Menthol

Menthol is an organic compound made synthetically or obtained from corn mint, peppermint, or other mint oils. 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 kappa opioid receptor agonist.

The (+)- and (–)-enantiomers of menthol are the most stable among these based on their cyclohexane conformations. With the ring itself in a chair conformation, all three bulky groups can orient in equatorial positions.

The two crystal forms for racemic menthol have melting points of 28 °C and 38 °C. Pure (−)-menthol has four crystal forms, of which the most stable is the α form, the familiar broad needles.

Profile:

• 📂 CAS N° 2216-51-5

• ⚖️ MW — 156.26 g/mol

• 📝 Odor Type — Fresh

• 📈 Odor Strength — High

• 👃🏼 Odor Profile — Refreshing, light, diffusive odor with a sweet pungency. The characteristic resemblance to the main odor of Peppermint, and a cooling effect upon the mucous membranes. However, the cooling effect is not perceptible at the same low level at which the material is olfactory perceptible. 

• 👅 Flavor Profile — Cooling mouthfeel, refreshing, sweet taste reminiscent of part of the Peppermint picture. At very low concentrations, there is no cooling effect, but still a perceptible flavor. 

• ⚗️ Uses — l-Menthol, synthetic or natural, is widely used in perfumes and flavors. Its main use is in flavors as a fortifier for Peppermint flavors or as a flavor ingredient with a cooling effect and little or no typical bouquet notes of Peppermint. 

Smaller amounts are used in perfumes to give refreshing lift and power, mainly to Rose, Geranium, Lavender, Fougere and similar types. Concentrations from 0.5 to 2.500 are usually required to achieve such effects in perfume. 

Separately from the addition of perfume to certain cosmetic products, Menthol may be added to introduce a cooling effect in shave creams, after-shave lotions, etc. The amount of Menthol may be higher than the total amount of perfume in such cases. 

Apart from its conventional role in Peppermint, Spearmint, and other Mint flavors, Menthol is used in traces in imitation Butter, Caramel, fruit complexes, etc. and very often along with Anise or Anethole in Licorice flavorings.

The concentration in the finished product will be 35 to 400 ppm, but it can reach 1000 to 1200 in chewing gum or dentifrice (the latter being a non-edible product, therefore rarely included in such statistics). 

Menthol Production:

• Method 1

by freezing from Mentha Viridis or Mentha arvensis oils. The Menthone rich liquid phase may yield further quantities of Menthol (Iaevo and racemic) by catalytic reduction, normally with Sodium. 

• Method 2

from Thymol or Piperitone by hydrogenation, or from laevo-iso-Pulegol or Citronella via Pulegol to Menthol, Numerous other methods and variations of the above methods are used in the manufacture of synthetic Menthol. It is estimated that more than 50%. of the world production of l-Menthol is obtained as Natural Menthol. 

Biological Properties:

Menthol's ability to chemically trigger the cold-sensitive TRPM8 receptors in the skin is responsible for the well-known cooling sensation it provokes when inhaled, eaten, or applied to the skin. In this sense, it is similar to capsaicin, the chemical responsible for the spiciness of hot chilis (which stimulates heat sensors, also without causing an actual change in temperature).

Menthol's analgesic properties are mediated through selective activation of κ-opioid receptors. Menthol also blocks voltage-sensitive sodium channels, reducing neural activity that may stimulate muscles. A study showed that topical absorption of ibuprofen is not increased by menthol, but does note the complementary effect of the menthol as a pain reliever itself. Topically applied menthol does not actually reduce inflammation of tissues or influence the cause of pain.

Some studies show that menthol acts as a GABAA receptor positive allosteric modulator and increases GABAergic transmission in PAG neurons. Menthol also shares anesthetic properties similar to propofol, by modulating the same sites of the GABAA receptor.

Menthol is widely used in dental care as a topical antibacterial agent, effective against several types of streptococci and lactobacilli.

Sources

• Perfume and flavor chemicals II - Steffen Arctander 

• Wikipedia

• National Center for Biotechnology Information (2020). PubChem Compound Summary for CID 16666, l-Menthol. Retrieved November 25, 2020 from https://pubchem.ncbi.nlm.nih.gov/compound/l-Menthol.