• Archives of Pharmacal Research
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• v.22 no.6
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• pp.614-618
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• 1999

A reversed-phase high-performace liquid chromatographic method was developed to determine the optical purity of metoprolol enantiomers. The enantiomers were converted to diastereomeric derivatives using (-)-menthyl chloroformate reagent. Separation of the enantiomers as diastereomers was achieved by reversed-phase HPLC within 30 min using Inertsil C8 column. This method allowed determination of 0.05% of either enantiomer in the presence of its stereoisomer and method validation showed adequate linearity over the required range. Owing to the reaction condition during the derivatization with (-)-menthyl chloroformate, the possibility of racemization had to be established. Different ratios of (S)-(-)-metoprolol and (R)-(+)-metoprolol were prepared. Enantiomeric separation of these mixtures took place on a chiralcel OD column or, after derivatization with (-)-menthyl chloroformate, on a C8 column. The results form the these two independent separation systems were compared with trace racemization and were in very good agreement. No racemization was found during the experiment.

• Archives of Pharmacal Research
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• v.22 no.6
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• pp.608-613
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• 1999

Optimum conditions of chiral derivatization reaction of $\beta$-blockers (acebutolol, arotinolol, betaxolol, bisoprolol, celiprolol, metoprolol and pindolol) with (-)-menthyl chloroformate were investigated for the resolution by HPLC. With more than 30 times molar excess of (-)-methyl chloroformate chiral derivatization reactions were completed within one hour at room temperature except arotinolol and celiprolol. Diastereomeric derivatives of $\beta$-blockers were well resolved on the ODS column using acetonitrile-methanol-water as a mobile phase.

• Journal of the Korean Chemical Society
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• v.65 no.5
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• pp.309-312
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• 2021

The solvolysis of (1s)-(+)-menthyl chloroformate (1) were studied kinetically in 28 pure and various mixed solvents. The analysis using the extended Grunwald-Winstein equation in the solvolysis of 1 obtained the l value of 2.46 ± 0.18, the m value of 0.91 ± 0.07, and the correlation coefficient of 0.950. The solvolysis of 1 might proceed via an associative S_N2 mechanism enhancing bond making than bond breaking in the transition state (TS). The value of l/m is 2.7 within the ranges of value found in associative S_N2 reaction. This interpretation is further supported by a relatively large solvent kinetic isotope effect (SKIE, 2.16).

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.220.3-220.3
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• 2003

Enantiomers of pindolol were prepared by chromatographic method. Racemic pindolol was derivatized with S-(-)-menthyl chloroformate((-)-MCF) forming its diastereomer, R-(+)-pindolol-(-)-MCF and S-(-)-pindolol-(-)-MCF. The diastereomer mixture was then chromatographically resolved to each diastereomer. Each diastereomer was further hydrolyzed with alkali to each enantiomer quantitatively. Racemization was not occurred in this process. Pindolol enantiomers were recovered producing good yield over 30% over all process.

• Archives of Pharmacal Research
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• v.23 no.6
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• pp.568-573
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• 2000

A reversed-phase high-performance liquid chromatographic method was developed to determine the optical purity of bevantolol enantiomers. (S)-(-)-Menthyl chloroformate((-)-MCF), (S)-(-)-$\alpha$-methylbenzyl isocyanate((-)-MBIC) and 2,3,4,6-tetra-O-acetyl-$\beta$-D-glucopyranosyl isothiocyanate(GITC), which can react with the secondary amine group of bevantolol were investigated as chiral derivatization reagents. Among them indirect chiral HPLC method using CITC gave the best result. The derivatization proceeded quantitatively within 20 min at room temperature. Separation of the enantiomers as diastereomers was achieved by reversed-phase HPLC within 20min using ODS column. Different ratios of (S)-(-)-bevantolol and (R)-(+)-bevantolol were prepared. Enantiomeric separation of these mixtures took place on a chiralcel OD column or, after derivatization with GITC, on a ODS column. No racemization was found during the experiment. This method allowed determination of 0.05% of either enantiomer in the presence of its stereoisomer and method validation showed adequete linearity over the required range.