Tetrazines, amination

H-Azepine derivatives form a diene complex with tricarbonyliron, leaving uncomplexed the third of the double bonds. If the 3-position is substituted, two different such complexes are possible, and are in equilibrium, as seen in the NMR spectrum. An ester group in the 1-position of the complex can be removed by hydrolysis, to give an NH compound which, in contrast to the free 1/f-azepine, is stable. The 1-position can then be derivatized in the manner usual for amines (Scheme 22). The same tricarbonyliron complex can, by virtue of the uncomplexed 2,3-double bond, serve as the dienophile with 1,2,4,5-tetrazines. The uncomplexed N-ethoxycarbonylazepine also adds the tetrazine, but to the 5,6-double... 

The reaction of dimethyl-1,2,4,5-tetrazine-3,6-dicarboxylate 353 with aromatic amines gave (82CB683) pyrazolo[3,4-e][l,2,4]triazines 354 (Scheme 75). 

The inverse-electron-demand Diels-Alder reaction of 3,6-dichloro[l,2,4,5]tetrazine with alkenes and alkynes provides the synthesis of highly functionalized pyridazines. ° Also, the 4 + 2-cycloaddition reactions of the parent [l,2,4,5]tetrazine with donor-substituted alkynes, alkenes, donor-substituted and unsubstituted cycloalkenes, ketene acetals, and aminals have been investigated. ... 

The reaction of aromatic amines with tetrazine (151) gave either 1,2,4-triazoles (154) or pyrazolo[4,3-e]-l,2,4-triazines (155), depending on the substituents. While aniline, p-toluidine, p-anisidine and p-chloroaniline afford 155, the bromo and p-nitro derivatives give 154. Intermediates 152 and 153 were postulated (Scheme 22) (82CB683). 

HMX, Octagen, Octahydro-l,3,5,7-tetranitro-l,3,5,7-tetrazine RDX, Cyclonite, Hexahydro-l,3,5-trinitro-l,3,5-triazine Secondary Aliphatic Amines Selenium... 

Oxadiazolo[3,4- ][l,2,3>4]tetrazine 4,6-di-A -oxide 35 is obtained as a yellow crystalline compound (m.p. 110-112 °C (decomp.)) by reaction of the amine 44 with excess nitronium tetrafluoroborate in acetonitrile at —20°C (Scheme 1). Compound 35 is very sensitive to shock and, although it can be stored for long periods at 0 °C, it should be handled with care. The authors propose the mechanism shown in Scheme 1 to account for the formation of compound 35. When the counterion is tetrafluoroborate, the intermediate 46 cyclizes to the bicyclic cation 47, which liberates... 

The pyrazolo[3,4-( ][l,2,3,4]tetrazine derivative 49 has been reported to be formed by treatment of the hydrochloride salt of the amine 48 with sodium nitrite in aqueous ethanol at room temperature. Only a single example was described. Compound 49 was obtained as red crystals (m.p. >300°C). The product is presumed to form from the diazonium cation 50 which cyclizes via the hydrazone tautomer 51 (Scheme 2) <1998MI11>. 

Under the alternative low-temperature procedure, animation is conducted in liquid ammonia. The use of KNH2, which is more soluble than NaNH2 in this solvent, is preferable. The reaction occurs under homogeneous conditions and does not show the previous dependence on substrate basicity. Diazines, triazines, and tetrazines, which usually undergo destruction in the high temperature process, are aminated successfully in liquid ammonia. 

Of all the aza-heterocycles, pyridine possesses the least electron deficiency. Because of this, pyridine itself does not form a a-complex in liquid ammonia and cannot be aminated under these conditions. By the contrast, highly ir-deficient polyaza-heterocycles (diazines, triazines, tetrazines, pteridines, etc.) undergo oxidative amination, sometimes even by liquid ammonia itself. Sodamide converts 4-methylpyrimidine successively into the 2-mono- and 2,6-di-amino derivatives, and pyrazine gives... 

Tetrazines (624) react also with the C=N double bond of aliphatic aldehyde dimethylhydrazones. Elimination of nitrogen from the adducts (629) affords 4-aminodihydro- 1,2,4-triazines (630). The elimination of amine from (630) to give (625) has not been reported (Scheme 20) (79AP452, 81AP376). 

The use of ammonia or amines instead of sodium hydroxide for the dimerization of ethyl diazoacetate leads to the formation of dihydro-1,2,4,5-tetrazine-3,6-dicarboxamides. The products isolated were formulated either as l,2-dihydro-l,2,4,5-tetrazine derivatives (314), as l,6-dihydro-l,2,4,5-tetrazine derivatives (315), or as mixtures of both. The dimerization is usually run in alcoholic solution at temperatures from cold to 100 °C (78HC 33)1075, pp. 1157, 1158, 76G1). 

Compounds such as methylene chloride or methylene bromide (73ACS779, 72ACS1258, 63USP3086016) or tris(chloromethyl)amine (74LA1851), which can be treated as formaldehyde precursors or substitutes, have also been used for the preparation of hexahydro-1,2,4,5-tetrazines (377). 

Azobis(l,2,4,5-tetrazin-3-amine), see 3,3 -Azobis(6-amino-l,2,4,5-tetrazine), 1434b... 

A great variety of 3-alkyl- and 3-aryl-1,2,4,5-tetrazines can also easily be alkylaminated when treated with appropriate primary alkylamines in the presence of potassium permanganate (Scheme 30). The yields vary depending on the size of the alkyl group in the amine. Attempts to introduce an arylamino group were unsuccessful. 

The monocyclic diazines, triazines, and tetrazines are all theoretically subject to electrophilic attack at one or more of their annular nitrogen atoms by protons alkylating, acylating, and aminating reagents and peracids. Coordination with metals could also be classified under this heading. 

The synthesis of these compounds is relatively facile using trinitroethanol and the corresponding amines, while for the synthesis of TTD diaminotetrazole, BTTD TTD and for BTAT, diamino-tetrazine was used (Fig. 9.18). At pH values above 6, trinitroethanol behaves as an acid, so that for the Mannich reaction shown in Figure 9.18, two different mechanisms can be discussed. 

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