Chiral Ion Research Articles

Separation of enantiomers of 4-aryldihydropyrimidines by direct enantioselective HPLC. A critical comparison of chiral stationary phases

The separation of the enantiomers of 29 racemic 4-aryldihydropyrimidine-5-carboxylates (DHPMs), aza-analogs of nifedipine-type dihydropyridine calcium channel modulators, was evaluated in direct enantioselective HPLC, employing the following commercially available chiral stationary phases (CSPs): Chiralcel OD-H, ChiraDex, Chirobiotic V and T, and Whelk-O1. In addition, a 1,2-diphenyl-1,2-diaminoethane based CSP and two quinine carbamate based chiral ion exchangers were also employed. For all 29 DHPMs separation of individual enantiomers could be achieved with at least one CSP with α-values ranging from 1.10 to 8.67.

Chiral Ions in the Gas Phase. 1. Intramolecular Racemization and Isomerization of O-Protonated (S)-trans-4-Hexen-3-ol

The acid-catalyzed racemization and regioisomerization of (S)-trans-4-hexen-3-ol (1S) has been investigated in gaseous CH4 and C3H8 at 720 Torr and in the 40−120 °C temperature range. The contribution to the racemization and isomerization products by free 1-methyl-3-ethylallyl cations, arising from unimolecular fragmentation of excited O-protonated (S)-trans-4-hexen-3-ol (IS), was evaluated by generating them from protonation of isomeric 2,4-hexadienes and by investigating their behavior toward H218O under the same experimental conditions. The rate constant of the gas phase racemization of IS (1.4−21.3 × 106 s-1) was found to exceed that of its isomerization (1.0−9.9 × 106 s-1) over the entire temperature range. The experimental results, combined with ab initio theoretical calculations on the model [C3H5+/H2O] system, are consistent with a gas phase intramolecular IS racemization and isomerization involving the intermediacy of structured ion−molecule complexes, wherein the H2O molecule is coplanarly coordinated to the hydrogen atoms of the 1-methyl-3-ethylallyl moiety. The rate of formation of these structured complexes, their relative stability, and the dynamics of their evolution to the racemized and isomerized products depend, in the gas phase, on the specific conformation of IS. The relevant activation parameters point to transition structures wherein a substantial fraction of the positive charge is located on the allyl moiety. The results obtained in the present gas phase investigation confirm previous indications about the occurrence and the role of intimate ion−molecule pairs in acid-catalyzed racemization and isomerization of optically active alcohols, including allylic alcohols, in solution.

Stereoselective reaction of a chiral assisted amide enolate ion with 1-iodonaphthalene by the SRN1 mechanism

Stereoselective reaction of a chiral assisted amide enolate ion with 1-iodonaphthalene by the SRN1 mechanism

Application of circularly polarized luminescence spectroscopy to the solution structure of racemic polyaminocarboxylate lanthanide (III) complexes

Circularly polarized luminescence from 1:1 complexes of Eu(III) with triethylenetetra-aminehexaacetic acid (TTHA) following excitation with circularly polarized light is reported. This observation is consistent with a solution structure for this complex that is chiral, and stable on the emission time scale of Eu(III) (approximately 1.2ms). Additional measurements show only a slight dependence on temperature, and an estimate for the activation energy for racemization (23 kcal/mol) may be obtained. Attempts at detecting enantio-selective quenching of Tb(TTHA) 3- by optically active Ru(phen) 2+ 3 are also reported. Although significant quenching was observed, and the time-decay of the Tb(III) emission was not mono-exponential, no enantio-selectivity was found. This latter result may be interpreted in terms of the lack of discriminating short-range diastereomeric interactions between the chiral ion pairs.

Acid‐catalysed solvolysis of optically active 1‐Phenyl‐1‐methoxythane. The role of ion– molecule pair intermediates

AbstractThe acid‐catalysed solvolysis of (R)‐1‐phenyl‐1‐methoxyethane was studied in mixtures of dilute aqueous perchloric acid and acetonitrile at 50°C. The rate of loss of optical activity (kα) was found to be the same as the rate of solvolysis (ksolv) at both low and high water contents of the solvent. These results are not in accord with literature data on racemization and oxygen exchange of 1‐phenylethanol in water, which has been discussed in terms of interconversion of chiral ion–dipole pair intermediates. The mechanistic implications of the results are discussed.

Electrochirally controlled bistable surface switching in nematic liquid crystals

We present an electrically controlled bistable surface switching for nematic liquid crystals, in cells with the usual display geometry. The surface bistability is controlled by means of an electrochiral effect, by doping a nematic with chiral ions. The alternate transient commutation between the two surface states is related to the sign of an applied pulsed electric field. The threshold behavior allows a writing surface time of 32 μs for a field of 21 V/1.3 μm. In the birefringence mode, the optical texture response time is 0.3 ms. The effect, comparable with the one used with ferroelectric smectic liquid crystals, could be used to realize high definition video passive matrix displays.

