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Synlett 2010(20): 3027-3030  
DOI: 10.1055/s-0030-1259053
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Unexpected Regioselectivity in Cycloisomerization of 2-Alkynyl-3-nitro­thiophenes

Inga Cikotiene*a, Rokas Sazinasa, Rita Mazeikaiteb, Linas Labanauskasb
a Department of Organic Chemistry, Faculty of Chemistry, Vilnius University, Naugarduko 24, 03225 Vilnius, Lithuania
Fax: +370(5)2330987; e-Mail: inga.cikotiene@chf.vu.lt;
b Center for Physical Sciences and Technology, Institute of Chemistry, Akademijos 7, 08412 Vilnius, Lithuania
Further Information

Publication History

Received 7 October 2010
Publication Date:
17 November 2010 (online)

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Abstract

The intramolecular cycloizomerization of 2-alkynyl-3-nitrothiophenes was catalyzed by AuCl3 or CF3CO2Ag to produce the corresponding thieno[3,2-c]isoxazoles bearing carbonyl functionality in position 3 instead of expected 5-substituted 6H-thieno[3,2-b]pyrrol-6-one 4-oxides.

Key words

2-alkynyl-3-nitrothiophenes - thieno[3,2-c]isoxazoles - cycloizomerization - catalysis

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8

Crystal Structure Analysis for 2a
C12H7NO2S, M r = 229.25 g mol-¹, orthorombic, space group P212121, a = 3.86590 (10), b = 9.5511 (4), c = 26.7855 (12) Å, α = β = γ = 90.00, V = 989.02 (7) ų, ρ = 1.540 g/cm³, F(000) = 472. X-ray diffraction data were collected on a Nonius Kappa CCD diffractometer at the temperature 293 K using graphite-monochromated MoKα radiation (λ = 0.71073 Å). Structure 2a was solved by direct methods with SIR97 program¹0 and refined by full-matrix least squares techniques with anisotropic nonhydrogen atoms. Hydrogen atoms were refined in the riding model. The refinement calculations were carried out with the help of SHELX97 program.¹¹ ORTEP¹² view of the molecule is shown in Figure  [¹] . Crystallographic data for structure 2a have been deposited at the Cambridge Crystallographic Data Centre (CCDC number 795865. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif).

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Typical Procedures for the Cycloisomerization of 2-Alkynyl-3-nitrothiophenes 1Method A
To a solution of the corresponding 2-arylethynyl-3-nitrothiophene 1 (0.3 mmol) in dry CH2Cl2 (5 mL) AuCl3 (5 mol%) was added. The resulting reaction mixture was stirred for 15-60 min at r.t. After the evaporation of solvent, the crude was purified by column chromatography, eluting with benzene and hexane mixtures.
Method B
To a solution of the corresponding 2-arylethynyl-3-nitrothiophene 1 (0.3 mmol) in dry DCE (5 mL) silver trifluoroacetate (10 mol.%) was added. The resulting reaction mixture was refluxed for 1.5-2 h. After the evaporation of solvent, the crude was purified by column chromatography, eluting with benzene and hexane mixtures.
Phenylthieno[3,2- c ]isoxazol-3-yl Methanone (2a)
Yield 97%; mp 114-115 ˚C. IR (KBr): νmax = 1635 (C=O) cm-¹. ¹H NMR (300 MHz, CDCl3): δ = 7.15 [1 H, d, J = 5.4 Hz, C(6)H], 7.57-7.63 (2 H, m, ArH), 7.68-7.73 (1 H, m, ArH), 7.70 [1 H, d, J = 5.4 Hz, C(5)H], 8.35-8.38 (2 H, m, ArH) ppm. ¹³C NMR (75 Hz, CDCl3): δ = 112.0 [C(6)], 127.0 [C(3a)], 128.8 (ArC), 130.1 (ArC), 134.0 (ArC), 135.0 (ArC), 143.1 [C(5)], 158.2 [C(6a)], 170.5 [C(3)], 179.3 (C=O) ppm. Anal. Calcd for C12H7NO2S: C, 62.87; H, 3.08; N, 6.11. Found: C, 62.90; H, 3.10; N, 6.08.
Thieno[3,2- c ]isoxazole-3-carbaldehyde (2f)
Yield 87%; mp 66-67 ˚C. IR (KBr): νmax = 1683 (C=O) cm-¹. ¹H NMR (300 MHz, CDCl3): δ = 7.15 [1 H, d, J = 5.4 Hz, C(6)H], 7.68 [1 H, d, J = 5.4 Hz, C(5)H], 10.14 (1 H, s, CHO) ppm. ¹³C NMR (75 Hz, CDCl3): δ = 111.7 [C(6)], 123.4 [C(3a)], 142.4 [C(5)], 156.8 [C(6a)], 171.0 [C(3)], 177.3 (C=O) ppm. Anal. Calcd for C6H3NO2S: C, 47.05; H, 1.97; N, 9.15. Found: C, 47.00; H, 2.01; N, 9.18.
1-Thieno[3,2- c ]isoxazol-3-yl-1-pentanone (2g)
Yield 90%; mp 62-63 ˚C. IR (KBr): νmax = 1681 (C=O) cm-¹. ¹H NMR (300 MHz, CDCl3): δ = 0.95 (3 H, t, J = 7.5 Hz, CH2CH2CH2CH 3), 1.44 (2 H, sext, J = 7.5 Hz, CH2CH2CH 2CH3), 1.76 (2 H, sext, J = 7.5 Hz, CH2CH 2CH2CH3), 3.04 (2 H, t, J = 7.5 Hz, CH 2CH2CH2CH3), 7.09 [1 H, d, J = 5.4 Hz, C(6)H], 7.63
[1 H, d, J = 5.4 Hz, C(5)H] ppm. ¹³C NMR (75 Hz, CDCl3): δ = 13.8 (CH2CH2CH2 CH3), 22.3 (CH2CH2 CH2CH3), 25.5 (CH2 CH2CH2CH3), 39.3 (CH2CH2CH2CH3), 111.9 [C(6)], 123.4 [C(3a)], 142.7 [C(5)], 157.4 [C(6a)], 170.9 [C(3)], 188.6 (C=O) ppm. Anal. Calcd for C10H11NO2S: C, 57.39; H, 5.30; N, 6.69. Found: C, 57.45; H, 5.31; N, 6.88.

14

Compounds 1a-h, 2b-d,h, 4a,b, and 5a,b were also fully characterized by IR, ¹H NMR, ¹³C NMR spectroscopic and microanalytical data.