Toward N--Annulated Planar Blatter Radical through aza-Pschorr and Photocyclization.

Preparation of the elusive N--annulated planar Blatter radicals was attempted using aza-Pschorr and photocyclization methods. In both methods, substrates containing N-Me and N-Ac groups yielded a zwitterionic heterocycle lacking the N-substituent as the main product, while in one of them a carbazole derivative representing a new heterocyclic system was also obtained. The formation of the zwitterion and the carbazole suggests the formation of the desired planar Blatter radical, which undergoes facile fragmentation through homolysis of the N-R bond.

The Effect of High Pressure on Polymorphs of a Derivative of Blatter's Radical: Identification of the Structural Signatures of Subtle Phase Transitions.

The effect of pressure on the α and β polymorphs of a derivative of Blatter's radical, 3-phenyl-1-(pyrid-2-yl)-1,4-dihydrobenzo[][1,2,4]triazin-4-yl, has been investigated using single-crystal X-ray diffraction to maximum pressures of 5.76 and 7.42 GPa, respectively.

A first-order phase transition in Blatter's radical at high pressure.

The crystal structure of Blatter's radical (1,3-diphenyl-1,4-dihydrobenzo[e][1,2,4]triazin-4-yl) has been investigated between ambient pressure and 6.07 GPa. The sample remains in a compressed form of the ambient-pressure phase up to 5.

"Upper" Ring Expansion of the Planar Blatter Radical via Photocyclization: Limitations and Impact on the Electronic Structure.

Photocyclization of 8-aryloxybenzo[][1,2,4]triazines leads to the formation of π-expanded flat Blatter radicals for three phenanthryloxy and pyren-1-yloxy derivatives, whereas no photoreaction is observed for the perylen-3-yloxy precursor. Two of the new radicals are nonplanar, out of which one is unstable to isolation. The radical with the fused pyrene ring constitutes the largest thus far paramagnetic polycyclic π-system containing seven fused rings with 27 sp-hybridized atoms and 29 π-delocalized electrons.

Redox Active Quinoidal 1,2,4-Benzotriazines.

Modifying the para-quinonimine 1,3-diphenyl-1,2,4-benzotriazin-7(1 H)-one (2a) ( E -1.20 V), by replacing the N1-phenyl by pentafluorophenyl, the C3-phenyl by trifluoromethyl, or the C7 carbonyl by ylidenemalononitrile, led to improved electron affinities as determined by cyclic voltammetry and computational studies. Combining structural changes further improved electron accepting abilities: the most electron deficient analogues ( E ∼ -0.

Synthesis and Characterization of Isodiphenylfluorindone and Isodiphenylfluorindinone.

Isodiphenylfluorindone 6 and isodiphenylfluorindinone 7 are synthesized. The former reacts with NaOMe to give the 13-methoxyisodiphenylfluorindone 22 (95%), while the latter reacts with 70% perchloric acid to give the bisperchlorate 21 (87%) and with MnO dimerizes to give 13,13'-bi(isodiphenylfluorindone) 4 (60%). UV-vis, NMR, CV, and DFT computational studies support the structural assignments of all products.

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

Cell viability studies for benzo[1,2,4]triazin-7-ones and 1,2,4-benzotriazinyl (Blatter-type) radical precursors are described with comparisons made with 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO). All of the stable free radicals were several orders of magnitude less cytotoxic than the benzo[1,2,4]triazin-7-ones. The synthesis and evaluation of two new pyrid-2-yl benzo[1,2,4]triazin-7-ones are described, where altering the 1,3-substitution from phenyl to pyrid-2-yl increased cytotoxicity against most cancer cell lines, as indicated using National Cancer Institute (NCI) one-dose testing.

Oxidation of Isodiphenylfluorindine: Routes to 13-Oxoisodiphenylfluorindinium Perchlorate and Fluorindine Cruciform Dimers.

Isodiphenylfluorindine (5) reacts with KCrO/H to give 13-oxoisodiphenylfluorindinium perchlorate (7) (75%), but with phenyliodine bis(trifluoroacetate) (PIFA) or MnO it gives the zwitterionic and quinoidal cruciform 13,13'-dimers 11 (85%) and 12 (89%), respectively. The zwitterionic 13,13'-dimer 11 can be rapidly converted with MnO into the quinoidal 13,13'-dimer 12 (100%). UV-vis, NMR, single-crystal X-ray diffraction, and density functional theory studies support the structural assignments of all products.

Preparation of Blatter Radicals via Aza-Wittig Chemistry: The Reaction of N-Aryliminophosphoranes with 1-(Het)aroyl-2-aryldiazenes.

Reacting N-aryliminophosphoranes with 1-(het)aroyl-2-aryldiazenes in preheated diphenyl ether at ca. 150-250 °C for 5-25 min affords in most cases the 1,3-diaryl-1,4-dihydrobenzo[e][1,2,4]triazin-4-yls (aka Blatter radicals) in moderate to good yields. All new compounds are fully characterized, including EPR and CV studies for the radicals.

