4- Pyrones 3-hydroxy

A unimolecular pyrolysis/rearrangement sequence leading to stable reaction products without the need for nucleophiles was reported by Katritzky et al. Thus, 6-(2-oxoalkyl)-l,3-dioxin-4-ones, when heated or irradiated, gave 6-substituted-4-hydroxy-2-pyrones in good yields <2005JOC4854>. a,7-Dioxoketenes are discussed as intermediates (Scheme 25). 

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>. 

Schulte and coworkers (62AP801) have prepared a number of 3-propargyl-4-hydroxy-2-pyrone derivatives (210) by condensation of /3-dicarbonyl compounds (208) with propargyl-malonyl chloride (209). On heating (210) with zinc carbonate, ring closure took place to give the corresponding furo[3,2-c]pyrone derivatives (211 Scheme 40). 

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... 

Hovorka SW, Hageman MJ, Schoneich C. Oxidative degradation of a sulfonamide-containing 5,6-dihydro-4-hydroxy-2-pyrone in aqueous/organic cosolvent mixtures. Pharm Res 2002 19 538-545. 

Hydrolysis of 3-methyl-2-aminochromones (e.g., 451) and aminopyrones (e.g., 453) with 10% aqueous hydrochloric acid/ ethanol afforded 4-hydroxycoumarins 452 and 4-hydroxy-2-pyrones 454, respectively (Scheme 80) <1996JOC3218>. 

C-NMR spectroscopy can be a used to differentiate 4-alkoxy-2-pyrones from 2-alkoxy-4-pyrones. Some selected examples are included in Table III. The examples show two differences absortions for C4 carbon atoms are shifted by 10 ppm or more towards lower fields in 4-pyrones as compared with the isomeric 2-pyrones and the same effect is observed for C5 (8-17 ppm). Data for 1 and 2 and other 4-hydroxy-2-pyrones are also included for comparison. Further examples of C-NMR data for isomeric methyl ethers have been reported (83TL1917, 83TL3O55 87JOC5326). 

Detailed studies on 6-alkyI-4-hydroxy-2-pyrones (71ACS3441) and on 2 (67T2807) have been reported. 

Hydroxy-2-pyrones are acidic compounds. Some pK values have been determined in water 1,4.94 2, 5.26 25a, 3.93 [83JCS(P2)471]. Data for the less acidic Schiff bases of 2 are also available [83JCS(P2)1011]. 

Trimerization of ketenes [77HCA3007 89IJC(B)285] and treatment of acetyl chloride with aluminum trichloride (73USP3743658) produce 4-hydroxy-2-pyrones. 

Acetonyl-4-hydroxy-2-pyrone (tetraacetic acid lactone) (73) is also a natural product (67JA676). 

Acetonyl-4-hydroxy-2-pyrone 67JA676 71T3025 67JA676... 

The general behavior of 4-hydroxy-2-pyrones towards aldehydes has been used in the synthesis of helipyrone (92) from 55 (70TL5105 82P243). 

The pronounced tendency of 4-hydroxy-2-pyrones to form enol ethers is the reason for the difficulties encountered on alkylation of position C3, as already discussed. 

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