Acidity 4-hydroxy-2-pyrones

Hydroxy pyridine 1-oxides are also tautomeric the 4-isomer exists in about equal amounts of forms (783) and (784). 4-Hydroxy-pyrones and -pyridones exhibit a different type of tautomerism the a-one (e.g. 785) structure is favored relative to the y-one structure. (3-Hydroxy-4-pyrones such as kojic acid (786) show phenolic properties (CHEC 3.28, Scheme 30). a- and 3-Hydroxy cations (e.g. 787) are the conjugate acids of pyridones and pyrones and are considered in the next section. 

Kojic Acid, 5-Hydroxy-2-(hydroxymethyl)-4H-py-ran-4-one 5-hydroxy-2-(hydroxymethyl)-4-pyrone 2-hydroxymethyl -5 -hydroxy-> -pyrone. mol wt 142.11. 

To overcome this drawback the core structure of the molecules was modified. We switched to other cyclic ketoenol subclasses, e.g., tetronic acids, pyrazolidin-3,5-diones, 4-hydroxy-pyrones and 6-hydroxy-thiazinones. 

Meconic acid (3-hydroxy -pyrone-2,6-dicarboxylic acid) [497-59-6] M 200.1, m 100° (loses H2O), pK... 

From the ligands having oxygen donor atoms the monohydric and poly-hydric phenoles, o-phenolecarboxylic acids, hydroxy-4-pyrones are of particular interest for binding UO in complexes and its spectrophotometric determination in aqueous solution. The monodentate phenolic hydroxyl is already bound giving UO complexes stable against hydrolysis up to pH 5. 

For the preparation of 4-substituted coumarins, a phenol may be condensed with ethyl acetoacetate under the influence of sulphuric acid. Thus resorcinol (II) readily undergoes this condensation (which is represented diagrammatically above) to give 7-hydroxy-4-methyl-coumarin (III). Note that the coumarins, like all 2 pyrones, are systematically lactones. 

A careful assessment of the constitution of compound 10 led to the development of a rather efficient strategy featuring the Diels-Alder reaction (see Scheme 3). Although the unassisted intermole-cular reaction between 3-hydroxy-2-pyrone (16)23 and a,/ -unsatu-rated ester 17 is unacceptable in terms of both regioselectivity and chemical yield, compounds 16 and 17 combine smoothly in refluxing benzene and in the presence of phenylboronic acid to give fused bicyclic lactone 12 (61% yield) after workup with 2,2-... 

Dihydro-2f/-pyran-2-one has been prepared by reductive cycliza-tion of 5-hydroxy-2-pentynoic acid [2-Pentynoic acid, 5-hydroxy-], which is obtained in two steps from acetylene [Ethyne] and ethylene oxide [Oxirane] 3 and by the reaction of dihydropyran [277-Pyran, 3,4-dihydro-] with singlet oxygen [Oxygen, singlet].4,5 2ff-Pyran-2-one has been prepared by pyrolysis of heavy metal salts of coumalic acid [2//-Pyran-5-carboxylic acid, 2-oxo-],8 by pyrolysis of a-pyrone-6-carboxylic acid [211 - Pyran-6-carboxyl ic acid, 2-oxo-] over copper,7 and by pyrolysis of coumalic acid over copper (66-70% yield).8... 

The intermediate J4 was prepared by an "intramolecular Narasaka type Diels-Alder reaction" of dienophile 10 and 3-hydroxy-2-pyrone (J L) in the presence of phenylboronic acid [7] ... 

The Lewis acid-mediated condensation reaction of a,/3-unsaturated carboxylic acids with 4-hydroxy-2-pyrones has been utilized to prepare Fleischmann s a,a-bispyrone 2 and Praill s a,7-bispyrone 3 and confirm their assignments <2000TL1901>. 

Aminomethylfurans are converted into 3-hydroxypyridines by acid and an oxidizing agent, e.g. (219) —+ (220). 2-Hydroxymethylfurans with chlorine in aqueous methanol give 3-hydroxy-4-pyrones. 3-Hydroxypyridines can conveniently be prepared by reaction of 2-acylfurans with ammonia (Scheme 75). Pyrrole and dichlorocarbene give some 3-chloropyridine (Section 3.3.1.7.1). 

Industrially, a selectivity to DAA of between 90—95% can be achieved (64). The principal by-products are mesityl oxide and acetone trimers. j W-Triacetone dialcohol [3682-91-5] can form by condensation of acetone with diacetone alcohol (116). Dehydration of ry/ -triacetone dialcohol can yield semiphorone [5857-71-6] (6-hydroxy-2,6-dimethyl-2-hepten-4-one), which may in turn ring close to form 2,2,6,6-tetramethyl-y-pyrone [1197-66-6/, or ultimately dehydrate to phorone [504-20-1] (2,6-dimethyl-2,5-heptadien-4-one) (146). Similarly, an unsymmetrical acetone trimer can also be formed which dehydrates to 2,4-dimethyl-2,4-heptadiene-6-one. These impurities complicate the high purity recovery of DAA, and are thought to be responsible for a yellow discoloration of DAA. The addition of dibasic acid (147) or nitrogen containing carboxylic or phosphonic acids (148) has been patented as refined product stabilizing agents. 

Soft carbon nucleophiles other than malonate derivatives follow similar patterns of regioselectivity, as shown by the addition of cyclopentadiene anion (equation 211)>os and the highly acidic 4-hydroxy-6-methyl-2-pyrone (equation 212).393... 

In this section the synthesis of coumalic acid (92), representing the a(2)-pyrone system, is described. a-Pyrones readily undergo a simple lactone-amide transformation, and the conversion of coumalic acid into the tautomeric 6-hydroxy-nicotinic acid (93) provides a further illustration of the conversion of a six-membered oxygen heterocycle into the corresponding nitrogen system. 

The palladium [Pd(Ph3)4]-catalysed 3 + 3-cycloaddition of trimethylenemethane with azomethineimines produced hexahydropyridazine derivatives under mild conditions (40 °C).171 The Lewis acid-catalysed formal oxa-[3 + 3]-cycloaddition of a,f+ unsaturated aldehydes with 6-methyl-4-hydroxy-2-pyrone, 1,3-diketones, and viny-logous silyl esters yielded a variety of pyrones at room temperature.172 Croton-aldehyde has been converted to 6-hydroxy-4-methylcyclohex-l-enecarboxaldehyde by an enantioselective 3 + 3-cycloaddition catalysed by proline. This methodology was used in the synthesis of (—)-isopulegol hydrate, (—)-cubebaol, and (—)-6-hydroxy-4-methylcyclohex-l-ene-1-methanol acetate, an intermediate in the total synthesis of the alkaloid magellanine.173... 

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