The synthesis of 5-substituted 3-benzoylamino-6-(2-substituted amino-1-ethenyl)-2H-pyran-2-ones and their transformations into 2H-pyrano[3,2-c]pyridine derivatives

A new approach to the 2H-pyrano[3,2-c]pyridine system is described. 5,6-Disubstituted 3-benzoylamino-2H-pyran-2-ones 3a,b , prepared from the corresponding 1,3-dicarbonyl compounds 1a,b and methyl (Z)-2-benzoylamino-3-dimethylaminopropenoate ( 2 ), were converted into 3-benzoylamino-6-(2-dimethylamino-1-ethenyl)-5-ethoxycarbonyl-2H-pyran-2-one ( 4a ) and 5-acetyl derivative 4b . The exchange of the dimethylamino group in 4a,b with aromatic amines 5a-f,m , héteroaromatic amines 5g-i , and benzylamines 5j-l produced 5-ethoxycarbonyl-3-benzoylamino-6-(2-arylamino- or heteroarylamino-or benzylamino-1-ethenyl)-2H-pyran-2-ones 6a-l , and its 5-acetyl analog 6m . The compounds 6 were cyclized in basic media into 2H-pyrano[3,2-c]pyridine derivatives 7a-h . Analogously react also α-amino acid derivatives 8a-c and 11 as nitrogen nucleophiles producing 9a-c, 10 and 12 .     

Reaction of ketenes with N,N-disubstituted α-aminomethyleneketones. X. Synthesis of N,N-disubstituted 6-alkyl-4-amino-3,3-dichloro-3,4-dihydro-2H-pyran-2-ones and of 6-alkyl-4-amino-3-chloro-2H-pyran-2-ones

Cycloaddition of dichloroketene to N,N-disubstituted 1-amino-4-methyl-1-penten-3-ones and 1-amino-4,4-dimethyl-1-penten-3-ones occurred in moderate to fair yield only in the case of aromatic N-substitution to give N,N-disubstituted 6-alkyl-4-amino-3,3-dichloro-3,4-dihydro-2H-pyran-2-ones, which were dehydrochlorinated with DBN to afford in good yield N,N-disubstituted 6-alkyl-4-amino-3-chloro-2H-pyran-2-ones. In the case of aliphatic N,N-disubstitution, cyclo-addition led directly to 6-alkyl-4-dialkylamino-3-chloro-2H-pyran-2-ones only for N,N-disubstituted 1-amino-4,4-dimethyl-1-penten-3-ones. The reaction between 1-dimethylamino-4-methyl-1-penten-3-one and dichloroketene gave 3-chloro-4-dimethylamino-3,6-dihydro-6-isopropylidene-2H-pyran-2-one in low yield.     

Reaction of ketenes with N,N-disubstituted α-aminomethyleneketones VIII. Synthesis of N,N-disubstituted 4-amino-3-chloro-6-phenyl-2H-pyran-2-ones

The dipolar 1,4-cycloaddition of dichloroketene to N,N-disubstituted 3-amino-1-phenyl-2-propene-1-onesled directly to N,N-disubstituted 4-amino-3-chloro-6-phenyl-2H-pyran-2-ones only in the case of an usual aliphatic N,N-disubstitution. In the case of partial or full aromatic N-substitution, N,N-disubstituted 4-amino-3,3-dichloro-3,4-dihydro-6-phenyl-2H-pyran-2-ones were instead obtained, which were dehydrochlorinated with DBN to the corresponding 4-amino-3-chloro-6-phenyl-2H-pyran-2-ones.     

