Julie L. L. Cartera,
Catherine C. Santinib,
Loïc J. Bluma and
Bastien Doumèche*a
aGEMBAS, ICBMS UMR 5246, Université Lyon 1, CNRS, 43 bd du 11 Novembre 1918, 69622 Villeurbanne Cedex, France. E-mail: doumeche@univ-lyon1.fr; Fax: +33 472 44 79 70; Tel: +33 472 43 14 84
bC2P2, UMR 5265, Université Lyon 1, CNRS, CPE, 43 bd du 11 Novembre 1918, 69622 Villeurbanne Cedex, France
First published on 25th February 2015
Imidazolium-based ionic liquids were discovered to contain micromolar (μM) quantities of a peroxide species. A general approach using catalase (aqueous solution) or a salen–manganese complex (neat IL) for reducing the presence of the peroxide species is described herein.
The preparation of these ILs, whether commercially or academically, plays a crucial role in the quality of the product. Unlike a traditional organic solvent, it is not possible to purify an ionic liquid using distillation due to its non-volatile nature and any impurities can alter its properties significantly, including the salt's color.11 The factors at play resulting in a colorless product instead of one that is colored are not entirely understood but most likely correspond to impurities already present in the reagents, thermal degradation of the reagents and/or oxidation products.11 For these reasons, our team routinely synthesizes a water-miscible IL, 1,3-dimethylimidazolium dimethyl phosphate, [MMIm][Me2PO4], using the approach by Kuhlmann12 in order to obtain a more optically pure product in contrast to commercial options.13 Synthesizing the liquid at low temperatures (≤80 °C), protected from light and under inert atmosphere minimizes the possibility of contamination, especially from water, which can act as a nucleophile during the quaternarization reaction.
For the current study, we discovered the presence of a peroxide species in an aqueous solution of [MMIm][Me2PO4] using horseradish peroxidase (HRP) and its substrate, 2,2′-Azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS), as the system of detection.14 The H2O2 was indirectly detected spectrophotometrically at 420 nm, which corresponds to the subsequent oxidation of ABTS by HRP in the presence of H2O2. The reaction takes place as follows:
To our knowledge, the formation or existence of peroxide species in ionic liquids has not been previously described in the literature. However, a peroxide species present in an IL should be considered as an important contaminant since even trace amounts of impurities could have a negative effect on chemical reactions. For instance, Heimer and co-workers recently demonstrated an oxidation reaction in different ionic liquids which involves the oxidative folding of peptides containing cysteine-rich regions.15 Depending on its concentration, the peroxide species present in an IL could interfere with the oxidation mechanism by disrupting disulfide bond formation within the peptide, keeping it locked in an unfolded state or leading to its misfolding.
The original concentration of the peroxide species detected in the sample was calculated by using the method of standard addition for a range of H2O2 concentrations from 0–45 μM to take into account the fact that the HRP's activity might be altered in different types of ILs (Fig. 1).
In order to determine whether the peroxide present in the samples could be a byproduct of IL synthesis, the starting materials used to obtain [MMIm][Me2PO4], methylimidazolium [MIm] and trimethyl phosphate [Me3PO4], were also tested for peroxide presence (Fig. 1). The non-redistilled MIm was compared to a redistilled MIm. While the trimethyl phosphate showed no significant peroxide species contamination (<0.2 μM), the concentration detected in the redistilled MIm was 63 μM. This result was significantly less than the 767 μM peroxide species concentration found in the non-redistilled MIm. Since it is thought that the color of an ionic liquid is influenced by contaminant compounds,16 it is important to note that the non-redistilled MIm, containing the highest concentration of the peroxide species, was an intense yellow-colored solution, whereas the redistilled MIm, containing the least amount of peroxide species, was a colorless solution.
Taking into account these results, fresh batches of [MMIm][Me2PO4] were synthesized using the redistilled MIm and the non-redistilled MIm. The [MMIm][Me2PO4] synthesized with the redistilled MIm had the least amount of peroxide detected, 123 μM, and was a colorless solution similar to the starting material (Fig. 2). The [MMIm][Me2PO4] synthesized with the non-redistilled MIm contained as much as 394 μM of peroxide species and was an intensely yellow-colored liquid like the non-redistilled MIm. Indeed, after vacuum evaporation of excess starting materials, the amount of peroxide in each sample had been significantly reduced: 23% for the non-redistilled [MMIm][Me2PO4] and 32% for redistilled [MMIm][Me2PO4] (Fig. 2).
Recent advances in the field have led to the development of distillable protic ILs based on Bronsted acids and base pairs whereby the neutral precursors are formed after proton displacement during distillation and eventually lead to peroxide elimination.17,18 Nevertheless, imidazolium-type ILs cannot be purified in this way since they retain their charge (aprotic ILs). However, the starting materials used in their fabrication are classically volatile compounds that can be distilled.19 This results in decomposition of the peroxide species.20 The reduction of excess MIm and Me3PO4 after vacuum evaporation was also verified by 1H-NMR and 31P-NMR (ESI†).
