Determination of enantiomeric excess by 13C NMR spectroscopy

Oxazolidine derivatives of β-amino alcohols such as ephedrine have been resolved by ¹³C NMR spectroscopy using Eu(hfc)₃ as a chiral shift reagent. The method is quantitative in the determination of enantiomeric excess, and is advantageous where ¹H NMR is of limited use owing, for example, to significant line broadening.     

Simple31P NMR method for the determination of the enantiomeric purity of chiral O-alkylalkylthiophosphonic acids

The³¹P-(¹H) NMR spectra of bis(alkylalkoxythiophosphoryloxy)phosphonites may be utilized to determine the enantiomeric purity (p) of O-alkylalkylthiophosphonic acids with the application of the Oro equation, p= (Q – Q)/(Q + Q), where Q is the integral intensity of the d, -form, and Q is the integral intensity of the meso forms.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 10, pp. 2225–2228, October, 1989.     

Determination of the enantiomeric composition of chiral carboxylic acids using chiral derivatization and HPLC

Summary The enantiomers of chiral carboxylic acids were separated as their diastereomeric amides with (1R,2R)-(−)-1-(4-nitrophenyl)-2-amino-1,3-propanediol (“levobase”) and with “dextrobase” (the enantiomer of levobase) by high-performance liquid chromatography using a conventional C-18 column and various solvent systems containing acetonitrile, methanol, water, and phosphoric acid.     

A simple method for the determination of enantiomeric excess and identity of chiral carboxylic acids

The association between an achiral copper(II) host (1) and chiral carboxylate guests was studied using exciton-coupled circular dichroism (ECCD). Enantiomeric complexes were created upon binding of the enantiomers of the carboxylate guests to the host, and the sign of the resultant CD signal allowed for determination of the configuration of the studied guest. The difference in magnitudes and shapes of the CD signals, in conjunction with linear discriminant analysis (LDA), allowed for the identity of the guest to be determined successfully. A model was created for the host-guest complexes which successfully predicts the sign of the observed CD signal. Further, Taft parameters were used in the model, leading to rationalization of the observed magnitudes of the CD signals. Finally, the enantiomeric excess (ee) of unknown samples of three chiral carboxylic acid guests was determined with an average absolute error of ±3.0%.     

31P NMR spectroscopy as a powerful tool for the determination of enantiomeric excess and absolute configurations of alpha-amino acids

An easy method for the determination of the enantiomeric excess (ee) of mixtures of alpha-amino acids, and also for the elucidation of the absolute configuration of each component of the mixture, is reported. The method is based on the formation of diastereoisomers by reaction of the enantiomerically pure acetylacetonate derivative [Pd(acac-O,O')(P(2)-dach)]ClO(4) (4) [P(2)-dach = (1R,2R)-C(6)H(10)(NHPPh(2))(2)] with d,l-mixtures of alpha-amino acids AaH (Pd:AaH = 1:1 molar ratio, refluxing MeOH). The reaction occurs with protonation of the acac ligand and N,O-coordination of the amino acidate group, giving the corresponding [Pd(Aa-N,O)(P(2)-dach)]ClO(4) complexes l-5 and d-6. The composition of these mixtures of amino acidate complexes was analyzed by integration of the corresponding peaks (four doublets, two for each diastereomer) in their (31)P((1)H) NMR spectra. A series of 14 alpha-amino acids was studied (a, alanine; b, 2-aminobutyric acid; c, valine; d, phenylalanine; e, proline; f, leucine; g, isoleucine; h, norleucine; i, serine; j, threonine; k, methionine; l, aspartic acid; m, glutamine; n, cysteine), and excellent agreement between the expected values of ee and those obtained from integration of the (31)P((1)H) NMR spectra was obtained. Moreover, the position of the signals of each isomer is diagnostic, in such a way that the outer doublets are always due to the l-derivatives 5a-l, while the inner ones are due to the d-derivatives 6a-l, allowing the assignation of absolute configurations to each isomer in the mixture.     

Determination of enantiomeric excess and concentration of unprotected amino acids, amines, amino alcohols, and carboxylic acids by competitive binding assays with a chiral scandium complex

A practical UV-vis sensing method for enantioselective microanalysis of unprotected amino acids, amines, amino alcohols, and carboxylic acids in aqueous solution has been developed. Both concentration and enantiomeric composition of a wide range of chiral substrates can be determined with high accuracy by two simple competitive binding assays using a scandium complex derived from 1,8-bis(3-(3',5'-dimethylphenyl)-9-acridyl)naphthalene N,N'-dioxide.     

