Thymol and menthol

PerioGard, Peridex, Listerine, and Plax are trade name examples other similar generic rinsing agents are commercially available. Essential oils contain eucalyptol, methyl salicylate, thymol, and menthol. 

Pure meto-cresol has been used for manufacture of synthetic musk— musk ambrette, used as a fixative to perfumes, for manufacture of synthetic Thymol and Menthol amd also leather preservative p-chloro-meto-cresol, synthetic pyre-throids, and lastly for manufacture of 2,3,6-trimethylphe-nol—an intermediate for vitamin E. o-Cresol has been used for manufacture of Coumarin and some derivatives which are employed in perfumery as fixative. o-Cresol has also been used for making Novolac and epoxy resins and also for the herbicides based on di-nitro-oAt/io-cresol, etc. In sum, individual cresols have been very successfully converted to important intermediates in the organic chemical synthesis. It is expected that further development work will lead to synthesis of many more organic chemicals of vital importance. While new chemicals using individual cresols are in the pipeline... 

Some of the esters and ethers of 79-cresol and its derivatives have become very popular in the manufacture of synthetic perfumes. Prominent among them are 79-cresyl methyl ether, p-cresyl acetate, p-cresyl phenyl acetate, etc. Some of them are very popular in the manufacture of Indian agarbattis (incense sticks). Thymol and menthol which were traditionally obtained from the natural sources are now synthetically made from m-cresol and are much cheaper as flavor and fragrance chemical than the natural ones. BAYER AG of Germany is the largest manufacturer of synthetic thymol and menthol. 

Haeseler G, Maue D, Grosskreutz J, Bufler J, Nentwig B, Piepenbrock S, Dengler R, Leuwer M (2002) Voltage-dependent block of neuronal and skeletal muscle sodium channels by thymol and menthol. Eur J Anaesthesiol 19 571... 

Odoriferous substances and their mixtures (e.g. essential oils) show a number of beneficial effects for which they have found use as pharmaceuticals, pharmaceutical ingredients and food additives. Bactericidal and anti-inflammatory effects are seen in bomeol, eugenol, pinenes, camphor, thymol and menthol, choHnolytic (spasmolytic) effects preventing a drop in blood pressure and suppressing the secretory activity of various organs are found in camphor, pinenes and camphene, and analeptic effects (stimulating activity of circulation and respiratory system) are seen in camphene. The essential oils of many spices (such as marjoram, sage, thyme and many others) exhibit antioxidant effects, and therefore find use as natural antioxidants of fats. 

Read the labels on household products such as sanitizers, mouthwashes, cold remedies, rubbing alcohol, and flavoring extracts. Look for names of alcohols, such as ethyl alcohol, isopropyl alcohol, thymol, and menthol. 

The most reliable work on the isomeric menthols is that of Pickard and Littlebury.2 Starting from the mixture of alcohols which Brunei had obtained by the reduction of thymol, and which he had described under the name of thymomenthol, they isolated from it about 60 per cent, of isomeric menthols, 30 per cent, of menthones, and several other compounds. They prepared the phthalic acid esters and converted them into their magnesium and zinc salts, which were then fractionally crystallised. 

A mixture of essential oils consisting of thymol 0.06%, eucalyptol 0.09%, methyl salicylate 0.06%, and menthol 0.04% in an alcohol-based vehicle (26.9%) provides the plaque-inhibiting properties of rinsing agents such as Listerine. 

Monoterpenes, 10-carbon-containing terpenoids, are composed of two isoprene units, and found abundantly in plants, e.g. (+)-limonene from lemon oil, and (—)-linalool from rose oil. Many monoterpenes are the constituents of plant volatile oils or essential oils. These compounds are particularly important as flavouring agents in pharmaceutical, confectionery and perfume products. However, a number of monoterpenes show various types of bioactivity and are used in medicinal preparations. For example, camphor is used in liniments against rheumatic pain, menthol is used in ointments and liniments as a remedy against itching, bitter-orange peel is used as an aromatic bitter tonic and as a remedy for poor appetite and thymol and carvacrol are used in bactericidal preparations. 

