Coumarin
Names | |
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IUPAC name
2H-Chromen-2-one
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Preferred IUPAC name
2H-1-Benzopyran-2-one | |
Other names
1-Benzopyran-2-one
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Identifiers | |
3D model (
JSmol ) |
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383644 | |
ChEBI | |
ChEMBL | |
ChemSpider | |
DrugBank | |
ECHA InfoCard
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100.001.897 |
EC Number |
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165222 | |
KEGG | |
PubChem CID
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RTECS number
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UNII | |
CompTox Dashboard (EPA)
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Properties | |
C9H6O2 | |
Molar mass | 146.145 g·mol−1 |
Appearance | colorless to white crystals |
Odor | pleasant, like vanilla beans |
Density | 0.935 g/cm3 (20 °C (68 °F)) |
Melting point | 71 °C (160 °F; 344 K) |
Boiling point | 301.71 °C (575.08 °F; 574.86 K) |
0.17 g / 100 mL | |
Solubility | very soluble in ether, diethyl ether, chloroform, oil, pyridine soluble in ethanol |
log P | 1.39 |
Vapor pressure | 1.3 hPa (106 °C (223 °F)) |
−82.5×10−6 cm3/mol | |
Structure | |
orthorhombic | |
Hazards | |
GHS labelling: | |
Warning | |
H302, H317, H373 | |
P260, P261, P264, P270, P272, P280, P301+P312, P302+P352, P314, P321, P330, P333+P313, P363, P501 | |
NFPA 704 (fire diamond) | |
Flash point | 150 °C (302 °F; 423 K) |
Lethal dose or concentration (LD, LC): | |
LD50 (median dose)
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293 mg/kg (rat, oral) |
Safety data sheet (SDS) | Sigma-Aldrich |
Related compounds | |
Related compounds
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Chromone; 2-Cumaranone |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Coumarin (
Coumarin is a colorless crystalline solid with a sweet
Etymology
Coumarin is derived from coumarou, the French word for the
History
Coumarin was first isolated from
Also in 1820, Nicholas Jean Baptiste Gaston Guibourt (1790–1867) of France independently isolated coumarin, but he realized that it was not benzoic acid.
In 1835, the French pharmacist A. Guillemette proved that Vogel and Guibourt had isolated the same substance.[9] Coumarin was first synthesized in 1868 by the English chemist William Henry Perkin.[10]
Coumarin has been an integral part of the fougère genre of perfume since it was first used in Houbigant's Fougère Royale in 1882.[11]
Synthesis
Coumarin can be prepared by a number of
Biosynthesis
From
Natural occurrence
Coumarin is found naturally in many plants. Freshly ground plant parts contain higher amount of desired and undesired phytochemicals than powder. In addition, whole plant parts are harder to counterfeit; for example, one study showed that authentic
- Vanilla grass (Anthoxanthum odoratum)
- Sweet woodruff (Galium odoratum)
- Sweet grass (Hierochloe odorata)
- Sweet-clover (genus Melilotus)
- Tonka bean (Dipteryx odorata)
- Cinnamon; a 2013 study showed different varieties containing different levels of coumarin:[15]
- Ceylon cinnamon or true cinnamon (Cinnamomum verum): 0.005 to 0.090 mg/g
- Chinese cinnamon or Chinese cassia (C. cassia): 0.085 to 0.310 mg/g
- Indonesian cinnamon or Padang cassia (C. burmannii): 2.14 to 9.30 mg/g
- Saigon cinnamon or Vietnamese cassia (C. loureiroi): 1.06 to 6.97 mg/g
- Deertongue (Carphephorus odoratissimus),[16]
- Tilo (
- Mullein (genus Verbascum)
- Many cherry blossom tree varieties (of the genus Prunus).[19]
- Related compounds are found in some but not all specimens of genus licorice derives.[20]
Coumarin is found naturally also in many edible plants such as
Coumarins were found to be uncommon but occasional components of propolis by Santos-Buelga and Gonzalez-Paramas 2017.[21]
Biological function
Coumarin has appetite-suppressing properties, which may discourage animals from eating plants that contain it. Though the compound has a pleasant sweet odor, it has a bitter taste, and animals tend to avoid it.[22]
Metabolism
The
Derivatives
Coumarin is used in the pharmaceutical industry as a precursor reagent in the synthesis of a number of synthetic anticoagulant pharmaceuticals similar to
Uses
Coumarin is often found in
Toxicity
Coumarin is moderately
European health agencies have warned against consuming high amounts of
The European Regulation (EC) No 1334/2008 describes the following maximum limits for coumarin: 50 mg/kg in traditional and/or seasonal bakery ware containing a reference to cinnamon in the labeling, 20 mg/kg in breakfast cereals including muesli, 15 mg/kg in fine bakery ware, with the exception of traditional and/or seasonal bakery ware containing a reference to cinnamon in the labeling, and 5 mg/kg in desserts.
