Eucalyptol

Eucalyptol (also called cineole) is a monoterpenoid colorless liquid, and a bicyclic ether.^[1] It has a fresh camphor-like odor and a spicy, cooling taste.^[1] It is insoluble in water, but miscible with organic solvents. Eucalyptol makes up about 70–90% of eucalyptus oil.^[2][3] Eucalyptol forms crystalline adducts with hydrohalic acids, o-cresol, resorcinol, and phosphoric acid. Formation of these adducts is useful for purification.^[4]

Eucalyptol

Names
IUPAC name 1,3,3-Trimethyl-2-oxabicyclo[2.2.2]octane
Other names 1,8-Cineole 1,8-Epoxy-p-menthane cajeputol 1,8-epoxy-p-menthane, 1,8-oxido-p-menthane eucalyptole 1,3,3-trimethyl-2-oxabicyclo[2.2.2]octane cineol cineole.
Identifiers
CAS Number	470-82-6 Y
3D model (JSmol)	Interactive image
Beilstein Reference	105109 5239941
ChEBI	CHEBI:27961
ChEMBL	ChEMBL485259 Y
ChemSpider	2656 Y
DrugBank	DB03852 Y
ECHA InfoCard	100.006.757
EC Number	207-431-5
Gmelin Reference	131076
IUPHAR/BPS	2464
KEGG	D04115 Y
PubChem CID	2758
UNII	RV6J6604TK Y
CompTox Dashboard (EPA)	DTXSID4020616
InChI InChI=1S/C10H18O/c1-9(2)8-4-6-10(3,11-9)7-5-8/h8H,4-7H2,1-3H3 Y Key: WEEGYLXZBRQIMU-UHFFFAOYSA-N Y InChI=1/C10H18O/c1-9(2)8-4-6-10(3,11-9)7-5-8/h8H,4-7H2,1-3H3 Key: WEEGYLXZBRQIMU-UHFFFAOYAY
SMILES O2C1(CCC(CC1)C2(C)C)C
Properties
Chemical formula	C10H18O
Molar mass	154.249 g/mol
Density	0.9225 g/cm3
Melting point	2.9 °C (37.2 °F; 276.0 K)
Boiling point	176–177 °C (349–351 °F; 449–450 K)
Magnetic susceptibility (χ)	−116.3×10−6 cm3/mol
Pharmacology
ATC code	R05CA13 (WHO)
Hazards
GHS labelling:
Pictograms
Signal word	Danger
Hazard statements	H226, H304, H315, H317, H319, H411
Precautionary statements	P210, P233, P240, P241, P242, P243, P261, P264, P272, P273, P280, P301+P310, P302+P352, P303+P361+P353, P305+P351+P338, P321, P331, P332+P313, P333+P313, P337+P313, P362, P363, P370+P378, P391, P403+P235, P405, P501
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

In 1870, F. S. Cloez identified and ascribed the name "eucalyptol" to the dominant portion of Eucalyptus globulus oil.^[2]

Uses

Because of its pleasant, spicy aroma and taste, eucalyptol is used in flavorings, fragrances, and cosmetics.^[1] Cineole-based eucalyptus oil is used as a flavoring at low levels (0.002%) in various products, including baked goods, confectionery, meat products, and beverages.^[1][5] In a 1994 report released by five top cigarette companies, eucalyptol was listed as one of the 599 additives to cigarettes.^[6] It is claimed to be added to improve the flavor.^[1]

Eucalyptol is an ingredient in commercial mouthwashes,^[1] and has been used in traditional medicine as a cough suppressant.^[7]

Other

Eucalyptol exhibits insecticidal and insect repellent properties.^[8][9]

In contrast, eucalyptol is one of many compounds that are attractive to males of various species of orchid bees, which gather the chemical to synthesize pheromones; it is commonly used as bait to attract and collect these bees for study.^[10] One such study with Euglossa imperialis, a nonsocial orchid bee species, has shown that the presence of cineole (also eucalyptol) elevates territorial behavior and specifically attracts the male bees. It was even observed that these males would periodically leave their territories to forage for chemicals such as cineole, thought to be important for attracting and mating with females, to synthesize pheromones.^[11]

Toxicology

Eucalyptol has a toxicity (LD₅₀) of 2.48 grams per kg (rat).^[1] Ingestion in significant quantities is likely to cause headache and gastric distress, such as nausea and vomiting.^[1] Because of its low viscosity, it may directly enter the lungs if swallowed, or if subsequently vomited. Once in the lungs, it is difficult to remove and can cause delirium, convulsions, severe injury or death.^[1]

