5- Aminotetrazoles

In a rather different reaction, aminotetrazoles treated with bromine lose nitrogen and give isocyanide dibromides (77AHC(2l)323) probably the mechanism is as shown in Scheme 54. 

Attempted diazotization in dilute acid sometimes yields primary nitroso compounds. Reactions of 3- and 5-amino-1,2,4-thiadiazoles with sodium nitrite and acid give primary nitrosamines (e.g. 432->433) (65AHC(5)n9) which can be related to the secondary nitrosamines (434) prepared in the normal way. 1-Substituted 5-aminotetrazoles with nitrous acid give stable primary nitrosamines (435). Primary nitrosamines have been isolated in the imidazole series. 

The thermal conversion of 1-substituted 5-aminotetrazole (423) into a 5-substituted aminotetrazole (424) can be rationalized by a similar 1,5-dipolar cyclization. 

In the same way, l-substituted-5-aminotetrazoles react with benzyl chloride to give 1-substituted 4-benzyl-5-iminotetrazolines. ... 

As was concluded (97MI84), many other factors that may affect the position of the amino-imino tautomerism of aminotetrazoles remain to be elucidated. 

The hydroxy group of furazan 263 reacted with cyanogen bromide in glyme in the presence of Li2C03 to give cyanate 264 in 70-85% yield (97MI8). Upon treatment with Mc4NN3 and subsequently with a basic solution of hydroxylamine-0-sulfonic acid, /V-aminotetrazole 265 was obtained in 35% yield (Scheme 171). 

The 3-formyl group of 8-substituted 3-formyl-2-hydroxy-4//-pyrido[l,2-n]pyrimidin-4-one was reacted with (cyanomethyl)- and (terr-butoxycarbo-nylmethylene)triphenylphosphorane in THF, and with 5-aminotetrazole in boiling MeOH for 9h to yield ( )-3-propenenitrile, terr-butyl ( )-3-propenoate and 3-[(2//-tetrazol-5-yl)imino]methyl derivatives, respectively (OlMIPl). 

In 1951, aminotetrazoles were reported to exist in the imino form 210 rather than in the amino form (2H) on the basis of chemical... 

The high reactivity of heterocyclic diazonium ions in azo coupling reactions is the reason why in some cases the primary diazotization products cannot be isolated. For example, diazotization of 2-methyl-5-aminotetrazole (2.14) directly yields the triazene 2.15, i. e., the N-coupling product, since the intermediate diazonium ion is reactive enough to give the N-coupling product with the parent amine even under strongly acidic conditions (Scheme 2-8 Butler and Scott, 1967). 

See 5-Aminotetrazole Nitrous acid See other DIAZONIUM SALTS, TETRAZOLES... 

Diazotised 5-aminotetrazole is unstable under the conditions recommended for its use as a biochemical reagent. While the pH of the diazotised material (the cation of which contains 87% nitrogen) at 0°C was being reduced to 5 by addition of potassium hydroxide, a violent explosion occurred [1], This may have been caused by a local excess of alkali causing the formation of the internal salt, 5-diazoniotetrazolide, which will explode in concentrated solution at 0°C [2], The diazonium chloride is also very unstable in concentrated solution at 0°C. Small-scale diazotisation (2 g of amine) and susequent coupling at pH 3 with ethyl cyanoacetate to prepare ethyl 2-cyano-(l//-tetrazol-5-ylhydrazono)acetate proceeded uneventfully, but on double the scale a violent explosion occurred [3], The importance of adequate dilution of the reaction media to prevent explosions during diazotisation is stressed [4]. 

The reaction of 73 with 2-aminotetrazole hydrate gave different products depending on the reaction conditions. Under the conditions applied for the preparation of 74 4-oxo-3-phenylpyrido[2,1 -/] [ 1,2,4]triazinium-2-olate 75 was obtained, whereas the amino derivative 76 was obtained by using diisopropylethylamine (Hunig s base) as the base (Scheme 1) <1996T11349>. 

Aminotetrazole reacts with 4,5-dichloro-l,2,3-dithiazolium chloride 166 to afford the bis(imino-l,2,3-dithiazole) 167 (20%) which in warm DMSO or DMF converts into the 1,2,3-clithiazolimine 168 (25%) (Scheme 16) <2002J(P1)1535>. 

Other approaches to tetrazoles were also recently published. Primary and secondary amines 195 were reacted with isothiocyanates to afford thioureas 196, which underwent mercury(II)-promoted attack of azide anion, to provide 5-aminotetrazoles 197 . A modified Ugi reaction of substituted methylisocyanoacetates 198, ketones, primary amines, and trimethylsilyldiazomethane afforded the one-pot solution phase preparation of fused tetrazole-ketopiperazines 200 via intermediate 199 <00TL8729>. Microwave-assisted preparation of aryl cyanides, prepared from aryl bromides 201, with sodium azide afforded aryl tetrazoles 202 . 

The synthesis of the polycyclic 5-5-6-5 derivative 81 was realized by nucleophilic substitution of the 5,6-dichloro[ 1,2,5]oxadiazolo[5,4-7]pyrazine 79 with 5-aminotetrazole 80 (Scheme 17). This conversion took place at room temperature and the product 81 was isolated in moderate 36% yield. Many other heterocyclizations with N,N, N,0-, /V,.Y-bidentate nucleophiles gave the corresponding reaction in up to 93% yield <1997CHE1352>. 

In Scheme 20, another ring closure starting from 5-aminotetrazole is shown, which should be discussed in more detail. Nenajdenko and co-workers carried out studies on ring closure reactions taking place between 1,1,1-trifluoro-4-sulfonyl-but-3-ene-2,2-diols 107 and a series of aminoazoles <2002S901>. They found that the reaction can take place in two different ways and, thus, the isomers 108 and 109 can be formed. Reaction of 107 with 5-aminotetrazole 106 was found to proceed regioselectively, and yielded the 5-trifluoromethyl compound 108 as the main product in good yield (72%). The other isomer 109 was found only in traces. 

Table 9 Synthesis of tetrazolo[1,5-a]pyrimidines starting from 5-aminotetrazole...

The reaction sequence starts from tetrazolyldiazonium salt 42 prepared from aminotetrazole 41 by diazotation. This compound when reacted with arylformylacetonitrile 43 leads to the intermediate formation of the condensation product 44, which easily undergoes ring closure to 45. This tetrazolo[5,l-z][l,2,4]triazine compound, however, forms an equilibrium with the valence bond isomeric azide 46, which can participate in a different ring closure than the reverse route, and yields the tetrazolo[l,5-A][l,2,4]triazine product 47. The reaction was carried out with a series of various aryl derivatives and proceeded in good to excellent yields (68-87%). 

Formation of the partially saturated nitro derivatives 60 and 61 was reported by a Russian team <1994KGS1129>. The two products were obtained under fairly complicated reaction conditions when aminotetrazole 42 was first treated with potassium amidosulfonate and formaldehyde at pH = 4 followed by addition of nitric acid, methylamine, and acetic anhydride, product 60 was obtained in 24% yield. The same reaction, however, carried out at pH = 6 gave rise to formation of the acetoxy compound 61 in 21% yield. 

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