Reaction of ketenes with N,N-disubstituted α-aminomethyleneketones. XII. Synthesis of N,N-disubstituted 4-amino-3-chloro-6-(2-methyl-l-propenyl) (2-phenylethenyl)-2H-pyran-2-ones

Cycloaddition of dichloroketene to N,N-disubstituted (E)-amino-5-methyl-1,4-hexadien-3-ones IV and (E,E)-1-amino-5-phenyl-1,4-pentadien-3-ones V occurred in moderate to good yield only in the case of aromatic N-substitution to give N,N-disubstituted 4-amino-3,3-dichloro-3,4-dihydro-6-(2-methyl-l-propenyl) (2-phenylethenyl)-2H-pyran-2-ones, which were dehydrochlorinated with DBN to afford in good yield N,N-disubstituted 4-amino-3-chloro-6-(2-methyl-propenyl)(2-phenylethenyl)-2H-pyran-2-ones. In the case of aliphatic N,N-disubstitution (dimethylamino group) of enaminones IV and V, the Cycloaddition led directly in low yield to 3-chloro-4-dimethylamino-6-(2-methyl-l-propenyl)(2-phenylethenyl)-2H-pyran-2-ones.     

Reaction of piperidine and morpholine with 2H-pyran-2-ones, 2H-thiopyran-2-ones, 2H-pyran-2-thiones,and 2H-thiopyran-2-thiones. A novel route to thiophene derivatives

The reaction of piperidine or morpholine with 2H-pyran-2-ones was found to give open chain δ-oxoamides, while with 2H-thiopyran-2-ones, thiophene derivatives were formed. For 2H-pyran-2-thiones, either open chain δ-oxothioamides or thiophene derivatives were obtained. From the ¹ H nmr data of the pyran derivatives, the effect of the replacement of ring and carbonyl oxygens with sulphur on the chemical shift of the H-3 proton could be studied.     

Synthese von einigen 2H-Pyran-2-on-Derivaten

The Synthesis of Some 2H-Pyran-2-one Derivatives Derivatives of 6-unsubstituted 2H-pyran-2-one have been synthesized by several different methods. The 4-chloro-2H-pyran-2-one ( 9 ) is the most important, since it serves as starting material for the synthesis of different 4-substituted 2H-pyran-2-ones (Scheme 2). Also described are simple transformations of cumalic-acid derivatives producing 5-(2,2-dichlorovinyl)-2H-pyran-2-one ( 23 ), 2-oxo-2H-pyran-2-carbonitrile ( 26 ), and 4,5-bis(trifluoromethyl)-2H-pyran-2-one ( 32 ) (Scheme 3 and 4).     

Synthesis and reaction of 6-substituted 3-methoxycarbonyl-4-methylthio-2H-pyran-2-one derivatives

Reaction of aryl and styryl methyl ketones 1a-m with dimethyl bis(methylthio)methylenemalonate ( 2 ) in the presence of potassium hydroxide in dimethyl sulfoxide gave the corresponding methyl 6-aryl- and 6-styryl-4-methylthio-2-oxo-2H-pyran-3-carboxylates 3a-m . 6-Aryl derivatives 3a-d,g were treated with sodium methoxide in methanol to give the corresponding 6-aryl-4-methoxy-2H-pyran-2-ones 8a-d and 9. Phenylcoumalin ( 7a ) and paracotoin ( 7b ) were synthesized by the desulfurization of 6-aryl-4-methylthio-2H-pyran-2-ones 4a,b. Similarly, anibine ( 8e ) was also synthesized from 3g . Treatment of 3 with hydrogen peroxide or 3-chloroperoxybenzoic acid gave the corresponding 4-methylsulfiny-2H-pyran-2-ones 10a-f in good yields. Displacement reactions of 10a-f with nucleophilic reagents are also described.     

Enzymatic resolution of 4-methyl-, 4-phenyl- and 6-phenyltetrahydro-2H-pyran-2-one using esterases

Enantioselective hydrolysis of racemic tetrahydro-2H-pyran-2-ones (δ-valerolactones) using esterase resulted in the formation of optically active (R)-4-methyl-, (R)-4-phenyl- or (R)-6-phenyltetrahydro-2H-pyran-2-ones and the corresponding (S)-8-hydroxypentanoic acid derivatives.     

