Separability of diastereomer salt pairs of 1-phenylethylamine with enantiomeric 2-substituted phenylacetic acids by fractional crystallization, and its relation to physical and phase properties

Anandamanoharan, P.; Cains, Peter W.; Jones, Alan G.

doi:10.1016/j.tetasy.2006.06.038

Cited by 16 publications

(31 citation statements)

References 12 publications

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“…Recently, several investigations have shown the importance of the CH-π interactions in the crystal structure, including selective enantiomeric enrichment, [34][35][36][37] properties of coordination complexes, [38][39][40][41] and mainly the folding and properties of molecular biological systems. [42][43][44][45] This weak electrostatic interaction can be seen in the ACSQ structure and also can be contributing to the hydrogen bonds for the torsion between the squarate and phenyl ring.…”

Section: Resultsmentioning

confidence: 99%

Role of the Substituent Effect over the Squarate Oxocarbonic Ring: Spectroscopy, Crystal Structure, and Density Functional Theory Calculations of 1,2-Dianilinosquairane

et al. 2010

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This work presents the crystal structure and the investigation under a supramolecular perspective of a squaric acid derivative obtained from the replacement of the hydroxyl groups by anilines. The squaraine obtained (1,2-dianilinesquaraine) crystallizes in the Pbcn space group, in a unit cell with a = 26.5911(8) Å, b = 6.1445(10) Å, and c = 7.5515(5) Å. The bond lengths in the oxocarbon ring, squarate-N and C−O bonds present the character of double bonds. Also the difference between the longer and shorter C-C bond in the four-membered ring (ΔCC) is 0.0667 Å, showing a good degree of equalization of these bond lengths. The phenyl rings are slightly distorted in relation to the squarate ring, and the angle measured between the best plane fitted in each ring is 37.2(9)°. Each molecule is connected to the other through a hydrogen bond involving the N-H···O moieties, where the donor···acceptor distance is 2.826(1) Å, forming ribbons in a unidimensional arrangement C(5)R22(10) along the b axis. These structures are mutually connected by π-stacking interactions extending the supramolecular structure in a two-dimensional fashion. Besides, an interesting crossed structure can be easily identified in the formed sheets that are built through the C-H/π interactions. DFT calculations at the B3LYP/6-311++G(d,p) level of theory show an approximately planar molecular structure for the isolated molecule. However, when a dimer model built from hydrogen bonds is considered, the optimized structure presents considerable torsion between the phenyl and squarate rings, as observed in the experimental data. The electronic spectrum shows a strong absorption band at 341 nm that is red-shifted compared to the squarate maximum absorption (290 nm), indicating a more effective electronic delocalization. The most characteristic vibrational modes of the oxocarbon species were used as spectroscopic probe to understand how the substituent groups affect the oxocarbon moiety and, consequently, the vibrational spectra. The analysis shows that the modes associated with the C-Cox bonds are the most affected. Also the character of the double bond of squarate-N and the single bond for the phenyl-N are easily identified. In a general form, the calculated vibrational modes of the dimer model were in better accordance with the experimental data, mainly when the mode has a contribution from the acceptor molecule in the intermolecular interaction.

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Section: Resultsmentioning

confidence: 99%

Role of the Substituent Effect over the Squarate Oxocarbonic Ring: Spectroscopy, Crystal Structure, and Density Functional Theory Calculations of 1,2-Dianilinosquairane

et al. 2010

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“…One method to isolate a high‐purity enantiomer from a racemic mixture is by diastereomeric salt formation. Racemic basic (or acidic) target compounds are reacted with optically active compounds such as enantiopure acidic (or basic) resolving agents to form a pair of diastereomeric salts that can be separated by fractional crystallization , and the resulting salt subjected to a neutralization process to give a pure enantiomer. Faigl et al summarized optimal techniques for the resolution of racemates by diastereomeric salt crystallization and modes for predicting the efficiency of the resolution depending on the investigation of the physicochemical properties of the reactants.…”

Section: Introductionmentioning

confidence: 99%

Resolution via Diastereomeric Salt Crystallization of Ibuprofen Lysine: Ternary Phase Diagram Studies

et al. 2018

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Numerous pharmaceutical ingredients are chiral and generally only one isomer shows the desired therapeutic activity. Therefore, enantioseparation, e.g., by crystallization, is a key step in the pharmaceutical industry. In this work, ternary phase diagrams of the diastereomeric salt formation of ibuprofen lysine in aqueous ethanol are generated. The solubilities of the formed diastereomeric salts are measured in a defined temperature range. Investigation of the X‐ray powder diffraction patterns confirmed ibuprofen lysine as a simple eutectic system in agreement to the previously reported observations. The metastable zone widths of diastereomeric salt pairs of ibuprofen lysine are discussed with a resolution procedure proposed using the phase diagram that achieves maximum possible yield.

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“…4 Although several researchers have been tried to clarify the chiral recognition mechanism from the viewpoint of phase diagrams, computational method, structural similarity, it is still difficult to predict an appropriate resolving agent for a racemate. [5][6][7] Therefore, it is necessary to apply several resolving agents to find a suitable combination by a trial-and-error approach, and a variety of new resolving agents have been developed to meet the demand. 8,9 For the design of new resolving agents, natural compounds are preferable candidates as inexpensive chiral sources.…”

Section: Introductionmentioning

confidence: 99%

Solvent‐induced chirality control in the enantioseparation of 1‐phenylethylamine via diastereomeric salt formation

et al. 2010

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Solvent-induced chirality control in the enantioseparation of 1-phenylethylamine 1 by N-(p-toluenesulfonyl)-(S)-phenylalanine 2 via diastereomeric salt formation was studied. (S)-1·(S)-2 was preferentially crystallized as a less-soluble salt from aqueous alcohol, while (R)-1·(S)-2 salt was mainly obtained by addition of solvents with a six-membered ring such as dioxane, cyclohexane, tetrahydropyran, and cyclohexene to 2-propanol. Further investigations were carried out from the viewpoints of molecular structures, optical rotation measurement, and X-ray crystallographic analyses. Crystallographic analyses have revealed that incorporation of the six-membered ring solvent molecule in (R)-1·(S)-2 without hydrogen bonds changed the molecular conformation of (S)-2 to stabilize the salt, which changed the selectivity of 1 in the enantioseparation.

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Separability of diastereomer salt pairs of 1-phenylethylamine with enantiomeric 2-substituted phenylacetic acids by fractional crystallization, and its relation to physical and phase properties

Cited by 16 publications

References 12 publications

Role of the Substituent Effect over the Squarate Oxocarbonic Ring: Spectroscopy, Crystal Structure, and Density Functional Theory Calculations of 1,2-Dianilinosquairane

Role of the Substituent Effect over the Squarate Oxocarbonic Ring: Spectroscopy, Crystal Structure, and Density Functional Theory Calculations of 1,2-Dianilinosquairane

Resolution via Diastereomeric Salt Crystallization of Ibuprofen Lysine: Ternary Phase Diagram Studies

Solvent‐induced chirality control in the enantioseparation of 1‐phenylethylamine via diastereomeric salt formation

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