Thymol

Thymol is present in volatile oil of thyme and ajowan, mint seeds from which it may be extracted with sodium hydroxide, liberated from the sodium compound with acid and purified by crystallization. It has a woody, burnt, smoky odor. 

Thymol, isopropyl meta-cresol, is a precursor of L-menthol. Meta-cresol with a purity of 98.5% must be used as the starting material for thymol production, because the isomer, 2-iso-propyl-4-methyl phenol derived from p-cresol is the main contaminant and cannot be easily separated from thymol. 

In the industrial process employed by Bayer AG, Germany, m-cresol and propylene, both in the liquid state, are pumped through a pressure tube reactor, filled with activated alumina. The process is performed at a molar ratio of m-cresol propylene of 1.07 at 350-360°C, 5kg/cm and LHSV of 0.25 hr. The reaction product consists of 25% m-cresol, 60% th3nnol and 15% other products. Thymol of 99% + purity is obtained by rectification of the crude product [1]. 

Undesired alkylates of m-cresol (2-,4- and 5-isopropyl-m-cresol, 2,6- and 4,6-diisopropyl m-cresol) are recycled to the reaction zone to achieve a high overall 3neld of desired thymol. 

A gas phase process for thymol manufacture using medium pore-sized zeolites (erionite, mordenite, or ZSM-23) as heterogeneous catalyst was developed in 1988. It was reported that reaction temperatures were lower (230-270°C) than in the older liquid phase process. Reaction pressure was reported to be normal or slightly elevated. 

Addo trimico 3-p-cymenol p-cymen-3-ol Flavinol 3-hydroxy-p-cymene 3-hydroxy-l-methyl-4-isopropylbenzene Intrasol isopropyl cresol isopropyl-w-cresol 6-isopropyl-m-cresol isopropyl metacresol 2-isopropyl-5-methylphenol 1-methyl-3-hydroxy-4-isopropylbenzene 5-methyl-2-isopropyl-phenol 5-methyl-2-(l-methylethyl) phenol Medophyll thyme camphor thymic acid m-thymol timol. 

Thymol is also a true antioxidant and has been used at concentrations of 0.01% as an antioxidant for halothane, trichloroethylene, and tetrachloroethylene. 

More recently, thymol has been shown to enhance the in vitro percutaneous absorption of a number of drugs, including 5-fluorouracil, piroxicam, propranolol, naproxen, and tamoxifen. Studies have also demonstrated that the melting point of lidocaine is significantly lowered when it is mixed with thymol.  

The inhalation of thymol, in combination with other volatile substances, is used to alleviate the symptoms of colds, coughs, and associated respiratory disorders. Externally, thymol has been used in dusting powders for the treatment of fungal skin infections. Thymol was formerly used in the treatment of hookworm infections but has now been superseded by less toxic substances. 

In dentistry, thymol has been mixed with phenol and camphor to prepare cavities before filling, and mixed with zinc oxide to form a protective cap for dentine. 

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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. 

To prepare the standard pH buffer solutions recommended by the National Bureau of Standards (U.S.), the indicated weights of the pure materials in Table 8.15 should be dissolved in water of specific conductivity not greater than 5 micromhos. The tartrate, phthalate, and phosphates can be dried for 2 h at 100°C before use. Potassium tetroxalate and calcium hydroxide need not be dried. Fresh-looking crystals of borax should be used. Before use, excess solid potassium hydrogen tartrate and calcium hydroxide must be removed. Buffer solutions pH 6 or above should be stored in plastic containers and should be protected from carbon doxide with soda-lime traps. The solutions should be replaced within 2 to 3 weeks, or sooner if formation of mold is noticed. A crystal of thymol may be added as a preservative. 

Thymol blue, thymol-sulfonphthalein (indicator) dissolve 0.1 g in 10.75 mL 0.02ANaOH and dilute with water to 250 mL or dissolve 0.1 g in 20 mL warm alcohol and dilute with water to 100 mL pH range (acid) red 1.2-2.8 yellow, and (alkaline) yellow 8.0-9.6 blue. 

Thymol Acetanilide, antipyrine, camphor, chlorohydrate, menthol, quinine sulfate, ure-thene... 

Other synthetics with cost advantages and large volume productions are L-carvone [6485-40-17, the primary component in natural spearmint essence D-carvone [2244-16-8], the primary component in natural diU and caraway anethol [4180-23-8], in place of anise and fennel spices and smaller amounts of thymol [89-83-8] replacing thyme and disulfide synthetics for onion and gadic. AH of these synthetics must be labeled as artificial which may limit their use among consumers. 

Other lodo Compounds. Thymol iodide, C2OH24I2O2, mol wt 550.23, 46.13% I, is a reddish brown or reddish yeUow bulky powder that... 

A)-Menthol can also be made synthetically by hydrogenation of thymol [89-83-8], which can be produced by isopropylation of y -cresol with propylene (143,144). 

Methylene chloride is one of the more stable of the chlorinated hydrocarbon solvents. Its initial thermal degradation temperature is 120°C in dry air (1). This temperature decreases as the moisture content increases. The reaction produces mainly HCl with trace amounts of phosgene. Decomposition under these conditions can be inhibited by the addition of small quantities (0.0001—1.0%) of phenoHc compounds, eg, phenol, hydroquinone, -cresol, resorcinol, thymol, and 1-naphthol (2). Stabilization may also be effected by the addition of small amounts of amines (3) or a mixture of nitromethane and 1,4-dioxane. The latter diminishes attack on aluminum and inhibits kon-catalyzed reactions of methylene chloride (4). The addition of small amounts of epoxides can also inhibit aluminum reactions catalyzed by iron (5). On prolonged contact with water, methylene chloride hydrolyzes very slowly, forming HCl as the primary product. On prolonged heating with water in a sealed vessel at 140—170°C, methylene chloride yields formaldehyde and hydrochloric acid as shown by the following equation (6). 

Technical-grade chloroform generally contains one or more stabilizers, which vary according to specification requirements. The most common is 50 ppm 2-methyl-2-butene [513-35-9]. Other stabilizers are industrial methylated spirit (0.2%), absolute alcohol (0.6—1%), thymol, /-butylphenol, or -octylphenol (0.0005—0.01%). A representative technical quaUty chloroform contains the following amounts of the indicated substances (maximum) ... 

In the known absence of bromoform, iodoform, chloral, and other halogenated methanes, the formation of phenyhsonitrile with aniline provides a simple and faidy sensitive but nonspecific test for the presence of chloroform, the carbylamine test. Phenyhsonitrile formation is the identification test given in the British Pharmacopoeia. A small quantity of resorcinol and caustic soda solution (10% concentration) added to chloroform results in the appearance of a yellowish red color, fluorescing yeUow-green. When 0.5 mL of a 5% thymol solution is boiled with a drop of chloroform and a small quantity of potassium hydroxide solution, a yellow color with a reddish sheen develops the addition of sulfuric acid causes a change to brilliant violet, which, diluted with water, finally changes to blue (33). 

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... 

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