N-Heterocyclic carbene-catalyzed oxidative esterification of ferroceneboronic acid by aromatic and heteroaromatic aldehydes affords the new ferrocenol hetaryl and aryl esters 1 - 4, 6 - 8 and 9 - 11. The reaction takes place under mild conditions. The X-ray crystal structure of ferrocenyl esters 3, 6, 11 was determined.
Ferrocene is considered to be one of the most prominent molecules in modern organic and organometallic chemistry [
Nesmeyanov first reported hydroxyferrocene in 1959, generating it from either ferroceneboronic acid FcB (OH)2 (via reaction with Cu(OAc)2 and then potassium hydroxide) [
Recently oxidative esterification of aromatic (heteroaromatic) aldehydes was disclosed [
Oxygen of the air is evidently the terminate oxidant. Therefore, we tried to bubble the air into the reaction vessel to improve the yield. However, only in the case of compound 11, the yield increased to some extent, with other compound yields being unaffected by this improvement.
At room temperature, esters 8 and 9 decompose during storage over 3 - 4 days. Indeed, the stability of esters 1-11 has a decisive influence on the yields (
Below is shown the X-ray crystal structure of compound 1 (
Scheme 1. Synthesis of compounds 1-11.
Compound | R | Temperature, ˚C | Time (h) | Flash mixture, petroleum ether-ethylacetate | Yield (%) |
---|---|---|---|---|---|
1 | 3,4-(MeO)2C6H3 | 50 | 3 | 5:1 | 76 |
2 | 3,4,5-(MeO)3C6H2 | 70 | 6 | 10:1 | 16 |
3 | 4-(CF3)C6H4 | 70 | 3 | 20:1 | 35 |
4 | 1-naphtyl | 50 | 6 | 10:1 | 76 |
5 | CH=CHPh | 50 | 3 | 10:1 | 36 |
6 | 2-furyl | 50 | 3 | 10:1 | 34 |
7 | 2-thienyl | 50 | 3 | 10:1 | 35 |
8 | 2-pyridyl | 50 | 6 | 5:1 | 17 |
9 | 3-pyridyl | 50 | 6 | 3:1 | 33 |
10 | 4-pyridyl | 50 | 6 | 3:1 | 17 |
11 | ferrocenyl | 70 | 6 | 10:1 | 6 |
11a | ferrocenyl | 70 | 6 | 10:1 | 28 |
In accord with XRD data, two independent molecules of ferrocenyl isonicotinate 10 are crystallized in the unit cell (
The melting points were determined on the PTP apparatus and are uncorrected. NMR spectra were recorded in CDCl3 using a Varian Mercury Plus 300 at 300 MHz (1Н) and 75 (13С) МHz. Chemical shifts were referenced to solvent signals (13С) and GMDS (1Н). The IR spectra were recorded in Nujol on Bruker IFS 66 ps. Elemental analysis was carried out on CHNS Leco 9321P analyzer. The reaction mixture was qualitatively analyzed by GC-MS Agilent Technologies 6890N/5975B system with НР-5 ms, 30,000 × 0.25 mm column. The column was heated up to 260˚C. The same device was used for recording mass-spectra (EI, 70 eV). The crude product was purified by column chromatography on Silica gel 60 (AlfaAesar, 0.032 - 0.070 mm).
A mixture of ferroceneboronic acid (0.105 g, 0.5 mmol), corresponding aldehyde (0.65 mmol), CsCO3 (0.244 g, 0.75 mmol) and 1,3-bis(2,4,6-trimethyphenyl)-4,5-dihydro-1H-imidazol-3-ium chloride (0.017 g, 0.05 mmol) was suspended in toluene (10 ml), and stirred in air at 50˚C or at 70˚C for 3 or 6 h (
Yield 76%, yellow prisms from methanol. Mp.: 131˚C - 134˚C. FT-IR (Nujol, cm−1): 3078, 1727, 1596, 1517, 1417, 1349, 1289, 1273, 1250, 1233, 1214, 1193, 1172, 1142, 1105, 1084, 1025, 1001, 931, 905, 893, 810, 768, 758, 609, 513, 501, 489. 1H NMR (300 MHz, CDCl3): δ 3.94 (3H, s, MeO), 3.95 (3H, s, MeO), 4.00 (2H, s, Fc), 4.26 (5H, s, Fc), 4.56 (2H, s, Fc), 6.76 (1H, d, J = 8.4 Hz, H-5'), 7.58 (1H, s, H-2'), 7.75 (1H, d, J = 8.4 Hz, H-6'). 13C NHC (75 MHz, CDCl3): δ 55.99, 60.87, 63.28, 69.35, 110.23, 112.08, 116.23, 122.05, 123.93, 148.64, 153.25, 164.64. EI-MS (rel. int.%): 367 (5) [M+1]+, 336 (24) [M]+. Anal. Calc. for C16H13FeNO2: C, 62.3; H, 4.9%. Found: C, 62.0; H, 4.9%.
