Chinese Chemical Letters  2016, Vol.27 Issue (01): 104-108   PDF    
N-Methylimidazolium perchlorate as a new ionic liquid for the synthesis of bis(pyrazol-5-ol)s under solvent-free conditions
Nader Ghaffari Khaligha , Sharifah Bee Abd Hamida, Salam J. J. Titinchib    
a Nanotechnology & Catalysis Research Centre, NANOCAT, University Malaya, Kuala Lumpur, Malaysia;
b Department of Chemistry, University of the Western Cape, Cape Town, South Africa
Abstract: N-Methylimidazolium perchlorate([MIm]ClO4) was synthesized and some of its physico-chemical properties, such as density, surface tension were investigated. A thermo gravimetric analysis(TGA) and solvent performance were also studied. The results show that this ionic liquid is an excellent catalyst for the synthesis of 4,4'-(arylmethylene)bis(1H-pyrazol-5-ol) derivatives under solvent-free conditions. This method has the advantages of high yield, clean transformation, simple operation and short reaction time. The ionic liquid can be recycled without significant loss of activity.
Key words: Ionic liquid     N-Methylimidazolium perchlorate     Bis(pyrazol-5-ol)s     Recycle    
1. Introduction

Ionic liquids (ILs) are used in many fields due to their unique physical and chemical properties. Their recycle-ability and low environment impact are the most impressive factors in the present era. In the past few years,significant progress has been made in the preparation,characterization and application of ILs [1]. The physicochemical properties of ILs depend on the nature and size of both their cation and anion constituents; therefore,different ILs can be finetuned using different cations and anions tomeet the requirements of the application of interests. Fluorinated ionic liquids were investigated for recovery/recycling of perfluorocarbon contaminants such as greenhouse perfluorocarbons gases and perfluoroalkyl acids of industrial effluents that are persistent,bioaccumulative,and toxic. The partial or total replacement of inert perfluorocarbons in oxygen therapeutic emulsions was achieved by enhancing the emulsion stability and increasing the solubility of respiratory gas [2]. 1-Butyl-3- methylimidazolium perchlorate,[BMIM][ClO4],was used as a reducing agent to upgrade a selected heavy oil [3].

Although ILs with perfluoroanions are stable,during reaction they would produce HF,which is a toxic and corrosive gas [4] and the costs of perfluoroanions are high. On the other hand, chloroaluminated ionic liquids are cheaper but they are extremely sensitive to air and water. Bearing these aspects in mind,additional effort is needed to search for new environment-protective ionic liquids for academic and industrial applications,which should meet the technically desired properties. To introduce new,low cost ionic liquids,we synthesized N-methylimidazolium perchlorate to explore its catalytic activity.

Pyrazoles,including 4,4'-(arylmethylene)bis(1H-pyrazol-5-ol) derivatives appear widely in various molecules exhibiting significant antipyretic,analgesic and anti-inflammatory [5],anticancer [6],antiviral [7],anti-proliferative [8],hypoglycemic [9] and antioxidant [10] activities. These compounds have been employed as inhibitors of Mycobacterium tuberculosis [11],antibacterial and antifungal [12, 13],pesticides [14] and dyestuffs [15].

Consequently,a variety of synthetic strategies have been developed for the preparation of 4,4'-(arylmethylene)bis(1Hpyrazol- 5-ol) derivatives [16, 17].

In our view,the one-pot multi-component reaction of a tandem Knoevenagel-Michael reaction orMannich type reaction [17] is the most appropriate method for the preparation of 4,4'-(arylmethylene)- bis(1H-pyrazol-5-ols) since 1,3-disubstituted-1H-pyrazol- 5(4H)-ones are expensive,especially 3-methyl-1H-5-pyrazolone.

2. Experimental 2.1. Synthesis of N-methylimidazolium perchlorate ([MIm]ClO4)

N-Methylimidazole (8.21 g,100 mmol) was added to a solution of perchloric acid 70% (8.6 mL,100 mmol) and the mixture was stirred continuously for 24 h at room temperature. The product was dried by rotary evaporation and a colorless liquid was obtained in 94% yield. The obtained ionic liquid was dried in vacuum at 80 ℃ for 24 h; IR (KBr): νmax 3390,3150,3120,2950, 2940,1570,1465,1170,1108,1078,616,465 cm-1; 1H NMR (400 MHz,DMSO-d6): δ 3.845 (s,3H,NCH3),7.611 (dd,1H, J = 1.6 Hz,NCHCHN),7.662 (dd,1H,J = 1.6 Hz,NCHCHN), 9.014-9.015 (d,1H,J = 0.4 Hz,NCHN),14.222 (br s,1H); 13C NMR (400 MHz,DMSO-d6): δ 35.805,120.147,123.610,136.218; ESI(+)-MS (m/z) for [MIm] 83; ESI(-)-MS (m/z) [ClO4] 99 and 101.

