Thymol

Thymol is produced by the alkylation of m-cresol and propene:{{cite book|last1=Stroh|first1=R.|last2=Sydel|first2=R.|last3=Hahn|first3=W.|editor1-last=Foerst|editor1-first=Wilhelm|title=Newer Methods of Preparative Organic Chemistry, Volume 2|date=1963|publisher=Academic Press|location=New York|isbn=9780323150422|page=344|edition= 1st|url=https://books.google.com/books?id=LG2J6i1sUAMC&pg=PA344}}{{Ullmann |doi=10.1002/14356007.a19_313|title=Phenol Derivatives |year=2000 |last1=Fiege |first1=Helmut |last2=Voges |first2=Heinz-Werner |last3=Hamamoto |first3=Toshikazu |last4=Umemura |first4=Sumio |last5=Iwata |first5=Tadao |last6=Miki |first6=Hisaya |last7=Fujita |first7=Yasuhiro |last8=Buysch |first8=Hans-Josef |last9=Garbe |first9=Dorothea |last10=Paulus |first10=Wilfried |isbn=3527306730 }}

: {{chem2|CH3C6H4OH + CH2CHCH3 -> ((CH3)2CH)CH3C6H3OH}}

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.

File:Thymol biosynthesis.svg

Ancient Egyptians used thyme for embalming.{{Cite web|url=http://www.history.com/news/hungry-history/a-brief-history-of-thyme|title=A Brief History of Thyme - Hungry History|website=HISTORY.com|access-date=2016-06-09|url-status=live|archive-url=https://web.archive.org/web/20160613081647/http://www.history.com/news/hungry-history/a-brief-history-of-thyme|archive-date=2016-06-13}} The ancient Greeks used it in their baths and burned it as incense in their temples, believing it was a source of courage. The spread of thyme throughout Europe was thought to be due to the Romans, as they used it to purify their rooms and to "give an aromatic flavour to cheese and liqueurs".{{cite web|url=http://botanical.com/botanical/mgmh/t/thygar16.html|title=Thyme. A Modern Herbal|edition=Hypertext version of the 1931|work=botanical.com|last=Grieve|first=Mrs. Maud|access-date=9 February 2008|url-status=live|archive-url=http://archive.wikiwix.com/cache/20110223130247/http://botanical.com/botanical/mgmh/t/thygar16.html|archive-date=23 February 2011}} In the European Middle Ages, the herb was placed beneath pillows to aid sleep and ward off nightmares.Huxley, A., ed. (1992). New RHS Dictionary of Gardening. Macmillan. In this period, women also often gave knights and warriors gifts that included thyme leaves, because it was believed to bring courage to the bearer. Thyme was also used as incense and placed on coffins during funerals, because it was supposed to ensure passage into the next life.{{cite web|url=http://www.englishplants.co.uk/thyme.html|title=Thyme (thymus)|work=englishplants.co.uk|publisher=The English Cottage Garden Nursery|url-status=live|archive-url=https://web.archive.org/web/20060927050614/http://www.englishplants.co.uk/thyme.html|archive-date=2006-09-27}}

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.{{cite book|last=Tilford |first=Gregory L. |date=1997 |title=Edible and Medicinal Plants of the West |location=Missoula, MT |publisher=Mountain Press Publishing |isbn=978-0-87842-359-0}}

