New synthesis of 2(1H)-pyridone derivatives

The reaction of N¹-acyl-2-ethoxycarbonylacetamidrazones 1 with diethyl ethoxymethylenemalonate (EMME) is reported. By refluxing equimolecular amounts of 1 and EMME in DMSO/toluene (or ethanol) solution, the 1-acylamino-2(1H)-pyridones 2 were obtained in good yield. When the reaction was performed in ethanolic solution in the presence of triethylamine, the 6-acylhydrazino-2(1H)-pyridones 3 were obtained.     

Synthesis of 4-methylthio-2(1H)-pyridone derivatives using ketene dithioacetals

Reaction of various active methylene compounds with ketene dithioacetals, bis(methylthio)methylenemalononitrile (1a) and bis(methylthio)methylenecyanoacetamide (1b) gave the corresponding 3-cyano-4-methylthio-2(1H)-pyridone derivatives. The transformation of 4-methylthio-2-oxo-2H-pyran-3-carbonitrile in-to 4-methylthio-2(1H)-pyridone derivatives was also described.     

Novel reaction of carbon suboxide. Synthesis of 6-amino-4-hydroxy-2(1H)-pyridone derivatives

The reaction of 2-cyanoacetamidines 1 with carbon suboxide 2 afforded 6-amino-4-hydroxy-2(1H)-pyri-dones 4 . Compounds 4 were also obtained by reaction of amidines 1 and 2,4,6-trichlorophenylmalonates 3 .     

1H and 13C spectral assignment of 2(1H)-pyridone derivatives

1H and 13C NMR spectroscopic data for 4-aryl-3,4-dihydro-6-methyl-2(1H)pyridone derivatives were fully assigned by a combination of one- and two- dimensional experiments (DEPT, HMBC, HMQC, COSY, NOE).     

5-甲基-2(1H)吡啶酮的合成

以5-甲基-2-氨基吡啶为起始原料,通过重氮盐水解反应,合成了5-甲基-2(1H)吡啶酮,并对其合成工艺进行了研究,其结构经IR确证。     

Synthesis of 4-chloro-7-ethoxy-2(3H)-benzoxazolone-6-carboxylic acid

As a part of metabolic studies of mosapride ( 1 ), a potential gastroprokinetic agent, the synthesis of 4-chloro-7-ethoxy-2(3H)-benzoxazolone-6-carboxylic acid ( 7 ) as a derivative of 4-amino-5-chloro-2-ethoxy-3-hydroxybenzoic acid ( 6 ), which has served a benzoic acid part of the metabolites 4 and 5 , is described. Treatment of methyl 3-amino-4-substituted amino-5-chloro-2-ethoxybenzoate derivatives 11a-c with sodium nitrate in acidic medium gave the benzotriazole derivatives 13x,y instead of the objective 3-hydroxy counterpart. The synthesis of 7 started from o-vanillin acetate ( 15 ) and proceeded through the intermediates 2-hydroxy-3-methoxy-4-nitrobenzaldehyde ( 18 ), methyl 4-amino-2,3-dihydroxybenzoate ( 23 ), and methyl 7-hydroxy-2(3H)-benzoxazolone-6-carboxylate ( 30 ). Compound 30 was alternatively prepared from 23 via methyl 4-ethoxycarbonylamino-2-ethoxycarbonyloxy-3-hydroxybenzoate ( 29 ), which is the product resulting from the migration of the ethoxycarbonyl group of methyl 4-amino-2,3-diethoxycar-bonyloxybenzoate ( 27 ).     

C-acylation of heterocyclic keto-enols Communication 9. Acetyl derivatives of 4-hydroxy-6-methyl-1-phenyl-2(1H)-pyridone

Conclusions A study was made of the acetylation of 4-hydroxy-6-methyl-1-phenyl-2(1H)-pyridone with acetic acid in presence of polyphosphoric acid and of phosphoryl chloride. The structures of the C- and O-acetyl derivatives obtained were proved by independent synthesis and from IR and UV spectral data.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 9, pp. 1605–1607, September, 1966.     

