Synthesis of Furoxans from Styrenes under Basic or Neutral Conditions

Ryosuke Matsubara; Yuta Saeki; Jianhua Li; Kazuo Eda

doi:10.1055/s-0033-1338436

Synthesis, Inhaltsverzeichnis

Synthesis 2013; 45(11): 1524-1528
DOI: 10.1055/s-0033-1338436

paper

Synthesis of Furoxans from Styrenes under Basic or Neutral Conditions

Ryosuke Matsubara*

Department of Chemistry, Graduate School of Science, Kobe University, Nada, Kobe, 657-8501, Japan Fax: +81(78)8035799 eMail: matsubara.ryosuke@people.kobe-u.ac.jp

,

Yuta Saeki

Department of Chemistry, Graduate School of Science, Kobe University, Nada, Kobe, 657-8501, Japan Fax: +81(78)8035799 eMail: matsubara.ryosuke@people.kobe-u.ac.jp

,

Jianhua Li

Department of Chemistry, Graduate School of Science, Kobe University, Nada, Kobe, 657-8501, Japan Fax: +81(78)8035799 eMail: matsubara.ryosuke@people.kobe-u.ac.jp

,

Kazuo Eda

Department of Chemistry, Graduate School of Science, Kobe University, Nada, Kobe, 657-8501, Japan Fax: +81(78)8035799 eMail: matsubara.ryosuke@people.kobe-u.ac.jp

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Abstract

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Abstract

Furoxans (1,2,5-oxadiazole 2-oxides) can be synthesized from the corresponding styrenes using NOBF₄ under basic or even almost neutral reaction conditions. Acid-sensitive functional groups are tolerated under the developed basic conditions. For the substrates having poor reactivity, almost neutral conditions (using pyridine equimolar to NOBF₄) are suitable for better yields.

Key words

heterocycles - nitrogen-containing compounds - furoxans - styrenes - cyclization

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Referenzen

References

1a Sheremetev AB, Makhova NN, Friedrichsen W. Adv. Heterocycl. Chem. 2001; 78: 65
1b Gasco A, Boulton AJ. Adv. Heterocycl. Chem. 1981; 29: 251

2a Fruttero R, Crosetti M, Chegaev K, Guglielmo S, Gasco A, Berardi F, Niso M, Perrone R, Panaro MA, Colabufo NA. J. Med. Chem. 2010; 53: 5467
2b Rai G, Sayed AA, Lea WA, Luecke HF, Chakrapani H, Prast-Nielsen S, Jadhav A, Leister W, Shen M, Inglese J, Austin CP, Keefer L, Arnér ES. J, Simeonov A, Maloney DJ, Williams DL, Thomas CJ. J. Med. Chem. 2009; 52: 6474
2c Cena C, Bertinaria M, Boschi D, Giorgis M, Gasco A. ARKIVOC 2006; (vii): 301
2d Grosso ED, Boschi D, Lazzarato L, Cena C, Stilo AD, Fruttero R, Moro S, Gasco A. Chem. Biodiversity 2005; 2: 886
2e Medana C, Ermondi G, Fruttero R, Stilo AD, Ferretti C, Gasco A. J. Med. Chem. 1994; 37: 4412
2f Calvino R, Fruttero R, Ghigo D, Bosia A, Pescarmona GP, Gasco A. J. Med. Chem. 1992; 35: 3296
2g Feelisch M, Schönafinger K, Noack E. Biochem. Pharmacol. 1992; 44: 1149
2h Ghigo D, Heller R, Calvino R, Alessio P, Fruttero R, Gasco A, Bosia A, Pescarmona G. Biochem. Pharmacol. 1992; 43: 1281

3a Cena C, Lolli ML, Lazzarato L, Guaita E, Morini G, Coruzzi G, McElroy SP, Megson IL, Fruttero R, Gasco A. J. Med. Chem. 2003; 46: 747
3b Fruttero R, Boschi D, Stilo AD, Gasco A. J. Med. Chem. 1995; 38: 4944

4a Curini M, Epifano F, Marcotullio MC, Rosati O, Ballini R, Bosica G. Tetrahedron Lett. 2000; 41: 8817
4b Klamann D, Koser W, Weyerstahl P, Fligge M. Chem. Ber. 1965; 98: 1831

5 Wiley RH, Wakefield BJ. J. Org. Chem. 1960; 25: 546
6 Alimenti G, Grifantini M, Gualteri F, Stein ML. Tetrahedron 1968; 24: 395

7a Dinh NH, Ly NT, Hoan PV. J. Heterocycl. Chem. 2006; 43: 1657
7b Gasco AM, Fruttero R, Sorba G, Gasco A. Liebigs Ann. Chem. 1991; 1211
7c Fruttero R, Ferrarotti B, Serafino A, Stilo AD, Gasco A. J. Heterocycl. Chem. 1989; 26: 1345

8 Aliphatic internal alkenes such as oct-4-ene and cyclohexene were tried as substrates in this furoxan synthesis transformation, but the desired furoxans were obtained in much lower yield (<10%) than in the cases using styrene derivatives as substrates.
9 Velázquez C, Rao PN. P, McDonald R, Knaus EE. Bioorg. Med. Chem. 2005; 13: 2749
10 The reaction of NOBF₄ and pyridine has been reported, see: Olah GA, Olah JA, Overchuk NA. J. Org. Chem. 1965; 30: 3373
11 CCDC 922872 (2a) and CCDC 922871 (2l) contain supplementary crystallographic data for this paper. These data can be obtained free of charge at www.ccdc.cam.ac.uk/conts/retrieving.html or from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; Fax +44(1223)336033; E-mail: deposit@ccdc.cam.ac.uk.

12a Mallory FB, Cammarata A. J. Am. Chem. Soc. 1966; 88: 61
12b Freeman JP. J. Org. Chem. 1963; 28: 2508

13 The structures of the minor regioisomers were assigned by NMR spectroscopy and GC-MS analysis.
14 The proposed reaction mechanism is as follows: Electrophilic addition of a nitrosyl cation to an alkene, followed by deprotonation by pyridine, affords a nitrosoalkene. A second addition of a nitrosyl cation to the nitrosoalkene and cyclization leads to a furoxan.
15 Mitchell WR, Paton RM. ARKIVOC 2009; (xiv): 200

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