Anionic Azoles

These ions (7.9-7.13) are produced via proton loss from an NH group and are therefore found under basic conditions. 

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Simple complexes. Many examples are known of complexes between metal cations and both neutral azoles and azole anions. Azoles can form stable compounds in which metallic and metalloid atoms are linked to nitrogen. For example, pyrazoles and imidazoles N-substituted by B, Si, P, Ga, Ge, Sn, and Hg groups are made in this way. Overlap between the d-orbitals of the metal atom and the azole -orbitals is believed to increase the stability of many of these complexes. 

Table 7 H NMR Spectral Data for Ring Hydrogens of Azole Anions...

Although UV spectra have been measured for a large number of substituted azoles, there has been no systematic attempt to explain substituent effects on such spectral maxima. Readily available data are summarized in Table 25, and some major trends are apparent. However, detailed interpretation is hindered by the fact that different solvents have been used and that in aqueous media it is not always clear whether a neutral, cationic or anionic species is being measured. Furthermore, values below 220 nm are of doubtful quantitative significance. 

Reactivity of neutral azoles Azolium salts Azole anions... 

Orientation in azole rings containing three or four heteroatoms Effect of azole ring structure and of substituents Proton acids on neutral azoles basicity of azoles Proton acids on azole anions acidity of azoles Metal ions... 

Azole anions are derived from imidazoles, pyrazoles, triazoles or tetrazoles by proto loss from a ring NH group. In contrast to the neutral azoles, azole anions show enhance reactivity toward electrophiles, both at the nitrogen (Section 4.02.1.3.6) and carbon aton (Section 4.02.1.4.1(i)). They are correspondingly unreactive toward nucleophiles. 

Similar ambiguities arise in the reactions of azole anions. At least as regards alkylation reactions in the 1,2,3-triazole series (79), the product appears to depend on the reagent used. In the 1,2,4-triazole series (80) a single product is formed, whereas tetrazole (81) gives mixtures. 

Proton acids on azole anions acidity of azoles... 

Many examples are known of complexes between metal cations and both neutral azoles and azole anions. Overlap between the cf-orbltals of the metal atom and the azole rr-orbitals is believed to increase the stability of many of these complexes. 

Diazo coupling is expected to occur only with highly reactive systems, and experiment bears this out. Diazonium ions couple with the anions of N-unsubstituted imidazoles at the 2-position (e.g. 125 yields 126) and with indazoles (127) in the 3-position. In general, other azoles react only when they contain an amino, hydroxyl, or potential hydroxyl group, e.g. the 4-hydroxypyrazole (128), the triazolinone (129) and the thiazolidinedione (130) (all these reactions occur on the corresponding anions). 

Oxidation of azole anions can give neutral azole radicals which could, in principle, be tt (139) or a- (140) in nature. ESR spectra indicate structure (141 hyperfine splittings in G) for imidazolyl radicals, but both tt- and cr-character have been observed for pyrazolyl radicals. Tetrazolyl radicals (142 4 143) are also well known (79AHC(25)205). Oxidation of 2,4,5-triarylimidazole anions with bromine gives l,l -diimidazolyls (144) which are in equilibrium with the dissociated free radical (145) (70AHQ 12)103). 

If the fV-aryl group is strongly activated, then it can be removed in nucleophilic substitution reactions in which the azole anion acts as leaving group. Thus l-t2,4-dinitrophenyl)pyrazole reacts with N2H4 or NaOMe. 

The pyrazole ring is particularly difficult to cleave and, amongst the azoles, pyrazoles together with the 1,2,4-triazoles are the most stable and easiest to work with. This qualitative description of pyrazole stability covers the neutral, anionic and cationic aromatic species. On the other hand, the saturated or partially saturated derivatives can be considered as hydrazine derivatives their ring opening reactions usually involve cleavage of the N—C bond and seldom cleavage of the N—N bond. It should be noted, however, that upon irradiation or electron impact the N—N bond of pyrazoles can be broken. 

Pyrazole and indazole anions, in a manner similar to other azole anions, show the expected inversion of reactivity when compared with the cations. They are more reactive towards electrophiles, both at the nitrogen and carbon atoms, and less reactive towards nucleophiles than the corresponding neutral molecules. For practical purposes most of the N -alkylated pyrazoles and indazoles are prepared from the corresponding anions. 

The general discussion (Section 4.02.1.4.1) on reactivity and orientation in azoles should be consulted as some of the conclusions reported therein are germane to this discussion. Pyrazole is less reactive towards electrophiles than pyrrole. As a neutral molecule it reacts as readily as benzene and, as an anion, as readily as phenol (diazo coupling, nitrosation, etc.). Pyrazole cations, formed in strong acidic media, show a pronounced deactivation (nitration, sulfonation, Friedel-Crafts reactions, etc.). For the same reasons quaternary pyrazolium salts normally do not react with electrophiles. 

Tire and NMR parameters of some 1-alkyl-4-benzimidazolyl-2-idene- (type 72) and l-alkyl-4-(5-methylpyrazolyl-3-idene)-l,4-dihydro pyridines (type 73) were discussed in 89CC1086 and 91JOC4223. Comparison of the shifts for DMSO-dg and CDCI3 solutions with data reported for quaternary pyridinium compounds as well as anionic species in the azole series and data obtained for mesoionic betaines of the azinium azolate class left no doubt that these heterofulvalenes have a betaine character and, therefore, the NMR signals correspond to their dipolar resonance form. 

Minghetti, G., BanditeDi, G. and Bonati, E. (1979) Metal derivatives of azoles. 3. The pyrazolato anion (and homologs) as a mono- or bidentate ligand preparation and reactivity of tri-, hi-, and mononudear... 

All of the azoles showed a linear variation of these values except the pyrazoles, which belong to a parallel line 4.5 pK units apart. Fully optimized INDO geometries have been calculated for 12 azoles, as well as their cations and anions, both isolated and specifically solvated by five water molecules166. Evaluation of the protonation and deprotonation energies of the solvated molecules indicates a behaviour similar to that found experimentally in solution. In particular, the difference between pyrazoles (and indazoles) and all the other azoles is a consequence of the protonation of the nitrogen contiguous to NH, that is due to a difference in basicity. 

The addition of anionic heteroatom-centered nucleophiles (HO, MeO, pyr-azolate, etc.) and carbanions (CN , enolates, aUcyl or alkynyl reagents) to the cationic allenylidenes [Ru( 7 -C9H7)(=C=C=CR R )(PPh3)2][PF6] [125-128,... 

Bensaude et al. (78T2259) have used T-jump relaxation spectrophotometry to determine the rates of protonation and deprotonation of 3(5)-methyl-5(3)-phenylpyrazole anion (416") and cation (416H ), respectively. This study is a fundamental cornerstone in understanding annular tautomerism in azoles. The nondissociative intramolecular proton transfer in azoles is not observed (78T2259 86BSF429). 

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