Unexpected Decarbonylation of Acylethynylpyrroles under the Action of Cyanomethyl Carbanion: A Robust Access to Ethynylpyrroles
Abstract
:1. Introduction
2. Results and Discussion
Entry | Base, eq. | Content in the crude, % (1H NMR) | |||
---|---|---|---|---|---|
1a | 2a | 3a | 4a | ||
1 | n-BuLi, 2 | traces | 10 | 78 | 12 |
2 | t-BuOLi, 2 | ~100 | traces | traces | traces |
3 | t-BuONa, 2 | traces | traces | 85 | 15 |
4 | t-BuOK, 1 | 18 | 16 | traces | 66 |
5 | t-BuOK, 2 | traces | 10 | traces | 90 |
6 b | t-BuOK, 2 | traces | traces | traces | ~100 d |
7 c | t-BuOK, 2 | traces | traces | traces | ~100 e |
3. Experimental Section
3.1. General Information
3.2. Synthesis of Ethynylpyrroles 4a–k, Ethynylindole 6, Ethynylfuran 8, General Procedure
- 1-Benzyl-2-ethynyl-4,5,6,7-tetrahydro-1H-indole (4a). Yield: 197 mg (84%), colorless oil; 1H NMR (400.13 MHz, CDCl3): δ 7.37–7.24 (m, 3H, Hm,p, Ph), 7.13–7.08 (m, 2H, Ho, Ph), 6.37 (s, 1H, H-3, pyrrole), 5.14 (s, 2H, CH2-Ph), 3.35 (s, 1H, ≡CH), 2.54–2.49 (m, 2H, CH2-7), 2.43–2.38 (m, 2H, CH2-4), 1.82–1.68 (m, 4H, CH2-5, CH2-6); 13C NMR (100.6 MHz, CDCl3): δ 138.3, 130.9, 128.7 (2C), 127.3, 126.7 (2C), 118.0, 114.2, 99.7, 81.2, 77.0, 47.9, 23.5, 23.2, 23.1, 22.5; IR (KBr) 3287, 3087, 3063, 3030, 2928, 2849, 2097, 1495, 1457, 1388, 1357, 1301, 1130, 1077, 1029, 928, 795, 722, 696, 545, 457 cm−1; Anal. Calcd for C17H17N: C, 86.77; H, 7.28; N, 5.95%. Found: C, 86.47; H, 7.31; N, 6.14%.
- 2-Ethynyl-1-methyl-4,5,6,7-tetrahydro-1H-indole (4b). Yield: 137 mg (86%), white crystals, mp 53–54 °C; 1H NMR (400.13 MHz, CDCl3): δ 6.26 (s, 1H, H-3, pyrrole), 3.50 (s, 3H, NMe), 3.37 (s, 1H, ≡CH), 2.52–2.50 (m, 2H, CH2-7), 2.47–2.45 (m, 2H, CH2-4), 1.83–1.80 (m, 2H, CH2-5), 1.73–1.71 (m, 2H, CH2-6); 13C NMR (100.6 MHz, CDCl3,): δ 130.9, 117.4, 113.6, 112.6, 81.1, 76.9, 30.8, 23.6, 23.2, 23.0, 22.4; IR (film) 3288, 3100, 2929, 2847, 2097, 1570, 1462, 1442, 1386, 1302, 1130, 1055, 790, 667, 536 cm−1; Anal. Calcd for C11H13N: C, 82.97; H, 8.23; N, 8.80%. Found: C, 82.71; H, 8.44; N, 8.58%.
