Compound 5

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Compound data: CIF

Compound data: FCF

Synthetic procedure: See article for the definitive version of this procedure and for full experimental details.

Isolated in 48% yield using the following general conditions: a mixture of picolinamide (0.2 mmol, 1.0 equiv), Pd(OAc)₂ (6.7 mg, 0.03 mmol, 0.15 equiv), and PhI(DMM) (200 mg, 0.6 mmol, 3.0 equiv) in chlorobenzene (4 mL) in a 12 mL glass vial (purged with Ar, sealed with PTFE cap) was heated at 110 ^oC for 12 hours. The reaction mixture was cooled to rt and diluted with Ethyl Acetate, then washed with Sat. NaHCO₃ and brine. The organic phase was dried over anhydrous Na₂SO₄, and concentrated in vacuo. The residue was purified by silica gel flash chromatography to give the desired product. Single crystals for X-ray studies were grown by slow diffusion of hexane into toluene solution of 5 at room temperature. (R_f = 0.4, 20% Ethyl Acetate in Hexanes). ¹H NMR (CDCl₃, 400 MHz, ratio of rotamers: 5.6/1) δ 8.78 (d, J = 4.4 Hz, 0.18H), 8.64 (d, J = 4.6 Hz, 1H), 8.25 (d, J = 7.8 Hz, 1H), 8.13 (d, J = 7.8 Hz, 0.18H), 7.91 (m, 0.18H), 7.88 (td, J = 7.7, 1.4 Hz, 1H), 7.51 (dd, J = 7.1, 4.9 Hz, 0.18H), 7.44 (dd, J = 6.6, 4.8 Hz, 1H), 7.24 (t, J = 8.0 Hz, 1H), 7.14 (t, J = 8.2 Hz, 0.18H), 7.08 (d, J = 7.4 Hz, 1H), 6.91 (d, J = 7.7 Hz, 0.18H), 6.62 (d, J = 8.6 Hz, 1H), 6.57 (m, 0.18H), 5.83 (s, 2H), 5.28 (s, 0.36H), 3.88 (s, 0.48H), 3.87 (s, 3H); ¹³C NMR (CDCl₃, 100 MHz) δ 164.17, 161.14, 153.39, 153.11, 151.36, 151.26, 151.00, 150.84, 148.47, 148.40, 137.15, 137.02, 130.05, 129.77, 126.35, 125.97, 124.39, 124.10, 114.31, 112.08, 111.84, 111.45, 106.37, 104.86, 64.67, 57.39, 56.45, 56.38; HRMS Calcd for C₁₄H₁₃N₂O₂ [M+H⁺]: 241.0972, found: 241.0972. IR (film) 3063, 2976, 1651, 1598, 1476, 1454, 1432, 1345, 772 cm^-1. The X-ray structure is deposited in the Cambridge Crystallographic Data Centre CCDC 1430314. A colorless needle shaped crystal of compound 5 (C₁₄H₁₂N₂O₂) with approximate dimensions 0.07 x 0.12 x 0.19 mm, was used for the X-ray crystallographic analysis. The X-ray intensity data were measured at 298(2) K, on a Bruker SMART APEX CCD area detector system equipped with a graphite monochromator and a MoKα fine-focus sealed tube (λ = 0.71073Å) operated at 1600 watts power (50 kV, 32 mA). The detector was placed at a distance of 5.8 cm from the crystal. A total of 1450 frames were collected with a scan width of 0.3º in ω and an exposure time of 10 seconds/frame. The total data collection time was about 7 hours. The frames were integrated with the Bruker SAINT software package using a narrow-frame integration algorithm. The integration of the data using a Monoclinic unit cell yielded a total of 5849 reflections to a maximum θ angle of 28.26^o (0.90 Å resolution), of which 2807 were independent, completeness = 97.2%, Rint = 0.0182, Rsig = 0.0298 and 2065 were greater than 2σ(I). The final cell constants: a = 19.359(4)Å, b = 6.8992(14)Å, c = 17.688(4)Å, α = 90°, β = 98.906(4)°, γ = 90°, volume = 2334.0(8)ų, are based upon the refinement of the XYZ-centroids of 1393 reflections above 20σ(I) with 2.331° <θ <24.786°. Analysis of the data showed negligible decay during data collection. Data were corrected for absorption effects using the multiscan technique (SADABS). The ratio of minimum to maximum apparent transmission was 0.7828. The structure was solved and refined using the Bruker SHELXTL (Version 6.1) Software Package, using the space group C2/c, with Z = 8 for the formula unit, C₁₄H₁₂N₂O₂. The final anisotropic full-matrix least-squares refinement on F² with 164 variables converged at R1 = 5.43%, for the observed data and wR2 = 14.33% for all data. The goodness-of-fit was 1.031. The largest peak on the final difference map was 0.205 e^-/ų and the largest hole was -0.285 e^-/ų. Based on the final model, the calculated density of the crystal is 1.367 g/cm³ and F(000) amounts to 1008 electrons.