Measurement of the Dimerization Equilibrium Constants of Enantiomers

Baciocchi, Renato; Zenoni, Gianmarco; Valentini, Massimiliano; Mazzotti, Marco; Morbidelli, Massimo

doi:10.1021/jp020352n

J. Phys. Chem. A

2002

DOI: 10.1021/jp020352n

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Measurement of the Dimerization Equilibrium Constants of Enantiomers

Renato Baciocchi

Gianmarco Zenoni

Massimiliano Valentini

et al.

Abstract: The formation of homochiral and heterochiral dimers in solutions of enantiomers causes a number of remarkable phenomena, such as the enantiomeric enrichment of nonracemic mixtures on achiral chromatographic columns when chiral monomers and dimers exhibit different retention behavior. In this work, such effects on optical rotation and UV absorbance are analyzed theoretically and experimentally. In particular, it is demonstrated how optical rotation measurements can be used to estimate the dimerization equilibri… Show more

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Cited by 36 publications

(23 citation statements)

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“…The procedure for the determination of the dimerization equilibrium constants by optical-rotation measurements is based on combining the description of the dimerization process through an equation linking the instrument reading with the composition of the solution to be measured. This is shown in this section, summarizing results reported in our previous paper [23].…”

supporting

confidence: 80%

“…The first case is that of omeprazole, where a strong nonlinear effect in optical rotation was observed, and a rather accurate estimate of the equilibrium constants could be made. This is similar to the binaphthol enantiomers in CHCl 3 [23]. In the case of Pirkle×s alcohol, on the contrary, the nonlinear effect was weaker, thus leading to a loss of accuracy in the estimation of the equilibrium constants, whose order of magnitude only (twice smaller than that of omeprazole) could be determined.…”

mentioning

confidence: 53%

“…4, b, provided the best-fit value of K hetero 25.2 AE 4.0 l/mol. It is worth observing that the K hetero /K homo ratio is close to the statistical ratio of 2, thus suggesting that there is only a small difference between the enthalpies of formation of the homochiral and of the heterochiral dimers [23].…”

mentioning

confidence: 80%

“…Recently, we developed a procedure for the determination of the dimerization equilibrium constants of enantiomers forming dimers [23]. This is based on using a polarimeter and analyzing its signal while accounting for the association behavior of the enantiomers in solution.…”

mentioning

confidence: 99%

“…10. Following the procedure reported in detail elsewhere [23], the parameters in Eqn. 10 are independently evaluated in three steps.…”

mentioning

confidence: 99%

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Determination of the Dimerization Equilibrium Constants of Omeprazole and Pirkle's Alcohol through Optical‐Rotation Measurements

Baciocchi

Juza²,

Classen³

et al. 2004

Helvetica Chimica Acta

Self Cite

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A new procedure to measure the equilibrium constants for the dimerization (homochiral and heterochiral) reactions of enantiomers in solution was applied to two different compounds, namely omeprazole and Pirkle×s alcohol, both in CHCl 3 . This procedure is based on the measurement of the optical rotation of the solution as a function of its composition, which exhibits a nonlinear dependence on the enantiomer enrichment. Such nonlinearity depends on the extent of dimerization, and it is a strong effect in the case of omeprazole, whose equilibrium constants are 14.0 AE 3.5 l/mol and 25.2 AE 4.0 l/mol for the formation of homochiral and of heterochiral dimers, respectively. Pirkle×s alcohol exhibits a weaker effect that allows only to estimate the order of magnitude of these constants, i.e., ca. 0.10 and 0.34 l/mol, respectively. Although, in solution, enantiomers and racemates of chiral compounds usually exhibit identical NMR spectra, small differences in the chemical shifts are sometimes observed (see [18] for an overview, as well as the ref. cit. therein). It is also known that nonracemic mixtures of enantiomers of compounds that strongly self-associate, e.g., amino alcohols, amides, and carboxylic acids, can exhibit anisochrony, thus reflecting the enantiomer composition even in the absence of shift reagents [19]. Association is often limited to the formation of dimers that may take place through the formation of H-bonds between enantiomers. This is the case for the enantiomers of the chiral [1,1'-binaphthalene]-2,2'-diol ( binaphthol) and 1-(anthracen-9-yl)-2,2,2-trifluoroethanol ( Pirkle×s alcohol). In the case of the enantiomers of binaphthol in CHCl 3 , we have recently been able, using an achiral chromatography column, to collect two fractions constituted of the pure enantiomer present in excess (reaching 100% e.e.) and of the racemic mixture, respectively [20]. In the case of Pirkle×s alcohol, the enantiomer enrichment of a nonracemic solution in hexane/CH 2 Cl 2 was also achieved through achiral chromatography on a silica stationary phase [12].

