. [35]
  Kefayati H, Delafrooz A, Homayoon S. Ultrasound-Assisted Synthesis of Pyrazolo[1, 2-b]phthalazines and Dihydrospiro[Indoline-3, 1'-Pyrazolo[1, 2-b]phthalazines] Using TBAF as an Efficient Phase-Transfer Catalyst[J]. Russ J Gen Chem, 2016,86(7):1735-1740. doi: 10.1134/S107036321607032X
36. [36]
  Lamera E, Bouacida S, Merazig H. DMAP as a New Efficient Catalyst for the One-Pot Synthesis of Condensed Phthalazines[J]. Z Naturforsch B, 2017,72(5):361-368. doi: 10.1515/znb-2016-0262
37. [37]
  Koyel P, Sanjay P, Asish R D. Synthesis of a Diversified Combinatorial Library of 1H-pyrazolo[1, 2-b]phthalazine-5, 10-dione Derivatives Applying Sustainable Carbon-based Solid Acid Catalyst Involving a Domino Four-component Reaction[J]. Monatsh Chem, 2014,145(8):1343-1352. doi: 10.1007/s00706-014-1195-8
38. [38]
  Franca B, Silvia C, Leonetto F. Clean Synthesis in Water.Part 2:Uncatalysed Condensation Reaction of Meldrum's Acid and Aldehydes[J]. Tetrahedron Lett, 2001,42(31):5203-5205. doi: 10.1016/S0040-4039(01)00978-9
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