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Synlett 2004(9): 1484-1488  
DOI: 10.1055/s-2004-829066
LETTER
© Georg Thieme Verlag Stuttgart · New York

Clean and Simple Chemoselective Reduction of Imines to Amines Using Boric Acid-Activated Sodium Borohydride under Solvent-Free Conditions

Byung Tae Cho*, Sang Kyu Kang
Department of Chemistry, Hallym University, Chuncheon, Kangwondo 200-702, Republic of Korea
Fax: +82(33)2518491; e-Mail: btcho@hallym.ac.kr;
Further Information

Publication History

Received 26 March 2004
Publication Date:
01 July 2004 (online)

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Abstract

The first clean and highly effective solvent-free chemoselective reduction of functionalized aldimines and ketimines bearing easily reducible functional groups, such as ketone, carboxylic acid, ester, nitrile, amide, nitro, furyl and alkenyl groups, to the corresponding amines using boric acid-activated ­sodium borohydride is described.

Key words

imines - reductions - chemoselectivity - sodium borohydride - solvent-free reaction

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General Procedure for Chemoselective Reduction of Aldimines and Ketimines. A mixture of imine derivatives 1 (10 mmol), NaBH4 (10 mmol) and boric acid (10 mmol) was ground with an agate mortar and pestle for 0.5-1.0 h until TLC showed complete disappearance of the starting material. The mixture was quenched with a sat. aq solution of NaHCO3, followed by filtration of the resultant suspension to give product amines 2. When the product was liquid, it was isolated from extraction with CH2Cl2 or Et2O instead of filtration. N -Phenyl-4-acetylbenzylamine ( 2a): Yield: 98%; white solid; mp 74-75 °C. IR (KBr): 3379, 3024, 2994, 2838, 1663, 1602, 1507, 1273, 749, 691 cm-1. 1H NMR (300 MHz, CDCl3): δ = 2.58 (s, 3 H), 4.17 (br s, 1 H), 4.40 (s, 2 H), 6.58 (d, J = 8.80 Hz, 2 H), 6.70 (t, J = 7.29 Hz, 1 H), 7.14 (t, J = 7.56 Hz, 2 H), 7.43 (d, J = 7.98 Hz, 2 H), 7.90 (d, J = 8.25 Hz, 2 H). 13C NMR (75 MHz, CDCl3): δ = 27.0, 48.2, 113.1, 118.1, 121.1, 127.5, 128.9, 129.1, 129.5, 136.3, 145.4, 147.9, 197.8. Anal. Calcd for C15H15NO: C, 79.97; H, 6.71; N, 6.22. Found: C, 79.96; H, 6.73; N, 6.22. N -Phenyl-4-carboxybenzylamine ( 2b): Yield: 99%; white solid; mp 196-198 °C. IR (KBr): 3412, 3360, 3050, 2933, 2836, 1684, 1603, 1317, 1291, 760 cm-1. 1H NMR (300 MHz, DMSO-d 6): δ = 3.64 (br s, 1 H), 4.31 (s, 2 H), 6.35 (br s, 1 H), 6.48 (t, J = 7.15 Hz, 1 H), 6.52 (d, J = 7.43 Hz, 2 H), 7.00 (t, J = 7.84 Hz, 2 H), 7.42 (d, J = 7.98 Hz, 2 H), 7.87 (d, J = 7.98 Hz, 2 H). 13C NMR (75 MHz, CDCl3): δ = 46.9, 112.9, 116.5, 127.7, 129.5, 130.0, 130.4, 146.2, 149.0, 168.2. Anal. Calcd for C14H13NO2: C, 73.99; H, 5.77; N, 6.16. Found: C, 73.98; H, 5.75; N, 6.18. N -Phenyl-4-methoxycarbonylbenzylamine ( 2c): Yield: 98%; oil. IR (neat): 3415, 3024, 2951, 2840, 1698, 1616, 1521, 1123, 763, 698 cm-1. 1H NMR (300 MHz, CDCl3):
