4.3. Synthesis1-Methyl-3-diethylaminomethylindole was prepared as per the literature in 80% yield and verified via 1H NMR [25].
1H NMR (300 MHz, CDCl3) δ 7.71 (d, J=7.9, 1H), 7.28 (d, J=8.1, 1H), 7.24–7.16 (m, 1H), 7.13–7.06 (m, 1H), 6.98 (s, 1H), 3.78 (s, 2H), 3.76 (s, 3H), 2.56 (q, J=7.1, 5H), 1.09 (t, J=7.1, 7H).
3-((Diethylamino)methyl)-1-methyl-1H-indole-2-carbaldehyde (3a)A solution of n-BuLi (5.0 mL, 12.5 mmol, and 2.5 M) was added to a Schlenk flask containing 1-methyl-3-diethylaminomethylindole (2a) (2.70 g, 12.5 mmol) dissolved in 30 mL THF at −78°C. The solution was warmed to 30°C and stirred at this temperature for 1 h, followed by an additional hour at room temperature. Then DMF (1.9 mL; 25 mmol) was added at −30°C and the reaction was allowed to come to room temperature over 24 h. The reaction was quenched by addition of 30 mL saturated ammonium chloride solution. This was extracted with DCM (2 × 50 mL). The organic layers were combined and washed with H2O (2 × 50 mL) and brine (2 × 50 mL). The DCM was dried over sodium sulfate, filtered and the solvent removed at reduced pressure to give a brown oil which was purified by column chromatography (silica) with DCM/pentane as the eluent to yield a brown oil in 85% yield (2.60 g; 10.6 mmol).
1H NMR (400 MHz, CDCl3) δ 10.38 (s, 1H, CHO), 7.88 (d, J=8.3 Hz, 1H), 7.40 (t, J=7.2 Hz, 1H), 7.34 (d, J=8.3 Hz, 1H), 7.15 (t, J=7.4 Hz, 1H), 4.07 (s, 3H, NCH3), 3.99 (s, 2H, CH2), 2.55 (q, J=6.9 Hz, 4H, NCH2CH3), 1.06 (t, J=6.9 Hz, 6H, NCH2CH3).
13C NMR (101 MHz, CDCl3) δ 183.62 (CHO), 139.71, 132.48, 127.93, 127.11, 122.25, 120.51, 118.18, 110.34, 47.09 (CH2), 47.00 (NCH2CH3), 31.98 (CH3), 12.03 (NCH2CH3).
ES-MS: m/z 172 [M–NCH2CH3]+.
IR (KBr disk, cm−1): 3052, 2966, 2933, 2871, 2807, 1684, 1812, 1525, 1469, 1380, 1201, 1166, 1118, 1060, 883, 742.
N-((2-(Cyclopenta-2, 4-dienylidenemethyl)-1-methyl-1H-indol-3-yl)methyl)-N-ethylethanamine (4a)3-((Diethylamino)methyl)-1-methyl-1H-indole-2-carbaldehyde (3a) (2.5 g, 10 mmol) was dissolved in MeOH (70 mL). Freshly cracked cyclopentadiene (0.85 mL; 10 mmol) was added to the solution followed by pyrrolidine (0.84 mL; 10 mmol), and the colour gradually changed from yellow to red. After 20 h, acetic acid (1 mL) was added to the reaction, and the product was extracted with DCM (2 × 50 mL). The organic layers were combined and washed with H2O (2 × 50 mL) and brine (2 × 50 mL). The DCM was dried over sodium sulphate, and the solvent removed at reduced pressure to give a red oil, which was purified by column chromatography (silica) with DCM as the eluent to yield a red oil in 83% yield. (2.51 g; 8.56 mmol).
1H NMR (400 MHz, CDCl3) δ 7.89 (t, J=7.3, 1H), 7.34–7.25 (m, 3H), 7.12 (t, J=7.3, 1H), 6.60 (d, J=5.2, 1H), 6.53 (d, J=5.2, 1H), 6.37 (d, J=5.2, 1H), 6.27 (d, J=5.3, 1H), 3.72 (s, 1H), 3.70 (s, 3H), 2.46 (q, J=7.1, 4H), 1.03–0.94 (m, 6H).
13C NMR (101 MHz, CDCl3) δ 139.50, 134.50, 132.26, 131.63, 128.44, 127.78, 126.89, 126.07, 125.65, 123.15, 122.04, 120.95, 120.29, 110.12, 48.12, 46.80, 31.77, 11.84.
λmax [nm], (ε) [L mol−1 cm−1], CHCl3: 262 (13200), 388 (9500).
ES-MS: m/z 220 [M–NCH2CH3]+.
IR (KBr disk, cm−1): 2940, 2856, 2808, 2756, 1634, 1611, 1545, 1456, 1419, 1340, 1315, 1255, 1202, 1044, 1075, 1009, 889, 771, 761.
