Tetrazoles ring fragmentation

A benzofuran ring replaces one of the benzene rings of the biphenyl moiety present in many of the sartans in the rather more complex drug saprisartan (80-10). It is of note, further, that the acidic proton is provided in this case by a trifluorosulfo-namide instead of the more common tetrazole ring. Construction of the imidazole fragment begins by nitrosation of the (3-ketoester (79-1) by means of sodium nitrite in acid to afford the oxime (79-2). Reaction with acetyl chloride leads to the ester (79-3). Reaction of this last intermediate with the iminoether from propionitrile then affords the imidazole (79-4). 

Dipolar cycloreversion was found for several, mainly the heteroatom-rich, compounds such as pentazole (48), tetrazoles (38,46,47,48), tetrazo-lines (43), tetrazolinones (44) and -thiones (45), 1,3,4-thiadiazolines (39), 1,3,4-oxadiazolidines (42), 13,4-oxathiazolinone (40), and 1,2,3-thiadiazole (49). When the compound has an exocyclic double bond, this ring fragmentation produces two compounds with cumulated double bonds. 

Recently, the photolysis reactions of a range of tetrazoles have been investigated. Photolysis of tetrazoles in general involves ring fragmentation with evolution of nitrogen, but the specific reaction varies with the composition of the tetrazole species. 

In the modified procedure one of several heteroaromatic sulfones is used. The crucial role of the heterocyclic ring is to provide a nonreductive mechanism for the elimination step, which occurs by an addition-elimination mechanism that results in fragmentation to the alkene. The original example used a benzothiazole ring,279 but more recently tetrazoles have been developed for this purpose.280... 

An intramolecular cyclization of a tetrazole-containing nucleoside 64 has been observed by Chu and co-workers <1997JOC7267> (cf. other properties of this compound in Table 3). These authors reported that the 3-OH group on the arabinofuranose ring participates in an addition reaction at position 7 of the tetrazolo[l,5-c]pyrimidine ring to form 65 which is a dihydro derivative of the parent heterocycle. The final structure elucidation has been carried out with the help of the tricyclic tandem mass spectrometry (MS/MS) fragment 66. 

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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