Startseite Preparation of 1H-pyrazolo[1,2-b]phthalazine-5,10-diones using ZrO2 nanoparticles as a catalyst under solvent-free conditions
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Preparation of 1H-pyrazolo[1,2-b]phthalazine-5,10-diones using ZrO2 nanoparticles as a catalyst under solvent-free conditions

  • Mohammad Piltan EMAIL logo
Veröffentlicht/Copyright: 23. September 2017
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Heterocyclic Communications
Aus der Zeitschrift Heterocyclic Communications Band 23 Heft 5

Abstract

Zirconium oxide nanoparticles are an efficient catalyst for the preparation of 1H-pyrazolo[1,2-b]phthalazine-5,10-diones via a three-component reaction of phthalhydrazide, aromatic aldehydes and malononitrile under solvent-free conditions.

Keywords: aromatic aldehydes; multicomponent reaction; nanoparticles; phthalhydrazide; solvent-free; zirconium oxide

Introduction

Multi-component reactions (MCRs) have become a powerful, fast and convenient approach for the synthesis of complex heterocyclic compounds from simple and readily available starting materials [1]. MCRs have advantages over classical reaction strategies including greater efficiency and shorter reaction time [2], [3]. Nanometer-sized particles have recently been considered as an alternative matrix for supporting catalytic reactions. Reusable nanoscale heterogeneous catalysts show high catalytic activity due to a high specific surface area and low-coordination sites [4].

1H-Pyrazolo[1,2-b]phthalazine-5,10-dione derivatives containing fused hydrazine are an important class of pharmaceutical compounds that exhibit a wide spectrum of biological activities [5], [6], [7]. Such compounds are relatively difficult to synthesize [8], [9], [10], [11], [12], [13], [14], [15], [16], [17].

Therefore, the development of simple methods for the synthesis of pyrazolo[1,2-b]phthalazine-5,10-diones is important. In continuation of our efforts to develop a new methodology for the synthesis of heterocyclic compounds [18], [19], [20], [21], we now report the use of ZrO2 nanoparticles as an efficient catalyst for the preparation of 1H-pyrazolo[1,2-b]phthalazine-5,10-diones 4a–g from phthalhydrazide, aromatic aldehydes and malononitrile (Scheme 1).

Scheme 1 Synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-diones 4a–g.
Scheme 1

Synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-diones 4a–g.

Results and discussion

Initially, different reaction parameters for the synthesis of compound 4a by the three-component condensation reaction using benzaldehyde as a model reaction were optimized. The scrutinized parameters were temperature, time of reaction solvents, including ethanol, tetrahydrofuran, acetonitrile, dichloromethane and water, and solvent-free conditions. The best results were obtained under solvent-free conditions. When 10 mol%, 15 mol% and 20 mol% of ZrO2 nanoparticles were used, the yields of 4a were 82%, 91% and 91%, respectively, and the yields were much lower in any solvent. Only 20% of 4a was obtained in the absence of a catalyst. Under optimized solvent-free conditions, the reaction was conducted with 15 mol% of the catalyst at 100°C for 45 min and furnished 4a with a 91% yield. The reactions with other aromatic aldehydes conducted using this optimized procedure were also similarly effective. All reactions were completed within 35–45 min and afforded good yields of products 4b–g. The aromatic aldehydes substituted with either electron-donating or electron-withdrawing groups underwent the reaction smoothly and afforded the products in good yields. As seen from Table 1, the method compares well with other known preparations of the model product 4a. The suggested mechanism for the formation of products 4 involves generation of the intermediate compounds 5–7, as shown in Scheme 2.

Table 1

Comparison of the results of different preparations of 4a.

EntryCatalystConditionsTime (min)Yield (%) [Ref]
1p-TSA (30 mol%)[Bmim]Br/100°C18094 [8]
2TBBDA/PBBSEtOH, 100°C15/4089/65 [9]
3Et3N (20 mol%)EtOH, 50°C, ultrasound6090 [10]
4[Bmim]OH (20 mol%)MW, 100 W, 45°C496 [11]
5CuI NPsSolvent-free, 70°C2791 [12]
7APTES-MNPs (10 mol%)Solvent-free, rt1992 [14]
8NiCl26H2OEtOH, reflux18087 [16]
9AL-KIT-6EtOH, 60°C24093 [17]
10ZrO2 NPsSolvent-free, 100°C4091 (present work)
Scheme 2 A plausible mechanism for the formation of compounds 4.
Scheme 2

A plausible mechanism for the formation of compounds 4.