- 2-Ethynyl-1-vinyl-4,5,6,7-tetrahydro-1H-indole (4c). Yield: 127 mg (74%), colorless oil; 1H NMR (400.13 MHz, CDCl3): δ 6.97 (dd, J = 16.1, 9.4 Hz, 1H, Hx), 6.34 (s, 1H, H-3, pyrrole), 5.34 (d, J = 16.1 Hz, 1H, Ha), 4.83 (d, J = 9.4 Hz, 1H, Hb), 3.39 (s, 1H, ≡CH), 2.66–2.63 (m, 2H, CH2-7), 2.48–2.45 (m, 2H, CH2-4), 1.83–1.80 (m, 2H, CH2-5), 1.71–1.69 (m, 2H, CH2-6); 13C NMR (100.6 MHz, CDCl3): δ 130.5, 119.5, 116.8, 112.3, 102.1, 99.7, 82.1, 76.8, 24.2, 23.4, 23.1, 23.0; IR (film) 3292, 3128, 3049, 2932, 2849, 2099, 1643, 1577, 1483, 1438, 1387, 1324, 1294, 1136, 966, 871, 802, 669, 558 cm−1; Anal. Calcd for C12H13N: C, 84.17; H, 7.65; N, 8.18%. Found: C, 83.85; H, 7.81; N, 8.36%.
- 5-Ethynyl-2,3-dimethyl-1-vinyl-1H-pyrrole (4d). Yield: 52 mg (36%), colorless oil; 1H NMR (400.13 MHz, CDCl3): δ 6.91 (dd, J = 16.0, 9.2 Hz, 1H, Hx), 6.36 (s, 1H, H-3, pyrrole), 5.46 (d, J = 16.1 Hz, 1H, Ha), 4.94 (d, J = 9.2 Hz, 1H, Hb), 3.37 (s, 1H, ≡CH), 2.21 (s, 3H, Me), 1.99 (s, 3H, Me); 13C NMR (100.6 MHz, CDCl3): δ 130.8, 127.8, 119.0, 116.7, 111.6, 104.5, 81.7, 76.9, 11.4, 11.1; IR (film) 3291, 3106, 2920, 2866, 2099, 1643, 1483, 1432, 1392, 1335, 1310, 1162, 1113, 965, 879, 806, 671, 562 cm−1; Anal. Calcd for C10H11N: C, 82.72; H, 7.64; N, 9.65%. Found: C, 82.94; H, 7.49; N, 9.80%.
- 2-Ethynyl-1-methyl-5-phenyl-1H-pyrrole (4e). Yield: 172 mg (95%), colorless oil; 1H NMR (400.13 MHz, CDCl3): δ 7.42–7.34 (m, 5H, Ph), 6.55 (d, J = 3.8 Hz, 1H, H-3, pyrrole), 6.16 (d, J = 3.8 Hz, 1H, H-4, pyrrole), 3.69 (s, 3H, NMe), 3.44 (s, 1H, ≡CH); 13C NMR (100.6 MHz, CDCl3): δ 136.7, 132.9, 128.9 (2C), 128.6 (2C), 127.5, 116.1, 115.6, 108.6, 82.0, 76.5, 33.2; IR (film) 3287, 3106, 3060, 2948, 2102, 1602, 1498, 1457, 1390, 1324, 1234, 1155, 1074, 1028, 758, 698, 568 cm−1; Anal. Calcd for C13H11N: C, 86.15; H, 6.12; N, 7.73%. Found: C, 85.75; H, 5.86; N, 7.48%.
- 2-Ethynyl-5-(4-methylphenyl)-1-vinyl-1H-pyrrole (4f). Yield: 174 mg (84%), colorless oil; 1H NMR (400.13 MHz, CDCl3): δ 7.34–7.28 (m, 2H, Ho, Ph), 7.24–7.17 (m, 2H, Hm, Ph), 6.82 (dd, J = 15.9, 9.0 Hz, 1H, Hx), 6.63 (d, J = 3.8 Hz, 1H, H-3 pyrrole), 6.17 (d, J = 3.8 Hz, 1H, H-4, pyrrole), 5.53 (d, J = 15.9 Hz, 1H, Ha), 4.99 (d, J = 9.0 Hz, 1H, Hb), 3.43 (s, 1H, ≡CH), 2.38 (s, 3H, Me); 13C NMR (100.6 MHz, CDCl3): δ 137.6, 136.1, 131.1, 129.6, 129.2 (2C), 129.1 (2C), 118.5, 114.5, 109.9, 107.0, 82.5, 76.8, 21.3; IR (KBr) 3287, 3112, 3024, 2921, 2102, 1643, 1547, 1510, 1466, 1419, 1389, 1324, 1297, 1226, 1113, 963, 889, 822, 775, 672, 571, 500 cm−1; Anal. Calcd for C15H13N: C, 86.92; H, 6.32; N, 6.76%. Found: C, 86.68; H, 6.51; N, 6.85%.
