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The quantitative performance of a simple home-built preparative gas chromatography (prep-GC) arrangement was tested, incorporating a micro-fluidic Deans switch, with collection of the target compound in a deactivated uncoated capillary tube. Repeat injections of a standard solution and peppermint sample were made into the prep-GC instrument. Individual compounds were eluted from the trapping capillary, and made up to constant volume. Chloronaphthalene internal standard was added in some cases. Recovered samples were quantitatively assayed by using GC-MS. Calibration linearity of GC-MS for menthol standard area response against number of injections (2-20 repeat injections) was excellent, giving R(2) of 0.996. For peppermint, menthol correlation over 2-20 repeated injections was 0.998 for menthol area ratio (versus IS) data. Menthone calibration for peppermint gave an R(2) of 0.972. (1) H NMR spectroscopy was conducted on both menthol and menthone. Good correspondence with reference spectra was obtained. About 80 μg of isolated menthol and menthone solute was collected over a sequence of 80 repeat injections from the peppermint sample, as assayed by 600 MHz (1) H NMR analysis (∼100% recovery for menthol from peppermint). A procedure is proposed for prediction of number of injections required to acquire sufficient material for NMR detection.

During a program dedicated to the biocatalytic access of structurally useful α-hydroxy ketones, we made the unexpected observation that epoxy enol acetates derived from (+)- and (–)-menthone stereoselectively rearranged on exposure to silica through a diastereoselective process, providing easy access to the complete set of α-hydroxymenthone stereoisomers. The absolute configurations of the four stereoisomers were unambiguously established by IR-VCD and X-ray diffraction, thus clarifying some literature discrepancy. Two of the four stereoisomers could also be obtained through astereoconvergent process, thus avoiding the inherent 50 % yield limitations of such diastereoselective reactions. A solvent-free version allowing an extremely rapid reaction (< 2 h) is also described. Finally, the observed diastereoselection was investigated by DFT calculations.

A new enantiopure heteroscorpionate ligand HOPhbpm3menth (2) was synthesized in a one-pot synthesis. Ligand 2 was obtained in a pyridine-catalysed Peterson rearrangement starting from menthopyrazole, thionyl chloride, and salicylaldehyde. The evidence of κ3-coordination of the ligand was shown by the formation of a tetrahedral zinc complex [Zn-κ3-(OPhbpm3menth)CH3] (3) as well as an molybdenum complex [Mo-κ3-(OPhbpm3menth)O2Cl] (4).

The conformational analysis of a series of menthone and isomenthone imines was accomplished by 1HNMR spectroscopy and was compared with molecular modeling computations. The (E) menthone derivatives contain about 20% of a 2,5-diaxial chair conformer at room temperature (22–23°C), whereas in the (E)- and (Z)-isomenthone counterparts the major conformer has axial isopropyl and equatorial methyl groups. These peculiar conformations are a consequence of pseudo-allylic A(1,3) interactions between the isopropyl group and the non-bonded pair of electrons of the nitrogen, which dominate the axial–axial interactions between the alkyl chains and the protons of the ring in the isomenthone imines and are of considerable importance in the menthone derivatives. Copyright © 1999 John Wiley & Sons, Ltd.

Direct separation of the enantiomers of the two diastereomers, menthone and isomenthone, was performed using an octakis-(3-O-butyryl-2,6-di-O-pentyl)-α-cyclodextrin phase. Enantiomerically pure (—)-menthone and (+)-isomenthone were detected in many oils of Mentha, Micromeria fruticosa (L.) Druce and Calamintha incana (Sm.) Heldr. High enantiomeric purities of (+)-menthone and (—)-isomenthone were detected in commercial and freshly distilled geranium oils.

By acetalisation of L-menthone (2) with mercaptoacetic acid and derivatives of benzylamine, the spirocyclic N,S-acetals 3 were obtained as single diastereomers. The reaction of an epimeric mixture of unsubstituted thiazolidinones 4 with acetic anhydride or allyl iodide afforded homochiral N-acetyl (5) or N-allyl N,S-acetals (6), respectively. The configuration of the new stereogenic centres were proven by X-ray crystallography.

Asymmetrical oxidation was performed of menthone dithiolane obtained in 95–98% yield by condensation of menthone with 1,2-ethanedithiol in the presence of boron trifluoride etherate. 6-Isopropyl-9-methyl-1,4-dithiaspiro[4,5]decane-1,4-dioxide (yield 5–55%) and 6-isopropyl-9-methyl-1,4-dithiaspiro[4,5]-decane-1,1,4-trioxide (yield 65–70%) were synthesized. Chemical structures of compounds obtained were proved by XRD analysis, NMR and IR spectroscopy.