Lithium-ethylamine reduction at one or both double bonds of carvone, and of carvenone (58) to carvomenthone only, is reported.The effect of solvent on the lithium or potassium amide-reduction of p-cymene to menthenes and menthadienes has been examined.Hydrogenation of carvone (Vol. 4, p. 32), using palladium-polysaccharide exchange resin, favours endocyclic over exocyclic double-bond reduction, more so than with Pd-C or Pd-BaS04, whereas platinum or rhodium on exchange resins exhibit no special selectivity.Optimum conditions for the catalytic hydrogenation of thymol, and the catalytic dehydrogenation of menthol, to menthone have been determined.Cathodic reduction of carvomenthone (to... 

Time-course studies with 14COa showed that in a Thymus sp., y-terpinene was converted into p-cymene and thymol in sequence,916 and the appropriate y-terpinene synthetase (MW ca. 96 000) was partially purified. Tracer studies indicated that loss of a proton from C-5 of the a-terpinyl-like precursor to form the A4-un-saturation was accompanied, perhaps concertedly, by a 1,2-hydride shift from C-4 to C-8 to form y-terpinene.917 Neomenthyl-p-D-glucoside was a major metabolite of menthone in Mentha spp.,918 and a cell-free extract also acetylated menthol.919 Detailed in vivo and in vitro investigations revealed that in leaf discs the bulk of the neomenthol and menthol (produced from menthone) was converted into the gluco-... 

A Japanese patent (126) discloses the preparation of amorphous materials with diverse compositions and their resulting activities for different transformations. One of these specimens, a Ni49Al50Cri alloy, is active in the hydrogenation of thymol to menthols at high pressure (10.1 MPa, 403 K). Treatment with hydrogen (523 K, 1 h) increases the selectivity of the formation of /-menthol (71 versus 54%), whereas a 2-h heat treatment at 873 K decreases markedly the activity (96.7—10.2%). 

The catalytic properties of Pt, Rh and Ir catalysts in the reduction of thymol have been compared, with respect to their activities and stereoselectivities in the formation of menthones and menthols. The reduction over Pt and Rh proceeds essentially via the ketone intermediates, whereas the direct route is predominant on Ir. The formation of the cis isomers is always highly favored. The stereoselectivity of thymol reduction is controlled by the relative proportions of these two routes and by their stereoselectivities. 

Classification Specially denatured alcohol Definition Ethyl alcohol (100 gal) denatured with eucalyptol NF (45 fl. oz), thymol NF (30 oz), and menthol USP (20 oz)... 

Monoterpenes Constituents of essential oils, e.g., geraniol, menthol, and thymol, and of iridoids, e.g., loganin and secologanin... 

The EO of Ziziphora clinopodioid.es ssp. rigida (blue mint bush) was isolated by hydrodistillation of the dried aerial parts, which was collected during the anthesis. The main compounds are thymol and 1,8-cineole with a content of 8% and 2.7%, respectively. Different extracts were tested by the DPPH assay to determine the antioxidative activity and showed that the free radical scavenging activity of the menthol extract was superior to all other extracts. Polar extracts exhibited stronger antioxidant activity than nonpolar extracts (Salehi et al., 2005). 

The most important monoterpene alcohols are menthol, cis- and trans-piperitol, cis- and trans-pulegol, isopulegol, cis- and trans-caiveol, thymol, carvacrol, terpinen-4-ol, and a-terpineol. The latter two bear a tertiary alcohol function. Terpinen-4-ol is a major antibacterial component of tea tree oil Melaleuca alternifolia). a-Terpineol is a major compound in cardamom oil. (—)-Menthol is a main constituent in mint oils Mentha x piperita and other Mentha species). Terpinen-4-ol is typically found in marjoram oils Origanum majorana) a-terpineol occurs in various essential oils including those from Melaleuca viridiflora and nutmeg Myristica fragrans). Thymol and carvacrol are... 

