Preferences help
enabled [disable] Abstract
Number of results
2003 | 1 | 3 | 260-276
Article title

Synthesis of 4-aryloxy-7-nitrobenzofurazan derivatives from 4-chloro-7-nitrobenzofurazan and various phenoxide anions (including pharmaceuticals) in the presence of crown ethers

Title variants
Languages of publication
4-Chloro-7-nitrobenzofurazan reacts by nucleophilic substitution with phenoxide anions derived from estriol (2c), ethynylestradiol (2d), phenol (3e), guaiacol (3f), 2,6-dimethoxyphenol (3g), eugenol (3h), isoeugenol (3i), the cytostatic Etoposide (4), and Reichardt’s betaine (5) in the presence of crown ethers affording the corresponding 4-aryloxy-7-nitrobenzofurazan derivatives 6c, 6d, 7e-7i, 8, and 9. The structure of these compounds was confirmed by NMR spectra. Hydrophobicity/hydrophilicity parameters were investigated by reverse phase thin-layer chromatography.
Physical description
1 - 9 - 2003
1 - 9 - 2003
  • [1] P.B. Ghosh and M.W. Whitehouse: “7-Chloro-4-nitrobenzo-2-oxa-1,3-diazole: a new fluorigenic reagent for amino acids and the other amines”, Biochem. J., Vol. 108, (1968), pp. 155–156.
  • [2] D.J. Birkett, N.C. Price, G.K. Radda, A.G. Salmon: “The reactivity of SH groups with a fluorogenic reagent”, FEBS Lett., Vol. 6, (1970), pp. 346–348.[Crossref]
  • [3] R.A. Kenner and A.A. Aboderin: “A new fluorescent probe for protein and nucleoprotein conformation. Binding of 7-(p-methoxybenzylamino)-4-nitro benzoxadiazole to bovine trypsinogen and bacterial ribosomes”, Biochemistry, Vol. 10, (1971), pp. 4433–4440.[Crossref]
  • [4] R.W. Frei and J.F. Lawrence: “Fluorigenic labelling in high-speed liquid chromatography”, J. Chromatogr., Vol. 83, (1973), pp. 321–330.[Crossref]
  • [5] D. Lancet and I. Pecht: “Spectroscopic and immunochemical studies with nitrobenzoxadiazolealanine, a fluorescent dinitophenyl analogue”, Biochemistry, Vol. 16, (1977), pp. 5150–5157.[Crossref]
  • [6] K. Blau and G.S. King: Handbook of Derivatives for Chromatography, Heyden, London, 1977, p. 367.
  • [7] K. Imai and Y. Watanabe: “Fluorimetric determination of secondary amino acids by 7-fluoro-4-nitrobenzo-2-oxa-1,3-diazole”, Anal. Chim. Acta, Vol. 130, (1981), pp. 377–383.[Crossref]
  • [8] M. Ahnoff, I. Grundevik, A. Arfwidsson, J. Fonselius, B.-A. Persson: “Derivatization with 4-chloro-7-nitrobenzofurazan for liquid chromatographic determination of hydroxyproline in collagen hydrolysate”, Anal. Chem., Vol. 53, (1981), pp. 485–489. [Crossref]
  • [9] H. Umagat, P. Kucera, L.-F. Wen: “Total amino acid analysis using pre-column fluorescence derivatization”, J. Chromatogr., Vol. 239, (1982), pp. 463–474.[Crossref]
  • [10] L. Johnson, S. Lagerkvist, P. Lindroth, M. Ahnoff, K. Martinsson: “Derivatization of secondary amino acids with 7-nitro-4-benzofurazanyl ethers”, Anal. Chem., Vol. 54, (1982), pp. 939–942.[Crossref]
