Triazoles and Tetrazoles

It is known that 1//-1,2,3-triazoles can exist in equilibrium with diazo-imines. In the conversion of 1 into 2 as intermediate the diazo-imine 3 can 

A complete structural assignment of some nitrotriazoles has been carried out [565], The tautomerism and the isomerism of triazoles make the structure analysis of 

Pevzner et al. widely used NMR spectroscopy in their structural investigations of diverse 1,2,4-triazole nitro derivatives [566-581], In the series of 5-substituted l-methyl-3-nitro-1,2,4-triazoles the correlation between the A-methyl group proton chemical shifts induced by 5-substituents (A8) and the substituent Hammett constants has been found to divide into two branches [577], This nonordinal event is explained by impossibility of any additional contribution to the shielding of substituents having two and more lone electron pairs [577], 

In the reaction of 3-nitro-177-1,2,4-triazole with benzyl chloride it was possible to obtain l-benzyl-3-nitro-177-l,2,4-triazole (60%), l-benzyl-5-nitro-17/-l,2,4-triazole (10%), and 4-benzyl-3-nitro-177-l,2,4-triazole (4%), whose structures were determined by H and 13C NMR with homonuclear NOE difference spectroscopy (Table 3.21) [559], The tautomerism of C-nitro-substituted 1,2,4-triazoles was studied by NMR and IR spectroscopy [582], 31P NMR spectroscopy was employed for the identification of nitrated triazolyl-1 phosphates [583, 584], 

In the reaction of 3-nitro-5-R-l,2,4-triazolate-anion with 3,5-dinitro-l-(2-oxo-propyl)-l,2,4-triazole both the products of nucleophilic substitution in position 5 and condensed compounds [5-methyl-5-(3-nitro-5-R-l,2,4-triazol-l-yl)-5,6-dihydroxazolo[3,2-b]-l,2,4-triazoles] are formed. Their structures were established by H NMR and IR spectroscopy [585], 

Proton spectra were used for establishing the structure of thermal decomposition product of 15N-labeled 3-nitro-l,2,4-lriazol-5-one [587], l,4-dimelhoxy-2-(3-nitro-l, 

Sodium hydride in DMF at room temperature induces rearrangement of some l,4-dialkyl-4 T-l,2,4-triazolium salts to 5-aminoimidazoles the reaction can be generalized to permit synthesis of 4-acyl-5-aminoimidazoles from readily accessible starting materials, but yields are only moderate (21-60%) [22]. 

Relative Aromaticity of Five-Membered Ring Heterocycles  

The bond lengths for the 1/f-1,2,4-triazole are shown below, which impact the coupling constants in their H-NMR spectra. 

4-triazole s H-NMR spectrum, the chemical shift for both H3 and H5 is the same (due to the tautomerization between the nitrogen atoms) at 8.32 ppm. Like other NH-containing heterocycles, the chemical shift of triazole s NH largely depends on the solvent used to do the NMR spectrum. 

Mi iiiijiiiiprii iiii niiiFiii iiii in1ipfffTW T ff7 rnYmTiTininlYfmiiTlTr[MiVfiTu Tiii iTiTiTmi7iTiJiTii rrMfiW  

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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). 

The situation is more complex for triazoles and tetrazoles where qther effects such as lone-pair repulsions intervene see discussion in (76AHC(SD296). 

Imidazoles and benzimidazoles (155) react with acid chloride and alkali to give compounds of type (157), but these are reactions of the cation (156). 1,2,4-Triazoles and tetrazoles similarly undergo ring opening. 

Discussion of these compounds is divided into isomers of aromatic compounds, and dihydro and tetrahydro derivatives. The isomers of aromatic azoles are a relatively little-studied class of compounds. Dihydro and tetrahydro derivatives with two heteroatoms are quite well-studied, but such compounds become more obscure and elusive as the number of heteroatoms increases. Thus dihydrotriazoles are rare dihydrotetrazoles and tetrahydro-triazoles and -tetrazoles are unknown unless they contain doubly bonded exocyclic substituents. 

The classical age of preparative organic chemistry saw the exploration of the extensive field of five-membered heterocyclic aromatic systems. The stability of these systems, in contrast to saturated systems, is not necessarily affected by the accumulation of neighboring heteroatoms. In the series pyrrole, pyrazole, triazole, and tetrazole an increasing stability is observed in the presence of electrophiles and oxidants, and a natural next step was to attempt the synthesis of pentazole (1). However, pentazole has eluded the manifold and continual efforts to synthesize and isolate it. 

Similar isomerization reactions were observed in CDCI3 solutions of N-( -aminomethyl)-l,2,4-triazoles and -tetrazoles (90T633). As for the analogous benzotriazoles, these reactions are-intermolecular and slow at 20°C in the NMR time scale. 

It should be emphasized that the correct description of the peculiar effect brought about by the presence of two or more sp -nitrogen centers within a molecule can be reproduced reliably only by high level ah initio calculations accounting for electron correlation. This conclusion is well justified by the examples of benzotriazole, 3-amino-l,2,4-triazole, and tetrazole, as described in Sections II,B,3 II,B,4 and II,B,5, respectively. 

