Chromone with hydroxylamine

The fragmentation pattern of isoxazoles on electron impact has been well studied. It has been used as an important tool for the structural assignment of isoxazoles obtained from the reaction of chromones with hydroxylamine 79MI41600, 77JOC1356). For example, the structures of the isoxazoles (387) and (388) were assigned on the basis of their fragmentation patterns. Ions at mje 121 (100%) and mje 93 (19.8%) were expected, and indeed observed, for the isoxazole (388), and an ion at mje 132 (39.5%>) was similarly predicted and observed for the isoxazole (387). 

Sosnovskikh VY, Moshkin VS, Kodess MI (2008) Reactions of 3-(polyfluoroacyl)chromones with hydroxylamine synthesis of novel R -containing isoxazole and chromone derivatives. Tetrahedron 64 7877-7889... 

A companion volume has been published which brings up to date an important treatise on flavonoids. The final part of a comprehensive review of pyrylium salts provides full documentation of this field which has also been reviewed in Russian. The synthesis and reactions of kojic acid have been reviewed as also (in Japanese) have those of 1,4-dithiins. The proceedings of the 6th International Symposium on Flavonoids and Bioflavonoids (1981) have been published and contain both reviews and shorter original contributions. Amongst the former are reviews on such topics as the reactions of chromones with hydroxylamine, the synthesis and reactions of 3-acylchromones, chemical and biomimetic studies on condensed... 

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. 

With hydroxylamine, the pyrylium salt 115 undergoes ring opening to an intermediate 1,5-enedione oxime 116 intramolecular conjugate addition of the, -unsaturated ketone gives 117, which in the presence of acid forms the isoxazole 118 (Scheme 61). Likewise, the reaction of pyrylium salt 115 with a hydrazine results in the pyrazoline 119. A similar transformation of chromone is described in Section 3.2.1.6.4.4. 

A series of new substituted oestradiols has been synthesized. The reaction of oestradiol with acetyl chloride gave the 2-acetyl derivative (133a). Condensation with ethyl formate (see Scheme 11), followed by brief exposure to acid, afforded the steroidal chromone (134). Whereas treatment of (134) with hydrazine hydrate provided the 3 -phenylpyrazole (135), reaction with hydroxylamine yielded a mixture of the 5 -phenylisoxazole (136) and of the isomeric 3 -phenyl-isoxazole (137). When the oxime (133b) was allowed to react with benzenesul-phonyl chloride in pyridine solution, the methylbenzoxazole (138) was obtained. 

Chromones behave similarly towards both hydroxylamine and hydrazines. Ring opening via C-2 followed by recyclization giving azoles is of preparative interest. This is demonstrated by the reaction of chromone with phenylhydrazine, which leads either to the phenylhydrazone 5 or (via the enehydrazine 4) to the pyrazole 6 ... 

The final target, 3-(IH-tetrazol-5-yl)chromones (5), were synthesized by the reaction of sodium azide in the presence of anhydrous aluminum chloride and 4-OXO-4H-1-benzopyran-3 -carbonitri les ( ) which were obtained in one step from with hydroxylamine (22, 2 ) (Figure 2). 

The reaction of hydroxylamine with 2-substituted chromones (392) where R = Me, Ph (76MI41601) or CO2H (79MI41600) gave exclusively 5-(o-hydroxyphenyl)isoxazoles (393). 

Hydroxylamine reacts with chromone to give different products according to the reaction conditions in dry methanol, hydroxylamine hydrochloride produces chromone oxime in ethanolic solution, ring opening and re-closure produces isoxazoles. Both types of product are formed via adducts in which a nucleophile has added to C-2. In the former case, the oxime is formed not by direct attack on the carbonyl group of the chromone but via a methanol C-2 adduct. 

Scheme 74 Reactions of chromones 226 with hydrazine and hydroxylamine...

When 3-cyano-2-(polyfluoroalkyl)chromones 229, prepared from 3-(polyfluoro-acyl)chromones 230 (see Sect. 3.4.1), were treated with H2SO4, amides 231 were obtained in high yields. Heterocyclization of 229 with hydrazines, hydroxylamine and acetamidine resulted in pyrazoles 232, 5-aminoisoxazole oxime 233, and pyrimidin-5-ones 234 in variable yields [117] (Scheme 75). 

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