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Synlett 2002(7): 1093-1096
DOI: 10.1055/s-2002-32596
LETTER
© Georg Thieme Verlag Stuttgart · New York

N-Azinylpyridinium N-Aminides: An Approach to Pyrazolopyridines via an Intramolecular Radical Pathway

Araceli Nuñez, Aránzazu García de Viedma, Valentín Martínez-Barrasa, Carolina Burgos, Julio Alvarez-Builla*
Departamento de Química Orgánica, Universidad de Alcalá, 28871 Alcalá de Henares, Madrid, Spain
Fax: +34(91)88546 86; e-Mail: julio.alvarez@uah.es;
Further Information

Publication History

Received 3 May 2002
Publication Date:
07 February 2007 (online)

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Abstract

Intramolecular radical arylation, under thermal conditions, to a π-deficient pyridinium, linked to a π-excessive 2-azinyliminopyridine moiety is described. The method allows a new entry to pyrazolo[1,5-a]pyridine nucleus.

Key words

aminides - pyrazolopyridines - intramolecular radical reactions - ylides

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Typical Procedure, Method A: 3-Chloro-dipyrido[1,2- b; 3′2′- d ]pyrazole 5a: A solution of tris(trimethylsilyl)silane (TTMSS) (0.149 g 0.6 mmol) and AIBN (0.099 g, 0.6 mmol) in 6 mL of dry benzene was diluted with 14 mL of dry acetonitrile. The resulting solution was added dropwise by a syringe pump during 16 h, to a dispersion of potassium carbonate (0.083 g, 0.6 mmol) and the aminide 1c (0.062 g, 0.3 mmol) in 50 mL of dry acetonitrile, stirred at 80ºC (bath temperature), under an atmosphere of dry argon. After being stirred at the same temperature until 24 h, full consumption of 1c was observed (TLC analysis). The reaction mixture was allowed to warm to r.t. and distilled water (5 mL) was added. The organic extracts were dried (Na2SO4) and concentrated in vacuo, providing a crude product that was purified by flash chromatography [silicagel, ethyl acetate:hexane (1:1) (Rf ≈ 0.30)]. Yellow solid (0.034 g, 56% yield, toluene, mp = 212-214 ºC). 1H NMR (300 MHz, CDCl3): δ = 8.87 (ddd, 1 H, J = 6.9, 1.2 and 1.1 Hz), 8.80 (d, 1 H, J = 2.4 Hz), 8.39 (d, 1 H, J = 2.4 Hz), 8.11 (ddd, 1 H, J = 8.5, 1.4 and 1.1 Hz), 7.51 (ddd, 1 H, J = 8.5, 7.3 and 1.2 Hz), 7.33 (ddd, 1 H, J = 7.3, 6.9 and 1.4 Hz). 13C NMR (75 MHz, CDCl3): δ = 157.7, 152.2, 146.5, 134.4, 129.0, 127.7, 124.0, 122.8, 118.5, 117.8. IR (KBr): 2922, 1706, 1641, 1437 cm-1. MS (CI): m/z = 204, 206 ([M+ + 1], 100, 32). EIMS HR: calcd for C10H6 35ClN3: [M+] 203.0246. Found: 203.0240.

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Potassium carbonate could abstract a proton from the substituted dihydropyridine radical 6 (Scheme [2] ), to form the radical 7, that would be converted in the arylated compound 5 (see ref. [15b] [c] ). In the absence of potassium carbonate, dihydropyridine radical 6 did not evolve to 5, and only decomposition products and N-N reduction compounds were observed.

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Typical Procedure, Method E: Pyridinium N -(3′-bromo-5′-chloropyrazin-2′-yl)aminide 1e: To a solution of pyridinium (N-(2′-pyrazinyl)aminide 1b (0.172 g, 1 mmol) in dry dichloromethane (5 mL) stirred at 0 ºC was added dropwise a solution of N-chlorosuccinimide (NCS) (0.160 g, 1.2 mmol) in dry dichloromethane (10 mL). The reaction mixture was stirred for 1 h at the same temperature, allowed to warm up to r.t. and stirring for a further 24 h. The solvent was evaporated and the residue was purified by flash chromatography [silicagel, ethanol, (Rf ≈ 0.25)] to yield 0.149 g (72%) of pyridinium N-(5′-chloropyrazin-2′-yl)aminide 8b: Yellow solid (ethyl acetate, mp = 158-161 ºC). 1H NMR (300 MHz, CD3OD): δ = 8.76 (dd, 2 H, J = 5.7 and 1.3 Hz), 8.13 (tt, 1 H, J = 8.2 and 1.3 Hz), 7.86 (dd, 2 H, J = 8.2 and 5.7 Hz), 7.62 (d, 1 H, J = 1.4 Hz), 7.60 (d, 1 H, J = 1.4 Hz). 13C NMR (75 MHz, CD3 OD): δ = 160.8, 145.0, 140.3, 139.5, 135.4, 132.1, 128.7. Anal. Calcd for C9H7ClN4: C, 52.31; H, 3.41; N, 27.11. Found: C, 52.32; H, 3.69; N, 27.31. To a solution of pyridinium N-(5′-chloro-pyrazin-2′-yl)aminide 8b (0.206 g, 1 mmol) in dry dichloro-methane (5 mL) stirred at r.t., was added dropwise a solution of N-bromosuccinimide (NBS) (0.214 g, 1.2 mmol) in dry dichlorometane (10 mL). The reaction mixture was stirred until 24 h at the same temperature, the solvent was eva-porated and the residue was purified by flash chromato-graphy [silicagel, ethanol (Rf ≈ 0.75)] to yield 0.231 g (81%) of pyridinium N-(3′-bromo-5′-chloropyrazin-2′-yl)aminide 1e: Yellow-orange solid (ethyl acetate, mp = 203-205 ºC). 1H NMR (300 MHz, CD3OD): δ = 8.70 (dd, 2 H, J = 6.9 and 1.4 Hz), 8.25 (tt, 1 H, J = 7.8 and 1.4 Hz), 7.93 (dd, 2 H, J = 7.8 and 6.9 Hz), 7.60 (s, 1 H). 13C NMR (75 MHz, CD3OD): δ = 158.4, 146.2, 141.4, 139.6, 130.8, 129.0, 126.0; Anal. Calcd for C9H6BrClN4: C, 37.86; H, 2.12; N, 19.62. Found: C, 38.01; H, 2.43; N, 19.31.