δ = 3.87 (s, 3 H), 4.15 (br s, 1 H), 4.35 (s, 2 H), 6.56 (d, J = 7.70 Hz, 2 H), 6.69 (t, J = 7.43 Hz, 1 H), 7.13 (t, J = 7.84 Hz, 2 H), 7.38 (d, J = 7.98 Hz, 2 H), 7.96 (d, J = 8.25 Hz, 2 H). 13C NMR (75 MHz, CDCl3): δ = 48.3, 52.4, 113.1, 118.0, 127.3, 129.2, 129.5, 130.1, 145.2, 148.0, 167.1. Anal. Calcd for C15H15NO2: C, 74.67; H, 6.27; N, 5.81. Found: C, 74.70; H, 6.37; N, 5.86. N -Methyl-4-methoxycarbonylbenzyl-amine ( 2d): Yield: 99%; white solid; mp 152-153 °C. IR (KBr): 3236, 3018, 1004, 2952, 1704, 1428, 1286, 1168, 894 cm-1. 1H NMR (300 MHz, CDCl3): δ = 2.42 (d, J = 5.78 Hz, 3 H), 3.59 (dd, J = 9.77, 13.62 Hz, 1 H), 3.93 (s, 3 H), 4.30 (dd, J = 2.89, 13.89 Hz, 1 H), 4.39 (br s, 1 H), 7.39 (d, J = 8.25 Hz, 2 H), 8.05 (d, J = 8.25 Hz, 2 H). 13C NMR (75 MHz, CDCl3): δ = 40.8, 60.7, 129.7, 130.5, 130.8, 166.6. Anal. Calcd for C10H13NO2: C, 67.02; H, 7.31; N, 7.82. Found: C, 67.01; H, 7.33; N, 7.83. N - tert -Butyl-4-methoxycarbonyl-benzylamine ( 2e): Yield: 98%; white solid; mp 30-31 °C. IR (KBr): 3316, 3187, 2961, 2877, 1716, 1437, 1281, 1110, 1019, 769 cm-1. 1H NMR (300 MHz, CDCl3): δ = 1.18 (s, 9 H), 1.43 (s, 1 H), 3.77 (s, 2 H), 3.90 (s, 3 H), 7.40 (d, J = 7.98 Hz, 2 H), 7.96 (d, J = 8.25 Hz, 2 H). 13C NMR (75 MHz, CDCl3): δ = 29.5, 47.3, 51.2, 52.5, 128.3, 128.7, 129.9, 147.1, 167.3. Anal. Calcd for C13H19NO2: C, 70.56; H, 8.65; N, 6.33. Found: C, 70.58; H, 8.67; N, 6.33. N -Phenyl-4-cyanobenzylamine ( 2f): Yield: 99%; mp 83-84 °C. IR (KBr): 3425, 3047, 2911, 2864, 2220, 1600, 1507, 1332, 1266, 818, 765, 697 cm-1. 1H NMR (300 MHz, CDCl3): δ = 4.20 (br s, 1 H), 4.40 (s, 2 H), 6.55 (d, J = 7.70 Hz, 2 H), 6.71 (t, J = 7.29 Hz, 1 H), 7.14 (t, J = 7.01 Hz, 2 H), 7.44 (d, J = 7.98 Hz, 2 H), 7.58 (d, J = 8.25 Hz, 2 H). 13C NMR (75 MHz, CDCl3): δ = 48.1, 111.1, 113.1, 118.3, 119.1, 127.9, 129.6, 132.6, 145.6, 147.6. Anal. Calcd for C14H12N2: C, 80.74; H, 5.81; N, 13.45. Found: C, 80.76; H, 5.78; N, 13.46. N -Methyl-4-cyanobenzylamine ( 2g): Yield: 98%; white solid; mp 108-109 °C. IR (KBr): 3158, 3013, 2854, 2260, 1520, 1350, 1169, 853 cm-1. 1H NMR (300 MHz, CDCl3):