Normal Phase TLC Separation of Enantiomers Using Chiral Ion Interaction Agents

Abstract A method for the thin layer chromatographic (TLC) separation of enantiomers and diastereomers involving the use of chiral ion interaction agents is described. Several aromatic amino alcohols were resolved by TLC on diol and/or high performance silica gel plates using a mobile phase containing (1R)-(-)- ammonium-10-camphorsulfonate or N-benzoxycarbonyl-glycyl-L-proline (ZGP). Many of these chiral aromatic amino alcohols are of pharmacological importance as α- and β-adrenergic blockers, adrenergic compounds, and anti-glaucoma agents. A comparison was made between various N-CBZ-amino acid derivatives as chiral counter ions/chiral mobile phase additives (CMAs). These separations could not be achieved on other normal phase TLC stationary phases including microcrystalline cellulose, alumina and ordinary silica gel plates.

The Phenomenon of Conglomerate Crystallization. XVII. Clavic Dissymmetry in Coordination Compounds. XV. The Effect of the Charge Compensating Ions on the Phenomenon of Conglomerate Crystallization

Abstract In this report, we discuss the effect of the counter ion on the crystallization behaviour of chiral ions which may produce racemic or conglomerate crystals. We demonstrate that the counter ion is often capable of influencing the crystallization pathway and provide examples of substances in which the same chiral ion produces enantiomorphic crystals or racemic crystals depending on the nature of the counter ion. Moreover, we demonstrate that the crystal structures of such species amply demonstrate the reasons for such differences in crystallization pathway. In the species selected for the illustrations, the underlying phenomenon being influenced by the choice of counter ion is hydrogen bonding. This summary provides examples of counter ion pairs as varied as halides vs NO3 −, halides vs NO2 −, K+1 vs Ag+, etc., influencing the choice of crystallization pathway. Also, we illustrate the fact that the same ion (i.e., NO3 −) can play either a positive or a negative role in such a selection.

The effect of external electric fields on molecular liquids and induced translational motion

Abstract A computer simulation is reported of the enantiomer S CHBrClF subjected in the liquid state to intense external fields of force : i) uniaxial electric field EZ; ii) circularly polarised field at optical frequencies. The molecular dynamics are quantified in detail at field - on equilibrium in case i) using a range of auto correlation functions. The foremost result of the investigation is that the simple uniaxial field EZ makes the sample translate in a well defined direction. The direct effect of EZ on an isolated molecule of S-CHBrClF is purely rotational, but intramolecular rotation/translation coupling converts this rotation into coherent centre of mass translation. This gives rise to direct, laboratory frame , cross correlations of the type J T(o)> where v is the molecular centre of mass translational velocity and J T the transposed molecular angular momentum vector. (The existence of these invalidates the classical theory of the Kerr effect.) The molecular dynamics of the hypothetical chiral ion S-CHBrClF− are looked at with a view to corroborating the predictions by Baranova et al. concerning their response to electric field treatment. Despite the inherent instability of such an ensemble of like-charged ions the simulation can be used to produce a range of auto and cross-correlation functions with which to characterise the ionic dynamics. The effect of treating the ionic ensemble with a field EZ is reported briefly in terms of the non-vanishing ensemble averaged centre of mass velocity ;. The induced translation in an electric field may be demonstrated on most liquids using a simple experimental set up. Its importance in optically active systems is such that it may be used to separate a racemic mixture into its enantiomers, the translational motion induced in the one enantiomer is necessarily, by symmetry, opposite to that induced in the other enantiomer. The observation therefore has technological importance. Other applications are discussed.

Normal-phase dynamic (solvent-generated) molecular complexation chromatography using anionic ion exchangers : II. Separation of optical isomers

A chiral ion exchanger, (+)- and (−)-antipodes of 10-camphorsulphonic acid, was applied for the normal-phase solvent-generated molecular complexation chromatography of optical isomers of alkaloids. It was dissolved in the less polar phase of a three-component eluent mixture consisting of solvents having different polarities. Separations were performed on a polar bonded stationary phase (cyanopropylsilica). Remarkably high relative retentions were archieved, permitting rapid chiral separation of different eburnane alkaloids selected as models for the investigations. The influence of mobile phase composition and optical antipode selection of the ion exchanger on the selectivity and efficiency of the separation is discussed. Some applications of the proposed method, including the separation of eight optical isomers of vincamine, are discussed.