- 1-Benzyl-2-ethynyl-5-(4-methoxyphenyl)-1H-pyrrole (4g). Yield: 253 mg (88%), white crystals; mp 92–93 °C; 1H NMR (400.13 MHz, CDCl3): δ 7.30–7.22 (m, 3H, Hm,p, Ph), 7.20–7.15 (m, 2H, Ho, Ph), 6.99–6.93 (m, 2H, Hm, Ph), 6.87–6.82 (m, 2H, Ho, Ph), 6.63 (d, J = 3.7 Hz, 1H, H-3 pyrrole), 6.16 (d, J = 3.7 Hz, 1H, H-4, pyrrole), 5.25 (s, 2H, CH2-Ph), 3.80 (s, 3H, MeO), 3.29 (s, 1H, ≡CH); 13C NMR (CDCl3, 100.6 MHz): δ 159.3, 138.8, 136.7, 130.4 (2C), 128.6 (2C), 127.2, 126.3 (2C), 125.3, 116.1, 115.5, 114.0 (2C), 108.8, 81.8, 76.6, 55.4, 48.9; IR (KBr) 3287, 3087, 3063, 3031, 2955, 2934, 2836, 2100, 1611, 1575, 1547, 1510, 1463, 1442, 1392, 1358, 1321, 1288, 1249, 1178, 1110, 1087, 1031, 977, 909, 836, 767, 731, 695, 575, 524, 459 cm−1; Anal. Calcd for C20H17NO: C, 83.59; H, 5.96; N, 4.87; O, 5.57%. Found: C, 83.31; H, 6.02; N, 5.02%.
- 2-Ethynyl-5-(2-fluorophenyl)-1-vinyl-1H-pyrrole (4h). Yield: 192 mg (91%), colorless oil; 1H NMR (400.13 MHz, CDCl3): δ 7.40–7.30 (m, 2H, Hm, Ph), 7.22–7.08 (m, 2H, Ho,p, Ph), 6.84 (dd, J = 15.9, 8.9 Hz, 1H, Hx), 6.66 (d, J = 3.7 Hz, 1H, H-3 pyrrole), 6.24 (d, J = 3.7 Hz, 1H, H-4, pyrrole), 5.34 (d, J = 15.9 Hz, 1H, Ha), 4.91 (d, J = 8.9 Hz, 1H, Hb), 3.45 (s, 1H, ≡CH); 13C NMR (100.6 MHz, CDCl3): δ 159.9 (d, J = 249.1 Hz, C-2, 2-FC6H4), 132.1 (d, J = 2.0 Hz, C-6, 2-FC6H4), 130.9, 130.1 (d, J = 8.2 Hz, C-4, 2-FC6H4), 129.2, 124.24 (d, J = 3.3 Hz, C-5, 2-FC6H4), 120.6 (d, J = 15.5 Hz, C-1, 2-FC6H4), 118.1, 116.1 (d, J = 22.0 Hz, C-3, 2-FC6H4), 115.2, 111.8, 106.4, 82.7, 76.4; IR (KBr) 3293, 3115, 3068, 2924, 2104, 1645, 1580, 1547, 1498, 1465, 1397, 1300, 1229, 1109, 963, 890, 817, 780, 759, 672, 577, 471 cm−1; Anal. Calcd for C14H10FN: C, 79.60; H, 4.77; F, 8.99; N, 6.63%. Found: C, 79.24; H, 4.96; F, 8.75; N, 6.39%.
