Pyridine-containing heterocyclic systems

N-heterocyclic compounds containing six-membered rings (pyridine and analogues) behave as excellent -acceptors and in turn they provide a rather soft site for metal ion coordination. The 7r-excessive five-membered pyrazole is a poorer 7r-acceptor and a better 7r-donor and it acts as relatively hard donor site. Inclusion of six- and five-membered N-heterocycles like pyridine and pyrazole in one ligand system leads to very attractive coordination chemistry with variations of the electronic properties.555 The insertion of a spacer (e.g., methylene groups) between two heterocycles, which breaks any electronic communication, makes the coordination properties even more manifold. 

In this new book, Jack Li and Gordon Gribble have compiled an impressive array of richly referenced examples of the use of palladium in heterocyclic chemistry. The book is organized by class of heterocycle (pyrroles, indoles, pyridines, etc.) and each chapter contains the syntheses of heterocyclic precursors as well as details of uses of palladium to both synthesize and functionalize these heterocyclic systems. This book will appeal to anybody involved in heterocyclic chemistry, and will provide an easy entry into the field for those unfamiliar with the area. 

A variety of heterocyclic systems containing unsaturated nitrogen can partake in directed aromatic or heteroaromatic lithiations. Pyrazole (II,D), tetrazole (II,G,2), imidazoline (V,B,2), and pyridine (IV,A,4) derivatives were discussed in the sections indicated. In addition, lithio derivatives of 2-oxazoline 178 (76LA183), 4,4-dimethyl-2-oxazoline 179 (790R1 85T837),... 

Similarly, 2-methyl-3-cyanopyridines were converted into novel heterocyclic systems containing a 3-(tetrazole-5-yl)-pyridine unit 554 via the corresponding 2-azidomethyl derivatives (Scheme 82) <2004TL9127>. 

Nucleophilic Reactions of Aromatic Heterocyclic Bases Heterocyclic aromatic compounds containing a formal imine group (pyridine, quinoline, isoquinoline, and acridine) also react readily with nucleophilic reagents. A dihydro-derivative results, which is readily dehydrogenated to a new heteroaromatic system. Since the nucleophile always attacks the a-carbon atom, the reaction formally constitutes an addition to the C=N double bond. An actual localization of the C=N double bond in aromatic heterocyclic compounds is incompatible with molecular orbital theory. The attack of the nucleophilic reagent occurs at a site of low 77-electron density, which is not... 

The concept of aromaticity is not restricted to hydrocarbons. Heterocyclic systems, whether of the pyrrole type 1.38 with trigonal nitrogen in place of one of the C=C double bonds, or of the pyridine type 1.39 with a trigonal nitrogen in place of a carbon atom, are well known. The n orbitals of pyrrole are like those of the cyclopentadienyl anion, and those of pyridine like benzene, but skewed by the presence of the electronegative heteroatom. The energies and coefficients of heteroatom-containing systems like these cannot be worked out with the simple... 

Those heterocyclic systems attacked by complex metal hydrides are required to be relatively electron deficient. Nitrogen heterocycles in which the heteroatom contributes a single electron to the n system are considered electron deficient (e.g., 1). However, systems where the nitrogen atom contributes two electrons are considered electron rich (e.g., 2) and are not normally attacked by metal hydrides. Aromatic species that contain both a pyridine-like (1) and a pyrrole-like (2) heteroatom (e.g., 3) exhibit be-... 

In the present review, an analysis is made of the synthesis and properties of six isomeric heterocyclic systems containing two fused pyridine rings with different mutual arrangements of nitrogen atoms - naphthyridines (pyridopyridines, diaza-naphthalenes). They include two groups of compounds - V(l),V(7)-naphthyridines (i — 5, 6, 7, 8) 1-4 and V(2),V(/)-naphthyridines (J — 6, 7) 5, 6. 

The reaction of nucleophilic radicals, under acidic conditions, with heterocycles containing an imine unit is by far the most important and synthetically useful radical substitution of heterocyclic compounds. Pyridines, quinolines, diazines, imidazoles, benzothiazoles, and purines are amongst the systems which have been shown to react with a wide range of nucleophilic radicals, selectively at positions a and 7 to the nitrogen, with replacement of hydrogen. Acidic conditions are essential because N-protonation of the heterocycle both greatly increases its reactivity and promotes regioselectivity towards a nucleophilic radical, most of which hardly react at all with... 

Several examples of intramolecular Boger reactions toward the synthesis of pyridine-containing heterocyclic systems were reported by the Taylor group and the Snyder group, For instance, intramolecular cyclization of triazine 219, after loss of nitrogen, afforded 220. Alternatively, triazine 221 generated bicyclic systems 222, which was then oxidized to 223. ... 

Pyridine is considered as one of the commonest heterocycles among nitrogen-containing heterocychc compounds. Substituent effects in meta-and para-X-substituted pyridines (with X = OMe and Me) on their basicity have been studied in water and ionic hquid (IL, l-buthyl-3-methyl-imidazolium hexafluorophosphate) (2010JOC(75)3912). The equibbrimn constants were evaluated by spectrophotometric titration of pyridine solution with trifluoroacetic acid. The results of the Hammett approach (Eqn (1)), applied to aU studied systems, allow one to state that pyridine basicity is almost twice as less sensitive to the substituent effect in IL than in water (Figure 2). 

In addition to these pyridine-containing helical macrocycles, there are numerous reports of polyaza-macrocyclic species that are chiral due to the adaptation of a non-planar conformation. Some current examples included the ruffled benzimidazole-based ligands and the distorted phthalocyanines recently prepared by the groups of Chan [40] and Kobayshi [41], respectively. These systems do not fall within the context of this Chapter due to their resemblance to porphyrinic systems but they nevertheless represent an interesting class of chiral macrocycles based upon the incorporation of heterocyclic rings. 

---