Aromatic pyridine

A variety of conditions (solution, dry media, solvent-free) has been used for microwave-assisted synthesis of Hantzsch 1,4-DHP only procedures involving solvent-free conditions under the action of irradiation led to the aromatized pyridine derivatives. 

Kinetic studies on the quaternization reaction of pentamethylpyridine (154A, Scheme 64) and its deuterated congener suggest that there may be an equilibium between this aromatic pyridine and its valence isomer, pentamethyl-Dewar-pyridine (154B). It is known that such valence isomers are stabilized by steric factors such as encountered in pentamethylpyridine.194195 On determining conductometrically the initial rate of quaternization with methyl iodide for polymethylpyridines in acetone, it was found that all but one followed clean bimolecular kinetics. Pen-... 

There is some uncertainty whether this complex should be described as [Vm(bipy- )3] or as [V°(bipy)3], In fact, given that 2,2 -bipyridine can act either as a cr-donor or a n-acceptor, the metal-ligand bond in these complexes is constituted by a cr-bond between the lone pair of electrons of the nitrogen atom and an unoccupied s-orbital of the metal. Such electron donation, increasing the electron density on the metal, can in turn favour a back-bonding from the d-orbitals of the metal and the unoccupied rt -orbitals of the aromatic pyridine ring. In short, if the metal ion is in a high oxidation state pyridine will act as a a donor, whereas if the metal is in a low oxidation state pyridine will act as a n acceptor. 

Nicotine is an oily, volatile liquid and is the principal alkaloid found in tobacco Nicotiana tabacum). It can be seen to be a combination of two types of heterocycle, i.e. the aromatic pyridine and the non-aromatic N-methylpyrrolidine. 

The 1,4-dUiydropyridines, for example, nifedipine, nicardipine and amlodip-ine, are a well-established class of anti-hypertensive drugs. They are photolabile, some markedly so, for example, nifedipine. In all cases, the major light degradation product is the resonance-stabilised, fuUy aromatic, pyridine analogue [38]. 

According to the figure below, reacting 2,6-dimethylanilme with the acid chloride of pyridine-carboxylic acid first gives the 2,6-xylidide of a-picoUnic acid (2.2.4). Then the aromatic pyridine ring is reduced to piperidine by hydrogen in the presence of a platinum on carbon catalyst. 

The simple non-aromatic pyridines discussed in this Section are represented by nine structures (l)-(9). These are the fully saturated piperidine (1), the tetrahydropyridines (2)-(4) and the dihydropyridines (5)-(9). In this section (2), (3) and (4) will be referred to as A5-, A2- and A1-piperideine as well as 1,2,3,6-, 1,2,3,4- and 2,3,4,5-tetrahydropyridine. The former designation is rather archaic but less cumbersome and it has also been used by other authors of the review literature in this area (74HC(14-Sl)i). The latter designation is used by Chemical Abstracts. 

In general, the syntheses described in this section start with those suitable for saturated six-membered heterocyclic rings and proceed through increasing degrees of unsaturation to the fully aromatic pyridines. 

Triazines react also with electron-rich dienophiles such as ethyl vinyl ether (401 R = Et) or vinyl acetate (401 R = Ac) in boiling dioxane to yield the pyridine derivatives (376). After the usual [4 + 2] cycloaddition and nitrogen elimination from the bicyclic compound (402), the dihydropyridines (403) eliminate ethanol or acetic acid to give the aromatic pyridines (376). The dienophiles (401) can therefore be used as alkyne equivalents (69TL5171). 

The first addition of a fully aromatic pyridine, as opposed to a 2-pyridone, across the 2,5-positions, which might be a concerted Diels-Alder reaction, takes place between the bis-dimethylaminopyridine (161) and DMAD at 110°. The product (163) was obtained in 67% yield and appears to be formed via 162, which undergoes a retro-Diels-... 

When substitution occurs at C-6 or C-7, only one resonance structure that retains an aromatic pyridine ring is possible. 

The basis of the chemistry was the photo-oxidation of dihydropyridines (DHP) and similar materials. It was believed that the oxidation resulted in formation of an aromatic pyridine derivative, which added adhesiveness to the coating surface. A number of dihydropyridine derivatives were prepared from readily available aldehydes and acetoacetic esters. Typical of these was derivative I. 

Basic nitrogen compounds such as condensed aromatic pyridines can be separated from neutral or slightly acidic types such as condensed... 

Protonation occurs on the nitrogen atom having the sp2 lone pair because both lone pairs contribute and the resulting delocalized cation is still aromatic. Pyridine is also protonated on its sp2 lone pair (it is the only one it has ) and the pyridinium ion is also obviously aromatic—it still has three conjugated 7t bonds in the ring. 

Thermolytic conversions of aromatic pyridines into pyrazines have been reported, albeit in minute yield. Thus vacuum pyrolysis of 4-dichloroamino-2,3,5,6-tetrafluoropyridine (69) at 550°C gave at least 12 products in which 2,3,5,6-tetrafluoropyrazine (70) could be identified 1320 and flow thermolysis of 4-azido-2,3,5,6-tetrafluoropyridine in nitrogen at 300°C gave l,2-difluoro-l,2-bis(3,5,6-trifluoropyrazin-2-yl)ethylene (71), isolated in 0.1% yield.1322... 

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