An investigation from the Danish Veterinary and Food Administration in 2013 shows that bakery goods characterized as fine bakery ware exceeds the European limit (15 mg/kg) in almost 50% of the cases.[35] The paper also mentions tea as an additional important contributor to the overall coumarin intake, especially for children with a sweet habit.
Coumarin was banned as a food additive in the United States in 1954, largely because of the hepatotoxicity results in rodents.
Coumarin is subject to restrictions on its use in perfumery,[40] as some people may become sensitized to it, however the evidence that coumarin can cause an allergic reaction in humans is disputed.[41]
Minor neurological dysfunction was found in children exposed to the anticoagulants acenocoumarol or phenprocoumon during pregnancy. A group of 306 children were tested at ages 7–15 years to determine subtle neurological effects from anticoagulant exposure. Results showed a dose–response relationship between anticoagulant exposure and minor neurological dysfunction. Overall, a 1.9 (90%) increase in minor neurological dysfunction was observed for children exposed to these anticoagulants, which are collectively referred to as "coumarins." In conclusion, researchers stated, "The results suggest that coumarins have an influence on the development of the brain which can lead to mild neurologic dysfunctions in children of school age."[42]
Coumarin's addition to
Alcoholic beverages sold in the European Union are limited to a maximum of 10 mg/L coumarin by law.[46] Cinnamon flavor is generally cassia bark steam-distilled to concentrate the cinnamaldehyde, for example, to about 93%. Clear cinnamon-flavored alcoholic beverages generally test negative for coumarin, but if whole cassia bark is used to make mulled wine, then coumarin shows up at significant levels.[citation needed]
References
- ^ a b c d e f g h i "Coumarin". PubChem, National Library of Medicine, US National Institutes of Health. 4 April 2019. Retrieved 13 April 2019.
- ^ a b "Coumarins and indandiones". Drugs.com. 2016. Retrieved 24 December 2016.
- ^ "Warfarin, Molecule of the Month for February 2011, by John Maher". www.chm.bris.ac.uk. Retrieved 2023-12-20.
- .
- ^ Vogel, A. (1820). "De l'existence de l'acide benzoïque dans la fève de tonka et dans les fleurs de mélilot" [On the existence of benzoic acid in the tonka bean and in the flowers of melilot]. Journal de Pharmacie (in French). 6: 305–309.
- ^ Guibourt, N. J. B. G. (1820). Histoire Abrégée des Drogues Simples [Abridged History of Simple Drugs] (in French). Vol. 2. Paris: L. Colas. pp. 160–161.
- ^ "Societe du Pharmacie de Paris". Journal de Chimie Médicale, de Pharmacie et de Toxicologie. 1: 303. 1825.