Dihydrochloride Derivative of bis-[((1-methyl-3-diethylaminomethyl)indol-2-yl)methylcyclopentadienyl] titanium (IV) dichloride (5a)Super Hydride (LiBEt3H) (8.6 mL, 8.6 mmol, and 1 M) in THF was concentrated by removal of the solvent by heating it to 60°C under reduced pressure of 10−2 mbar for 40 min and then to 90°C for 20 min in a Schlenk flask. N-((2-(cyclopenta-2,4-dienylidenemethyl)-1-methyl-1H-indol-3-yl)methyl)-N-ethylethanamine (4a) (2.5 g; 8.6 mmol) was added to a Schlenk flask and dissolved in dry diethyl ether (100 mL) to give a red solution. The red fulvene solution was transferred to the Super Hydride solution via cannula. The solution was left to stir for 16 h, in which time a yellow precipitate of the lithium cyclopentadienide intermediate formed, and the solution had changed its colour from red to white. The precipitate was filtered on to a frit. The white precipitate was dried briefly under reduced pressure and was transferred to a Schlenk flask under nitrogen. The lithium cyclopentadienide intermediate was dissolved in dry THF (50 mL) to give a pale yellow solution. Titanium tetrachloride (1.0 mL; 1.0 mmol) was added to the lithium cyclopentadienide intermediate solution to give a dark red solution. The dark red titanium solution was stirred for 16 h. The solvent was then removed under reduced pressure. The remaining residue was extracted with DCM (100 mL) and filtered through celite to remove the remaining LiCl. The solvent was removed under reduced pressure to yield an orange solid in 30% yield (1.00 g; 1.42 mmol). A portion of this solid (0.10 g; 0.14 mmol) was then dissolved in DCM (10 mL), an ethereal solution of hydrogen chloride (0.14 mL; 2 M) was added and a precipitate immediately formed. Diethyl ether (30 mL) was then added. After 15 min stirring, the solid was filtered to give a brown powder in 90% yield (0.10 g; 0.13 mmol).
1H NMR (400 MHz, DMSO) δ 10.30 (s, 2H, NHCH2CH3), 7.77 (d, J=7.8 Hz, 2H), 7.43 (d, J=7.8 Hz, 2H), 7.17 (t, J=7.4 Hz, 2H), 7.11 (t, J=7.4 Hz, 2H), 6.77 (s, 4H, C5H4), 6.45 (s, 4H, C5H4), 4.47 (s, 4H,), 4.46 (s, 4H), 3.63 (s, 6H, NCH3), 3.09 (s, 8H, NCH2CH3), 1.29 (t, J=6.9, 12H, NCH2CH3).
13C NMR (101 MHz, DMSO) δ 141.03, 136.98, 132.98, 127.90, 125.20 (C5H4), 122.09, 120.45, 119.03, 116.46 (C5H4), 110.37, 101.19, 46.90, 46.21 (NCH2CH3), 30.76 (NCH3), 26.47, 9.18 (NCH2CH3).
IR (KBr disk, cm−1): 3401, 2979, 2763, 1828, 1631, 1471, 1403, 1361, 1033, 894, 804, 746.
UV-Vis (CH2Cl2): λ 219 nm (ε 76,240), λ 282 nm (ε 23,666), λ 292 nm (ε 22,800), λ 400 nm (weak).
Microanalysis calculated for C42H58Cl4N4Ti (778.23 g/mol): Calcd. C, 62.38%; H, 7.23%; N, 6.93%; Found C, 62.56%; H, 7.98%; N, 6.41%.
5-Methoxy-1-methyl-1H-indole-2-carbaldehyde was prepared as per published procedure in 62% yield and verified by 1H NMR [26].
1H NMR (300 MHz, CDCl3) δ 9.84 (s, 1H), 7.27 (dd, J=9.7, 6.7 Hz, 1H), 7.14 (s, 1H), 7.12–7.07 (m, 2H), 4.06 (s, 3H), 3.85 (s, 3H).
3-((Diethylamino)methyl)-5-methoxy-1-methyl-1H-indole-2-carbaldehyde (3b)5-Methoxy-1-methyl-1H-indole-2-carbaldehyde (2b) (2.00 g, 10.5 mmol) was dissolved in acetic acid (40 mL), diethylamine (2.2 mL; 21 mmol) was added, and the solution was cooled to 30°C. Formaldehyde (2.3 mL, 21 mmol, and 30% in H2O) was added, and the solution was allowed to stand for 2 h. The mixture was then added to an ice/NaOH (100 mL; 9 M) solution and stirred vigorously for 10 min until a yellow precipitate formed. This was filtered, washed with water, and suction-dried to give a yellow solid in 72% yield (2.1 g; 7.7 mmol).
1H NMR (400 MHz, CDCl3) δ 10.31 (s, 1H, CHO), 7.24 (m, 2H), 7.09 (dd, J=9.1, 2.5, 1H), 4.05 (s, 3H, OCH3), 3.95 (s, 2H, CH2), 3.87 (s, 3H, NCH3), 2.55 (q, J=7.1, 4H, NCH2CH3), 1.06 (t, J=7.1, 6H NCH2CH3).
13C NMR (101 MHz, CDCl3) δ 183.05, 154.31, 135.25, 132.54, 127.00, 126.75, 118.85, 111.11, 101.68, 55.66 (CH2), 47.03, 46.75 (NCH2CH3), 31.87(NCH3), 11.91(NCH2CH3).
