A Highly Regioselective Synthesis of N-Acyl-2-acyl(aroyl)indolium Chloride through Palladium-Copper Catalysis Followed by Friedel–Crafts Reaction

Abstract

2-Trimethylsilylethynyl acetanilides, obtained from the palladium-catalyzed reactions of 2-iodoacetanilides with trimethylsilylacetylene, underwent Friedel–Crafts acylation reactions yielding the N-acyl-2-acyl(aroyl)indolium chlorides in good yields.

Key words

indolium chloride - palladium–copper catalysis - ­Friedel–Crafts acylation

• References and Notes

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• 33 Analytical data for 2-trimethylsilylethynylacetanilide 5: Crystalline solid; mp 94–95 °C. IR (KBr): 3327 (NH), 2158 (C≡C), 1695 (C=O), 1672, 1576, 1516, 1444 cm^–1; ¹H NMR (400 MHz CDCl₃): δ = 8.39 (d, J = 8.3 Hz, 1 H, Ar-H), 7.99 (br. s, 1 H, NH), 7.41 (dd, J = 8.0, 8.3 Hz, 1 H, Ar-H), 7.32 (dd, J = 8.0, 8.3 Hz, 1 H, Ar-H), 7.01 (d, J = 8.0 Hz, 1 H, Ar-H), 2.21 (s, 3 H, COCH₃), 0.30 (s, 9 H, SiMe₃); ¹³C NMR (100 MHz, CDCl₃): δ = 168.0 (CO), 139.5, 131.4, 129.9, 123.10, 118.9, 111.5, 102.2, 100.2, 24.7 (CH₃), 0.10 (SiMe₃); UV (EtOH): λ_max = 296.2, 250.8 nm. Anal. Calcd. for C₁₃H₁₇SiNO: C, 67.48; H, 7.40; N, 6.05. Found: C, 67.09; H, 7.43; N, 6.03.
• 34 Selected analytical data for N-acetyl-2-acetyl(aroyl)-indolium chlorides; N-Acetyl-2-acetyl indolium chloride 13: Crystalline solid; mp 84–86 °C. IR (KBr): 3221 (NH), 1684 (C=O), 1652, 1608, 1576, 1560, 1502, 1130 cm^–1; ¹H NMR (400 MHz CDCl₃): δ = 11.06 (br. s, 1 H, NH), 8.59 (d, J = 8.0 Hz, 1 H, Ar-H), 7.65 (t, J = 8.0 Hz, 1 H, Ar-H), 7.46 (d, J = 8.0 Hz, 1 H, Ar-H), 7.05 (t, J = 8.0 Hz, 1 H, Ar-H), 6.10 (s, 1 H, H-3), 2.18 (s, 3 H, COCH₃), 2.12 (s, 3 H, COCH₃). ¹³C NMR (400 MHz, CDCl₃): δ = 194.31 (C=O), 185.31 (C=O), 168.89, 140.152, 135.85, 133.83, 129.06, 122.41, 121.02, 98.02, 25.40 (COCH₃), 23.15 (COCH₃); UV (EtOH): λ_max = 334, 305.4, 259.8, 238.4 nm. N-Acetyl-2-anisoyl indolium chloride 15: Pale-yellow crystals; mp 112–113 °C. IR (KBr): 3327.9 (NH), 1683.7 (C=O), 1610, 1576.7, 1500, 1413, 1360, 1175 cm^–1; ¹H NMR (400 MHz, CDCl₃): δ = 11.04 (br. s, 1 H, NH), 8.62 (d, J = 8.0 Hz, 1 H, Ar-H), 7.91 (d, J = 8.0 Hz, 2 H, Ar-H), 7.77 (d, J = 8.0 Hz, 1 H, Ar-H), 7.51 (t, J = 7.2 Hz, 1 H, Ar-H), 7.12 (d, J = 7.2 Hz, 1 H, Ar-H), 6.97 (d, J = 8.0 Hz, 2 H, Ar-H), 6.70 (s, 1 H, H-3), 3.88 (s, 3 H, Ar-OCH₃), 2.22 (s, 3 H, COCH₃). ¹³C NMR (100 MHz, CDCl₃): δ = 193.46 (C=O), 180 (C=O), 168.93, 163.41, 139.83, 133.60, 131.17, 128.99, 126.14, 123.38, 122.75, 121.46, 114.09, 94.00, 55.53 (OCH₃), 25.48 (COCH₃); UV (EtOH): λ_max = 380.80, 360.6, 238.0 nm; Anal. Calcd for C₁₈H₁₆ClNO₃: C, 65.56; H, 4.89; N, 4.25. Found: C, 65.87; H, 4.75; N, 4.52. N-Acetyl-2-toluoyl indolium chloride 16: Amorphous solid; mp 64–65 °C. IR (KBr): 3325 (NH), 1687 (C=O), 1569, 1508, 1446, 1423, 1365, 1190, 756 cm^–1; ¹H NMR (400 MHz, CDCl₃): δ = 11.07 (br. s, 1 H, NH), 8.63 (d, J = 8.0 Hz, 1 H, Ar-H), 7.83 (d, J = 8.0 Hz, 2 H, Ar-H), 7.78 (d, J = 8.0 Hz, 1 H, Ar-H), 7.49 (t, J = 7.2 Hz, 1 H, Ar-H), 7.27 (d, J = 7.2 Hz, 2 H, Ar-H), 7.11 (t, J = 8 Hz, 1 H, Ar-H), 6.74 (s, 1 H, H-3), 2.41 (s, 3 H, COCH₃), 2.21 (s, 3 H, Ar-CH₃). ¹³C NMR (100 MHz, CDCl₃): δ = 198.92 (C=O), 179.85 (C=O), 168.88, 143.45, 139.97, 133.74, 131.71, 128.83, 126.16, 123.16, 122.68, 121.12, 120.81, 94.48, 25.48 (COCH₃), 21.62 (Ar-CH₃); UV (EtOH): λ_max = 361.4, 256.6 nm; Anal. Calcd for C₁₈H₁₆ClNO₂: C, 68.90; H, 5.14; N, 4.46. Found: C, 69.20; H, 5.40; N, 4.77. N-Acetyl-2-acetyl-5-chloro-1H-indolium chloride 18: Colorless crystalline solid; mp 51–52 °C; R_f 0.75 (n-hexane–ethyl acetate, 5:1). IR (KBr): 3298.0 (NH), 1706.9 (C=O), 1581.5, 1541.0 (C=C), 1438, 1276, 1168.8, 756.0 cm^–1; ¹H NMR (400 MHz, CDCl₃): δ = 8.00 (br. s, 1 H, NH), 7.80 (d, J = 9.2 Hz, 1 H, H-7), 7.41 (d, J = 2.0 Hz, 1 H, H-4), 7.18 (dd, J = 9.2, 2.0 Hz, 1 H, H-6), 6.34 (s, 1 H, H-3), 2.97 (s, 3 H, COCH₃), 2.72 (s, 3 H, COCH₃); ¹³C NMR (100 MHz, CDCl₃): δ = 180.05 (C=O), 170.05 (C=O), 144.13, 134.90, 131.20, 128.63, 123.47, 119.63, 115.94, 107.52, 22.55 (COCH₃), 13.93 (COCH₃).