(-)-Menthol (2216-51-5) Physical and Chemical Properties
(-)-Menthol
Naturally occurring (-)-menthol is a monoterpenoid alcohol widely used in flavor, fragrance and topical formulations, procured for its cooling sensory properties and enantiomer-specific performance in industrial and pharmaceutical applications.
| CAS Number | 2216-51-5 |
| Family | Monoterpenoid alcohols |
| Typical Form | Crystalline solid (pellets or granules) |
| Common Grades | BP, EP, FCC, Food Grade, JP, Reagent Grade, USP |
(-)-Menthol is a monocyclic monoterpene alcohol (p-menthan-3-ol) belonging to the cyclohexanol structural class. The molecule is configurationally defined as (1R,2S,5R) (levomenthol), with three defined stereocenters and a single hydroxyl functional group on a saturated cyclohexane ring bearing methyl and isopropyl substituents. Electronically it is dominated by aliphatic hydrocarbon character with a single polar hydroxyl; this produces limited polarity (topological polar surface area \(\,20.2\)) and a modest capacity for hydrogen bonding (one H-bond donor, one H-bond acceptor). Computed descriptors indicate a compact, low‑complexity monofunctional alcohol with molecular formula C10H20O and molecular weight \(\,156.26\,\mathrm{g}\,\mathrm{mol}^{-1}\).
Because it is a neutral secondary/tertiary-type alcohol (non-ionizable under ambient conditions), menthol exhibits low aqueous solubility and appreciable lipophilicity (reported log P/log Kow values around 3.3–3.4). It is chemically stable under typical storage but will oxidize under strong oxidative conditions to ketones (e.g., menthone) and other oxidized metabolites; it is incompatible with strong oxidizers. Thermal decomposition produces irritant combustion products (carbon monoxide/CO2 and acrid fumes). Physically, the optically active form is a white, waxy crystalline solid at ambient temperature that melts slightly above room temperature and sublimes or volatilizes slowly under warm conditions; it is readily soluble in organic solvents (alcohols, ethers, chloroform, acetone, benzene) but only sparingly soluble in water.
Common commercial grades reported for this substance include: BP, EP, FCC, Food Grade, JP, Reagent Grade, USP.
Basic Physical Properties
Density
Reported density values include: 0.904 at \(\,59\,^\circ\mathrm{F}\) (NTP, 1992) — less dense than water; will float. Additional measured values: 0.890 and 0.901 (20°); 0.891 (30°). An aggregate laboratory value is also reported as DENSITY: 0.904 @ \(\,15\,^\circ\mathrm{C}/15\,^\circ\mathrm{C}\). These values indicate a typical liquid/solid-phase bulk density below that of water.
Melting Point
Reported melting points: 100 \(\,^\circ\mathrm{F}\) (NTP, 1992); single-value reports of 43 and 43 \(\,^\circ\mathrm{C}\); and a range of 41–43 \(\,^\circ\mathrm{C}\). Use the crystalline melting range of approximately 41–43 \(\,^\circ\mathrm{C}\) for specification and processing considerations.
Boiling Point
Reported boiling points include: 421 \(\,^\circ\mathrm{F}\) at 760 mmHg (NTP, 1992). Additional numeric entries appear as "212" and "212 \(\,^\circ\mathrm{C}\)"; reported values vary depending on data source and measurement conditions. For high-temperature processing and distillation design, the higher reported boiling point near the 210–216 \(\,^\circ\mathrm{C}\) range (at atmospheric pressure) should be used with caution and confirmed experimentally for the specific material/grade.
Vapor Pressure
Reported vapor pressures: approximately 1 mmHg at 133 \(\,^\circ\mathrm{F}\) (NTP, 1992) and measured/quoted values of 0.06 mmHg. These low vapor pressures at moderate temperatures indicate low volatility at ambient conditions but significant vaporization at elevated temperatures; use vapor‑pressure data appropriate to the process temperature when assessing inhalation exposure or vapor loss.
Flash Point
A flash point of 196 \(\,^\circ\mathrm{F}\) (NTP, 1992) is reported. Menthol is combustible; precautions for ignition sources are required during handling and storage.