It has been suggested that imidazole, 1,3,4-triazole, and tetrazole are ionized in the solid state (cf. 13). However, a careful assessment of X-ray, dipole moment, and ultraviolet spectral evidence by Zimmerman led to the conclusion that imidazoles are associated but not ionized. The same author has also interpreted the infrared spectra of... 

Since HF calculations have a tendency to underestimate the N—N and the C—N bond lengths in triazoles [98JPC(A)620, 98JPC(A) 10348], the structural parameters should be computed at least at the DFT or MP2 levels. This is particularly true if electron-donating substituents are attached to the ring. Nitrogen NMR shielding tensors were computed for a set of methylated triazoles and tetrazoles but will be discussed in the context of tetrazoles (cf. Section IV,B). 

The nitrogen NMR shieldings in methylated triazoles and tetrazoles were computed at the GIAO/HF/6-31-I--I-G level and more recently using multireference... 

In an analogous way heteroaromatic diazonium ions that contain an acidic NH group in the heteroaromatic ring, e. g., the diazole, triazole, and tetrazole derivatives 5.1, 5.2, and 5.3, lose that proton even in weakly to strongly acidic solutions, as... 

The synthesis and chemistry of pyrazoles, imidazoles, and 1,2,3-triazoles were actively pursued in 2006. A review on the cross-coupling reactions on azoles with two and more heteroatoms for pyrazoles and imidazoles has been published <06EJO3283>. Publications relating to 1,2,4-triazole and tetrazole chemistry were not particularly well represented this year. The solid-phase and combinatorial chemistry of these ring systems have not been investigated compared to past years. No attempt has been made to incorporate all the exciting chemistry or biological applications that have been published this year. 

These methods have been applied mainly to imidazol-, benzimidazol-, thiazol-, and benzthiazol-based car-benes,255,274,275 but there are also examples with triazols and tetrazoles.274 In the following, a few representative examples are presented which illustrate the strategies. The complex with a carbazol ligand shows strong luminescence (Scheme 69).272... 

The synthesis of nitriles from halides is valuable in medicinal chemistry because nitriles are flexible building blocks readily converted into carboxylic acids, amides, amines, or a variety of heterocycles, e. g. thiazoles, oxazolidones, triazoles, and tetrazoles. The importance of the tetrazole group in medicinal chemistry is easily understood if we consider that it is the most commonly used bioisostere of the carboxyl group. 

A comprehensive study of the vibrational spectra of 1,2,4-triazole in comparison to those of 1,2,3-triazole and tetrazole has been carried out <2000JST(530)183>. The tautomerism displayed by simple 1,2,4-triazole thiones has also been studied using vibrational spectroscopic techniques and the preferred tautomers present in the solid state determined <1997SAA699>. 

The 1,3-dipoles were generated by the addition of Et3N in 20% excess. Only imidazole was basic enough to generate a nitrile oxide in the absence of triethy-lamine. Due to prototropic tautomerism, reactions of triazoles and tetrazoles led to mixtures of two isomers. With unsubstituted pyrazole and imidazole only one hydroximoylazole was formed (117). 

Figure 2.3 Use of triazole and tetrazole derivatives for glycosyl fluoride synthesis.

Spin cross-over iron(II)-triazole and -tetrazole complexes have been reviewed. 

J0rgensen [111] and Vicario [112] independently described the conjugate addition of both triazole and tetrazole based nucleophiles to a,P-unsaturated aldehyde substrates as an alternative method for C-N bond formation. These reactions were catalysed by the diarylprolinol and imidazolidinone scaffolds with equal efficiency showing the complementarity and efficacy of both these catalyst architectures. In addition, Jprgensen has also shown succinimide to be an effective Michael donor (see Sect. 2.3.5 Scheme 49 for further details) [113]. 

As shown in Fig. 5, the pX,s of the azoles (imidazoles, 1,2,4-triazoles, and tetrazoles) which do not protonate next to an NH group are linearly related to the pX,s of the corresponding pyridines. It is interesting to notice that the... 

Triazoles and Tetrazoles with Fused Six-membered Rings Volume 5 References... 

According to the indices, pyrazole is more aromatic than imidazole. The stability of azoles generally increases with an increasing number of aza-groups, though some exceptions are known. The relative aromaticities of triazoles and tetrazole are questionable. 2H-1,2,3-Triazole (/= 88%) which is the more stable in the gas phase reveals more bond levelling than 1//-1,2,3-triazole (1=13%). 

Substituted 1,2,3-triazoles, 1,2,4-triazoles and tetrazoles are metallated by n-butyllithium at low temperature at the 5-position. At room temperature 5-lithium derivatives tend to undergo ring opening. No direct lithiation of a 2-substituted 1,2,3-triazole has been reported. 

In effect, antifoggants enhance the difference between the rate of formation of the desired image density and that of fog density. Many heterocyclic compounds have been claimed to restrain fog. These include suitably substituted benzotriazoles, benzimidazoles, indazoles, oxazoles, thiazoles, triazoles and tetrazoles. Heterocyclic compounds bearing a thiol substituent invariably show some antifoggant activity. Thus phenylmercaptotetrazole (16) which contains both a thiol group and a tetrazole ring is very effective (59MI11400). 

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