Menthol

Synthetic Ingredient Overview

• 🔎 Chemical Name: 2-Isopropyl-5-methylcyclohexanol

• 🧪 Synonyms: Menthol, (–)-Menthol, dl-Menthol (racemic)

• 🧬 Chemical Formula: C₁₀H₂₀O

• 📂 CAS N°: 2216-51-5

• 📘 FEMA: 2665

• ⚖️ MW: 156.26 g/mol

• 📝 Odor Type: Fresh, Minty

• 📈 Odor Strength: High

• 👃🏼 Odor Profile: Peppermint-like, sweet, diffusive, pungent, cooling without menthone harshness

• ⚗️ Uses: Cooling modifier, top note booster, flavoring agent, TRPM8 activator

• 🧴 Appearance: White crystalline solid; melts ~36–38 °C

What is Menthol?

Menthol is a mint-sourced or synthetically produced terpene alcohol found predominantly as the (–)-enantiomer in nature. It crystallizes from mint oils such as Mentha arvensis or can be synthesized via hydrogenation of thymol, citronellal, or pulegone intermediates. Commercial grades may be enantiomerically pure or racemic depending on production route.

Its olfactory perception is tightly coupled with its somatosensory cooling effect, though the two thresholds differ—menthol may be smelled at sub-ppm levels, while its TRPM8 receptor-mediated cold sensation occurs at higher concentrations. Menthol is structurally stabilized by a chair conformation, allowing its hydroxyl, methyl, and isopropyl groups to adopt equatorial positions, enhancing physical and sensory stability.

Biological Properties of Menthol

Menthol exhibits diverse biological activity beyond its olfactory and flavoring functions. It acts as a selective agonist of the TRPM8 ion channel, a cold-sensing receptor present in sensory neurons. Activation of TRPM8 by menthol triggers the familiar cooling sensation without an actual decrease in temperature, making it valuable in topical analgesic and cosmetic applications. Menthol is also a weak κ-opioid receptor agonist, contributing to its analgesic effects, and a GABA_A receptor positive allosteric modulator, which imparts mild sedative and anesthetic properties similar to propofol. Furthermore, menthol blocks voltage-gated sodium channels, decreasing neuronal excitability and enhancing its use in localized pain relief. In oral care, menthol demonstrates antibacterial activity against streptococci and lactobacilli, supporting its role in preventing dental plaque and oral biofilm formation.

Menthol Production Methods

Menthol can be obtained by both natural extraction and synthetic synthesis. The natural form is typically isolated from Mentha arvensis or Mentha piperita oils through steam distillation, followed by fractional crystallization at low temperatures. The menthone-rich residual fraction can be further hydrogenated to yield additional menthol. Synthetic production routes involve hydrogenation of thymol, pulegone, or isopulegol, yielding either racemic menthol or specific stereoisomers depending on the reaction pathway. Another industrial method derives menthol from citronellal via isopulegol intermediates. While natural menthol remains dominant in Asian markets, synthetic menthol accounts for a growing share of global production, offering higher stereoisomeric control and cost efficiency. Most commercial menthol is sold as the (–)-enantiomer, although racemic mixtures are used in technical applications.

Olfactory Profile & Perfumery Applications

Menthol imparts a diffusive, clean minty freshness, with a secondary sweetness and a mild pungency. It is widely used in:

• Fougères and Aromatic Florals – enhancing lavender, geranium, rose

• Soaps and toiletries – lending clean, hygienic freshness

• Functional perfumery – e.g., shaving products, aftershaves

• Mint accords – spearmint, peppermint, menthone systems

Typical concentrations in perfume:

• 0.5%–2.5% in concentrate for freshening and boosting

• Used to lift and cool heavy florals or medicinal blends

Flavor applications include chewing gum, mint blends, caramel, licorice, imitation butter, fruit complexes.

Suggested internal link: See Smell of Specific Chemical Groups for terpene-based cooling and mint profiles.

Molecular Behavior & Pharmacological Properties

Menthol’s physiological and pharmacological behavior is linked to its interaction with TRPM8 cold receptors, which respond to moderate cooling stimuli. When inhaled, consumed, or topically applied, menthol activates cold-sensitive ion channels, triggering a sensation of coolness without temperature change. This makes it distinct among aroma compounds for its dual sensory-olfactory impact.

Menthol also acts as:

• A κ-opioid receptor agonist, providing mild analgesia

• A GABA_A positive allosteric modulator, contributing to mild sedative and anesthetic effects(mechanism shared with propofol)

• A voltage-gated sodium channel blocker, which inhibits nerve impulse transmission in topical analgesics

Topical menthol is used in rubefacient creams, yet it does not reduce inflammation directly. Additionally, it shows topical antibacterial activity against Streptococcus and Lactobacillus strains, contributing to its long-standing use in dental care.

Crystallographically, menthol exists in multiple polymorphs, with the α-form being the most stable and familiar—broad, needle-like crystals with a melting point near 38 °C.

Industrial & Technical Uses

Menthol is used across multiple industries:

Perfumery:

• Freshening agent in personal care and functional fragrance

• Booster in floral-mint, fougère, and soap perfumes

• Adds cooling contrast in hot-spice and camphoraceous accords

Flavor:

• Mint (peppermint/spearmint) fortifier

• Used in traces for fruit, caramel, licorice, and imitation butter

• Max typical concentration:

  • 35–400 ppm (general food)

  • 1000–1200 ppm (chewing gum, dentifrice)

Cosmetics & Therapeutics:

• Shaving creams, aftershaves, cooling gels

• Topical analgesics and skin-relief formulations

• Oral hygiene products: toothpaste, mouthwash

• Carrier compound for over-the-counter muscle rubs

Regulatory & Safety Overview

• FEMA GRAS: 2665

• IFRA-compliant: Generally permitted within product-specific limits

• ECHA REACH Status: Not classified as hazardous under normal conditions

• Toxicology:

  • Non-carcinogenic, non-mutagenic

  • Potential irritant at high concentrations

  • Cooling effect may cause mucous membrane discomfort

Storage advice: Store in sealed containers, below melting point, in cool/dry environments. Flammable in vapor form; standard safety protocols apply.

Sources

• Perfume and Flavor Chemicals II – Steffen Arctander

• PubChem Compound Summary – CID 16666

• Wikipedia – Menthol Entry

• FEMA GRAS Database

• NCBI Scientific Literature

• Scentspiracy Archives