Four-Component One-Pot Synthesis of Functionalized Ynamines from Reaction of Benzoyl Chlorides, Secondary Amines, Acetylenic Esters and Ammonium Thiocyanate

Abstract

An efficient one-pot synthesis of functionalized ynamines is described. This involves the four-component reaction of ammonium thiocyanate, benzoyl chlorides, and secondary amines in the presence of dialkyl acetylenedicarboxylates.

Key words

four-component reaction - ynamine - benzoyl chloride - activated acetylenes - ammonium thiocyanate - secondary amines

References and Notes

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9

Methyl 2-(Benzoylimino)-4-pipiridino-3-butynoate (5a): To a stirred solution of ammonium thiocyanate (0.15 g, 2 mmol) in acetone (15 mL) was added benzoyl chloride (0.28 g, 2 mmol), and the mixture was refluxed for 5 min. Then, a solution of piperidine (0.17 g, 2 mmol) in acetone (10 mL) was added at a rate that the solution boiled gently. After 30 min, dimethyl acetylenedicarboxylate (0.28 g, 2 mmol) was added slowly and the reaction mixture was refluxed for 3 h. The white precipitate (ammonium chloride) was separated by filtration. The solvent was removed under reduced pressure, and the residue was purified by column chromatography (SiO₂; hexane-EtOAc) to afford 5a as colorless crystals; yield: 0.39 g (65%); mp 101-103 °C. IR (KBr): 1702, 1521, 1244 cm^-1. ¹H NMR: δ = 1.72-1.74 (m, 6 H, 3 × CH₂), 3.60-3.62 (m, 4 H, 2 × CH₂), 3.76 (s, 3 H, OMe), 7.39-7.45 (m, 3 H, 3 × CH), 7.76 (dd, ³ J = 9.5 Hz, ⁴ J = 2.4 Hz, 2 H, 2 × CH). ¹³C NMR: δ = 23.9 (CH₂), 25.1 (2 × CH₂), 49.2 (2 × CH₂), 51.5 (OMe), 59.5 (C), 109.1 (C), 127.5 (2 × CH), 128.9 (CH), 129.8 (2 × CH), 134.8 (C), 160.2 (C=N), 162.4, 170.8 (2 × C=O). EI-MS: m/z = 298 (4) [M⁺], 137 (85), 105 (30), 97 (40), 69 (45), 57 (100). Anal. Calcd for C₁₇H₁₈N₂O₃ (298.34): C, 68.44; H, 6.08; N, 9.39. Found: C, 68.50; H, 6.10; N, 9.42. Compound 5b: yellow powder; yield: 0.34 g (55%); mp 98-100 °C. IR (KBr): 1702, 1521, 1244 cm^-1. ¹H NMR: δ = 1.25 (t, ³ J = 8.8, 3 H, 3 × CH), 1.69-1.71 (m, 6 H, 3 × CH₂), 3.59-3.61 (m, 4 H, 2 × CH₂), 4.24 (q, ³ J = 8.8 Hz, 2 H, 2 × CH), 7.36-7.42 (m, 3 H, 3 × CH), 7.74 (dd, ³ J = 9.4 Hz, ⁴ J = 2.1 Hz, 2 H, 2 × CH). ¹³C NMR: δ = 14.2 (Me), 22.9 (CH₂), 25.1 (2 × CH₂), 49.2 (2 × CH₂), 63.2 (OCH₂), 68.1, 109.7 (2 × C), 127.4 (2 × CH), 128.8 (CH), 129.8 (2 × CH), 134.8 (C), 161.9 (C=N), 167.7, 170.7 (2 × C=O). All other novel compounds isolated possessed spectroscopic and analytical data in accordance with their proposed structures.