Synthesis,halogenation, and nitration of 6-methyl-3-phenyl-2-pyrone derivatives

Simple methods for the synthesis of 3-aryl-6-methyl-2-pyrones and 3-aryl-5-carbalkoxy-6-methyl-2-pyrones by the reaction of ethyl -formylarylacetates with acetone and acetoacetic acid esters, respectively, are proposed. Some electrophilic substitution reactions of 6-methyl-3-phenyl-2-pyrone and 5-carbethoxy-6-methyl-3-phenyl-2-pyrone were studied.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1477–1480, November, 1985.     

Fast atom bombardment mass spectrometry of reaction products between C3O2 and stabilized phosphorus ylides

A fast atom bombardment (FAB) mass spectrometric study on the open-chain compound 1,3-bis(cyanomethylenetriphenylphosphorane)propane-1,3-dione and on the cyclic zwitterionic compounds 4-oxy-5-triphenylphosphonium-6-methyl-2-pyrone and 4-oxy-5-triphenylphosphonium-6-phenyl-2-pyrone, obtained by reaction of carbon suboxide, C₃O₂, with stabilized phosphorus ylides, Ph₃PCHX (X?CN, COMe, COPh), is described. The FAB mass spectrometric behaviour of these compounds is compared with that shown by tri-phenylphosphoranilideneketene, Ph₃P ? C ? C ? O, and by 4-hydroxy-6-methyl-2-pyrone, with the aid of metastable ion data and collision spectroscopy.     

Stereoselective total synthesis of (+)-strictifolione and (6R)-6[(E,4R,6R)-4,6-dihydro-10-phenyl-1-decenyl)-5,6-dihydro-2H-2-pyrone

The stereoselective total synthesis of two naturally occurring α-pyrone derivatives, (+)-strictifolione and (6R)-6[(E,4R,6R)-4,6-dihydroxy-10-phenyl-1-decanyl]-5,6-dihydro-2H-2-pyrone has been accomplished involving the Sharpless kinetic resolution and olefin cross-metathesis as the key reactions.     

A study of the acylation of 4-hydroxy-6-methyl-2-pyrone and 4 hy(lroxy-6-phenyl-2-pyrone

The acylation of 4-hydroxy-6-melhyl-2-pyrone (1) and 4-hydroxy-6-phenyl-2-pyrone (XXII) with aliphatic acid anhydrides, or with aliphatic acid chlorides in trifluoroacetic acid, has been found to product; first the corresponding ester, which then rearranges, partially or wholly, depending on the conditions and on the nature of the acyl moiety, to form the corresponding 3-acylpyrone. With aromatic acid chlorides in pyridine or in trichloroacetic acid only the corresponding ester was obtained. These esters, however, could be rearranged to the corresponding 3-acylpyrones with aluminum chloride. Acetoaeetylation of 1 and 4-hydroxycoumarin (XXIX) with diketene gave, in both cases, the C-acetoacetylated product.     

Ring closure of 1-[4-(imidazol-1-yl)phenyl]-3-phenyl-2-propen-1-one derivatives to potential biologically active compounds

1-[4-(Imidazol-1-yl)phenyl]-3-phenyl-2-propen-1-one 1 reacted with acetone cyanohydrin, ethyl phenylacetate and cyanoacetamide to give the adducts 2, 8 and 10 respectively. Action of hydrazine hydrate on both the γ-ketonitrile 2 and the corresponding γ-ketoacid 4 led to pyridazine derivatives 3 and 5 . 4,5-Dihydropyridazinone 5 was dehydrogenated by the action of bromine in acetic acid to give pyridazinone 6 . Cyclization of acid 8 in acetic medium resulted in α-pyrone 9 . Cyanopentanamide 10 was converted with hydrochloric acid into δ-ketoacid 13 which led to α-pyrone 14 via an intramolecular dehydration. Refluxing 10 in the presence of acetic acid and ammonium acetate gave 3,4-dihydropyridone 11 which was dehydrogenated to produce pyridone 12 .     

A one-pot reaction of (chlorocarbonyl) phenyl ketene with β-ketoamides and thiochromen-2-one

Readily available (chlorocarbonyl)phenyl ketene and a varied set of β-ketoamides were reacted in a one-step procedure to produce 2-pyrone derivatives. β-Ketoamide derivatives are versatile intermediates for the synthesis of heterocyclic compounds. For instance, 1-morpholino-3-phenyl-1,3-propanedione, 1-phenyl-3-piperidino-1,3-propanedione, 1-phenyl-3-pyrrolidino-1,3-propanedione, 1-piperidino-1,3-butanedione, 1-morpholino-2-phenyl ethanone were used in these reactions to produce 2-pyrone derivatives. In addition, the preparation of 4-hydroxy-3-phenylthiochromeno[4,3-b]pyran-2,5-dione derivatives and 4-hydroxy-7-methyl-3-phenyl pyrano[3,2-c]chromeno-2,5-dione were described. For the synthesis of these compounds 4-hydroxy-2H-thiochromen-2-ones and 4-hydroxy-8-methyl-2H-chromen-2-one were reacted with (chlorocarbonyl)phenyl ketene and the final products were isolated in good yields.     

