4-Hydroxycoumarin, oxidation

Huebner and Link870 have prepared 4-arylazo-2-pyrazolin-5-ones by the reaction of hydrazines with 4-hydroxycoumarin, 3,3 -methylene-bis(4-hydroxycoumarin) and with 2,3,4-triketochroman derivatives. In the case of the 4-hydroxycoumarins oxidation by phenylhydrazine occurs to give the bisphenylhydrazone of an a,/ -ketoester. The reaction then proceeds as previously discussed for such compounds. 

Oxidation. Coumarin is not readily oxidized by chromic acid but, by action of the Fenton s reagent, it is converted into 7-hydroxycoumarin (umbeUiferone) [93-35-6] (28). 

The pyranocoumarin 105 can be prepared via a three-component Diels-Alder reaction between 4-hydroxycoumarin, ethyl vinyl ether and an a-dicarbonyl compound. Similarly to the above, upon treatment of 105 with sulfuric acid in THF, hydrolysis and rearrangement occur to give the furofurochromenone 106. The hemiacetal functionality in 106 may then be oxidized with pyridinium chlorochromate (PCC) to give the lactone 107 <2001EJ03711> (Scheme 28). 

Cycloaddition Reactions with Other Nucleophiles The anodic two-electron oxidation of catechol affords o-quinone that may react with the enolates of 4-hydroxycoumarine or 5,5-dimethyl-1,3-cyclohexanedione (dimedone). The resulting adducts undergo a second anodic oxidation leading to benzofuran derivatives in good yields (90-95%) (Scheme 53) [75, 76]. 

Another example of an intermolecular cyclization is the anodic generation of a neutral molecule acting as an electrophile which reacts with the nucleophile present. We have shown [44] that the anodic oxidation of cathecol (QH2) at a graphite anode using controlled potential electrolysis in the presence of 4-hydroxycoumarin gave 6i/-benzofuro[3,2c][l]-benzopyran-6-one, 9, in yields higher than 90%, irrespective of the applied potential (E = 0.4 or 1.1 V vs SCE) with consumption of 4 F/mol at either potentials (Scheme 10). 

In order to explain the formation of the product 9 during oxidation at two different potentials we have performed the experiments with cyclic voltammetry [45]. The cyclic voltammogram of catechol (QH2) exhibits the anodic wave at 0.25 V vs SCE (Fig. la) corresponding to the formation of o-quinone (Q) which is reduced in the cathodic sweep at 0.05 V vs SCE. The cathodic counterpart of the anodic peak disappears, when a sufficient amount of 4-hydroxycoumarin was added, and a second irreversible peak at 0.95 V vs SCE appeared (Fig. lb). 

Mechanistic aspects of the intermolecular cyclization reaction in the anodic oxidation of catechol in the presence of 4-hydroxycoumarin were discussed in Sect. 2.2. This reaction is a synthetically simple and versatile method for the preparation of formally [3 + 2] cycloadducts between a -diketo compound and catechol [44,45]. Anodic oxidation of catechol using controlled potential electrolysis (E = 0.9-1.1 V vs SCE) or constant current electrolysis (i = 5 mA/cm ) was performed in water solution containing sodium acetate (0.15 mol/1) in the presence of various nucleophiles such as 4-hydroxycoumarin,... 

Many plants produce coumarins coumarin itself is found in sweet clover and contributes to the smell of new-mown hay. However, if sweet clover is allowed to ferment, oxidative processes initiated by the microorganisms lead to the formation of 4-hydroxycoumarin rather than coumarin. 4-Hydroxycoumarin then reacts with formaldehyde, also produced via the microbial degradative reactions, and provides dicoumarol. 

