Oxygen pyrone

The synthesis of a large number of y-pyrones and y-pyranols from enamines has been brought about through the use of a wide variety of bifunctional molecules. These molecules include phenolic aldehydes (126,127), phenolic Mannich bases (128), ketal esters (129), and diketene (120-132). All of these molecules have an electrophilic carbonyl group and a nucleophilic oxygen center in relative 1,4 positions. This is illustrated by the reaction between salicylaldehyde (101) and the morpholine enamine of cyclohexanone to give pyranol 102 in a quantitative yield (127). 

The puzzling discovery of Collie and Tickle in 1899 that 2,6-dimethyl-4-pyrone (8) affords crystalline salts (9) with acids, which were the first monocyclic pj rylinm salts to be isolated, was interpreted by a formula (21) with tetracovalent oxygen.An active period of research followed. The methosulfate or methiodide of 2,6-dimethylpyrone was converted by ammonia into 4-methoxy-2,6-lutidine, therefore, the exocyclic oxygen of the pyrone must be involved in the salt formation. Thus, formula 21 was disproved and formula 22 was demonstrated for these salts. 

Baeyer and Piccard were the first to prepare crystalline monocyclic pyrylium salts without hydroxy or alkoxy substituents, from y-pyrones and Grignard reagents in 1911. They ascribed a correct structure to these salts, although the bonds in the ring and the valency of the oxygen heteroatom remained contested topics for the next 20 years. The discussions around the formula of pyrylium... 

Electrophilic reagents become bonded to the carbonyl oxygen or sulfur atom of (thio)pyrones, leading to pyrylium salts. 

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 lactone-peroxides 17 are derived from the corresponding ot-pyrones. Singlet oxygenation at low temperature affords the unstable a-pyrone endoperoxides which, on warming up, readily decarboxylate into 1,2-diacylethylenes. However, subambient diimide reduction leads to the desired lactone peroxides 17 (Eq. 12)29). 

The cleavage of kojic acid by hot alkali, to fragments containing one to three carbon atoms, could not be definitely shown to commence at the ring oxygen atom, but what was said earlier about y-pyrones in general renders this conclusion probable. 

A 2-step route to oxygenated bicyclo[n.3.0]alkanes via bicyclic 4-pyrones such as 133 has been reported (equation 2)62. Irradiation in hydroxy lie solvents caused ring contraction to the zwitterion, followed by solvent incorporation to give fused bicyclic cyclopentenone 134. Good regioselectivity in favor of solvent capture at the more substituted oxyallyl terminus was seen in differentially substituted examples, presumably due to increased... 

Oxygen-free reactions of psoralens, when in close proximity to the target, proceed via the first excited states in which the 3,4-and the 4, 5 7r-bonds of the pyrone and furan moieties, respectively, can undergo C4-cyclization reactions with, e.g., unsaturated bonds of lipids, or the C5=C6 double bonds of thymine in DNA. In reactions with DNA the psoralen is believed to intercalate with DNA in the dark. Subsequent irradiation at 400 nm usually leads to furan-side 4, 5 -monoadduct formation, whereas irradiation at 350 nm increases the formation of crosslinks in which the furan and pyrone rings form C4 cycloadducts to thymines on opposite strands [95], Subsequent irradiation of the 4, 5 -monoadducts at 350 nm leads to formation of crosslinks and conversion into pyrone-side 3,4-monoadducts. Shorter wave-... 

Structurally related to the triarylmethanes is the xanthene chromogen (1.30), in which two of the aryl nuclei are linked by an oxygen atom to form a pyrone ring. Similar terminal groupings (amino, hydroxy, or both) are usually present. Xanthene dyes have mainly... 

Heterocyclic systems have played an important role in this historical development. In addition to pyridine and thiophene mentioned earlier, a third heterocyclic system with one heteroatom played a crucial part protonation and methylation of 4//-pyrone were found by J. N. Collie and T. Tickle in 1899 to occur at the exocyclic oxygen atom and not at the oxygen heteroatom, giving a first hint for the jr-electron sextet theory based on the these arguments.36 Therefore, F. Arndt, who proposed in 1924 a mesomeric structure for 4//-pyrone, should also be considered among the pioneers who contributed to the theory of the aromatic sextet.37 These ideas were later refined by Linus Pauling, whose valence bond theory (and the electronegativity, resonance and hybridization concepts) led to results similar to Hiickel s molecular orbital theory.38... 

Intermediates such as 224 resulting from the nudeophilic addition of C,H-acidic compounds to allenyl ketones such as 222 do not only yield simple addition products such as 225 by proton transfer (Scheme 7.34) [259]. If the C,H-acidic compound contains at least one carbonyl group, a ring dosure is also possible to give pyran derivatives such as 226. The reaction of a similar allenyl ketone with dimethyl mal-onate, methyl acetoacetate or methyl cyanoacetate leads to a-pyrones by an analogous route however, the yields are low (20-32%) [260], The formation of oxaphos-pholenes 229 from ketones 227 and trivalent phosphorus compounds 228 can similarly be explained by nucleophilic attack at the central carbon atom of the allene followed by a second attack of the oxygen atom of the ketone at the phosphorus atom [261, 262], Treatment of the allenic ester 230 with copper(I) chloride and tributyltin hydride in N-methylpyrrolidone (NMP) affords the cephalosporin derivative 232 [263], The authors postulated a Michael addition of copper(I) hydride to the electron-... 

C16 and H15 to C13, C14 and C17. These correlations established the connectivities of C13-C18. Taking into consideration the number of oxygen atoms contained in 74 and the chemical shifts of C14 and C18, one oxygen atom must be inserted between C14 and Cl8. Thus, the existence of an a-pyrone unit in 74 was confirmed, as shown in Figure 22. 

The same product is obtained from 3-phenylchehdamic acid, the pyrone oxygen of which is already substituted by imino-nitrogen, only three molecules of biguanide being required for the formation of the final product (CXLVII). Similar reactions occur (464) with the parent chelidonic acid and with y-pyrone. 

It has been known since the turn of the century that amongst oxygen-containing compounds crystalline salts with protonic acids are most readily formed by 2,6-dimethyl-4-pyrone [190] (Collie and... 

Tickle, 1899). Which of the two oxygens was the site of proton addition became clear only when Hantzsch (1919) demonstrated the close optical analogy between the salts and methiodides of dimethyl-pyrone and pyridinium salts and argued that a benzene-like ring arises in the pyroxonium salts [191]. The discussion of the structure... 

Degani et al., 1968). A comparison of the basicity of these compounds with those of the corresponding pyridone analogues (2- and 4-quinolones and 9-acridones) is given in Table 4. The order of basicities for these compounds is NH > S > Se > O. They are all protonated on the carbonyl oxygen. Such is the resonance stabilization of the pyrone cations that they do not accept any further... 

The alternative structural situation of an exocyclic methylene group in conjugation with a ring oxygen is found in methylene-4-pyrans (vinylogous pyrones), in which a 4-pyrone-like resonance [230] occurs. These compounds are little known. Their synthesis... 

The use of enolates and ends has not been investigated in such great detail systematically, but 2-pyrones can be made by processes which, formally at least, are related to the above reactions of enamines and enamides (equations 122 and 123). In many 2-pyrone-producing reactions ambiguity exists as to the origin of the ring oxygen atom equation (122) appears... 

Both 1,2- and 1,4-pyrones (91 and 92, respectively) should be mentioned. It also seems appropriate to mention oxygen derivatives of this type, because some properties of these molecules are to a large extent determined by their topology. Properties of the C=Y bonds, the heats of combustion, the UV and IR spectra,88 and dipole moment data... 

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