Thymol provides the distinctive flavor of the culinary herb thyme, also produced from T. vulgaris.[4] Thymol is only slightly soluble in water at neutral pH, but due to deprotonation of the phenol, it is highly soluble in alcohols, other organic solvents, and strongly alkaline aqueous solutions.
A predicted method of biosynthesis of thymol in thyme and oregano begins with the cyclization of geranyl diphosphate by TvTPS2 to γ-terpinene. Oxidation by a cytochrome P450 in the CYP71D subfamily creates a dienol intermediate, which is then converted into a ketone by short-chain dehydrogenase. Lastly, keto-enol tautomerization gives thymol. Its dissociation constant (pKa) is 10.59±0.10.[8] Thymol absorbs maximum UV radiation at 274 nm.[9]
Thymol was first isolated by German chemist Caspar Neumann in 1719.[11] In 1853, French chemist Alexandre Lallemand[12] (1816-1886) named thymol and determined its empirical formula.[13] Possible antiseptic properties of thymol were discovered in 1875,[14] and it was first synthesized by Swedish chemist Oskar Widman (1852-1930) in 1882.[15]
Extraction
The conventional method of extracting is hydro-distillation (HD), but can also be extracted with solvent-free microwave extraction (SFME). In 30 minutes, SFME yields similar amounts of thymol with more oxygenated compounds than 4.5 hours of hydro-distillation at atmospheric pressures without the need for solvent.[16]
Predicted biosynthesis of thymol in thyme and oregano. Reconstruction of figure 4 in Krause et. al. (2021).[17]
Uses
During the 1910s, thymol was used for hookworm infection in the United States.[18][19] People of the Middle East continue to use za'atar, a delicacy made with large amounts of thyme, to reduce and eliminate internal parasites.[20] It is also used as a preservative in halothane, an anaesthetic, and as an antiseptic in mouthwash. When used to reduce plaque and gingivitis, thymol has been found to be more effective when used in combination with chlorhexidine than when used purely by itself.[21]
Thymol is a fragrance ingredient in some cosmetics.[4] Thymol has been used to successfully control varroa mites and prevent fermentation and the growth of mold in bee colonies.[22] Thymol is also used as a rapidly degrading, non-persisting pesticide,[4][23] such as insecticides and fungicides which are leveraged in plant care products. Thymol can also be used as a medical disinfectant and general purpose disinfectant.[24] Thymol is also used in the production of menthol through the hydrogenation of the aromatic ring.[25]
In 2009, the U.S. Environmental Protection Agency (EPA) reviewed the research literature on the toxicology and environmental impact of thymol and concluded that "thymol has minimal potential toxicity and poses minimal risk".[40]
Environmental breakdown and use as a pesticide
Studies have shown that hydrocarbon monoterpenes and thymol in particular degrade rapidly (DT50 16 days in water, 5 days in soil[23]) in the environment and are, thus, low risks because of rapid dissipation and low bound residues,[23] supporting the use of thymol as a pesticide agent that offers a safe alternative to other more persistent chemical pesticides that can be dispersed in runoff and produce subsequent contamination. Though, there has been recent research into sustained released systems for botanically derived pesticides, such as using natural polysaccharides which would be biodegradable and biocompatible.[41]
^Norwitz G, Nataro N, Keliher PN (1986). "Study of the Steam Distillation of Phenolic Compounds Using Ultraviolent Spectrometry". Anal. Chem. 58 (639–640): 641. doi:10.1021/ac00294a034.
^Tilford GL (1997). Edible and Medicinal Plants of the West. Missoula, MT: Mountain Press Publishing. ISBN978-0-87842-359-0.
^Neuman C (1724). "De Camphora". Philosophical Transactions of the Royal Society of London. 33 (389): 321–332. doi:10.1098/rstl.1724.0061. On page 324, Neumann mentions that in 1719 he distilled some essential oils from various herbs. On page 326, he mentions that during these experiments, he obtained a crystalline substance from thyme oil, which he called "Camphora Thymi" (camphor of thyme). (Neumann gave the name "camphor" not only to the specific substance that today is called camphor but to any crystalline substance that precipitated from a volatile, fragrant oil from some plant.)
