Stereochemical analysis of menthol and menthylamine isomers using calculated and experimental optical rotation data

Abstract

a b s t r a c tThe complete series of menthol isomers and their corresponding amino derivatives (base and protonated/HCl forms), were investigated using experimental and theoretical data. Our study focused on the conformational and configurational analysis, and revealed that experimental data should be used in combination with calculated data. Furthermore, even in the case of the highly studied member, menthol, discrepancies were found among previously published literature values. We show that the correct determination of the population mix is a must for the correct prediction of the absolute configuration (AC) of neoisomenthol. The neoiso forms are of special interest since a number of structural inconsistences can be found in the literature. We present a stringent proof of the AC of neoisomenthol based on literature information. To the best of our knowledge, the AC of neoisomenthylamine is for the first time shown using experimental and calculated optical rotation data. A correction of a series of publications containing an important error in the assignment of (þ)-menthylamine (correct: (þ)-neomenthylamine) is presented. With 26 data pairs (experimental versus calculated) of optical rotation values a regression is performed. The AC of all 12 compounds, even the most difficult neoiso forms, could be predicted correctly using experimental low-temperature NMR data. Furthermore, if only experimental data with an optical rotation outside the range of À10 < [a] > þ10 are used, all 12 compounds would have been correctly assigned without lowtemperature NMR data as restraints.

Continuous flow synthesis of menthol via tandem cyclisation–hydrogenation of citronellal catalysed by scrap catalytic converters

“…The menthols (having a high concentration of (−)-menthol) were sequentially isolated by distillation (in order to remove the solvent and low boiling substances) and chromatographic purification on a silica column. The optical rotation of the isolated menthols, derived from the optical rotation of (−)-menthol ([α] 20 D =-50) 43 and its isomers, was measured to be [α] 20 D =-38. In order to validate the proposed system in comparison with a conventional supporting material as well as with commercially available catalysts, the best reaction conditions were applied using Fe/SiO2 and commercial 5%wtPt/C and 5%wtPd/C as catalysts, as illustrated in Table 6.…”

Construction and Optimization of a Biocatalytic Route for Menthone Amination

“…Subsequently, dielectrically controlled resolution (DCR) of racemic neomenthol by (R, R)-tartaric acid and electrochemical synthesis with mercury pool cathode were both used to produce optical pure (+)-neomenthylamine stereoselectively (Schopohl et al 2003;Kulisch et al 2011;Schmitt et al 2014;Reinscheid and Reinscheid 2016). In recent reports, hydrogenation of menthone oxime to amines via gold catalysts has excellent yields in high temperature.…”

Construction and optimization of a biocatalytic route for the synthesis of neomenthylamine from menthone

“…An alternative approach was to reduce menthone oxime to amines under Bouveault–Blanc conditions using an excess equivalent of sodium (Han et al 2017 ). Besides, dielectrically controlled resolution (DCR) of racemic neomenthol by ( R , R )-tartaric acid and electrochemical synthesis with mercury pool cathode were both used to produce optically pure (+)-neomenthylamine stereoselectively (Kulisch et al 2011 ; Schmitt et al 2014 ; Reinscheid and Reinscheid 2016 ). In recent reports, hydrogenation of menthone oxime to amines via gold catalysts could afford excellent yields at 100 °C.…”