Pyridines compared with azoles

The reactivity of isoxazole toward quaternization is compared with those of pyridine-2-carbonitrile, pyridine and five other azoles in Table 6 (73AJC1949). Isoxazole is least reactive among the six azoles and times less reactive than pyridine. There is also a good correlation between the rate of quaternization and basicity of the azole. 

It should be expected that the orientation and rate of electrophilic substitution in the isoxazole nucleus would be affected by both hetero atoms. Because of the electron-accepting effect of the nitrogen atom, electrophilic substitution of the isoxazole nucleus should proceed less readily than in the case of benzene and should occur essentially at the position jS to the nitrogen atom, just as in pyridine and other azoles. Simultaneously the electron-donating oxygen atom should facilitate such reactions in isoxazole as compared with the substitution in pyridine. These predictions are confirmed by the available experimental evidence. 

Other reactants containing a primary amino gronp will also convert pyryliums into A -substituted nitrogen heterocycles iV-amino azoles are amongst several types of hydrazine derivatives to have been utilised these give iV-(heteroaryl)-pyridinium salts. Reaction of pyryliums with hydroxylamine comparably leads (predominantly) to the formation of pyridine iV-oxides. " ... 

The chemistry of azole-iV-oxides is relatively underdeveloped compared, for example, with that of pyridine iV-oxides, largely because of difficulty in their preparation from the azoles themselves. Some ring synthetic methods can be used, for example the reaction of 1,2-dicarbonyl-mono-oximes with imines as shown. ... 

Metal-nitrogen distances, as observed in a very large number of crystal structure determinations, are almost the same as those observed for the azole ligands (see Table 2) within experimental error. Comparing pyridine with substituted ligands, it is observed that substituents at position 2 (and 6) next to the donor atom have a dramatic effect upon the stoichiometry and properties of the compounds formed. It appears that a stoichiometry M(Rpy)4(anion)2 with a trans orientation of the anions is not possible, because the methyl group effectively blocks the axial coordination sites. This results in square-planar low-spin compounds for Ni and tetrahedral geometry for some other metals such as Co " and... 

Electrophilic substitution in the azoles is intermediate in facility between pyridine and pyrroles, thiophene and furans the presence of the electron-with-drawing azomethine unit has an effect on the five-membered aromatic heterocycles just as it does when incorporated into a six-membered aromatic framework, i.e. the comparison is like that between benzene and pyridine (chapter 4). The order of reactivity - pyrrole > furan > thiophene - is echoed in the azoles, though the presence of the basic nitrogen complicates such comparisons. The regiochemistry of electrophilic attack can be seen nicely by comparing the character of the various ring positions - those that are activated in being five-membered in character and those that are deactivated by their similarity to a-and y-positions in pyridine. 

Because of the good results for pyridine and azole derivatives, we decided to test the OVGF(AMl) method for some halogen-substituted pyridines (shown in Scheme 1) and to compare the results with the SAMI and MNDO/d calculations. The calculated and experimental data for Cl- and Br-substituted pyridines are summarized in Table 4. 

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