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Journal of the Chilean Chemical Society

versión On-line ISSN 0717-9707

J. Chil. Chem. Soc. vol.59 no.1 Concepción mar. 2014

http://dx.doi.org/10.4067/S0717-97072014000100006 

 

SULFONIC ACID FUNCTIONALIZED NANOPOROUS SILICA (SBA-PR-SO3H) AS AN EFFICIENT CATALYST FOR THE ONE-POT SYNTHESIS OF 2H-INDAZOLO[1,2-B]PHTHALAZINE-TRIONES

 

GHODSI MOHAMMADI ZIARANI1*, ALIREZA BADIEI2, NINA HOSSEINI MOHTASHAM1, NEGAR LASHGARI2

1 Department of Chemistry, Alzahra University, Vanak Square, Tehran, 1993893973, Iran
2
School of Chemistry, College of Science, University of Tehran, Tehran, Iran
* email: gmohammadi@alzahra.ac.ir


ABSTRACT

Sulfonic acid functionalized SBA-15 (SBA-Pr-SO3H) with a pore size of 6 nm is an efficient catalyst in the green three-component condensation of phthalhydrazide, dimedone and aldehydes to give 2H-indazolo[1,2-b]plithalazine-triones under solvent-free conditions in excellent yields and short reaction times.

Keywords: Sulfonic acid functionalized SBA-15; Phthalhydrazide; Dimedone; Nano-reactor; One-pot reaction.


 

1. INTRODUCTION

In recent years, heterogeneous catalysts have gained great importance due to economic and environmental considerations.1-3 Among the various heterogeneous catalysts, particularly, Santa Barbara Amorphous (SBA-15) is significant mesoporous silica with exclusive and important properties such as thick walls, profusely large surface area, huge pore volume and hydrothermal stability which render it as a promising catalyst for wide applications.4 Moreover, functionalization and modification of SBA-15 could enhance and optimize its catalytic activity.4 Applications of these nano catalysts in organic synthesis and one-pot reactions under green conditions are significant and growing. In continuation of our studies, on the application of nanoporous heterogeneous solid catalysts to organic synthesis,5-9 herein, we want to report a suitable method for the preparation of 2H-indazolo[1,2-b]phthalazine-trione derivatives using SBA-Pr-SO3H as a nanoporous heterogeneous acid catalyst.

The development of simple synthetic routes for construction of complex organic molecules from readily available reagents is an important task in organic synthesis. Multi-component reactions (MCRs) are powerful and valuable tools for the rapid and efficient synthesis of a wide variety of organic molecules.10, 11

In the past few decades, the synthesis of nitrogen-containing heterocyclic compounds has gained prominence as they are widespread in nature. 12 Among a large variety of N-containing heterocyclic compounds, heterocycles containing hydrazine moiety as 'fusion site' have received considerable attention due to their pharmacological properties and clinical applications.13 Moreover, fused phthalazine derivatives were found to possess multiple biological activities such as anticonvulsant,14 cardiotonic,15 vasorelaxant,16 antifungal,17 and anticancer18 activities. Many methods are available for the synthesis of phthalazine derivatives,19-22 however, some of these methods suffered from several drawbacks such as hazardous organic solvents, high cost, long reaction times, excess amounts of acids, and harsh reaction conditions with non-recyclable catalysts. Therefore, the development of a new, efficient, and environmentally benign procedure which allows the simple synthesis of heterocycles containing phthalazine ring fragment is necessary. In this paper, we want to report the application of SBA-Pr-SO3H as a highly active nanoporous heterogeneous acid catalyst in the preparation of 2H-indazolo[1,2-ft] phthalazine-trione derivatives.

2. EXPERIMENTAL

Materials and Methods

All chemicals were obtained commercially and used without further purification. The IR spectra were recorded from KBr disk using a FT-IR Bruker Tensor 27 instrument. Melting points were measured by using the capillary tube method with an electro thermal 9200 apparatus. The 1H NMR spectra was run on a Bruker DPX, at 400 MHz using TMS as an internal standard. GC-Mass analysis was performed on a GC-Mass model: 5973 network mass selective detector, Gc 6890 Agilent. SEM analysis was performed on a Philips XL-30 field-emission scanning electron microscope operated at 16 kV while TEM was carried out on a Tecnai G2 F30 at 300 kV.

