Anethole is an aromatic, unsaturatedether related to lignols. It exists as both cis–trans isomers (see also E–Z notation), involving the double bond outside the ring. The more abundant isomer, and the one preferred for use, is the trans or E isomer.[4]
Like related compounds, anethole is poorly soluble in water. Historically, this property was used to detect adulteration in samples.[5]
Most anethole is obtained from turpentine-like extracts from trees.[3][6] Of only minor commercial significance, anethole can also be isolated from essential oils.[7][8][9]
Essential oil
World production
Trans-anethole
Anise
8 tonnes (1999)
95%
Star anise
400 tonnes (1999), mostly from China
87%
Fennel
25 tonnes (1999), mostly from Spain
70%
Currently Banwari Chemicals Pvt Ltd situated in Bhiwadi, Rajasthan, India is the leading manufacturer of anethole. It is prepared commercially from 4-methoxypropiophenone,[4][10] which is prepared from anisole.[3]
Uses
Flavoring
Anethole is distinctly sweet, measuring 13 times sweeter than sugar. It is perceived as being pleasant to the taste even at higher concentrations. It is used in alcoholic drinks ouzo, rakı, anisette and absinthe, among others. It is also used in seasoning and confectionery applications, such as German Lebkuchen, oral hygiene products, and in small quantities in natural berry flavors.[8]
As well as an insect pesticide, anethole is an effective insect repellent against mosquitos.[26]
Ouzo effect
Anethole is responsible for the "ouzo effect" (also "louche effect"), the spontaneous formation of a microemulsion[27][28] that gives many alcoholic beverages containing anethole and water their cloudy appearance.[29] Such a spontaneous microemulsion has many potential commercial applications in the food and pharmaceutical industries.[30]
Precursor to illicit drugs
Anethole is an inexpensive chemical precursor for paramethoxyamphetamine (PMA),[31] and is used in its clandestine manufacture.[32] Anethole is present in the essential oil from guarana, which has psychoactive effects typically attributed to its caffeine content. The absence of PMA or any other known psychoactive derivative of anethole in human urine after ingestion of guarana leads to the conclusion that any psychoactive effect of guarana is not due to aminated anethole metabolites.[33]
Anethole has estrogenic activity.[35][36][37] It has been found to significantly increase uterine weight in immature female rats.[38]
Fennel, which contains anethole, has been found to have a galactagogue effect in animals. Anethole bears a structural resemblance to catecholamines like dopamine and may displace dopamine from its receptors and thereby disinhibit prolactin secretion, which in turn may be responsible for the galactagogue effects.[39]
Safety
In the USA, anethole is generally recognized as safe (GRAS). After a hiatus due to safety concerns, anethole was reaffirmed by Flavor and Extract Manufacturers Association (FEMA) as GRAS.[40] The concerns related to liver toxicity and possible carcinogenic activity reported in rats.[41] Anethole is associated with a slight increase in liver cancer in rats,[41] although the evidence is scant and generally regarded as evidence that anethole is not a carcinogen.[41][42] An evaluation of anethole by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) found its notable pharmacologic properties to be reduction in motor activity, lowering of body temperature, and hypnotic, analgesic, and anticonvulsant effects.[43] A subsequent evaluation by JECFA found some reason for concern regarding carcinogenicity, but there is currently insufficient data to support this.[44] At this time, the JECFA summary of these evaluations is that anethole has "no safety concern at current levels of intake when used as a flavoring agent".[45]
In large quantities, anethole is slightly toxic and may act as an irritant.[46]
History
That an oil could be extracted from anise and fennel had been known since the Renaissance by the German alchemist Hieronymus Brunschwig (c. 1450 – c. 1512), the German botanist Adam Lonicer (1528–1586), and the German physician Valerius Cordus (1515–1544), among others.[47] Anethole was first investigated chemically by the Swiss chemist Nicolas-Théodore de Saussure in 1820.[48] In 1832, the French chemist Jean Baptiste Dumas determined that the crystallizable components of anise oil and fennel oil were identical, and he determined anethole's empirical formula.[49] In 1845, the French chemist Charles Gerhardt coined the term anethol – from the Latin anethum (anise) + oleum (oil) – for the fundamental compound from which a family of related compounds was derived.[50] Although the German chemist Emil Erlenmeyer proposed the correct molecular structure for anethole in 1866,[51] it was not until 1872, that the structure was accepted as correct.[47]
^Bodsgard, B. R.; Lien, N. R.; Waulters, Q. T. (2016). "Liquid CO2 Extraction and NMR Characterization of Anethole from Fennel Seed: A General Chemistry Laboratory". Journal of Chemical Education. 93 (2): 397–400. Bibcode:2016JChEd..93..397B. doi:10.1021/acs.jchemed.5b00689.
