SnO2 nanoparticles as an efficient heterogeneous catalyst for the synthesis of 2H-indazolo[2,1-b]phthalazine-triones

General

All reagents and common solvents were purchased from Loba chemie and Sigma-Aldrich and used without further purification. The products were isolated and characterized by physical and spectral analysis. ¹ H NMR and ¹³ C NMR spectra were recorded on Bruker (DRX Avance-400) spectrometer in the presence of tetramethylsilane as an internal standard. The IR spectra were recorded on Bruker (ATR FT-IR) apparatus using Zn-Se technique. Reactions were monitored by TLC using precoated silica gel plates and melting points were determined on an electro thermal apparatus, and are uncorrected. Powder X-ray diffraction (XRD) was carried out on a Philips diffractometer of X’pert Company with monochromatized Cu Ka radiation ( k  = 1.5406 A˚). Field emission scanning electron microscopy (FE-SEM) and the X-ray dispersive analysis were recorded by FE-SEM (LEO 1455VP), operated at a 15 kV accelerating voltage.

General procedure for the preparation of the SnO2 nanoparticles

The SnO ₂ NPs were prepared by taking 2 g (0.1 M) of stannous chloride dihydrate (SnCl ₂ ·2H ₂ O) in 50 ml of distilled water and dissolved. Simultaneously, an aqueous ammonia solution was added drop by drop under continuous stirring for 15–20 min while maintaining the pH of the solution between 9 and 11. The resulting gel was washed with deionized water until the pH reached 7, filtered and dried at 80 °C for 24 h to remove water. Then, the powdered sample was calcinated at 600 °C for 2 h and the finally obtained powder sample was characterized with FT-IR, powder X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM) and X-ray dispersive analyses.

General procedure for the synthesis of 2H-indazolo[2,1-b]phthalazine-trione derivatives

An equimolar mixture of phthalhydrazide (1.0 mmol), aromatic aldehyde (1.0 mmol), 5,5-dimethyl-1,3-cyclohexanedione or 1,3-cyclohexanedione (1.0 mmol) and 10 mol % of SnO ₂ NPs was magnetically stirred over an oil bath at 80 °C under solvent-free condition for an appropriate time. The completion of the reaction was monitored by TLC using ethyl acetate–hexane (1:1) as the eluent. After completion of the reaction, the reaction mass was cooled to room temperature and 3 ml of chloroform was added and stirred well. The product was soluble in chloroform and the catalyst was recovered by simple filtration. The catalyst was washed with 3 ml of acetone and dried at 100 °C. Finally, the recovered catalyst was subjected to the next run of the reaction. The solvent was removed under vacuum to get the crude product, which on further recrystallization with ethanol afforded the pure product (compared with literatures Ref. [16–18, 26–28]). The pure products were characterized with FT-IR, ¹ H and ¹³ C NMR spectroscopic techniques.

Characterization of SnO2 NPs

The SnO ₂ NPs were synthesized using an already reported procedure [ ³⁸ ]. The synthesized SnO ₂ NPs were characterized by Fourier transform-infrared spectroscopy, powder X-ray diffraction, field emission scanning electron microscopy and energy dispersive X-ray spectroscopy.

