Thymol
Thymol
Thymol3D.png
Names
Preferred IUPAC name
5-Methyl-2-(propan-2-yl)phenol[1]
Systematic IUPAC name
5-Methyl-2-(propan-2-yl)benzenol
Other names
2-Isopropyl-5-methylphenol, isopropyl-m-cresol, 1-methyl-3-hydroxy-4-isopropylbenzene, 3-methyl-6-isopropylphenol, 5-methyl-2-(1-methylethyl)phenol, 5-methyl-2-isopropyl-1-phenol, 5-methyl-2-isopropylphenol, 6-isopropyl-3-methylphenol, 6-isopropyl-m-cresol, Apiguard, NSC 11215, NSC 47821, NSC 49142, thyme camphor, m-thymol, and p-cymen-3-ol
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.001.768 Edit this at Wikidata
EC Number
  • 201-944-8
KEGG
UNII
  • InChI=1S/C10H14O/c1-7(2)9-5-4-8(3)6-10(9)11/h4-7,11H,1-3H3 checkY
    Key: MGSRCZKZVOBKFT-UHFFFAOYSA-N checkY
  • InChI=1/C10H14O/c1-7(2)9-5-4-8(3)6-10(9)11/h4-7,11H,1-3H3
    Key: MGSRCZKZVOBKFT-UHFFFAOYAS
  • CC(C)c1ccc(C)cc1O
Properties
C10H14O
Molar mass 150.221 g·mol−1
Density 0.96 g/cm3
Melting point 49 to 51 °C (120 to 124 °F; 322 to 324 K)
Boiling point 232 °C (450 °F; 505 K)
0.9 g/L (20 °C)[2]
1.5208[3]
Pharmacology
QP53AX22 (WHO)
Hazards
GHS labelling:
GHS05: Corrosive
GHS07: Exclamation mark
GHS09: Environmental hazard
Warning
H302, H314, H411
P260, P264, P270, P273, P280, P301+P312, P301+P330+P331, P303+P361+P353, P304+P340, P305+P351+P338, P310, P321, P330, P363, P391, P405, P501
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
checkY verify (what is checkY☒N ?)

Thymol (also known as 2-isopropyl-5-methylphenol, IPMP), C10H14O, is a natural monoterpenoid phenol derivative of p-Cymene, isomeric with carvacrol, found in oil of thyme, and extracted from Thymus vulgaris (common thyme), ajwain,[4] and various other plants as a white crystalline substance of a pleasant aromatic odor and strong antiseptic properties. Thymol also provides the distinctive, strong flavor of the culinary herb thyme, also produced from T. vulgaris. Thymol is only slightly soluble in water at neutral pH, but it is extremely soluble in alcohols and other organic solvents. It is also soluble in strongly alkaline aqueous solutions due to deprotonation of the phenol. Its dissociation constant (pKa) is 10.59±0.10.[5] Thymol absorbs maximum UV radiation at 274 nm.[6]

Chemical synthesis

Thymol is produced by the alkylation of m-cresol and propene:[7][8]

CH3C6H4OH + CH2CHCH3 → ((CH3)2CH)CH3C6H3OH

History

Ancient Egyptians used thyme for embalming.[9] 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".[10] In the European Middle Ages, the herb was placed beneath pillows to aid sleep and ward off nightmares.[11] 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.[12]

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.[13]

Thymol was first isolated by German chemist Caspar Neumann in 1719.[14] In 1853, French chemist Alexandre Lallemand named thymol and determined its empirical formula.[15] Thymol was first synthesized by Swedish chemist Oskar Widman in 1882.[16]

Research

An in vitro study found thymol and carvacrol to be highly effective in reducing the minimum inhibitory concentration of several antibiotics against zoonotic pathogens and food spoilage bacteria such as Salmonella typhimurium SGI 1 and Streptococcus pyogenes ermB.[17] In vitro studies have found thymol to be useful as an antifungal against food spoilage and bovine mastitis.[18] Thymol demonstrates in vitro post-antibacterial effect against the test strains E. coli and P. aeruginosa (gram negative), and Staphylococcus aureus and B. cereus (gram positive).[19] This antibacterial activity is caused by inhibiting growth and lactate production, and by decreasing cellular glucose uptake.[20]

Thyme essential oil is useful in preservation of food. The antibacterial properties of thymol, a major part of thyme essential oil, as well as other constituents, are in part associated with their lipophilic character, leading to accumulation in bacterial membranes and subsequent membrane-associated events, such as energy depletion.[21]

The antifungal nature of thymol against some fungi that are pathogenic to plants is due to its ability to alter the hyphal morphology and cause hyphal aggregates, resulting in reduced hyphal diameters and lyses of the hyphal wall.[22]

Uses

Thymol
Thymol

Thymol during the 1910s was the treatment of choice for hookworm infection in the United States.[23][24] People of the Middle East continue to use za'atar, a delicacy made with large amounts of thyme, to reduce and eliminate internal parasites.[25] 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.[26] 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.[27] Thymol is also used as a rapidly degrading, non-persisting pesticide.[18][28] Thymol can also be used as a medical disinfectant and general purpose disinfectant.[29]

List of plants that contain thymol

Toxicology and environmental impacts

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".[43]

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[28]) in the environment and are, thus, low risks because of rapid dissipation and low bound residues,[28] 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.

