Tetrazole, 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). 

Extensive studies of the annular tautomerism of tetrazoles have been reported. These can be broadly divided between the gaseous, liquid solution and solid states. 

The observed annular tautomerism in tetrazoles involves the IH form (26) and the 2H form (28). 

Most of the experimental work on the annular tautomerism of 5-substituted tetrazoles has been carried out on solutions and a number of major studies are described in CHEC-I <84CHEC-I(5)79l>. Nitrogen-15 NMR spectra of 5-substituted tetrazoles and their N-1 and N-2-methyl isomers show... 

Annular tautomerism inherent to NH-unsubstituted tetrazoles and tetrazolium ions governs many chemical and physicochemical properties of these compounds. Since the 1950s, this type of protolytic equilibrium has been investigated by various teams. In this section, we analyze the results of experimental and theoretical studies on the annular tautomerism of NH-tetrazoles and their conjugate acids. The results of investigations published within the last decade are considered from the viewpoint of the classical concepts based on earlier research. 

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...

Measured dipole moments for a series of substituted tetrazoles gave interesting comparisons (56JA4197). The moments for 1-ethyltetrazole (5.46 D) and 2-ethyl tetrazole (2.65 D) were at either side of the mesoionic compound (7) (4.02 D) and the dipole moments could not be used to identify mesoionic structures. The dipole moments for the 1,5-disubstituted tetrazole structure were consistently high, >5.3 D, while those of the 2,5-disubstituted structure were low, <2.65 D theoretical calculations support this (61T237). Recently, dipole moment measurements were made on 5-(p-tolyl)tetrazole in dioxane (fio 4.99), its 1-methyl isomer 6.03) and its 2-methyl isomer (jUd 2.41) (80JHC1374). These results, when applied to the annular tautomerism of 5-( p-tolyl)tetrazole, suggested 60 10% of the 1-NH form in this medium. 

The main methods by which the annular tautomerism (1) (2) has been studied are NMR spectroscopy, dipole moment measurements and theoretical calculations. The latter two approaches (Section 4.13.2.2) indicate similar energies for both forms and suggest that the predominance of the 1,2,3,4-tetrazole form (1), observed in solutions, may be due to a solvation effect. In the gas phase the 1,2,3,5-tetrazole form (2) appears to be the preferred form <77AHC(21)323j> ... 

Four pairwise degenerate tautomeric forms referred to as the IH (27a and 27d) and IH (27b and 27c) tautomers are needed to describe the annular prototropic tautomerism of unsubstituted tetrazole 27 (R = H) (Scheme 14). 

Araujo-Andrade et al. reported an interesting investigation on (tetrazol-5-yl)-acetic acid (TAA). Monomers of the compound were obtained by sublimation and isolated in a N2 matrix at 13 K. In gas phase, TAA may adopt two tautomeric modifications, IH- and 2H-, depending on the position of the annular hydrogen atom (Fig. 7), but in the crystalline state only tautomer H- is present. Each of the tautomeric forms of TAA has several different possible conformers. In their study, Araujo-Andrade and coworkers presented a mechanistic explanation for the observed 1H- 2H tautomerization of TAA upon sublimation of the compound, and simultaneous partial decomposition into 5-methyl-tetrazole and CO2. Such mechanism implies the occurrence of a concerted proton transfer (O-H N) between vicinal TAA molecules along the molecular chains of the crystal, to form the 2Ff-tautomer and generate CO2 and 5-methyl-tetrazole at the crystal boundaries and crystal defects. A detailed characterization of the conformational and tautomeric compositions of... 

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