Menthol 250g
Menthol 250g
Menthol is an organic compound made synthetically or obtained from the oils of corn mint, peppermint, or other mints. It is a waxy, crystalline substance, clear or white in color, which is solid at room temperature and melts slightly above.
The main form of menthol occurring in nature is (−)-menthol, which is assigned the (1R,2S,5R) configuration. Menthol has local anesthetic and counterirritant qualities, and it is widely used to relieve minor throat irritation. Menthol also acts as a weak κ-opioid receptor agonist.
In 2017, it was the 193rd most commonly prescribed medication in the United States, with more than two million prescriptions.
Chemical Properties
Properties | |
---|---|
C10H20O | |
Molar mass | 156.269 g·mol−1 |
Appearance | White or colorless crystalline solid |
Density | 0.890 g·cm−3, solid (racemic or (−)-isomer) |
Melting point | 36–38 °C (97–100 °F; 309–311 K) racemic 42–45 °C, (−)-isomer, α crystalline form |
Boiling point | 214.6 °C (418.3 °F; 487.8 K) |
Slightly soluble, (−)-isomer |
Chemical Structure Menthol 250g
Safety
Irritant
Description
Biosynthesis
The biosynthesis of menthol has been investigated in Mentha × piperita and the enzymes involved in have been identified and characterized.[12] It begins with the synthesis of the terpene limonene, followed by hydroxylation, and then several reduction and isomerization steps.
More specifically, the biosynthesis of (−)-menthol takes place in the secretory gland cells of the peppermint plant. Geranyl diphosphate synthase (GPPS), first catalyzes the reaction of IPP and DMAPP into geranyl diphosphate. Next (−)-limonene synthase (LS) catalyzes the cyclization of geranyl diphosphate to (−)-limonene. (−)-Limonene-3-hydroxylase (L3OH), using O2 and NADPH, then catalyzes the allylic hydroxylation of (−)-limonene at the 3 position to (−)-trans-isopiperitenol. (−)-trans-Isopiperitenol dehydrogenase (iPD) further oxidizes the hydroxyl group on the 3 position using NAD+ to make (−)-isopiperitenone. (−)-Isopiperitenone reductase (iPR) then reduces the double bond between carbons 1 and 2 using NADPH to form (+)-cis-isopulegone. (+)-cis-Isopulegone isomerase (iPI) then isomerizes the remaining double bond to form (+)-pulegone. (+)-Pulegone reductase (PR) then reduces this double bond using NADPH to form (−)-menthone. (−)-Menthone reductase (MR) then reduces the carbonyl group using NADPH to form (−)-menthol.[12]
Production
Natural menthol is obtained by freezing peppermint oil. The resultant crystals of menthol are then separated by filtration.
Total world production of menthol in 1998 was 12,000 tonnes of which 2,500 tonnes was synthetic. In 2005, the annual production of synthetic menthol was almost double. Prices are in the $10–20/kg range with peaks in the $40/kg region but have reached as high as $100/kg. In 1985, it was estimated that China produced most of the world’s supply of natural menthol, although it appears that India has pushed China into second place.[13]
Menthol is manufactured as a single enantiomer (94% e.e.) on the scale of 3,000 tonnes per year by Takasago International Corporation.[14] The process involves an asymmetric synthesis developed by a team led by Ryōji Noyori, who won the 2001 Nobel Prize for Chemistry in recognition of his work on this process:
The process begins by forming an allylic amine from myrcene, which undergoes asymmetric isomerisation in the presence of a BINAP rhodium complex to give (after hydrolysis) enantiomerically pure R–citronellal. This is cyclised by a carbonyl-ene-reaction initiated by zinc bromide to isopulegol , which is then hydrogenated to give pure (1R,2S,5R)-menthol.
Another commercial process is the Haarmann–Reimer process (after the company Haarmann & Reimer, now part of Symrise)[15] This process starts from m-cresol which is alkylated with propene to thymol. This compound is hydrogenated in the next step. Racemic menthol is isolated by fractional distillation. The enantiomers are separated by chiral resolution in reaction with methyl benzoate, selective crystallisation followed by hydrolysis.
Racemic menthol can also be formed by hydrogenation of thymol, menthone, or pulegone. In both cases with further processing (crystallizative entrainment resolution of the menthyl benzoate conglomerate) it is possible to concentrate the L-enantiomer, however this tends to be less efficient, although the higher processing costs may be offset by lower raw material costs. A further advantage of this process is that D-menthol becomes inexpensively available for use as a chiral auxiliary, along with the more usual L-antipode.