Thymol was first isolated by German chemist Caspar Neumann in 1719.{{cite journal|first=Carolo |last=Neuman |date=1724 |title=De Camphora |journal=Philosophical Transactions of the Royal Society of London |volume=33 |issue=389 |pages=321–332 |url=http://rstl.royalsocietypublishing.org/content/33/381-391/321.full.pdf+html |doi=10.1098/rstl.1724.0061|doi-access=free }} 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.) In 1853, French chemist Alexandre LallemandMarie-Étienne-Alexandre Lallemand (December 25, 1816 - March 16, 1886) (1816-1886) named thymol and determined its empirical formula.{{cite journal|first=A. |last=Lallemand |date=1853 |url=http://gallica.bnf.fr/ark:/12148/bpt6k29948/f502.image.langEN |title=Sur la composition de l'huile essentielle de thym |trans-title=On the composition of the essential oil of thyme |language=fr |journal=Comptes Rendus |volume=37 |pages=498–500}} Antiseptic properties of thymol were discovered in 1875,{{Cite book |last=Oettingen |first=Wolfgang Felix Von |url=https://books.google.com/books?id=reaUWvD-bhYC&pg=PA78 |title=Phenol and Its Derivatives: The Relation Between Their Chemical Constitution and Their Effect on the Organism |date=1949 |publisher=U.S. Government Printing Office |isbn=978-0-598-95964-5 |language=en}} and it was first synthesized by Swedish chemist Oskar WidmanKarl Oskar Widman (aka Carl Oskar Widman) (January 2, 1852 - August 26, 1930) (1852-1930) in 1882.{{cite journal|first=Oskar |last=Widmann |date=1882 |url=http://gallica.bnf.fr/ark:/12148/bpt6k90694n/f169.image.langEN |title=Ueber eine Synthese von Thymol aus Cuminol |trans-title=On a synthesis of thymol from cuminol |language=de |journal=Berichte der Deutschen Chemischen Gesellschaft zu Berlin |volume=15 |pages=166–172 |doi=10.1002/cber.18820150139}}

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.{{Cite journal |last1=Lucchesi |first1=Marie E |last2=Chemat |first2=Farid |last3=Smadja |first3=Jacqueline |date=2004-07-23 |title=Solvent-free microwave extraction of essential oil from aromatic herbs: comparison with conventional hydro-distillation |url=https://www.sciencedirect.com/science/article/pii/S0021967304008672 |journal=Journal of Chromatography A |volume=1043 |issue=2 |pages=323–327 |doi=10.1016/j.chroma.2004.05.083 |pmid=15330107 |issn=0021-9673}}

File:Thymolum by Danny S. - 001.JPG

Thymol during the 1910s was the treatment of choice for hookworm infection in the United States.{{cite book|last=Ferrell|first=John Atkinson|title=The Rural School and Hookworm Disease|url=https://books.google.com/books?id=omYAAAAAYAAJ|series=US Bureau of Education Bulletin|volume=20, Whole No. 593|year=1914|publisher=U.S. Government Printing Office|location=Washington, DC}}{{cite book|surname=Milton|given=Joseph Rosenau|title=Preventive Medicine and Hygiene|url=https://books.google.com/books?id=mVfQAAAAMAAJ&pg=PA119|year=1913|publisher=D. Appleton|page=119}} People of the Middle East continue to use za'atar, a delicacy made with large amounts of thyme, to reduce and eliminate internal parasites.{{Cite news|last1=Inskeep|first1=Steve|last2=Godoy|first2=Maria|date=2013-06-11|title=Za'atar: A Spice Mix With Biblical Roots And Brain Food Reputation|language=en|work=NPR|url=https://www.npr.org/sections/thesalt/2013/06/11/190672515/zaatar-a-spice-mix-with-biblical-roots-and-brain-food-reputation|access-date=2022-02-24}} 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.{{cite journal | last1 = Filoche | first1 = S. K. | last2 = Soma | first2 = K. | last3 = Sissons | first3 = C. H. | year = 2005 | title = Antimicrobial effects of essential oils in combination with chlorhexidine digluconate | journal = Oral Microbiol. Immunol. | volume = 20 | issue = 4| pages = 221–225 | doi = 10.1111/j.1399-302X.2005.00216.x | pmid = 15943766 }} Thymol is also the active antiseptic ingredient in some toothpastes, such as Johnson & Johnson's Euthymol. Thymol has been used to successfully control varroa mites and prevent fermentation and the growth of mold in bee colonies.{{cite news|last=Ward |first=Mark |date=2006-03-08 |url=http://news.bbc.co.uk/2/hi/science/nature/4780034.stm |title=Almond farmers seek healthy bees |website=BBC News |publisher=BBC}} Thymol is also used as a rapidly degrading, non-persisting pesticides such as insecticides and fungicides which are leveraged in plant care products, where its environmentally friendly, rapid degradation ensures it doesn’t leave persistent residues while effectively controlling pests and fungal issues.{{Cite web |title=T-Guard: The Ultimate Insect Fungus Control Product |url=https://growscripts.com/products/t-guard-the-ultimate-insect-fungus-control-product |access-date=2024-10-07 |website=GrowScripts Plant Food Fertilizer |language=en}} Thymol can also be used as a medical disinfectant and general purpose disinfectant.{{cite web|url=http://archive.epa.gov/pesticides/reregistration/web/pdf/3143fact.pdf|title=Thymol|publisher=US Environmental Protection Agency|date=September 1993}} Thymol is also used in the production of menthol through the hydrogenation of the aromatic ring.{{Cite web |date=2023-10-06 |title=Menthol {{!}} Definition, Structure, & Uses {{!}} Britannica |url=https://www.britannica.com/science/menthol |access-date=2023-10-30 |website=www.britannica.com |language=en}}

