Annular nitrogen atoms, tautomerism

Annular tautomerism (e.g. 133 134) involves the movement of a proton between two annular nitrogen atoms. For unsubstituted imidazole (133 R = H) and pyrazole (135 R = H) the two tautomers are identical, but this does not apply to substituted derivatives. For triazoles and tetrazoles, even the unsubstituted parent compounds show two distinct tautomers. Flowever, interconversion occurs readily and such tautomers cannot be separated. Sometimes one tautomeric form predominates. Thus the mesomerism of the benzene ring is greater in (136) than in (137), and UV spectral comparisons show that benzotriazole exists predominantly as (136). 

Tautomerism Involving Only Annular Nitrogen Atoms. 52... 

Alkylation of potentially tautomeric heteroaromatic systems under basic phase-transfer catalytic conditions normally occurs on the softer heteroatom [cf 57]. Thus, although 2- and 4-pyridones are alkylated on the annular nitrogen atom and the exocyclic oxygen atom, -alkylation of the 2-pyridones predominates to the extent of ca. 5 1 (or greater under soliddiquid reaction conditions [58]), whereas the relative predominance of A -alkylation of the 4-isomer is only ca. 3 1 [59] (Table 5.37 and 5.38). These ratios are comparable with those obtained for the base-catalysed alkylation of the pyridones by traditional methods and, not unexpectedly, S-alkyla-tion of the corresponding pyridthiones occurs to the total exclusion of A-alkylation [60]. Catalysed soliddiquid acylation has also been reported [58]. 

C-Aminoindoles autoxidize extremely rapidly. Consequently, comparatively few chemical reactions have been examined. The 2-amino derivative exists in the 3H-indole tautomeric form (473) and is protonated and alkylated on the annular nitrogen atom (72HC(25-2)179). The 1-methyl derivative (474) exits predominantly as such and not as the alternative 2-imino-3//-indole tautomer and is protonated at the 3-position to give a cation having the same electronic structure as that of the protonated (473). Acylation of (473) yields l-acetyl-2-acetylaminoindole, via the initial acylation of the annular nitrogen atom. Confirmation of this route has been established by the observation that 2-acetylaminoindole, obtained by hydrolysis of the diacetylated compound, is acetylated under identical conditions... 

The C spectrum (15.04 MHz) of perimidine (13 R = H) (Table 1) is consistent with a symmetrical structure, reflecting rapid prototropic tautomerism between the annular nitrogen atoms as found for H NMR. Tautomerism is excluded in 1-alkyl derivatives as shown for (13 R = Me) in Table 1. The relative C chemical shifts parallel those of the corresponding protons in the H NMR spectrum. The relative order of the chemical shifts in C NMR of 1,8-naphthalenediamine is the same as in perimidine. All carbocyclic peaks other than C9b exhibit a pronounced upfield shift, in accord with the 7r-excessive character of the carbocyclic rings in the perimidine system. On the other hand, C2... 

Apnular tautomerism has been defined as the class of tautomeric rearrangements in which only annular nitrogen or carbon atoms are involved [76AHC(S1), p. 266], In azoles, the latter case is frequently energetically un-... 

Such modifications can be produced either in the kinetic aspects (proton transfer) or in the equilibrium constant. Both effects are mediated by intramolecular hydrogen bonds. For instance, Navarro et al. (93MI69) showed that the rate of proton transfer between the two nitrogen atoms of pyrazole (annular tautomerism) is considerably reduced in macrocycles containing oxygen or nitrogen atoms in the macroring. 

Chemical shifts for aromatic azoles are recorded in Tables 17 and 18. Fast tautomerism renders two of the 13C chemical shifts equivalent for the NH derivatives (Table 17a), as in the proton spectra (Table 8a). However, data for the N-methyl derivatives (Table 17b) clearly indicate that the carbon adjacent to a pyridine-type nitrogen shows a chemical shift at lower field than that adjacent to a pyrrole-type TV-methyl group (in contrast to the H chemical shift behaviour). Solid-state studies on imidazole (and pyrazole) show there are three distinct signals for the annular carbon atoms (imidazole C(2), 136.3 C(4), 126.8 C(5), 115.3 ppm). Proton exchange does not occur in the solid, hence the spectra describe the structure in the crystal. Comparison with the corresponding chemical shifts for 1-methylimidazole (137.6, 129.3, 119.7 ppm) implies that tautomerism has been frozen in the solid state <1981CC1207>. Solid-state examination of 2,2/-bis-17/-imidazole also reveals frozen tautomerism. 

Table 42 gives an overview of annular tautomerism data for azoles in the gas phase and in solution or crystals. In the gas phase the stability of alternative tautomers largely depends on their relative aromaticities. In Section 2 A.4.2.2 it was noted that 1,2-relationships between pyrrole- and pyridine-type nitrogen atoms favor aromaticity (Figure 21) and this is consistent with the relative stabilities of triazole and tetrazole tautomers in the gas phase (Table 42) <2010T2695>. In solution (and crystals) other factors such as solvent polarity, hydrogen bonding, and temperature become important and the relative stabilities can be reversed. Polar solvents tend to stabilize the tautomer with the largest dipole moment and this probably accounts for the observation of both 2H-1,2,3-triazole (p = 0.12D) and H-1,2,3-triazole (p = 4.55D) in...

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