Efficient Preparation of Pyridinyl‐1,2,4‐Triazines via Telescoped Condensation with Diversely Functionalized 1,2‐Dicarbonyls

Abstract

The development of materials for efficient chemoselective extraction of minor actinides remains at the forefront of research efforts in the area of separation science. Lewis basic complexants derived from nitrogen‐donor scaffolds are often employed in this area due to favorable complexation with the transuranic element americium. In the present work an efficient procedure for the preparation of eight useful 3‐pyridin‐2‐yl‐1,2,4‐triazines (2 novel) is demonstrated via telescoped condensation with the requisite 1,2‐dicarbonyl in two‐pots without additives, differentially extractive work‐up procedures, or recrystallization. Additional efforts in this area have demonstrated the utility of polar aprotic solvents for the preparation of nine functionalized pyridinyl‐2,6‐bis‐1,2,4‐triazines (4 novel) directly from the requisite 2,6‐pyridine dicarbonitrile in 49–99% yield over four total steps. The streamlined preparation of these important materials and detailed synthetic procedures is reported herein.

Convergent access to bis-1,2,4-triazinyl-2,2′-bipyridines (BTBPs) and 2,2′-bipyridines via a Pd-catalyzed Ullman-type reaction

“…Conditions pursuant to the Weix procedures 15 with NiBr 2 $3H 2 O and manganese metal under reductive conditions afforded the proto-dehalogenated variant of 8 [MTPPhen] (entry 1). 16 A similar observation was made with entries 3 and 5. This result is suggestive that the starting material had successfully accomplished an oxidative addition or, potentially a two-electron reduction with manganese or magnesium metal, but the subsequent transmetalation and reductive elimination steps did not transpire consequently affording the protodemetalated or dehalogenated 8.…”

Synthesis of Functionalized Hemi‐1,2,4‐triazinyl‐[2,2′]‐bipyridines via Telescoped Condensation of [2,2′]‐bipyridinyl‐6‐carbonitrile

“…Isolated, purified yields ranged from 34% to 80% over two steps from 2 (entries 1 – 10 ). Interestingly, hemi ‐TBP complexants appear to display electronic environment sensitivity to heterocycle formation that was previously encountered in earlier work from this lab , whereby resonance donating substitutents, such as the 3,3′‐OMe substituent in 19 , inhibited the condensation reaction leading to lower conversion of 10 and similarly lower isolated yields presumably via suppression of the electrophilicity of the 1,2‐dione carbonyl. Synthesis of the 4,4′‐OMe constitutional isomer of 19 was attempted, but resulted in incomplete conversion and a complex mixture of materials unable to be separated chromatographically.…”

“…Complexants 11 – 14 and 19 were accessed from commercially available 4,4′‐benzil reagents. Di‐4‐alkylphenyl‐1,2,4‐triazinyl‐[2,2′]‐bipyridines 15 – 18 as well as 20 required preparation of the 1,2‐dicarbonyl (Scheme ). Isolated, purified yields ranged from 34% to 80% over two steps from 2 (entries 1 – 10 ).…”

“…While previously prepared complexants successfully address some important challenges, work over the last three decades has yet to identify the ideal complexant . Efforts in this laboratory seek to develop streamlined synthetic methods to address complexant solubility challenges, in addition to employing modular concepts for the rapid, convergent construction of novel scaffolds .…”

Pd‐Catalyzed Amination of Functionalized 6‐Bromo‐pyridinyl‐1,2,4‐triazine Complexant Scaffolds

“…The desire to solvate polar heteroaromatic moieties in extremely nonpolar solvents with low dielectric constants adds an additional challenge for working in this area. Frequently, synthetic approaches to the design of 1,2,4‐triazinyl complexants are focused on linear efforts relying on commercially available reagents while employing condensation chemistry with limited functional‐group variability and a noticeable lack of convergence . Efforts from this laboratory have successfully demonstrated the ability to leverage Pd‐catalyzed transformations for the convergent enhancement of complexant properties from common scaffolds …”