Yield 16%, brown solid. Mp.: 123˚C - 127˚C. FT-IR (Nujol, cm−1): 1731, 1587, 1503, 1331, 1234, 1212, 1181, 1170, 1130, 1104, 1097, 1033, 994, 940, 865, 824, 803, 779, 757, 647, 512, 499. 1H NMR (300 MHz, CDCl3): δ 3.91 (3H, s, 4-MeO), 3.93 (6H, s, 3,5-MeO), 4.10 (2H, s, Fc), 4.35 (5H, s, Fc), 4.67 (2H, s, Fc), 7.33 (2H, s, Ar-2,6). 13C NMR (75 MHz, CDCl3): δ 45.42, 56.34, 60.94, 61.27, 63.99, 70.25, 107.16, 152.95, 161.38, 164.32. EI-MS (rel. int.%): 397 (8) [M+1]+, 396 (25) [M]+. Anal. Calc. for C20H20FeO5: C, 60.6; H, 5.1. Found: C, 60.7; H, 5.5%.
Yield 35%, red powder, Mp.: 106˚C - 107˚C. FT-IR (Nujol, cm−1): 3117, 1735, 1695, 1412, 1334, 1307, 1281, 1238, 1161, 1115, 1107, 1095, 1069, 1019, 1001, 927, 859, 814, 768, 698, 662, 592, 513, 484. 1H NMR (300 MHz, CDCl3): δ 4.01 (2Н, t, J = 1.8 Hz, Fc), 4.25 (5H, s, Fc), 4.57 (2Н, t, J = 1.8 Hz, Fc), 7.74 (2Н, d, J = 8.1 Hz, H-3', 5'), 8.72 (2Н, d, J = 8.1 Hz, H-2', 6'). 13C NMR (75 MHz, CDCl3): δ 60.84, 63.46, 69.42, 99, 95, 125.45, 125.55, 130.22. EI-MS (rel. int.%): 375 (12) [M+1]+, 374 (49) [M]+. Anal. Calc. for C18H13FeO2: C, 57.78; H, 3.50. Found: C 57.76; H 3.49%.
Yield 76%, red crystals, Mp.: 95˚C - 101˚C. FT-IR (Nujol, cm−1): 1732, 1690, 1593, 1575, 1510, 1411, 1348, 1276, 1231, 1189, 1121, 1106, 1069, 1032, 1024, 1001, 987, 923, 869, 810, 779, 648, 610, 559, 509, 489. 1H NMR (300 MHz, CDCl3): δ 4.03 (2Н, t, J = 1.8 Hz, Fc), 4.29 (5H, s, Fc), 4.62 (2Н, J = 2.0 Hz, Fc), 7.50 - 7.70 (3Н, m, H-7',6',3'), 7.89 (1Н, d, J = 8.1 Hz, H-5'), 8.05 (1Н, d, J = 8.1 Hz, H-4'), 8.28 (1Н, dd, J = 7.4 Hz, J = 1.1 Hz, H-2'), 8.96 (1Н, d, J = 8.7 Hz, H-8'). 13C NMR (75 MHz, CDCl3): δ 61.13, 63.42, 69.39, 124.49, 125.65, 126.34, 128.01, 128.62, 130.66, 133.86, 133.87. EI-MS (rel. int.%): 357 (12) [M+1]+, 356 (48) [M]+. Anal. Calc. for C18H13FeO2: C 70.81; H 4.53. Found: C, 70.61; H, 4.20%.