Conclusions

The reaction between phthalhydrazide, malononitrile and aromatic aldehydes in the presence of nano-ZrO2 offers a simple one-pot access to pyrazolo[1,2-a][1,2,4]triazole-1,3-dione derivatives of potential synthetic and pharmacological interest. The simplicity, easy workup, as well as the safety and reusability of the catalyst are advantages of this method.

Experimental

Melting points were determined on an Electrothermal 9100 apparatus and are not corrected. Infrared (IR) spectra were recorded in KBr pellets on a Shimadzu 460 spectrometer. 1H NMR (400 MHz) and 13C NMR (100 MHz) spectra were recorded on a Bruker AVANCE 400 spectrometer using DMSO-d6 as a solvent. Electron impact mass spectra were obtained at 70 eV on a Finnigan MAT 8430 mass spectrometer. Elemental analyses for C, H and N were obtained on a Heraeus CHNO Rapid analyzer. All commercially available chemicals and reagents were used without further purification. In all experiments, ZrO2 (5–25 nm, Plasma Chem GmbH) was used.

General procedure for the preparation of 1H-pyrazolo[1,2-b]phthalazine-5,10-diones 4a–g

A mixture of phthalhydrazide (1 mmol), aromatic aldehyde (1 mmol), malononitrile (1 mmol) and ZrO2 nanoparticles (15 mol%) was stirred at 100°C under solvent-free conditions for 35–45 min. After completion of the reaction, the resultant precipitate was crystallized from MeOH to afford pure product 4.

3-Amino-1-phenyl-5,10-dihydro-5,10-dioxo-1H-pyrazolo[1,2-b]phthalazine-2-carbonitrile (4a)

Yellow powder; yield 0.29 g (91%); mp 276–278°C; IR: 3361, 3292, 3248, 2198, 1659, 1567 cm−1; 1H NMR: δ 6.12 (s, 1H, CH), 7.31–7.46 (m, 5H, ArH), 7.92–8.26 (m, 6H, ArH and NH2); 13C NMR: δ 61.8, 62.8, 116.3, 126.6, 126.7, 127.1, 128.2, 128.5, 128.7, 129.1, 133.7, 134.6, 138.4, 149.8, 153.6, 156.8; EI-MS: m/z 316. Anal. Calcd for C18H12N4O2 (316.32): C 68.35, H 3.82, N 17.71. Found: C 68.28, H 3.75, N 17.78.

3-Amino-1-(2-methylphenyl)-5,10-dihydro-5,10-dioxo-1H-pyrazolo[1,2-b]phthalazine-2-carbonitrile (4b)

Yellow powder; yield 0.29 g (88%); mp 247–249°C; IR: 3383, 3300, 2207, 1659, 1603 cm−1; 1H NMR: δ 2.43 (3H, s, CH3), 6.30 (1H, s, CH), 7.17–7.28 (4H, m, Ar), 7.96–8.25 (6H, m, Ar and NH2); 13C NMR: δ 20.1, 61.2, 62.9, 122.0, 126.7, 127.2, 127.7, 128.1, 128.3, 128.5, 129.0, 130.3, 133.8, 134.8, 135.2, 136.5, 153.7, 154.2, 156.9; EI-MS: m/z 330. Anal. Calcd for C19H14N4O2 (330.35): C 69.09, H 4.27, N 16.95. Found: C 68.95, H 4.25, N 16.96.