Biosynthesis

Eucalyptol is generated from geranyl pyrophosphate (GPP) which isomerizes to (S)-linalyl diphosphate (LPP). Ionization of the pyrophosphate, catalyzed by cineole synthase, produces eucalyptol. The process involves the intermediacy of alpha-terpinyl cation.^[12][13][14] 

Plants containing eucalyptol

• Aframomum corrorima^[15]
• Artemisia tridentata^[16]
• Cannabis^[17]
• Cinnamomum camphora, camphor laurel (50%)^[18]
• Eucalyptus globulus^[19]
• Eucalyptus largiflorens^[20]
• Eucalyptus salmonophloia^[21]
• Eucalyptus staigeriana^[22]
• Eucalyptus wandoo^[23]
• Hedychium coronarium, butterfly lily^[24][25]
• Helichrysum gymnocephalum^[26]
• Kaempferia galanga, galangal, (5.7%)^[27]
• S. officinalis subsp. lavandulifolia (syn. S. lavandulifolia), Spanish sage (13%)^[28]
• Turnera diffusa, damiana^[29]
• Umbellularia californica, pepperwood (22.0%)^[30]
• Zingiber officinale, ginger^[31]

See also

• Camphor
• Citral
• Eucalyptus oil
• Lavandula
• Menthol
• Mouthwash

References

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3. "GCMS – Gas Chromatography Mass Spectrometry Analysis" (PDF). New Direction Aromatics. Archived (PDF) from the original on 28 October 2020. Retrieved 7 December 2022.
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7. "Tea tree oil". Drugs.com. 17 June 2019. Retrieved 31 July 2019.
8. Klocke, J. A.; Darlington, M. V.; Balandrin, M. F. (December 1987). "8-Cineole (Eucalyptol), a Mosquito Feeding and Ovipositional Repellent from Volatile Oil of Hemizonia fitchii (Asteraceae)". Journal of Chemical Ecology. 13 (12): 2131–41. doi:10.1007/BF01012562. PMID 24301652. S2CID 23271137.
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15. Sebsebe Demissew (1993). "A description of some essential oil bearing plants in Ethiopia and their indigenous uses". Journal of Essential Oil Research. 5 (5). Taylor & Francis: 465–479. doi:10.1080/10412905.1993.9698266. The chemical composition of … Aframomum corrorima (l, 8-cineole 41.9%) … is also presented.
16. Crowell, M.M.; et al. (2018). "Dietary partitioning of toxic leaves and fibrous stems differs between sympatric specialist and generalist mammalian herbivores". Journal of Mammalogy. 99 (3): 565–577. doi:10.1093/jmammal/gyy018.
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24. Ali, S.; Sotheeswaran, S.; Tuiwawa, M.; Smith, R. (2002). "Comparison of the Composition of the Essential Oils of Alpinia and Hedychium Species—Essential Oils of Fijian Plants, Part 1". Journal of Essential Oil Research. 14 (6): 409–411. doi:10.1080/10412905.2002.9699904. S2CID 95463805.
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27. Wong, K. C.; Ong, K. S.; Lim, C. L. (2006). "Composition of the Essential Oil of Rhizomes of Kaempferia galanga L.". Flavour and Fragrance Journal. 7 (5): 263–266. doi:10.1002/ffj.2730070506.
28. Perry, N. S.; Houghton, P. J.; Theobald, A.; Jenner, P.; Perry, E. K. (2000). "In-vitro inhibition of human erythrocyte acetylcholinesterase by Salvia lavandulaefolia essential oil and constituent terpenes". J Pharm Pharmacol. 52 (7): 895–902. doi:10.1211/0022357001774598. PMID 10933142. S2CID 34457692.
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30. Kelsey, R. G.; McCuistion, O.; Karchesy, J. (2007). "Bark and Leaf Essential Oil of Umbellularia californica, California Bay Laurel, from Oregon". Natural Product Communications. 2 (7): 779–780. doi:10.1177/1934578X0700200715.
31. Gupta S, Pandotra P, Ram G, Anand R, Gupta AP, Husain K, Bedi YS, Mallavarapu GR (January 2011). "Composition of a monoterpenoid-rich essential oil from the rhizome of Zingiber officinale from north western Himalayas". Natural Product Communications. 6 (1): 93–6. doi:10.1177/1934578X1100600122. PMID 21366054. S2CID 20981360.