A Convenient Synthesis of Triflate Anion Ionic Liquids and Their Properties

A solvent- and halogen-free synthesis of high purity triflate ionic liquids via direct alkylation of organic bases (amines, phosphines or heterocyclic compounds) with methyl and ethyl trifluoromethanesulfonate (methyl and ethyl triflate) has been developed. Cheap and non-toxic dimethyl and diethyl carbonate serve as source for the methyl and ethyl groups in the preparation of methyl and ethyl triflate by this invented process. The properties of ionic liquids containing the triflate anion are determined and discussed.


Introduction
Ionic liquids (ILs) with the triflate anion ([CF 3 SO 3 ] − ; OTf) are of interest for practical application in various fields [1][2][3][4]. Triflate ionic liquids are hydrolytically stable and in many cases they are the preferred reaction media in comparison to ionic liquids with the hydrolytically unstable [PF 6 4 ] gives only 9-12% yield [5]. Recently it was demonstrated that [BMIM][OTf] is also a suitable reaction medium for fluorolactonization of unsaturated carboxylic acids [6]. The combination of [BMIM][OTf] with triflic acid (CF 3 SO 3 H, cat.) provides good conditions for the Schmidt reaction, i.e., the conversion of aryl alkyl ketones to the corresponding carboxamides [7]. In triflate ionic liquids polymerization of methyl methacrylate (MMA) generally yields the highest molecular weight [8]. These examples demonstrate the utility of triflate ionic liquids in organic synthesis or in polymer chemistry, but there are further applications for triflate ILs. Due to their high thermal and electrochemical stability these ionic liquids are of interest as heat transfer materials, lubricants and as components of electrolytes for electrochemical cells. The purity of ionic liquids is particularly important for their use in electrochemistry, and quality control should be always in the focus during the preparation of ILs for this application [2].
Typically triflate ionic liquids are prepared by means of the metathesis reaction of the corresponding chlorides, bromides or methylsulfates with metal triflates, CF 3 SO 2 OM, for instance M = K [9,10], Na [11], Li [12], Ag [13], with ammonium triflate [14] or triflic acid, CF 3 SO 3 H [15]. The ionic liquids prepared by means of this methodology have to be purified from the side products: metal chlorides or bromides, or HCl. The side products then need to be disposed of. The reactions referred above were carried out in organic solvents such as dichloromethane, chloroform, acetone, or methanol, but if we are considering ionic liquids as replacements for volatile organic solvents to perform chemical reactions, then logically the ionic liquids themselves should be produced without the use of organic solvents [16]. Mikami wrote "It is also important to underline that to justify the green solvents label, ionic liquids have to be prepared in an ecological way, without the generation of a large amount of waste material" [17].
Recently, the syntheses of ionic liquids under solvent free conditions were tested by application of microwave (MW), power ultrasound (US) and combined MW/US irradiation [18,19]. The authors have carried out the one pot synthesis of triflate ionic liquids by reacting pyridine or N-methylpyrrolidine, or N-methylimidazole with 1-chlorobutane or 1-chlorooctane in the presence of potassium triflate, KOTf. The reaction mixture was heated under MW-irradiation up to 180 °C after an initial step (10-15 min at 120 °C). This reaction gives the corresponding ionic liquids in 60% to 79% yield [18]. KCl is formed as a side product in this reaction. Replacement of 1-chloroalkanes by 1-bromoalkanes reduced the reaction temperature to 80-90 °C [19]. The yield of ionic liquids increased up to 90%, but KBr is formed as a side product. The final products prepared by means of this methodology have to be purified using organic solvents (acetone, dichloromethane, diethyl ether) to reduce the halogen (chloride or bromide) impurities [18,19].
According to an assessment recently carried out by Deetlefs and Seddon [20] applications of microwave (MW), ultrasound (US) or combined MW/US irradiation to the syntheses of ionic liquids do not meet the principles of green chemistry to the full extent. This technology provides only low-medium atom economy and has a poor E-factor value. Preparation of ionic liquids by alkylation of organic substances with a suitable alkylating reagent is much "greener" in comparison to the metathesis protocol.
Triflic acid is the starting material for the production of all variety of triflates, i.e., metal salts, organic salts, triflic anhydride and alkytriflates, CF 3 SO 2 OR. Methyl trfiflate, CF 3 SO 2 OCH 3 , was first synthesised by Gramstadt and Haszeldine by the reaction of silver triflate with methyl iodide [23] (Scheme 1). Scheme 1. Synthesis of methyl triflate by the reaction of silver triflate with methyl iodide [23].
Later on Booth et al. [24] used triflic anhydride as a starting material for the synthesis of methyl triflate, CF 3 SO 2 OCH 3 , via reaction with methanol (Scheme 2). Scheme 2. Synthesis of methyl triflate by the reaction of triflic anhydride with methanol [24].
This method can be used to prepare various alkyl triflates, CF 3 SO 2 OR, [25,26], but it is not very economical because half of the triflic anhydride is lost. The yield of methyl triflate in this reaction is also not satisfying. A simpler and less expensive procedure for methyl triflate preparation was developed Beard et al. [27] (Scheme 3), but additional efforts are required to utilize the side product, sulphuric acid, contaminated with toxic dimethylsulfate. Scheme 3. Synthesis of methyl triflate by the reaction of triflic acid with dimethylsulfate [27].