Chemical Properties
Solubility and Phase Behavior
Quantitative solubility reports include: "less than 1 mg/mL at 70 \(\,^\circ\mathrm{F}\)" (NTP, 1992), "0.49 mg/mL at 25 \(\,^\circ\mathrm{C}\)" and "In water, 456 mg/l @ 25 \(\,^\circ\mathrm{C}\)". These values indicate very limited aqueous solubility (on the order of 10^-3 to 10^-4 \(\,\mathrm{g}\,\mathrm{mL}^{-1}\)), while menthol is freely or very soluble in typical organic solvents: alcohols, chloroform, ether, petroleum ether, acetone, benzene, glacial acetic acid and in lipid vehicles such as liquid petrolatum. Phase behavior: solid at ambient temperatures (crystalline pellets or flakes), melts near \(\,41!-!43\,^\circ\mathrm{C}\), and forms clear or white waxy crystals. In mixed solvent systems (e.g., ethanol–water), menthol can partition strongly into the organic phase and may be expelled as an oily layer on dilution with water.
Reactivity and Stability
Menthol is chemically stable under normal ambient storage but reacts with strong oxidizing agents and certain reactive reagents. Reported incompatibilities include butylchloral hydrate, camphor, phenol, chloral hydrate, betanaphthol, resorcinol, thymol (in triturations), potassium permanganate, chromium trioxide and pyrogallol; it should therefore be kept away from strong oxidizers and reactive halogenating/chlorinating agents. On heating to decomposition, menthol emits acrid smoke and irritating fumes (combustion products). Hydrolysis is not applicable (no hydrolyzable functional group), but oxidative biotransformation and chemical oxidation (to menthone and other oxidized products) are relevant reactivity pathways.
Thermodynamic Data
Standard Enthalpies and Heat Capacity
No experimentally established value for this property is available in the current data context.
Molecular Parameters
Molecular Weight and Formula
Molecular formula: C10H20O. Molecular weight: \(\,156.26\,\mathrm{g}\,\mathrm{mol}^{-1}\). Exact/monoisotopic mass: 156.151415257.
LogP and Polarity
Computed and experimental lipophilicity descriptors reported include XLogP3-AA = 3 (computed), experimental/log Kow entries of 3.3 and 3.4, and a reported log P = 3.40. Topological polar surface area (TPSA) = 20.2, H-bond donor count = 1, H-bond acceptor count = 1. These descriptors are consistent with a moderately lipophilic neutral alcohol that partitions preferentially into organic phases and biological membranes.
Structural Features
IUPAC name (computed): (1R,2S,5R)-5-methyl-2-propan-2-ylcyclohexan-1-ol. SMILES: C[C@@H]1CCC@HC(C)C. InChI: InChI=1S/C10H20O/c1-7(2)9-5-4-8(3)6-10(9)11/h7-11H,4-6H2,1-3H3/t8-,9+,10-/m1/s1. The molecule contains a saturated cyclohexane ring substituted at three positions including a hydroxyl group; stereochemical configuration of the natural enantiomer is (1R,2S,5R). Rotatable bond count is low (1), reflecting the rigid cyclic scaffold that confers a defined chiral topology and characteristic odor and pharmacological interaction profile.
Identifiers and Synonyms
Registry Numbers and Codes
CAS: 2216-51-5
Other machine identifiers present in the chemical annotation include: - InChIKey: NOOLISFMXDJSKH-KXUCPTDWSA-N - SMILES: C[C@@H]1CCC@HC(C)C - UNII: YS08XHA860 (as supplied in the identification metadata) - FEMA Number: 2665 - KEGG: C00400 / D00064
(Only identifiers supplied in the available annotation are listed above.)
Synonyms and Structural Names
Depositor-supplied synonyms and common names include: l-Menthol; (-)-menthol; Levomenthol; l-(-)-Menthol; Levomentholum; U.S.P. Menthol; (-)-Menthyl alcohol; (1R)-(-)-Menthol; (1R,2S,5R)-5-methyl-2-(propan-2-yl)cyclohexan-1-ol; (1R,2S,5R)-Menthol; p-Menthan-3-ol; Hexahydrothymol; Menthomenthol; Peppermint camphor; and many trade/standard designations (USP, EP, JP, FCC, Reagent Grade). The molecule is commonly referred to as levomenthol or L‑menthol for the naturally occurring (1R,2S,5R) enantiomer.