Spectroscopic studies on methyl torsional behavior in 1-methyl-2(1H)-pyridone, 1-methyl-2(1H)-pyridinimine, and 3-methyl-2(1H)-pyridone. I. Excited state

The laser induced fluorescence excitation and dispersed fluorescence spectra of three nitrogen heterocyclic molecules 1-methyl-2(1H)pyridone (1MPY), 1-methyl-2(1H)pyridinimine (1MPI), and 3-methyl-2(1H)pyridone (3MPY) have been studied under supersonic jet cooled condition. The methyl torsional and some low frequency vibrational transitions in the fluorescence excitation spectrum were assigned for 1MPY. These new assignments modify the potential parameters to the methyl torsion reported earlier. Some striking similarities exist between the torsional and vibrational transitions in the fluorescence excitation spectra of 1MPY and 1MPI. Apart from pure torsional transitions, a progression of vibration-torsion combination bands was observed for both these molecules. The excitation spectrum of 3MPY resembles the spectrum of its parent molecule, 2-pyridone. The barrier height of the methyl torsion in the excited state of 3MPY is highest amongst all these molecules, whereas the barrier in 1MPI is higher than that of 1MPY. To get an insight into the methyl torsional barrier for these molecules, results of the ab initio calculations were compared with the experimental results. It was found that the conformation of the methyl group undergoes a 60 degrees rotation in the excited state in all these molecules with respect to their ground state conformation. This phase shift of the excited state potential is attributed to the pi*-sigma* hyperconjugation between the out-of-plane hydrogen of the methyl group and the molecular frame. It has been inferred that the change in lowest unoccupied molecular orbital energy plays the dominant role in the excited state barrier formation.     

Synthesis and functionalization of 4-arylamino-2-pyridone derivatives

New approaches to the synthesis of the previously unknown pyrimidine, 4-amino-2-pyridone, and 4-aminopyridine derivatives were developed based on the reactions of enaminoamides with dimethylformamide dimethyl acetal. New structural modifications of 4-amino-2-pyridone derivatives were performed. Numerous compounds of this type, which are of interest for biological studies, were prepared. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1421–1432, August, 2006.     

Synthesis of tri- and tetramethylene[b]pyrrole derivatives from 2-(1-ethoxy-2-bromoethyl)cycloalkanones

Tri- and tetramethylene[b]pyrrole derivatives were synthesized by treatment of the corresponding 2-(1-ethoxy-2-bromoethyl)cycloalkanones with an aqueous solution of sodium hydroxide and a methanol solution of a primary amine. The transformation proceeds through a step involving 1,3-dehydrobromination and opening of the three-membered ring in the intermediately formed spirocyclic ketones.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 37–39, January, 1992.     

Nucleosides and nucleotides. 2. Synthesis of both anomers of 1-(5'-O-phosphoryl-2'-deoxy-D-ribofuranosyl)-2(1H)-pyridone

The two anomeric 1-(2′-deoxy-D -ribofuranosyl)-2(1H)-pyridones 6 and 7 were synthesized from 2-pyridone and 3,5-di-(O-p-toluoyl)-2-deoxy-D -ribofuranosyl chloride ( 2 ) via the di-O-p-toluoyl derivatives 3 and 4 using the mercuric halide procedure. Phosphorylation of the nucleosides 6 and 7 by bis-(2,2,2-trichloroethyl)-chlorophosphate gave the phosphate esters 8 and 9 together with some 2-(bis-[2,2,2-trichloroethyl]-phosphoryloxy)-pyridine 10 , which proved to be very labile. Structure and configuration of compounds 6 to 9 were established by spectral methods, the configurations being derived from the chemical shifts of the sugar protons and the splitting patterns of the anomeric protons (‘triplet-quartet rule’). The specific rotations of 3 , 4 , 6 , 7 , 8 and 9 show that the three pairs of anomers represent exceptions to Hudson's rule of isorotation. Reductive removal of the trichloroethyl groups in 8 and 9 with zinc proceeds stepwise, yielding the phosphoro-diesters 13 and 14 and the two desired anomeric 5′-nucleotides 15 and 16 . These latter were purified and characterised as the ammonium salts. Enzymatic cleavage by the 5′-nucleotidase of Crotalus adamanteus venom took place only in the ‘natural’ β-series. The ‘unnatural’ α-anomers were resistent to the enzyme. The structure of 10 was established by spectral methods and confirmed by synthesis.     