Convenient replacement of the hydroxy by an amino group in 4 hydroxycoumarin and 4-hydroxy-6-methyl-2-pyrone under microwave irradiation

The reaction of 4-hydroxycoumarin (1) with some primary amines 2a-h and morpholine (2i) under microwave irradiation occurred without opening of the lactone ring to give N-substituted 4-aminocoumarins 3a-i in excellent yields. Under the same experimental conditions, 4-hydroxy-6-methyl-2-pyrone (4) reacted with benzylamine (2e) or 2-phenyl- ethylamine (2f) to give the corresponding N,N'-disubstituted 4-amino-6-methyl-2-pyridones 5e,f. The main advantages of this procedure are dramatically shortened reaction times, higher amine utilization and considerably improved yields.     

Zur Reaktion von Diketen mit Keton-anilen

Zusammenfassung Die Umsetzung von Diketen (1) mit Cyclanonanilen (2) gibt als Hauptprodukte 5.6-Polymethylen-4-pyridone (5) neben, geringen Mengen von 4-Pyronderivaten (4). Bei der Umsetzung von1 mit Aralkylketonanilen6 entstehen, außer den entsprechenden 4-Pyridonen8 beträchtliche Mengen an 1-Phenyl-1.5-bis-(phenylamino)-1.4-hexadien-3-onen (7), welche beim Erhitzen mit HCl Ringschluß zu8 erleiden. Benzoylessigester (9) reagiert mit1 zum 3-Acetyl-4-hydroxy-6-phenyl-2-pyron (11).

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Syntheses of heterocycles, CLIII: Reaction of diketene with ketone aniles

The reaction of diketene (1) with cyclanone aniles (2) gives mainly 5.6-polymethylene-4-pyridones (5) besides some 4-pyrone derivatives (4). The action of1 on aralkyl ketone aniles (6) yields the corresponding 4-pyridones (8), and a considerable amount of 1-phenyl-1.5-bis-(phenylamino)-1.4-hexadien-3-ones (7). The latter undergo ring closure (with HCl) affording the 4-pyridones (8). Diketene (1) reacts with ethyl benzoylacetate (9) yielding 3-acetyl-4-hydroxy-6-phenyl-2-pyrone (11).

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Aus der DissertationI. Herbst, Universität Graz, Februar 1968.     

Reactions of regioisomeric 3,3-dimethyl- and 2,2-dimethyl-6-trifluoromethyl-2,3-dihydro-4-pyrones with N-nucleophiles

Reactions of 2,2-dimethyl-6-trifluoromethyl-2,3-dihydro-4-pyrone with ethylenediamine, hydrazine, or hydroxylamine yield 5-methyl-7-trifluoromethyl-2,3-dihydro-1H-1,4-diazepine, 3(5)-(2-hydroxy-2-methylpropyl)-5(3)-trifluoromethylpyrazole, and 5-hydroxy-3-(2-hydroxy-2-methylpropyl)-5-triflouromethyl-Δ², respectively. The same compounds were obtained from 2-amino-1,1,1-trifluoro-6-hydroxy-6-methylhept-2(Z)-en-4-one and 2-hydroxy-6, 6-dimethyl-2-trifluoromethyltetrahydro-4-pyrone.     

Generation of diverse 2-pyrones via palladium-catalyzed site-selective Suzuki-Miyaura couplings of 3-bromo-4-tosyloxy-2-pyrone

Based on different reactivity of the (pseudo)halide substituents in the 2-pyrone (3-Br and 4-OTs), palladium-catalyzed sequential site-selective Suzuki-Miyaura cross-coupling reactions of 3-bromo-6-methyl-4-tosyloxy-2-pyrone are described, which afford the diverse 2-pyrones in good yields.     

Brominated derivatives of 4-hydroxy- and 4-methoxy-6-methyl-2H-pyran-2-ones

Twenty-five different brominated derivatives of 4-hydroxy-6-methyl-2-pyrone (triacetic acid lactone) and 3-acetyl-4-hydroxy-6-methyl-2-pyrone (dehydroacetic acid) have been prepared. Fifteen derivatives have not been previously described and the preparations of a few known products have been improved. Bromination at C-3, C-5, methyl group at C-6 and deacetylations at C-3 have been the types of reactions used.     

Prototropie et synthèses nouvelles dans la série des dihydro-5,6 hydroxy-4 pyrones-2 et pyridones-2

The multistep catalytic reduction of 6-methyl-4-hydroxy-2-pyrone allows isolation of two intermediate compounds: the biologically active parasorbic acid ( 5 ) and the 6-methyl-5,6-dihydro-4-hydroxy-2-pyrone ( 2 ). The desmotropic keto-enol equilibrium lies on the enol side, with the 4rhydroxy structure. Primary arylamines readily react with 2 , leading to corresponding 2-pyridones 8 ; with methylamine, the aliphatic intermediate 7 resulting from ring attack at the 2 position can be isolated. Also further functionnalization of both dihydropyrone and 2-pyridone is possible by selective bromination at position 3.     

