Synthesis of Substituted Indolizines and Pyrrolo[2,1-a]isoquinolines from
1,1-Diiodo-2,2-dinitroethylene

Abstract

The synthesis of iodo-nitro-substituted indolizines and pyrrolo[2,1-a]isoquinolines has been achieved by reaction of 1,1-diiodo-2,2-dinitroethylene with pyridinium and isoquinolinium salts containing active methylene groups.

Key words

indolizines - pyrrolo-fused heterocycles - cycloaddition - nitro compounds - iodine

References

• 1a Nitroalkenes: Conjugated Nitro Compounds   Perekalin VV. Lipina ES. Berestovitskaya VM. Efremov DA. Wiley; Chichester: 1994. 
• 1b Rajappa S. Tetrahedron  1999,  55:  7065 
• 1c Denmark SE. Thorarensen A. Chem. Rev.  1996,  96:  137 
• 2 Tominaga Y. Ichihara Y. Hosomi A. Heterocycles  1988,  27:  2345 
• 3 Tominaga Y. Hidaki S. Matsuda Y. Kobayashi G. Yakagaku Zasshi  1984,  104:  440 
• 4 Biltz H. Kedesdy E. Chem. Ber.  1900,  33:  2190 
• 5 Baum K. Bigelow SS. Nguyen NV. Archibald TG. Gilardi R. Flippen-Anderson JL. George C. J. Org. Chem.  1992,  57:  235 
• 6 For a discussion of heteroaryl halides see: Palladium in Heterocyclic Chemistry   Li JJ. Gribble GW. Pergamon; Amsterdam: 2000. 
• 7 See: The Nitro Group in Organic Synthesis   Ono N. Wiley-VCH; New York: 2001.  Chap. 6. p.170-181  

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Procedure for the synthesis of ethyl 2-iodo-1-nitro indolizine-3-carboxylate 3b: A solution of ethyl 2-pyridinium-1-ylacetate bromide (0.49 g, 0.002 mol) and triethylamine (0.84 mL, 0.006 mol) in dichloromethane (5 mL) was treated dropwise with a solution of 1,1-diiodo-2,2-dinitroethylene [5] (0.74 g, 0.002 mol) in dichloromethane (3 mL) and the resulting solution stirred at room temperature for 24 h. The mixture was washed with water (5 mL) and the aqueous layer extracted with dichloromethane (5 × 15 mL). The combined dichloromethane extracts were dried over magnesium sulfate, filtered and evaporated to give a brown oil which was flash-chromatographed over silica. Gradient elution with light petroleum-ethyl acetate afforded the product as bright yellow crystals (0.31 g, 43%), mp 160-161 °C. ¹H NMR (250 MHz, CDCl₃): δ 1.51 (3 H, t, J = 7 Hz, CH₃), 4.52 (2 H, q, J = 7Hz,CH₂), 7.12 (1 H, td, J = 7 Hz, 1, H-6), 7.52 (1 H, ddd, J = 9, 7, 1 Hz, H-7), 8.58 (1 H, d, J = 9 Hz, H-8), 9.67 (1 H, d, J = 7 Hz, H-5). ¹³C NMR (100 MHz, CDCl₃): δ 14.7 (CH₃), 62.0 (CH₂), 116.5, 116.6, 117.7, 119.2, 128.6, 129.8, 130.1, 135.5, 169.9 (CO). IR (KBr): 1696 (C=O), 1540 and 1366 (NO₂), 1212 (C-O) cm^-1. HRMS: found m/z 359.9602, C₁₁H₉IN₂O₄ requires: 359.9607.

9

Structural parameters for 3b: data collection: Bruker SMART 1000 CCD diffractometer; radiation: MoKα; wavelength: 0.71703 Å; crystal size: 0.21 × 0.20 × 0.18 mm³; crystal system: monoclinic; space group: P2₁/c; unit cell: a = 8.2382(6) Å, b = 11.5831(9) Å, c = 12.5068(10) Å, α = 90°, β = 90.888(2)°, γ = 90°; cell volume = 1193.30(16) ų; Z: 4; density; 2.004 g cm^-3; absorption coefficient: µ = 2.692 mm^-1; F(000): 696; reflections for cell refinement: 7771 (θ range 2.40° to 28.93°); θ range for data collection: 2.40° to 28.91°; index ranges: h -10 to 11, k -14 to 15, l -16 to 16; completeness to θ = 26.00°: 100.0%; intensity decay: 0%; reflections collected: 10350; independent reflections: 2884 (R_int = 0.0128); reflections with F² > 2σ: 2666; min and max transmission: 0.602 and 0.643; structure solution: direct methods; refinement method: full-matrix least squares on F²; final R indices [F² > 2σ]: R1 = 0.0186, wR2 = 0.0455; R indices (all data) r1 = 0.0214, wR2 = 0.0469; goodness-of-fit on F²: 1.063; extinction coefficient: 0.00106(18); largest and mean shift/su: 0.002 and 0.000; largest diff. peak and hole: 0.503 and -0.503 e Å^-3.