Results and Discussion
Recently Merck KGaA (Darmstadt, Germany) has developed a new protocol for the preparation of methyl triflate [28] (Scheme 4). Scheme 4. Synthesis of methyl triflate by the reaction of triflic anhydride with dimethylcarbonate [28].
Commercial available dimethyl carbonate serves as source for the methyl groups in this reaction. This invented method provides a very convenient access to methyl triflate, CF 3 SO 2 OCH 3 . This chemical is formed in a very good yield and CO 2 is the only side product in this process. Traces of triflic acid (which is typically present in the commercial triflic anhydride) are enough to catalyse the conversion of triflic acid anhydride and dimethyl carbonate into methyl triflate (Scheme 4). The possible mechanism of this reaction can be described as follows (Scheme 5).

Scheme 5.
Proposed mechanism of the reaction of triflic anhydride with dimethylcarbonate catalyzed by triflic acid.
In the first step triflic acid protonates dimethyl carbonate (Equation 1) inducing the methyl cation transfer to the triflate anion resulting in methyl triflate (Equations 1 and 2). Triflic acid is regenerated in the reaction of triflic anhydride with the water which is formed by decomposition of carbonic acid (Scheme 5, Equation 3). According to this mechanism the triflic acid anhydride plays a role as water scavenger.
The disadvantage of this method is the use of the relatively expensive starting material triflic acid anhydride. To reduce the production costs the combination of triflic acid and acyl or aryl chlorides can be used instead of triflic acid anhydride in this process (Scheme 6) [29]. Acyl or aryl chlorides (for instance cheap and readily available benzoyl chloride) play the role of scavenger of the alcohol and water which are generated as intermediates during the process. Scheme 6. Syntheses of methyl and ethyl triflate by the reaction of triflic acid with dimethyl-and diethyl-carbonate in the presence of benzoyl chloride [29].
This method provides a very convenient and simple access not only to methyl triflate, but also to ethyl triflate (Scheme 6). Ethyl triflate or methyl triflate can easily be distilled out of the reaction mixture. The residue consists of ethyl or methyl benzoate, which are valuable products as well.
The alkylation ability of methyl triflate is comparable to that of the Meerwein salt [41]. We have used the alkylation power of methyl triflate to convert ionic liquids with chloride or bromide counteranions to the corresponding ILs with triflate anion (Scheme 7) [42,43]. Scheme 7. Preparation of triflate ionic liquids from corresponding chlorides or bromides [42,43]. This is a very convenient method to prepare triflate ionic liquids with various substituents R and R'. The reaction progresses very fast at room temperature under solvent free conditions. The gaseous CH 3 Cl or very volatile CH 3 Br are the only side products in this process. Trimethylsilyl triflate is less active in these reactions, but more convenient to handle [42,43]. The side product, trimethylchlorosilane, can be easily utilised.
To avoid the formation of any side products, the direct alkylation of amines, phosphines or heterocyclic compounds with ethyl or methyl triflate is favored (Scheme 8) [28,29]. This water and halogen free process gives the possibility to prepare triflate ionic liquids of very high quality with residual water below 10 ppm and non-detectable halogenide impurities. This is particularly important for the electrochemical applications of ionic liquids [2].

Scheme 8. Preparation of triflate ionic liquids by means of alkylation with methyl or ethyl triflate.
This method can be applied to the alkylation of trialkylamines, trialkylphosphines, N,N,N',N'-tetramethylguanidine and N,N,N',N'-tetramethylurea (see Experimental section). The synthesis can be carried out under solvent free conditions at 0 °C. The product yield is close to quantitative. It means that atom economy is very high (close to 100%) and the E-factor has an excellent value [20]. If a solid material is formed during the alkylation process (for example N,N-dimethylpyrrolidium triflate), diluting the reaction mixture with hexane, which can be easily regenerated, is favored.
2-Methyl-5-ethylpyridine and the 2,4,6-trimethylpyridine can be methylated with methyl triflate in quantitative yield (Scheme 9). But, if the steric hindrance is too strong, for example, in the case of 2,4,6-tris(t-butyl)pyridine, the reaction proceeds very slowly and the product yield is low (see Experimental section).
Ionic liquids with the triflate anion possess high thermal stability (see Figure 1 and Table 1), good electrochemical stability (see Figure 2 and Table 2) and fairly low viscosity (see Tables 3 and 4).      Table 3). The triflate anion is less coordinating than the CH 3 OSO 3 -anion. Weaker interaction between the [CF 3 SO 3 ] anion and the EMIM-cation reduces the viscosity of triflate ionic liquids in comparison to methylsulfate ILs [44]. Nevertheless, triflate ILs are more viscous than ionic liquids with weekly coordinating anions such as [(C 2 F 5 ) 3 PF 3 ] [45] and [(CF 3 SO 2 ) 2 N] ( Table 4). The viscosity of triflate ionic liquids is influenced by water or organic solvents impurities (decrease of viscosity) and metal triflate impurities (increase of the viscosity value), which can remain in the triflate ILs after metathesis reaction. The possible applications of triflate ionic liquids themselves or in combination with Brønsted acids for dehydration of alcohols, deprotection of ketals or synthesis of chromane derivatives are described in the cited patents applications [46][47][48].

