1.2.4- Triazoles annular 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). 

In NMR speetra of trialkyltin derivatives of 1,2,3-triazoles, C(4) and C(5) atoms show one eommon signal at the lowest attained temperature of solution, -50°C [77JOM(132)69]. This observation was explained by the symmetrie strueture 42c of the eompounds (R = COOMe) [77JOM(127)273]. However, rapid annular tautomerism explains this observation equally well and eannot be ruled out. 

More recently, activity in the held of the preparation of phthalocyanine-like compounds useful in material science concentrated on compounds containing only one triazole subunit (triazolophthalocyanines) 89 [94JCS(CC)1525 95ICA(230)153].These aromatic compounds (without or with metals in the cavity) present a problem of annular tautomerism of triazoles, but as yet it is known only that the NH is outside the cavity. 

For azapentalenes of type A (e.g. 80,73b 52, and 28160), rule ii should favor the a structure shown in each case. Unfortunately, the position of equilibrium in these compounds has not been measured. A rare case where the annular tautomerism of a type A azapentalene has been investigated is the pyrazolo[3,4-d]-i -triazole 90. Although results from dipole moment measurements were inconclusive, it is likely that 90a and 90c predominate at equilibrium.367... 

Most work has been done by the same group of workers,360 363, 364, 367 433, 435,440 and practically all examples are from type B systems except for a study of the annular tautomerism (Section IV,A1) of 4-methyl-6-phenylpyrazolo[3,4-d]-u-triazole (90),367 a type A system. Values shown here are expressed in Debyes (D), using dioxane as solvent. 

There is a structural and energetic relationship between the isomerism of azolides (18) (acylotropy) and the annular tautomerism of the corresponding NH-azoles [34], This is due to the lability of the azole-COR bond for instance, in 1,2,4-triazole the most stable tautomer is the 1H (60a, X = H) and the only known azolide the 1-COR (related to 25). 

Systematic replacement of CH in pyrrole 1 (Chapter 2.3) by N leads to nine additional monocyclic heteroaromatic nitrogen systems 2-10 (Figure 1), which are known collectively as azoles. Annular tautomerism is an important feature of all azoles having an NH function. For example, the triazoles 4 and 6, the triazoles 5 and 7, and the tetrazoles 8 and 9 can equilibrate by proton transfer (see Section 2.4.5). N-Substituted derivatives cannot equilibrate. Tautomers of the parent ring systems of all the azoles except pentazole 10 are known TV-aryl derivatives of pentazole have been characterized . 

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...

Besides the annular tautomerism and the Dimroth rearrangement (Section 4.02.3.5) ring-chain tautomerism of certain 1,2,3-triazoles have been discussed and, in some cases, shown by means of spectroscopic methods. Thus, cyanogen azide reacts with acetylene to form a 1 1 adduct, which was proved by means of IR, UV and temperature-dependent... 

Table 17 Annular Tautomerism of 1,2,3-Triazole and Benzotriazole 76Ahc(S1)296>...

The molecular geometry of 1,2,4-triazoles has been studied mostly in relation to annular tautomerism, especially that of simple compounds in which IH and 4H tatuomers have different symmetries. 

If an experimental investigation is decided on, fixed tautomers for which R = alkyl, preferably Me, will be required to preserve tautomeric integrity and it will be necessary to use pK correction factors [9]. For triazoles these are A(NMe) 0.3 for an isolated nitrogen atom and 0.55 when two are contiguous, with A(OMe) 1.0 in all cases. However, we have indications [40] that isoxazoles behave abnormally and the same will probably be true for 53 and 54. Note that no model is needed for 54b unless it is the minor tautomer since annular tautomerism in 54a is improbable. 

Annular prototropie tautomerism of 1,2,3-triazole (v-triazole) and its C-substituted derivatives involves the equilibrium of three possible isomers 24a-24c. In the ease of the parent eompound (R = H), 24a and 24c are degenerate isomers (Seheme 11). 

Annular prototropic tautomerism of 1,2,4-triazoles (s-triazoles) involves an equilibrium between three possible forms (26a-26c) (Scheme 13). 

The annular prototropic tautomerism of the parent 1,2,3-triazole and benzotriazole are described in CHEC-I <84CHEC-I(5)691> and was reviewed earlier <76AHCS295>. 

The tautomerism of 1,2,4-triazoles (see Chapter 4.01 and (76AHC(S1)i)) may involve one or more of the following possibilities annular prototropy, prototropy involving both the ring and substituents and tautomerism restricted to the substituent. Only the first two of these will be considered. 

Prototropy in triazoles is particularly complex when substituents such as OH, SH and NHR are available to donate protons to annular N. A detailed discussion of all possible sub-cases of this type is beyond the scope of this chapter, but the main aspects of this matter are reviewed in a broad critical context (76ahc(s1)i. p. 388, 4i4, 444) tabulating generalizations and their levels of reliability. The section on reactivity (Section 4.12.3) gives examples of the variability of tautomeric preference in some reactions. 

---