^Marie-Étienne-Alexandre Lallemand (December 25, 1816 - March 16, 1886)
^Ferrell JA (1914). The Rural School and Hookworm Disease. US Bureau of Education Bulletin. Vol. 20, Whole No. 593. Washington, DC: U.S. Government Printing Office.
^ abcHu D, Coats J (2008). "Evaluation of the environmental fate of thymol and phenethyl propionate in the laboratory". Pest Manag. Sci. 64 (7): 775–779. doi:10.1002/ps.1555. PMID18381775.
^"Thymol"(PDF). US Environmental Protection Agency. September 1993.
^Baser KH, Tümen G (1994). "Composition of the Essential Oil of Lagoecia cuminoides L. from Turkey". Journal of Essential Oil Research. 6 (5): 545–546. doi:10.1080/10412905.1994.9698448.
^Zamureenko VA, Klyuev NA, Bocharov BV, et al. (1989). "An investigation of the component composition of the essential oil of Monarda fistulosa". Chemistry of Natural Compounds. 25 (5): 549–551. doi:10.1007/BF00598073. ISSN1573-8388. S2CID24267822.
^ abBouchra C, Achouri M, Idrissi Hassani LM, et al. (2003). "Chemical composition and antifungal activity of essential oils of seven Moroccan Labiatae against Botrytis cinerea Pers: Fr". Journal of Ethnopharmacology. 89 (1): 165–169. doi:10.1016/S0378-8741(03)00275-7. PMID14522450.
^Liolios CC, Gortzi O, Lalas S, et al. (2009). "Liposomal incorporation of carvacrol and thymol isolated from the essential oil of Origanum dictamnus L. and in vitro antimicrobial activity". Food Chemistry. 112 (1): 77–83. doi:10.1016/j.foodchem.2008.05.060.
^Ozkan G, Baydar H, Erbas S (2009). "The influence of harvest time on essential oil composition, phenolic constituents and antioxidant properties of Turkish oregano (Origanum onites L.)". Journal of the Science of Food and Agriculture. 90 (2): 205–209. doi:10.1002/jsfa.3788. PMID20355032.
^Lagouri V, Blekas G, Tsimidou M, et al. (1993). "Composition and antioxidant activity of essential oils from Oregano plants grown wild in Greece". Zeitschrift für Lebensmittel-Untersuchung und -Forschung A. 197 (1): 1431–4630. doi:10.1007/BF01202694. S2CID81307357.
^Kanias GD, Souleles C, Loukis A, et al. (1998). "Trace elements and essential oil composition in chemotypes of the aromatic plant Origanum vulgare". Journal of Radioanalytical and Nuclear Chemistry. 227 (1–2): 23–31. doi:10.1007/BF02386426. S2CID94582250.
^Figiel A, Szumny A, Gutiérrez Ortíz A, et al. (2010). "Composition of oregano essential oil (Origanum vulgare) as affected by drying method". Journal of Food Engineering. 98 (2): 240–247. doi:10.1016/j.jfoodeng.2010.01.002.
^ abGoodner K, Mahattanatawee K, Plotto A, et al. (2006). "Aromatic profiles of Thymus hyemalis and Spanish T. vulgaris essential oils by GC–MS/GC–O". Industrial Crops and Products. 24 (3): 264–268. doi:10.1016/j.indcrop.2006.06.006.
^Lee SJ, Umano K, Shibamoto T, et al. (2005). "Identification of volatile components in basil (Ocimum basilicum L.) and thyme leaves (Thymus vulgaris L.) and their antioxidant properties". Food Chemistry. 91 (1): 131–137. doi:10.1016/j.foodchem.2004.05.056.
^Moldão Martins M, Palavra A, Beirão da Costa ML, et al. (2000). "Supercritical CO2 extraction of Thymus zygis L. subsp. sylvestris aroma". The Journal of Supercritical Fluids. 18 (1): 25–34. doi:10.1016/S0896-8446(00)00047-4.
