Tetrazoles, mesoionic

In general, tetrazolium salts are stable in mineral acids. This stability has allowed a number of synthetic transformations such as ester and amide hydrolysis and demethylation of ethers etc.209-212 This is not the case with tetrazolium salts containing a heterocyclic substituent in the 3-position. They tend to decompose in mineral acid to the corresponding tetrazoles.230 Tetrazolyl-substituted tetrazoliums (146) and mesoionic tetrazoles, e.g., 145, are unaffected by acids.228,232... 

The mesoionic tetrazole dehydrodithizone is transformed by iron penta-carbonyl into 4-phenyl-2-phenylazo-A2-l,3,4-thiadiazolin-5-one, presumably by a mechanism of ring opening, complexation, carbonyl insertion and subsequent ring closure (Scheme 128).193 Unfortunately, analogous processes do not occur on other mesoionic compounds in the 1,2,3-oxadiazole, s-triazole or tetrazole series, and the scope of this unusual carbonylation is probably limited. 

The photochemical reaction of azide-functionalized tetrazole derivatives such as 38 leads to the formation of the 5-5 bicyclic ring system 40 (Scheme 5) in very moderate yields <1999JHC863>. This reaction is believed to proceed via the singlet nitrene intermediate 39. Attack at the aromatic substituent in ortho position leads to product 40 <1974JOG2546> by subsequent cyclization. This intermediate is deprotonated during the workup conditions to the mesoionic tricyclic derivative 41. 

An alternative approach to 5-5 bicyclic fused ring systems utilizing a condensation reaction was described by Moderhack et al. <2000JPC591> (Scheme 10). The amino-substituted tetrazole derivatives 52 and 54 gave the neutral 53 as well as the mesoionic derivatives 55 in moderate to excellent yields (16-86% R = CH3 or Ph). 

Dehydrodithizone (252) adds directly to DMAD to give the thiazolo-tetrazole 253 with no loss of fragments that are usually extruded during cycloadditions to mesoionic compounds.124... 

Measured dipole moments for a series of substituted tetrazoles gave interesting comparisons (56JA4197). The moments for 1-ethyltetrazole (5.46 D) and 2-ethyl tetrazole (2.65 D) were at either side of the mesoionic compound (7) (4.02 D) and the dipole moments could not be used to identify mesoionic structures. The dipole moments for the 1,5-disubstituted tetrazole structure were consistently high, >5.3 D, while those of the 2,5-disubstituted structure were low, <2.65 D theoretical calculations support this (61T237). Recently, dipole moment measurements were made on 5-(p-tolyl)tetrazole in dioxane (fio 4.99), its 1-methyl isomer 6.03) and its 2-methyl isomer (jUd 2.41) (80JHC1374). These results, when applied to the annular tautomerism of 5-( p-tolyl)tetrazole, suggested 60 10% of the 1-NH form in this medium. 

Treatment of acylhydrazines with diazonium salts gives rise to tetrazenes (199) which can be readily dehydrated with base to give 1,5-disubstituted tetrazoles (Scheme 33). The reaction is also effective with 1,2-diacylhydrazines since one of the acyl groups is cleaved during the dehydrative cyclization, which may be conveniently carried out in situ without isolation of the tetrazene. This reaction can be useful for the synthesis of 1-aryltetrazoles using 1,2-diformylhydrazine as substrate (B-67MI41300). Mesoionic tetrazolium 5-oxides (8a) are obtained on treatment of bis(alkylsulfonyl)methanes with diazonium salts. Hydra-zones of type (200) are also obtained from these reactions and the tetrazenes... 

Although in most cyclization reactions the 5(4//)-oxazolones react as 1,3-dipolar reactants (azo-methine ylides) through the mesoionic tautomers, they serve as dipolarophiles with nitrile imines <92H(34)315>. The nitrile imines, generated by the thermal decomposition of tetrazoles (82), add across the 2,3 double bond to generate triazoles (83) after further reaction (Scheme 26). Since the 5(4//)-oxazolones with a hydrogen at position 4 are in equilibrium with the 5(2//)-oxazolones under the reaction conditions, the addition of the nitrile imine also occurs across the 3,4-double bond of these compounds to afford an isomeric triazole (84). Pyrazines (85), which are products of the thermal decomposition of 5(4 0 Oxazolones <76HCA2149>, as well as diarylethylenes (86), are also formed. 

Treatment of a suspension of an excess of the disodium salt 1 with 3% sulfuric acid afforded a compound in 41 % yield whose elemental analysis is in agreement with the structure of the mesoionic pentazine 2.14 15N-Labeling experiments are also in agreement with the proposed structure. In the IR spectra of 2, the following bands can be observed 995, 1050, 1100, 1165, 1200 and 1410 cm - l tetrazole anion 1636 cm-1 C=N 1938 cm -1 N-N = N group of pentazine 3410-3470 cm-1 water of crystallization 3570 cm-1 N —H. 

Some further alkylation reactions leading to mesoionic tetrazoles are in Section III,D. 

Recent studies of mesoionic tetrazoles have centered mainly on 2,3-diphenyl-2//-tetrazolium-5-thiolate (72), also known as dehydro-dithizone, and on the synthesis of some new tetrazoles. The structure of the product formed when dithizone (207) was oxidized with a number of oxidizing agents was correctly formulated as 72 by Ogilvie and Corwin446 and has since been confirmed by X-ray analysis."3,134... 

A full review of the chemistry of mesoionic compounds including the early work on tetrazoles, has been published recently.468... 

The synthesis, spectral characteristics, and the reactions of electrophiles with 1//- and (mesoionic) 2//-pyrrolotetrazoles were studied <01JCS(P1)720, 729>. The synthesis and crystal structure of a a-keto tetrazole-based dipeptide mimics has been reported <01TL5641>. Novel tetrazol-5-yl-isoquinolinium zwitterions have been synthesized and confirmed by X-ray diffraction analysis <01JHC199>. Application of natural bond orbital analysis to delocalization and aromaticity in C-substituted tetrazoles has been investigated <01JOC8737>. 

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