CHIRALITY 27:320–325 (2015)
Chiral Discrimination by Ionic Liquids: Impact of Ionic Solutes CHRISTOPHER J. BROWN, AND TODD A. HOPKINS* Department of Chemistry, Butler University, Indianapolis, Indiana
ABSTRACT Chiral ionic liquids hold promise in many asymmetric applications. This study explores the impact of ionic solutes on the chiral discrimination of five amino acid methyl ester-based ionic liquids, including L- and D-alanine methyl ester, L-proline methyl ester, L-leucine methyl ester, and L-valine methyl ester cations combined with bis(trifluoromethanesulfonimide) anion. Circularly polarized luminescence spectroscopy was used to study the chiral discrimination by measuring the racemization equilibrium of a dissymmetric europium complex, Eu(dpa)33 (where dpa = 2,6-pyridinedicarboxylate). The chiral discrimination measured was dependent on the concentration of Eu(dpa)33 and this concentration-dependence was different in each of the ionic liquids. Ionic liquids with L-leucine methyl ester and L-valine methyl ester even switched enantiomeric preference based on the solute concentration. Changing the cation of the Eu(dpa)33 salt from tetrabutylammonium to tetramethylammonium ion also affected the chiral discrimination demonstrated by the ionic liquids. Chirality 27:320–325, 2015. © 2015 Wiley Periodicals, Inc.
KEY WORDS: chiral ionic liquids; circularly polarized luminescence; racemization; chiral discrimination Ionic liquids are low-melting-point salts that have attracted interest as solvents in numerous applications.1–7 One of the driving forces behind the interest in ionic liquids (ILs) is that they offer synthetic control over properties through the choice and design of the cations and anions involved. When the cation and/or anion are chiral, the IL can be used as a chiral solvent for chiral discriminatory processes.8–10 There are numerous examples of chiral ILs that have application in chiral separations, catalysis, and asymmetric synthesis.10–15 In order to fully exploit chiral ILs as solvents for these applications, it is important to understand the chiral discriminatory solute–solvent interaction in chiral ILs. Previously, we studied the chiral discrimination demonstrated by a series of amino acid methyl ester bis (trifluoromethanesulfonimide) ionic liquids by measuring their influence on a racemization equilibrium.16 The primary aim of that study was to relate the structural differences of amino acid methyl esters, including L-alanine methyl ester (L-AlaC1), D-alanine methyl ester (D-AlaC1), L-proline methyl ester (L-ProC1), and L-leucine methyl ester (L-LeuC1), to the chiral discrimination observed.16 The study showed that the handedness of chiral discrimination by the ILs depends on the stereochemistry of the amino acid methyl ester, where all of the L isomers (alanine, proline, and leucine methyl ester) shifted the equilibrium in one direction, while the D isomer shifted the equilibrium in the opposite direction. The thermodynamics of the chiral discrimination indicated that the size of the amino acid methyl ester played an important role in the discrimination, where leucine methyl ester, the largest IL cation, demonstrated chiral discrimination that was entirely entropically driven (i.e. no enthalpic contributions). The previous study focused on the impact of the solvent, and this article describes a study to understand how the solute impacts the chiral discrimination by the amino acid methyl ester ILs. Our method involves measuring how the chiral IL influences a racemization equilibrium process.16 The equilibrium is an interconversion between the Λ and Δ enantiomers of the luminescent coordination complex, © 2015 Wiley Periodicals, Inc.
