Route to Benzo- and Pyrido-Fused 1,2,4-Triazinyl Radicals via N′-(Het)aryl-N′-[2-nitro(het)aryl]hydrazides

Abstract

A two-step route to 1,3-disubstituted benzo- and pyrido-fused 1,2,4-triazinyl radicals is presented. The route involves the N'-(2-nitroarylation) of easily prepared N'-(het)arylhydrazides via nucleophilic aromatic substitution of 1-halo-2-nitroarenes, which in most cases gives N'-(het)aryl-N'-[2-nitro(het)aryl]hydrazides in good yields. Mild reduction of the nitro group followed by an acid-mediated cyclodehydration gives the fused triazines, which upon alkali treatment afford the desired radicals. Fifteen examples of radicals are presented bearing a range of substituents at N-1, C-3, and C-7, including the pyrid-2-yl and 8-aza analogues. This route to the N'-(het)aryl-N'-[2-nitro(het)aryl]hydrazides, which works well with benzo- and picolinohydrazides, required a modification for aceto- and trifluoroacetohydrazides that involved a multistep synthesis of asymmetrically 1,1-diaryl-substituted hydrazines.

New Blatter-type radicals from a bench-stable carbene

“…Amidrazones such as ( E )- 5 are also intermediates in the conventional synthetic route to Blatter-type radicals from imidoyl or hydrazonyl chlorides236303132. Similar to the literature-proposed mechanism303132, conversion of ( E )- 5 to 3 could thus involve the initial in situ formation of 1,2,4-triazabutadienes 6 , followed by electrocyclic ring closure to benzotriazines and further oxidation. Alternatively, the amidrazone could undergo one-electron oxidation to a hydrazonyl radical 7 followed by ring closure to a benzotriazine and further oxidation (Fig.…”

“…Addition of small amounts of water (≤10 v/v%) to a solution of Nitron 2 in acetonitrile was found to improve the yield of radical 3 ; however, higher volumes resulted in significantly lower yields of radical and gave triazabutadiene 8 as major product (see Supplementary Methods). The oxidative cyclization of amidrazones is known to be accelerated by a variety of oxidants and catalysts3036373839404142. Addition of Ag 2 O or PbO 2 and base to acetonitrile solutions of 2 increased the rate of conversion although yields were similar.…”

The Planar Blatter Radical: Structural Chemistry of 1,4‐Dihydrobenzo[e][1,2,4]triazin‐4‐yls

“…Thus, the exceptional stability, spin π‐delocalization, narrow electrochemical window, and low excitation energies made benzo[ e ][1,2,4]triazin‐4‐yl derivatives, such as 1 (Figure ), attractive for application in controlled polymerization, molecular electronics, photodetectors, and liquid crystalline photoconductors . In this context several synthetic methods for accessing this radical system have been recently improved and developed, and transformations of functional groups in the presence of the unpaired electron demonstrated . In addition, the planar π system has been extended by annulation at positions 6–7 and 7–8 of the prototypical Blatter radical 1 , thus providing access to new materials with tunable properties.…”

Anti-Cancer Activity of Phenyl and Pyrid-2-yl 1,3-Substituted Benzo[1,2,4]triazin-7-ones and Stable Free Radical Precursors

“…The preparation of benzotriazinyl radicals 3a and 3b has previously been reported [ 9 ]. New pyridyl-substituted benzotriazinones 4a and 4b were prepared from the MnO 2 -mediated oxidation [ 3 ] of benzotriazin-4-yls 3a and 3b in 90 and 46% yields, respectively ( Scheme 1 ).…”

“…MALDI-TOF MS was conducted on a Bruker BIFLEX III time-of-flight (TOF) mass spectrometer (Bruker, Billerica, MA, USA). 3-Phenyl-1-(pyrid-2-yl)-1,4-dihydrobenzo[ e ][1,2,4]triazin-4-yl ( 3a ) and 1-phenyl-3-(pyrid-2-yl)-1,4-dihydrobenzo[ e ][1,2,4]triazin-4-yl ( 3b ) were prepared according to literature procedures [ 9 ].…”