Preparation of 6-(nitron-c-yl)- and 6-(1,3-butadienyl)-2-pyrones and their cycloaddition reactions

6-(N-Substituted nitron-C-yl)-2-pyrones 1 and 6-(4-substituted 1,3-butadienyl)-2-pyrone 2 were prepared and their cycloaddition reactions with three kinds of diene systems were investigated. Namely, the reactions of 1 with methyl acrylate, vinyl crotonate and divinylsulfone took place at the nitrone moiety to afford 3-substituted isoxazolidines 9–14 , and that of 2 with maleimide took place at the 2-pyrone moiety to give a bis-adduct 17 via elimination of carbon dioxide.     

Total syntheses of (+/-)-crinine, (+/-)-crinamine, and (+/-)-6a-epi-crinamine via the regioselective synthesis and Diels-Alder reaction of 3-aryl-5-bromo-2-pyrone

We have devised a new unified synthetic protocol to (+/-)-crinine, (+/-)-crinamine, and (+/-)-6a- epi-crinamine from the Diels-Alder cycloadduct of 3-(3,4-methylenedioxyphenyl)-5-bromo-2-pyrone with TBS vinyl ether. The requisite 3-(3,4-methylenedioxyphenyl)-5-bromo-2-pyrone was prepared from the C3-selective Stille coupling reaction of 3,5-dibromo-2-pyrone. Also noted is that the vinyl bromide can be used as a handle for further derivatization.     

Halo-2-pyrones in the Ullmann reaction. 1

The Ullmann reaction was used for the first time for the synthesis of poly-2-pyrones. 3-Halo-2-pyrones were obtained by halogenation of the corresponding 6-aryl-2-pyrones. The Ullmann reaction was carried out by heating a mixture of the 3-halo-2-pyrone with activated copper in a stream of an inert gas. The reaction products were the previously undescribed bis-2-pyrones, in which the -pyrone rings are interlinked by means of the 3-C atoms.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 173–176, February, 1979.     

Reactions of 2- and 4-pyrones with secondary phosphine chalcogenides: a facile synthesis of functional phosphorylated pyrones

The oxidative cross-coupling between 4-hydroxy-6-methyl-2-pyrone or 3-hydroxy-2-methyl-4-pyrone and secondary phosphine chalcogenides proceeds in CCl₄/Et₃N under mild conditions (20–52 °С, 0.75–10 h) through the hydroxyl group to give O-(6-methyl-2-oxo-2H-pyran-4-yl) diorganylphosphinochalcogenoates or O-(2-methyl-4-oxo-4H-pyran-3-yl) diorganylphosphinochalcogenoates, in high yields.     

Reaction of pyridinium disubstituted methylides with diphenylcyclopropenethione

Diphenylcyclopropenethione undergoes nucleophilic attack by pyridinium disubstituted ylides 1a-1e to produce the corresponding 2-pyranthione 3a , 2-pyrone 4a or 4c , thiopyran-2-one 6a, 6b, 6d or 6e , and/or 5H-thieno[3,2-b]thiopyran 5a .     

Studies on triacetic acid lactone-annulated heterocycles: synthesis of 3-aryloxyacetyl-6-methyl-2,3-dihydrothieno[3,2-c]pyran-4-ones by tandem cyclization

The hitherto unreported 3-aryloxyacetyl-6-methyl-2,3-dihydrothieno[3,2-c]pyran-4-ones were synthesized in 62–71% yield by the sulfoxide rearrangement of 4-(4′-aryloxybut-2′-ynylthio)-6-methyl-2-pyrone. The substrates were synthesized by phase-transfer-catalysed alkylation of the hitherto unreported 4-mercapto-6-methylpyran-2-one.     

Regioselectivity in the Sonogashira coupling of 4,6-dichloro-2-pyrone

The Sonogashira cross-coupling of 4,6-dichloro-2-pyrone with terminal acetylenes proceeds in good yields and high regioselectivity for the 6-position; dibenzylidene acetone (dba) type ligands play a non-innocent role in reactions mediated by Pd(dba)2/PPh3; theoretical studies indicate that C-6 oxidative addition is favoured both kinetically and thermodynamically.     

Synthetic studies of fluorine-containing compounds for household insecticides

The discovery stories of three fluorine-containing insecticides in our laboratory are described, i.e. amidoflumet, a new trifluoromethanesulfonanilide with high miticidal activity against various house dust mites, Metofluthrin, a potent new fluorinated pyrethroid with extremely high knockdown activity against various mosquitoes, and a new α-pyrone compound, 3-[1R-trans-(2-trifluoromethyl)cyclopropanecarbonyl]-4-hydroxy-6-methyl-2-pyrone with outstanding insecticidal activity against Blattella germanica.