SnCl₂·2H₂O-Catalyzed Solvent-Free Synthesis of α-Amino Ketones and Tetrasubstituted Pyrazines

Abstract

Solvent-free reaction of various anilines with α-hydroxy ketones catalyzed by SnCl₂·2H₂O provides α-amino ketones in excellent yields. While a similar reaction with aliphatic amines is applicable for the synthesis of substituted pyrazines, SnCl₂·2H₂O permits versatility in the solvent-free reaction of α-hydroxy ketones with ammonium acetate to give the corresponding substituted pyrazines in good to excellent yields.

Key words

pseudo-four-component reaction - α-amino ketone - α-hydroxy ketone - SnCl₂·2H₂O - aromatic amines - pyrazine

• References and Notes

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• 17 General Procedure for Synthesis of α-Amino Ketones SnCl₂·2H₂O (10 mol%) was added to a stirred mixture of benzoin (2 mmol) and amine (2 mmol) in a round-bottom flask at 80 °C. The resulting mixture was stirred for the given time and progress of the reaction was followed by TLC (EtOAc–hexane, 20:80). After completion of the reaction, EtOAc was added (50 mL), and the mixture was filtered to remove the catalyst. Then the organic layer was washed with 10% NaHCO₃ and water, dried over Na₂SO₄, filtered, and concentrated to give the product. Although additional purification was not required in most cases, the crude products may be recrystallized from H₂O–EtOH (60:40). Analytical Data for 2-[(4-Acetylphenyl)amino]-1,2-diphenylethanone (2j) Pale yellow solid; yield for reaction in 2 mmol scale: 300 mg (92%); mp 158–160 °C. FT-IR (KBr): 3375 (NH stretch), 1676, 1664 (C=O stretch), 1600, 1520, 1479, 1447, 1273, 1170 cm^–1. ¹H NMR (400 MHz, DMSO-d ₆): δ = 2.40 (s, 3 H), 5.49 (s, 1 H), 6.59 (d, J = 7.6 Hz, 1 H), 6.87 (d, J = 8.8 Hz, 2 H), 7.21–7.66 (m, 8 H), 7.71 (d, J = 8.8 Hz, 2 H), 8.17 (d, J = 7.2 Hz, 2 H) ppm. ¹³C NMR (100 MHz, DMSO-d ₆): δ = 26.42, 61.07, 112.67, 126.89, 128.41, 128.52, 128.86, 129.24, 129.32, 129.34, 130.00, 130.09, 134.22, 135.15, 137.90, 137.92, 151.59, 195.75, 197.11 ppm. Anal. Calcd for C₂₂H₁₉NO₂: C, 80.22; H, 5.81; N, 4.25; O, 9.71. Found: C, 80.25; H, 5.98; N, 4.27; O, 9.80.
• 18 General Procedure for Synthesis of Substituted Pyrazines To a mixture of benzoin (2 mmol) and NH₄OAc (2.2 mmol) was added SnCl₂·2H₂O (10 mol%), and the mixture was stirred for the requisite time at 80 °C. After completion of the reaction (TLC), EtOH (3 mL), and water (7 mL) were added, the mixture was stirred, and the product was isolated by filtration. The pyrazine products were analytically pure and showed the expected characterization data without additional purification. Analytical Data
  2,3,5,6-Tetraphenylpyrazine (1a) Yellow solid; yield for reaction at 2 mmol scale: 346 mg (90%); mp 252–254 °C. FT-IR (KBr): 3054, 1628 (C=N stretch), 1599, 1521, 1461, 1393, 1175, 1025 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.26–7.34 (m, HAr, 12 H), 7.65 (t, J = 6.8 Hz, HAr, 8 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 148.47, 138.52, 129.94, 128.62, 128.52, 128.30 ppm. 1,4-Dibenzyl-2,3,5,6-tetraphenyl-1,4-dihydropyrazine (20) Yellow solid; yield for reaction at 2 mmol scale: 510 mg (90%); mp 157–160 °C. FT-IR (KBr): 1601, 1448 (C=C stretch), 1027 (C–N stretch) cm^–1. ¹H NMR (400 MHz, DMSO-d ₆): δ = 5.18 (s, 4 H), 6.77 (d, J = 6.8 Hz, 3 H), 7.15–7.25 (m, HAr, 9 H), 7.30–7.41 (m, HAr, 3 H), 7.43–7.49 (m, HAr, 12 H), 7.67–7.69 (m, HAr, 3 H) ppm. ¹³C NMR (100 MHz, DMSO-d ₆): δ = 48.16, 106.28, 126.10, 126.58, 126.76, 127.68, 128.59, 129.02, 129.08, 129.32, 129.37, 129.43, 130, 68, 131.06, 131.25, 131.31, 135.00, 137.36, 137.79 ppm. Anal. Calcd for C₄₂H₃₄N₂: C, 89.01; H, 6.05; N, 4.94. Found: C, 88.98; H, 6.03; N, 4.97.
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