• Illicium verum
• Euphrasia rostkoviana{{cite journal | pmid = 26000025 | doi=10.1155/2015/734101 | volume=2015 | title=Composition and Antimicrobial Activity of Euphrasia rostkoviana Hayne Essential Oil | pmc=4427012 | journal=Evid Based Complement Alternat Med | pages=1–5 | last1 = Novy | first1 = P. | last2 = Davidova | first2 = H. | last3 = Serrano Rojero | first3 = C. S. | last4 = Rondevaldova | first4 = J. | last5 = Pulkrabek | first5 = J. | last6 = Kokoska | first6 = L.| year=2015 | doi-access=free }}
• Lagoecia cuminoides{{cite journal |doi=10.1080/10412905.1994.9698448 |title=Composition of the Essential Oil of Lagoecia cuminoides L. from Turkey |year=1994 |last1=Baser |first1=K. H.C. |last2=Tümen |first2=G. |journal=Journal of Essential Oil Research |volume=6 |issue=5 |pages=545–546 }}
• Monarda didyma{{cite journal|author1=Donata Ricci|author2=Francesco Epifano|author3=Daniele Fraternale|editor=Olga Tzakou|title=The Essential Oil of Monarda didyma L. (Lamiaceae) Exerts Phytotoxic Activity In Vitro against Various Weed Seeds|journal=Molecules (Basel, Switzerland)|publisher=Molecules|date=February 2017|volume=22|issue=2|pages=222|pmc=6155892|pmid=28157176|doi=10.3390/molecules22020222|doi-access=free}}
• Monarda fistulosa{{cite journal|first1=V. A. |last1=Zamureenko |first2=N. A. |last2=Klyuev |first3=B. V. |last3=Bocharov |first4=V. S. |last4=Kabanov |first5=A. M. |last5=Zakharov |title=An investigation of the component composition of the essential oil of Monarda fistulosa |journal=Chemistry of Natural Compounds |volume=25 |issue=5 |date=1989 |pages=549–551 |doi=10.1007/BF00598073 |s2cid=24267822 |issn=1573-8388}}
• Mosla chinensis
• Ocimum gratissimum L.{{Cite journal |last1=Escobar |first1=Angélica |last2=Pérez |first2=Miriam |last3=Romanelli |first3=Gustavo |last4=Blustein |first4=Guillermo |date=2020-12-01 |title=Thymol bioactivity: A review focusing on practical applications |journal=Arabian Journal of Chemistry |volume=13 |issue=12 |pages=9243–9269 |doi=10.1016/j.arabjc.2020.11.009 |issn=1878-5352|doi-access=free |hdl=11336/139451 |hdl-access=free }}
• Origanum compactum
• Origanum dictamnus{{cite journal