Synthesis and Functionalization of SBA-15

The nanoporous compound SBA-15 was synthesized and functionalized according to our previous report8 and the modified SBA-15-Pr-SO3H was used as nanoporous solid acid catalyst in the following reaction.

General Procedure for the Synthesis of 2H-Indazolo[1,2-b]phthalazine-trione Derivatives (4a-k)

The SBA-Pr-SO3H (0.02 g) was activated in vacuum at 100 °C. After cooling to room temperature, phthalhydrazide 1 (1 mmol, 0.16 g), aromatic aldehyde 2 (1 mmol), and dimedone 3 (1 mmol, 0.14 g) were added to it. The mixture was heated at 80 °C under solvent-free condition until the reaction was completed. After completion of the reaction (monitored by TLC), the solid product was dissolved in hot ethanol (2 × 10 mL) and the heterogeneous solid catalyst was removed by simple filtration. Then, the filtrate was cooled to give the pure products 4a-k.

Selected Spectral Data

3,4-Dihydro-3,3-dimethyl-13-(2-methoxyphenyl)-2H-indazolo[1,2-b] phthalazine-1,6,11(13H)-trione (4i)

Color: Yellow. Yield: 79%. M.p.: 240-242 °C. FT-IR (KBr, v, cm-1): 2895, 1661, 1600, 1555, 1494, 1328, 1218, 1078, 788. MS (EI, m/z): 402 (M+, 7), 371 (11), 327 (31), 295 (27), 274 (25), 162 (52), 130 (21), 104 (100), 76 (94), 55 (60).

3,4-Dihydro-3,3-dimethyl-13-(2,3-dimethoxyphenyl)-2H-indazolo[1,2-b] phthalazine-1,6,11(13H)-trione (4j)

Color: Yellow, Yield: 88%. M.p.: 230-232 °C. FT-IR (KBr, v, cm-1): 3165, 3016, 3894, 1661, 1599, 1556, 1489, 1369, 1224, 751. 1H NMR (400 MHz, CDCl3, δ, ppm): 6.86-8.38 (m, 7H, ArH), 6.67 (s, 1H, CHN), 3.84 (s, 6H, 2OMe), 3.27-3.41 (AB system, J = 19.2 Hz, 2H, CHaHbCO), 2.33 (s, 2H, CH2C), 1.13 (s, 6H, 2Me). MS (EI, m/z): 432 (M+, 20), 401 (49), 312 (31), 257 (30), 162 (100), 132 (20), 104 (85), 76 (43), 51 (26).

3,4-Dihydro-3,3-dimethyl-13-(2,6-dichlorophenyl)-2H-indazolo[1,2-b] phthalazine-1,6,11(13H)-trione (4k)

Color: Yellow. Yield: 80%. M.p.: 264-266 °C. FT-IR (KBr, v, cm-1): 3445, 3067, 2965, 2929, 1745, 1661, 1623, 1600, 1309, 1267, 1168, 705. 1H NMR (400 MHz, CDCl3, δ, ppm): 7.29-8.41 (m, 7H, ArH), 7.19 (s, 1H, CHN), 3.243.42 (AB system, J = 19.2 Hz, 2H, CHaHbCO), 2.36 (s, 2H, CH2C), 1.24 (s, 6H, 2Me). MS (EI, m/z): 440 (M+, 3), 405 (2), 295 (19), 162 (100), 132 (22), 104 (99), 76 (42), 50 (22).

RESULTS AND DISCUSSION

In this paper, an efficient, one-pot, three-component condensation of phthalhydrazide 1, aromatic aldehydes 2 and dimedone 3 in the presence of SBA-Pr-SO3H for the preparation of 2H-indazolo[1,2-b]phthalazine-trione derivatives 4a-k under solvent-free conditions has been studied (Scheme 1). We initially investigated the solvent effects in this reaction. As shown results in Table 1, among the tested solvents such as H2O, EtOH, EtOH/H2O (1:1), MeCN, and solvent-free system, the best result was obtained after 5 min under solvent-free condition at 80 °C in excellent yield. Therefore, this reaction condition was developed with different aldehydes and the results were summarized in the Table 2. It was reported that in the absence of any catalyst and under solvent-free conditions, this reaction afforded compound 4a after 60 hours in trace amount.23

 

Scheme 1. Synthesis of 2H-indazolo[1,2-b]phthalazine-trione derivatives in the presence of SBA-Pr-SO3H.

