Palladium-Catalyzed Selective Amination of Haloaromatics on KF-Alumina Surface

Abstract

An efficient palladium-catalyzed amination, including polyaminations of aromatic bromides mediated on a surface of KF-alumina, is reported. The solvent-free one-pot protocol avoids the use of a strong base (sodium tert-butoxide) making it applicable to substrates containing a base-sensitive functional group. It proceeds without concomitant reductive bromination and provides access to selective amination of polyhaloaromatics.

Key words

aryl halides - aryl amines - amination - palladium - KF-alumina

References

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10

General Procedure for the Amination Reactions:
A: A mixture of Pd₂ (dba)₃ (2 mol%) and BINAP (4 mol%) was admixed intimately with KF-Alumina (2:3; 2 g) and heated at 80-90 °C for 15 min. Aryl bromide (2 mmol) and amine (5 mmol) were added to the solid surface and the mixture was stirred at 80-90 °C for 1 h. An orange color developed while mixing and gradually disappeared over 1 h. The solid mass was then cooled, packed on a column of silica gel and eluted with EtOAc-light petroleum (1:19) to afford the mono-aryl amines. All the products were identified by IR, ¹H and ¹³C NMR spectral data.
Condition B: The reaction conditions were identical except the quantity of amine was increased to 7-8 equiv, KF-alumina was used in the ratio of 3:2, and the solid mixture was heated at 135 °C for 3 h. Pure bis-amines were obtained by chromatography over silica gel and elution with EtOAc-light petroleum (1:9). The spectral data were consistent with the assigned structures.

11

Selected Spectral Data for Mono- and Bis-Coupled ProductsTable 1, Entry 5: 1-(4-Piperidin-1-yl-phenyl)ethanone: IR (Nujol): 1675, 1206.5 cm^-1. ¹H NMR (CDCl₃, 300 MHz): δ = 1.65 (m, 6 H), 2.50 (s, 3 H), 3.34 (m, 4 H), 6.84 (d, 2 H, J = 9.0 Hz), 7.85 (d, 2 H, J = 9.0 Hz). ¹³C NMR (CDCl₃, 75 MHz): δ = 24.3, 25.3, 26.0, 48.6, 113.3, 126.7, 130.5, 154.4, 196.4.
Table 1, Entry 7: 1, 3-Dipiperidino Benzene: IR (Nujol): 1201.6, 1124.4 cm^-1. ¹H NMR (CDCl₃, 300 MHz): δ = 1.55-1.62 (m, 4 H), 1.70-1.78 (m, 8 H), 3.16 (t, 8 H, J = 5.4 Hz), 6.49 (dd, 2 H, J = 8.1, 2.2 Hz), 6.61 (s, 1 H), 7.15 (m, 1 H). ¹³C NMR (CDCl₃, 75 MHz): δ = 24.4, 26.0, 51.2, 106.1, 108.7, 129.3, 153.2.
Table 1, Entry 11: 1,4-Dimorpholino Benzene: IR (Nujol): 1234.4, 1120.6 cm^-1. ¹H NMR (CDCl₃, 300 MHz): δ = 3.01 (t, 8 H, J = 4.7 Hz), 3.80 (t, 8 H, J = 4.7 Hz), 6.85 (s, 4 H). ¹³C NMR (CDCl₃, 75 MHz): δ = 50.5, 66.9, 117.4, 145.8.
Table 1, Entry 13: 1,4-Di-[8-(1,4-dioxa-8-aza-spiro[4,5]decane)]benzene: IR (Nujol): 1125 cm^-1. ¹H NMR (acetone-d ₆, 300 MHz): δ = 1.76 (t, 8 H, J = 5.7 Hz), 3.16 (t, 8 H, J = 5.7 Hz), 3.94 (s, 8 H), 6.88 (s, 4 H). ¹³C NMR (acetone-d ₆, 75MHz): δ = 34.7, 48.6, 63.9, 107.5, 117.9.
Table 1, Entry 15: (2-Bromophenyl)cyclohexylamine: IR (Nujol): 1321.1, 1016.4 cm^-1. ¹H NMR (CDCl₃, 300 MHz): δ = 1.20-1.44 (m, 6 H), 1.75-1.79 (m, 2 H), 2.02-2.1 (m, 2 H), 3.30 (m, 1 H), 4.26 (br s, 1 H), 6.5 (m, 1 H), 6.6 (d, 1 H, J = 8.1 Hz), 7.14 (m, 1 H), 7.40 (d, 1 H, J = 8.8 Hz). ¹³C NMR (CDCl₃, 75 MHz ): δ = 24.8, 25.8, 33.0, 51.6, 109.8, 111.8, 117.1, 128.3, 132.5, 144.
Table 1, Entry 17: 8-(10-Bromoanthracene-9-yl)-1,4-dioxa-8-aza-spiro[4,5]decane: IR (Nujol): 1122.5 cm^-1. ¹H NMR (CDCl₃, 300 MHz): δ = 2.05 (t, 4 H, J = 5.3 Hz), 3.57 (t, 4 H, J = 5.3 Hz), 4.10 (s, 4 H), 7.48-7.60 (m, 4 H), 8.48 (d, 2 H, J = 8.7 Hz), 8.56 (d, 2 H, J = 8.7 Hz). ¹³C NMR (CDCl₃, 75 MHz ): δ = 36.4, 49.9, 64.4, 107.6, 125.2, 125.3, 126.9, 128.3, 131.2, 131.4, 134.1, 145.3.
Table 1, Entry 19: 1,3,5-Tripiperidino Benzene: IR (Nujol): 1199.6, 1122.5 cm^-1. ¹H NMR (CDCl₃, 300 MHz): δ = 1.51-1.58 (m, 6 H), 1.66-1.73 (m, 12 H), 3.10 (t, 12 H, J = 5.3 Hz), 6.14 (s, 3 H). ¹³C NMR (CDCl₃, 75 MHz): δ = 24.3, 26.0, 51.5, 99.2, 153.7.