ES-MS: m/z 202 [M–NCH2CH3]+.
IR (KBr disk, cm−1): 2964, 2831, 1660, 1523, 1490, 1461, 1384, 1238, 1168, 1043, 883, 802, 754.
N-((2-(Cyclopenta-2,4-dienylidenemethyl)-5-methoxy-1-methyl-1H-indol-3-yl)methyl)-N-ethylethanamine (4b)3-((Diethylamino)methyl)-5-methoxy-1-methyl-1H-indole-2-carbaldehyde (3b) (1.5 g; 5.5 mmol) was dissolved in MeOH (70 mL). Freshly cracked cyclopentadiene (0.46 mL; 5.5 mmol) was added to the solution followed by pyrrolidine (0.45 mL; 5.5 mmol), and the colour gradually changed from yellow to red. After 16 h, acetic acid (1 mL) was added the reaction, and the product was extracted with DCM (2 × 50 mL). The organic layers were combined and washed with H2O (2 × 50 mL) and brine (2 × 50 mL). The DCM was dried over sodium sulphate, and the solvent removed at reduced pressure to give a red oil which was purified by column chromatography (silica) with DCM as the eluent to yield a red oil in 60% yield. (1.05 g; 3.26 mmol).
1H NMR (400 MHz, CDCl3) δ 7.39 (d, J=2.4, 1H), 7.30 (s, 1H), 7.27–7.26 (m, J=5.5, 1H), 6.95 (d, J=2.5, 1H), 6.61 (s, 1H), 6.51 (s, 1H), 6.37 (d, J=5.0, 1H), 6.27 (d, J=5.2, 1H), 4.05 (s, 2H), 3.95 (s, 1H), 3.87 (s, 3H), 2.47 (q, J=7.1, 7H), 1.01 (t, J=7.1, 9H).
13C NMR (101 MHz, CDCl3) δ 146.77, 134.42, 131.47, 130.91, 128.74, 126.10, 125.68, 122.25, 118.85, 114.79, 113.75, 111.11, 110.17, 102.37, 55.82, 48.34, 46.61, 32.01, 11.91.
ES-MS: m/z 250 [M–NCH2CH3]+.
λmax [nm], (ε) [L mol−1 cm−1], CHCl3: 270 (14100), 390 (9800).
IR (KBr disk, cm−1): 2933, 2852, 2809, 2762, 1624, 1600, 1553, 1449, 1419, 1340, 1315, 1255, 1202, 1075, 1044, 1075, 1009, 889, 771, 761.
Dihydrochloride Derivative of bis-[((5-methoxy-1-methyl,3-diethylaminomethyl)indol-2-yl)methylcyclopentadienyl] Titanium (IV) Dichloride (5b)Super Hydride (LiBEt3H) (5.0 mL, 5.0 mmol, and 1 M) in THF was concentrated by removal of the solvent by heating it to 60°C under reduced pressure of 10−2 mbar for 40 min and then to 90°C for 20 min in a Schlenk flask. N-((2-(cyclopenta-2,4-dienylidenemethyl)-5-methoxy-1-methyl-1H-indol-3-yl)methyl)-N-ethylethanamine (4b) (1.60 g; 5.00 mmol) was added to a Schlenk flask and dissolved in dry diethyl ether (100 mL) to give a red solution. The red fulvene solution was transferred to the Super Hydride solution via cannula. The solution was left to stir for 16 h, in which time a yellow precipitate of the lithium cyclopentadienide intermediate formed, and the solution had changed its colour from red to white. The precipitate was filtered on to a frit. The white precipitate was dried briefly under reduced pressure and was transferred to a Schlenk flask under nitrogen. The lithium cyclopentadienide intermediate was dissolved in dry THF (50 mL) to give a pale yellow solution. Titanium tetrachloride (0.85 mL; 0.85 mmol) was added to the lithium cyclopentadienide intermediate solution to give a dark red solution. The dark red titanium solution was stirred for 8 h. The solvent was then removed under reduced pressure. The remaining residue was extracted with DCM (100 mL) and filtered through celite to remove the remaining LiCl. The solvent was removed under reduced pressure to yield a brown solid in 79% yield (1.51 g; 1.97 mmol). A portion of this solid (0.10 g; 0.13 mmol) was then dissolved in DCM (10 mL), and an ethereal solution of hydrogen chloride (0.14 mL; 2 M) was added, and a precipitate immediately formed. Diethyl ether (30 mL) was then added. After 15 min stirring, the solid was filtered to give a brown powder in 90% yield (0.10 g; 0.13 mmol).
1H NMR (300 MHz, DMSO) δ 10.13 (s, 2H, NH), 7.41 (m, 4H), 6.89 (s, 2H), 6.43 (s, 4H, C5H4), 6.35 (s, 4H, C5H4), 4.44 (s, 4H), 4.16 (s, 4H), 3.88 (s, 6H, OCH3), 3.68 (s, 6H, NCH3), 3.16 (s, 8H, NCH2CH3), 1.32 (d, J=7.0, 12H, NCH2CH3).
