2-Coumaranone
Chemical compound
From Wikipedia, the free encyclopedia
2-Coumaranone (sometimes also called 2-Cumaranone[3]) is a bicyclic heteroaromatic compound in which a six-membered benzene ring is annulated with a five-membered γ-butyrolactone ring. The 2(3H)-benzofuranone can also be considered as a lactone of (2-hydroxyphenyl)acetic acid. The benzofuranone basic structure is the basis of some natural products – such as rosmadial,[4] which is isolatable from rosemary oil, and some substances with high pharmacological activity, such as griseofulvin and rifampicin. Furthermore, 2-cumaranone is utilized as a starting material for the preparation of chemiluminescent and fluorescent dyes, for synthetic pharmaceutical agents, like the antiarrhythmic drug dronedarone, and especially for the fungicide azoxystrobin.
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| Names | |
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| Preferred IUPAC name
1-Benzofuran-2(3H)-one | |
| Identifiers | |
3D model (JSmol) |
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| ChEMBL | |
| ChemSpider | |
| ECHA InfoCard | 100.008.230 |
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PubChem CID |
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| UNII | |
CompTox Dashboard (EPA) |
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| Properties | |
| C8H6O2 | |
| Melting point | 49–51 °C[1] |
| Hazards | |
| GHS labelling:[2] | |
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| Warning | |
| H315, H317, H319 | |
| P261, P264, P264+P265, P272, P280, P302+P352, P305+P351+P338, P321, P333+P317, P337+P317, P362+P364, P501 | |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Occurrence and synthesis
In 1884, Adolf von Baeyer and Paul Fritsch disclosed the synthesis of 2-coumaranone, which they described as the lactone of o-oxyphenylacetic acid, through the distillation "over free fire" of (2-hydroxyphenyl)acetic acid.[5]
The lactone 3H-benzofuran-2-one forms in this process under intramolecular water splitting at high temperature and in an impure state.
A similar fragmentation by oxidative intramolecular ring closure from phenylacetic acid also yields only modest returns (< 20%) due to the oxidation sensitivity of the methylene group and the formation of several by-products 2-coumaranone.[6]
The Ozonolysis of 2-allylphenol obtained by the alkylation of phenol with 3-bromopropene to produce phenylallyl ether and subsequently its Claisen rearrangement, gives rise to 2-hydroxyphenylacetic acid, which, through water splitting, yields 2-coumaranone. Despite this method having good yields, its economic and safety considerations make it unsuitable for an industrial process.[7]
On an industrial scale, the well-filtered starting materials cyclohexanone and glyoxylic acid are first transformed in an acid-catalyzed aldol condensation to form the (predominantly) cis-2-oxocyclohexylidene acetic acid (A). This then, in a second step, is transformed into the so-called enollactone (B) through water elimination (90% yield). The enollactone is continuously dehydrogenated at 250 °C in the vapor phase on a palladium catalyst to form 2-coumaranone (C) dehydrogenation (yield approximately 67%).[8][9][10]
An alternative process that uses glyoxylic acid methyl ester methylhemiacetals rather than glyoxylic acid as a starting material has not gained widespread acceptance.[11]
Properties
Pure 2-coumaranone manifests as an off-white to pale yellow solid with an aromatic odor.[1] On purification by distillation, "a colorless oil passes which solidifies in the receiver into splendid, transparent, well-formed crystals".[12] 3H-benzofuran-2-one is soluble in hot water, diethyl ether[5] and acetonitrile.[11] The lactone hydrolyzes slowly in hot water and rapidly in aqueous alkalis to form 2-hydroxyphenylacetic acid or its alkali salt.[5]
Applications
5-Nitro-3H-benzofuran-2-one is formed during the nitration of 2-coumaranone with nitrating acid.[13][14]
The 5-amino-3H-benzofuran-2-one can be obtained from the nitro compound using catalytic hydrogenation at a palladium catalyst.[13]
Lactones such as 2-coumaranone ('I) are readily cleaved by nucleophiles, leading to ring opening. Thus, 5-nitro-3H-benzofuran-2-one reacts with secondary amines to form 2-hydroxyphenylacetic acid amides. Through hydrogenation, these transform into corresponding 3-amino-6-hydroxyphenylethylamines, which are useful precursors for hair dyeing.[14]
Condensation of 5-nitro-3H-benzofuran-2-one (II) with a mixture of valeric acid (III) and valeric anhydride (IV) results in the enollactone (V), which upon heating rearranges to the substituted benzofurancarboxylic acid (VI), a key precursor for the antiarrhythmic drug Dronedarone.[15]
The basic structure of 2-coumaranone also underlies a class of antioxidants and radical scavengers, especially for stabilizing polypropylenes. In the synthesis of a model compound, glyoxylic acid reacts with 2 moles of 4-tert-butylphenol in the presence of methanesulfonic acid CH3SO3H to form a phenolic intermediate and is then esterified with benzoic acid.[16]
A one-pot reaction, carried out as a Tscherniak-Einhorn reaction of fluorophenols (X), glyoxylic acid (Y), and carbamates, such as carbamic acid methyl ester[17] or carbamic acid mesityl ester (Z), yields 2-coumaranones with carbamide side chains. These compounds react with strong bases such as diazabicycloundecene or potassium tert-butanolate, and show pronounced chemiluminescence in the presence of oxygen.[18][19][20]
The most notable application of 2-coumaranone by volume is as a starting material for the synthesis of the fungicide azoxystrobin[21] (known as Amistar from Syngenta) in the class of strobilurins.