Heterocycles pyranones

Coverage is restricted to halogenation of conjugated heterocycles. Although not all of these can be classified as aromatic (e.g., pyranones, fulvalenes), there are aspects of their reactivities that have parallels in the series traditionally classified as heteroaromatic. Processes that produce a halogenoaromatic product from a nonaromatic substrate (e.g., quinolone to chloroquinoline) are usually included. 

In another example of the ease of polycondensation of heterocyclic diesters, diethyl 4-pyranone-2,6-dicarboxylate (diethyl chelidonate) (130) has been reported to undergo rapid polymerization at room temperature when mixed with 1,6-hexanediamine (Scheme 38) (75MI11104). The polymerization is believed to occur subsequent to an initial CT complex formation, and was accelerated in the presence of direct sunlight. 

Pyrazolinones belong to the heterocyclic class of coupler and are widely used the sulfonamide (124) is representative of this type (51USP2537098). Substituted thiophenes (125) (58GEP1025265) and hydroxypyridones (126) (47USP2431190) are couplers which form blue-violet dyes resistant to light. Pyranones (127), analogous to the latter, have also been used (51USP2542849). 

Disparity between the observed moment and that calculated by vector addition of the individual group moments may indicate that the actual structure is not truly represented by the simple molecular diagram. There are several instances of the application of this technique to structural investigations in the field of O- heterocyclic chemistry, not the least of which is the question of the aromaticity of pyranones and their benzologues. 

In this approach to pyranone synthesis, it is thought that the carbanionic site in the betaine attacks the cyclopropenone in a Michael fashion. Subsequent opening of the three-membered ring may lead directly to the pyranone (route a) or the heterocyclic system may form via the ketene (route b Scheme 98). 

A convenient preparation of pyran-4-ones involves heating carboxylic acids or their anhydrides in polyphosphoric acid (67JCS(C)828). Yields are satisfactory, although when the synthesis is applied to a mixture of acids, a mixture of pyranones results. Only symmetrical pyranones (421) are formed, suggesting that the anhydride, rather than the acid, is the precursor of the heterocycle (Scheme 141). 

From a preformed heterocyclic ring (i) From pyranones... 

Three dimers are formed269 from the related oxygen heterocycle, 4,6-dimethyl-2-pyranone, by photolysis in benzene two of these are... 

Hydroxy-2H-pyranones-2. These heterocycles are formed on reaction of si-lyl enol ethers with carbon suboxide in ether at — 20 - 250.1... 

Furanones and pyranones are oxygen-containing heterocyclic compounds associated with caramelized flavor notes. Most common flavors of these compounds are caramel-like, sweet, fruity and burnt (40). 2,5-Dimethyl-4-hydroxy-3(2H)-furanone (DMHF) was one... 

Studies on the tautomerism of heterocycles, including pyrans and derivatives, have been extensively reviewed <2006AHC(91)1>. Computational studies have been used to examine a number of 3-hydroxy-4-pyranones such as maltol 68, ethyl maltol 69, and pyromeconic acid 70, and it has been determined that the 3-hydroxy-4-oxo tautomer is the most stable <2003JMT(639)87>. 

The thiopyranopyrandione derivative (92) is reduced by lithium borohydride yielding the product (93) in moderate yield <88JCS(Pl)663>, and the chiral heterocycle (94) gives the chiral 2-pyranone derivative (95) when treated with nickel boride <9iH(32)i875>. 

Fused pyranone derivatives are converted into the corresponding fused pyridone derivatives by the action of an appropriate amine. Thus, heterocycle (308) yields naphthyridone (417) in moderate yield when reacted with ethanolic ammonia solution <62JCS4528>. Compound (418) and tryptamine gives the indole derivative (419) (82% yield) <76H(4)247>, which was used in the synthesis of nauclefine (420), and compound (421) and tryptamine gave heterocycle (422) (80% yield) <75H(3)627>, which was used in the synthesis of angustine (423). 

Tellurachromanone, and similar heterocycles with thiophene fused to the pyranone ring, are derived from aryl tellurium bromides bearing a 3-./V,Ar-dimethylamino-prop-2-cn-oyl substituent in the ortho-position in refluxing pyridine in the presence of an excess of hypophosphorous acid. These formations can be regarded as the intramolecular addition of the tellurium bromide to the olefin1. 

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>. 

The same reaction has been also carried out with heterocyclic aminomethyleneketone derivatives of, e.g., 4-pyranones, chromanones and derivatives and 4-piperidones (equation 202). A useful dienophile is dichloroketene, produced from dichloroacetyl chloride and triethylamine. It enables the enaminone oxygen to be incorporated into the functional group of a lactone instead of a sultone (equation 202). 

Heterocyclic enones seem to be much more efficient acceptors in the TMM-Pd addition26. The product from a pyranone is formed in near-quantitative yield as a single m-fused stereoisomer the degree to which pre-existing stereochemistry in the substrate can influence the product distribution is discussed in more detail in Section 1.6.1.2.3.2. 

In contrast, on the basis of a new aromaticity index (Ig) for six-membered heterocycles, 1,2,6-thiadiazin-4-one 1,1-dioxide (60) has been assigned an value of 54.2 (benzene 1 = 100) and is reckoned to have moderate to low aromatic character and is deemed to be more aromatic than pyranones but less aromatic than 4-pyridones <86T89>. 

Additional general reactions are the synthesis of 11 -acyldipyridoimidazolium salts such as (174 R = Ac, Bz) by condensation of l-acylmethyl-2-chloropyridinium salts with pyridine and substituted pyridines under mild conditions <76CB3646, 77LA1692), and a 1,3-dipolar cycloaddition of a nitrone (196) with heterocyclic alkenes. A derivative (198) of the parent system (35) has been obtained by the reaction of (196) with 5,6-dihydro-2-pyranone (197) (Equation (10)) <93T3857>. A similar reaction occurs with 2,3-dihydropyran yields (172), a perhydro derivative of the parent system (34) <82JOC230, 90JCS(P1)2593>. 

An important role play carbonyl-bearing heterocycles, e.g. 2H- and 4//-pyranones, pyridones, diazinones and the benzo systems derived thereof, as well as hydrogenated heteroarenes like tetrahydropyrane, chromane, piperidine, morpholine and piperazine. 

An interesting application of this oxidizing agent is in the formation of spiroisoxazolines from o-hydroxyarylacetoxime derivatives, as well as the more well-known transformation of 2-(l-hydroxyalkyl)furans to the pyranones. The cycloamination of an aromatic compound bearing a sulfonamide side chain provides access to A-heterocycles. 

Tsubuki, M., K. Kanai, and T. Honda Enantioselective Synthesis of 6-Substituted 5,6-Dihydro-a-pyranones, (-f)-Goniothalamin and (-)-Argentilactone. Heterocycles, 35, 281 (1993). 

Similarly, pyran rings are a common early-stage synthetic intermediate in a variety of syntheses. In Kutay and Gademann s synthesis of anguinomycin C, they prepare the heterocyclic portion of the target by combination an electron-rich diene with an unsaturated aldehyde in the presence of Jacobsen s chromium (III) catalyst. Ghosh used the same asymmetric catalyst to promote the reaction of an aldehyde and an electron-rich diene in his synthesis of brevisamide. Rawal synthesized a pyranone for use in his synthesis of pederin by combination of a chiral dienophile with Danishefsky s diene. In his synthesis of phorboxazole B, Burke treated Brassard diene 119 with chiral aldehyde 118 and a europium catalyst to yield pyranone 120. ... 

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