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. 

Active agents vary according to use. For controlling bad breath, 2iac salts, sodium lauryl sulfate, and flavors are used. To destroy oral microorganisms, chlorhexidine, cetylpyridinium chloride [123-03-5] and ben2alkonium chloride [68391-01-5] are valuable. Essential oils, such as thymol [89-83-8] eucalyptol [470-82-6] menthol, and methyl salicylate [119-36-8] reduce plaque-related gingivitis (see Oils, essential). Sodium fluoride aids ia caries coatrol. 

Camphor [126-04-5] (11), menthol [89-78-1] (12), and thymol [89-83-8] (13) ate used in topical over-the-counter cough and cold preparations. Camphor is isolated from the camphor tree, Cinnomomum camphora T. Nees Eherneier, or prepared synthetically from a-pinene or isobomeol. About 75% of the camphor sold in the United States is synthetic. Menthol, commercially the most important terpene alcohol, is obtained by crysta11i2ation from... 

Menthol (hRf 15) and menthyl acetate hRt 55) yielded blue chromatogram zones caryophyllene hRf 90) and caryophyllene epoxide hRf 20 — 25) appeared red-violet and thymol hRf 40 — 45) appeared brick red in color. 

Fig. 1 Schematic sketch (A) of the separation of essential oil components (ca. 500 ng of each component) and reflectance scan of the mixture (B). Menthol (1), caryophyllene epoxide (2), thymol (3), menthyl acetate (4), caryophyllene (5), mixture (G).

According to Read and Smith i piperitone is, under natural conditions, optically inactive. By fractional distillation under reduced pressure, it is prepared, by means of its sodium bisulphite compound, in a laavo-rotatory form. The slight laevo-rotation is probably due to the presence of traces of cryptal. By fractional distillation alone, it is usually obtained in a laevo-rotatory form whether this is due to decomposition products or not is unknown. Piperitone has a considerable prospective economic value, as it forms thymol by treatment with formic chloride, inactive menthone by reduction when a nickel catalyst is employed, and inactive menthol by further reduction. Its char-Mters are as follows —... 

The synthetic process starts with the isopropylation of m-cresol to yield thymol. After catalytic hydrogenation a mixture of stereoisomers is obtained from which (+)-menthol is isolated. The process requires much separation and recycling work. In contrast, the semi-synthetic process of Takasago (Scheme 5.5) leads essentially to stereopure (—)-menthol [19]. 

The remaining isomeric menthols, neomenthol, isomenthol, and a trace of neoisomenthol, can be epimerized, under the conditions used for the thymol hydrogenation, to give ca. 6 3 1 equilibrium mixture of ( )-menthol, ( )-neomenthol, and ( )-isomenthol, respectively. ( )-Menthol can, again, be distilled from the equilibrium mixture. 

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. 

Alkylation of m-cresol with propene in the presence of an aluminium catalyst results in the formation of thymol, which upon hydrogenation gives a rnkture of all eight isomers of menthol, D-menthol, L-menthol, neomenthol, isomenthol and neoisomenthol (Scheme 13.3). The preferred isomer is L-menthol, because of its ability to induce physiologically the sense of cold which is desired in many products such as chewing gum and toothpaste L-menthol is about... 

Besides thymol, other terpenes have been tested for their toxicity against Varroa jacobsoni. Imdorf et al. determined in vitro the effective miticidal air concentrations, but with minimal effects on the bees as follows 5-15 pg/litre air for thymol, 50-150 pg/litre for camphor and 20-60 pg/litre for menthol 1,8-cineole was too toxic for honey bees [86], Another interesting paper considered the efficacy of different isomers of menthol on Acarapis woodi [87]. The natural crystals obtained from the plant, synthetic crystals and the L-form gave more than 96% mite mortality, while the D-form crystals only a 37% mortality. 

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