13C NMR (75 MHz, DMSO) δ 154.49, 148.64, 146.08, 141.85, 132.50 (C5H4), 132.04 (C5H4), 128.02, 111.45, 110.86, 101.48, 100.24, 56.04, 45.89, 43.49, 30.47 (NCH3), 26.57 (C5H4CH2), 9.05 (NCH2CH3).
IR (KBr disk, cm−1): 3491, 2981, 2362, 1828, 1621, 1486, 1234, 1162, 1037, 890, 835, 687.
UV-Vis (CH2Cl2): λ 223 nm (ε 83,450), λ 295 nm (ε 28,400), λ 400 nm (weak).
Microanalysis calculated for C44H62Cl4N4O2Ti (838.59 g/mol): C, 60.84%; H, 7.19%; N, 6.45%; found C, 60.12%; H, 7.42%; N, 6.34%.
N-((4-Bromo-1-methyl-1H-indol-3-yl)methyl)-N-ethylethanamine (2c)4-Bromo-1-methyl-1H-indole (1.52 g, 7.15 mmol) was dissolved in acetic acid (40 mL), dimethylamine (1.5 mL; 14.3 mmol) was added, and the solution was cooled to 30°C. Formaldehyde (1.8 mL, 14.3 mmol, and 30% in H2O) was added, and the solution was allowed to stand for 2 h. The mixture was then added to an ice/NaOH (100 mL; 9 M) solution and stirred vigorously for 10 min until a yellow precipitate formed. This was filtered, washed with water, and suction-dried to give a yellow solid in 81% yield (1.71 g; 5.78 mmol).
1H NMR (400 MHz, CDCl3) δ 7.24 (d, J=7.8, 1H), 7.21 (d, J=7.8, 1H), 7.12 (s, 1H, H-2), 7.00 (t, J=7.8, 1H, H-6), 4.08 (s, 2H, CH2), 3.73 (s, 3H, NCH3), 2.67 (q, J=6.7, 4H, NCH2CH3), 1.08 (t, J=7.1, 6H, NCH2CH3).
13C NMR (101 MHz, CDCl3) δ 138.36, 129.57 (C-2), 128.29, 126.04, 123.45, 121.95 (C-6), 114.27, 108.42, 49.15 (CH2), 46.70 (NCH2CH3), 32.91 (NCH3), 11.76 (NCH2CH3).
ES-MS: m/z 222 [M–NCH2CH3]+.
IR (KBr disk, cm−1): 2966, 2929, 2869, 2807, 2360, 1658, 1550, 1454, 1415, 1313, 1195, 1066, 838, 765.
3-((Diethylamino)methyl)-1-methyl-1H-indole-4-carbaldehyde (3c)A solution of n-BuLi (2.3 mL, 5.8 mmol, and 2.5 M) was added to a Schlenk flask containing N-((4-bromo-1-methyl-1H-indol-3-yl)methyl)-N-ethylethanamine (2c) (1.7 g; 5.8 mmol) dissolved in 30 mL THF at −78°C. The solution was warmed to 30°C and stirred at this temperature for 1 h, followed by an additional hour at room temperature. Then DMF (0.9 mL; 12 mmol) was added at −30°C, and the reaction was allowed to come to room temperature over 24 h. The reaction was quenched by addition of 30 mL saturated ammonium chloride solution. This was extracted with DCM (2 × 50 mL). The organic layers were combined and washed with H2O (2 × 50 mL) and brine (2 × 50 mL). The DCM was dried over sodium sulfate, filtered, and the solvent removed at reduced pressure to give a brown oil. This was purified by acidic extraction to give a brown oil in 85% yield (1.41 g; 5.77 mmol).
1H NMR (400 MHz, CDCl3) δ 10.80 (s, 1H, CHO), 7.79 (d, J=7.8, 1H), 7.52 (d, J=7.8, 1H), 7.30 (t, J=7.9, 1H, H-6), 7.15 (s, 1H, H-2), 3.82 (s, 2H, CH2), 3.81 (d, 3H, NCH3), 2.56 (q, J=6.9, 4H, NCH2CH3), 1.00 (t, J=6.6, 6H, NCH2CH3).
13C NMR (101 MHz, CDCl3) δ 194.95 (CHO), 138.93, 131.67 (C-2), 130.27, 127.40, 121.03 (C-6), 120.19, 114.77, 113.25, 51.31(CH2), 45.85 (NCH2CH3), 32.86 (NCH3), 11.08 (NCH2CH3).
ES-MS: m/z 172 [M–NCH2CH3]+.
IR (KBr disk, cm−1): 2967, 2933, 2804, 1671, 1608, 1550, 1456, 1402, 1317, 1199, 1054, 929, 765.
