Chiral ionic liquids (CILs) are attractive for their potential applications in chiral analysis. The recent increase in ILs derived from amino acids that are chiral, ‘green', biocompatible and less toxic has also created interest in CILs. The synthesis and analysis of CILs derived from both enantiomeric forms of alanine and leucine ester chlorides and lithium bis- (pentafluoroethylsulfonyl)imide is described. The resultant CILs were liquids and thermally stable up to 288°C. The L-alanine-based IL had a melting point of 25°C and showed chiral recognition for enantiomers of 2,2,2-trifluoroanthrylethanol, indicating potential as media for chiral separations.

Introduction
Chiral compounds are often used to make pharmaceutical drugs. However, enantiomers of the same chiral compound can produce different pharmacological effects in the human body [1]. In this past decade, rising numbers of chiral drugs approved for retailing and use contain a single enantiomer as the therapeutically active form. This is due to stricter regulations by the U.S Food and Drug Administration (FDA) regarding the manufacture, use and marketing of chiral drugs, and the European Union (EU) requirement for investigation of chiral active substances [2]. Unfortunately, most chiral drugs are produced as a mixture of both enantiomers. Hence, there is an increased need to develop techniques and analytical assays that can separate enantiomers.

Chiral ionic liquids are organic salts containing a combination of either chiral cations and/or chiral anions and represent a class of liquid organic salts commonly known as room temperature ILs. These molecules are popular for their application in chiral separations including their use as stationary phases for gas chromatography (GC) and additives in high performance liquid chromatography (HPLC) or capillary electrophoresis (CE). [3] Despite many reports of CILs derived from amino acids, there are only a few cases where the chiral cation is an amino acid ester (AAE). The presence of an ester group can increase the biodegradability of such CILs. Bwambok et al recently reported AAE based CILs for enantiomeric recognition. [3,4] In 2005, Tao et al prepared CILs from amino acids containing methyl and ethyl ester groups.

[5] In this study, we report the synthesis and characterization of both enantiomeric forms of new CILs from alanine and leucine tert butyl ester cations and a less common anion, bis-(pentafluoroethylsulfonyl)imide.

Materials and Methods

Reagents
Tetramethyl silane (TMS), deuterated dimethylsulfoxide (d6-DMSO), enantiomerically pure R- and S-2,2,2-Trifluoro-1-(9-anthryl)ethanol (TFAE), L- and D- alanine tert butyl ester hydrochloride, L- and D-Leucine tert butyl ester hydrochloride were purchased from Sigma and/or TCI America and lithium bis-(pentafluoroethylsulfonyl) imide (LiBETA) from 3M. All products were used as received.

Instrumental Methods
Nuclear magnetic resonance (NMR) spectra were recorded in d6-DMSO on a Bruker-250 MHz instrument using TMS as an internal standard. The thermal decomposition temperatures were determined by thermal gravimetric analysis using a thermal analysis instrument TGA Q50. A 5^oC min-1 heating rate was used in nitrogen from 25^oC and 50^oC to 500^oC. Melting point and glass transition temperatures were determined by differential scanning calorimetry using a Shimadzu DSC-60 at a rate of 5^oC min-1 by cooling the samples from 50°C to -50°C, followed by heating from -50°C to 50°C. Fluorescence measurements were taken using a Photon Technology International QuantaMaster System equipped with a 75 W xenon lamp and a photomultiplier detector. Sample measurements were taken with a 10-mm quartz cuvette with 2 nm slit widths and excited at 366 nm.

Synthesis
The synthesis of both enantiomers of alanine tert butyl ester bis-(pentafluoroethylsulfonyl) imide (L- and D- Ala t-butyl ester BETA) was accomplished by mixing two equimolar solutions of L - and D -alanine tert butyl ester hydrochlorides with lithium bis-(penta­fluoroethylsulfonyl)imide (LiBETA) (Scheme 1) for 2 hours at room temperature and obtaining the bottom layer of the resulting two layers. The bottom layer was purified by washing several times with water and then dried under vacuum for two days. Colorless low-viscous liquids were obtained with 75% overall yield. ¹H NMR (250 MHz, d6 DMSO) δ (ppm) 8.25 (s, 3H), 4.00 (q, 1H), 1.50 (s, 9H), 1.35 (d, 3H). 13C NMR δ (ppm) 170.00, 83.24, 48.74, 27.99, 16.27.

Similarly, L- and D- leucine tert butyl ester bis-(pentafluoroethyl­sulfonyl) imide (L- and D- Leu t-butyl ester BETA) were synthesized from L- and D-leucine tert butyl ester hydrochlorides and LiBETA (Scheme 1). Colorless slightly more viscous liquids were obtained with 85% overall yields. ¹H NMR (250 MHz, d6 DMSO) δ (ppm) 8.15 (s, 3H), 3.87 (t, 1H), 1.62 (dd, 2H), 1.58 (m, 1H), 1.47 (s, 9H), 0.91 (d, 3H), 0.90 (d, 3H). 13C NMR (ppm) 169.60, 122.50, 117.38, 83.38, 51.46, 27.87, 24.27, 22.42.