2.2. Preparation of 4,4'-(arylmethylene)bis(1H-pyrazol-5-ol)

derivatives In a 25 mL round bottom flask a mixture of ethyl acetoacetate (10 mmol),aromatic aldehyde (5 mmol),phenylhydrazine or hydrazine hydrate (10 mmol) was stirred in the presence of N-methylimidazolium perchlorate (50 mg) at 60 ℃ under solventfree conditions for an appropriate period of time. After the completion of the reaction (monitored by TLC analysis),the reaction mixture was cooled to room temperature and water (5 mL) was added with stirring. The precipitate was collected by filtration and evaporation of the mother liquors under reduced pressure led to the recovery of the catalyst,which could be reused in the next run. The crude products were purified by recrystallization from ethanol (95%).

3. Results and discussion

The focus of our research is to develop an eco-efficient methodology that decreases both the amount of waste generated and use of hazardous materials. Recently,4-(succinimido)-1- butane sulfonic acid (SBSA) was prepared in our laboratory by stirring succinimide and 1,4-butanesultone for 10 h at 40-60 ℃ using solar energy [18]. The current synthesis of N-methylimidazolium perchlorate ([MIm]ClO4) involved merely stirring N-methylimidazole and perchloric acid at room temperature for 24 h (Scheme 1). The structure of ionic liquid was confirmed by FT-IR and 1H NMR.

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Scheme 1.Synthesis of N-methylimidazolium perchlorate ([MIm]ClO4).

The peaks at 3150 and 3120 cm-1 in ionic liquid were assigned to the stretching for C-H vibrations of the imidazole ring in the FT-IR spectrum of [MIm]ClO4. Stretching vibration peaks of C-H from the methyl group of imidazole ring appeared at 2950 and 2940 cm-1. Skeletal vibration peaks of imidazole ring were seen at 1570 and 1465 cm-1; in-plane bending vibration peak of C-H from imidazole ring was located at 1170 cm-1. On the other hand,the asymmetric and symmetric stretching vibration peaks of anion perchlorate were located at 1108,1078 and 616 cm-1,respectively. The bending vibration peak also was seen at 461 cm-1 [19]. In addition,a broad,intense band centered on 3390 cm-1 indicated the presence of water.

1H NMR spectrum of [MIm]ClO4 showed two deshielded ring protons at 7.611 and 7.662 ppm (two overlapped doublets respectively). The protons of the methyl group attached to the ring were shown at 3.845 ppm (singlet). However,the signal of the CH- group attached to the electronegative N atom ring was detected at 9.014 ppm. The signal of acidic proton was not clear and was detected at 14.222 ppm. The ESI-MS of [MIm]ClO4 in methanol of a concentration of ca. 3-4 × 10-8 mol/L was determined. Characteristic signals were detected corresponding to the IL cation (C+) in ESI(+) (MIm+ at m/z 83) and IL anion (A-) in ESI(-) (ClO4- at m/z 99 and 101). For [MIm]ClO4,two weak signals (m/z 265) and (m/z 281) corresponding to a C2A+ and CA2- cluster were also observed in ESI(+) and ESI(-),respectively. The rest of the peaks in the spectra,such as m/z 180,m/z 222,m/z 296 in ESI(+) and m/z 143,m/z 199,m/z 2=,m/z 267 in ESI(-),were also observed by ESI-MS of methanol,and therefore might not be related to [MIm]ClO4.

The water content in [MIm]ClO4 was determined to be less than 0.3% by the Karl-Fischer titration method. The density was measured to be approximately 1.22 g/mL at 20 ℃ using the bottle method and the surface tension was 47.9 mN/m at 20 ℃ measured by the method of bubbling. Also,water absorption of ionic liquid was tested and it was seen from the fact that the mass of [MIm]ClO4 ionic liquid increased with the prolonged exposure but the mass gain was insignificant,and changes slowed after 8 h with just 3.2% mass fraction after 24 h.

The TGA results of [MIm]ClO4 showed that the obtained ionic liquid is comparably stable to 325 ℃. Evaporation of some water causes the mass loss around 100 ℃,which is consistent with the results of the water absorption experiments. The mass loss of 80% around 325 ℃ is hypothesized to be caused by the decomposition of the ionic liquid. These results indicate that ionic liquid has good thermal stability with high decomposition temperature and can be used at a wide temperature range. [MIm]ClO4 was soluble in water, methanol,ethanol,acetone and ethyl acetate. However it was immiscible with non-polar solvents such as toluene and diethyl ether. Consequently the catalyst can be separated conveniently from products by simple phase separations.