Three (6a – c) of the four conceivable diastereomeric 1-ferrocenylalkylamines can be synthesized from I-(−)-menthone and ferrocene in high enantiomeric purity. The many potential applications of such compounds, including their use as chiral templates in diastereoselective four component condensations (4CC, Ugi Reaction) are examined. Furthermore, NMR evidence for the first example of up-down-isomerism, a new type of conformational stereoisomerism of ferrocene derivatives, is discussed.

The two diastereomers of spirocyclic 5,6-dimethyl-4H-1,3-dioxin-4-one (5,6) have been synthesized by acetalization of tert-butyl 2-methyl-3-oxobutanoate (2) with (-)-menthone (4). Their structures have been determined by NMR analysis.

The titled compound was prepared by the Beckmann rearrangement of (−)-menthone oxime in polyphosphoric acid, and the value of its optical rotation was revised.

Three (6a – c) of the four conceivable diastereomeric 1-ferrocenylalkylamines can be synthesized from I-(−)-menthone and ferrocene in high enantiomeric purity. The many potential applications of such compounds, including their use as chiral templates in diastereoselective four component condensations (4CC, Ugi Reaction) are examined. Furthermore, NMR evidence for the first example of up-down-isomerism, a new type of conformational stereoisomerism of ferrocene derivatives, is discussed.

1,3-Dioxan-4-ones 6and 7 derived from (–)-menthone can be utilized in resolution of 3-hydroxycarboxylic acids and asymmetric synthesis of 2-substituted 3-hydroxycarboxylic acids.

Two chiral auxiliaries and the role they play in the preparation of chiral carbonyl compounds and heterocyclic compounds are presented. Key reactions include SN2′ displacements, Mitsunobu with hydrazoic acid, and 3,3-sigmatropic rearrangements. One of the auxiliaries serves many functions and is removed either by oxidative cleavage or RCM reaction.

The two diastereomers of spirocyclic 5,6-dimethyl-4H-1,3-dioxin-4-one (5,6) have been synthesized by acetalization of tert-butyl 2-methyl-3-oxobutanoate (2) with (-)-menthone (4). Their structures have been determined by NMR analysis.

trans-2-Isopropyl-5-methylcyclohexanone (menthone) may be considered as locked in the diequatorial conformer. However, the cis isomer (isomenthone) may exist in two major conformations with the isopropyl group either equatorial or axial. No measure of the equilibrium mix has been determined previously. Proton NMR allows such a determination at room temperature via the vicinal couplings between protons on carbons 5 and 6. Combined with modelling results, the calculated value with the isopropyl axial was 79%, of the total in good agreement with an earlier prediction. Two different conformer searching programs were employed to determine the various conformer populations. It was found that molecular mechanics estimates of the Boltzmann distributions varied considerably from the experimental results. These differences were not due to substituent electronegativity effects or to hydrogen bonding with the deuterochloroform solvent. Semiempirical PM3 and low-level ab initio calculations of the conformer energies also failed to account adequately for the conformer populations. DFT calculations (Becke3LYP/6–31G*) with zero-point energy corrections gave results most consistent with the experimentally determined values (67.5% axial isopropyl conformer). © 1988 John Wiley & Sons, Ltd.

Asymmetric desymmetrization of prochiral 2,2′,6,6′-biphenyltetrol by acetalization with l -menthone affords isomenthonide 5b of S -axial chirality. A variety of ( S )-6,6′-dialkoxy-2,2′-biphenyldiols of high enantiomeric purities are synthesized by using 5b as an intermediate. Thus, etherification of the hydroxy groups of 5b followed by hydrolysis of the isomenthonide moiety give the corresponding 6,6′-dialkoxy-2,2′-biphenyldiols ( 12 ). Intermolecular cyclization of 5b with 1,ω-dibromoalkanes followed by hydrolysis yields 2,2′-biphenyldiols 13 with alkylenedioxy bridges at the 6 and 6′ positions. Regioselective functionalization of 13 leading to 3,3′-dimethyl, -diphenyl, and -bis(TBS) derivatives is achieved either via directed lithiation of a carbamate derivative or via regioselective bromination reaction of 13 . Origin of the stereoselectivity in acetalization reaction as well as thermal stability of the axial chirality of 2,2′-biphenyldiols is also discussed.