Industrial and Commercial Applications
Representative Uses and Industry Sectors
(-)-Menthol is widely used as a flavoring and fragrancing agent in toothpastes, mouthwashes, confectionery, chewing gum, lozenges and beverages; as an odorant in perfumes and consumer products; and as an active counterirritant/antipruritic and mild topical anesthetic in pharmaceutical formulations (creams, ointments, inhalers, cough drops). It is used in personal-care and cosmetic products, some household cleaners, and certain industrial formulations (paints, adhesives, metal care products, disinfectants) where a cooling odor or mild sensory effect is desired. Typical industry sectors include flavor and fragrance manufacturing, food and beverage production, personal-care and cosmetics, pharmaceuticals, and some specialty chemical applications.
Role in Synthesis or Formulations
Menthol serves as an end‑use active (sensory agent) and as a building block for derivatization (e.g., menthyl esters to modify odor profiles). Industrial manufacture is by isolation from peppermint/cornmint essential oils or by synthetic routes (hydrogenation of thymol or related precursors). In formulary contexts it functions as a solute in organic vehicles, a penetration enhancer in transdermal formulations (synergistic effects with ethanol), and a counterirritant in topical products. Common commercial grades used in formulations include: BP, EP, FCC, Food Grade, JP, Reagent Grade, USP — selection depends on regulatory and purity requirements for the target application.
Safety and Handling Overview
Acute and Occupational Toxicity
Key toxicological findings and acute toxicity values reported include: - ORAL (LD50): Acute: \(2900\,\mathrm{mg}\,\mathrm{kg}^{-1}\) [Rat], \(3100\,\mathrm{mg}\,\mathrm{kg}^{-1}\) [Mouse] (various reports). - Additional LD50 entries: LD50 Rat oral \(3300\,\mathrm{mg}\,\mathrm{kg}^{-1}\); LD50 Rat ip \(700\,\mathrm{mg}\,\mathrm{kg}^{-1}\); LD50 Mouse ip \(6600\,\mathrm{mg}\,\mathrm{kg}^{-1}\); LD50 Mouse oral \(3400\,\mathrm{mg}\,\mathrm{kg}^{-1}\).
Hazard classification information aggregated across notifications characterizes menthol primarily as a skin and eye irritant (GHS codes H315, H319/H320 in many notifications) and notes potential for narcotic effects at high exposures (H336) and aquatic toxicity (H402) in some classifications. Clinical observations include dermal and mucous membrane irritation, potential contact hypersensitivity in susceptible individuals, and, in severe poisoning, neurological symptoms (drowsiness, ataxia, seizures) and respiratory depression. Menthol activates cold‑sensitive TRPM8 receptors and can produce a pronounced cooling sensation at typical product concentrations.
First‑aid guidance (generalized): in case of eye contact, flush with copious water for at least 20–30 minutes and obtain medical attention; for skin contact, remove contaminated clothing and wash with soap and water; if inhaled, move to fresh air and seek medical attention for respiratory symptoms; if ingested, do not induce vomiting and seek medical assistance. For all exposures, consult medical professionals and refer to product‑specific safety documentation.
Storage and Handling Considerations
Menthol is combustible and should be stored away from ignition sources and strong oxidizing agents. Recommended precautions for handling: use local exhaust ventilation where dusts or vapors may be generated; avoid inhalation and contact with eyes and skin; use appropriate gloves, eye protection and protective clothing. For weighing and handling of neat material, use respiratory protection appropriate for organic vapors and dust/mist if airborne concentrations are possible. Small solid spills can be collected and removed using ethanol‑dampened absorbent; avoid introducing water into concentrated alcoholic solutions where menthol may separate out. Store under ambient conditions, in tightly closed containers, protected from oxidizers and excessive heat. For detailed hazard, transport and regulatory information, users should refer to the product‑specific Safety Data Sheet (SDS) and local legislation.