Table 1. Influence of different solvents on the synthesis of 2H-indazolo[1,2-b]phthalazine-trione derivatives.

 

Table 2. SBA-Pr-SO3H Catalyzed the synthesis of 2H-indazolo[1,2-b]phthalazine-trione derivatives 4a-k under solvent-free condition.

 

We propose a (plausible) mechanism for this reaction (Scheme 2). The reaction is thought to proceed in a stepwise manner. Firstly, we assume that the solid acid catalyst protonates the carbonyl group of aldehyde and then a Knoevenagel condensation between compounds 5 and 7 results in the intermediate 9 which immediate Michael addition of phthalhydrazide 1 to the C=C bond of this compound leads to the formation of intermediate 11. Cyclocondensation through of amino and carbonyl groups of the compound 11, followed by elimination of water produces the desired products 4a-k in excellent yields. The effect of nano pore size about 6 nm of solid acid catalyst enables it to act as a nano-reactor in which the reaction proceeds faster (Fig. 1).

 

Scheme 2. Proposed mechanism.

 

Fig. 1. SBA-Pr-SO3H acts as a nano-reactor.

The synthesis of 2H-indazolo[1,2-b]phthalazine-trione derivatives has been reported under different conditions with several catalysts and solvents in the literature as shown in Table 3. The high yield and shortest reaction time in this table is attributed to the high efficiency of the nano catalyst of SBA-Pr-SO3H.

Table 3. Comparison of different conditions in the synthesis of 4a.
 
 

a p-Toluenesulfonic acid; b Trimethylsilyl chloride; c Silica supported polyphosphoric acid; d 1-Butyl-3-methyl imidazolium tetrafluoroborate; e Phosphomolybdic acid; f 2,4,6-Trichloro-1,3,5-triazine (cyanuric chloride); g N, N, N', N'-Tetrabromobenzene-1,3-disulfonamide; h Poly(N-bromo-N-ethylbenzene-1,3-disulfonamide); i (S)-Camphorsulfonic acid; j Dodecylphosphonic acid

A schematic illustration for the preparation of SBA-Pr-SO3H was shown in Fig. 2. First, the calcined SBA-15 silica was functionalized with (3-mercaptopropyl) trimethoxysilane (MPTS) and then, the thiol groups were oxidized to sulfonic acid by hydrogen peroxide.

 

Fig. 2. Schematic illustration for the preparation of SBA-Pr-SO3H.

The surface area, average pore diameter calculated by the BET method and pore volume of SBA-Pr-SO3H are 440 m2g-1, 6.0 nm and 0.660 cm3 g-1, respectively (Table 4) which are smaller than those of SBA-15 because of the stabilization of sulfonosilane groups into the pores.8

Table 4. Porosimetery values for SBA-15 and functionalized SBA-15.

 

Fig. 3 illustrates the SEM and TEM images of SBA-Pr-SO3H. SEM image (Fig. 3a) shows uniform particles about 1μm. The same morphology was observed for SBA-15. It can be concluded that morphology of solid was saved without change during the surface modifications. On the other hand, the TEM image (Fig. 3b) reveals the parallel channels, which resemble the pores configuration of SBA-15. This indicates that the pore of SBA-Pr-SO3H was not collapsed during two-steps reactions.

 

Fig. 3. SEM (a) and TEM (b) images of SBA-Pr-SO3H.

3. CONCLUSION

In summary, we have developed a solvent-free reaction for the synthesis of 2H-indazolo[1,2-b] phthalazine-triones via one-pot, three-component condensation reaction of aromatic aldehydes with dimedone and phthalhydrazide using the reusable and environmentally benign sulfonic acid functionalized nanoporous silica (SBA-Pr-SO3H) as a green solid acid catalyst. The merits of this protocol are high product yields, shorter reaction times, solvent-free condition, and simple workup.

ACKNOWLEDGEMENTS

We gratefully acknowledge the financial support from the Research Council of Alzahra University and the University of Tehran.

 

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(Received: January 15, 2013 - Accepted: December 13, 2013)