Pyridines and Related Heterocyclics

In recent years, a few stereoselective methods for the asymmetric hydrogenation of pyridines and related heterocycles have been developed <20050BC4171>. A chiral auxiliary method starts with an oxazolidinone-substituted pyridine which on reduction with H2/Pd(OH)2 in acetic acid affords the corresponding piperidine in good yield and high enantiopurity. The chiral auxiliary is cleaved during the reaction and can be recovered (Equation 100) <2004AGE2850>. 

Dimethyldioxirane (1) is a mild and efficient oxidant for pyridine pyiidines and quinolines have also been oxidized in good yield by r-pentylhydroperoxide in the presence of molybdenum(V) chloride. A(-Halogenation and other oxidative reactions of pyridines and related heterocycles have been re-viewed. " Thus, pyridines and some diazines can be aminated by mesitylenesulfonylhydtoxylamine... 

A theme of this section is making reactions work. Usually that means making reactions that already work quite well work much better. But we start with a reaction - electrophilic aromatic substitution on pyridines and related heterocycles - that, doesn t really work at all. We shall see why not and how the reaction can be successfully realised. This involves some serious mechanistic thinking and questions of regioselectivity are vital to the solution. This is new chemistry with a great future. 

Bemis JE et al (2009) Discovery of oxazolo[4,5-b]pyridines and related heterocyclic analogs as novel SIRT1 activators. Bioorg Med Chem Lett 19(8) 2350-2353... 

The methods of homolytic alkylation of pyridine and related heterocycles developed by Minisci (73S1, 74AHC123) are used to introduce C-alkyl groups into IP molecules. 

Nitrogen heterocycles have a strong affinity for platinum(II), and complexes of these ligands, particularly pyridine and related diimines such as bipy, are ubiquitous.189,190 The favorable electronic (strong cr-donor/weak 7r-acceptor) and steric properties of such ligands lead to the... 

Halopyridines and other re-deficient nitrogen heterocycles are excellent reactants for nucleophilic aromatic substitution.112 Substitution reactions also occur readily for other heterocyclic systems, such as 2-haloquinolines and 1-haloisoquinolines, in which a potential leaving group is adjacent to a pyridine-type nitrogen. 4-Halopyridines and related heterocyclic compounds can also undergo substitution by nucleophilic addition-elimination but are somewhat less reactive. 

Bhandari A, Li B, Gallop MA, Solid-phase synthesis of pyrrolo[3,4-6]pyridines and related pyridine-fused heterocycles, Synthesis, 11 1951-1960, 1999. 

Pyridines and related nitrogen heterocyclic (azabenzenoid) compounds Polyfluoroaromatic nitrogen heterocyclic systems are all activated, relative to the corresponding benzenoid compounds, towards nucleophilic aromatic substitution. The magnitude of this activation is illustrated by the effects of a ring nitrogen, relative to C—F at the same position, for attack by ammonia [91] (Figure 9.32). 

Pyrazine may be represented as a resonance hybrid of the canonical structure illustrated (21a -<+ 21d). The molecule is planar, and Pauling (114) states that it is stabilized by about 40kcal/mol as in benzene and pyridine, but resonance energies derived by different methods show considerable variation. Some of these resonance energies together with values for benzene and related heterocycles are summarized in Table 1.2 (115-117). More recent measurements of heats of hydrogenation are given in Section IV. 1B. 

Certain ylides react with arylcyclopropenones via 1,4-addition to give a-pyrone and its heterocyclic derivatives the formation of the l,3-oxazin-6-one 336 from reaction of the pyridine-iV-imine 335 with 14 is representative. Pyrimidones, pyridines and related... 

Also under acidic conditions, enamines are reduced to amines via iminium ions by NaBHsCN (eq 15). This type of conversion is also effected with NaBH3CN/ZnCl2. Pyridines and related nitrogen heterocycles are reduced by NaBH3CN/H+ to di-or tetrahydro derivatives (eq 16)4 Likewise, pyridinium and related salts (e.g. quinolinium, isoquinolinium) are reduced. With 4-substituted derivahves, 1,2,5,6-tetrahydropyridine products are produced (eq ll) ... 

In the case of pyrrole, furan and thiophen, the six jr-electrons derive four from the carbon atoms and two (the lone pair ) from the hetero atom. For this reason Albert has termed these heterocyclic compounds Ti-exccssive, in contrast to pyridine, and related compounds, which are referred to as 7r-dejS.cient, because the hetero atom tends to withdraw jr-electrons from, the molecular orbitals and thus reduce the resonance energy. 

When pyridine-1-oxides and related heterocyclic W-oxides in which there are no alkyl groups at the 2- or 4-positions are heated with acetic anhydride, (9-acetylation occurs. This is followed by rearrangement to the acetoxypyridine (XII-424), which is hydrolyzed readily to the pyridone. " Acetoxylation... 

Reactions of Pyridine and Related Six-Membered Ring Aromatic Heterocycles a. Protonation (Sec. 13.1)... 

Reactions of Pyridine and Related Six-Membered Ring Heterocycles... 

Three C-N bonds were formed in one pot. Copper-promoted amination of the benzylic C( p )-H bond is a key step of this multiple C-N bond-forming sequence. This protocol not only provides a useful approach for synthesis of imidazo[l,5-a] pyridines and related fused heterocycles, but also offers a new strategy for retro-synthetic analysis of certain A -heterocycles. 

A wide class of aiyl-based quaternary surfactants derives from heterocycles such as pyridine and quinoline. The Aralkyl pyridinium halides are easily synthesized from alkyl halides, and the paraquat family, based upon the 4, 4 -bipyridine species, provides many interesting surface active species widely studied in electron donor-acceptor processes. Cationic surfactants are not particularly useful as cleansing agents, but they play a widespread role as charge control (antistatic) agents in detergency and in many coating and thin film related products. 

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