3-Amino-1-(3-methylphenyl)-5,10-dihydro-5,10-dioxo-1H-pyrazolo[1,2-b]phthalazine-2-carbonitrile (4c)

Yellow powder; yield 0.29 g (89%); mp 250–252°C; IR: 3361, 3259, 2194, 1658, 1570 cm−1; 1H NMR: δ 2.25 (3H, s, CH3), 6.08 (1H, s, CH), 7.11–7.22 (4H, m, Ar), 7.97–8.26 (6H, m, Ar and NH2); 13C NMR: δ 21.0, 61.2, 62.8, 122.0, 122.3, 127.0, 127.4, 127.9, 128.4, 128.6, 128.9, 131.4, 134.2, 134.7, 135.8, 136.4, 154.1, 154.4, 157.3; EI-MS: m/z 330.

Anal. Calcd for C19H14N4O2 (330.35): C 69.09, H 4.27, N 16.95. Found: C 69.12, H 4.18, N 16.85.

3-Amino-1-(3-methoxyphenyl)-5,10-dioxo-5,10-dihydro-1H-pyrazolo[1,2-b]phthalazine-2-carbonitrile (4d)

Yellow powder; yield 0.30 g (87%); mp 247–249°C; IR: 3363, 3260, 2189, 1655, 1567 cm−1; 1H NMR: δ 3.76 (s, 3H, OCH3); 6.15 (s, 1H), 6.90 (d, 3J=8.0 Hz, 1H), 6.96–6.99 (m, 2H), 7.26 (t, 3J=7.5 Hz, 1H), 7.65–7.99 (m, 2H), 8.09–8.12 (m, 3H, NH2, CH), 8.25–8.28 (m, 1H); 13C NMR: δ 55.7, 61.2, 62.6, 112.8, 114.5, 119.2, 124.3, 126.8, 127.2, 128.9, 129.1, 129.2, 129.6, 134.3, 137.6, 150.6, 153.2, 157.1, 160.0; EI-MS: m/z 346. Anal. Calcd for C18H11N5O4 (346.35): C 65.89, H 4.07, N 16.18. Found: C 65.78, H 4.15, N 16.24.

3-Amino-1-(4-chlorophenyl)-5,10-dihydro-5,10-dioxo-1H-pyrazolo[1,2-b]phthalazine-2-carbonitrile (4e)

Yellow powder; yield 0.33 g (93%); mp 273–275°C; IR: 3362, 3256, 2188, 1661, 1652 cm−1; 1H NMR: δ 6.17 (1H, s, CH), 7.43–7.54 (4H, m, Ar), 7.94–8.18 (6H, m, Ar and NH2); 13C NMR: δ 61.7, 62.6, 116.7, 126.8, 127.7, 128.2, 128.7, 129.3, 129.4, 133.3, 134.0, 134.7, 137.4, 150.2, 154.1, 157.3; EI-MS: m/z 350. Anal. Calcd for C18H11N4O2Cl (350.77): C 61.64, H 3.16, N 15.97. Found: C 61.53, H 3.13, N 16.03.

3-Amino-1-(4-nitrophenyl)-5,10-dioxo-5,10-dihydro-1H-pyrazolo-[1,2-b]phthalazine-2-carbonitrile (4f)

Yellow powder; yield 0.35 g (96%); mp 226–228°C; IR: 3371, 3301, 3079, 2185, 1662, 1554 cm−1; 1H NMR: δ 6.30 (s, 1H); 7.81 (d, 3J=8.6 Hz, 2H), 7.97–8.09 (m, 3H), 8.22 (brs, 2H, NH2), 8.24 (d, 3J=8.6 Hz, 2H), 8.26–8.29 (m, 1H); 13C NMR δ 61.5, 62.9, 116.5, 126.1, 127.9, 128.1, 128.8, 129.1, 129.4, 134.5, 134.9, 146.4, 147.6, 150.8, 154.0, 157.2; EI-MS: m/z 361. Anal. Calcd for C18H11N5O4 (361.32): C 59.84, H 3.07, N 19.38. Found: C 60.13, H 3.13, N 19.23.