  • [11] T. Toyo’oka and K. Imai: “New fluorogenic reagent having halogenobenzofurazan structure for thiols: 4-(Aminosulfonyl)-7-fluoro-2,1,3-benzoxadiazole”, Anal. Chem., Vol. 56, (1984), pp. 2461–2464.[Crossref]
  • [12] K. Imai, T. Toyo’oka, H. Miyano: “Fluorigenic reagents for primary and secondary amines and thiols in high-performance liquid chromatography”, Analyst, Vol. 109, (1984), pp. 1365–1373.[Crossref]
  • [13] T. Toyo’oka, T. Suzuki, Y. Saito, S. Uzu, K. Imai: “Evaluation of benzofurazan derivatives as fluorogenic reagents for thiols and amines using high-performance liquid chromatography”, Analyst, Vol. 114, (1989), pp. 1233–1240.[Crossref]
  • [14] H. Matsunaga, T. Santa, K. Hagiwara, H. Homma, K. Imai, S. Uzu, K. Nakashima, S. Akiyama: “Development of an efficient amino acid sequencing method using fluorescent Edman reagent 7-[(N,N-Dimethylamino)sulfonyl]-2,1,3-benzoxadiazol-4-yl isothiocyanate”, Anal. Chem., Vol. 67, (1995), pp. 4276–4282.[Crossref]
  • [15] T. Santa, A. Takeda, S. Uchiyama, T. Fukushima, H. Homma, S. Suzuki, H. Yokosu, C.K. Lim, K. Imai: “N-(4-nitro-2,1,3-benzoxadiazoyl-7-yl)-N-methyl-2-aminoacetohydrazide (NBD-CO-Hz) as a precolumn fluorescent derivatization reagent for carboxylic acids in high-performance liquid chromatography”, J. Pharm. and Biomed. Anal., Vol. 17, (1998), pp. 1065–1070.[Crossref]
  • [16] S. Uchiyama, T. Santa, K. Imai: “Semi-empirical PM3 calculation reveals the relationships between the fluorescence characteristics of 4,7-disubstituted benzofurazan compounds, the LUMO energy and the dipole moment directed from the 4- to the 7-position”, J. Chem. Soc. Perk. T., 2, (1999), pp. 569–576.[Crossref]
  • [17] S. Uchiyama, T. Santa, K. Imai: “Fluorescence characteristics of six 4,7-disubstituted benzofurazan compounds: an experimental and semi-empirical MO study”, J. Chem. Soc. Perk. T. 2, (1999), pp. 2525–2532.[Crossref]
  • [18] S. Uchiyama, T. Santa, N. Okiyama, K. Azuma, K. Imai: “Semi-empirical PM3 calculations predict the fluorescence quantum yields (Φ) of 4-monosubstituted benzofurazan compounds”, J. Chem. Soc. Perk. T. 2, (2000), pp. 1199–1207.
  • [19] T. Kajiro, T. Fukushima, T. Santa, K. Imai: “Development of water-soluble fluorogenic reagents having a 2,1,3-benzoxadiazole structure and their application to the determination of peptides”, Analyst, Vol. 125, (2000), pp. 1115–1121.[Crossref]
  • [20] S. Uchiyama, T. Santa, K. Imai: “Study on the fluorescent ‘on-off’ properties of benzofurazan compounds bearing an aromatic substituent group and design of fluorescent ‘on-off’ derivatization reagents”, Analyst, Vol. 125, (2000), pp. 1839–1845.[Crossref]
  • [21] A. Toriba, K. Azuma, T. Santa, K. Imai: “Development of an amino acid sequence and D/L-Configuration determination method of peptide with a new fluorescence Edman reagent, 7-Methylthio-4-(2,1,3-benzoxadiazolyl) Isothiocyanate”, Anal. Chem., Vol. 72, (2000), pp. 732–739.
