Ceric Ammonium Nitrate Catalyzed aza-Michael Addition of Aliphatic Amines to α,β-Unsaturated Carbonyl Compounds and Nitriles in Water [1]

Abstract

Ceric ammonium nitrate (3 mol%) efficiently catalyzes the aza-Michael reaction of amines with α,β-unsaturated carbonyl compounds in water to produce the corresponding β-amino carbonyl compounds in good to excellent yields (55-99%) for most of the compounds under mild conditions. The reaction is procedurally simple and displays limited chemoselectivity, as aromatic amines were found to be unreactive.

Key words

ceric ammonium nitrate - aza-Michael reaction - aliphatic amines - α,β-unsaturated carbonyl compounds

1

IICT Communication number: 050617.

References and Notes

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1

IICT Communication number: 050617.

12

Representative Procedure.
A mixture of amine (1.2 mmol), α,β-unsaturated compound (1 mmol) and CAN (0.017 g, 3 mol%) in H₂O (2 mL) was stirred at r.t. for the time specified in Table [2] and Table [3] . After the reaction was over, the reaction mixture was filtered, and extracted with Et₂O (3 × 10 mL). The combined organic layers were dried over Na₂SO₄, concentrated in vacuo and purified by column chromatography on silica gel with EtOAc and n-hexane (1:4) as eluent to afford the corresponding β-amino product in pure form. The products were characterized by comparison of their NMR and mass spectra with those of authentic samples. All new compounds gave satisfactory spectral data in accordance to their proposed structures.
Spectral Data for Selected Compounds.
3-(4-Phenylpiperazin-1-yl) Propanenitrile (Table 2, Entry 2).
Yellow needles; mp 72-74 °C. ¹H NMR (300 MHz, CDCl₃): δ = 7.30-7.22 (m, 2 H), 6.96-6.83 (m, 3 H), 3.21 (t, J = 4.5 Hz, 4 H), 2.77 (t, J = 6.0 Hz, 2 H), 2.65 (t, J = 6.0 Hz, 4 H), 2.55 (t, J = 7.5 Hz, 2 H) ppm. MS: m/z = 216 [M + 1].
3-(4-Methylpiperazin-1-yl) Propanenitrile (Table 2, Entry 3).
Brown oil. ¹H NMR (300 MHz, CDCl₃): δ = 2.69 (t, J = 6.0 Hz, 2 H), 2.55-2.49 (m, 10 H), 2.30 (s, 3 H) ppm. MS: m/z = 154 [M + 1].
3-(4-Benzylpiperazin-1-yl) Propanenitrile (Table 2, Entry 4). Brown oil. ¹H NMR (300 MHz, CDCl₃): δ = 7.31-7.25 (m, 5 H), 3.63 (s, 2 H), 2.68 (t, J = 7.5 Hz, 2 H), 2.60-2.43 (m, 10 H) ppm. MS: m/z = 230 [M + 1].
3-[4-(2-Cyanoethyl)piperazin-1-yl] Propanenitrile (Table 2, Entry 6).
Light brown oil. ¹H NMR (300 MHz, CDCl₃): δ = 2.68 (t, J = 6.0 Hz, 4 H), 2.56-2.47 (m, 12 H) ppm. MS: m/z = 193 [M + 1].
Methyl 3-Tetrahydro-1 H -1-pyrrolylpropanoate (Table 3, Entry 2).
Oil. ¹H NMR (300 MHz, CDCl₃): δ = 3.67 (s, 3 H), 2.86 (t, J = 7.0 Hz, 2 H), 2.34 (m, 6 H), 1.17 (m, 4 H) ppm. MS: m/z = 158 [M + 1].
Methyl 3-Piperidinylpropionate (Table 3, Entry 4b).
Oil. ¹H NMR (300 MHz, CDCl₃): δ = 3.62 (s, 3 H), 2.61 (t, J = 8.0 Hz, 2 H), 2.47 (t, J = 7.9 Hz, 2 H), 2.34 (m, 4 H), 1.55-1.36 (m, 6 H) ppm. MS: m/z = 193 [M + 1].
Methyl 3-(Dibenzylamine) Propanoate (Table 3, Entry 8).
Solid. ¹H NMR (300 MHz, CDCl₃): δ = 7.42-7.26 (m, 10 H), 3.65 (s, 3 H), 3.60 (s, 4 H), 2.84 (t, J = 7.3 Hz, 2 H), 2.47 (t, J = 7.3 Hz, 2 H) ppm. MS: m/z = 283 [M⁺].