Chemicals
Commercially available chemicals have been used. Triflic acid and triflic acid anhydride was provided by Merck KGaA (Darmstadt, Germany) company and used without further purification. Methyl trifluoromethanesulfonate (methyl triflate) and ethyl trifluoromethanesulfonate (ethyl triflate) were obtained and distilled as described below and stored under a nitrogen atmosphere. Heterocyclic bases were distilled over CaH 2 and stored under a nitrogen atmosphere.

NMR Spectroscopy
NMR samples were measured in 5 mm precision glass NMR tube (Wilmad 507 or 528 PPT) at 24 °C. NMR spectra were recorded in the deuterium-locked mode on a Bruker Avance III spectrometer equipped with a 9.3980 T cryomagnet. The 1 H-and 19 F-NMR spectra were acquired using a 5 mm 1 H/ 19 F combination probe operating at 400.17 and 376.54 MHz respectively. 13 C-NMR spectra were obtained using a 5 mm broad-band inverse probe operating at 100.61 MHz. Spectra were recorded using various memory sizes, optimal acquisition times, and relaxation delays (0.5-2 s). The 1 H-NMR chemical shifts were referenced with respect to tetramethylsilane (TMS) using the chemical shifts for the solvents CH 2 Cl 2 (5.32 ppm) and CH 3 CN (1.95 ppm). The 13 C-NMR chemical shifts were referenced with respect to TMS using the chemical shifts for the solvents CH 2 Cl 2 (53.5 ppm) and CH 3 CN (118.7 ppm). The 19 F-NMR spectra were referenced with respect to CFCl 3 using either the internal standards C 6 F 6 (−162.9 ppm) or C 6 H 5 CF 3 (−63.9 ppm) or externally to a neat CFCl 3 reference sample at 24 °C.

Elemental Analysis
Elemental analysis was performed using a HEKATECH EA 3000 elemental analyser (HEKAtech GmbH, Wegberg, Germany) with Callidus software.

Thermal Analyses
The thermal analyses were performed using a NETZSCH 409C STA (Selb, Germany).

Viscosity
Viscosity and density of ionic liquids were measured on the viscosimeter SVM 3000 (Anton Paar, Graz, Austria).

Cyclic Voltammetry
For electrochemical stability measurements an Autolab PGSTAT 30 (Metrohm Autolab B.V., Utrecht, The Netherlands) was used. Cyclic voltammograms were recorded for 0.5 M solutions in CH 3 CN at glassy carbon (gc) working electrode; auxiliary electrode was Pt and Ag/AgNO 3 (CH 3 CN) was used as reference electrode. The purity (quality) of triflate ionic liquids was proven by measuring of residual water (Karl-Fischer titration; 831 KF-Coulometer, Metrohm, Filderstadt, Germany) and chloride or bromide (ion-chromotography, Metrohm Advanced IC System; stationary phase: Metrosep A SUPP4-150). Contents of residual water and halides were below 100 ppm. Trifluoromethanesulfonic acid (918 g, 6.12 mol) was slowly added to freshly distilled benzoyl chloride (860 g, 6.12 mol) under a very slight positive N 2 pressure with mechanical stirring. After the addition was completed (20 min), the solution was heated to 95 °C. Freshly distilled diethyl carbonate (690 g, 5.83 mol) was then dropped slowly into the solution under vigorous stirring over a period of 3 h. During the addition a gas stream of of CO 2 and HCl passed through the H 2 SO 4 -filled bubbler. Stirring was continued for 1 h at 100 °C to complete the reaction. The raw product was distilled off immediately over a short column under a dry atmosphere until the head-temperature raised above 125 °C. The yield of the colourless raw product was 92%. Purification by fractional distillation gives 874 g

1-Ethyl-3-methylimidazolium Trifluoromethanesulfonate [C 6 H 11 N 2 ][CF 3 SO 3 ]
Freshly distilled ethyl trifluoromethanesulfonate (895 g, 5.02 mol) was dropped slowly into magnetically stirred N-methylimidazole (400 g, 4.87 mol) at 0 °C over a period of 6 h. Stirring  26 mmol] was stirred at room temperature for 4 h. The residue was dried for 30 min under vacuum at 0.13 mbar and 120 °C (oil-bath temperature), giving 2.81 g (a quantitative yield) of 1-hexyl-3-methylimidazolium triflate. The product was characterised by means of NMR spectroscopy. The spectra are identical to those of the product obtained by Method (a).

Conclusions
New economical syntheses of methyl and ethyl triflate from dimethyl-and diethyl carbonate and triflic acid has been developed. These chemicals were used in solvent and halogen free syntheses of high purity triflate ionic liquids via direct alkylation of organic bases: amines, phosphines or heterocyclic compounds. Ionic liquids with the triflate anion possess high thermal and electrochemical stability and fairly low viscosity.