Iodine/tert‐Butyl Hydroperoxide‐Mediated Reaction of Indoles with Dimethylformamide/Dimethylacetamide to Synthesize Bis‐ and Tris(indolyl)methanes

Abstract

Here we report a metal-free iodine/tert-butyl hydroperoxide mediated reaction of N-substituted indoles with dimethylformamide (DMF) / dimethylacetamide (DMA). The reaction produces bis-and tris(indolyl)methanes (BIMs and TIMs), in which DMF/DMA provides the methylene (of BIMs) and methine carbons (of TIMs). We have established different optimized conditions for their synthesis. Iodine (10 mol %) with TBHP (in decane, 1.0 equivalent) in DMF/DMA at 130 8C is required for the BIMs synthesis, whereas iodine (20 mol %) with TBHP (in water, 3.0 equivalent) in DMF-H 2 O or DMA-H 2 O (9:1) is needed for the TIMs. This methodology could be used to synthesize a variety of BIMs and TIMs. We believe, this is the first report of their metal-free synthesis through CÀH functionalization using one carbon source. The use of inexpensive, metal-free and environmentally benign catalyst made the method handy.[a] Dr.

Directly Bridging Indoles to 3,3′‐Bisindolylmethanes by Using Carboxylic Acids and Hydrosilanes under Mild Conditions

“…[15] Furthermore, the amount of formic acid and hydrosilane werei nvestigated in detail, and the optimal amountsofformic acid and Et 3 SiH compared with 1a were 2a nd 4.5 equivalents, respectively (entries 4a nd [13][14][15]. Polar solventa cetonitrile was am ore suitable solvent (entry 4) compared with ethers and arenes (entries [16][17][18][19]. This solvent effect maybeattributed to the stability of the intermediate in the polar solvent.…”

“…Bis(1‐methyl‐1 H ‐indol‐3‐yl)methane (1 c) : White solid (63.0 mg, 92 %); m.p. : 118–119 °C; 1 H NMR (400 MHz, CDCl 3 ): δ =7.62 (d, J= 7.9 Hz, 2 H), 7.29 (d, J= 8.2 Hz, 2 H), 7.21 (d, J= 7.2 Hz, 2 H), 7.09 (t, J= 7.4 Hz, 2 H), 6.79 (s, 2 H), 4.22 (s, 2 H), 3.70 ppm (s, 6 H); 13 C NMR (101 MHz, CDCl 3 ): δ =137.3, 128.1, 127.1, 121.5, 119.4, 118.7, 114.5, 109.2, 32.7, 21.1 ppm; HRMS (ESI): C 19 H 18 N 2 Na + for [ M +Na] + calculated: 297.1362; found: 297.1368.…”

“…Bis(1‐ethyl‐1 H ‐indol‐3‐yl)methane (2 c) : Colorless liquid; 1 H NMR (400 MHz, CDCl 3 ): δ =7.62 (d, J= 7.9 Hz, 2 H), 7.32 (d, J= 8.2 Hz, 2 H), 7.23–7.17 (m, 2 H), 7.11–7.03 (m, 2 H), 6.86 (s, 2 H), 4.23 (s, 2 H), 4.09 (q, J= 7.3 Hz, 4 H), 1.40 ppm (t, J= 7.3 Hz, 6 H); 13 C NMR (101 MHz, CDCl 3 ): δ =136.2, 128.2, 125.4, 121.3, 119.5, 118.6, 114.4, 109.3, 40.8, 21.2, 15.6 ppm; HRMS (ESI): C 21 H 22 N 2 Na + for [ M +Na] + calculated: 325.1675; found: 325.1680; HRMS (ESI): C 21 H 22 N 2 K + for [ M +K] + calculated: 341.1415; found: 341.1409.…”

“…After completion, 1,1,2,2-tetrachloroethane (42.0 mg) were added as an internal standard, and then as ample was taken to determine the yield through 1 HNMR spectroscopy.A ll reactions were performed at least twice to ensure reproducibility. Bis(1-methyl-1 H-indol-3-yl)methane (1 c): [19] White solid (63.0 mg, 92 %);m .p. :…”

“…cyclopropylmethyl-1 H-indol-3-yl)methane (5 c):O il; 1 HNMR (400 MHz, CDCl 3 ): d = 7.62 (d, J = 7.8 Hz, 2H), 7.33 (d, J = 8.2 Hz, 2H), 7.19 (t, J = 7.6 Hz, 2H), 7.07 (t, J = 7.4 Hz, 2H), 6.95 (s, 2H), 4.25 (s, 2H), 3.90 (d, J = 6.5 Hz, 4H), 1.22 (dd, J = 14.5, 8.2 Hz, 2H), 0.55 (d, J = 7.2 Hz, 4H), 0.30 ppm (d, J = 4.0 Hz, 4H); 13 CNMR (101 MHz, CDCl 3 ): d = 136.7, 128.2, 126.0, 121.4, 119.6, 118.6, 114. 3, 109.4, 50.5, 21.3, 11.5, 4.1 ppm;G C-MS (EI, 70 eV) m/z (%): 354.2100 (100.00), 299.1551 (63.62), 353.2022 (50.87), 257.1084 (26.47), 355.2137 (25.85), 130.0656 (25.40), 245.1083 (20.31).Bis(1-allyl-1 H-indol-3-yl)methane (6 c):[19] Milky oil; 1 HNMR (400 MHz, CDCl 3 ): d = 7.61 (d, J = 7.9 Hz, 2H), 7.29 (d, J = 8.2 Hz, 2H), 7.19 (dd, J = 11.2, 4.0 Hz, 2H), 7.12-7.03 (m, 2H), 6.84 (s, 2H), 5.95 (ddt, J = 17.0, 10.4, 5.3 Hz, 2H), 5.15 (dd, J = 10.2, 1.3 Hz, 2H), 5.06 (dd, J = 17.1, 1.4 Hz, 2H), 4.65 (dt, J = 5.3, 1.5 Hz, 4H), 4.23 ppm (s, 2H); 13 CNMR (101 MHz, CDCl 3 ): d = 136.7, 133.9, 128.3, 126.2, 121.6, 119.6, 118.9, 117.1, 114.7, 109.6, 48.8, 21.2 ppm;H RMS (ESI): C 23 H 22 N 2 Na + for [M+ +Na] + calculated:3 49.1675;f ound: 349.1678. Bis(1-(ethan-1-ol)-1 H-indol-3-yl)methane (7 c):Y ellow oil; 1 HNMR (400 MHz, CDCl 3 ): d = 7.61 (d, J = 7.9 Hz, 2H), 7.31 (d, J = 8.2 Hz, 2H), 7.19 (dd, J = 11.2, 4.0 Hz, 2H), 7.08 (t, J = 7.4 Hz, 2H), 6.88 (s, 2H), 4.20 (s, 2H), 4.13 (t, J = 5.2 Hz, 4H), 3.81 (t, J = 5.3 Hz, 4H), 1.71 ppm (s, 2H); 13 CNMR (101 MHz, CDCl 3 ): d = 136.8, 128.3, 126.5, 121.8, 119.6, 119.1, 114.9, 109.5, 62.1, 48.6, 21.1 ppm;H RMS (ESI): C 21 H 22 N 2 O 2 Na + for [M+ +Na] + calculated:3 57.1573;f ound:3 57.1575.…”