δ = 2.43 (d, J = 5.50 Hz, 3 H), 3.64 (dd, J = 7.35, 13.75 Hz, 1 H), 4.26 (dd, J = 3.58, 13.75 Hz, 1 H), 4.68 (br s, 1 H), 7.47 (d, J = 8.25 Hz, 2 H), 7.70 (d, J = 8.25 Hz, 2 H). 13C NMR (75 MHz, CDCl3): δ = 41.0, 60.4, 112.9, 118.6, 130.6, 133.0, 139.1. Anal. Calcd for C9H10N2: C, 73.94; H, 6.89; N, 19.16. Found: C, 73.99; H, 6.95; N, 19.17. N - n -Heptyl-4-cyanobenzylamine ( 2h): Yield: 98%, white solid; mp 63-64 °C. IR (KBr): 3193, 2955, 2926, 2856, 2228, 1457, 1160, 897, 854 cm-1. 1H NMR (300 MHz, CDCl3): δ = 0.86 (t, J = 6.60 Hz, 3 H), 1.13-1.27 (m, 6 H), 1.58-1.74 (m, 4 H), 2.61-2.67 (m, 2 H), 3.77 (dd, J =8.12, 13.34 Hz, 1 H), 4.08 (br s, 1 H), 4.17 (dd, J = 4.26, 13.34 Hz, 1 H), 7.46 (d, J = 8.25 Hz, 2 H), 7.69 (d, J = 8.53 Hz, 2 H). 13C NMR (75 MHz, CDCl3): δ = 14.5, 22.9, 26.6, 27.0, 29.2, 31.9, 54.3, 59.2, 112.9, 118.5, 130.6, 132.9, 139.4. Anal. Calcd for C15H22N2: C, 78.21; H, 9.63; N, 12.16. Found: C, 78.23; H, 9.64; N, 12.17. N- 2-Furfuryl-4-cyanobenzyl-amine ( 2i): Yield: 97%; oil. IR (neat): 3203, 2962, 2927, 2852, 2230, 1504, 1167, 1010, 821, 739 cm-1. 1H NMR (300 MHz, CDCl3): δ = 3.72 (dd, J = 8.94, 14.99 Hz, 1 H), 3.83 (d, J = 5.50 Hz, 2 H), 3.87 (br s, 1 H), 4.10 (dd, J = 3.30, 14.30 Hz, 1 H), 6.30-6.34 (m, 2 H), 7.25 (d, J = 8.53 Hz, 2 H), 7.35 (m, 1 H), 7.55 (d, J = 8.25 Hz, 2 H). 13C NMR (75 MHz, CDCl3): δ = 51.9, 57.4, 111.3, 111.9, 112.8, 118.6, 130.8, 132.7, 139.0, 143.7, 147.5. Anal. Calcd for C13H12N2O: C, 73.56; H, 5.70; N, 13.20. Found: C, 73.55; H, 5.69; N, 13.22. N -Phenyl-4-acetamido-benzylamine ( 2j): Yield: 98%; oil. IR (neat): 3426, 3301, 3193, 3050, 2931, 2840, 1662, 1601, 1511, 1315, 745, 689 cm-1. 1H NMR (300 MHz, CDCl3): δ = 2.12 (s, 3 H), 4.03 (br s, 1 H), 4.24 (s, 2 H), 6.58 (dd, J = 1.10, 8.53 Hz, 2 H), 6.68 (t, J = 7.30 Hz, 1 H), 7.13 (dd, J = 7.43, 8.53 Hz, 2 H), 7.25 (d, J = 8.25 Hz, 2 H), 7.42 (d, J = 8.25 Hz, 2 H), 7.76 (br s, 1 H). 13C NMR (75 MHz, CDCl3): δ = 24.9, 48.1, 113.1, 117.8, 120.6, 128.2, 129.5, 135.6, 137.1, 148.2, 168.9. Anal. Calcd for C15H16N2O: C, 74.97; H, 6.71; N, 11.66. Found: C, 74.95; H, 6.75; N, 11.68. N -Phenyl-4-nitrobenzyamine ( 2k): Yield: 99%; oil. IR (neat): 3423, 3052, 2923, 2843, 1614, 1506, 1334, 761, 701 cm-1. 1H NMR (300 MHz, CDCl3): δ = 4.27 (br s, 1 H), 4.43 (s, 2 H), 6.54 (d, J = 8.53 Hz, 2 H), 6.70 (t, J = 7.29 Hz, 1 H), 7.13 (t, J = 7.70 Hz, 2 H), 7.47 (d, J = 8.25 Hz, 2 H), 8.12 (d, J = 8.44 Hz, 2 H). 13C NMR (75 MHz, CDCl3): δ = 47.9, 113.1, 118.3, 124.1, 127.9, 129.6, 147.2, 147.5, 147.8. Anal. Calcd for C13H12N2O2: C, 68.41; H, 5.30; N, 12.27. Found: C, 68.43; H, 5.32; N, 12.25. N -Methyl-4-nitrobenzyamine ( 2l): Yield: 99%; yellow solid; mp 111-112 °C. IR (KBr): 3200, 3069, 2999, 2951, 1465, 1290, 1164, 894 cm-1. 