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Current Organic Synthesis

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ISSN (Print): 1570-1794
ISSN (Online): 1875-6271

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Research Article

Synthesis of 3-Amino-7-(N,N-Dimethylamino)-2-Substituted-5-Phenylphenazin-5-Ium Chlorides by Oxidative Cyclization

Author(s): Yuan Liu*, Ling Jin, Jun-feng Liu, Yu-qi Wang and Zhi-xiang Zhou

Volume 16, Issue 2, 2019

Page: [283 - 287] Pages: 5

DOI: 10.2174/1570179416666181228122731

Price: $65

Abstract

Aim and Objective: Phenazines are substances with an extensive range of important applications. Recently, the synthesis of N-arylation has been made more feasible owing to the advent of a new methodology. But because the toxicity of the used oxidant and the low yield, it is necessary to find a nonpoisonous or less toxic oxidant. We report on the use of potassium permanganate as an oxidant to synthesize phenylphenazin-5- ium chlorides via sequential aniline arylation.

Materials and Methods: The corresponding 2-substituted-3-amino-5-phenyl-7-N,N-dimethylamino phenazinium chlorides were obtained via various o-substituted toluidines reacted with 4-amino-N,N-dimethyamine and aniline using potassium permanganate as an oxidant under different conditions such as temperature, pH, reaction time and the ratio of raw materials. Infrared (IR) absorption data were acquired on a Thermo Nicolet Nexus 670 FT-IR spectrometer with DTGS KBr detector. All the products were characterized by Mass, 1H and 13C NMR spectroscopy. The total C, H, N, content was measured by the elemental analyzer.

Results: The yields of 3-amino-7-(N,N-dimethylamino)-2-substituted-5-phenylphenazin-5-ium chlorides are from 42.5% to 75.8% based on the electrophilic ability of different substituted groups under the temperature of 95°C, pH 4.5 and the reaction time of 8hrs.

Conclusion: 3-Amino-7-(N,N-dimethylamino)-2-substituted-5-phenylphenazin-5-ium chlorides have been synthesized in high yields via the oxidative cyclization with potassium permanganate. This route is a simple, economic, efficient and environmentally friendly.

Keywords: Nitroaniline, aniline, phenzine, derivatives, potassium permanganate, oxidative cyclizatio, synthesis.