- 5-Ethynyl-2,3-diphenyl-1-vinyl-1H-pyrrole (4i). Yield: 242 mg (90%), white crystals; mp 93–94 °C; 1H NMR (400.13 MHz, CDCl3): δ 7.39–7.34 (m, 3H, Ho,p, Ph), 7.31–7.26 (m, 2H, Ho, Ph), 7.21–7.15 (m, 2H, Hm, Ph), 7.15–7.09 (m, 3H, Hm,p, Ph), 6.84 (s, 1H, H-3 pyrrole), 6.71 (dd, J = 15.9, 9.2 Hz, 1H, Hx), 5.47 (d, J = 15.9 Hz, 1H, Ha), 4.91 (d, J = 9.2 Hz, 1H, Hb), 3.46 (s, 1H, ≡CH); 13C NMR (100.6 MHz, CDCl3): δ 135.1, 131.9, 131.8, 131.4 (2C), 130.8, 128.7 (2C), 128.3 (2C), 128.2 (3C), 126.1, 123.8, 118.6, 113.7, 106.5, 82.8, 76.5; IR (KBr) 3274, 3080, 3057, 2923, 2100, 1641, 1601, 1557, 1495, 1446, 1386, 1320, 1305, 1177, 1031, 964, 889, 800, 769, 699, 587, 522 cm−1; Anal. Calcd for C20H15N: C, 89.19; H, 5.61; N, 5.20%. Found: C, 88.89; H, 5.45; N, 5.34%.
- 2-Ethynyl-1-methyl-5-(thiophen-2-yl)-1H-pyrrole (4j). Yield: 174 mg (93%), colorless oil; 1H NMR (400.13 MHz, CDCl3): δ 7.32–7.28 (m, 1H, H-5, thiophene), 7.10–7.05 (m, 2H, H-3,4, thiophene), 6.51 (d, J = 3.9 Hz, 1H, H-3 pyrrole), 6.26 (d, J = 3.9 Hz, 1H, H-4, pyrrole), 3.76 (s, 3H, N-CH3), 3.43 (s, 1H, ≡CH); 13C NMR (100.6 MHz, CDCl3): δ 134.4, 129.2, 127.5, 125.8, 125.3, 116.6, 115.6, 109.7, 99.7, 82.2, 33.2; IR (KBr) 3288, 3106, 3074, 2944, 2922, 2101, 1445, 1417, 1395, 1345, 1314, 1201, 1034, 845, 766, 698, 570, 493 cm−1; Anal. Calcd for C11H9NS: C, 70.55; H, 4.84; N, 7.48; S, 17.12%. Found: C, 70.26; H, 4.69; N, 7.28; S, 16.82%.
- 1-Benzyl-2-ethynyl-1H-pyrrole (4k). Yield: 145 mg (80%), colorless oil; 1H NMR (400.13 MHz, CDCl3): δ 7.36–7.27 (m, 3H, Hm,p, Ph), 7.16–7.14 (m, 2H, Ho, Ph), 6.68–6.65 (m, 1H, H-3, pyrrole), 6.54–6.51 (m, 1H, H-5, pyrrole), 6.13–6.10 (m, 1H, H-4, pyrrole), 5.19 (s, 2H, CH2-Ph), 3.33 (s, 1H, ≡CH); 13C NMR (CDCl3, 100.6 MHz): δ 137.9, 128.8 (2C), 127.7, 127.3 (2C), 123.1, 116.0, 114.7, 108.7, 81.7, 76.0, 51.3; IR (KBr) 3288, 3106, 3064, 3031, 2925, 2853, 2103, 1495, 1466, 1455, 1435, 1300, 1018, 722, 694, 569, 522 cm−1; Anal. Calcd for C13H11N: C, 86.15; H, 6.12; N, 7.73%. Found: C, 85.84; H, 5.89; N, 7.45%.
- 3-Ethynyl-1-methyl-1H-indole (6). Yield: 113 mg (73%); Spectral characteristics are the same as previously published [64].
