Synthesis of 2-Arylamino-1,3,5-triazines from 2-Aminotriazines with Aryl Halides via CuI-Catalyzed Ullmann Coupling Reaction

Abstract

An efficient copper-catalyzed synthesis of 2-arylamino-1,3,5-triazines from 2-aminotriazines with aryl halides under mild conditions has been developed. The reaction occurred in moderate to good yields and tolerated aryl iodides containing functionalities such as nitriles, ethers, amides, and halogens. Aryl bromides were also well tolerated.

Key words

aryl halides - 2-aminotriazines - 2-arylamino-1,3,5-triazines - copper catalyst - coupling reaction

• References and Notes

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• 8 Typical Experimental Procedure: To a mixture of 1,3,5-triazine (0.5 mmol), aryl halide (0.5 mmol), DMEDA (0.45 mmol) and K₂CO₃ (1 mmol) in MeCN (3 mmol) was added CuI (0.15 mmol). The resulting mixture was stirred at reflux. After completion of the reaction, the reaction mixture was cooled to r.t., concd NH₃ (4 mL) and sat. NaCl (10 mL) were added, and the organic phase was then extracted with EtOAc (3 × 15 mL). The organic phase was dried over anhyd Na₂SO₄. The crude residue was obtained after evaporation of the solvent in vacuum, and the residue was purified by flash chromatography with petroleum and EtOAc as the eluent to give the pure product. N ²-(4-Methoxyphenyl)-N ⁴,N ⁴-dimethyl-6-phenyl-1,3,5-triazine-2,4-diamine (3a): white solid; mp 166–167 °C. ¹H NMR (500 MHz, CDCl₃): δ = 8.43 (dd, J = 8.2, 1.4 Hz, 2 H), 7.58 (d, J = 9.0 Hz, 2 H), 7.46–7.53 (m, 3 H), 7.17 (br, 1 H), 6.91 (d, J = 9.0 Hz, 2 H), 3.83 (s, 3 H), 3.34 (s, 3 H), 3.23 (s, 3 H). ¹³C NMR (125 MHz, CDCl₃): δ = 170.6, 165.9, 164.5, 155.6, 137.4, 132.4, 131.3, 128.4, 128.2, 121.8, 114.1, 55.6, 36.4. IR (KBr): 3353, 3066, 2944, 1604, 1506, 1211, 1039, 829, 778, 704 cm^–1. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₈H₂₀N₅O: 322.1668; found: 322.1684. N ²-(4-Methoxyphenyl)-N ⁴,N ⁴-dimethyl-1,3,5-triazine-2,4-diamine (3s): white solid; mp 161–163 °C. ¹H NMR (500 MHz, CDCl₃): δ = 8.40 (br, 1 H), 8.25 (s, 1 H), 7.50 (d, J = 8.2 Hz, 2 H), 6.88 (d, J = 8.2 Hz, 2 H), 3.80 (s, 3 H), 3.19 (s, 3 H), 3.16 (s, 3 H). ¹³C NMR (125 MHz, CDCl₃): δ = 165.3, 164.5, 163.3, 155.8, 131.8, 122.3, 114.0, 55.5, 36.3. IR (KBr): 3434, 3195, 2951, 1613, 1512, 1197, 1037, 831, 805 cm^–1. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₂H₁₆N₅O: 246.1355; found: 246.1377. 4-Morpholino-N-(4-nitrophenyl)-6-phenyl-1,3,5-triazin-2-amine (3u): yellow solid; mp 277–278 °C. ¹H NMR (500 MHz, DMSO-d ₆): δ = 10.41 (s, 1 H), 8.39 (dd, J = 8.5, 1.5 Hz, 2 H), 8.23 (d, J = 9.2 Hz, 2 H), 8.05 (d, J = 9.2 Hz, 2 H), 7.57–7.61 (m, 1 H), 7.52–7.58 (m, 2 H), 3.95 (br, 2 H), 3.83 (br, 2 H), 3.68–3.76 (m, 4 H). ¹³C NMR (125 MHz, DMSO-d ₆): δ = 170.3, 164.5, 164.3, 146.5, 141.1, 136.2, 132.0, 128.5, 128.2, 124.9, 119.1, 65.9, 43.6. IR (KBr): 3310, 2950, 2858, 1606, 1497, 1332, 1270, 1215, 1107, 846, 779, 701 cm^–1. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₉H₁₉N₆O₃: 379.1519; found: 379.1524. N ²-(4-Methoxyphenyl)-N ⁴,6-diphenyl-1,3,5-triazine-2,4-diamine (3v): white solid; mp 143–145 °C. ¹H NMR (500 MHz, CDCl₃): δ = 8.44 (d, J = 7.3 Hz, 2 H), 7.65 (d, J = 6.4 Hz, 2 H), 7.49–7.58 (m, 5 H), 7.46 (br, 2 H), 7.35 (t, J = 7.3 Hz, 2 H), 7.11 (t, J = 7.4 Hz, 1 H), 6.92 (d, J = 8.4 Hz, 2 H), 3.84 (s, 3 H). ¹³C NMR (125 MHz, CDCl₃): δ = 171.7, 164.9, 164.7, 156.2, 138.5, 136.5, 131.8, 131.3, 128.9, 128.4, 123.4, 123.0, 122.9, 120.5, 114.1, 55.6. IR (KBr): 3338, 3061, 2832, 1597, 1516, 1244, 1208, 1036, 826, 777, 756, 700 cm^–1. HRMS (ESI): m/z [M + H]⁺ calcd for C₂₂H₂₀N₅O: 370.1668; found: 370.1671.