Racemic menthol

Piperitone is of considerable technical im portance. It is a colourless oil of a pleasant peppermint-like smell. (-)-Piperilone has b.p. 109-5-110-5 C/I5mm. Piperitone yields thymol on oxidation with FeCl. On reduction with hydrogen in presence of a nickel catalyst it yields menthone. On reduction with sodium in alcoholic solution all forms of piperitone yield racemic menthols and womenthols together with some racemic a-phel)andrene. 

Uses ndReactions. The largest use of myrcene is for the production of the terpene alcohols nerol, geraniol, and linalool. The nerol and geraniol are further used as intermediates for the production of other large-volume flavor and fragrance chemicals such as citroneUol, dimethyloctanol, citroneUal, hydroxycitroneUal, racemic menthol, citral, and the ionones and methylionones. 

Racemic menthol 11 is converted into the optically pure ester with lipase62. 

Chemical Properties. Hydrogenation of menthols yields / -menthane oxidation with chromic acid or catalytic dehydrogenation yields menthones. Dehydration under mild conditions yields 3-/ -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. 

Occurs in essential oils. It is synthesized by esterification of racemic menthol. Its odor is crisper and less fruity than that of (—)-menthyl acetate. It is used for essential oil compositions and occasionally in household perfumery. 

Thymol is used as a dry top note in lavender compositions, in men s fragrances, and as a disinfectant in oral care products. It is also important as a starting material for the production of racemic menthol. 

Lipase-Catalyzed Resolution of Racemic Menthol Esters... 

Haarmann Reimer (Holzminden, Germany) in collaboration with Rolf Schmid s group at the University of Stuttgart developed a process based on the resolution of racemic menthol esters, such as acetate or benzoate esters. The team employed several lipases such as Candida cyclindracea which resulted in enantio-selectivities up to 100% e.e. (Bomscheuer, 2002). 

Optical resolution of menthol (28) with DBTA in hexane suspension is quite efficient (S = 0.374, Table 5 [38]) but complex formation is slow. In order to increase the reaction rate, the highest possible concentrations of the reactants were reached by solving DBTA monohydrate in the melt of racemic menthol. [41]... 

Likewise, vanillin is now largely produced synthetically. The world leader in this area is Rhone-Poulenc, which has a unit in Saint-Fons to which was added a unit bought from Monsanto in 1986 on the West Coast of the United States. In the latter plant, vanillin is still extracted from paper pulp liquor. Menthol from plantations in Brazil and China is also produced by synthesis since Haarmann Reimer, bought by Bayer in 1954, managed to carry out industrially the resolution of racemic menthol, thus isolating the levoiso-mer. Anethole, synthesized by Hercules from pine oil, is two to three times cheaper than when it is extracted from star anise. 

Menthol is natural laevo-menthol, obtained from the volatile oils of various species of Mentha (Labiatae), or synthetic laevo-menthol, or racemic menthol. 

SYNS FEMA No. 2665 4-ISOPROPYL-l-METHYL-CYCLOHEXAN-3-OL dl-3-p-MENTHANOL 3-p-MENTHOL MENTHOL racemic MENTHOL racemique (FRENCH) 5-METHYL-2-(l-METHYLETHYL)-CYCLOHEXANOL (l-0,2-P,5-a)... 

Hexahydrothymol 2-isopropyl-5-methylcyclohexanol 4-iso-propyl-l-methylcyclohexan-3-ol 3-p-menthanol p-menthan-3-ol dZ-menthol peppermint camphor racemic menthol. 

Menthol is widely used in pharmaceuticals, confectionery, and toiletry products as a flavoring agent or odor enhancer. In addition to its characteristic peppermint flavor, /-menthol, which occurs naturally, also exerts a cooling or refreshing sensation that is exploited in many topical preparations. Unlike mannitol, which exerts a similar effect due to a negative heat of solution, /-menthol interacts directly with the body s coldness receptors. d-Menthol has no cooling effect, while racemic menthol exerts an effect approximately half that of /-menthol. 

Racemic menthol is prepared synthetically via a number of routes, e.g. by hydrogenation of thymol. 

Michor et al. (93) compared four lipases and an esterase for the resolution of racemic menthol by transesterification [Eq. (15)] ... 

Michor et al. investigated four lipases and an esterase in the stereospecific transesterification of racemic ( )-menthol and ( )-citronellol in SCCO2. The transesterification of racemic menthol was reasonably fast and gave high... 

In 1938 Stankiewicz reproduced the asymmetric 2-butanol decomposition experiments of Schwab (1932) at a higher temperature and atmospheric pressure and extended studies to the asymmetric decomposition of racemic menthol and 3-methylheptan-3-ol. Over a Cu-r/-quartz catalyst the latter substrate produced a maximal optical rotation of -0.26° and the decomposition of 2-butanol gave a reaction mixture with a rotation of +0.25°. 

Decomposition studies of racemic menthol and 3-methylheptan-3-ol gave similar results (Scheme 2.2.). Thus dehydration of racemic menthol over Cu-/-quartz in a flowing N2-air mixture at 430-460°C results in a product with a rotation of -0.16°, which indicated preferential decomposition of the (+)-enantiomer of menthol. The same picture was obtained, but to a somewhat greater extent, for the dehydrogenation of 3-methylheptan-3-ol on Cu-/-quartz in which the (+)-enantiomer reacted and the product exhibited a rotation of -0.12°. 

Dehydration of racemic menthol on Ni-/-quartz at 560°C gave products containing 62.4% menthenes and a rotation of -0.15°. This catalyst was strongly carbonized during reaction and lost its activity, but alter oxidation and reduction with hydrogen it gave a product with a rotation of -0.08. ... 

Synonyms Cyclohexanol, 2-isopropyl-5-methyl- Cyclohexanol, 5-methyl-2-(1-methylethyl)- Hexahydrothymol 2-lsopropyl-5-methylcyclohexanol 3-p-Menthanol p-Menthan-3-ol 5-Methyl-2-isopropylcyclohexanol 5-Methyl-2-isopropyl hexahydrophenol 5-Methyl-2-(1-methylethyl) cyclohexanol Peppermint camphor Racemic menthol Classification Diterpene alcohol Definition Alcohol obtained from diverse mint oils, Mentha spp. or prepared synthetically may be levorotatory (I-), from natural or syn. sources, or racemic (dl-)... 

Racemic limonene. See dl-Limonene Racemic mandelic acid. See Mandelic acid Racemic menthol. See Menthol Racemic pantothenyl alcohol. See DL-Panthenol... 

In this case the resolving agent should be added to the racemic compound and the mixture should be warmed until it melted then is should be cooled while one of the diastereoisomers crystallizes from the melt. The ciystalline material can be separated by filtration from the residue of the melt (as in case of enantiomeric mixtures). An example for this method is the resolution of racemic menthol (MEN) with 0,0 -dibenzoyl-(J ,J )-tartaric acid ((R,R)-DBTA). The crystalline molecular complex (diastereoisomer) contains the (lJ ,2S,5J )-menthol (the L-menthol (L-MEN)), while the remained melt is enriched in the other enantiomer ... 

Scheme 9.1 An early production process for racemic menthol and resolution to (—)-menthol...

Thymol is obtained by alkylation and is then further hydrogenated into racemic menthol ... 

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