3-Amino-1-(2-nitrophenyl)-5,10-dioxo-5,10-dihydro-1H-pyrazolo-[1,2-b]phthalazine-2-carbonitrile (4g)

Yellow powder; yield 0.34 g (95%); mp 261–263°C; IR: 3380, 3165, 2192, 1694, 1655 cm−1; 1H NMR: δ 6.64 (1H, s, CH), 7.59–8.28 (10H, m, Ar and NH2); 13C NMR δ 61.1, 62.8, 106.5, 124.1, 126.8, 127.3, 128.1, 128.9, 129.2, 129.7, 133.4, 134.0, 134.6, 135.0, 148.4, 151.8, 154.2, 157.0; EI-MS: m/z 361. Anal. Calcd for C18H11N5O4 (361.32): C 59.84, H 3.07, N 19.38. Found: C 59.98, H 3.15, N 19.16.

Acknowledgments

We gratefully acknowledge financial support from the Research Council of Islamic Azad University, Sanandaj Branch.

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Received: 2017-7-4
Accepted: 2017-8-10
Published Online: 2017-9-23
Published in Print: 2017-10-26

©2017 Walter de Gruyter GmbH, Berlin/Boston

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Artikel in diesem Heft

  1. Frontmatter
  2. Review
  3. Chemical constituents from the genus Saussurea and their biological activities
  4. Preliminary Communication
  5. A new imidazoline-containing Bunte salt: synthesis, molecular and electronic structure
  6. Research Articles
  7. One-pot synthesis of 1-substituted 1H-1,2,3,4-tetrazoles from 2aminothiazoles using tributylmethylammonium chloride as a catalyst
  8. A new method for the synthesis of 4H-1,3,5-oxadiazine derivatives
  9. Simple access to spirooxadiazole compounds containing a quinoxaline moiety using a nitrile imine intermediate generated in situ
  10. A convenient regioselective synthesis of spirooxindolinopyrrolizidines incorporating the pyrene moiety through a [3 + 2]-cycloaddition reaction
  11. An efficient green synthesis of 5H-spiro[benzo[4,5]imidazo[1,2-c]quinazoline-6,3′-indolin]-2′-ones catalyzed by iodine in ionic liquids
  12. A selective fluorescence probe based on benzothiazole for the detection of Cr3+
  13. Spectrophotometric and quantum-chemical study of acid-base and complexing properties of (±)-taxifolin in aqueous solution
  14. Preparation of 1H-pyrazolo[1,2-b]phthalazine-5,10-diones using ZrO2 nanoparticles as a catalyst under solvent-free conditions
  15. Microwave-assisted synthesis of bis(N-substituted thiazol-2-amine) derivatives and their biological activities
https://doi.org/10.1515/hc-2017-0142
Schlagwörter für diesen Artikel
aromatic aldehydes; multicomponent reaction; nanoparticles; phthalhydrazide; solvent-free; zirconium oxide
Creative Commons
BY-NC-ND 3.0

Artikel in diesem Heft

  1. Frontmatter
  2. Review
  3. Chemical constituents from the genus Saussurea and their biological activities
  4. Preliminary Communication
  5. A new imidazoline-containing Bunte salt: synthesis, molecular and electronic structure
  6. Research Articles
  7. One-pot synthesis of 1-substituted 1H-1,2,3,4-tetrazoles from 2aminothiazoles using tributylmethylammonium chloride as a catalyst
  8. A new method for the synthesis of 4H-1,3,5-oxadiazine derivatives
  9. Simple access to spirooxadiazole compounds containing a quinoxaline moiety using a nitrile imine intermediate generated in situ
  10. A convenient regioselective synthesis of spirooxindolinopyrrolizidines incorporating the pyrene moiety through a [3 + 2]-cycloaddition reaction
  11. An efficient green synthesis of 5H-spiro[benzo[4,5]imidazo[1,2-c]quinazoline-6,3′-indolin]-2′-ones catalyzed by iodine in ionic liquids
  12. A selective fluorescence probe based on benzothiazole for the detection of Cr3+
  13. Spectrophotometric and quantum-chemical study of acid-base and complexing properties of (±)-taxifolin in aqueous solution
  14. Preparation of 1H-pyrazolo[1,2-b]phthalazine-5,10-diones using ZrO2 nanoparticles as a catalyst under solvent-free conditions
  15. Microwave-assisted synthesis of bis(N-substituted thiazol-2-amine) derivatives and their biological activities
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