Addition of catalase to a [MMIm][Me2PO4] sample provided further confirmation that the contaminant in the different ILs was indeed a peroxide species (Fig. 2A). Metalloproteins such as catalase catalyze dismutation reactions by breaking down H2O2 into water and oxygen as shown by the following reaction:
Catalase: 2H2O2 → 2H2O + O2 |
After catalase treatment, the concentration of H2O2 in the aqueous sample of [MMIm][Me2PO4] (15% v/v) was found to be negligible as expected. Therefore addition of catalase in aqueous reactions involving ILs should be recommended. For non-aqueous medium applications, salen–manganese complexes can be used to reduce the presence of peroxide species as they exhibit both superoxide dismutase (SOD) and catalase-like activities.19 As a proof of concept, we used the salen–manganese complex despite the fact that it does not possess the best catalase-like activity.21 After 2 hours of salen treatment, a decrease in peroxide species concentration was observed and, after 48 hours, its presence was reduced by 99% from 394 μM to 3 μM (Fig. 2B). While removing peroxide species from the IL was faster using the enzymatic approach, the salen–manganese complex proved to be an efficient method for anhydrous chemical purposes. Furthermore, the oxidation of imidazolium-based ILs by H2O2, or ion pairing by nucleophilic attack of O2−˙ with the imidazolium cation, can both give rise to imidazolones and other byproducts.22,23 Unfortunately, we were unable to identify such a compound. We then compared the concentration of H2O2 detected in an older sample, 244 μM, to a more recently synthesized batch of [MMIm][Me2PO4]. The presence of peroxide in the latter was 198 μM. This corresponds to a 19% increase in the quantity of the peroxide species in the older batch and also shows that its presence in the ionic liquid increases overtime, probably due to moisture or oxygen dissolution.
In addition, several commercially-available water soluble ILs were tested and their peroxide content measured (Table 1). The data confirms that a peroxide species was detected in each of the samples analysed. While the dicyanamide and acetate-based ILs had lower quantities of peroxide, the phosphate and sulphate-based ILs showed varying results depending on the sample. The age of the IL is also important as the frequency with which the IL is exposed to light and moisture seems to increase the amount of peroxide present in the sample over time.
Type of IL | [H2O2] μM |
---|---|
a Reaction conditions: 15% (v/v) IL, [HRP] 1.30 U mL−1, [ABTS] 2 mM, [H2O2] 0–45 μM, phosphate buffer pH 7.6, 20 mM, 25 °C. | |
1,3-Dimethylimidazolium dimethyl phosphate | 34 ± 0.04 |
1-Ethyl-3-methylimidazolium diethyl phosphate | 155 ± 0.04 |
1-Butyl-3-methylimidazolium hexafluorophosphate | 12 ± 0.04 |
1-Ethyl-3-methylimidazolium ethyl sulfate | 57 ± 0.04 |
1-Butyl-3-methylimidazolium octyl sulfate | 177 ± 0.04 |
1-Butyl-3-methylimidazolium acetate | 7 ± 0.04 |
1-Butyl-3-methylimidazolium dicyanamide | 22 ± 0.04 |
1-Butyl-1-methylpyrrolidinium dicyanamide | 27 ± 0.04 |
We propose a mechanism in which the natural composition of the IL is sufficient enough to promote peroxide species formation (Scheme 1). It is well-established that the 2-position of imidazolium rings can readily deprotonate to form a stabilized carbon (II).24 We propose this carbon could react with dissolved molecular oxygen to form an intermediate (III). This may occur directly or via the formation of an endoperoxide as it was described for the oxidation of histidine by singlet molecular oxygen.25 The resulting intermediate could be further stabilized to the peroxide species (IV) and accumulate over time in the IL as oxygen continues to dissolve in the absence of water. This peroxide species could degrade into an imidazolone or hydroxy-imidazolone species in the presence of water.25 Such degradation products could appear after long-time storage and could participate in the apparition of color in the ILs. Their concentration (a few hundred μM) compared to the concentration of the neat IL (some molar) make them highly difficult to isolate. In addition, this could explain why Gu and co-workers observed the formation of hydrogen peroxide during the alkylation reaction of a cyclohexanone with an indole using a Brønsted acid ionic liquid.26 This reaction works best in the presence of oxygen, which could become activated by the IL, thereby forming the peroxide species. In this way, the peroxide species could have originated directly from the IL, instead of resulting from the reaction itself.
Organic reactions using in situ generation of hydrogen peroxide in ILs have been demonstrated and are proposed as an alternative to the industrial use of toxic, non-specific oxidants.27 While ILs have already been used in the polymerization of arenes28 and the reduction of dimethyl maleate and benzaldehyde,29 water-containing ILs have recently been shown to generate hydrogen peroxide by electroreduction of oxygen.30 The in situ generated hydrogen peroxide can then be used for the epoxidation of alkenes for example.30 Oxygen activated by imidazolium-based ILs could offer a catalytic-free alternative for these reactions.
In conclusion, we have shown for the first time the presence of a peroxide species in imidazolium-based ILs used in organic synthesis, biocatalysis and (bio)electronics. In light of these results, some previous studies dealing with oxidation reactions (electrochemical, chemical and biochemical) should possibly be regarded from a different perspective. Peroxides are normally unstable at room temperature but it is possible that room-temperature ILs might stabilize peroxide structures, thereby contributing to peroxide species propagation over time. Furthermore, the peroxide species present in starting materials greatly contributes to the quantity of peroxide species present in the IL. Distillation and vacuum evaporation can help to reduce the amount of peroxide found in starting materials and, consequently, in the finished products. We have also demonstrated that addition of catalase or salen–manganese complexes can eliminate the peroxide species in the IL. While the mechanism of peroxide formation in this medium remains unknown, these findings could help to improve reaction performance in ILs and to reduce unwanted side-reactions.
Footnote |
† Electronic supplementary information (ESI) available: Materials/methods, NMR spectra, dosage of H2O2, UV-vis spectra. See DOI: 10.1039/c5ra01080b |
This journal is © The Royal Society of Chemistry 2015 |