Chemical Properties

Free-flowing or agglomerated, crystalline powder or prismatic or acicular, colourless, shiny crystals

Physical properties

Physical Properties. The eight optically active menthols differ in their sensory properties. (?)-Menthol has a characteristic peppermint odor and also exerts a cooling effect. The other isomers do not possess this cooling effect and are, therefore, not considered to be “refreshing.” Racemic menthol occupies an intermediate position; the cooling effect of the (?)-menthol present is distinctly perceptible. The enantiomeric menthols have identical physical properties (apart from their specific rotations), but the racemates differ from the optically active forms in, for example, theirmelting points.Although the differences between the boiling points are small, the (racemic) stereoisomers can be separated by fractional distillation. Boiling points (in °C at 101.3 kPa) are as follows: rac-neomenthol, 211.7 rac-neoisomenthol 214.6 rac-menthol, 216.5 rac-isomenthol, 218.6 Other physical constants of commercially available levorotatory and racemic menthols are as follows: (?)-menthol, mp 43 °C, [α]20 D ?50° (ethanol, 10%); racemic menthol, mp 38 °C. Chemical Properties. Hydrogenation of menthols yields p-menthane; oxidation with chromic acid or catalytic dehydrogenation yields menthones. Dehydration under mild conditions yields 3-p-menthene as the main product. Reaction with carboxylic acids or their derivatives yields menthyl esters, which are used mainly as aroma substances and in pharmaceutical preparations and formulations. The esterification of menthols with benzoic acid is used on an industrial scale in the resolution of racemic menthol.

Occurrence

Has apparently not been reported to occur in nature

Preparation

By hydrogenation of thymol followed by separation from its other isomers.

Indications

Menthol, a cyclic alcohol (derived from peppermint, other mint oils, or prepared synthetically), relieves itching by generating a cool sensation. It is usually used in 0.25% to 2% concentrations but is present in concentrations as high as 16% in some OTC products.

Toxicity evaluation

The acute oral LD50 in rats has been reported as 3180 mg/kg by Jenner, Hagan, Taylor, Cook & Fitzhugh (1964) and as 2900 mg/kg by Herken (1961). The acute oral LD50 in cats was reported to be 1500-1600 mg/kg (Flury & Seel, 1926). The sc LD50 in the mouse was reported as 1400-1600 mg/kg (Flury & Seel, 1926) and the ip LD50 as 750 mg/kg in the rat (Herken, 1961) and 1500-1600 mg/kg in the cat (Flury & Seel, 1926). In rabbits, the ip LD50 was reported to be approximately 2000 mg/kg (Herken, 1961), while the acute dermal LD50 exceeded 5000 mg/kg (Levenstein, 1973).

Safety Profile

Moderately toxic by ingestion, intraperitoneal, and subcutaneous routes. An eye and skin irritant. K%en heated to decomposition it emits acrid smoke and irritating fumes. See also MENTHOL and 1-MENTHOL.

Metabolism

Rabbits are said to eliminate 59% of dl-menthol as glucuronide (Williams, 1938).

Who Evaluation

Evaluation year: 1998