1H NMR (300 MHz, CDCl3): δ = 2.47 (d, J = 5.78 Hz, 3 H), 3.72 (dd, J = 9.35, 13.75 Hz, 1 H), 4.30 (dd, J = 3.85, 13.75 Hz, 1 H), 4.71 (br s, 1 H), 7.54 (d, J = 8.53 Hz, 2 H), 8.25 (d, J = 8.80 Hz, 2 H). 13C NMR (75 MHz, CDCl3): δ = 41.1, 60.1, 124.4, 130.9, 140.9, 148.2. Anal. Calcd for C8H10N2O2: C, 57.82; H, 6.07; N, 16.86. Found: C, 57.84; H, 6.10; N, 16.87. N -Phenyl- trans -cinnamylamine ( 2m): Yield: 98%; oil. IR (neat): 3416, 3023, 2925, 2833, 1601, 1505, 1320, 1251, 747, 693 cm-1. 1H NMR (300 MHz, CDCl3): δ = 3.77 (br s, 1 H), 3.88 (dd, J = 1.22, 5.49 Hz, 2 H), 6.29 (m, 1 H), 6.55-6.75 (m, 4 H), 7.13-7.37 (m, 7 H). 13C NMR (75 MHz, CDCl3): δ = 46.8, 113.7, 118.2, 127.0, 127.7, 128.2, 129.2, 129.9, 132.1, 137.5, 148.7. Anal. Calcd for C15H15N: C, 86.08; H, 7.22; N, 6.69. Found: C, 86.09; H, 6.67; N, 6.68. N -Phenyl-α-methyl-(4-cyanobenzyl)amine ( 2n): Yield: 98%; mp 99-101 °C. IR (KBr): 3373, 3029, 2962, 2864, 2228, 1605, 1512, 1497, 1324, 1259, 832, 754, 693 cm-1. 1H NMR (300 MHz, CDCl3): δ = 1.51 (d, J = 6.60 Hz, 3 H), 4.07 (br s, 1 H), 4.49 (q, J = 6.79 Hz, 1 H), 6.41 (d, J = 7.70 Hz, 2 H), 6.66 (t, J = 7.43 Hz, 1 H), 7.07 (dd, J = 7.56, 8.39 Hz, 2 H), 7.46 (d, J = 8.53 Hz, 2 H), 7.58 (d, J = 8.25 Hz, 2 H). 13C NMR (75 MHz, CDCl3): δ = 25.4, 53.7, 101.9, 113.4, 118.0, 119.2, 126.8, 129.4, 132.8, 146.7, 151.2. Anal. Calcd for C15H14N2: C, 81.05; H, 6.35; N, 12.60. Found: C, 81.07; H, 6.37; N, 12.65. N -Phenyl-α-methyl-(4-nitro-benzyl)amine ( 2o): Yield: 97%; oil. IR (neat): 3409, 3052, 2971, 2927, 2869, 1614, 1588, 1450, 1013, 744, 702 cm-1. 1H NMR (200 MHz, CDCl3): δ = 1.54 (d, J = 6.72 Hz, 3 H), 4.09 (br s, 1 H), 4.57 (q, J = 6.72 Hz, 1 H), 6.44 (d, J = 7.63 Hz, 2 H), 6.68 (t, J = 7.33 Hz, 1 H), 7.10 (t, J = 7.94 Hz, 2 H), 7.55 (d, J = 8.85 Hz, 2 H), 8.18 (d, J = 8.85 Hz, 2 H). 13C NMR (50 MHz, CDCl3): δ = 25.6, 54.0, 114.0, 118.7, 124.8, 127.4, 129.9, 147.2, 147.8, 153.9. Anal. Calcd for C14H14N2O2: C, 69.41; H, 5.82; N, 11.56. Found: C, 69.43; H, 5.82; N, 11.55. N -Phenyl-2-(1′-cyclohexenyl)ethyl-amine ( 2p): Yield: 97%; oil. IR (neat): 3410, 3050, 2925, 2855, 1602, 1504, 1319, 749, 691 cm-1. 1H NMR (300 MHz, CDCl3): δ = 1.28 (d, J = 6.88 Hz, 3 H), 1.48-1.64 (m, 4 H), 1.94-1.99 (m, 4 H), 3.75 (q, J = 6.60 Hz, 1 H), 3.76 (m, 1 H), 5.66 (s, 1 H); 6.54 (d, J = 7.43 Hz, 2 H), 6.63 (t, J = 7.29 Hz, 1 H), 7.11 (dd, J = 7.15, 8.53 Hz, 2 H). 13C NMR (75 MHz, CDCl3): δ = 21.7, 23.1, 23.2, 24.7, 25.4, 55.1, 113.3, 117.0, 121.8, 129.2, 139.6, 147.9. Anal. Calcd for C14H19N: C, 83.53; H, 9.51; N, 6.96. Found: C, 83.52; H, 9.54; N, 6.98.