Menthol isomers

Menthol Manufacture. Of the menthol isomers, only (-)-menthol [2216-51 -5] and (+)-menthol [15356-70-4] are of commercial importance. The most important natural sources of (—)-menthol are the oUs of Mentha arvensis (75—90%) and Mentha piperita (50—65%). The main suppUers ate Japan, China, BrazU, and Taiwan for the former and the United States, CIS, Bulgaria, and Italy for the latter. (—)-Menthol is known for its refreshing, diffusive odor characteristic of peppermint. It also is known for its strong physiological cooling effect, which is useful in cigarettes, dentifrices, cosmetics, and pharmaceuticals. 

The menthol isomers are equilibrated, then fractionally distilled, to recover the (+)-mentbol. The other menthol isomers are recycled. 

Addition of propylene to m-cresol produces thymol. Hydrogenation of thymol gives a mixture of menthol isomers. Treatment of any one of the eight isomers with the same copper chromite catalyst that is used for thymol hydrogenation causes racemization to the same equilibrium mixture of isomers. This fact is used to good effect in the process. The hydrogenation product is optically inactive, being composed of equal amounts of d- and L-isomers of each of the four conformational isomers. The balance between these is 62-64% menthol, 18-20% neomenthol, 10-12% isomenthol and 1-2% neoisomenthol. Since these are pairs of diastereomers, their physical properties differ. Thus,... 

II-Beta zeolite, loaded with 3 wt % Ir.catalyzes the one-pot full conversion of citronellal to menthol by consecutive acid catalysed cyclization and Ir-catalyzed hydrogenation, with 95 % selectivity for the menthol isomers of which 75 % is the desired (-)-mcnthol [81]. Conditions The catalytic tests were performed at 80 °C in a stirred stainless steel autoclave using IB pressures in the range 0.5-1.5 Mpa, 50 mg catalyst, 1 ml citronellal and 7 ml solvent (cyclohexane or 2 propanol). 

We have investigated the changes in the product distribution and in the stereoisomeric composition of the menthol isomers, using well characterized Pt, Pd and Ir catalysts with the same high dispersion (1-2 nm large particles) and on the same active charcoal support. Moreover the hydrogenation of pure menthone was studied on the same catalysts and under the reaction conditions used for thymol hydrogenation. 

It is the existence of the eight menthol isomers that makes the chemical synthesis onerous. In many procedures, more than one isomers form as a final product, and needs to be separated out at the end. These byproducts, the isomers of (-)-menthol, all have cooling and refreshing effects, but none of them is as potent as menthol itself. So the presence of these isomers lowers the quality of the final product. Another option is to look for a chemical reaction that produces (-)-menthol exclusively. This was achieved from meta-cresol by the company Haarman and Reimer, which is also a major vanillin producer, whereas a Japanese chemical company, Takasago,... 

Eccles, R., D.H. Griffiths, C.G. Newton, and N.S. Tolley, 1988. The effects of menthol isomers on nasal sensation of airflow. Clin. Otolaryngol., 13 25-29. 

Finally, —)-menthyl benzoate is separated by crystallization, and the final product (—)-menthol is obtained by the reverse reaction, that is, by hydrolysis with methanol. The (-F)-menthol benzoate is also hydrolyzed, and the resulting (+)-menthol is converted into a racemic mixture of all menthol isomers. This mixture is combined with the iso- and neomenthol separated by rectification and used as feed for the epimerization. 

Figure 6.17.4 Laboratory-scale continuous fixed bed reactor (liquid phase externally saturated with H2to suppress dehydrogenation to menthone) used for kinetic studies on the epimerization of menthol isomers (P pressure, T temperature, L level,...

Influence of Mass Transfer on the Epimerization of Menthol Isomers... 

Example 6.17.1 Molecular and effective diffusion coefiidents of menthol isomers... 

Figure 6.17.9 Typical experimental results obtained by means of the Jost potto determine the diffusion coefficient of menthol isomers at 423 l< (150°C) (Etzold, 2007).

Figure 6.17.13 Simulation of a batch reactor forthe epimerization of menthol isomers (catalyst particles 100 p.m in diameter, 175 °C, 50 bar hydrogen, concentration of catalyst 1 wt%, typical industrial feed mixture). Data from Etzold (2007).

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