N-((4-(Cyclopenta-2,4-dienylidenemethyl)-1-methyl-1H-indol-3-yl)methyl)-N-ethylethanamine (4c)3-((Diethylamino)methyl)-1-methyl-1H-indole-4-carbaldehyde (3c) (0.80 g; 3.3 mmol) was dissolved in MeOH (70 mL). Freshly cracked cyclopentadiene (0.27 mL; 3.3 mmol) was added to the solution followed by pyrrolidine (0.27 mL; 3.3 mmol), and the colour gradually changed from yellow to red. After 2 h, acetic acid (1 mL) was added the reaction, and the product was extracted with DCM (2 × 50 mL). The organic layers were combined and washed with H2O (2 × 50 mL) and brine (2 × 50 mL). The DCM was dried over sodium sulphate, and the solvent removed at reduced pressure to give a red oil in 82% yield, which could be used without further purification. (0.80 g; 2.72 mmol).
1H NMR (400 MHz, CDCl3) δ 8.61 (s, 1H), 7.30 (dt, J=20.6, 6.6, 3H), 6.99 (s, 1H), 6.69 (d, J=5.2, 1H), 6.66–6.60 (m, 1H), 6.55 (d, J=5.1, 1H), 6.44 (d, J=5.1, 1H), 3.77 (s, 3H), 3.66 (s, 2H), 2.70–2.56 (m, 4H), 1.05 (t, J=7.1, 6H).
13C NMR (101 MHz, CDCl3) δ 144.77, 140.42, 136.47, 133.11, 129.74, 129.10, 128.78 126.58, 125.27, 122.84, 120.89, 120.56, 112.65, 109.31, 55.81 (CH2), 46.62 (NCH2CH3), 32.21 (NCH3), 11.93 (NCH2CH3).
ES-MS: m/z 220 [M–NCH2CH3]+.
λmax [nm], (ε) [L mol−1 cm−1], CHCl3: 280 (14500), 370 (8900).
IR (KBr disk, cm−1): 2933, 2852, 2809, 2762, 1624, 1600, 1553, 1449, 1419, 1340, 1315, 1255, 1202, 1075, 1044, 1075, 1009, 889, 771, 761.
Dihydrochloride Derivative of bis-[((1-Methyl,3-diethylaminomethyl)indol-4-yl)methylcyclopentadienyl] Titanium (IV) Dichloride (5c)Super Hydride (LiBEt3H) (3.6 mL, 3.6 mmol, and 1 M) in THF was concentrated by removal of the solvent by heating it to 60°C under reduced pressure of 10−2 mbar for 40 min and then to 90°C for 20 min in a Schlenk flask. N-((4-(cyclopenta-2,4-dienylidenemethyl)-1-methyl-1H-indol-3-yl)methyl)-N-ethylethanamine (4c) (1.06 g; 3.60 mmol) was added to a Schlenk flask and dissolved in dry diethyl ether (100 mL) to give a red solution. The red fulvene solution was transferred to the Super Hydride solution via cannula. The solution was left to stir for 16 h, in which time a yellow precipitate of the lithium cyclopentadienide intermediate formed, and the solution had changed its colour from red to white. The precipitate was filtered on to a frit. The white precipitate was dried briefly under reduced pressure and was transferred to a Schlenk flask under nitrogen. The lithium cyclopentadienide intermediate was dissolved in dry THF (50 mL) to give a pale yellow solution. Titanium tetrachloride (0.45 mL; 0.45 mmol) was added to the lithium cyclopentadienide intermediate solution to give a dark red solution. The dark red titanium solution was stirred for 8 h. The solvent was then removed under reduced pressure. The remaining residue was extracted with DCM (100 mL) and filtered through celite to remove the remaining LiCl. The solvent was removed under reduced pressure to yield a brown solid in 85% yield (1.08 g; 1.52 mmol). A portion of this solid (0.10 g; 0.14 mmol) was then dissolved in DCM (10 mL), and an ethereal solution of hydrogen chloride (0.14 mL; 2 M) was added, and a precipitate immediately formed. Diethyl ether (30 mL) was then added. After 15 min stirring, the solid was filtered to give a brown powder in 85% yield (0.090 g; 0.11 mmol).
1H NMR (400 MHz, D2O) δ 7.34 (s, 2H, H-2), 7.27 (d, J=8.0, 2H), 6.98 (t, J=7.8, 2H, H-6), 6.47 (d, J=8.0, 2H), 6.01 (s, 4H, C5H4), 5.92 (s, 4H, C5H4), 4.00 (s, 4H), 3.95 (s, 4H, CH2), 3.66 (s, 6H, NCH3), 3.09–2.90 (m, J=7.0, 8H, NCH2CH3), 1.11–0.99 (m, 12H, NCH2CH3).
13C NMR (101 MHz, D2O) δ 137.71, 137.54, 133.57 (C-2), 129.53, 124.73, 122.48 (C-6), 122.19, 118.24 (C5H4), 115.81 (C5H4), 109.68, 101.46, 49.24 (CH2), 46.10 (NCH2CH3), 33.27 (C5H4CH2), 32.57 (NCH3), 8.01 (NCH2CH3).
IR (KBr disk, cm−1): 3401, 2975, 2942, 2682, 2653, 2360, 1625, 1542, 1452, 1421, 1265, 1211, 985, 838, 752.
UV-Vis (CH2Cl2): λ 225 nm (ε 78,400), λ 290 nm (ε 27,500), λ 300 nm (ε 21,100), λ 400 nm (weak).
