2-Pyridones 1-hydroxy- from

In an ab initio study of the tautomerism of 2- and 4-hydroxy-pyridines, 4,-hydroxypyridine was calculated to be 2.4 kcal/mol more stable than 4-pyridone. 2-Pyridone was calculated to be 0.3 kcal /mol more stable than 2-hydroxypyridine and this is in good agreement with experimental values obtained from tautomeric studies in the gas phase.61 A study of the bromination of the 2-pyridone/2-hydroxypyridine system has revealed that reaction occurs via the principal "one" tautomer at pH<6 and via the conjugate anion at pH>6. Attack on the "one occurs preferentially at the 3-position, whereas on the anion it probably occurs mainly at the 5-position. The facile formation of 3i5-dibromo-2-pyridone results from the comparable reactivity of the monobromopyridones at pH<1 and pH>4- Practical procedures have been reported for the preparation of 3-bromo-2-pyridone and... 

Acetyl-4-hydroxy-6-phenyl-2-pyridone, 635 from 5-acetyl-4-hydroxy-6-phenyl-(2tf)-2-pyrone, 658 5-benzoyl-4-hydroxy-6-methyl-(2f )-2-pyrone, 658... 

A third synthesis which has resulted in the preparation of rieinine and a number of its derivatives is due to Schroeter, Seidler, Sulzbacher and Kanitz,i2 who foimd that cyanoacetyl chloride polymerises spontaneously to 6-chloro-2 4-dihydroxy-3-cyano-pyridine. The di-sodium derivative of this with methyl sulphate produces A -methyl-6-chloro-4-hydroxy-3-cyano-2-pyridone (6-chlororicininic acid), the mono-sodium derivative of which, with methyl bromide or sulphate, is converted into 6-chlororicinine and the latter is reduced by zinc and sulphuric acid to rieinine. A fourth synthesis, starting from 3-nitro-4-pyridone, is due to Reitmann. ... 

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. 

Methyl- and 3-phenyl-4-hydroxy-2-oxo-2//-pyrido[2,1 -Z)]oxazinium inner salts were prepared in the reaction of 2-pyridone and 2-substituted malonyl chloride, prepared in situ from 2-substituted malonic acid with PCI5 in CH2CI2 (00JCS(P2)2096). 

Second generation COMT inhibitors were developed by three laboratories in the late 1980s. Apart from CGP 28014, nitrocatechol is the key structure of the majority of these molecules (Fig. 3). The current COMT inhibitors can be classified as follows (i) mainly peripherally acting nitrocatechol-type compounds (entacapone, nitecapone, BIA 3-202), (ii) broad-spectrum nitrocatechols having activity both in peripheral tissues and the brain (tolcapone, Ro 41-0960, dinitrocatechol, vinylphenylk-etone), and (iii) atypical compounds, pyridine derivatives (CGP 28014,3-hydroxy-4-pyridone and its derivatives), some of which are not COMT inhibitors in vitro but inhibit catechol O-methylation by some other mechanism. The common features of the most new compounds are excellent potency, low toxicity and activity through oral administration. Their biochemical properties have been fairly well characterized. Most of these compounds have an excellent selectivity in that they do not affect any other enzymes studied [2,3]. 

In the second instance, two approaches seem to be worthy of special note. The synthetic utility of elemental phosphorus based on it acting as a radical trap appears to be quite valuable, but additional effort is required to determine the variability of the source of the organic free radicals. (Is there some other, more efficacious, source of organic free radicals that works better with this system than acylated iV-hydroxy-2-pyridones ) The other approach that appears ripe for development is the hydrolysis/elimination with "phosphorates" derived from the oxidative addition of white phosphorus to alkenes. We look forward to the continued development of such facile approaches toward the preparation of fundamental phosphonic acids. 

Leucaena spp. contain mimosine, which is degraded to 3-hydroxy-4(l//)-pyridone (3,4-DHP see Section 2.2.4 for more detail). Leucaena, while toxic to unadapted ruminants, is a good source of protein and minerals for many livestock species in some countries. However, if Leucaena is ingested as 50% or more of the diet it will depress growth, cause hair loss, and reduce reproductive performance. Mimosine is a toxin that animals may become adapted to. Ruminal adaptation can be transferred from animal to animal, suggesting a specific set of rumen organisms are capable of detoxifying this amine. 

Many analogs of 75 with substituents in the pyridine rings have also been prepared ° although 6-alkoxy-2,2 -bipyridines react with ethylene dibromide to afford the pyridone 76 rather than 4-alkoxy analogs of 75. Derivatives of 75 with alkyl substituents on the ethylene bridge (i.e., 6 and/or 7 positions) can likewise be prepared from 2,2 -bipyridines and appropriate dibromoalkanes. " " 6-Hydroxy-substituted derivatives of 75, for example, compound 78, are accessible by ring closure of j8-carbonyl monoquaternary salts of 2,2 -bipyridine, such as compound 77, with acid. 

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],... 

For preparation of cyclopirox from l-hydroxy-4-methyl-6-cyclohexyl-2-pyridone was added 2-aminoethanol (1 1). 

The reaction mixture was then dissolved in methylene chloride, the amine was removed by shaking with dilute hydrochloric acid, the reaction product was extracted from the organic phase by means of dilute sodium hydroxide solution and the alkaline solution was acidified with acetic acid to a pH value of 6. The l-hydroxy-4-cnethyl-6-cyclohexyl-2-pyridone precipitated in crystalline form. It was filtered off with suction, washed with water and dried. The yield was 1.05 g (49% of theory) melting point 143 C. 

In early 1977, Barton et al. [48] published the X-ray crystal-structure analysis of a Ptblue derived from cM,-[Pt(NH3)2(H2C))2]2+ and a-pyridone. The compound was shown to consist of two dinuclear entities containing two head-to-head-oriented a-pyridonato ligands and two ds-diammineplat-inum residues, associated by an unsupported (H-bonds excluded) Pt-Pt bond between the two 0,0-coordinated Pt ions. The average Pt oxidation state of this blue is +2.25. Formally, the Pt4 chain thus consists of three Pt11 ions and one Ptm ion, with the unpaired electron delocalized over the Pt4 chain (Scheme 3). The choice of the cyclic amide a-pyridone (1-hydroxy pyridine) by Lippard and co-workers had been a fortunate one in that it reduced the... 

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