^Ryu, J.; Seo, J.; Lee, Y.; Lim, Y.; Ahn, J. H.; Hur, H. G. (2005). "Identification of syn- and anti-anethole-2,3-epoxides in the metabolism of trans-anethole by the newly isolated bacterium Pseudomonas putida JYR-1". Journal of Agricultural and Food Chemistry. 53 (15): 5954–5958. doi:10.1021/jf040445x. PMID16028980.
^De, M.; De, A. K.; Sen, P.; Banerjee, A. B. (2002). "Antimicrobial properties of star anise (Illicium verum Hook. f.)". Phytotherapy Research. 16 (1): 94–95. doi:10.1002/ptr.989. PMID11807977. S2CID27196549.
^Kubo, I.; Fujita, K. (2001). "Naturally occurring anti-Salmonella agents". Journal of Agricultural and Food Chemistry. 49 (12): 5750–5754. doi:10.1021/jf010728e. PMID11743758.
^Camurça-Vasconcelos, A. L.; Bevilaqua, C. M.; Morais, S. M.; Maciel, M. V.; Costa, C. T.; Macedo, I. T.; Oliveira, L. M.; Braga, R. R.; Silva, R. A.; Vieira, L. S. (2007). "Anthelmintic activity of Croton zehntneri and Lippia sidoides essential oils". Veterinary Parasitology. 148 (3–4): 288–294. doi:10.1016/j.vetpar.2007.06.012. PMID17629623.
^Knio, K. M.; Usta, J.; Dagher, S.; Zournajian, H.; Kreydiyyeh, S. (2008). "Larvicidal activity of essential oils extracted from commonly used herbs in Lebanon against the seaside mosquito, Ochlerotatus caspius". Bioresource Technology. 99 (4): 763–768. Bibcode:2008BiTec..99..763K. doi:10.1016/j.biortech.2007.01.026. PMID17368893.
^Cheng, S. S.; Liu, J. Y.; Tsai, K. H.; Chen, W. J.; Chang, S. T. (2004). "Chemical composition and mosquito larvicidal activity of essential oils from leaves of different Cinnamomum osmophloeum provenances". Journal of Agricultural and Food Chemistry. 52 (14): 4395–4400. doi:10.1021/jf0497152. PMID15237942.
^Morais, S. M.; Cavalcanti, E. S.; Bertini, L. M.; Oliveira, C. L.; Rodrigues, J. R.; Cardoso, J. H. (2006). "Larvicidal activity of essential oils from Brazilian Croton species against Aedes aegypti L.". Journal of the American Mosquito Control Association. 22 (1): 161–164. doi:10.2987/8756-971X(2006)22[161:LAOEOF]2.0.CO;2. PMID16646345. S2CID33429927.
^Park, I. K.; Choi, K. S.; Kim, D. H.; Choi, I. H.; Kim, L. S.; Bak, W. C.; Choi, J. W.; Shin, S. C. (2006). "Fumigant activity of plant essential oils and components from horseradish (Armoracia rusticana), anise (Pimpinella anisum) and garlic (Allium sativum) oils against Lycoriella ingenua (Diptera: Sciaridae)". Pest Management Science. 62 (8): 723–728. doi:10.1002/ps.1228. PMID16786497.
^Chang, K. S.; Ahn, Y. J. (2002). "Fumigant activity of (E)-anethole identified in Illicium verum fruit against Blattella germanica". Pest Management Science. 58 (2): 161–166. doi:10.1002/ps.435. PMID11852640.
^Kim, D. H.; Ahn, Y. J. (2001). "Contact and fumigant activities of constituents of Foeniculum vulgare fruit against three coleopteran stored-product insects". Pest Management Science. 57 (3): 301–306. doi:10.1002/ps.274. PMID11455661.
^Padilha de Paula, J.; Gomes-Carneiro, M. R.; Paumgartten, F. J. (2003). "Chemical composition, toxicity and mosquito repellency of Ocimum selloi oil". Journal of Ethnopharmacology. 88 (2–3): 253–260. doi:10.1016/s0378-8741(03)00233-2. PMID12963152.
^Sánchez Domínguez, M.; Rodríguez Abreu, C. (2016). Nanocolloids: A Meeting Point for Scientists and Technologists. Elsevier Science. p. 369. ISBN978-0-12-801758-6. Retrieved 2018-08-02. O/W and W/O nano-emulsions can also be formed without a surfactant by self-emulsification, using the so-called Ouzo effect. The major components of Ouzo (a Greek drink) are trans-anethole, ethanol, and water. Anethole is almost insoluble ...
^Spernath, A.; Aserin, A. (2006). "Microemulsions as carriers for drugs and nutraceuticals". Advances in Colloid and Interface Science. 128–130: 47–64. doi:10.1016/j.cis.2006.11.016. PMID17229398.
^Waumans, D.; Hermans, B.; Bruneel, N.; Tytgat, J. (2004). "A neolignan-type impurity arising from the peracid oxidation reaction of anethole in the surreptitious synthesis of 4-methoxyamphetamine (PMA)". Forensic Science International. 143 (2–3): 133–139. doi:10.1016/j.forsciint.2004.02.033. PMID15240033.