Micro analysis calculated for C42H58Cl4N4Ti (778.23 g/mol): Calcd. C, 62.38%; H, 7.23%; N, 6.93%; Found C, 61.96%; H, 7.47%; N, 6.75%.
5-Bromo-1-methyl-1H-indole-2-carbaldehyde was prepared as per literature in 90% yield and verified via 1H NMR [27].
1H NMR (300 MHz, CDCl3) δ 9.9 (s, 1H), 8.46 (s, 1H), 7.66 (s, 1H), 7.44 (dd, J=8.5, 1H) 7.22 (d, J=7.2 1H) d 3.86 (3H, s).
5-Bromo-2-(cyclopenta-2,4-dienylidenemethyl)-1-methyl-1H-indole (4d)5-Bromo-1-methyl-1H-indole-2-carbaldehyde (3d) (2.0 g; 8.4 mmol) was dissolved in MeOH (70 mL). Freshly cracked cyclopentadiene (0.71 mL; 8.4 mmol) was added to the solution followed by pyrrolidine (0.68 mL; 8.4 mmol), and the colour gradually changed from yellow to red. After 16 h an orange solid precipitated, this was filtered to give a 60% yield. (1.31 g; 4.54 mmol).
1H NMR (400 MHz, CDCl3) δ 7.93 (s, 1H, H-4), 7.54 (s, 1H, H-2), 7.40–7.31 (m, 2H), 7.34 (s, 1H, C5H4CH), 7.20 (d, J=8.7, 1H), 6.71 (s, 1H, C5H4), 6.67–6.58 (m, 1H, C5H4), 6.46 (s, 1H,), 6.42–6.34 (m, 1H, C5H4), 3.84 (s, 3H, NCH3).
13C NMR (101 MHz, CDCl3) δ 141.07, 135.67, 133.67 (C5H4), 132.22(C-2), 129.77 (C5H4CH), 129.06, 128.85 (C5H4), 126.91 (C5H4), 125.75, 121.71 (C-4), 121.68, 119.26 (C5H4), 114.57, 112.85, 111.21, 33.51 (NCH3).
λmax [nm], (ε) [L mol−1 cm−1], CHCl3: 275 (13000), 380 (9800).
ES-MS: m/z 207 [M–Br + H]−.
IR (KBr disk, cm−1): 2923, 1612, 11527, 1454, 1390, 1338, 1292, 1240, 1078, 900.
Bis-[((5-bromo-1-methyl)indol-3-yl)methylcyclopentadienyl] Titanium (IV) Dichloride (5d)Super Hydride (LiBEt3H) (2.8 mL, 2.8 mmol, and 1 M) in THF was concentrated by removal of the solvent by heating it to 60°C under reduced pressure of 10−2 mbar for 40 min and then to 90°C for 20 min in a Schlenk flask. 5-Bromo-2-(cyclopenta-2,4-dienylidenemethyl)-1-methyl-1H-indole (4d) (0.80 g; 2.8 mmol) was added to a Schlenk flask and dissolved in dry diethyl ether (100 mL) to give a red solution. The red fulvene solution was transferred to the Super Hydride solution via cannula. The solution was left to stir for 16 h, in which time a light green precipitate of the lithium cyclopentadienide intermediate formed, and the solution had changed its colour from red to yellow. The precipitate was filtered on to a frit. The precipitate was dried briefly under reduced pressure and was transferred to a Schlenk flask under nitrogen. The lithium cyclopentadienide intermediate was dissolved in dry THF (50 mL) to give a pale green solution. Titanium tetrachloride (1.1 mL, 1.1 mmol, and 1 M) was added to the lithium cyclopentadienide intermediate solution to give a dark brown solution. The solution was stirred for 8 h. The solvent was then removed under reduced pressure. The remaining residue was extracted with DCM (100 mL) and filtered through celite to remove the remaining LiCl. The solvent was removed under reduced pressure to yield a dark green solid, which was washed with ether (50 mL) followed by pentane (50 mL) to give a green solid in 58% yield (0.56 g; 0.81 mmol).
1H NMR (400 MHz, CDCl3) δ 7.62 (s, 2H, H-4), 7.32–7.25 (m, 2H, H-6), 7.21–7.09 (m, 2H, H-7), 6.88 (s, 2H, H-2), 6.37–6.22 (m, 8H, C5H4), 4.15 (s, 4H, CH2), 3.71 (s, 6H, NCH3).
13C NMR (101 MHz, CDCl3) δ 137.72, 135.67, 129.32, 128.91 (C-2), 124.53 (C-6), 122.09 (C5H4), 121.53 (C-4), 116.02 (C5H4), 112.46, 111.95, 110.89 (C-7), 33.01 (NCH3), 26.43 (CH2).
IR (KBr disk, cm−1): 3114, 3012, 2925, 1475, 1435, 1375, 1214, 1045, 754.
UV-Vis (CH2Cl2): λ 219 nm (ε 80,100), λ 300 nm (ε 27,600), λ 410 nm (ε 4000).
