Pyridines -pyridones

Pyridines, pyridones, and pyrones containing an amino or hydroxy group also undergo diazo coupling, nitrosation, and Mannich reactions, as do their benzenoid analogues, phenol or aniline. Such reactions take place under conditions of relatively low acidity where less of the compound is in the form of an unreactive cation. 

M. Akhtar and C. Jones, Tetrahedron 34, 813-832 (1978). Pyridine-pyridone tautomerism ... 

Alkylation of Hydroxy pyridines, Pyridones and their Benzo Analogues 349... 

Vinamidinium salts are important intermediates in the synthesis of heterocycles. The 2-chloro-l,3-bis(dimethylamino)trimethinium hexafluorophosphate salt has been used in the preparation of the highly selective Cox-2 inhibitor etoricoxib (Scheme 1). This method describes a straight-forward preparation of the hexafluorophosphate salt which is a crystalline, thermally and shock-stable, non-hygroscopic solid. The submitters have extensively studied the preparation of vinamidinium salts and demonstrated that the method is applicable to substituted acetic acids that contain an electron-withdrawing group (Table 1)." The annulation reaction is also general and useful for the preparation of pyridines, pyridones and pyridine N-oxides. ... 

Providing the two carbonyl groups are sufficiently different in reactivity, only one of the two possible isomeric pyridine/pyridone products is formed via reaction of the more electrophilic carbonyl group with the central carbon of the 3-amino-enone, 3-amino-acrylate, or cyanoacetamide. ° ... 

Rhodium-catalyzed [2+2+2] cycloadditions for the synthesis of substituted pyridines, pyridones, and thiopyranimines 13H(87)1017. Synthesis of six-membered azaheterocycles by means of the P-lactam synthon method 13MR01. 

Substituted pyridines and pyridazines represent privileged scaffolds and are present in various therapeutic agents and in multiple classes of natural products (08CHEC(7)1, 08CHEC(8)1). Diverse approaches for the synthesis of pyridines, pyridones, and pyridazines using RCM as the key step are described below. 

Scheme 1. Representative structures of alkaloids belonging to the four basic ring systems exemplifying the mesenArine, Joubertiamine, pyridine-pyridone, and tortuosamine subgroups.

Takahashi T, Tsai F-Y, li Y et al (2002) Selective neparation of pyridines pyridones and iminopyridines fiom two different alkynes via azazireonacycles. J Am Chem Soc 124 5059-5067... 

Scheme 2 Schematic representations of the molecular structures found in crystal structures of some pyridine/pyridones...

Both J(C-3,C-6) and j(C-5,C-6) were used successfully as probes to examine the keto-enol tautomerism in derivatives of 2-OH-pyridine 52 in solution, which is strongly dependent on the solvent s dielectric constant and type/position of the substitution [96], Experimental J values of the pyridine-pyridone tautomers were measured in natural abundance with the INADEQUATE technique, and theoretical values were computed at DFT level of theory considering the solvent by the SCRF-PCM model [96],... 

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