5350-56-1Relevant academic research and scientific papers
Direct amination of 1-substituted 3,5-dinitrobenzenes by 1,1,1-trimethylhydrazinium iodide
Rozhkov, Vladimir V.,Shevelev, Svyatoslav A.,Chervin, Ivan I.,Mitchell, Alexander R.,Schmidt, Robert D.
, p. 2498 - 2501 (2007/10/03)
The amination of 1-X-3,5-dinitrobenzenes via the vicarious nucleophilic substitution of hydrogen (VNS) with 1,1,1-trimethylhydrazinium iodide (TMHI) in the presence of t-BuOK or NaOMe in DMSO was studied. It was observed (when X = OMe, OCH2CF3, OCH2CF2CF2H, OPh) that the amination occurs regioselectively (ratio of ortho/para-isomers is ～9:1) and with high yield. For X = SPh or SCH2Ph, the reaction proceeded with a low yield (less than 20%), with a ratio of ortho/para-isomers ≈1:1. For X = PhSO2 and 2 equiv of TMHI, a double amination occurs and 2,4-diamino-3,5- dinitro-1-phenylsulfonylbenzene predominates in the mixture of isomers. Under the same conditions, 1,3,5-trinitrobenzene undergoes a double amination to yield 2,4-diamino-1,3,5-trinitrobenzene. A proposed mechanism for this reaction is discussed.
Hypoxia-Selective Agents Derived from Quinoxaline 1,4-Di-N-oxides
Monge, Antonio,Palop, Juan A.,Cerain, Adela Lopez de,Senador, Virginia,Martinez-Crespo, Francisko J.,et al.
, p. 1786 - 1792 (2007/10/02)
Hypoxic cells, which are a common feature of solid tumors, but not normal tissues, are resistant to both anticancer drugs and radiation therapy.Thus the identification of drugs with selective toxicity toward hypoxic cells is an important objective in anticancer chemotherapy.The benzotriazine di-N-oxide (SR 4233, Tirapazamine) has been shown to be an efficient and selective cytotoxin for hypoxic cells.Since the bioreductive activation of Tirapazamine is thought to be due to the presence of the 1,4-di-N-oxide moiety, a series of 3-aminoquinoxaline-2-carbonitrile 1,4-di-N-oxides with a range of electron-donating and -withdrawing substituents in the 6- and /or 7- positions has been synthesized and evaluated for toxicity to hypoxic cells.Electrochemical studies of the quinoxaline di-N-oxides and Tirapazamine showed that as the electron-withdrawing nature of the 6(7)-substituent increases, the reduction potential becomes more positive and the compound is more readily reduced.Apart from the unsubstituted 6a and the 6,7-dimethyl derivative 6c, the quinoxaline di-N-oxide have reduction potentials significantly more positive than Tirapazamine (Epc -0.90 V).The most potent cytotoxins to cells in culture were the 6,7-dichloro and 6,7-difluoro derivatives 6i and 6l, which were 30-fold more potent than Tirapazamine.The 6(7)-fluoro and 6(7)-chloro compounds, 6e and 6h, showed the greatest hypoxia selectivity.Four of the compounds, 6e, 6f, 6h and 6i, killed the inner cells of multicellular tumor spheroids in vitro.In vivo Balb/c mice tolerated a dose of these four compounds twice the size of that of Tirapazamine.This study demonstrates that quinoxaline 1,4-di-N-oxides could provide useful hypoxia-selective therapeutic agents.
Oxidation of Aryldialkylamines with Cerium(IV) Ammonium Nitrate and Thallium(III) Nitrate
Galliani, Guido,Rindone, Bruno
, p. 828 - 832 (2007/10/02)
Nine alkylmethylanilines were oxidised with cerium(IV)ammonium nitrate and thallium(III) nitrate in acetic acid, acetonitrile, and methanol.Reaction products were those deriving from demethylation, dealkylation, and aromatic nitration at positions ortho and para to the amino-group.The ratio between demethylation and dealkylation and between them and aromatic nitration is discussed in terms of (i) the oxidising power and electrophilicity of the reagent and (ii) the co-ordinative properties of the solvent.