Microanalysis calculated for C30H26Cl2N2Br2Ti (693.12 g/mol): Calcd. C, 51.99%; H, 3.78%; N, 3.94%; Found C, 52.48%; H, 3.89%; N, 3.84%.
5-Chloro-1-methyl-1H-indole-2-carbaldehyde was prepared as per the literature in 90% yield and verified via 1H NMR [28].
1H NMR (400 MHz, CDCl3) δ 9.93 (s, 1H), 8.28 (d, J=1.4, 1H), 7.65 (s, 1H), 7.32–7.18 (m, 2H), 3.85 (d, J=6.0, 3H).
5-Chloro-2-(cyclopenta-2,4-dienylidenemethyl)-1-methyl-1H-indole (4e)5-Chloro-1-methyl-1H-indole-2-carbaldehyde (3e) (2.60 g; 13.5 mmol) was dissolved in MeOH (70 mL). Freshly cracked cyclopentadiene (1.1 mL; 13.5 mmol) was added to the solution followed by pyrrolidine (1.1 mL; 13.5 mmol) and the colour gradually changed from yellow to red. After 16 h an orange solid precipitated, this was filtered to give a 56% yield. (1.81 g; 7.51 mmol).
1H NMR (400 MHz, CDCl3) δ 7.78 (s, 1H, H-4), 7.57 (s, 1H, H-2), 7.35 (s, 1H, C5H4CH), 7.30–7.21 (m, 2H), 6.79–6.69 (m, 1H, C5H4), 6.69–6.60 (m, 1H, C5H4), 6.50–6.43 (m, 1H, C5H4), 6.43–6.34 (m, 1H, C5H4), 3.85 (s, 3H, NCH3).
13C NMR (101 MHz, CDCl3) δ 140.92, 135.38, 133.64 (C5H4), 132.43 (C-2), 129.19 (C5H4CH), 128.81, 127.04 (C5H4), 126.90 (C5H4), 123.18 (C-4), 119.26 (C5H4), 118.61, 112.89, 110.82, 109.98, 33.57 (NCH3).
λmax [nm], (ε) [L mol−1 cm−1], CHCl3: 276 (12000), 370 (9000).
ES-MS: m/z 207 [M–Cl + H]−.
IR (KBr disk, cm−1): 3018, 2400, 1616, 1529, 1475, 1438, 1357, 1340, 1214, 1081, 902, 769.
Bis-[((5-chloro-1-methyl)indol-3-yl)methylcyclopentadienyl] Titanium (IV) Dichloride (5e)Super Hydride (LiBEt3H) (7.5 mL, 7.5 mmol, and 1 M) in THF was concentrated by removal of the solvent by heating it to 60°C under reduced pressure of 10−2 mbar for 40 min and then to 90°C for 20 min in a Schlenk flask. 5-Chloro-2-(cyclopenta-2,4-dienylidenemethyl)-1-methyl-1H-indole (4e) (1.80 g, 7.50 mmol) was added to a Schlenk flask and dissolved in dry diethyl ether (100 mL) to give a red solution. The red fulvene solution was transferred to the Super Hydride solution via cannula. The solution was left to stir for 16 h, in which time a light green precipitate of the lithium cyclopentadienide intermediate formed, and the solution had changed its colour from red to yellow. The precipitate was filtered on to a frit. The precipitate was dried briefly under reduced pressure and was transferred to a Schlenk flask under nitrogen. The lithium cyclopentadienide intermediate was dissolved in dry THF (50 mL) to give a pale green solution. Titanium tetrachloride (2.4 mL, 2.4 mmol, and 1 M) was added to the lithium cyclopentadienide intermediate solution to give a dark brown solution. The solution was stirred for 8 h. The solvent was then removed under reduced pressure. The remaining residue was extracted with DCM (100 mL) and filtered through celite to remove the remaining LiCl. The solvent was removed under reduced pressure to yield a dark green solid, which was washed with ether (50 mL) followed by pentane (50 mL) to give a green solid in 84% yield (1.88 g; 3.12 mmol).
1H NMR (400 MHz, CDCl3) δ 7.46 (s, 2H, H-4), 7.22–7.13 (m, 4H), 6.90 (s, 2H, H-2), 6.36–6.22 (m, 8H, C5H4), 4.15 (s, 4H, CH2), 3.71 (s, 6H, NCH3).
13C NMR (101 MHz, CDCl3) δ 137.71, 135.41, 128.98 (C-2), 128.63, 124.90, 122.06 (C-6), 121.97 (C5H4), 118.43 (C-4), 115.94 (C5H4), 112.00, 110.40 (C-7), 32.90 (NCH3), 26.42 (CH2).
IR (KBr disk, cm−1): 3351, 3110, 2922, 1610, 1481, 1423, 1375, 1286, 1240, 1141, 1078, 1049, 833.
UV-Vis (CH2Cl2): λ 219 nm (ε 82,100), λ 310 nm (ε 26,100), λ 410 nm (ε 4500).
Microanalysis calculated for C30H26Cl4N2Ti (604.21 g/mol): Calcd. C, 59.63%; H, 4.34%; N, 4.64%; Found C, 58.12%; H, 4.40%; N, 4.24%.