  • [22] P.B. Ghosh and M.W. Whitehouse: “Potential antileukemic and immunosuppressive drugs. Preparation and in vitro pharmacological activity of some benzo-2,1,3-oxadiazoles (benzofurazans) and their N-oxides (benzofuroxans)”, J. Med. Chem., Vol. 11, (1968), pp. 305–311.[Crossref]
  • [23] P.B. Ghosh and M.W. Whitehouse: “Potential antileukemic and immunosuppressive drugs. II. Further studies with benzo-2,1,3-oxadiazoles (benzofurazans) and their N-oxides (benzofuroxans)”, J. Med. Chem., Vol. 12, (1969), pp. 505–507.[Crossref]
  • [24] M.R. Crampton, J. Delaney, L.C. Rabbitt: “The reactions of 4-nitrobenzofuroxan with amines in DMSO; kinetic and equilibrium studies”, J. Chem. Soc. Perk. T. 2, (1999), pp. 2473–2480.[Crossref]
  • [25] G. Moutires, J. Pinson, F. Terrier, R. Goumont: “Electrochemical oxidation of σ-complex-type intermediates in aromatic nucleophilic substitutions”, Chem.-Eur. J., Vol. 7, (2001), pp. 1712–1719.<1712::AID-CHEM17120>3.0.CO;2-G[Crossref]
  • [26] D. Dal Monte, E. Sandri, L. Di Nunno, S. Florio, P. Todesco: “Reattività con i nucleofili dei 4-alogeno-7-nitrobenzofurazani”, Chimica e Industria, Vol. 53, (1971), pp. 940–942.
  • [27] R.A. Manderville and E. Buncel: “Regioselectivity and stereoelectronic factors in the reactions of aryloxide nucleophiles with 4-nitrobenzofuroxan”, J. Chem. Soc. Perk. T. 2, (1993), pp. 1887–1894.[Crossref]
  • [28] S. Uchiyama, T. Santa, T. Fukushima, H. Homma, K. Imai: “Effects of the substituent groups at the 4- and 7-positions on the fluorescence characteristics of benzofurazan compounds”, J. Chem. Soc. Perk. T. 2, (1998), pp. 2165–2173.[Crossref]
  • [29] A.J. Boulton and A.R. Katritzky: “N-Oxides and related compounds. Part XXII*). The rearrangement of 4-nitrobenzofuroxans to 7-nitrobenzofuroxans”, Rev. Roum. Chim., Vol. 7, (1962), pp. 691–697.
  • [30] R.K. Harris, A.R. Katritzky, S. Oksne, A.S. Bailey, W.G. Paterson: “N-Oxides and related compounds. Part XIX.* Proton resonance spectra and the structure of benzofuroxan and its nitro-derivatives”, J. Chem. Soc., (1963), pp. 197–203. [Crossref]
  • [31] A.J. Boulton, P.B. Ghosh, A.R. Katritzky: “N-Oxides and related compounds. Part XXVIII.1 5-Amino- and 5-hydroxy-benzofuroxans”, J. Chem. Soc.(C), (1966), pp. 971–977.
  • [32] A.J. Boulton, P.B. Ghosh, A.R. Katritzky: “Heterocyclic rearrangements. Part V.1 Rearrangement of 4-arylazo and 4-nitroso-benzofuroxans: new syntheses of the benzotriazole and benzofurazan ring systems”, J. Chem. Soc. (B), (1966), pp. 1004–1011.
  • [33] A.J. Boulton, A.R. Katritzky, M.J. Sewell, B. Wallis: “N-Oxides and related compounds. Part XXXI.1 The nuclear magnetic resonance spectra and tautomerism of some substituted benzofuroxans”, J. Chem. Soc. (B), (1967), pp. 914–919.
  • [34] A.R. Katritzky, M.F. Gordeev: “Heterocyclic rearrangements of benzofuroxans and related compounds”, Heterocycles, Vol. 35, (1993), pp. 483–518.[Crossref]
  • [35] L. Di Nunno, S. Florio, P.E. Todesco: “Oxidation of substituted anilines to nitroso-compounds”, J. Chem. Soc. (C), (1970), pp. 1433–1434.