31P NMR assays for rapid determination of enantiomeric excess in catalytic hydrosilylations and transfer hydrogenations

Chiral chlorophosphine (S)-(1,1′-binaphthalen-2,2′-dioxy)chlorophosphine (S)-2 was tested for its performance as a chiral-derivatizing agent (CDA) using solutions of various alcohols, amines, and N-BOC amino acids. Based on ³¹P NMR spectroscopy, the enantiomeric excess was determined within less than 5 min per sample, reaching an accuracy of ±1%. One-pot procedures for a combination of the method with typical homogenous catalytic transformations of prochiral ketones were established. Hydrosilylation products may be analyzed after conversion into alcohols using HF bound to PS-vinyl pyridine co-polymer beads. Transfer hydrogenations simply require solvent evaporation prior to the use of the CDA.     

HPLC-在线旋光仪联用确定不对称合成或对映体拆分过程的转化率及e．e％值变化

在手性合成和手性拆分中,检测e.e%值随进程或时间的变化对于确定适宜的反应终点至关重要.     

Determination of enantiomeric excess by capillary electrophoresis

Capillary electrophoresis (CE) is becoming an established method for the determination of chiral trace impurities. This paper provides an overview of the state of the art of CE for such determinations. Detection limits of 0.1% impurity is widely accepted as a minimum requirement for chiral trace impurity determinations. This can be relatively easily achieved with CE. However, determination of lower concentrations requires careful optimization of the separation system. Four factors that are of particular significance for trace enantiomeric determinations: resolution, limit of detection, linear range and type of detection, are discussed. Further, the advantages and disadvantages of derivatization in this context are treated as well as the separation approach, ie., direct chiral separation or separation after the formation of diastereomers. It is concluded that the limit of impurity detection can be about 0.05% when UV detection is employed. Using laser-induced fluorescence detection, a quantitative determination at the 0.005% level is often possible.     

Monoacylation of unprotected symmetrical diamines with resin-bound benzoic acids

A protocol for monoacylation of unprotected symmetrical diamines with a resin-bound benzoic acid is described. The nature of the resin (gel-based polystyrene vs highly crosslinked macroporous polystyrene) was found to play a minor role in acylation selectivity. Rather, the concentration of the diamine dictates the ratio of mono- and diacylated products. Thus, by employing a high concentration of symmetrical diamine (e.g., 1 M, 20 equiv), monoacylation can be selectively achieved for a variety of unprotected symmetrical alkyl and aryl diamines.     

Histamine-modified cationic beta-cyclodextrins as chiral selectors for the enantiomeric separation of hydroxy acids and carboxylic acids by capillary electrophoresis.

The enantiomeric separation of alpha-hydroxy acids and carboxylic acids was successfully performed by using 6-deoxy-6-N-histamino-beta-cyclodextrin (CD-hm), a monosubstituted positively charged beta-cyclodextrin (beta-CD) bearing a histamine moiety linked to the C6 of a glucose unit in the upper CD rim via the amino group. Good results were obtained at a low selector concentration (1 mM). The number of positive charges on the upper rim may be modulated as a function of pH, because of the different pKa of the amino and the imidazolyl groups, and was found to affect both the enantioselectivity and resolution factors. With the analogous 6-deoxy-[4-(2-aminoethyl)imidazolyl]-beta-cyclodextrin (CD-mh) bearing the histamine moiety linked to the C6 via the imidazolyl group, very poor results were obtained, showing that the proximity of the positive charge to the cavity plays an important role in the enantiomeric recognition. The complexation mode was studied by electrospray ionization-mass spectrometry (ESI-MS) and two-dimensional nuclear magnetic resonance (2-D NMR) ROESY experiments: the recognition model is consistent with an inclusion complexation of the aromatic ring of the analyte within the CD cavity coupled to electrostatic interactions between the carboxylate and the protonated amino group of the cyclodextrin.     

