4-Pyrones with hydrazines

The reactions of 4-pyrones with hydrazines and hydroxylamine, can lead to recyclisations involving the second heteroatom of the attacking nucleophile, producing pyrazoles and isoxazoles, respectively, however in the simplest examples 4-pyrones react with hydroxylamine, giving either l-hydroxy-4-pyridones or... 

The most common method for the preparation of pyrazoles from other heterocycles is from pyranone-type compounds. Condensation of 2,3-dihydro /7-pyran -ones 787 with various aryl hydrazines in the presence of montmorillonite KSF clay under mild conditions proceeded rapidly to afford enantiomerically pure 5-substituted pyrazoles 788 (Equation 172) <2004TL6033>. Comparable results were obtained when arylhydrazines were reacted with 2-formyl glycals under microwave irradiation <2004TL8587>. Phenylhydrazine and hydrazine were reacted with 3-acetyl-4-hydroxy-6-methyl-2/7-pyran-2-one to afford 4-acetoacetyl-3-methylpyrazolin-5-ones, which were employed in the synthesis of bipyrazoles and pyrazoloisoxazoles <1999JHC1291>. Reaction of 3,3-dialkyl-6-(trifluoromethyl)-2,3-dihy-dro -pyrones with hydrazine hydrate afforded 3-(trifluoromethyl)-5-substituted-pyrazoles <1998RCB1365>. 

Pyridazines are formed from pyrones or their thioxo analogs or from appropriate pyridones. Pyrones or pyridones react with diazonium salts to give the corresponding hydrazones (187) and (188) which are rearranged under the influence of acid or base into pyridazinones as shown in Scheme 107. On the other hand, kojic acid is transformed with hydrazine into a 1,4-dihydropyridazine and a pyrazole derivative. 4H-Pyran-4-thiones... 

However, chromones react differently, because the phenolic hydroxy group in the ring-opened intermediate is unreactive. Thus, isoxazoles (264) result from the reaction with hydroxylamine, and a pyrazole is formed with hydrazine. y-Pyrones also give pyrazoles with hydrazine. 

Eschenmoser s pyrone 38 on treatment with cyclopropenone ketal 39 in refluxing benzene afforded lactone 40 (73%). Lactone 40 on hydrolysis with acetic acid at 100°C afforded, after deprotection and decarboxylation, tropone 37 (70%). Introduction of the tropolonic hydroxyl group was achieved with hydrazine hydrate in ethanol, to give a mixture of deacetyl-colchiceinamides 41 (53%) and 42 (37%), followed by reaction with ethano-lic potassium hydroxide, which afforded tropolones 43 and 44, respectively. Tropolone 43 was converted to 44 which, therefore, became the major reaction product. Methylation of 44 gave a mixture of enol ether 18 and 45 which were separated by chromatography. 

The ester of isodehydroacetic acid, a derivative of a-pyrone, forms a 3-methylpyrazolin-5-one with hydrazine,407 although in certain papers a-pyrones and hydrazines are said to form 4-acylcarboxylic acid hydrazides408 and A-aminopyridones.409 A point of interest is that even nitrogenous heterocyclic compounds such as quinolin-4-ones... 

In the pyrone series, kojic acid is transformed by hydrazine into 3,6-dihydroxymethyl-4(lfl )-pyridazinone (42). In addition, a pyrazole (43) was isolated as by-product. 5-Methylkojic acid reacted with hydrazine to give only the pyrazole derivative and kojic acid and phenylhydrazine afforded a mixture of both types of compound. ... 

Hydrazine and 2,6-dimethyl-4-pyrone appear to give the bipyridone XII-772. Triaryl-2 -pyrones react with hydrazine and phenylhydrazine to give... 

Reactions of 3-(polyfluoroacyl)chromones 230 with hydrazine hydrate and methyl-hydrazine proceed via nucleophilic 1,4-addition followed by opening of the pyrone ring and heterocychzation at polyfluroacyl group into 4-(2-hydroxyaroyl)-3-(polyfluoroalkyl) pyrazoles 245 or aroyl group into 4-(polyfluoroalkyl)-2,4-dihydrochromeno[4,3-c] pyrazol-4-oles 246 [126] (Scheme 80). 

Although the xanthones contain a ketone oxygen atom, they, like the pyrones (see p. 385), do not react with hydroxylamine, or phenyl hydrazine. 

Glutaroyl chloride and Ar,A -diarylhydrazme have been used to prepare hexahydro-1,2-diazepine-3,7-diones <89CB1503>. Hydrazine and phenylhydrazine with 5-acetyl-4-anisylpyran-2,6-dione afforded different diazepinones (125) and (126), while with 4-anisyl-6-methyl-2-pyrones, they yield the same diazepine, of the type (125) <84H(22)1979>. 

The pyrone ring is opened by heating with aqueous alkalis [24,25], amines [151-155] or hydrazine [13, 157]. Much use has been made of the alkaline hydrolysis of chromones in the determination of structure [185, 186] for example, bromination of 7-hydroxychromone-2-carboxylic acid was shown to proceed at C-8 by degrading the product to 3-bromo-2,4-dihydroxyaceto-phenone (85) [25]. 

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