The condensation between ethyl acetoacetate,4- chlorobenzaldehyde (1b) and phenylhydrazine was carried out in the presence of different amount of [MIm]ClO4 (2.2,5.4 and 10.8 mol%) under solvent-free conditions (Scheme 2). It was observed that 5.4 mol% of ionic liquid was the optimum amount to furnish the desired product in high yield. Increasing the amount of the catalyst to 10.8 mol% did not increase the yield significantly. In addition different reaction temperatures (room temperature -80 ℃) were employed to identify the optimum temperature of the reaction. Results illustrated that 92% yield of 4,4'-[(4- chlorophenyl)-methylene]bis(3-methyl-1-phenyl-1H-pyrazol-5- ol) was obtained in the presence of 5.4 mol% [MIm]ClO4 at 50 ℃ within 20 min. Higher temperatures caused more spots on the TLC, which led us to conclude that by-products were being produced. In a control experiment without [MIm]ClO4,the reaction did not go to completion at the same temperature even after 8 h and only 26% of product 2b was produced. In the presence of 5.4 mol% imidazole and perchloric acid as catalysts 34% of 2b with fewer spots was observed within 8 h at 50 ℃. Consequently,it seems that the superior catalytic performance is due to the synergistic effect of imidazolium cation and perchlorate anion.

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Scheme 2.Synthesis of 4,4'-[(4-chlorophenyl)methylene)]bis(1H-pyrazol-5-ol) derivatives in presence of [MIm]ClO4 under various reaction conditions.

In order to evaluate the generality of the present method,a range of hetero and aryl aldehydes 1(a-l) were mixed with ethyl acetoacetate and phenylhydrazine or hydrazine hydrate under the optimized reaction conditions in the presence of [MIm]ClO4 (Table 1). The aryl aldehydes that possess electron-donating and electron-withdrawing substituents provided the desired products in good to high yields without little by-products (Table 1,entries 1-16). The shorter reaction times and higher yields were observed for the substrates with electron-withdrawing substituents (-NO2) compared to those with electron-donating substituents (CH3O-) (Table 1,entries 4,12 and 6,14). Furthermore,acid sensitive aldehydes,such as furfural and 2-thienaldehyde,were smoothly converted into the corresponding products,a conversion that is otherwise problematic in the presence of acidic catalysts (Table 1, entries 7,8 and 15,16). Aliphatic aldehydes produced two or more spots on the TLC and GC-MS spectrum under the optimized conditions. New products were characterized by IR,1H NMR,13C NMR and elemental analysis while known products were characterized by comparison of their melting points and spectral data with those of authentic samples. Ionic liquid was isolated and could be recycled up to five times without any significant loss of activity (Table 1,entry 2).

Table 1
Synthesis of 4,4'-(arylmethylene)bis(1H-pyrazol-5-ol)s in the presence of SBSA.a

Based on mechanisms reported in the literature [20c],a proposed mechanism for formation of the product is outlined in Scheme 3. In the first step,pyrazolone would be anticipated from the very fast condensation between phenylhydrazine or hydrazine hydrate with ethyl acetoacetate catalyzed by [MIm]ClO4. The activated carbonyl group of the aldehyde again by ionic liquid [MIm]ClO4 condenses with two equivalents of pyrazolone through a pyrazolenone intermediate resulting in the formation of 4,4'-(arylmethylene)bis(1H-pyrazol-5-ol)s via a tandem Knoevenagel- Michael reaction.

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Scheme 3.The proposed mechanism for the synthesis of 4,4'-(arylmethylene)bis(1H-pyrazol-5-ol)s in presence of [MIm]ClO4.

To validate the proposed mechanism,the synthesis of 2b was carried out in two steps. Firstly,pyrazolone was obtained by condensation between phenylhydrazine or hydrazine hydrate reacted with ethyl acetoacetate,then 2 equivalent of pyrazolone were reacted with one equivalent 4-chlorobenzaldehyde under the optimization reaction conditions to give the product 2b (88%) within 20 min.

To the best of our knowledge,there is only a few papers in the synthesis of 4,4'-(arylmethylene)bis(3-methyl-1H-pyrazol-5-ols) [20b, 21a]. To evaluate the overall utility of the current methodology, we compared our results with those of the methods reported in literature for the synthesis of 2d and 2g as shown in Table 2. It is clearly illustrated that the reaction in presence of [MIm]ClO4 affords a comparable yield and requires smaller mol% of catalyst and lower temperature than other protocols.

Table 2
Comparison of the present method with other reported strategies for the synthesis of 2d and 2g.
4. Conclusion

A novel ionic liquid was synthesized and its catalytic activity was investigated for the synthesis of 4,4'-(arylmethylene)bis(1Hpyrazol- 5-ol)s under solvent-free conditions. The current protocol has the advantages of simple experimental procedures,good to high yield of products,inexpensive substrates,reusability of the catalyst and being environmentally benign. The catalyst can be recycled up to five times without any significant loss of activity.

Acknowledgment

The authors are thankful to the partial support from University Malaya to Project GC 001A-14-AET.

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