Reactions of 6-Alkoxy(alkylthio)carbonylamino-4-hydroxy-2H-pyran-2-ones with Some Electrophilic Reagents

Alkoxy(alkylthio)-4-hydroxy-2H-pyran-2-ones readily react with electrophiles to give substitution products at C³. Hard electrophilic reagents replace hydrogen both in position 3 and in position 5 of the pyran ring. Methylation of 6-alkoxy(alkylthio)-4-hydroxy-2H-pyran-2-ones with diazomethane leads to formation of O- and N-methyl derivatives.     

Synthesis of acetylenic β-diketones and their conversion into 4H-pyran-4-ones,pyrazoles, and 1-hydroxy-4-pyridones

A simple method for the synthesis of acetylenic β-diketones is described. They can be cyclized to the corresponding 4H-pyran-4-ones with acids. Their reaction with hydrazine hydrate gave pyrazole derivatives isomeric with those obtained from 4H-pyran-4-ones. With hydroxyl-amine hydrochloride in ethanol, 1-hydroxy-4-pyridones are formed.     

Reaction of some coumarin and 4,6-diaryl-2H-pyran derivatives with secondary amines

The reaction of piperidine, morpholine, piperazine or dimethylamine with several coumarins, 3-bromocoumarin, 4,6-diaryl-2H-pyran-2-ones and 3-bromo-4,6-diaryl-2H-thiopyran-2-ones gave o-hydroxycinnamic acid amides, benzofurans, open-chain δ-oxoamides and thiophene derivatives, respectively.     

A New General Synthesis of 2,2-Dialkyl-2,3-dihydro-4H-pyran-4-ones and Their Application for the in situ Preparation of Electron-Rich Dienes in Carbonyl-Alkyne Exchange Reactions with Acetylenes

The substituted 2,2-dialkyl-2,3-dihydro-4H-pyran-4-ones of type II and III have been prepared by acid-catalyzed cyclization of the corresponding substituted acetylenic ketones I in good to excellent yields (Scheme 1). These 2,2-dialkyl-2,3-dihydro-4H-pyran-4-ones II and III have been used for the in situ preparation of highly reactive dienes of type IV – VI (Scheme 2) in carbonyl-alkyne exchange reactions with electron-poor alkynes VII to yield the highly substituted aromatic compounds VIII and IX. These reactions proceed in good yields and with excellent degree of regioselectivity. Aryl-substituted 2,2-dialkyl-2,3-dihydro-4H-pyran-4-ones III (R¹ = Ar) subsequently yield highly substituted biaryls. Reaction mechanisms are presented for the formation of the 2,2-dialkyl-2,3-dihydro-4H-pyran-4-ones as well as for the carbonyl-alkyne exchange reactions with electron-poor acetylenes.     

Synthesis,Properties, and Biological Activity of 4-Hydroxy-2H-Pyran-2-ones and Their Derivatives

The review summarizes published data on the methods for preparation, chemical properties, and biological activity of 4-hydroxy-2H-pyran-2-ones and their derivatives.     

A new synthesis of 3(2H)-furanones from acetylenic β-diketones

Thermal cyclization of 1,5-diarylpent-1-yne-3,5-diones led to the formation of 2-benzyliden-5-aryl-3(2H) furanones as well as 2,6-diaryl-4H-pyran-4-ones as minor products. The structure of the furanones was established from their ir, ¹H nmr and mass spectral data. Their reaction with hydrazine hydrate gave pyrazole derivatives.     

N,N-Disubstituted 4-amino-3-chloro-5,6-polymethylene-2H-pyran-2-ones

The title compounds were obtained by dehydrochlorination with collidine, DBN or triethyl-amine of N,N-disubstituted 4-amino-3,3-dichloro-3,4-dihydro-5,6-polymethylene-2H-pyran-2-ones already described.     

Stereoselective ring closure of 6-[[(methylamino)carbonyl]oxy]-2H-pyran-3(6H)-ones. Formation of the 5H-pyrano[3,2-d]oxazole-2,6-dione ring system

The stereospecific formation of the 5H-pyrano[3,2-d]oxazole-2,6-dione ring system from 2,2-disubstituted-6-[[(methylamino)carbonyl]oxy]-2H-pyran-3(6H)-one via an enolization at C-5 is presented. The outcome of the same reaction in the case of 2-monosubstituted 2H-pyran-3(6H)-ones is also discussed.     

