Pyrazole rings substituents

The principal results on the nitration of pyrazoles are shown in Scheme 23. If the substituent is a phenyl group, it can compete with the pyrazole ring and para-nitration is often observed (Sections 4.04.2.3.3(ii) and 4.04.2.3.10(i)). 

The mechanism of the reaction is now well known due to a series of kinetic studies by Katritzky et al. (Table 31). The nature, free base or conjugate acid, of the substrate depends on the substituents in the pyrazole ring and on the acidity of the nitrating mixture. 

According to Section 4.02.3.1.8 substituents removed from the pyrazole ring by two or more saturated carbon atoms and substituents on the benzene ring of indazoles are similar in reactivity to the corresponding aromatic derivatives. For instance, chloromethyl-pyrazoles are comparable to benzyl chlorides and 5-hydroxyindazoles to /3-naphthols in their reactivity. 

When the pyrazole ring bears two adjacent functional substituents, it reacts like an o-substituted benzene. For example, 4,5-diaminopyrazoles behave similarly to... 

Some tricyclic systems have been prepared by intramolecular cyclization from A-aryl-pyrazoles carrying substituents both in the pyrazole ring at C-5 and in the phenyl ring at the o-position. Thus pyrazolo[l,5-n]quinazolines (563) (69JHC947) and pyrazolo[l,5-n]-[l,4]benzodiazepines (564) (77JHC1163, 77JHC1171) can be prepared from suitable precursors. 

The conclusions about the influence of azole ring substituents on the tautomeric equilibria are summarized in Table VIII. Although sufficient data are available for pyrazoles and imidazoles, it is difficult to correlate them within any well-defined scheme. The energy differences between pairs of tautomers are generally quite small and attempts to analyze these using, for example, the Taft-Topson model failed [95JCR(S)172]. In the case of mono-substituted compounds, Hammet-type equations... 

An interesting result has been observed when 4-formylantipyrine 89 was converted into the corresponding pyridinium salt 90 and reacted with alkyl 3-aminobut-2-enoates. Tire expected 1,4-dihydropyridines 91 are transient species in these syntheses and readily lose the 4-substituent (antipyrine, 93) so that dialkyl 2,6-dimethylpyridine-3,5-dicarboxylates 92 are obtained (85-95%) (94H815). Protonation of the pyrazole ring by the evolved hydrochloric acid accounts for this particular behavior (Scheme 29). 

In general, it is diffieult to prediet the outeome of eyelizations of alkynylpyrazole diazonium salts, even with elosely related arrangements of funetional groups, sinee reaetion ean oeeur at both the a- and /3-earbon atoms of the aeetylenie substituent. Moreover, it is known that the eleetrophilieity of the diazo group and the nueleophilieity of a triple bond markedly depend on their positions in the pyrazole ring and that this ean affeet both the eourse and ease of eyelization and even its viability (83IZV688). 

Since l-heterobut-l-en-3-ynes are readily alkylated and functionalized at the terminal acetylenic carbon atom, their reaction with hydrazines makes it possible to introduce diverse (including functional) substituents into the pyrazole ring. For instance, from benzylated methoxybutenyne 112, isomeric 2-phenylethylpyrazoles 113 were obtained in 74% yield (81H146). 

Properties of nickel poly(pyrazol-l-yl)borate complexes such as solubility, coordination geometry, etc., can be controlled by appropriate substituent groups on the pyrazol rings, in particular in the 3- and 5-positions. Typical complexes are those of octahedral C symmetry (192)°02-604 and tetrahedral species (193). In the former case, two different tris(pyrazolyl)borate ligands may be involved to give heteroleptic compounds.602,603 Substituents in the 5-position mainly provide protection of the BH group. Only few representative examples are discussed here. 

In models C and D the phenyl substituent of the pyrazole ring is not present and here the 0 angles are 19° and 16°, respectively. Even without the trimethylphenyl moiety, the Pd coordination is more distorted than in model A, suggesting that the phenyl rings of the phosphine enhance the distortion. Furthermore, since the magnitude of the distortion observed in model C is almost the same as that in model D, it can be concluded that the effect of the phenyl phosphine groups on the coordination geometry is steric in nature and not electronic. 

The deviation from the square planar geometry at the Pd center in complexes 3 can be attributed wholly to steric factors. Calculations have shown that there is a moderate electronic preference favouring the planar coordination amounting to approximately 4.5 kcal/mol. However, steric interactions between the bulky trichlorosilyl ligands with both phenyl substituents of the phosphine and pyrazole ring result in a distortion away from the ideal square planar geometry. We further have found that the framework of the specific chelate backbone positions the pyrazole ring such that these interactions are enhanced. 

As is the case with 2H- and 3//-pyrroles, and with 3//- and 4H-pyrazoles, the 2//-imidazoles undergo both thermal and acid-catalyzed rearrangements. The products may be 1ft- or 4f/-imidazoies, depending on the ring substituents. 

---