17 The europium tris(2,6-pyridinedicarboxylate) (Eu(dpa)3 3 ). complex has three chelate rings that form a three-bladed propeller-like structure. The helicity along the trigonal symmetry axis defines the chirality of the enantiomers, where Δ = right-handed, and Λ = left-handed. The complex also has three twofold (digonal) symmetry axes, which have the opposite helicity of the trigonal axis (e.g., Λ is left-handed about the trigonal axis, but right-handed about the digonal axes). Figure 1 shows a structural representation of both enantiomers of Eu(dpa)33 along the trigonal (C3) axis. In the absence of a chiral perturbation, the Λ and Δ complexes exist as a racemic mixture. When dissolved in amino acid methyl ester ionic liquids, the strong interaction between the chiral amino acid methyl ester cations with the anionic europium complex shifts the equilibrium to a nonracemic population.16 The extent and preference (handedness) of the equilibrium shift is measured using circularly polarized luminescence (CPL) from the Eu(dpa)3 3 complexes. CPL is the difference in emission intensity of left (IL) versus right (IR) circularly polarized light. The observable in CPL that allows for comparison across different concentrations or luminescence efficiencies is the emission dissymmetry factor, gem (λ), and can be expressed as:
g em ðλÞ ¼
2jI L ðλÞ I R ðλÞj 2ΔI ðλÞ ¼ I L ðλÞ þ I R ðλÞ I ðλÞ
(1)
where ΔI(λ) is the CPL at wavelength λ, and I(λ) is the total luminescence at wavelength λ. The emission dissymmetry factor can have values that range from +2 to 2. Therefore, in these experiments the sign of gem shows the direction (handedness) that the racemization equilibrium is shifted, and the magnitude of gem shows the degree to which the *Correspondence to: Todd A. Hopkins, Department of Chemistry, Butler University, 4600 Sunset Ave., Indianapolis, IN 46208. E-mail: [email protected] Received for publication 18 June 2014; 2015; Accepted 27 January 2015 DOI: 10.1002/chir.22435 Published online 26 February 2015 in Wiley Online Library (wileyonlinelibrary.com).
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CHIRAL DISCRIMINATION BY IONIC LIQUIDS
Fig. 1. Space filling structural representation of the Δ (left side) and Λ 3 (right side) enantiomers of Eu(dpa)3 .
in the (X)3Eu(dpa)3 salt, where X = N4444+ or N1111+. Each of these cations is achiral, and has similar chemical properties. Therefore, the only influence the ammonium ions should have on the chiral discrimination by the ILs is based on their size, and how much that influences the interaction between the amino acid methyl ester cations and the Eu(dpa)33 ions. For the ILs studied, N4444+ is the largest cation and N1111+ is the smallest cation. The results of chiral discrimination of N4444+ vs. N1111+ (Eu(dpa)33) salts in [L-AlaC1][Tf2N] [D-AlaC1] [Tf2N], [L-ProC1][Tf2N], and [L-LeuC1][Tf2N] are measured in order to determine the impact of ionic size. MATERIALS AND METHODS
equilibrium is shifted. Therefore, the emission dissymmetry factor is a direct measure of the chiral discrimination by the amino acid methyl ester ILs. Because of their ionic nature, there is a unique aspect of the solvent properties of ILs when the solute is also ionic (i.e., a salt).18,19 For example, near ideal solution behavior is exhibited when ions of the salt closely match the size and chemistry of the ions in the IL.20 Because of the interesting properties that arise when ionic compounds are mixed, the study of mixtures of ionic liquids has seen steady growth.21–26 Given that the properties of ILs can change when dissolving salts, it is important to determine how an ionic solute, such as Eu(dpa)33, impacts the chiral discrimination ability of the chiral ILs. One of the goals of this study was to determine the impact of the concentration of Eu(dpa)33 on the chiral discrimination demonstrated by [L-AlaC1][Tf2N], [D-AlaC1][Tf2N], [L-ProC1] [Tf2N], and [L-LeuC1][Tf2N]. Numerous studies show that the shift of a racemization equilibrium, the Pfeiffer effect, depends strongly on the concentration of the added chiral probe.27 A study using L-histidine to perturb the racemization of Tb(dpa)33 (i.e., the Pfeiffer effect) demonstrates that the chiral discrimination increases with increasing L-histidine concentration.28 This concentration-dependent behavior was attributed to each L-histidine interacting with multiple Tb(dpa)33 complexes (i.e., the dissociated model). Another study showed that the Pfeiffer effect between praeseodymium (III) tris (oxydiacetate) (Pr(ODA)33), a similar propeller-blade like complex, and L-proline also showed an increase of chiral discrimination with increasing proline concentration.29 However, in this study the mechanism of discrimination was attributed to the formation of specific aggregates of Pr(ODA)33 and Lproline (i.e., the associated model). The results in this study are compared to Pfeiffer effect results to determine if the mechanisms of chiral discrimination apply when the chiral additive is also the solvent. The second goal of this study was to determine the impact of the cation in the Eu(dpa)33 salt on the chiral discrimination by amino acid methyl ester ILs. Previous studies on the addition of salts to ILs have shown that ions of similar size lead to near ideal solution behavior.20,24 In our previous study, only [L-LeuC1][Tf2N], with the largest cation, showed chiral discrimination with no enthalpic contribution.16 Therefore, the chiral discrimination was entirely driven by entropy in the IL with a cation, [L-LeuC1]+, similar in size to the tetrabutylammonium (N4444+) cation from the Eu(dpa)33 salt. This suggests that the relative size of the cations in the IL and salt impacts the chiral discrimination. In order to probe the impact of solute ionic size on chiral discrimination, both N4444+ and tetramethylammonium (N1111+) cations are used as the cation
All materials for preparation of the amino acid chiral ionic liquids, including lithium bis(trifluoromethanesulfonimide), amino acid methyl ester hydrogen chloride salts were purchased from Sigma-Aldrich (St. Louis, MO) and used without further purification. The amino acid methyl ester CILs were prepared following a literature procedure,30 where equimolar amounts of amino-acid methyl ester-HCl and lithium bi (trifluoromethanesulfonimide) were dissolved in a minimal volume of water. The solution forms two layers, and the amino acid CIL layer is separated from the aqueous layer using a separatory funnel. The amino acid CIL layer is then heated (
Chiral Discrimination by Ionic Liquids: Impact of Ionic Solutes CHRISTOPHER J. BROWN, AND TODD A. HOPKINS* Department of Chemistry, Butler University, Indianapolis, Indiana
ABSTRACT Chiral ionic liquids hold promise in many asymmetric applications. This study explores the impact of ionic solutes on the chiral discrimination of five amino acid methyl ester-based ionic liquids, including L- and D-alanine methyl ester, L-proline methyl ester, L-leucine methyl ester, and L-valine methyl ester cations combined with bis(trifluoromethanesulfonimide) anion. Circularly polarized luminescence spectroscopy was used to study the chiral discrimination by measuring the racemization equilibrium of a dissymmetric europium complex, Eu(dpa)33 (where dpa = 2,6-pyridinedicarboxylate). The chiral discrimination measured was dependent on the concentration of Eu(dpa)33 and this concentration-dependence was different in each of the ionic liquids. Ionic liquids with L-leucine methyl ester and L-valine methyl ester even switched enantiomeric preference based on the solute concentration. Changing the cation of the Eu(dpa)33 salt from tetrabutylammonium to tetramethylammonium ion also affected the chiral discrimination demonstrated by the ionic liquids. Chirality 27:320–325, 2015. © 2015 Wiley Periodicals, Inc.