  • [36] D. Nourescu, E.N. Hristea, M.T. Caproiu, A.C. Radutiu, M. Vasilescu, M. Bem, T. Constantinescu: “Synthesis and properties of the new estrone and estradiol derivatives of C-3 phenoxy ether type involving a 4-nitrobenzofurazan moiety”, Proc. Rom. Acad., Series B, Vol. 1, (2001), pp. 7–11.
  • [37] C. Reichardt, Solvent Effects in Organic Chemistry, 2nd Ed., VCH, Weinheim-New York, 1988.
  • [38] The Merck Index, 13th Edition, Merck & Co., Inc., Whitehouse Station, NJ, 2001, p. 3918, p. 687.
  • [39] F. Vögtle: Supramol. Chem., Wiley, Chichester, 1991, p. 27.
  • [40] C. Reichardt and R. Müller: “Pyridinium N-phenoxide betaines and their application for the characterization of solvent polarities. IX1)-The influence of substituents and solvents on the rate of the reaction between pyridinium N-phenoxide betaines and methyl iodide”, Justus Liebigs Ann. Chem., Vol. 11, (1976), pp. 1953–1963. [Crossref]
  • [41] M. Makosza and J. Winiarski: “Vicarious Nucleophilic substitution of hydrogen”, Accounts Chem. Res., Vol. 20, (1987), pp. 282–289.[Crossref]
  • [42] M. Makosza and M. Sypniewski: “Oxidative versus vicarious nucleophilic substitution of hydrogen in the reaction of dithiane derivatives with nitroarenes”, Tetrahedron, Vol. 50, (1994), pp. 4913–4920.[Crossref]
  • [43] M. Makosza, K. Stanski, C. Klepka: “Oxidative nucleophilic substitution of hydrogen in nitrobenzene with 2-phenylpropionitrile carbanion and potassium permanganate oxidant”, Chem. Commun., (1996), pp. 837–838. [Crossref]
  • [44] M. Makosza and K. Wojciechowski: “Application of vicarious nucleophilic substitution in organic synyhesis”, Liebigs Ann. Chem., (1997), pp. 1805–1816. [Crossref]
  • [45] M. Makosza and K. Stalinski: “Oxidative nucleophilic substitution of hydrogen in nitroarenes”, Chem.-Eur. J., Vol. 3, (1997), pp. 2025–2031. [Crossref]
  • [46] M. Makosza and M. Bialecki: “Nitroarylamines via the vicarious nucleophilic substitution of hydrogen: amination, alkylamination, and arylamination of nitroarenes with sulfenamides”, J. Org. Chem., Vol. 63, (1998), pp. 4878–4888.[Crossref]
  • [47] M. Makosza, T. Lemek, A. Kwast: “Effect of base concentration on the rate of the vicarious nucleophilic substitution of hydrogen and on the kinetic isotope effect”, Tetrahedron Lett., Vol. 40, (1999), pp. 7541–7544.[Crossref]
  • [48] T. Constantinescu, F. Marinescu, L. Mutihac, S. Radulescu, L. Papahagi, I. Duta, C. Stancioiu, N. Cristescu: “Process for the wood tar processing. 3.Isolation of 2-methoxyphenol and 2,6-dimethoxyphenol”, Rev. Roum. Chim., Vol. 44, (1993), pp. 1025–1033; Chem. Abstr., Vol. 121, (1994), p. 12072e.
  • [49] C. Hansch and A. Leo: Substituent Constants for Correlation Analysis in Chemistry and Biology, Wiley, New York, 1979.
  • [50] G. Ionita, T. Constantinescu, P. Ionita: “Normal and reversed-phase TLC of some hydrazine derivatives”, JPC-J. Planar Chromat., Vol. 11, (1998), pp. 141–144.
  • [51] R. Calvino, A. Gasco, A. Leo: “An analysis of the lipophilicity of furazan and furoxan derivatives using the CLOGP algorithm”, J. Chem. Soc. Perk. T. 2, (1992), pp. 1643–1646.[Crossref]
Document Type
Publication order reference
YADDA identifier
JavaScript is turned off in your web browser. Turn it on to take full advantage of this site, then refresh the page.