Abstract.
A novel intramolecular cyclization reaction is reported, in which various 1,2-bis(amidinohydrazone)s are converted into 3-amino-1,2,4-triazine or its substituted analogues. The reaction is easily carried out at microscale as well as ordinary scale level by heating the appropriate bis(amidinohydrazone) to roughly 200 °C in an inert atmosphere or in vacuo. No solvents or other reagents are needed. The products are easily isolated, being sublimed off from the starting material and forming single crystals. A microscale procedure employing glass ampoules as the reaction vessel is described. The reaction is rapid and offers a facile way of preparing large series of substituted 3-amino-1,2,4-triazines individually in crystalline form for screening purposes. Because large numbers of bis(amidinohydrazone)s have been synthesized for biochemistry and drug development and libraries exist, the present method may be more practical than combinatorial approaches for the production of 3-amino-1,2,4-triazines, as it allows simultaneous individual syntheses. As the reaction is intramolecular, it is probable that the method can also be used also for mixtures of bis(amidinohydrazone)s to produce several triazines in one ampoule. The structure of the products was confirmed by mass, NMR and IR spectroscopy, elemental analyses and comparison with authentic samples. The reaction was studied using five bis(amidinohydrazone)s of aliphatic glyoxals, phenylglyoxal bis(amidinohydrazone) as well as the bis(amidinohydrazone) of 1,2-cyclohexanedione as starting materials. From the compound mentioned last a bicyclic product was obtained. In the case of the unsymmetric starting material ethylglyoxal bis(amidinohydrazone), both possible isomers were formed. The safety of heating the nitrogen-rich starting materials in large-scale syntheses has not been verified.
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Matikainen, J., Elo, H. A Novel Intramolecular Cyclization Reaction: Facile Solvent-Free Microscale Synthesis Suitable for Rapid Production of Libraries of 3-Amino-1,2,4-Triazines and for Combinatorial Chemistry. Microchim. Acta 146, 49–53 (2004). https://doi.org/10.1007/s00604-003-0117-y
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DOI: https://doi.org/10.1007/s00604-003-0117-y