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[1]
McCullough, K.J. Rodd’s Chemistry of Carbon Compounds; Ansell, M.F., Ed.; Elsevier: Amsterdam, 1989.
[2]
Urleb, U. Methods of Organic Chemistry (Houben-Weyl), 4th ed; Schaumann, E., Ed.; Thieme: Stuttgart, 1998.
[3]
Bolton, R. Rodd’s Chemistry of Carbon Compounds; Sainsbury, M., Ed.; Elsevier: Amsterdam, 2000.
[4]
Laursen, J.B. Nielsen, phenazine natural products: Biosynthesis, synthetic analogues, and biological activity. J. Chem. Rev., 2004, 104, 1663-1685.
[5]
Beifuss, U.; Tietze, M. Methanophenazine and other natural biologically active phenazines. Top. Curr. Chem., 2005, 244, 77-113.
[6]
(a) Makgatho, M.; Anderson, R.; O’Sullivan, J.; Egan, T.; Freese, J.; Cornelius, N.; Van Rensburg, C. Tetramethylpiperidine-substituted phenazines as novel anti-plasmodial agents. Drug Dev. Res., 2000, 50, 195-202.
(b) Andrade-Nieto, V.F.de ; Goulart, M.O.; Da, S.F.J.; Da, S.; Pinto, M.C.; Pinto, A.; Zalis, M.; Carvalho, L.; Krettli, A. Antimalarial activity of phenazines from lapachol, beta-lapachone and its derivatives against Plasmodium falciparum in vitro and Plasmodium berghei in vivo. Bioorg. Med. Chem. Lett., 2004, 14, 1145-1149.
[7]
Neves-Pinto, C.; Malta, V.R.S.; Pinto, M.D.C.S.R.; Santos, R.H.A.; Castro, S.L.D.; Pinto, A. A trypanocidal phenazine derived from β-lapachone. J. Med. Chem., 2002, 45, 2112-2115.
[8]
Eicher, T.; Hauptmann, S. The Chemistry of Heterocycles: Structure, Reactions, Syntheses and Applications, 2nd ed; Wiley-VCH: Weinheim, 2003.
[9]
Muller, M.; Sorrell, T.C. Inhibition of the human platelet cyclooxygenase response by the naturally occurring phenazine derivative, 1-hydroxy-phenazine. Prostaglandins, 1995, 50, 301-311.
[10]
Cartwright, D.K.; Chilton, W.S.; Benson, D.M. Pyrrolnitrin and phenazine production by Pseudomonas cepacia, strain 5.5B, a biocontrol agent of Rhizoctonia solani. Appl. Microbiol. Biotechnol., 1995, 43, 211-216.
[11]
Lokhov, S.G.; Podyminogin, M.A.; Sergeev, D.S.; Silnikov, V.N.; Kutyavin, I.V.; Shishkin, G.V.; Zarytova, V.F. Synthesis and high stability of complementary complexes of N-(2-hydroxyethyl) phenazinium derivatives of oligonucleotides. Bioconjug. Chem., 1992, 3, 414-419.
[12]
Bahnmüller, U.; Keller-Schierlein, W.; Brandl, M.; Zähner, H.; Diddens, H. Metabolites of microorganisms. 248. Synthetic analogs of saphenamycin. J. Antibiot., 1988, 41, 1552-1560.
[13]
Spicer, J.A.; Gamage, S.A.; Atwell, G.J.; Finlay, G.J.; Baguley, B.C.; Denny, W.A. Bis(phenazine-1-carboxamides): Structure− activity relationships for a new class of dual topoisomerase I/II- directed anticancer drugs. J. Med. Chem., 2000, 43, 1350-1358.
[14]
Challand, S.R.; Herbert, R.B.; Holliman, F.G. A new phenazine synthesis. The synthesis of griseoluteic acid, griseolutein A, and methyl diacetyl-griseolutein B. J. Chem. Soc. Chem. Commun., 1970, 21, 1423-1425.
[15]
(a) Old, D.W.; Wolfe, J.P.; Buchwald, S.L. A highly active catalyst for palladium-catalyzed cross-coupling reactions: Room-temperature Suzuki Couplings and amination of unactivated aryl chlorides. J. Am. Chem. Soc., 1998, 120, 9722-9723.
(b) Hartwig, J.F.; Kawatsura, M.; Hauck, S.I.; Shaughnessy, K.H.; Alcazar-Roman, L.M. Room-temperature palladium-catalyzed amination of aryl bromides and chlorides and extended scope of aromatic C—N bond formation with a commercial ligand. J. Org. Chem., 1999, 64, 5575-5580.
(c) Hartwig, J.F. Carbon-heteroatom bond-forming reductive eliminations of amines, ethers, and sulfides. Acc. Chem. Res., 1998, 31, 852-860.
(d) Frost, C.G.; Mendonca, P. Recent developments in aromatic heteroatom coupling reactions. J. Chem. Soc., Perkin Trans. 1, 1998, 2615-2624.
(e) Iwaki, T.; Yasuhara, A.; Sakamoto, T. Novel synthetic strategy of carbolines via palladium-catalyzed amination and arylation reaction. J. Chem. Soc., Perkin Trans. 1, 1999, 1505-1510.
[16]
Jayatilake, G.S.; Thornton, M.P.; Leonard, A.C.; Grimwade, J.E.; Baker, B.J. Metabolites from an Antarctic sponge-associated bacterium, Pseudomonas aeruginosa. J. Nat. Prod., 1996, 59, 293-296.
[17]
Brisbane, P.G.; Janik, L.J.; Tate, M.E.; Warren, R.F. Revised structure for the phenazine antibiotic from Pseudomonas fluorescens 2-79 (NRRL B-15132). Antimicrob. Agents Chemother., 1987, 31, 1967-1971.
[18]
Budzikiewicz, H. Secondary metabolites from fluorescent pseudomonads. FEMS Microbiol. Rev., 1993, 104, 209-228.
[19]
Mavrodi, D.V.; Ksenzenko, V.N.; Bonsall, R.F.; Cook, R.J.; Boronin, A.M.; Thomashow, L.S. A Seven-gene locus for synthesis of phenazine-1-carboxylic acid by pseudomonas fluorescens 2-79. J. Bacteriol., 1998, 180, 2541-2548.
[20]
Pierson, L.S.I.; Thomashow, L.S. Cloning and heterologous expression of the phenazine biosynthetic locus from Pseudomonas aureofaciens 30-84. Mol. Plant Microbe Interact., 1992, 5, 330-339.
[21]
Chin-A-Woeng, T.F.C.; Thomas-Oates, J.E.; Lugtenberg, B.J.J.; Bloemberg, G.V. Introduction of the phzH gene of Pseudomonas chlororaphis PCL1391 extends the range of biocontrol ability of phenazine-1-carboxylic acid-producing Pseudomonas spp. strains. Mol. Plant Microbe Interact., 2001, 14, 1006-1015.
[22]
Laursen, J.B.; Jørgensen, C.G.; Nielsen, J. First synthesis of racemic saphenamycin and its enantiomers. investigation of biological activity. Bioorg. Med. Chem., 2003, 11, 723-731.
[23]
Land, C.W.V.; Mocek, U.; Floss, H.G. Biosynthesis of the phenazine antibiotics, the saphenamycins and esmeraldins, in Streptomyces antibioticus. J. Org. Chem., 1993, 58, 6576-6582.
[24]
Lian, Y.; Hummel, J.R.; Bergman, R.G.; Ellman, J.A. Facile synthesis of unsymmetrical acridines and phenazines by a Rh(III)- catalyzed amination/cyclization/aromatization cascade. ChemInform, 2014, 45(8), 12548-12551.
[25]
Liu, Y.; Jin, L.; Liu, J.F. A new route for synthesis of 2-substituted-3-amino-5-phenyl-7-N,Ndimethylamino phenazinium chloride salts. J. Heterocycl. Chem., 2017, 54(3), 1931-1936.

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