Efficient NMR chiral discrimination of carboxylic acids using rhombamine macrocycles as chiral shift reagent

Chiral rhombamine macrocycles 1a-b were prepared by a [2+2]cyclocondensation reaction of (R,R)-1,2-diaminocyclohexane with corresponding dialdehydes and were found to be useful as NMR chiral shift reagents for the determination of enantiomeric purity and the absolute configuration of a wide range of carboxylic acid and amino acid derivatives.     

Determination of the absolute configuration of chiral cyclic alcohols using diamine derivatizing agents by 31P NMR spectroscopy

The absolute configuration and enantiomeric excess of chiral cyclic alcohols can be predicted from the ³¹P NMR spectra of the two diastereoisomers obtained with organophosphorus diamino-derivatizing agents (CDAs) and the chiral secondary alcohol, according to a simplified model taking into account the spatial location of the substituents of the chiral alcohol center and the ³¹P NMR signals of the two diastereoisomers.     

Determination of the enantiomeric excess of α-hydroxy acids

This work describes a convenient and accurate method for optical purity determination of α-hydroxy acids. Their derivatization with commercially available valine methyl ester affords diastereoisomers easily separable by HPLC using achiral C₁₈ columns.     

Synthesis of new chiral calix[4]azacrowns for enantiomeric recognition of carboxylic acids

Two novel chiral calix[4]azacrown ethers 4 and 5 bearing a furfuryl group on the nitrogen atom were developed by the reaction of dibromo- or ditosyl derivatives of p-tert-butylcalix[4]arenes 2 and 3 with a chiral diol, 1. The enantioselective recognition of these receptors towards the enantiomers of racemic carboxylic acids has been studied by ¹H NMR spectroscopy. The molar ratio and the association constants of the chiral compounds 4 and 5 with each of the enantiomers of guest molecules were determined by using Job plots and a nonlinear least-squares fitting method, respectively. The Job plots indicate that both of the hosts form 1:1 instantaneous complexes with (R)- or (S)-mandelic acid and (l)- or (d)-dibenzoyltartaric acid. The receptors exhibited different chiral recognition abilities towards the enantiomers of racemic guests.     

Determination of enantiomeric excess and concentration of chiral compounds using a 1,8-diheteroarylnaphthalene-derived fluorosensor

Enantioselective fluorosensing using a rigid C₂-symmetric 1,8-diacridylnaphthalene N,N′-dioxide sensor allows accurate determination of both the enantiomeric composition and concentration of several analytes capable of chiral hydrogen bonding.     

Determination of enantiomeric excess of alpha-hydroxy-3-phenoxybenzeneacetonitrile and its n-butyl ester by chiral high-performance liquid chromatography

Determination of enantiomeric excess of alpha-hydroxy-3-phenoxybenzeneacetonitrile, an important intermediate in the production of several pyrethroid insecticides, is usually done after derivatization and gas chromatographic analysis on a beta-cyclodextrin-based column. In this communication we report a direct determination of enantiomeric excess of alpha-hydroxy-3-phenoxybenzeneacetonitrile and its n-butyl ester by chiral HPLC on Chiralcel OJ (Daicel, Japan) in a single run without derivatization.     

Determination of the enantiomeric excess of ferroelectric liquid crystals derived from three natural amino acids

The synthesis and 1H NMR spectra are presented for diastereoisomeric esters based on chiral alpha-chloro acids which are derived from natural available alpha-amino acids (L-valine, L-leucine and L-isoleucine) and commonly employed for the synthesis of ferroelectric liquid crystals possessing a high spontaneous polarization. Partial racemization is established as occurring within the formation of the chiral alpha-chloro acids and their esterification procedure. The enantiomeric excess exceeds 90% for L-isoleucine and L-valine derivatives, whereas an enantiomeric excess of 60% is found for L-leucine derivatives. On the basis of existing data in the literature, the differences in the spontaneous polarization of these derivatives is discussed with regard to the determined enantiomeric excess and their conformational freedom affecting the average lateral dipole moment of a single molecule.     

1H and 31P NMR spectra of substituted methylphosphonic acids with indirect determination of 31P shifts

Proton and phosphorus magnetic resonance spectra of substituted methylphosphonic acids have been determined as a function of pH. A method has been developed for measuring the ³¹P shift indirectly by optimal heteronuclear decoupling of the ¹H spectra of samples and standards. Control experiments have demonstrated the broad applicability of this technique to the characterization of low milligram samples of N-phosphonomethylglycine and potential metabolites.