Ring transformations of 1,3,4-oxadiazol-2(3H)-one derivatives into 1-amino and 1,3-diamino-2,4-imidazolidinedione (hydantoin) derivatives

Some ethyl 5-aryl(or benzyl)-2-oxo-1,3,4-oxadiazole-3(2H)-acetates were prepared and treated with ammonia, primary amines or hydrazine to give 1-amino-2,4-imidazolidinedione or 1,3-diamino-2,4-imidazolidinedione derivatives. The 1,3-bis(benzylideneamino)-2,4-imidazolidinedione was obtained by reacting ethyl bromoacetate with the 1,5-dibenzylidenecarbonohydrazide sodium salt.     

Synthesis of N-acetyl derivatives of 5-and 6-ethoxy-2-methylthiobenzimidazole and their cardiotonic activity

The regioselectivity of the N-acetylation of 5-and 6-ethoxy-2-methylthiobenzimidazole for various acetylating agents under various conditions has been investigated. The cardiotonic activity of the 1-acetyl-5-ethoxy-and 1-acetyl-6-ethoxy-2-methylthiobenzimidazoles synthesized and of their 5,6-diethoxy analog has been studied.Vilnius University, Vilnius LT-2006. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 765–771, June, 1997.     

Synthesis of 2-amino derivatives of levoglucosenone

2-Amino derivatives of levoglucosenone were prepared by reaction of the 2-methanesulfonyl (or p-toluenesulfonyl) derivatives with ammonia, methylamine, or octylamine under various conditions. The analogous reaction did not occur for saturated derivative 15. The 2-amino-3,4-dihydro derivative was prepared by catalytic hydrogenation of unsaturated amine 9.Translated from Khimiya Prirodnykh Soedinenii, No. 6, pp. 429–432, November–December, 2004.This revised version was published online in April 2005 with a corrected cover date.     

Assignment of the vibrational spectra of 2(1H)-pyridinone (2-pyridone) in the solid state,and in solution as centrosymmetrical dimer. Comparison with 1-methyl-2(1H)-pyridinone (N-methyl-2-pyridone)

The complete assignment of the vibrational spectra of 2(1H)-pyridinone (2-pyridone), 1-D-2(1H)-pyridinone (2-pyridone ND) and 1-methyl-2(1H)-pyridinone (N-methyl-2-pyridone) is obtained from a comparative analysis of their IR and Raman spectra (condensed phase and molar solutions in CHCl₃ or CDCl₃). For the 2-pyridone centrosymmetrical dimer, the strength of the NH…O hydrogen bond association is discussed. Comparison is made with the recent work of Medhi and of Nowak et al.     

C-acylation of heterocyclic keto-enols Communication 10. Cyclization of 3-acyl-4-hydroxy-6-methyl-2(1H)-pyridone phenylhydrazones and their 1-methyl and 1-phenyl derivatives

Conclusions The cyclization of 3-acyl-4-hydroxy-6-methyl-2 (1H)-pyridone phenyl hydrazones and their 1-methyl and 1-phenyl derivatives goes by reaction at the 4-position of the pyridone ring with formation of the corresponding 1H-pyrazolo[4,3-c]pyridin-4(5H)-one derivatives.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya No. 10, pp. 1785–1788, October, 1966.     

Origin of methyl torsional barrier in 1-methyl-2-(1H)-pyridone

The laser induced fluorescence excitation and single vibronic excitation dispersed fluorescence spectra have been studied for supersonic jet cooled 1-methyl-2(1h)-pyridone. The methyl torsional bands and some low frequency vibrational transitions were assigned for both ground and excited states. The torsional parameters V(3)=244 cm(-1) and V(6)=15 cm(-1) for the ground state and V(3)=164 cm(-1) and V(6)=40 cm(-1) for the excited state were obtained. To get the insight into the methyl torsional barrier, ab initio calculations were performed and compared with the experimental results. Origin of potential barrier was traced by partitioning the barrier energy into changes in bond-antibond interaction, structural, and steric energies accompanying methyl rotation using natural bond orbital analysis. The role of local interactions in ascertaining the barrier potential reveals that its nature cannot be understood without considering the molecular flexing. The hyperconjugation between CHsigma(*) and ring pi(*) observed in lowest unoccupied molecular orbital (LUMO) stabilizes the methyl group conformer that undergoes a 60 degrees rotation in the excited state with respect to that of the ground state, and it is the change in LUMO that plays important role in the excited state barrier formation.