5-Fluoro-1-methyl-1H-indole-2-carbaldehyde was prepared as per the literature in 90% yield and verified via 1H NMR [29].
1H NMR (400 MHz, CDCl3) δ 9.95 (s, 1H), 7.97 (dd, J=9.2, 2.5, 1H), 7.68 (s, 1H), 7.29–7.19 (m, 1H), 7.08 (td, J=9.0, 2.5, 1H), 3.86 (s, 3H).
5-Fluoro-2-(cyclopenta-2,4-dienylidenemethyl)-1-methyl-1H-indole (4f)5-Fluoro-1-methyl-1H-indole-2-carbaldehyde (3f) (2.0 g; 8.4 mmol) was dissolved in MeOH (70 mL). Freshly cracked cyclopentadiene (0.71 mL; 8.4 mmol) was added to the solution followed by pyrrolidine (0.68 mL; 8.4 mmol), and the colour gradually changed from yellow to red. After 16 h an orange solid precipitated, this was filtered to give a 60% yield (1.31 g; 4.54 mmol).
1H NMR (300 MHz, CDCl3) δ 7.59 (s, 1H, (C5H4CH)), 7.45 (d, J=11.2, 1H), 7.35 (s, 1H), 7.22–7.26 (m, 1H), 7.04 (t, J=8.7, 1H), 6.73 (s, 1H), 6.64 (s, 1H), 6.46 (s, 1H), 6.40 (s, 1H), 3.86 (s, 3H).
13C NMR (75 MHz, CDCl3) δ 161.03–159.62 (C-5), 133.46 (C5H4), 132.84 (C5H4CH), 130.42, 129.50, 128.63 (C5H4), 127.74, 127.63, 126.87 (C5H4), 119.26 (C5H4), 111.42–111.07, 110.64–110.51, 109.99, 104.41–104.09 (C-7), 33.62.
19F NMR (282 MHz, CDCl3) δ −122.50 (td, J=9.2, 4.2, 1F).
ES-MS: m/z 207 [M–F + H]−.
λmax [nm], (ε) [L mol−1 cm−1], CHCl3: 262 (15400), 390 (1100).
IR (KBr disk, cm−1): 2933, 2852, 2809, 2762, 1624, 1600, 1553, 1449, 1419, 1340, 1315, 1255, 1202, 1075, 1044, 1075, 1009, 889, 771, 761.
Bis-[((5-fluoro-1-methyl)indol-3-yl)methylcyclopentadienyl] Titanium (IV) Dichloride (5f)Super Hydride (LiBEt3H) (12.0 mL, 12.0 mmol, and 1 M) in THF was concentrated by removal of the solvent by heating it to 60°C under reduced pressure of 10−2 mbar for 40 min and then to 90°C for 20 min in a Schlenk flask. 5-fluoro-2-(cyclopenta-2,4-dienylidenemethyl)-1-methyl-1H-indole (4f) (2.70 g; 12.0 mmol) was added to a Schlenk flask and dissolved in dry diethyl ether (100 mL) to give a red solution. The red fulvene solution was transferred to the Super Hydride solution via cannula. The solution was left to stir for 16 h, in which time a sticky dark green precipitate of the lithium cyclopentadienide intermediate formed, and the solution had changed its colour from red to yellow. The solution was removed using a syringe and the intermediate was washed with ether (30 mL). The lithium cyclopentadienide intermediate was dissolved in dry THF (50 mL) to give a pale green solution. Titanium tetrachloride (2.4 mL, 2.4 mmol, and 1 M) was added to the lithium cyclopentadienide intermediate solution to give a dark green solution. The solution was stirred for 8 h. The solvent was then removed under reduced pressure. The remaining residue was extracted with DCM (100 mL) and filtered through celite to remove the remaining LiCl. The solvent was removed under reduced pressure to yield a dark green solid which was washed with ether (50 mL) followed by pentane (50 mL) to give a green solid in 55% yield (1.90 g; 3.31 mmol).
1H NMR (400 MHz, CDCl3) δ 7.22–7.09 (m, 4H), 7.00–6.87 (m, 4H), 6.33 (s, 4H, C5H4), 6.28 (s, 4H, C5H4), 4.14 (s, 4H, CH2), 3.71 (s, 6H, NCH3).
13C NMR (101 MHz, CDCl3) δ 158.80–156.47 (C-5), 137.72, 133.66, 129.22, 128.21, 122.14 (C5H4), 115.94 (C5H4), 112.30–112.25, 110.17–110.05, 109.96–109.90, 103.98–103.75, 32.95 (NCH3), 26.55 (CH2).
19F NMR (282 MHz, CDCl3) δ (−125.09)–(−125.19) (m, 1F).
UV-Vis (CH2Cl2): λ 225 nm (ε 85,200), λ 310 nm (ε 26,100), λ 410 nm (ε 4000).
Microanalysis calculated for C30H26Cl2N2F2Ti (571.31 g/mol): Calcd. C, 63.07%; H, 4.59%; N, 4.9%; Found C, 63.15%; H, 4.05%; N, 3.97%.