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

Inga Cikotiene; Rokas Sazinas; Rita Mazeikaite; Linas Labanauskas

doi:10.1055/s-0030-1259053

LETTER

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

Inga Cikotiene*^a, Rokas Sazinas^a, Rita Mazeikaite^b, Linas Labanauskas^b
^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

Abstract

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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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References and Notes

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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) Å^³, ρ = 1.540 g/cm^³, F(000) = 472. X-ray diffraction data were collected on a Nonius Kappa CCD diffractometer at the temperature 293 K using graphite-monochromated MoK_α radiation (λ = 0.71073 Å). Structure 2a was solved by direct methods with SIR97 program^¹0 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 ORTEP^¹² 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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<A NAME="RG30510ST-11">11</A> Sheldrick GM. SHELXL97, Program for the Refinement of Crystal Structures University of Göttingen; Germany: 1997.

<A NAME="RG30510ST-12">12</A> Johnson CK. ORTEP-II, Report ORNL-5138 Oak Ridge National Laboratory; Oak Ridge TN: 1976.

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): ν_max = 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): ν_max = 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): ν_max = 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.

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.

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

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