- 2-Ethynyl-3,6-dimethyl-4,5,6,7-tetrahydrobenzofuran (8). Yield: 139 mg (80%), colorless oil; 1H NMR (400.13 MHz, CDCl3): δ 3.55 (s, 1H, ≡CH), 2.67–2.62 (m, 1H, CH), 2.33–2.30 (m, 2H, CH2), 2.19–2.12 (m, 1H, CH), 2.00 (s, 3H, Me), 1.93–1.91 (m, 1H, CH), 1.85–1.81 (m, 1H, CH), 1.36–1.30 (m, 1H, CH), 1.07 (d, J = 6.7 Hz, 3H, CHMe); 13C NMR (100.6 MHz, CDCl3): δ 152.1, 131.5, 127.2, 118.4, 83.8, 74.7, 31.7, 31.2, 29.6, 21.5, 20.0, 9.0; IR (KBr) 3293, 2923, 2849, 2103, 1628, 1558, 1456, 1379, 1295, 1257, 1150, 1107, 1066, 1041, 774, 692 cm−1; Anal. Calcd for C12H14O: C, 82.72; H, 8.10; O, 9.18%. Found: C, 82.94; H, 7.88%.
3.3. Synthesis of Propargyl Alcohols 3a,c,d,f
- 5-(1-Benzyl-4,5,6,7-tetrahydro-1H-indol-2-yl)-3-hydroxy-3-(thiophen-2-yl)pent-4-ynenitrile (3a). Spectral characteristics are the same as previously published [36].
- 3-Hydroxy-3-phenyl-5-(1-vinyl-4,5,6,7-tetrahydro-1H-indol-2-yl)pent-4-ynenitrile (3c). Yield: 224 mg (71%), yellow oil; 1H NMR (400.13 MHz, CDCl3): δ 7.72–7.71 (m, 2H, Ho, Ph), 7.44–7.37 (m, 3H, Hm,p, Ph), 6.98 (dd, J = 15.9, 9.3 Hz, 1H, Hx), 6.40 (s, 1H, H-3, pyrrole), 5.34 (d, J = 15.9 Hz, 1H, Ha), 4.88 (d, J = 9.3 Hz, 1H, Hb), 3.03 (d, J = 4.8 Hz, 2H, CH2CN), 2.85 (s, 1H, OH), 2.67–2.65 (m, 2H, CH2-7), 2.49–2.47 (m, 2H, CH2-4), 1.83–1.81 (m, 2H, CH2-5), 1.74–1.73 (m, 2H, CH2-6); 13C NMR (CDCl3, 100.6 MHz): δ 141.7, 131.5, 130.4, 129.0, 128.8 (2C), 125.4 (2C), 119.9, 117.3, 116.4, 111.3, 103.2, 92.9, 81.4, 71.0, 35.7, 24.1, 23.3, 23.1, 23.0. IR (film) 3422, 3062, 3030, 2931, 2851, 2215, 1643, 1492, 1447, 1383, 1295, 1241, 1143, 1102, 1053, 968, 910, 805, 765, 733, 700, 646 cm−1; Anal. Calcd for C21H20N2O: C, 79.72; H, 6.37; N, 8.85; O, 5.06%. Found: C, 79.44; H, 6.20; N, 8.59%.