^Benoni, H.; Dallakian, P.; Taraz, K. (1996). "Studies on the essential oil from guarana". Zeitschrift für Lebensmittel-Untersuchung und -Forschung. 203 (1): 95–98. doi:10.1007/BF01267777. PMID8765992. S2CID45636969.
^Lachenmeier, D. W. (2008). "Thujon-Wirkungen von Absinth sind nur eine Legende—Toxikologie entlarvt Alkohol als eigentliche Absinthismus-Ursache" [Thujone-attributable effects of absinthe are only an urban legend—toxicology uncovers alcohol as real cause of absinthism]. Medizinische Monatsschrift für Pharmazeuten (in German). 31 (3): 101–106. PMID18429531.
^Newberne, P.; Smith, R. L.; Doull, J.; Goodman, J. I.; Munro, I. C.; Portoghese, P. S.; Wagner, B. M.; Weil, C. S.; Woods, L. A.; Adams, T. B.; Lucas, C. D.; Ford, R. A. (1999). "The FEMA GRAS assessment of trans-anethole used as a flavouring substance. Flavour and Extract Manufacturers' Association". Food and Chemical Toxicology. 37 (7): 789–811. doi:10.1016/S0278-6915(99)00037-X. PMID10496381.
^ abcNewberne, P. M.; Carlton, W. W.; Brown, W. R. (1989). "Histopathological evaluation of proliferative liver lesions in rats fed trans-anethole in chronic studies". Food and Chemical Toxicology. 27 (1): 21–26. doi:10.1016/0278-6915(89)90087-2. PMID2467866.
^Joint FAO/WHO Expert Committee on Food Additives. "trans-Anethole". WHO Food Additives Series. International Program on Chemical Safety (IPCS).
^Joint FAO/WHO Expert Committee on Food Additives (1998). "trans-Anethole". WHO Food Additives Series. International Program on Chemical Safety (IPCS).
^"Safety data for anethole". Physical & Theoretical Chemistry Laboratory Safety, Oxford University. Archived from the original on 2008-06-15. Retrieved 2009-03-10.
Lippmann, Edmund Oskar von (1921). "§ 339. Anethol". Zeittafeln zur Geschichte der Organischen Chemie [Timeline of the history of organic chemistry] (in German). Berlin: Springer-Verlag. p. 1. ISBN9783662246665.
Gildemeister, Eduard; Hoffmann, Friedrich (1900). "§ 307. Oil of anise". The Volatile Oils. Translated by Kremers, Edward. Milwaukee, Wisconsin: Review Publishing Co. pp. s558–s563.
Dumas, J. (1832). "Mémoire sur les substances végétales qui se rapprochent du camphre, et sur quelques huiles essentielles" [Memoir on plant substances that resemble camphor, and on several essential oils]. Annales de Chimie et de Physique. Série 2 (in French). 50: 225–240. On p. 234, Dumas provides an empirical formula C10H6O1/2 for anethol. If the subscripts are doubled and if the subscript for carbon is then halved (because Dumas, like many of his contemporaries, used the wrong atomic mass for carbon, 6 instead of 12), then Dumas' empirical formula is correct.
Dumas' finding that the crystallizable components of anise oil and fennel oil were identical was confirmed in 1833 by the team of Rodolphe Blanchet (1807–1864) and Ernst Sell (1808–1854). See: Blanchet, Sell (1833). "Ueber die Zusammensetzung einiger organischer Substanzen" [On the composition of some organic substances]. Annalen der Pharmacie (in German). 6 (3): 259–313. doi:10.1002/jlac.18330060304. See especially pp. 287–288.
Dumas' empirical formula for anethole was confirmed in 1841 by the French chemist Auguste Cahours. See: Cahours, A. A. T. (1841). "Sur les essences de fenouil, de badiane et d'anis" [On the essential oils of fennel, star anise, and anise]. Annales de Chimie et de Physique. Série 3 (in French). 2: 274–308. See pp. 278–279. Note that the subscripts of Cahours' empirical formula (C40H24O2) must be divided by 2 and then the subscript for carbon must be divided again by 2 (because, like many chemists of his time, Cahours used the wrong atomic mass for carbon, 6 instead of 12). If these changes are made, the resulting empirical formula is correct.
^Gerhardt, Charles (1845). "Ueber die Identität des Dragonöls und des Anisöls" [On the identity of tarragon oil and anise oil]. Journal für praktische Chemie (in German). 36: 267–276. doi:10.1002/prac.18450360159. [From p. 269:] Ich werde keinen neuen Namen für jede einzelne Art der folgenden physisch verschiedenen Arten annehmen. In meinem Werke bezeichne ich sie als Varietäten der Gattung „Anethol". [I will adopt no new name for any individual species of the following physically different species. In my work, I designate them as varieties of the genus anethol.]