KEY WORDS: chiral ionic liquids; circularly polarized luminescence; racemization; chiral discrimination Ionic liquids are low-melting-point salts that have attracted interest as solvents in numerous applications.1–7 One of the driving forces behind the interest in ionic liquids (ILs) is that they offer synthetic control over properties through the choice and design of the cations and anions involved. When the cation and/or anion are chiral, the IL can be used as a chiral solvent for chiral discriminatory processes.8–10 There are numerous examples of chiral ILs that have application in chiral separations, catalysis, and asymmetric synthesis.10–15 In order to fully exploit chiral ILs as solvents for these applications, it is important to understand the chiral discriminatory solute–solvent interaction in chiral ILs. Previously, we studied the chiral discrimination demonstrated by a series of amino acid methyl ester bis (trifluoromethanesulfonimide) ionic liquids by measuring their influence on a racemization equilibrium.16 The primary aim of that study was to relate the structural differences of amino acid methyl esters, including L-alanine methyl ester (L-AlaC1), D-alanine methyl ester (D-AlaC1), L-proline methyl ester (L-ProC1), and L-leucine methyl ester (L-LeuC1), to the chiral discrimination observed.16 The study showed that the handedness of chiral discrimination by the ILs depends on the stereochemistry of the amino acid methyl ester, where all of the L isomers (alanine, proline, and leucine methyl ester) shifted the equilibrium in one direction, while the D isomer shifted the equilibrium in the opposite direction. The thermodynamics of the chiral discrimination indicated that the size of the amino acid methyl ester played an important role in the discrimination, where leucine methyl ester, the largest IL cation, demonstrated chiral discrimination that was entirely entropically driven (i.e. no enthalpic contributions). The previous study focused on the impact of the solvent, and this article describes a study to understand how the solute impacts the chiral discrimination by the amino acid methyl ester ILs. Our method involves measuring how the chiral IL influences a racemization equilibrium process.16 The equilibrium is an interconversion between the Λ and Δ enantiomers of the luminescent coordination complex, © 2015 Wiley Periodicals, Inc.
17 The europium tris(2,6-pyridinedicarboxylate) (Eu(dpa)3 3 ). complex has three chelate rings that form a three-bladed propeller-like structure. The helicity along the trigonal symmetry axis defines the chirality of the enantiomers, where Δ = right-handed, and Λ = left-handed. The complex also has three twofold (digonal) symmetry axes, which have the opposite helicity of the trigonal axis (e.g., Λ is left-handed about the trigonal axis, but right-handed about the digonal axes). Figure 1 shows a structural representation of both enantiomers of Eu(dpa)33 along the trigonal (C3) axis. In the absence of a chiral perturbation, the Λ and Δ complexes exist as a racemic mixture. When dissolved in amino acid methyl ester ionic liquids, the strong interaction between the chiral amino acid methyl ester cations with the anionic europium complex shifts the equilibrium to a nonracemic population.16 The extent and preference (handedness) of the equilibrium shift is measured using circularly polarized luminescence (CPL) from the Eu(dpa)3 3 complexes. CPL is the difference in emission intensity of left (IL) versus right (IR) circularly polarized light. The observable in CPL that allows for comparison across different concentrations or luminescence efficiencies is the emission dissymmetry factor, gem (λ), and can be expressed as:
g em ðλÞ ¼
2jI L ðλÞ I R ðλÞj 2ΔI ðλÞ ¼ I L ðλÞ þ I R ðλÞ I ðλÞ
(1)
where ΔI(λ) is the CPL at wavelength λ, and I(λ) is the total luminescence at wavelength λ. The emission dissymmetry factor can have values that range from +2 to 2. Therefore, in these experiments the sign of gem shows the direction (handedness) that the racemization equilibrium is shifted, and the magnitude of gem shows the degree to which the *Correspondence to: Todd A. Hopkins, Department of Chemistry, Butler University, 4600 Sunset Ave., Indianapolis, IN 46208. E-mail: [email protected] Received for publication 18 June 2014; 2015; Accepted 27 January 2015 DOI: 10.1002/chir.22435 Published online 26 February 2015 in Wiley Online Library (wileyonlinelibrary.com).
