Amino Tetrazole Derivatives

Nomenclature, Formulas, Melting Points and Heats of Explosion of 5-Amino Tetrazole Derivatives Used as Experimental Propellant Additives (Ref 4)... 

The 1 1 complexes arising from interaction of the hydride (as a complex with ether or trimethylamine) and various tetrazole derivatives are explosive. Tetrazoles mentioned are 2-methyl-, 2-ethyl-, 5-ethyl-, 2-methyl-5-vinyl-, 5-amino-2-ethyl-, l-alkyl-5-amino-, and 5-cyano-2-methyl-tetrazole. 

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). 

The synthetic pathway to tetrazolo[l,5-tf]pyrimidines starting from 5-amino-tetrazoles has already been discussed in CHEC-II(1996) <1996CHEC-II(8)465>. During the recent period of time, several modifications of this approach have been described. The obtained products - among them some partly saturated derivatives - and the applied reagents as well as yields and references are summarized in Table 9. 

Amino-tetrazole and derivs 9 T115—T121 [N, N6-bis (a-tetrazolyl-5)]-hexazadiene 1 A260-A261... 

Amination at an azole ring nitrogen is known for N-unsubstituted azoles. Thus, 1,2,3-triazole and 4,5-diphenyl-l,2,3-triazole with hydroxylamine-O-sulfonic acid give 1-amino 145 and 2-amino 146 derivatives in a ratio of 4 1 and 1 3, respectively. 3-Amino-5-/isy/-butylpyrazole affords 147 and indazole and tetrazole give comparable amounts of the 1- and 2-amino derivatives, and ethyl benzothiazol-2-ylcarboxylate reacts at room temperature <2001JOC8528>. Pyrazole is easily N-nitrated with nitrogen dioxide in the presence of ozone <1996JCR(S)388>. 

The pyrazole- and thiazole analogues of the 3 -deoxy-3 -amino-4 -methoxy Combretastatin A-4 showed potent antimitotic (IC50 3.0 pM and IC50 10 pM) activity. The former showed also a potent cytotoxic activity (IC50 8.4 nM ). Moderate antimitotic activity (IC50 3.0 pM) and weak cytotoxic activity was observed for a triazole derivative, whereas tetrazole ring confers potent antimitotic (ICso 2.0 pM) as well as cytotoxic activity. Compounds with potent cjdotoxicity were further evaluated in vivo in the Colon murine tumor model. The best antitumor activity in vivo, expressed as tumour growth suppression, was observed for the thiazole and tetrazole derivatives with values comparable to the ones observed for 3 -deoxy-3 -amino Combretastatin A-4 hydrochloride. 

Several ring-fused tetrazole compounds have been reported. 2-Methyl-3-cyanopyridines were converted into their corresponding 2-azidomethyl derivatives, which underwent intramolecular cycloaddition reactions to give 3-(tetrazol-5-yl)pyridines 186 <04TL9127>. Fused tetrazole derivatives 187 were obtained via tandem cycloaddition and yV-allylation reactions <04JOC1346>. Expeditive synthesis of homochiral fused tetrazole piperazines 188 from 3-amino alcohols has been reported <04TL3725>. A novel Ugi-five-center-four-component reaction (U-5C-4CR) of aldehydes, primary amines, trimethylsilyl azide and 2-isocyanoethyl tosylate afforded tetrazolopiperazine type compounds <04TL6421>. 

In 2005, the first one-pot three-component Mannich reaction catalyzed by simple acyclic primary amino acids and their derivatives (e.g., tetrazole derivatives) was disclosed (Scheme 4.5) [28]. It was realized by the prior findings that natural acychc... 

Fokin et al. directly fluorinated several aminofurazans (Scheme 14) to prepare 3-(difluoramino)furazans [109,110]. Similarly, certain N-alkyl-5-amino-tetrazoles were amenable to direct fluorination to 5-(difluoramino)tetrazole derivatives [111,112]. NF2-containing 1,2,4-oxadiazoles were prepared by Shreeve and coworkers by reactions of sodium 5-[(difluoraminomethyl)di-fluoromethyl]tetrazolate with oxalyl chloride [113]. 

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