Compendial status

See also

Notes and references

  1. ^ "Front Matter". Nomenclature of Organic Chemistry : IUPAC Recommendations and Preferred Names 2013 (Blue Book). Cambridge: The Royal Society of Chemistry. 2014. p. 691. doi:10.1039/9781849733069-FP001. ISBN 978-0-85404-182-4.
  2. ^ "Thymol". PubChem. Retrieved 1 April 2016.
  3. ^ Mndzhoyan, A. L. (1940). "Thymol from Thymus kotschyanus". Sbornik Trudov Armyanskogo Filial. Akad. Nauk. 1940: 25–28.
  4. ^ O'Connell, John (27 August 2019). The book of spice : from anise to zedoary. New York: Pegasus. ISBN 978-1681774459. OCLC 959875923.
  5. ^ CAS Registry: Data obtained from SciFinder[full citation needed]
  6. ^ Norwitz, G.; Nataro, N.; Keliher, P. N. (1986). "Study of the Steam Distillation of Phenolic Compounds Using Ultraviolent Spectrometry". Anal. Chem. 58 (639–640): 641. doi:10.1021/ac00294a034.
  7. ^ Stroh, R.; Sydel, R.; Hahn, W. (1963). Foerst, Wilhelm (ed.). Newer Methods of Preparative Organic Chemistry, Volume 2 (1st ed.). New York: Academic Press. p. 344. ISBN 9780323150422.
  8. ^ Fiege, Helmut; Voges, Heinz-Werner; Hamamoto, Toshikazu; Umemura, Sumio; Iwata, Tadao; Miki, Hisaya; Fujita, Yasuhiro; Buysch, Hans-Josef; Garbe (2000). "Phenol Derivatives". Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH. doi:10.1002/14356007.a19_313.
  9. ^ "A Brief History of Thyme - Hungry History". HISTORY.com. Archived from the original on 13 June 2016. Retrieved 9 June 2016.
  10. ^ Grieve, Mrs. Maud. "Thyme. A Modern Herbal". botanical.com (Hypertext version of the 1931 ed.). Archived from the original on 23 February 2011. Retrieved 9 February 2008.
  11. ^ Huxley, A., ed. (1992). New RHS Dictionary of Gardening. Macmillan.
  12. ^ "Thyme (thymus)". englishplants.co.uk. The English Cottage Garden Nursery. Archived from the original on 27 September 2006.
  13. ^ Tilford, Gregory L. (1997). Edible and Medicinal Plants of the West. Missoula, MT: Mountain Press Publishing. ISBN 978-0-87842-359-0.
  14. ^ Neuman, Carolo (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.)
  15. ^ Lallemand, A. (1853). "Sur la composition de l'huile essentielle de thym" [On the composition of the essential oil of thyme]. Comptes Rendus (in French). 37: 498–500.
  16. ^ Widmann, Oskar (1882). "Ueber eine Synthese von Thymol aus Cuminol" [On a synthesis of thymol from cuminol]. Berichte der Deutschen Chemischen Gesellschaft zu Berlin (in German). 15: 166–172. doi:10.1002/cber.18820150139.
  17. ^ Palaniappan, Kavitha; Holley, Richard A. (2010). "Use of natural antimicrobials to increase antibiotic susceptibility of drug resistant bacteria". International Journal of Food Microbiology. 140 (2–3): 164–168. doi:10.1016/j.ijfoodmicro.2010.04.001. PMID 20457472..
  18. ^ a b Nieto, G (2017). "Biological Activities of Three Essential Oils of the Lamiaceae Family". Medicines. 4 (3): 63. doi:10.3390/medicines4030063. PMC 5622398. PMID 28930277.
  19. ^ Zarrini, G; Bahari-Delgosha, Z.; Mollazadeh-Moghaddam, K; Shahverdi, A. R. (2010). "Post-antibacterial effect of thymol". Pharmaceutical Biology. 48 (6): 633–636. doi:10.3109/13880200903229098. PMID 20645735. S2CID 39240936.
  20. ^ Evans, J.; Martin, J. D. (2000). "Effects of thymol on ruminal microorganisms". Curr. Microbiol. 41 (5): 336–340. doi:10.1007/s002840010145. PMID 11014870. S2CID 24460829.
  21. ^ Nychas G.J.E. In: Natural Antimicrobials from Plants. Gould G.W., editor. Blackie Academic Professional; London, UK: 1995. pp. 58–59. New Methods of Food Preservation.
