L-Hydroxy-2-pyridone

The name hydroxamic acid was first used by Losseii in 1869, in the case of oxalohj droxamic acid, obtained from diethyl oxalate and hydroxylamine. Where this grouping forms part of the main cyclic system, however, the compound is named as a derivative of this system. In this review, 2 and 3 would be named as 1-hydroxy-2-pyrrolidone and l-hydroxy-2-pyridone, respectively. 

The overall conversion of a 2-furyl ketal to a 6-substitutod l-hydroxy-2-pyridone (79) can be effected by electrolysis in methanol followed by reaction with hydroxylamine. A Grignard reagent can... 

In 1964, the syntheses of the cationic tris[l-oxopyridin-2-olato(l-)]-silicon(IV) complexes 39 1 were claimed, " based on elemental analyses and ESCA data for 39. " Very recently, we succeeded in synthesizing and characterizing the related complexes 42-44 (synthesis of 42 Scheme 24.5). Compound 42 C5H5NO2 (C5H5NO2 = l-hydroxy-2-pyridone or 2-hydroxy-pyridine 7V-oxide) was structurally characterized by single-crystal X-ray diffraction the Si coordination polyhedron was found to be a distorted octahedron. 

Pyridones from l-hydroxy-2-pyridones with reduction of oximes to amines... 

A soln. of l-hydroxy-2-pyridone-6-(a-oximino)propionic acid and stannous chloride in coned. HCl refluxed 19 hrs. -> 2-pyridone-6-alanine. Y 58.6%. R. B. Greenwald and C. L. Zirkle, J. Org. Chem. 33, 2118 (1968). 

Similar catalysis could be achieved with several other N-hydroxy compounds, for instance with l-hydroxy-2-pyridone. 

Methoxy-2,6-dimethylpyridine 4-Hydroxy-2,6-diraethylpyridine-l-oxide anion l-Hydroxy-2,6-dimethyl-4-pyridone 4-Methoxy-2,6-dimethylpyridine-l-oxide... 

Hydroxy-2-pyridones react with diethyl iV,A -dimethylaminomethylenemalonate to give a mixture of isomeric fused pyranones <1996JHC1041>. The three-component domino reaction of /3-keto esters with acrolein and primary amines in presence of 4A molecular sieves gives either [l,6]hydronaphthyridines or aminoazabicyclo[3.3.1]nonanes, depending on the nature of the primary amine, in a one-pot sequence (Scheme 34) <2003SL2301>. 

Hydroxylamine converts pyran-2-ones into pyridine IV-oxides by attack at the 1,2-bond for example, the pyran-2-one (278), obtained by heating 3-acetyI-4-hydroxy-6-methyl-pyran-2-one (dehydroacetic acid) and DMF dimethyl acetal in xylene, reacts with two moles of hydroxylamine under mild conditions to give the pyrano[2,3-6]pyridine JV-oxide (279) (77JHC931). Hydrazine converts pyran-2-ones into l-amino-2-pyridones (78JHC759). 

In a departure from the biomimetic catecholamide-based siderophores, Raymond s group have turned to derivatives of l-hydroxy-2(I//)-pyridone a structure which can be regarded as a cyclic hydroxamic acid264. Unlike hydroxamate siderophores, l,5-bis[l,2-dihydro-l-hydroxy-2-oxo-pyridin-6-yl)carbonyl]-l,5-diazaheptane (33) rapidly removes iron from transferrin. 

Heterocyclic coupling components that have been coupled with diazotized ami-nophenyltrimethylammonium chloride are l-alkyl-6-hydroxy-2-pyridone [93], 1-amino-3-hydroxy-isoquinoline [94], and 2,4-diamino-6-hydroxypyrimidine [95], The trialkylammoniumaryl residue may also be connected to the aromatic diazo component via a sulfone or a sulfonamido function [96], Disazo dyes in this series (e.g., 34) [77901-21-4] may also be generated from monoazo dyes that still contain a primary amino group by dimerization using phosgene [97] or cyanuric chloride [98],... 

Fig. 2.8. Idealized hydrogen exchange rate profile for deuteriation of l-hydroxy-2,6-di-methyl-4-pyridone.

At high acidity, 2,6-dimethyl-l-hydroxy-4-pyridone (9.34) reacted as the conjugate acid [68JCS(B)866] with a rate similar to that of 4-methoxy-2,6-dimethylpyridine N-oxide, so both must then react as conjugate acids of the structure type 9.39. In the intermediate acidity range pD +1 to H0 -2.5, the rate-acidity profile slope was zero for 9.34, indicating reaction on a neutral form. Since 4-methoxy-2,6-dimethylpyridine N-oxide (9.40) was much less reactive, the neutral form reacting must be 9.34 and not 9.41. 

Hydroxy-3-methylpyridine was hydrogenated to 3-methyl-2-piperidone in an 80% yield over Raney Ni in methanol at 200-240°C and 12 MPa H2 (eq. 12.28).40 At 280°C, hydrogenolysis to give 3-methylpiperidine and A-alkylation to give 1,3-di-methylpiperidine took place. In contrast, l-methyl-2-pyridone is hydrogenated under much milder conditions to the corresponding 2-piperidone over Raney Ni in ethanol (eq. 12.29).41... 

The tautomeric 6-hydroxy-7-azaindole shows a shift to longer wavelength, which is characteristic of 2-hydroxypyridine as the neutral molecule or of l-methyl-2-pyridone. The degree of tauto-merization is solvent-dependent, and Yakhontov et have determined the lactam/lactim R = Me) ratio from the position of... 

Furo-2-pyridones. 1,4-Dimethyl -3- cyano -5-propargyl -6- hydroxy -2-pyridone dissolved in coned. H2SO4, and poured on ice after a few min. 5,6- (2-methyl-furano)-l,4-dimethyl-3-cyano-2-pyridone. Y 70%. F. e. s. J. Reisch, Arch. Pharm. 297, 754 (1964) furo[3,2-c]coumarins s. Arch. Pharm. 299, 457 (1966). 

The sodium salt of diethyl acetonedicarboxylate reacts with aryl isocyanates to give 1-aryl-4,6-dihydroxy-2-pyridones (XU-104)and with phenyl isothiocyanate to give 3-carbethoxy4-hydroxy-2-mercapto-l-phenyl-6-pyridone, Th e compound formed on treatment of XI-104 (R = H) with acetic anhydride has been proposed to be 3,5-diacetyl-4,6-dihydroxy-l-phenyl-2-pyridone. Characterization was based on the infrared spectrum, ... 

Reactions between triacetic acid lactone (MI-243) and ammonia or amines to give 4-hydroxy-6-methyl-2-pyridones are well known. For example, glycine and XII-243 give l-carboxymethylene-4-hydroxy-6-methyl-2-pyii-done. This latter 4-hydroxy-2-pyridone has also been formed from diketene and glycine in aqueous base via XU-244, which can be deacetylated in concentrated sulfuric acid. Dehydroacetic acid does not appear to be an intermediate in the formation of xn-244. Under these conditions it reacted with glycine to form an isomeric product, which, however, was not characterized. ... 

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