Hydroalkylation leading to heterocyclic compounds. Part 1: New strategies for the synthesis of polysubstituted 2H-pyran-2-ones

Polysubstituted 2H-pyran-2-ones and 5,6-dihydro-2H-pyran-2-ones were synthesized via the MCRs initiated by the hydroalkylation of alkynoates with activated methylenes. Under the optimized reaction conditions, the desired products were obtained in 47-88% isolated yields. The experimental results showed that the groups on activated methylenes act important roles in the nucleophilic attack fashion.     

Five-Membered 2,3-Dioxo Heterocycles: XLV. Thermolysis of 5-Aryl-4-phenyl-2,3-dihydrofuran-2,3-diones in the Absence of Other Partners and in the Presence of Carbonyl Compounds

Aroyl(phenyl)ketenes generated by thermolysis of 5-aryl-4-phenyl-2,3-dihydrofuran-2,3-diones undergo [4+2]-cyclodimerization to 3-aroyl-6-aryl-3,5-diphenyl-3,4-dihydro-2H-pyran-2,4-diones. Heating of the latter leads to rearrangement with formation of 4-aroyloxy-6-aryl-3,5-diphenyl-2H-pyran-2-ones. Thermolysis of 5-aryl-4-phenyl-2,3-dihydrofuran-2,3-diones in the presence of carbonyl compounds yields 6-aryl-5-phenyl-4H-1,3-dioxin-4-ones.     

Reaction of sulfene and dichloroketene with open-chain N,N-disubstituted α-aminomethyleneketones. Synthesis of N,N-disubstituted 4-amino-3,4-dihydro-(5-methyl-6-phenyl)(5,6-diphenyl)-1,2-oxathiin 2,2-dioxides and of 4-amino-3-chloro-5-methyl-6-phenyl-2H-pyran-2-ones

Cycloaddition of sulfene to N,N-disubstituted 3-amino-2-methyl-1-phenyl-2-propen-1-ones (I) and 3-amino-1,2-diphenyl-2-propen-1-ones (II) occurred in good to moderate yield only in the case of aliphatic N-substitution to give 4-dialkylamino-3,4-dihydro-(5-methyl-6-phenyl)(5,6-diphenyl)-1,2-oxathiin 2,2-dioxides. Polar 1,4-cycloaddition of dichloroketene to I and II occurred only in the former case, giving in good to moderate yield N,N-disubstituted 4-amino-3,3-dichloro-3,4-dihydro-5-methyl-6-phenyl-2H-pyran-2-ones which were dehydrochlorinated with DBN to N,N-disubstituted 4-amino-3-chloro-5-methyl-6-phenyl-2H-pyran-2-ones. In the reaction of 2-methyl-1-phenyl-3-diphenylamino-2-propen-1-one with dichloroketene, a product was isolated which was proven by uv, ir, nmr and chemical evidence to be the dipolar ion VI, the supposed intermediate of the polar 1,4-cycloaddition of dichloroketene to N,N-disubstituted enaminones.     

α-pyrones. III Synthesis of 5,6-dihydro-1H-benzo[c]-quinolizin-1-ones from 6-(2-nitrostyryl)-2H-pyran-2-ones

The 6-(2-nitrostyryl)-2H-pyran-2-ones 1 were reduced with hydrogen over Pd/C at room temperature and atmospheric pressure giving the 2-benzoylamino-4-(1,2,3,4-tetrahydro-2-quinolinylidene-2-pentenedioic acid derivatives 2 which were converted, without isolation, into the 5,6-dihydro-1H-benzo[c]quinolizin-1-ones 4 in refluxing acetic anhydride. When α-aminoacids 2 were treated with acetic anhydride at room temperature oxazolones 3 were isolated, while by heating quinolizines 4 were found. Compounds 3 were transformed into 4 in refluxing acetic acid or anhydride.