... plus récemment, dans un essai de nomenclature chimique, lu à la section de Pharmacie de l'Académie royale de Médecine, il l'a désignée sous le nom de coumarine, tiré du nom du végétal coumarouna odorata ... [... more recently, in an essay on chemical nomenclature, [which was] read to the pharmacy section of the Royal Academy of Medicine, he [Guibourt] designated it by the name "coumarine," derived from the name of the vegetable Coumarouna odorata ...]
- ^ Guibourt, N. J. B. G. (1869). Histoire Naturelle des Drogues Simples (6th ed.). Paris: J. B. Baillière et fils. p. 377.
... la matière cristalline de la fève tonka (matière que j'ai nommée coumarine) ... [... the crystalline matter of the tonka bean (matter that I named coumarine ...]
- ^ Guillemette, A. (1835). "Recherches sur la matière cristalline du mélilot" [Research into the crystalline material of melilot]. Journal de Pharmacie. 21: 172–178.
- .
- ^ "Olfactory Groups - Aromatic Fougere". fragrantica.com. Retrieved 13 November 2020.
- .
- S2CID 212740956.
- S2CID 104289832.
- ^ Cassia Cinnamon as a Source of Coumarin in Cinnamon-Flavored Food and Food Supplements in the United States J. Agric. Food Chem., 61 (18), 4470–4476
- ISBN 978-9881607416. Retrieved 21 September 2020.
- PMID 10771205.
- S2CID 84525194. Archived from the originalon 2013-01-05. Retrieved 2010-06-26.
- S2CID 14467019.
- PMID 1941536.
- S2CID 221165130.
- PMID 13619027.
- PMID 1339448.
- ^ "Warfarin". Drugs.com. 7 March 2019. Retrieved 13 April 2019.
- ^ Coumarin Material Safety Data Sheet (MSDS) Archived 2004-10-21 at the Wayback Machine
- PMID 15141102.
- PMID 12480300.
- PMID 10418958.
- ^ "Frequently Asked Questions about coumarin in cinnamon and other foods" (PDF). The German Federal Institute for Risk Assessment. 30 October 2006. Archived from the original (PDF) on 19 April 2009.
- ^ "Chemical Sampling Information – Coumarin". Osha.gov. Retrieved 30 December 2015.
- ^ "Cassia cinnamon with high coumarin contents to be consumed in moderation - BfR". Bfr.bund.de. Retrieved 30 December 2015.
- ^ "German Christmas Cookies Pose Health Danger". NPR.org. 25 December 2006. Retrieved 30 December 2015.
- ^ a b c "High daily intakes of cinnamon: Health risk cannot be ruled out. BfR Health Assessment No. 044/2006, 18 August 2006" (PDF). bund.de. Retrieved 28 March 2018.
- ^ Engineering Resources – Bulk Density Chart Archived 2002-10-27 at the Wayback Machine
- .
- S2CID 23232507.
- ^ "Food and Drugs". Access.gpo.gov. Archived from the original on 5 February 2012. Retrieved 30 December 2015.
- ^ "FDA/CFSAN/OPA: EAFUS List". www.cfsan.fda.gov. Archived from the original on 3 September 2000. Retrieved 17 January 2022.
- ^ "Food and Drugs". Access.gpo.gov. Archived from the original on 5 February 2012. Retrieved 30 December 2015.
- ^ "Standards Restricted - IFRA International Fragrance Association". Archived from the original on 2012-01-06. Retrieved 2012-07-19.
- ^ "Cropwatch Claims Victory Regarding "26 Allergens" Legislation : Modified from article originally written for Aromaconnection, Feb 2008" (PDF). Leffingwell.com. Retrieved 2 December 2018.
- PMID 11408097.
- ^ "Jeffrey Wigand : Jeffrey Wigand on 60 Minutes". Jeffreywigand.com. Retrieved 30 December 2015.
- ^ "Tobacco On Trial". Tobacco-on-trial.com. Retrieved 30 December 2015.
- ^ "Industry Documents Library". Legacy.library.ucsf.edu. Retrieved 2 December 2018.
- .