Yield 36%, yellow crystals. Mp.: 82˚C - 83.5˚C. (lit.: 88.5˚C - 90˚C [
Yield 34%, orange powder, Mp.: 94˚C - 95˚C. FT-IR (Nujol, cm−1): 1741, 1578, 1568, 1552, 1410, 1393, 1293, 1236, 1173, 1105, 1097, 1074, 1013, 935, 917, 884, 826, 809, 595, 492. 1H NMR (300 MHz, CDCl3): δ 4.01 (2Н, t, J = 2.0 Hz, Fc), 4.28 (5H, s, Fc), 4.60 (2Н, t, J = 2.0 Hz, Fc), 6.58 (1H, dd, J = 3.5 Hz, J = 1.7 Гц, H-4׳), 7.30 (1H, dd, J = 3.5 Hz, J = 0.8 Hz, H-3') 7.66 (1H, dd, J = 1.7 Hz, J = 0.8 Hz, H-5'). 13C NMR (75 MHz, CDCl3): δ 60.26, 62.78, 68.95, 111.51, 115.46, 118.19, 143.76, 146.28, 156.14. EI-MS (rel. int.%): 297 (19) [M+1]+, 296 (100) [M]+. Anal. Calc. for C15H12FeO3: C, 60.84; H, 4.08. Found: C, 60.06; H, 4.00%.
Yield 35%, yellow solid. Mp.: 108˚C - 109˚C. FT-IR (Nujol, cm−1): 1734, 1522, 1355, 1266, 1245, 1233, 1213, 1103, 1076, 1061, 1018, 1009, 924, 859, 849, 838, 827, 807, 742, 614, 499, 486. 1H NMR (300 MHz, CDCl3): δ 4.04 (2H, s, Fc), 4.31 (5H, s, Fc), 4.61 (2H, s, Fc), 7.13 (1H, dd, J = 4.8 Hz, J = 2.7 Hz, H-4'), 7.60 (1H, d, J = 4.8 Hz, H-3'), 7.86 (1H, d, J = 2.7 Hz, H-5'). 13C NMR (75 MHz, CDCl3): δ 61.21, 63.81, 69.97, 127.89, 133.05, 134.04, 160.25. EI-MS (rel. int.%): 314 (6) [M+2]+., 313 (18) [M+1]+, 312 (87) [M]+. Anal. Calc. for C16H13FeNO2: C, 57.7; H, 3.9; S, 10.3%. Found: C, 57.5; H, 4.0; S, 10.1%.
Yield 17%, black solid. Compound is unstable in air (decomposes in 2 - 3 days at room temperature). FT-IR (Nujol, cm−1): 3231, 1777, 1705, 1666, 1625, 1593, 1567, 1259, 1047, 858, 765, 663. 1H NMR (300 MHz, CDCl3): δ 4.02 (2H, s, Fc), 4.26 (5H, s, Fc), 4.66 (2H, s, Fc), 7.53 (1H, m, H-5'), 7.89 (1H, m, H-3'), 8.19 (1H, m, H-4'), 8.82 (1H, m, H-6'). NMR 13С, δ 60.32, 62.85, 69.01, 124.94, 126.59, 126.60, 136.59, 140.87, 149.64, 162.74. EI-MS (rel. int.%): 308 (20) [M+1]+, 307 (100) [M]+. C16H13FeNO2. No correct elemental analysis could be obtained for this compound, despite several attempts.
Yield 33%, brown solid. Compound is unstable in air. Mp.: 69˚C - 76˚C. FT-IR (Nujol, cm−1): 1730, 1679, 1279, 1235, 1103, 1086, 1038, 1027, 835, 809, 700, 516, 506, 492. 1H NMR (300 MHz, CDCl3): δ 4.03 (2H, s, Fc), 4.27 (5H, s, Fc), 4.58 (2H, s, Fc), 7.48 (1H, m, H-5'), 8.37 (1H, d, J = 6.9 Hz, H-4'), 8.88 (1H, m, H-6'), 9.36 (1H, s, H-2'). NMR 13С (75 MHz, CDCl3): δ 60.42, 63.01, 68.98, 115.52, 123.12, 129.21 136.77, 150.69, 153.26, 163.18. EI-MS (rel. int.%): 308 (17) [M+1]+, 307 (86) [M]+. C16H13FeNO2. We failed to obtain correct elemental analysis for this compound.
Yield 17%, brown prisms from hexanes-AcOEt. Mp.: 82˚C - 85˚C. FT-IR (Nujol, cm−1): 1748, 1712, 1675, 1351, 1324, 1272, 1234, 1104, 1064, 923, 818, 753, 701, 490. 1H NMR (300 MHz, CDCl3): δ 4.03 (2H, s, Fc), 4.26 (5H, s, Fc), 4.58 (2H, s, Fc), 7.93 (2H, m, H-3',5'), 8.87 (2H, m, H-2',6'). 13C NHC (75 MHz, CDCl3): δ 60.74, 63.48, 69.42, 122.90, 129.38, 129.61, 150.71, 163.42. EI-MS (rel. int.%): 308 (21) [M+1]+, 307 (100) [M]+. Anal. Calc. for C16H13FeNO2: C, 62.6; H, 4.3; N, 4.6%. Found: C, 62.9; H, 4.7; N, 3.9%.
