Tetrazole ring reactivity

An azido-nitrile (formed in situ from the reactive chloropyridazine and sodium azide) is efficiently converted into a fused tetrazole ring on heating in DMF. 

Azole anions are derived from imidazoles, pyrazoles, triazoles or tetrazoles by proto loss from a ring NH group. In contrast to the neutral azoles, azole anions show enhance reactivity toward electrophiles, both at the nitrogen (Section 4.02.1.3.6) and carbon aton (Section 4.02.1.4.1(i)). They are correspondingly unreactive toward nucleophiles. 

The compounds referred to as azolides are heterocyclic amides in which the amide nitrogen is part of an azole ring, such as imidazole, pyrazole, triazole, tetrazole, benzimidazole, benzotriazole, and their substituted derivatives. In contrast to normal amides, most of which show particularly low reactivities in such nucleophilic reactions as hydrolysis, alcoholysis, aminolysis, etc., the azolides are characterized by high reactivities in reactions with nucleophiles within the carbonyl group placing these compounds at about the same reactivity level as the corresponding acid chlorides or anhydrides. 11... 

In the new structures of type (59) the reactive centre is the methanide site which behaves as a nucleophile. <86JCS(Pi)ii57, 92JCS(P1)1483> (Section 4.17.8). Tautomeric tetrazole-tetrazoline structures of general type (4 R = H) may show ambident reactivity with reactions occurring on the ring or the exocyclic X atom (Sections 4.17.6 and 4.17.7). 

REACTIVITY AT RING ATOMS AROMATIC AND NON-AROMATIC TETRAZOLES... 

Because of the deactivated ir-deficient nature of the ring, nucleophilic attack can readily occur on tetrazoles. Nucleophilic replacement of halogens at the C-5 position has been widely used for the synthesis of disubstituted tetrazoles, e.g. (56). Kinetic studies of the reaction between 5-bromo-l-methyltetrazole and the 2-methyl isomer with piperidine have shown the 1-methyl compound to be considerably more reactive. Comparison of these kinetics with similar reactions for a series of azoles has suggested that two to three deactivating doubly bound nitrogens (—N=) are required to overcome the electron release from one pyrrole-type nitrogen atom in these systems <67JCS(B)64l>. 

Thermal fragmentation of 2,5-disubstituted tetrazoles results in loss of Na and generation of a reactive nitrilimine intermediate (67). The Hammett p-values for the A -phenyl and C-phenyl rings of diaryltetrazoles (65) were +1.16 and -0.23, respectively, suggesting an unsymmetrical transition state of type (66) (68X3787). Subsequent additions of the nitrilimines to unsaturated bonds such as alkenes, imines, alkynes and nitriles give an added importance to the parent tetrazoles as synthetic precursors (Scheme 6). Among the most... 

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