FT-IR and XRD analysis

We have compared the FT-IR spectra of as-synthesized form and calcinated samples of SnO ₂ NPs (Fig.  ¹ ). Figure  ¹ a shows a broad band at 3460.78 cm ⁻¹ which represents the presence of water molecule bound to Sn surface. The band at 1573.15 cm ⁻¹ is due to the bending vibration of water molecules and the peak at 1423.15 cm ⁻¹ represents the unreactive SnCl ₂ . The band at 625 cm ⁻¹ indicates the Sn–OH. Furthermore, the calcinated sample has shown a band at 646.31 cm ⁻¹ corresponds to Sn–O–Sn and the band present at 553.94 cm ⁻¹ is due to the stretching vibration of Sn–O. The intensity of peaks due to water molecules is very much decreased in the case of calcinated sample. The observed results reveal that the Sn–O band is not present in the fresh sample. Figure  ¹ c shows the IR spectrum of the SnO ₂ catalyst after the sixth run of the reaction in which there is no change in the peak position and intensity when compared to that of the calcinated catalyst supporting its reusability results. From the X-ray diffraction spectrum, the formations of SnO ₂ NPs are confirmed (Fig.  ² ). All the diffraction peaks are in good agreement with the standard (JCPDS No- 41-1445) which can be indexed as the tetragonal structure of SnO ₂ with lattice constant of a  = 4.78, c  = 3.17 and unit cell volume d  = 72.66. No other diffraction peaks are observed in the XRD pattern that clearly indicates the purity of SnO ₂ NPs. The average crystallite size of the SnO ₂ NPs was calculated using Scherrer formula as, ( D  =  kλ / β cos θ ), where D is the average crystallite size, k is the Scherrer constant, λ is the wavelength of the X-ray beam, β is the ( π /2) FWHM (Full width at half maximum) and θ is the diffraction angle. The average crystallite size of the SnO ₂ NPs was found to be 23.4 nm. Meanwhile, these results were in good agreement with the literature report [ ⁴⁶ ].

Fig. 1

Fig. 2

FE-SEM and EDAX analysis

The field emission scanning electron microscopy (FE-SEM) that shows the morphology and size of the SnO ₂ NPs is presented in Fig.  ³ . The morphology and size of the individual particles could not be measured due to their extremely small size and heavy aggregation. In general, the formation of agglomerated nanoparticles can be explained by nucleation–aggregation–agglomeration–growth mechanism proposed by Rodriguez-Clemente et al. [ ⁴⁷ ]. The particle size of the SnO ₂ NPs is in the range of 44–71.79 nm approximately and also the SnO ₂ NPs have been aggregated in spherical morphology. Finally, the energy dispersive X-ray spectrum exhibits the atomic weight % of tin 33.33 and 66.67% of oxygen present in the SnO ₂ NPs (Fig.  ⁴ ).

Fig. 3

Fig. 4

Catalytic activity

The formation of SnO ₂ NPs made us to utilize the NPs as a catalyst for the one-pot synthesis of 2 H -indazolo[2,1- b ]phthalazine-triones under various reaction conditions. We have optimized the amount of catalyst required to catalyze the reaction where the temperature and solvent have also been screened. Initially, we have performed the model reaction with a mixture of 4-chlorobenzaldehyde (1 mmol), dimedone (1 mmol) and phthalhydrazide (1 mmol) without catalyst and solvent and found that there was no reaction even after five hours (Table  ¹ , Entry 1) revealing the need of a catalyst to activate the reaction. By employing 20 mol % of various Lewis acid catalysts such as NiCl ₂ .6H ₂ O, CuCl ₂ .2H ₂ O, CaCl ₂ .2H ₂ O and MnCl ₂ .4H ₂ O for the reaction, the yield of the expected product was very low even after 60 min of the reaction (Table  ¹ , Entries 2-5). Next, we investigated the reaction with 20 mol % of SnCl ₂ ·2H ₂ O, where the moderate yield of the product was observed (Table  ¹ , Entry 6). The model reaction when conducted at 80 °C with 10 mol % of SnO ₂ bulk led to prolonged reaction time with 72% yield (Table  ¹ , Entry 7) which made us to standardize the reaction using SnO ₂ NPs. Using 5 mol % SnO ₂ NPs, the reaction provided 70% of the product with lesser reaction time when compared with other metal chlorides (Table  ¹ , Entry 8) and 10 mol % of the SnO ₂ NPs catalyzed the reaction to an excellent yield of the product (Table  ¹ , Entry 9) with shorter reaction time. Further increase in the mol % of SnO ₂ NPs did not improve the yield of the product (Table  ¹ , Entries 10 and 11). Meanwhile, the model reaction was studied with 10 mol % of SnO ₂ NPs under various temperatures. At 80 and 90 °C, there was no change in the yield and reaction time, (Table  ¹ , Entry 12) but the yield decreased at 70 or 60 °C (Table  ¹ , entries 13 and 14).