321
CHIRAL DISCRIMINATION BY IONIC LIQUIDS
Fig. 1. Space filling structural representation of the Δ (left side) and Λ 3 (right side) enantiomers of Eu(dpa)3 .
in the (X)3Eu(dpa)3 salt, where X = N4444+ or N1111+. Each of these cations is achiral, and has similar chemical properties. Therefore, the only influence the ammonium ions should have on the chiral discrimination by the ILs is based on their size, and how much that influences the interaction between the amino acid methyl ester cations and the Eu(dpa)33 ions. For the ILs studied, N4444+ is the largest cation and N1111+ is the smallest cation. The results of chiral discrimination of N4444+ vs. N1111+ (Eu(dpa)33) salts in [L-AlaC1][Tf2N] [D-AlaC1] [Tf2N], [L-ProC1][Tf2N], and [L-LeuC1][Tf2N] are measured in order to determine the impact of ionic size. MATERIALS AND METHODS
equilibrium is shifted. Therefore, the emission dissymmetry factor is a direct measure of the chiral discrimination by the amino acid methyl ester ILs. Because of their ionic nature, there is a unique aspect of the solvent properties of ILs when the solute is also ionic (i.e., a salt).18,19 For example, near ideal solution behavior is exhibited when ions of the salt closely match the size and chemistry of the ions in the IL.20 Because of the interesting properties that arise when ionic compounds are mixed, the study of mixtures of ionic liquids has seen steady growth.21–26 Given that the properties of ILs can change when dissolving salts, it is important to determine how an ionic solute, such as Eu(dpa)33, impacts the chiral discrimination ability of the chiral ILs. One of the goals of this study was to determine the impact of the concentration of Eu(dpa)33 on the chiral discrimination demonstrated by [L-AlaC1][Tf2N], [D-AlaC1][Tf2N], [L-ProC1] [Tf2N], and [L-LeuC1][Tf2N]. Numerous studies show that the shift of a racemization equilibrium, the Pfeiffer effect, depends strongly on the concentration of the added chiral probe.27 A study using L-histidine to perturb the racemization of Tb(dpa)33 (i.e., the Pfeiffer effect) demonstrates that the chiral discrimination increases with increasing L-histidine concentration.28 This concentration-dependent behavior was attributed to each L-histidine interacting with multiple Tb(dpa)33 complexes (i.e., the dissociated model). Another study showed that the Pfeiffer effect between praeseodymium (III) tris (oxydiacetate) (Pr(ODA)33), a similar propeller-blade like complex, and L-proline also showed an increase of chiral discrimination with increasing proline concentration.29 However, in this study the mechanism of discrimination was attributed to the formation of specific aggregates of Pr(ODA)33 and Lproline (i.e., the associated model). The results in this study are compared to Pfeiffer effect results to determine if the mechanisms of chiral discrimination apply when the chiral additive is also the solvent. The second goal of this study was to determine the impact of the cation in the Eu(dpa)33 salt on the chiral discrimination by amino acid methyl ester ILs. Previous studies on the addition of salts to ILs have shown that ions of similar size lead to near ideal solution behavior.20,24 In our previous study, only [L-LeuC1][Tf2N], with the largest cation, showed chiral discrimination with no enthalpic contribution.16 Therefore, the chiral discrimination was entirely driven by entropy in the IL with a cation, [L-LeuC1]+, similar in size to the tetrabutylammonium (N4444+) cation from the Eu(dpa)33 salt. This suggests that the relative size of the cations in the IL and salt impacts the chiral discrimination. In order to probe the impact of solute ionic size on chiral discrimination, both N4444+ and tetramethylammonium (N1111+) cations are used as the cation
All materials for preparation of the amino acid chiral ionic liquids, including lithium bis(trifluoromethanesulfonimide), amino acid methyl ester hydrogen chloride salts were purchased from Sigma-Aldrich (St. Louis, MO) and used without further purification. The amino acid methyl ester CILs were prepared following a literature procedure,30 where equimolar amounts of amino-acid methyl ester-HCl and lithium bi (trifluoromethanesulfonimide) were dissolved in a minimal volume of water. The solution forms two layers, and the amino acid CIL layer is separated from the aqueous layer using a separatory funnel. The amino acid CIL layer is then heated (
