5-Substituted tetrazoles, tautomerism

Tautomeric Equilibrium Constants Kt = [ll/]/[21/] OF Substituted Tetrazoles 27 in DMSO Estimated from NMR Studies... 

Thus, the substituted tetrazoles 113 upon oxidation with lead tetraacetate gave rise to the fused tetrazoles 114, in most cases in high yields. Tetrazole derivatives 115, bearing an anisidine side chain, also underwent oxidative cyclization and afforded 10-methoxycarbonylmethyltetrazolo[l,5- ]quinoxaline 116 in good yield. This compound was obtained as a mixture of tautomers (with participation of the methylene hydrogen atoms) and the depicted tautomeric form 116 proved to be dominant. 

Proton and earbon NMR studies of interannular conjugation effects in aryl-substituted tetrazoles have been discussed <84CHEC-I(5)791>. The use of NMR spectroseopy to study tautomerism in tetrazole systems is eovered in Seetion 4.17.4. 

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... 

Besides pyrazoles and imidazoles, we have extended these studies to other azoles, for instance to C-halogeno 1/7-1, , 4-triazoles 60 (X = Cl, Br) [73] (for DFT studies of other C-substituted 1,2,4-triazoles, see [74]) and to 5-substituted tetrazoles 61 (X = H, CH3, t-Bu, C6H5, Cl, CF3, N02) [75], The 1,2,4-triazole series 60 was examined regarding tautomerism in solution and in the solid state (the most stable is 60a and the least stable 60c). The paper on 5-substituted tetrazoles 61 concerns, besides tautomerism, their ionization (proton loss) to tetrazolate anion 62. 

Acylation with the acylium ion in the gas phase. An unusual experiment was performed by Seldes et aL <20010MS1069>. The N2-tautomeric form of a 5-substituted tetrazole was reacted in the gas phase with an acyl ion generated as the secondary reactive chemical by ionization plasma in a mass spectrometer. It was suggested that the mechanism of this process involved the formation of an acylated tetrazole intermediate, which could not be isolated in a condensed phase, and by rearrangement with nitrogen loss afforded an oxadiazole <20010MS1069> (cf. Section 6.07.5.2.2, Equation 16). This experiment has no preparative value but provides important information on the interaction mechanism between the neutral N-unsubstituted tetrazoles and electrophilic agents in the gas phase. 

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. 

First, consider substituent effects on the tautomeric equihbria in C5-substituted tetrazole derivatives (Scheme 5). The substituent X acts not only on neighboring nitrogen atoms but also on other atoms. It can be assumed that the location of the proton depends on the electronic structure of the substituent, which can influence the abdity of nitrogen atoms to accept the proton. 

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). 

Tetrazole, l-(p-substituted phenyl)-antimicrobial activity, 5, 835 Tetrazole, 5-thio-rearrangements, 5, 823 Tetrazole, 2-thioacyl-reactions, 5, 109 Tetrazole, 5-(o-tolyl)-tautomerism, 5, 804 Tetrazole, 5-(p-tolyl)-dipole moments, 5, 795 tautomerism, 5, 804 Tetrazole, 5-(trimethylsilylamino)-synthesis, 5, 832 Tefrazolecarbaldehydes reactions, 5, 820 Tetrazole-5-carbaldehydes reactions, 5, 820 Tetrazolecarbonitriles reactions, 5, 820 Tetrazole carbonyl compounds reactions, 5, 820 Tetrazolecarboxylic acid, 5-aryl-acidity, 5, 816... 

All triazoles, tetrazoles, and unsymmetrically substituted imidazoles and pyrazoles can exist in two tautomeric forms, e.g., 1 2 and 3 4. However, attempts to isolate the individual tautomers have been unsuccessful, always leading to one isomer (for summaries of this aspect of the tautomerism of imidazoles, see references 1 and 2). Although the isolation of both tautomers of a number of com-... 

A detailed analysis of substituent effects on the pKa values of imidazoles and tetrazoles as well as benzimidazoles and naphthimidazoles has been made.308 The ortho effect is shown to parallel that of 2-substituted pyridines and quinolines47 190 and application of the Hammett equation to the tautomerism of these systems is also considered. The equation also satisfies the effect of substituents on the basicity of the nitrogen in the 1-position for 1-pyrazolines.309... 

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