Thymol

Thymol (also known as 2-isopropyl-5-methylphenol, IPMP), Template:Chem2, is a monoterpenoid, phenol derivative of p-cymene, isomeric with carvacrol.<ref name="pubchem">Template:Cite web</ref> It occurs naturally in oil of thyme and is extracted from Thymus vulgaris (common thyme), ajwain,<ref>Template:Cite book</ref> and various other plants, as a white crystalline substance with a pleasant aromatic odor.<ref name=pubchem/>

Thymol provides the distinctive flavor of the culinary herb thyme, also produced from T. vulgaris.<ref name=pubchem/> 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.

Chemical synthesis

Thymol is produced by the alkylation of m-cresol and propene.<ref>Template:Cite book</ref><ref>Template:Ullmann</ref> Template:Chem2

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 (pK_a) is Template:Val.<ref>CAS Registry: Data obtained from SciFinderTemplate:Full citation needed</ref> Thymol absorbs maximum UV radiation at 274 nm.<ref>Template:Cite journal</ref>

History

The bee balms Monarda fistulosa and Monarda didyma, North American wildflowers, are natural sources of thymol. The Blackfoot Native Americans recognized these plants' strong antiseptic action and used poultices of the plants for skin infections and minor wounds. A tisane made from them was also used to treat mouth and throat infections caused by dental caries and gingivitis.<ref>Template:Cite book</ref>

Thymol was first isolated by German chemist Caspar Neumann in 1719.<ref>Template:Cite journal 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.)</ref> In 1853, French chemist Alexandre Lallemand<ref>Marie-Étienne-Alexandre Lallemand (December 25, 1816 - March 16, 1886)</ref> (1816-1886) named thymol and determined its empirical formula.<ref>Template:Cite journal</ref> Possible antiseptic properties of thymol were discovered in 1875,<ref>Template:Cite book</ref> and it was first synthesized by Swedish chemist Oskar Widman (1852-1930) in 1882.<ref>Template:Cite journal</ref>

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.<ref>Template:Cite journal</ref>

Predicted biosynthesis of thymol in thyme and oregano. Reconstruction of figure 4 in Krause et. al. (2021).<ref name="r505">Template:Cite journal</ref>

Uses

During the 1910s, thymol was used for hookworm infection in the United States.<ref>Template:Cite book</ref><ref name="Rosenau1913">Template:Cite book</ref> People of the Middle East continue to use za'atar, a delicacy made with large amounts of thyme, to reduce and eliminate internal parasites.<ref>Template:Cite news</ref> 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.<ref>Template:Cite journal</ref>

Thymol is a fragrance ingredient in some cosmetics.<ref name=pubchem/> Thymol has been used to successfully control varroa mites and prevent fermentation and the growth of mold in bee colonies.<ref name=bees>Template:Cite news</ref> Thymol is also used as a rapidly degrading, non-persisting pesticide,<ref name=pubchem/><ref name="J. Coats 2008" /> 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.<ref>Template:Cite web</ref> Thymol is also used in the production of menthol through the hydrogenation of the aromatic ring.<ref>Template:Cite web</ref>

List of plants that contain thymol

• Illicium verum
• Euphrasia rostkoviana<ref>Template:Cite journal</ref>
• Lagoecia cuminoides<ref>Template:Cite journal</ref>
• Monarda didyma<ref>Template:Cite journal</ref>
• Monarda fistulosa<ref>Template:Cite journal</ref>
• Mosla chinensis
• Ocimum gratissimum L.<ref>Template:Cite journal</ref>
• Origanum compactum<ref name=ccaa />
• Origanum dictamnus<ref name=lict>Template:Cite journal</ref>
• Origanum onites<ref name=ihte>Template:Cite journal</ref><ref name=caae>Template:Cite journal</ref>
• Origanum syriacum
• Origanum vulgare<ref name=teeo>Template:Cite journal</ref><ref name=coeo>Template:Cite journal</ref>
• Satureja hortensis
• Satureja thymbra
• Thymus glandulosus<ref name=ccaa>Template:Cite journal</ref>
• Thymus hyemalis<ref name=apth />
• Thymus serpyllum
• Thymus praecox
• Thymus vulgaris<ref name=apth>Template:Cite journal</ref><ref name=ivcb>Template:Cite journal</ref>
• Thymus zygis<ref name=scet>Template:Cite journal</ref>
• Trachyspermum ammi

Toxicology and environmental impacts

Thymol powder

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".<ref>Template:Federal Register</ref>

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<ref name="J. Coats 2008">Template:Cite journal</ref>) in the environment and are, thus, low risks because of rapid dissipation and low bound residues,<ref name="J. Coats 2008"/> 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.<ref>Template:Cite journal</ref>

Compendial status

• British Pharmacopoeia<ref name=ib29>Template:Cite web</ref>
• Japanese Pharmacopoeia<ref name=jp15>Template:Cite web</ref>

See also

• Thymoquinone
• Nigella sativa
• Bromothymol