1.2.4- triazole tautomers

The relative stability of 1,2,3-triazole and benzotriazole tautomers can be rationalized based on the concept of aromaticity. The aromaticity of both 1,2,3-triazole tautomers probably being similar, the lone-lone pair repulsion accounts for the lower stability of 1//-1,2,3-triazole. In the case of benzotriazole, the aromaticity of the benzenoid 1//-benzotriazole has been considered greater than that of the quinonoid 2//-benzotriazole <89JA7348>. However, great care must be taken in measuring the difference in aromaticity between the two tautomers because this will depend strongly on the dielectric constant of the medium. 

The alkylation of 4-amino-l,2,4-triazolo-3-thione derivatives using haloalkyl nitriles to give the S-alkylated product as a result of alkylation of the 3-mercato-l,2,4-triazole tautomer, or the corresponding N-alkylated product resulting from reaction with the 3-thione tautomer, has been studied extensively optimum conditions have been developed to provide either the S- or the N-alkylated products in good yields <2000PS(167)219, 2003BML2601>. 

To the best of our knowledge the sensitivity of FEP calculations to this overestimation of electrostatic interaction has received little attention. Cox et al24 did use scaled 6-31G charges in their successful treatment of the 1,2,3-and 1,2,4-triazole tautomer equilibria, but no comparison was made with unsealed charges. This factor could however be of crucial importance in calculation of tautomeric equilibria, where fine differences are important. 

The aromaticity of triazole tautomers was assessed by the Bird indices 122 2H-1,2,3-triazole (91B, 1= 88) was found to be slightly more aromatic than its 1H-isomer (91A, 1= 73). The small difference in Bird indices supports only a weak influence of the aromaticity, and the lower stability of the 1 //-isomer was explained by the nitrogen lone-pair repulsion that destabilizes cyclic azo derivatives. 

Thus, we have studied theoretically the tautomerism of pyridones and 1,2,4-triazoles related to two crown ethers and two crown esters derived from these heterocycles [209], For the four macrocycles 262-265, Bradshaw identified a single tautomer by X-ray crystallography [210-213], To rationalize these findings, a series of calculations from simple models to crown derivatives were carried out. The most interesting case concerns the observation, for the first time, of a 4H-1,2,4-triazole tautomer 265b. 

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). 

Amino-l,2,4-triazole undergoes a cyclocondensation with 3-etlioxyacrolein (7) to form 1,2,4-triazolo[l,5-a]pyrimidine (3) or its [4,3-u] isomer (5), according to whether it reacts as IH or 4H tautomer 2 or 4. Moreover, the pyrimidines 3 and 5 can interconvert by a Dimroth rearrangement. Since the H NMR spectrum 30a does not enable a clear distinction to be made AMX systems for... 

Bis(3,4-diethyl-2-pyrrolylmethyl)-3,4-dietliyl-l//-pyrrole (2), prepared in situ from the di-t-butylester of the 5,5 -dicarboxylic acid (/), reacts with 4//-1,2,4-triazole-3,5-dialdehyde (3) in di-chloromethane in the presence of trifluoroacetic acid and 2,3-dichloro-5,6-dicyano-/)-benzoquino-ne as an oxidation reagent. Dark blue crystals are obtained after chromatographic purification. The dark violet chloroform solution fluoresces purple at 360 nm and gives the NMR experiments 39. Which compound and which tautomer of it has been formed ... 

The equivalence of the inner NH protons (Sm = - 2.35) as well as correlation signals with the pyrrolic carbons only (5c = 143.8, 141.6, 139.8 and 136.7) provide evidence for the diaza[18]-annulene tautomer 4a. Two separate NT/ proton signals and cross signals with the a-carbon atoms (5c = 159.3) of the triazole ring are expected, in contrast, for the tetraaza[18]annulene tautomer 4b. 

Contributions in this section are important because they provide structural information (geometries, dipole moments, and rotational constants) of individual tautomers in the gas phase. The molecular structure and tautomer equilibrium of 1,2,3-triazole (20) has been determined by MW spectroscopy [88ACSA(A)500].This case is paradigmatic since it illustrates one of the limitations of this technique the sensitivity depends on the dipole moment and compounds without a permanent dipole are invisible for MW. In the case of 1,2,3-triazole, the dipole moments are 4.38 and 0.218 D for 20b and 20a, respectively. Hence the signals for 20a are very weak. Nevertheless, the relative abundance of the tautomers, estimated from intensity measurements, is 20b/20a 1 1000 at room temperature. The structural refinement of 20a was carried out based upon the electron diffraction data (Section V,D,4). 

The crystal structure analysis of the parent 1,2,3-triazole in the solid state unambiguously demonstrated that it crystallizes as a 1 1 molecular complex of both possible tautomers 24a and 24b, linked by a N-H - N hydrogen bond [97AX(C)1846]. 

Whereas most 3-amino-l,2,4-triazoles prefer the amino form 60 [76AHC (SI), p. 439,445 80KGS1414], strong electron withdrawing substituents can lead to the predominance of the imino form, as is the case of the compound 65 (R = C3F7) (80KGS1414) or to 5-amino tautomer 61 (R = H, R = CF3) [98AX(C)442]. This conclusion was based on gas-phase IR and mass-spectroscopic studies. 

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