Synthesis of esters and amides of 1,4-dihydro-1,2,4,5-tetrazine-3,6-dicarboxylic acid

Abstract

Alkyl esters and alkyl amides of 1,4-dihydro-1,2,4,5-tetrazine-3,6-dicarboxylic acid were synthesised and characterised by IR, 1H NMR, EI-MS and elemental analysis. The structure of 1,4-dihydro-1,2,4,5-tetrazine-3,6-dicarboxylic was confirmed by X-ray diffraction analysis. Some selected compounds were evaluated against P-388 and A-549 cancer cell lines, but showed poor inhibitory activities.

Synthesis, Crystal Structures and Quantum Chemical Calculations of 3,6-diphenyl-1,2-dihydro- and 1,4-dihydro-1,2,4,5-tetrazine derivatives

“…From these, it is apparent that the compounds 2b and 3a are 1,4-dihydro-1,2,4,5-tetrazines, whereas 3g is a 1,2-dihydro-1,2,4,5-tetrazine. This is an unexpected result, because when 3,6-diaryl-1,2,4,5-tetrazines were reacted with alkyl chloroformates only 3,6-diaryl-1,2dihydro-1,2,4,5-tetrazine-1,2-dicarboxylates were isolated, but their isomers, 3,6-diaryl-1,4-dihydro-1,2,4,5-tetrazine-1,4dicarboxylates, 9,10 were not obtained.…”

“…8 The difficultly of accessing phenacylidenedimethylsulfurane is also the problem with this method. Rao et al 9,10 have attempted to synthesise 1,4-disubstituted-3,6-daryl-1,4-dihydro-1,2,4,5-tetrazine-1,4dicarboxylates from 1,4-dihydro-3,6-diaryl -1,2,4,5-tetrazines and chloroformates. Unexpectedly, they only obtained the isomeric 1,2-disubstituted-3,6-diaryl-1,2-dihydro-1,2,4,5tetrazine-1,2-dicarboxylates.…”

“…Unexpectedly, they only obtained the isomeric 1,2-disubstituted-3,6-diaryl-1,2-dihydro-1,2,4,5tetrazine-1,2-dicarboxylates. 9,10 Motivated by these findings, and as a continuation of our research into 1,2-or 1,4-disubstituted-3,6diaryl-dihydro-1,2,4,5-tetrazines, 11 we explored the acylation of 3,6-diphenyl-1,4-dihydro-1,2,4,5-tetrazine with acyl chlorides to establish whether the reaction affords 1,2-dihydro-1,2,4,5tetrazines or 1,4-dihydro-1,2,4,5-tetrazines.…”