- 5-(4,5-Dimethyl-1-vinyl-1H-pyrrol-2-yl)-3-hydroxy-3-phenylpent-4-ynenitrile (3d). Yield: 197 mg (68%), yellow crystals, mp 101–102 °C; 1H NMR (400.13 MHz, CDCl3): δ 7.72–7.70 (m, 2H, Ho, Ph), 7.42–7.40 (m, 2H, Hm,p, Ph), 6.91 (dd, J = 15.9, 9.1 Hz, 1H, Hx), 6.41 (s, 1H, H-3, pyrrole), 5.45 (d, J = 15.9 Hz, 1H, Ha), 4.99 (d, J = 9.1 Hz, 1H, Hb), 3.02 (d, J = 5.1 Hz, 2H, CH2CN), 2.86 (s, 1H, OH), 2.22 (s, 3H, Me), 2.00 (s, 3H, Me); 13C NMR (100.6 MHz, CDCl3): δ 141.7, 130.6, 128.9, 128.7 (2C), 128.6, 125.4 (2C), 119.5, 117.0, 116.4, 110.6, 105.6, 92.6, 81.4, 70.9, 35.6, 11.3, 11.1; IR (KBr) 3422, 3062, 3030, 2921, 2215, 1643, 1493, 1449, 1392, 1357, 1304, 1172, 1100, 1049, 967, 910, 809, 765, 733, 700, 634 cm−1; Anal. Calcd for C19H18N2O: C, 78.59; H, 6.25; N, 9.65; O, 5.51%. Found: C, 78.22; H, 6.02; N, 9.42%.
- 3-Hydroxy-3-phenyl-5-(5-(4-methylphenyl)-1-vinyl-1H-pyrrol-2-yl)pent-4-ynenitrile (3f). Yield: 281 mg (80%), yellow oil; 1H NMR (CDCl3, 400 MHz): δ 7.74–7.72 (m, 2H, Ho, Ph), 7.45–7.39 (m, 2H, Hm,p, Ph), 7.31 (d, J = 7.9 Hz, 2H, Ho, C6H4), 7.21 (d, J = 7.9 Hz, 2H, Hm, C6H4), 6.83 (dd, J = 15.8, 8.9 Hz, 1H, Hx), 6.67 (d, J = 3.8 Hz, 1H, H-4, pyrrole), 6.22 (d, J = 3.8 Hz, 1H, H-3, pyrrole), 5.52 (d, J = 15.8 Hz, 1H, Ha), 5.05 (d, J = 8.9 Hz, 1H, Hb), 3.06 (d, J = 5.0 Hz, 2H, CH2CN), 2.85 (s, 1H, OH), 2.39 (s, 3H, Me); 13C NMR (CDCl3, 100.6 MHz): δ 141.6, 137.8, 136.8, 131.2, 129.4, 129.3 (2C), 129.1 (3C), 128.8 (2C), 125.4 (2C), 118.9, 116.3, 113.7, 110.1, 108.0, 93.1, 81.4, 71.0, 35.6, 21.4; IR (KBr) 3416, 3061, 3028, 2922, 2218, 1643, 1515, 1472, 1449, 1418, 1389, 1324, 1301, 1224, 1112, 1042, 964, 909, 823, 773, 733,701, 622, 503 cm−1, Anal. Calcd for C24H20N2O: C, 81.79; H, 5.72; N, 7.95; O, 4.54%. Found: C, 81.35; H, 5.60; N, 7.68%.
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Sample Availability
References
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Tomilin, D.N.; Sobenina, L.N.; Belogolova, A.M.; Trofimov, A.B.; Ushakov, I.A.; Trofimov, B.A. Unexpected Decarbonylation of Acylethynylpyrroles under the Action of Cyanomethyl Carbanion: A Robust Access to Ethynylpyrroles. Molecules 2023, 28, 1389. https://doi.org/10.3390/molecules28031389
Tomilin DN, Sobenina LN, Belogolova AM, Trofimov AB, Ushakov IA, Trofimov BA. Unexpected Decarbonylation of Acylethynylpyrroles under the Action of Cyanomethyl Carbanion: A Robust Access to Ethynylpyrroles. Molecules. 2023; 28(3):1389. https://doi.org/10.3390/molecules28031389
Chicago/Turabian StyleTomilin, Denis N., Lyubov N. Sobenina, Alexandra M. Belogolova, Alexander B. Trofimov, Igor A. Ushakov, and Boris A. Trofimov. 2023. "Unexpected Decarbonylation of Acylethynylpyrroles under the Action of Cyanomethyl Carbanion: A Robust Access to Ethynylpyrroles" Molecules 28, no. 3: 1389. https://doi.org/10.3390/molecules28031389