This compound is already known [
The unit cell parameters and the X-ray diffraction intensities of compounds 1, 4 were measured on a Xcalibur R diffractometer. The empirical absorption correction was introduced by multi-scan method using SCALE3 ABSPACK algorithm [
A suitable crystal of compound 10 was selected and XRD analysis was accomplished on a Xcalibur, Eos diffractometer on standard procedure (MoK-irradiation, graphite monochromator, T = 295(2) K, ω-scanning with 1˚ step). Empirical absorption correction was applied [
Crystal Data of 1. C19H18FeO4, M = 366.18, triclinic, a = 7.8682(9) Å, b = 10.2613(10) Å, c = 11.2587(13) Å, α = 110.514(10)˚, β = 104.022(10)˚, γ = 104.022(10)˚, V = 816.95(15) Å3, T = 295(2), space group P-1, Z = 2, μ (Mo Kα) = 0.942 mm−1. The final refinement parameters: R1 = 0.0407, wR2 = 0.0924 (for all independent 3766 reflections, Rint = 0.0259); R1 = 0.0349, wR2 = 0.0879 [for observed 3347 reflections with I > 2σ(I)], S = 1.059. Largest diff. peak and hole 0.256 and −0.421 ēÅ−3.
Crystal Data of 4. C21H16FeO2, M = 356.19, monoclinic, a = 12.2242(18) Å, b = 7.6261(13) Å, c = 17.941(3) Å, β = 108.440(17)˚, V = 1586.7(5) Å3, T = 295(2), space group P21/n, Z = 4, μ (Mo Kα) = 0.960 mm−1. The final refinement parameters: R1 = 0.0457, wR2 = 0.1043 (for all independent 3686 reflections, Rint = 0.0347); R1 = 0.0385, wR2 = 0.0999 [for observed 3165 reflections with I > 2σ(I)], S = 1.064. Largest diff. peak and hole 0.427 and −0.473 ēÅ−3.
Crystal Data of 10. C16H13FeNO2, M = 306.13, triclinic, a = 7.5025(2) Å, b = 10.7990(4) Å, c = 16.9885(7) Å, α = 98.444(3)˚, β = 100.017(3)˚, γ = 90.630(3)˚, V = 1339.78(9) Å3, T = 295(2), space group P-1, Z = 4, μ (Mo Kα) = 1.125 mm−1. On the angles 1.91 < θ < 30.80˚ 12392 reflections measured, 7233 unique (5201 with I > 2σ(I), Rint = 0.0287) which were used in all calculations. Completeness for θ < 26.0˚ 100%. The final wR2 was 0.1495 (all data) and R1 was 0.0426 (I > 2σ(I)). Largest diff. peak and hole 0.564 and −0.431 ēÅ−3.
Herein, we disclose the simple straightforward method for synthesis of ferrocenol esters, beginning with easily accessible ferrocenol boronic acid and aryl-(hetaryl)-aldehydes. The reaction is catalyzed by N-heterocyclic carbene (IMes) and is suitable for synthesis of substituted benzoic acid, as well as for heterocyclic acids; however, 2- and 3-pyridylcarboxylic acid ferrocenol esters are rather unstable. Limitation and scope of the method are currently under investigation in our laboratory.
The authors thank engineer I.A. Borisova for recording the IR spectra, leading engineer O.A. Maiorova for recording the 1H and 13C NMR spectra, and researcher E.V. Baigacheva for performing elemental analyses. This study was performed under financial support by the Russian Foundation for Basic Research (Projects No. 14-03-31168-mol-a, 16-33-00147-mol-a).
CCDC 1034705 (compound 10), 1453993 (compound 1) and 1453994 (compound 4) contain the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via http://www.ccdc.cam.ac.uk.
Mikhail Denisov,Aleksey Gorbunov,Maksim V. Dmitriev,Pavel Slepukhin,Vladimir Glushkov,1 1, (2016) Synthesis and Structure of Ferrocenol Esters. International Journal of Organic Chemistry,06,107-116. doi: 10.4236/ijoc.2016.62012