Azide-tetrazole isomerization

Azide-tetrazole isomerism, or valence tautomerism, was not discussed for [5.6]bicyclic systems in the previous survey (76AHCS1). During recent years, this type of ring-chain tautomerism has been extensively studied for both six- and hve-membered heterocyclic azides. Tire tautomerism of [5.5]bicyclic tetrazole systems is covered in Section II,C. We discuss the tautomerism of the six-membered heterocyclic azides in this section. 

Azide-tetrazole isomerization has been studied by NMR spee-troseopy for 2-azidothiazolo[5,4-h]- and 2-azidothiazolo[4,5-c]pyridines, and the equilibrium eonstants were determined at various temperatures (77JHC1045). 

The azide-tetrazole isomerism in several polyazido 1,3,5-triazines and diazido-1,2,4,5-tetrazines has been investigated by ab initio quantum chemical methods <06EJI2210>. 

Obviously the investigator should also be aware of any ground state reactions peculiar to the system under study. For example 2-azidopyridines isomerize to tetrazoles which are usually less sensitive than the azide to irradiation (Fig. 3.1). The position of the equilibrium is both temperature, solvent and pH dependent. Even if the equilibrium constant for such an isomerization in solution is known the situation in a ligand binding site cannot be predicted. Azide-tetrazole isomerization was an important consideration in experiments using 2-azidoadenine derivatives which have recently been described by MacFarlane et al. (1982). 

Another factor that might be expected to influence the azide-tetrazole isomerism is the syn-anti isomerism about the C=N moiety, since presumably for ring closure to occur the nitrogen lone pair must be cis to the azide group. This factor does not appear to have been discussed in any detail in the literature to date. When the azidoazomethine system is present in a cyclic molecule, the geometrical orientation of the azide... 

Attempts to apply the azide-tetrazole isomerism to the synthesis of tetrazolo[l,5-a][l,3,5]triazines were published <88IZV491>. This equilibrium was found to be shifted generally to the ring opened azides (31), and the maximum amount of the tetrazole (32) of 15% was detected in DMSO-de at 20 °C in the case of = H, R = morpholino group. The same tetrazolo ring system was, however, found to be stable with 5-styryl and 7-thio substitution <87LA65> aminotetrazole (33) when reacted with cinnamoyl isothiocyanate alTorded the tetrazolotriazine-thione (34) most likely formed via cyclization of the intermediate thiourea. 

The tetrazole is very much less sensitive to photolysis than the azide, and for a number of such systems photochemical generation of the heteroaryl nitrene has failed. This problem is important in nucleotide and nucleic acid chemistry, where azidopurines and azidopyrimidines are, at first sight, attractive candidates for photogenerated reagents. The position of the azide-tetrazole isomerization equilibrium is solvent dependent, and it is not possible to specify under what conditions (or in what kinds of receptor site) useful levels of photogenerated aryl nitrene can be produced. In general, therefore, it may be safer to avoid such systems if reasonable alternatives exist. 

The imidoyl azide-tetrazole ring-chain isomerism of tetrazoles develops into a wide-ranging example of the Dimroth rearrangement in the thermal behavior of substituted 5-aminotetrazoles <84JHC627>. An example with 5-hydrazinotetrazoles is shown in Scheme 10 <88BSB543>. The reaction... 

The effects of solvent (polarity), temperature, and substituents (the Hammet cr constants) have been studied in the azide-tetrazole equilibrium for thiazolo [2,3 -e]tetrazoles (75BSB1189 77CJC1728, 77JHC1299) oxazolo[2,3-e]- and isoxazolo[2,3-d]-tetrazoles (77CJC1728) and tetra-zolo[4,5- >]-1, 3,4-thiadiazoles (81CHE721). A rough parallelism has been proposed between the azido-tetrazole isomerism and prototropic tau-tomerism (75BSB1189). 

The development of the chemistry of the tetrazoles up to the end of 1965 has been reviewed in two papers by Benson.1 2 Shorter reviews of specific aspects of tetrazole chemistry include alkylation reactions of tetrazoles,3 synthesis of tetrazoles from aminoguanidines,4 influence of solvents on tetrazole synthesis from 1,3-cycloadditions of azides,3 general aspects of tetrazole chemistry,6 azidoazomethine tetrazole isomerism,7,8 tetrazolinyl radicals,9 and complexes of 1,5-disubstituted tetrazoles.10... 

The kinetics of the reaction is first order in both nitrile complex and azide.909 NaN3 reacts with [Co(tetren)(NCMe)]3+ at pH 5.7 to give the 5-methyltetrazolato complex [Co(tetren)(N4CMe)]2+. The reaction is biphasic, involving the initial rapid formation of the AM-bonded tetrazole followed by the slow linkage isomerization to the N2-bonded complex.907... 

Because of the presence of two azide groups in positions adjacent to the ring nitrogen atoms in compound 13a, valence bond isomerization can result in formation of 6-azido-7-methyltetrazolo[l,5-A pyridazine 14a, 6-azido-8-methyltetrazolo[l,5-A pyridazine 15a, and the bis-tetrazole compound 16a. Calculations have been carried out by using hybrid density functional theory (B3LYP/6-311+G(d,p)) and complete basis set treatments (CBS-4M). All calculations revealed that the 8-methyl derivative 15a is the most stable isomer. Similar studies on the triazide derivative 13b, however, indicated that in this case the equilibrium is shifted to the 7-methyl form 14b. All these conclusions proved to be in entire agreement with the experimental findings (see Section 11.18.3.2.). 

The fused tetrazoles 10 containing various aryl groups in position 6 were boiled in acetic acid in the presence of either triphenylphosphine or copper and gave rise to the amino-substituted triazines 12. The reaction proceeds obviously via valence bond isomerization of 10 to the azide 11 and is regarded as a useful synthetic route to the diamino compounds 12. 

The tetramethylammonium triazine-olate 55 was treated with sodium azide, whereupon nucleophilic exchange of the trinitromethyl substituent took place to give the azide intermediate 56, which spontaneously underwent valence bond isomerization to the fused tetrazole 57. 

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