Abstract
The reaction of 1,6-diamino-2-oxo-1,2-dihydropyridine-3,5-dicarbonitriles, which are easily available through the reaction of cyanoacetohydrazide with arylmethylene malononitriles, with ninhydrin leads to the formation of novel dihydroindeno[1,2-e]pyrido[1,2-b][1,2,4]triazines. Another active carbonyl compound, glyoxal, reacts with 1,6-diamino-2-oxo-1,2-dihydropyridine-3,5-dicarbonitriles under mild conditions to give functionalized 6-oxo-6H-pyrido[1,2-b][1,2,4]triazine-7,9-dicarbonitriles.
1. Introduction
1,6-Diamino-2-oxo-1,2-dihydropyridine-3,5-dicarbonitriles 1 were first prepared by Soto and colleagues in 1981 by treating cyanoacethydrazide 2 with 2 eq. arylmethylene malononitriles 3 in the presence of bases [1] (Scheme 1). The compounds 1 can also be synthesized by ternary cyclocondensation of corresponding aromatic aldehydes with malononitrile and hydrazide 2 generated in situ. The title compounds 1 are highly functionalized pyridine derivatives and are promising reagents useful for the preparation of nitrogen-bridged polyheterocyclic ensembles [2]. However, despite the presence of neighboring active amino groups, there are only a few reports on the reactions of 1,6-diamino-2-oxo-1,2-dihydropyridine-3,5-dicarbonitriles with electrophilic agents such as active carbonyls [2]. Hence, we decided to fill this gap by performing reactions of the title compounds with ninhydrin and glyoxal.
Scheme 1.
Preparation of 1,6-diamino-2-oxo-1,2-dihydropyridine-3,5-dicarbonitriles 1.
2. Results and Discussion
First, we prepared 1,6-diamino-2-oxo-1,2-dihydropyridine-3,5-dicarbonitriles 1 according to the reported procedure [1]. As reported in the original paper of Soto and colleagues [1], pyridine-3,5-dicarbonitriles 1 can be isolated in high yields only when arylmethylene malononitriles 3 are taken in two-fold excess with respect to the starting hydrazide 2. So, the true oxidant needed to oxidize intermediate tetrahydropyridine species 4 (Scheme 1) is arylmethylene malononitrile 3, not air oxygen.
We found that, upon treatment of 1,6-diamino-2-oxo-1,2-dihydropyridine- 3,5-dicarbonitriles 1 with ninhydrin in boiling acetic acid, dihydroindeno[1,2-e]pyrido[1,2-b][1,2,4]triazines 5 were isolated in good yields (Scheme 2). The formation of spiro compounds 6 was not confirmed in the reaction.
Scheme 2.
The preparation of dihydroindeno[1,2-e]pyrido[1,2-b][1,2,4]triazines 5.
When compounds 1 were treated with a small excess of aqueous glyoxal, 8-aryl-6-oxo-6H-pyrido[1,2-b][1,2,4]triazine-7,9-dicarbonitriles 7 were isolated as deep green colored solids easily soluble in common organic solvents such as EtOAc or acetone. The compounds 7 are examples of the poorly studied heterocyclic system of pyrido[1,2-b][1,2,4]triazine. Obviously, the reaction proceeds through the formation of the corresponding semi-aminals 8 with subsequent dehydration (Scheme 3).
Scheme 3.
The preparation of pyrido[1,2-b][1,2,4]triazines 7 (R = Hal, MeO).
3. Experiments
Preparation of Dihydroindeno[1,2-e]pyrido[1,2-b][1,2,4]triazines 5
A mixture of pyridines 1 (0.01 mol) and ninhydrin (0.01 mol) was dissolved in a small amount of AcOH (1–2 mL) and then was heated under reflux. The reaction was monitored by TLC (eluent—EtOAc or acetone, Sorbfil-A plates). After complete consumption of 1, the reaction mixture was allowed to cool and left to stand overnight. The brick-red solid was filtered off and washed with EtOH to give pure dihydroindeno[1,2-e]pyrido[1,2-b][1,2,4]triazines 5.
Author Contributions
Conceptualization, methodology, V.V.D.; investigation, A.R.C.; writing—original draft preparation, A.A.D.; writing—review and editing, V.V.D.; supervision, V.V.D.; funding acquisition, V.V.D. All authors have read and agreed to the published version of the manuscript.
Funding
The research was funded by RFBR and the administration of Krasnodar Territory, project number 20-43-235002.
Informed Consent Statement
Not applicable.
Data Availability Statement
Data sharing is not applicable to this article.
Conflicts of Interest
The authors declare no conflict of interest.
References
- Ibrahim, M.A.; El-Gohary, N.M. Heterocyclization with Some Heterocyclic Diamines: Synthetic Approaches for Nitrogen Bridgehead Heterocyclic Systems. Heterocycles 2014, 89, 1125–1157. [Google Scholar] [CrossRef]
- Soto, J.L.; Seoane, C.; Zamorano, P.; Cuadrado, F.J. A convenient synthesis of N-amino-2-pyridones. Synthesis 1981, 1981, 529–530. [Google Scholar] [CrossRef]
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