1,3-Diphenylbenzo[e][1,2,4]triazin-7(1H)-one: Selected Chemistry at the C-6, C-7 and C-8 Positions

Abstract

1,3-Diphenylbenzo[e][1,2,4]triazin-7(1H)-one (6) reacts with tetracyanoethylene (TCNE) or tetracyanoethylene oxide (TCNEO) to give the deep green 2-[1,3-diphenylbenzo[e][1,2,4]triazin-7(1H)-ylidene]propanedinitrile (11) in 17 and 15% yields, respectively. Nucleophiles such as amines, alkoxides, thiols and Grignard reagents all reacted with the 1,3-diphenylbenzotriazinone 6 regioselectively at C-6, while halogenating agents reacted exclusively at C-8. Furthermore, 8-iodo-1,3-diphenylbenzo[e][1,2,4]triazin-7(1H)-one (32) undergoes palladium-catalysed Suzuki-Miyaura and Stille coupling reactions to give 8-aryl- or heteroaryl-substituted benzotriazinones. By combining both the C-6 and C-8 chemistries 1,3,6,8-tetraphenylbenzo[e][1,2,4]triazin-7(1H)-one (42) and 1,3-diphenyl-6,8-di(thien-2-yl)-benzo[e][1,2,4]triazin-7(1H)-one (43) can be prepared. All new compounds are fully characterized.

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

“…MALDI-TOF MS were conducted on a Bruker BIFLEX III time-of-flight (TOF) mass spectrometer. 1,3-Diphenylbenzo[1,2,4]triazin-7-one (1a), 3 6-amino-1,3-diphenylbenzo-[1,2,4]triazin-7-one (1b), 6 6-(methylamino)-1,3-diphenylbenzo[1,2,4]triazin-7-one (1c), 5 6-(ethylamino)-1,3-diphenylbenzo[1,2,4]triazin-7-one (1d), 6 6-(diethylamino)-1,3-diphenyl-benzo[1,2,4]triazin-7-one (1e), 7 1,3-diphenyl-6-(pyrrolidin-1-yl)benzo[1,2,4]triazin-7-one (1f), 7 1,3-diphenyl-6-(piperidin-1-yl)benzo[1,2,4]triazin-7-one (1g), 6 6-morpholino-1,3-diphenylbenzo[1,2,4]triazin-7-one (1h), 7 5 6-methoxy-1,3-diphenylbenzo[1,2,4]triazin-7-one (1k), 7 and 6-ethoxy-1,3-diphenylbenzo-[1,2,4]triazin-7-one (1l) 6 were synthesized according to literature procedures.…”

“…[3][4][5][6] Benzotriazinone 1a (R = H) and derivatives have been implicated as multi-target inhibitors in Alzheimer's disease of beta-amyloid (Aβ) aggregation and acetyl-(AChE)/butyryl-(BChE) cholinesterase. 7 Scaffold 1 contains a highly conjugated iminoquinone motif and an iminoquinone derivative of imidazo [5,4-f]benzimidazoles was shown to have good specificity (Pearson correlation coefficient of 0.51) towards NAD(P)H:quinone oxidoreductase 1 (NQO1) expression using COMPARE analysis of toxicity towards the 60 cell lines at the National Cancer Institute (NCI) Development Therapeutics Program (DTP).…”

Regioselective Fluorination of 7-Oxo-1,2,4-benzotriazines Using Selectfluor

“…1,3-Diphenylbenzo[ e ][1,2,4]triazin-7(1 H )-one ( 1a ) [18,19] and 1,3,6-triphenylbenzo[ e ][1,2,4]-triazin-7(1 H )-one ( 3a ) [18] were prepared according to literature procedures. 8-Chloro-1,3-diphenyl-benzo[ e ][1,2,4]triazin-7(1 H )-one ( 1b ) [18], 6-(benzylthio)-1,3-diphenylbenzo[ e ][1,2,4]triazin-7(1 H )-one ( 3b ) [18], 6,8-diphenyl[1,2,5]thiadiazolo[3′,4′:5,6]benzo[1,2- e ][1,2,4]triazin-4(6 H )-one ( 5a ) [17] and 6-phenyl-8-(trifluoromethyl)-[1,2,5]thiadiazolo[3′,4′:5,6]benzo[1,2- e ][1,2,4]triazin-4(6 H )-one ( 5b ) [17] were provided by Koutentis Research Laboratory (University of Cyprus), and used as received.…”

Recent Advances in the Synthesis of Heterocycles by the Aza-Wittig Reaction

“…In 2017, Koutentis and co-workers synthesized 1,3-diaryl-1,4-dihydrobenzo[e] [1,2,4]triazin-4-yls 245 via an aza-Wittig-mediated synthesis (Schemes 64 and 65). 58 [1,2,4]triazin-4-yls 245, known as Blatter radicals, are air-and moisture-stable organic compounds that can be converted into benzotriazinones 247 59 and 1,2-diphenylbenzimidazoles 246 60 in the presence of oxidizing and reducing agents, respectively (Scheme 64). Benzotriazinones 59 In 2012, Ding and co-workers reported the unexpected synthesis of 2,4,5-trisubstituted oxazoles 254 via intermolecular aza-Wittig reaction (Scheme 66).…”

“…58 [1,2,4]triazin-4-yls 245, known as Blatter radicals, are air-and moisture-stable organic compounds that can be converted into benzotriazinones 247 59 and 1,2-diphenylbenzimidazoles 246 60 in the presence of oxidizing and reducing agents, respectively (Scheme 64). Benzotriazinones 59 In 2012, Ding and co-workers reported the unexpected synthesis of 2,4,5-trisubstituted oxazoles 254 via intermolecular aza-Wittig reaction (Scheme 66). 61 Condensation of azides 91 with benzaldehydes 15 in the presence of piperidinium acetate gave various vinyl azides 92 that were subjected to the Staudinger reaction with Ph 3 P (20) to give vinyliminophosphoranes 253.…”