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• Origanum onites{{cite journal

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• Origanum vulgare{{cite journal

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| last2 = Szumny

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• Satureja hortensis
• Satureja thymbra
• Thymus glandulosus{{cite journal

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| first1 = Chebli

| title = Chemical composition and antifungal activity of essential oils of seven Moroccan Labiatae against Botrytis cinerea Pers: Fr

| journal = Journal of Ethnopharmacology

| volume = 89

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| pmid = 14522450

| last2 = Achouri

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• Thymus hyemalis
• Thymus serpyllum
• Thymus praecox
• Thymus vulgaris{{cite journal

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| title = Aromatic profiles of Thymus hyemalis and Spanish T. vulgaris essential oils by GC–MS/GC–O

| journal = Industrial Crops and Products

| volume = 24

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| year = 2006

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| first4 = J.

| last5 = Jordán

| first5 = M.}}{{cite journal

| last1 = Lee

| first1 = Seung-Joo

| title = Identification of volatile components in basil (Ocimum basilicum L.) and thyme leaves (Thymus vulgaris L.) and their antioxidant properties

| journal = Food Chemistry

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| last2 = Umano

| first2 = Katumi

| last3 = Shibamoto

| first3 = Takayuki

| last4 = Lee

| first4 = Kwang-Geun}}

• Thymus zygis{{cite journal

| last1 = Moldão Martins

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| title = Supercritical CO₂ extraction of Thymus zygis L. subsp. sylvestris aroma

| journal = The Journal of Supercritical Fluids

| volume = 18

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• Trachyspermum ammi

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".{{Federal Register|74|12613}}

Studies have shown that hydrocarbon monoterpenes and thymol in particular degrade rapidly (DT₅₀ 16 days in water, 5 days in soil{{cite journal|first1=D. |last1=Hu |first2=J. |last2=Coats |title=Evaluation of the environmental fate of thymol and phenethyl propionate in the laboratory |journal=Pest Manag. Sci. |volume=64 |issue=7 |pages=775–779 |date=2008 |doi=10.1002/ps.1555|pmid=18381775 }}) in the environment and are, thus, low risks because of rapid dissipation and low bound residues, 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.{{Cite journal |last1=Campos |first1=Estefânia V. R. |last2=Proença |first2=Patrícia L. F. |last3=Oliveira |first3=Jhones L. |last4=Bakshi |first4=Mansi |last5=Abhilash |first5=P. C. |last6=Fraceto |first6=Leonardo F. |date=2019-10-01 |title=Use of botanical insecticides for sustainable agriculture: Future perspectives |url=https://www.sciencedirect.com/science/article/pii/S1470160X18302917 |journal=Ecological Indicators |volume=105 |pages=483–495 |doi=10.1016/j.ecolind.2018.04.038 |issn=1470-160X|hdl=11449/179822 |s2cid=89798604 |hdl-access=free }}

• British Pharmacopoeia{{cite web

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|archive-url = https://web.archive.org/web/20090411071437/http://www.pharmacopoeia.co.uk/pdf/2009_index.pdf

|archive-date = 11 April 2009}}

• Japanese Pharmacopoeia{{cite web| title =Japanese Pharmacopoeia| url =http://jpdb.nihs.go.jp/jp15e/JP15.pdf| access-date =2010-04-21| url-status =dead| archive-url =https://web.archive.org/web/20110722105441/http://jpdb.nihs.go.jp/jp15e/JP15.pdf| archive-date =22 July 2011}}

• Thymoquinone
• Nigella sativa
• Bromothymol

{{reflist|30em}}

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{{GABAAR PAMs}}

{{Transient receptor potential channel modulators}}

{{Terpenoids}}

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Category:Monoterpenes

Category:Alkylphenols

Category:GABAA receptor positive allosteric modulators

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