A novel l-amino acid ionic liquid for quick and highly efficient synthesis of oxime derivatives – An environmental benign approach

1 Introduction

In synthetic organic chemistry, oximes are vital intermediate for many functional group transformations. These compounds were successfully transformed into amides (Owston et al., 2007), amines (Li et al., 2009), hydroxylamine (Mamani et al., 2011), hydroxylamine O-ethers (Miyabe et al., 2009), nitroalkanes (Kudyba et al., 2005), quinoxaline derivatives (Dong et al., 2008), etc. It is well-known intermediate for Beckmann rearrangement (Meng et al., 2011). Therefore, synthetic organic chemists are interested in the facilitation of oxime synthesis.

Although alternative methods exist (Liang et al., 2010), reaction of carbonyl compounds with hydroxylamine hydrochloride remains still the most important route. Many improvements of this methodology have been convoluted. Hean Luo described the treatment of ketones with hydroxylamine hydrochloride in the presence of an ion-exchange resin as the catalyst in ethanol gave oxime in high yields at room temperature and with a simple work-up procedure (You et al., 2008).

In the literature, there were reports on, irradiation of carbonyl compounds and hydroxylamine hydrochloride impregnated on wet basic Al₂O₃, or grinding them with molecular sieves gave the corresponding oximes (Kad et al., 2001). High yields of hydroxyiminocycloalkanes could also be achieved by treatment of the corresponding ketone with hydroxylamine or its salts in ionic liquid and the presence of additives, such as sodium acetate.

We required extensive amount of several oxime of carbonyl compound as starting material in a more comprehensive synthesis project through an environmentally benign process. In last 10 years, Ren et al. (2001) reported environmental friendly and economical method for the preparation of cyclic ketoximes using aqueous hydroxylamine in ionic liquid. Damljanovic et al. (2006) reported a synthesis of oximes by grinding carbonyl compounds and hydroxylamine hydrochloride in the presence of sodium hydroxide/silica gel as a catalyst, in the absence of solvent. Song et al. (2007) achieved highly selective synthesis of methyl ethyl ketone oxime through amino oximation over Ti-MWW catalyst. Zang et al. (2009) reported ultrasound-promoted synthesis of oximes catalyzed by a basic ionic liquid [bmim]OH. Recently, it has been reported that BF₃·OEt₂ in methanol using microwave irradiation could successfully achieve this condensation without any base (Sridhar et al., 2011).

This encouraged us to study the possibility of the condensation reaction of various carbonyl compounds with hydroxylamine hydrochloride in the presence of l-AAIL at room temperature. To our best knowledge, there is no report of using the ionic liquid l-AAIL, as catalyst for the preparation of oximes by grinding method. Herein, we desire to report a quick, facile synthesis of oximes in the presence of l-AAIL without solvent (Scheme 1).

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Scheme. 1

Synthesis of oximes in the presence of l-AAILs.

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Among the numerous methods for the synthesis of oximes, involved the use of some bases/catalysts which were not entirely environment friendly (Table 1). Ionic liquids play a vital role as dual catalyst and green solvent having enormous applications in synthetic organic chemistry due to their peculiar chemical and physical properties, such as wide liquid range with melting point around room temperature, good recyclability and stability in air and moisture, high solubility including inorganic, organic and even polymeric materials and negligible vapor pressure (Bica and Gaertner, 2006). The main goal of the present work is to design novel green catalyst (l-AAIL) by coupling l-asparagine with 1-(2-aminoethyl)-3-methyl-imidazolium bromide.

2 Experimental

3 Results and discussion

For the beginning of this study, acetophenone and hydroxylamine hydrochloride (1:1.2 mmol) were ground without base/catalyst in a pestle mortar for a duration of time at room temperature to compare the catalytic performance of the l-AAIL-2. The formation of oxime was not observed (Table 2, entry 1).

In the presence of NaOH/CH₃COONa the condensation occurs unhurriedly with a variation in temperature and concentration of the base (Table 2, entry 2). Subsequently, catalytic activity of different l-amino acids was tested for this reaction (Fig. 1), it is noted that glycine does not show catalytic role in these reactions (Table 2, entry 3). It is further observed that asparagine and l-proline showed poor activity (Table 2, entries 4 and 5). However, the reaction was a little accelerated obviously when 1-(3-carboxyethyl)-3-methyl imidazolium bromide and 1-(2-aminoethyl)-3-methyl imidazolium bromide were used for the condensation reaction (Table 2, entries 6 and 7). It may be due to the catalytic nature of these compounds.

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Figure 1

Different l-amino acids and ILs used for condensation reaction.

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It was observed that l-AAIL-2, showed excellent catalytic activity at ambient conditions (Table 2, entry 9). The results clearly indicated that this catalyst should be absolutely imperative for the condensation reaction l-AAIL-2 gave yield 96%, compared with the method (Ren and Ou, 2001) using more concentration of ILs bmiPF₆, bmim Cl, bmiBF₄, higher temperature and more time duration in the presence of additives like sodium acetate, methane sulfonic acid and also using Ti-MWW catalyst with elevated temperature (67 °C) and longer duration (Song et al., 2007). These methodologies offer disadvantages such as use of the volatile solvents, corrosive bases and metal catalysts, which are generating a huge amount of waste and consuming energy for recovery of the products. The present method is fulfilling the growing need of environmental protection and economic factors.

When the ionic liquid l-AAIL-1 was used, 68% yield of oxime was isolated (Table 2, entry 8) with more concentration of catalyst (0.1 mmol). These results are comparable with l-AAIL-2 indicating that more basic nature of catalyst played a significant role in the catalysis, with less duration (50 s) and minimum concentration (0.05 mmol). Having optimized the reaction conditions, the condensation of various carbonyl compounds was examined (Table 3). All the ketones with steric hindrance were investigated and found good yields ranging from 85% to 90% (Table 3, entries 1–6). However, the condensation of both aromatic aldehyde and cyclohexanone encompass less steric hindrance with hydroxyl amine hydrochloride led to excellent yields of oximes (Table 3, entries 7–10). The melting point of the oximes is comparable with the literature (Li et al., 2006).

The recycling performance of l-AAIL-2 in the condensation reaction was subsequently explored. The catalytic system could be separated for the next cycle, by adding deionized water into the reaction mixture followed by full extraction of the product three times with 5 mL diethyl ether per extraction and recovering the catalyst from the aqueous phase by removing water under vacuum distillation and can be exploited for the next cycle. Excellent conversion of acetophenone to oxime was obtained for five consecutive cycles (Fig. 2 and Table 4).

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Figure 2

Ionic liquids used for the synthesis of oximes derivatives of carbonyl compounds.

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4 Conclusion

An efficient, quick and environmental pleasant green protocol has been developed for the preparation of oximes using catalytic system consisting of l-AAIL-2. This catalyst possesses increased compatibility to different carbonyl compounds and the reaction is carried out at ambient conditions. The method does not require any toxic bases/metal catalysts or solvents. The reusability of this novel catalyst gave excellent yield even after use for five times. All these characteristics make this protocol applicable for an industrial purpose.