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supporting

confidence: 80%

mentioning

confidence: 53%

mentioning

confidence: 80%

mentioning

confidence: 99%

“…10. Following the procedure reported in detail elsewhere [23], the parameters in Eqn. 10 are independently evaluated in three steps.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Determination of the Dimerization Equilibrium Constants of Omeprazole and Pirkle's Alcohol through Optical‐Rotation Measurements

Baciocchi

Juza²,

Classen³

et al. 2004

Helvetica Chimica Acta

Self Cite

View full text Add to dashboard Cite

show abstract

Specific Optical Rotations and the Horeau Effect

Covington

Polavarapu

2015

Chirality

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The observation of nonequivalence of optical and enantiomeric purities, referred to as the Horeau effect, is thought to arise from molecular aggregation in liquid solutions. Although this effect was first observed in 1969, the conditions under which this effect may, or may not, be observable are not established. Considering the formation of dimers as the simplest form of aggregation, the expressions for specific optical rotations in the presence of homochiral and heterochiral monomer-dimer equilibria are presented. Analysis of these equations indicates that the Horeau effect will not be observable even in the presence of aggregation under either of the following two situations: 1) The specific optical rotation of the monomeric species is equal to that of the dimeric species; 2) The heterochiral equilibrium constant is twice that of the homochiral equilibrium constant.

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The self‐disproportionation of enantiomers (SDE): The effect of scaling down, potential problems versus prospective applications, possible new occurrences, and unrealized opportunities?

et al. 2019

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This commentary discusses an important, though not widely appreciated, chiral phenomenon of molecular chirality that effectively always occurs whenever nonracemic samples are subjected to practically any physicochemical process (e.g., force field, recrystallization, sublimation, even distillation, etc.) under totally achiral conditions external to the sample itself. The phenomenon is termed as the self‐disproportionation of enantiomers (SDE) and though ubiquitous, its presence may not always be readily apparent, or workers may be otherwise oblivious to its effects. In the particular case of chromatography, when the SDE is apparent, the enantiomeric excess (ee) of the chiral compound is observed to vary across an eluted peak, with anterior eluted portions either enantioenriched or enantiodepleted relative to the ee of the starting material, and conversely for the posterior eluted portions. Herein, we highlight various aspects of the SDE phenomenon as it pertains to chromatography and, in particular, the effect of scaling down chromatographic systems, the potential risk of problems that the SDE can cause, as well as opportunities for practical applications of the phenomenon, possible new occurrences of the SDE phenomenon to be searched for, and unrealized opportunities.

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Measurement of the Dimerization Equilibrium Constants of Enantiomers

Cited by 36 publications

References 23 publications

Determination of the Dimerization Equilibrium Constants of Omeprazole and Pirkle's Alcohol through Optical‐Rotation Measurements

Determination of the Dimerization Equilibrium Constants of Omeprazole and Pirkle's Alcohol through Optical‐Rotation Measurements

Specific Optical Rotations and the Horeau Effect

The self‐disproportionation of enantiomers (SDE): The effect of scaling down, potential problems versus prospective applications, possible new occurrences, and unrealized opportunities?

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