  22. ^ Numpaque, M. A.; Oviedo, L. A.; Gil, J. H.; García, C. M.; Durango, D. L. (2011). "Thymol and carvacrol: biotransformation and antifungal activity against the plant pathogenic fungi Colletotrichum acutatum and Botryodiplodia theobromae". Trop. Plant Pathol. 36: 3–13. doi:10.1590/S1982-56762011000100001.
  23. ^ Ferrell, John Atkinson (1914). The Rural School and Hookworm Disease. US Bureau of Education Bulletin. Vol. No. 20, Whole No. 593. Washington, DC: U.S. Government Printing Office.
  24. ^ Milton, Joseph Rosenau (1913). Preventive Medicine and Hygiene. D. Appleton. p. 119.
  25. ^ Inskeep, Steve; Godoy, Maria (11 June 2013). "Za'atar: A Spice Mix With Biblical Roots And Brain Food Reputation". NPR. Retrieved 24 February 2022.
  26. ^ Filoche, S. K.; Soma, K.; Sissons, C. H. (2005). "Antimicrobial effects of essential oils in combination with chlorhexidine digluconate". Oral Microbiol. Immunol. 20 (4): 221–225. doi:10.1111/j.1399-302X.2005.00216.x. PMID 15943766.
  27. ^ Ward, Mark (8 March 2006). "Almond farmers seek healthy bees". BBC News. BBC.
  28. ^ a b c Hu, 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. PMID 18381775.
  29. ^ "Thymol" (PDF). US Environmental Protection Agency. September 1993.
  30. ^ Novy, P.; Davidova, H.; Serrano Rojero, C. S.; Rondevaldova, J.; Pulkrabek, J.; Kokoska, L. (2015). "Composition and Antimicrobial Activity of Euphrasia rostkoviana Hayne Essential Oil". Evid Based Complement Alternat Med. 2015: 1–5. doi:10.1155/2015/734101. PMC 4427012. PMID 26000025.
  31. ^ Baser, K. H.C.; 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.
  32. ^ Donata Ricci; Francesco Epifano; Daniele Fraternale (February 2017). Olga Tzakou (ed.). "The Essential Oil of Monarda didyma L. (Lamiaceae) Exerts Phytotoxic Activity In Vitro against Various Weed Seeds". Molecules (Basel, Switzerland). Molecules. 22 (2): 222. doi:10.3390/molecules22020222. PMC 6155892. PMID 28157176.
  33. ^ Zamureenko, V. A.; Klyuev, N. A.; Bocharov, B. V.; Kabanov, V. S.; Zakharov, A. M. (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. ISSN 1573-8388. S2CID 24267822.
  34. ^ a b Bouchra, Chebli; Achouri, Mohamed; Idrissi Hassani, L. M.; Hmamouchi, Mohamed (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. PMID 14522450.
  35. ^ Liolios, C. C.; Gortzi, O.; Lalas, S.; Tsaknis, J.; Chinou, I. (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.
  36. ^ Ozkan, Gulcan; 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. PMID 20355032.
  37. ^ Lagouri, Vasiliki; Blekas, George; Tsimidou, Maria; Kokkini, Stella; Boskou, Dimitrios (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. S2CID 81307357.
  38. ^ Kanias, G. D.; Souleles, C.; Loukis, A.; Philotheou-Panou, E. (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. S2CID 94582250.
  39. ^ Figiel, Adam; Szumny, Antoni; Gutiérrez Ortíz, Antonio; Carbonell Barrachina, Ángel A. (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.
  40. ^ a b Goodner, K.L.; Mahattanatawee, K.; Plotto, A.; Sotomayor, J.; Jordán, M. (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.
  41. ^ Lee, Seung-Joo; Umano, Katumi; Shibamoto, Takayuki; Lee, Kwang-Geun (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.
  42. ^ Moldão Martins, M.; Palavra, A.; Beirão da Costa, M. L.; Bernardo Gil, M. G. (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.
  43. ^ 74 FR 12613
  44. ^ The British Pharmacopoeia Secretariat (2009). "Index, BP 2009" (PDF). Archived from the original (PDF) on 11 April 2009. Retrieved 5 July 2009.
  45. ^ "Japanese Pharmacopoeia" (PDF). Archived from the original (PDF) on 22 July 2011. Retrieved 21 April 2010.

External links

Media related to Thymol at Wikimedia Commons

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