Enamination of β-Dicarbonyl Compounds Catalyzed by CeCl₃·7H₂O at ­Ambient Conditions: Ionic Liquid and Solvent-Free Media

Abstract

Enamination of a wide various primary amines was successfully carried out in the presence of catalytic amounts of cerium chloride heptahydrate in ionic liquid and solvent-free conditions as ‘green’ media under mild reaction conditions.

ionic liquid - solvent-free - TBAB - CeCl₃·7H₂O - chemoselectivity - primary amine - catalyst

References

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<A NAME="RG07803ST-14">14</A>

Typical Experimental Procedure (Method A): To a mixture of ethyl acetoacetate (1.0 mmol) and aniline (1.0 mmol) under solvent-free conditions, CeCl₃·7H₂O (0.1 mmol) was added and the reaction mixture stirred at r.t. for the appropriate time according to Table [2] . After completion of the reaction as indicated by TLC, the mixture was washed with EtOAc. The crude products were separated by preparative chromatography on silica gel using n-heptane-EtOAc (10:1) as eluent. The pure b-enaminones were prepared in 50-87% yields.

<A NAME="RG07803ST-15">15</A>

Typical Experimental Procedure (Method B): To the molten of TBAB (0.5 mmol), CeCl₃·7H₂O (0.1 mmol) was added and the mixture cooled to r.t., then ethyl acetoacetate (1.0 mmol) and aniline (1.0 mmol) were added to it. The reaction mixture stirred magnetically at r.t. for the appropriate time as shown in Table [2] . The reaction was followed by TLC. When the reaction was completed, the mixture washed with EtOAc. The crude products were separated by preparative chromatography on silica gel using n-heptane/EtOAc (10:1) as eluent. The pure b-enaminones were prepared in 74-99% yields. Selected characterization data of compounds 8, 11, 13 and 20 are shown below.
Compound 8: mp 110-111 °C. IR (KBr): n_max = 3240, 2923, 1668, 1584, 1250, 1012, 955, 763 cm^-1. ¹H NMR (200 MHz, CDCl₃): d_H = 8.32 (br, 1 H, NH), 4.28 (t, J = 8.7 Hz, 2 H), 3.75 (t, J = 5.8, 2 H), 3.41 (q, J = 5.1, 2 H), 3.18 (br, 1 H, OH), 2.75 (t, J = 7.3 Hz, 2 H), 2.1 (s, 3 H, CH₃). ¹³C NMR (50 MHz, CDCl₃): d_c = 174.8, 158.4, 156.9, 85.2, 65.8, 62.1 45.7, 26.9. Anal. Calcd for C₈H₁₃NO₃: C, 56.13; H, 7.65; N, 8.18. Found: C, 56.00; H, 7.70; N, 8.30.
Compound 11: mp 92-94 °C IR (KBr): n_max = 3182, 3072, 2900, 1666, 1637, 1245, 1019, 955 cm^-1. ¹H NMR (200 MHz, CDCl₃): d_H = 9.9 (br, 1 H, NH), 7.25-7.00 (m, 4 H, Ar), 4.42 (t, J = 8 Hz, 2 H, OCH₂), 3.03 (t, J = 8.1 Hz, 2 H, =C-CH₂-), 2.45 (s, 3 H, CH₃), 2.08 (s, 3 H, CH₃). ¹³C NMR (50 MHz, CDCl₃): d_c = 174.4, 154.5, 147.8, 136.8, 135.2, 130.1, 124.9, 88.9, 65.8, 26.9, 21.3. Anal. Calcd for C₁₃H₁₅NO₂: C, 71.86; H, 6.95; N, 6.45. Found: C, 71.60; H, 7.00; N, 6.70.
Compound 13: mp 105-107 °C; IR (KBr): n_max = 3288, 2895, 1679, 1618, 1440, 1017, 760, 740, 696 cm^-1. ¹H NMR (200 MHz, CDCl₃): d_H = 8.72 (s, 1 H, NH), 7.42-7.20 (m, 5 H, Ph), 4.46 (d, J = 3.9 Hz, 2 H, CH₂N), 4.32 (t, J = 4.7 Hz, 2 H, OCH₂), 2.85 (t, J = 4.8 Hz, 2 H, CH₂C=), 1.95 (s, 3 H, CH₃). ¹³C NMR (50 MHz, CDCl₃): d_c = 174.6, 168.0, 157.4, 139.3, 129.2, 127.8, 127.0, 86.5, 65.6, 53.6, 47.1, 26.9, 16.8. Anal. Calcd for C₁₃H₁₅NO₂: C, 71.90; H, 7.00; N, 6.50. Found: C, 71.60; H, 7.00; N, 6.70.
Compound 20: mp 177-179 °C. IR (KBr): n_max = 3360, 3120, 1525, 1512, 1080, 800, 748, 705 cm^-1. ¹H NMR (200 MHz, CDCl₃): d_H = 11.6 (s, 2 H, NH), 8.17-7.1 (m, 10 H, Ph), 5.70 (s, 2 H, =CH-), 3.82-3.30 (m, 4 H, -CH₂), 2.10 (s, 6 H, CH₃). ¹³C NMR (50 MHz, CDCl₃): d_c = 188.7, 165.4, 140.5, 131.1, 128.7, 127.4, 93.4, 44.2, 19.7. Anal. Calcd for C₂₂H₂₄N₂O₂: C, 75.83; H, 6.94; N, 9.16. Found: C, 75.44; H, 6.80; N, 8.40.