The hydrolysis of the Schiff base 63 is an acid-catalyzed reaction initiated by the protons liberated during the anodic oxidation. A successful synthesis could be achieved in an undivided cell. The starting compound 63 was oxidized at the anode, and the liberated protons were reduced at the cathode the solution did not become too acidic. This reaction was applied to the oxidation of 3-arylidenamino-4-hydroxycoumarin, which gave the expected 1,3-oxazole derivatives.78 The mechanism of the conversion 63 -> 64 involves... 

Anodic cyclization of thiocarboxamides to 1,3-thiazoles is in certain cases a superior method compared to the chemical oxidation as usually performed, using an alkaline solution of potassium hexacyanoferrate(UI). Thus anodic oxidation of 3-anilinothiocarbonyl-4-hydroxycoumarin (110a X = O) and 3-anilinothiocarbonyl-4-hydroxy-2-quinolone (110b) yielded the corresponding 1,3-thiazole derivatives 111a and 111b, respectively. Chemical oxidation... 

Furo[3,2-c][l]benzopyran-4-ones have been prepared either by acid catalyzed condensation of 4-hydroxycoumarin with a benzoin derivative (equation 11) (81IJC(B)614) or from 3-allyl-4-hydroxycoumarins on oxidation with osmium tetroxide/potassium periodate followed by cyclization of the intermediary aldehyde with PPA (equation 12) (79G109). 

A very simple synthesis of coumestrol (228) has been described by Kappe and coworkers (Scheme 46) (74ZN(B)292). It is based upon dehydrogenation of 4-hydroxy-3-phenyl-coumarins to coumestans (720PP233). A number of 2 -hydroxy 3-phenylcoumarins were oxidized with lead tetraacetate to the corresponding coumestans 3-(l-acetoxy-4-methoxy-2-oxo-3,5-cyclohexadienyl)coumarins were obtained as by-products (76BCJ1955). Coumes-tan itself (226) has been obtained by photolysis of the phenol ether (232), which is in turn available from 4-hydroxycoumarin (229) and (diacetoxyiodo)benzene (Scheme 47) (78CB3857) via an iodonium ylide (231). 

Carbonylation of o-hydroxyacetophenone.1 The reaction of o-hydroxyacetophen-one (1) with Se (1 equiv.) and CO in the presence of DBU gives 4-hydroxycoumarin (2) in quantitative yield. Selenium can be used in catalytic amounts if nitrobenzene is added to oxidize H2Se to Se. 

Extraction of the proton allows the carboxylase to carbox-ylate the glutamate residue. The vitamin K intermediate is converted to vitamin K oxide, which must be reduced back to vitamin K. Vitamin K oxide is recycled back to vitamin K by vitamin K epoxide reductase arid vitamin K quinone reducta.se. Both of these enzymes are dithiol dependent and are inhibited by the 4-hydroxycoumarin anticoagulants. 

Coumestans represented by 321 are an oxygenated class of aromatic natural products, which have phytoalexin and estrogenic activities. From the biogenetic point of view, 321 will be formed from two units, 4-hydroxycoumarin (322) and catechol. Thus, the first synthesis of 321 was carried out by an electrochemical method. Catechol was initially oxidized to o-quinone, which was attacked by 322 to afford 321 in 95% yield (Scheme 69). ... 

Generally, the regioselective formation of o-quinones has been known to be accomplished by using polyphenol oxidase in chloroform and not in water, because of rapid inactivation of the enzyme in water. However, catechol underwent mushroom tyrosinase-catalyzed oxidation in phosphate buffer (pH 6.8) containing 4-hydroxycoumarin (322) to afford 321 in 96% yield, as shown in Scheme 69. 

In the bicyclic series, the reaction (ref. 46) of umbelliferone (7-hydroxycoumarin) with prenyl bromide (RBr) in dioxan containing silver oxide afforded, osthenol, 7-hydroxy-8 prenylcoumarin (7%), (Table 12.2, ref. 47), 7-hydroxy-6-prenylcoumarin (3%), 7-prenyloxycoumarin (9%) and a prenyl derivative at the benzylic position of the pyrano cyclisation product of osthenol. 

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