Ring cleavage reactions in the series of azoloazines with a bridging nitrogen atom (review)

A new approach to the synthesis of lamotrigine and other 3,5-diamino-1,2,4-triazine derivatives

“…1, Table 3). The geometric parameters of the molecule are close to the usual values for tetrazo lo [1,5 b] [1,2,4]triazines. 20 The azole and azine rings are coplanar; their mean plane forms a dihedral angle of 49.4 o with the phenyl group.…”

“…We found that cleavage of fused 6 aryl and 6 hetaryl 7 aminotetrazolo[1,5 b] [1,2,4]triazines (6a-j) is an effi cient and readily accessible method for the synthesis of a number of 6 substituted 3,5 diamino 1,2,4 triazine de rivatives 1a-j.…”

“…19 Salt 7 reacts with CH active components 8a-j in the presence of sodium carbonate or acetate. The reaction affords hydrazones 9a-j, which are converted into tetrazolo [1,5 b] [1,2,4]triazines 6a-j on refluxing in ace tic acid or DMF.…”

“…A. A mixture 6 aryl and 6 hetaryl 7 aminotetrazo lo [1,5 b] [1,2,4]triazine 6a-j (0.02 mol), a copper powder (2.52 g, 0.04 mol) freshly prepared by a known method, 27 and 5 mL of acetic acid was refluxed for 2 h. Aqueous ammonia (25%, 80 mL) was added and the product was filtered off, crys tallized, and dried. B.…”

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A new in principle method for the synthesis of 6 aryl(hetaryl) 3,5 diamino 1,2,4 triazines by decomposition of pre synthesized tetrazolo[1,5 b] [1,2,4]triazines was developed. The ad vantages of this method over traditional methods were demonstrated using the synthesis of a modern antiepileptic preparation lamotrigine, as an example.

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