With the optimized catalyst, solvent-mediated reaction did not succeed well which may be due to the interruption of solvent molecules for the direct contact between the reactants and the catalyst (Table  ¹ , entries 15–17). We have compared the yield of the product and the reaction time with previous literature in Table  ² , entries 1–10. Apparently, some of the reported catalysts afforded good yields but most of the catalysts were hazardous to the environment and the catalyst quantity needed was also more in addition to longer reaction time. The catalytic activity of SnO ₂ NPs may be due to the presence of more acidic (Sn ⁴⁺ ) and the basic (O ²⁻ ) surface sites [ ³⁷ ] that could readily induce the organic transformations. We have concluded that 10 mol % of SnO ₂ NPs at 80 °C was more favorable under solvent-free condition to provide excellent yield of the target product with shorter reaction time (Table  ¹ , entry 9) and the optimization results are presented in Table  ¹ . The reusability of the catalyst was also successfully checked up to seven runs.

Using the above optimized conditions, we have taken various aromatic aldehydes having different electron withdrawing and donating substituents in the ortho, meta and para positions and cyclic diketones for the synthesis of 2 H -indazolo[2,1- b ]phthalazine-trione derivatives (Table  ³ ). Almost all aldehydes provided good to excellent yields of the products irrespective of the position as well as electron donating and withdrawing nature of the group in the aryl aldehydes (Scheme  ¹ ).

The synthesized 2 H -indazolo[2,1- b ]phthalazine-trione derivatives were confirmed by ¹ H-NMR and ¹³ C-NMR spectroscopic techniques. The ¹ H-NMR spectrum of the compound 4p exhibited a peak at δ 2.24–3.59 ppm which could confirm the presence of six methylene protons in the cyclohexenone ring and another singlet appeared at δ 3.75 ppm which indicates the presence of 4-OCH ₃ on the aromatic ring. The methine (C–H) proton has given a single peak at δ 6.42 ppm and the remaining aromatic protons exhibited peaks at δ 6.84–8.35 ppm. The ¹³ C-NMR spectrum of the compound ( 4p ) exhibited peak at δ 22.35–64.60 ppm which corresponds to the presence of aliphatic carbon in the cyclohexenone ring and the peak appeared at δ 114.11 ppm due to the presence of methine carbon. The characteristic peak of carbonyl carbon appeared at δ 192.62 ppm and the rest of the aromatic carbons appeared at δ 159.74–119.68 ppm.

Scheme 1

The plausible reaction mechanism proposed for the synthesis of 2 H -indazolo[2,1- b ]phthalazine-trionederivatives is represented in Scheme  ² . Initially, the SnO ₂ NPs catalyzed the Knoevenagel condensation reaction between dimedone ( I ) and aromatic aldehyde ( II ) providing III . This step is facilitated by the activation of carbonyl group in aromatic aldehyde by SnO ₂ NPs. Michael addition of phthalhydrazide to III provides IV which on cyclization afforded the target product ( V ).

Scheme 2

Reusability of the catalyst

Next, we have also checked the reusability of SnO ₂ NPs. The reusability of the catalyst was investigated with the model reaction using an equimolar mixture of 4-chlorobenzaldehyde (1 mmol), dimedone (1 mmol) and phthalhydrazide (1 mmol) performed with 10 mol % of SnO ₂ NPs under solvent-free condition. After completion of the reaction, the reaction mass was cooled to room temperature and 3 ml of chloroform was added and stirred well. After that the product soluble in chloroform was separated by filtration. The recovered catalyst was washed with 3 ml of acetone to remove any organic residues present in the catalyst. The recovered catalyst was dried at 100 °C and subjected to the consecutive runs with same experimental condition. The yield of the product and the reaction time were not much affected up to fifth run after that a slight decrement in the yield of the product was observed. From these results, it has been concluded that 10 mol % of SnO ₂ NPs can be efficiently reused for more than five to six consecutive runs without loss in its catalytic activity (Fig.  ⁵ ). After the sixth run, the recovered SnO ₂ NPs were further subjected to FE-SEM analysis which was shown in Fig.  ⁶ .

Fig. 5

Fig. 6