Pyridines and pyridones

Unexpectedly strong intermolecular hydrogen bonding has been reported by IR spectroscopic studies for tetrahydro-4,7-phenanthroline-l,10-dione-3,8-dicarboxylic acids, which exist in the oxo-hydroxy form 165 in both solid state and in solution [78JCS(CC)369].Tlie conclusion was based on comparison of B-, C-, and D-type bands for 165 and their dimethyl esters (detection of hydrogen bonding) and on analysis of IR spectra in the 6 /xm region (pyridine- and pyridone-like bands). 

Heteroatom transfer in metallacyclopentadienes was first developed in the context of cobalt chemistry in the mid-1970s [27]. Cobaltacyclopentadienes were converted into various five-membered heterocyclic compounds such as pyrrole and thiophene, and into six-mem-bered heterocyclic compounds such as pyridine and pyridone derivatives. In the case of zirconacydopentadienes, the heteroatom compound must bear at least two halide substituents, since the Cp2Zr moiety is re-converted to the stable Cp2ZrX2. Indeed, this is the driving force behind the heteroatom transfer of zirconacydopentadienes. 

Cycloadditions where the 2ir component is an inline or iminium species have been much used for the synthesis of reduced pyridines and pyridones (B-87MI505-01), see also a general review of imine cycloadditions (87H(26)777). 

A.2.2.2 From equilibria. A study of equilibria can be used to estimate the relative contributions of aromaticity to equilibrating tautomers by relating their thermodynamic data to that of the corresponding saturated derivatives. This is illustrated by the relationship between the pyridine and pyridone tautomers shown in Scheme 8. In this way, 2-pyridone and 4-pyridone are calculated to be ca. 30 kj mol-1 less aromatic than the hydroxypyridines <2001CRV1421>. In the quinolones the difference in aromaticity between the two forms is less. The precise degree of aromatic character possessed by 2- and 4-pyranone is not settled various methods of estimation give different values. 

The hetero-DielsAlder reaction (hDA) using iminium species has been commonly used for the synthesis of reduced pyridines and pyridones . The aza-1,3-butadiene 107 was employed in hDA reaction to synthesize the key intermediate 108 in the total synthesis of the pyridine-based natural product piericidin (Scheme 60) <2005JA15704>. The reaction of Danishefskys diene with N-functionalized imine 109 in the presence of (A)-BINOL zinc complex has been utilized to produce 4-piperidones 110 in moderate to high enantioselectivity (Scheme 61) <2004SL711>. 

How to make pyridines and pyridones How to make pyridazines and pyrazoles... 

Grosche, P., Holtzel, A., Walk, T. B., Trautwein, A. W., Jung, G. Pyrazole, pyridine, and pyridone synthesis on solid support. Synthesis 1999, 1961-1970. 

Several saturated and unsaturated derivatives of pyridine and pyridone can serve as synthetic precursors to amino acids. The ring in N-benzoylpiperidine 2.161) was oxidatively cleaved with potassium permanganate to give 2.162.77 Hydrolysis of the amide moiety gave 5-aminopentanoic acid, 2.163. 

Alkene RCM for the Synthesis of Benzene Rings in Indoles, Carbazoles, Benzo-Fused Pyridines and Pyridones, and Benzo-Fused Imidazoles... 

Jiao et al. developed copper-catalyzed diverse constructions of 3,5-diarylpyridines and 2-(lTf)-pyridones through tandem Chichibabin-type cyclization, C(sp )-C(sp ) bond cleavage, and aerobic oxidation with high selectivity. Azide, ceric ammonium nitrate (CAN), and 2-aminopyridine are efficient nitrogen donors in this Cu catalytic system for the selective synthesis of pyridines and pyridones [151] (Scheme 8.81). 

In addition to the examples described above, many other heteroaromatic substrates have been employed in A -arylation reactions, including triazines [175], thiophenes and benzothiophenes [176-180], pyridines and pyridones [181-183], quinolines and quinolones [184, 185], coumarins [186, 187], chromenes and chromones [188, 189], pyridazines [190], azaindoles [191], pyrroles andpyrazolo-heteroarenes [192, 193], indazoles [194], indolizinones [195], triazines [196], and... 

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