Discovery of anti-cancer activity for benzo[1,2,4]triazin-7-ones: Very strong correlation to pleurotin and thioredoxin reductase inhibition.

The thioredoxin (Trx)-thioredoxin reductase (TrxR) system plays a key role in maintaining the cellular redox balance with Trx being over-expressed in a number of cancers. Inhibition of TrxR is an important strategy for anti-cancer drug discovery. The natural product pleurotin is a well-known irreversible inhibitor of TrxR.

The Suppression of Columnar π-Stacking in 3-Adamantyl-1-phenyl-1,4-dihydrobenzo[e][1,2,4]triazin-4-yl.

3-Adamantyl-1-phenyl-1,4-dihydrobenzo[e][1,2,4]triazin-4-yl (4) crystallizes as chains of radicals where the spin bearing benzotriazinyl moieties are isolated from each other. Magnetic susceptibility studies in the 5-300 K temperature region indicate that radical 4 demonstrates typical paramagnetic behavior stemming from non-interacting S = ½ spins.

Oxidation of Tetraphenylhexaazaanthracene: Accessing a Scissor Dimer of a 16π Biscyanine.

Tetraphenylhexaazaanthracene (TPHA), a fluorescent zwitterionic biscyanine with a closed-shell singlet ground state, on treatment with manganese dioxide or phenyliodine bis(trifluoroacetate) (PIFA), undergoes oxidative dimerization to give a near-zero dipole scissor 5,5'-dimer DI-TPHA. Both acene components of the new dimer DI-TPHA maintain their biscyanine closed-shell singlet ground state motifs, as judged by analysis of both single crystal X-ray crystallographic and density functional theory computational studies; however, unlike TPHA, DI-TPHA is only very weakly fluorescent.

Coordination Complexes of a Neutral 1,2,4-Benzotriazinyl Radical Ligand: Synthesis, Molecular and Electronic Structures, and Magnetic Properties.

A series of d-block metal complexes of the recently reported coordinating neutral radical ligand 1-phenyl-3-(pyrid-2-yl)-1,4-dihydro-1,2,4-benzotriazin-4-yl (1) was synthesized. The investigated systems contain the benzotriazinyl radical 1 coordinated to a divalent metal cation, Mn(II) , Fe(II) , Co(II) , or Ni(II) , with 1,1,1,5,5,5-hexafluoroacetylacetonato (hfac) as the auxiliary ligand of choice. The synthesized complexes were fully characterized by single-crystal X-ray diffraction, magnetic susceptibility measurements, and electronic structure calculations.

Tetraphenylhexaazaanthracenes: 16π Weakly Antiaromatic Species with Singlet Ground States.

Tetraphenylhexaazaanthracene, TPHA-1, is a fluorescent zwitterionic biscyanine with a closed-shell singlet ground state. TPHA-1 overcomes its weak 16π antiaromaticity by partitioning its π system into 6π positive and 10π negative cyanines. The synthesis of TPHA-1 is low yielding and accompanied by two analogous TPHA isomers: the deep red, non-charge-separated, quinoidal TPHA-2, and the deep green TPHA-3 that partitions into two equal but oppositely charged 8π cyanines.

A magnetostructural investigation of an abrupt spin transition for 1-phenyl-3-trifluoromethyl-1,4-dihydrobenzo[e][1,2,4]triazin-4-yl.

1-Phenyl-3-trifluoromethyl-1,4-dihydrobenzo[e][1,2,4]triazin-4-yl is the first example of a hydrazyl radical that shows a reversible sharp spin transition fully completed within 5(1) K. The nominally first-order transition takes place at ca. 58(2) K and proceeds via subtle changes of intra- and interstack interactions between two similar structural phases.

Structural, magnetic, and computational correlations of some imidazolo-fused 1,2,4-benzotriazinyl radicals.

1,3,7,8-Tetraphenyl-4,8-dihydro-1H-imidazolo[4,5g][1,2,4]benzotriazin-4-yl (5), 8-(4-bromophenyl)-1,3,7-triphenyl-4,8-dihydro-1H-imidazolo[4,5g][1,2,4]benzotriazin-4-yl (6), and 8-(4-methoxyphenyl)-1,3,7-triphenyl-4,8-dihydro-1H-imidazolo[4,5g][1,2,4]benzotriazin-4-yl (7) were characterized by using X-ray diffraction crystallography, variable-temperature magnetic susceptibility studies, and DFT calculations. Radicals 5-7 pack in 1 D π stacks made of radical pairs with alternate short and long interplanar distances. The magnetic susceptibility (χ vs.

Route to benzo- and pyrido-fused 1,2,4-triazinyl radicals via N'-(het)aryl-N'-[2-nitro(het)aryl]hydrazides.

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.