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.

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

References and Notes

<A NAME="RD28907ST-1">1</A> Collard-Motte J. Janousek Z. Top. Curr. Chem.  1986,  130:  89 

<A NAME="RD28907ST-2">2</A> Ficini J. Tetrahedron  1976,  32:  1449 

<A NAME="RD28907ST-3">3</A> Viehe HG. In Chemistry of Acetylenes   Viehe HG. Mercel Dekker; New York: 1968.  Chap. 12. p.861-912  

<A NAME="RD28907ST-4">4</A> Katrizky AR. Jiang R. Singh SK. Heterocycles  2004,  63:  1455 

<A NAME="RD28907ST-5">5</A> Viehe HG. Angew. Chem., Int. Ed. Engl.  1967,  6:  767 

<A NAME="RD28907ST-6A">6a</A> Furber M. In Comprehensive Organic Functional Group Transformations   Vol. 1:  Katritzky AR. Meth-Cohn O. Rees CW. Pergamon; Oxford: 1995.  p.997 

<A NAME="RD28907ST-6B">6b</A> Ficini J. Tetrahedron  1967,  32:  1449 

<A NAME="RD28907ST-6C">6c</A> Zificask CA. Mulder JA. Hsung RP. Rameshkumar C. Wei L. Tetrahedron  2001,  57:  7575 

<A NAME="RD28907ST-6D">6d</A> Tanaka K. Takeishi K. Synthesis  2007,  2920 

<A NAME="RD28907ST-7">7</A> Mantani T. Ishihara T. Konno T. Yamanaka H.
J. Fluorine Chem.  2001,  108:  229 

<A NAME="RD28907ST-8A">8a</A> Yavari I. Sabbaghan M. Hossaini Z. Synlett  2006,  2501 

<A NAME="RD28907ST-8B">8b</A> Yavari I. Djahaniani H. Tetrahedron Lett.  2006,  47:  2953 

<A NAME="RD28907ST-8C">8c</A> Yavari I. Moradi L. Tetrahedron Lett.  2006,  47:  1627 

<A NAME="RD28907ST-8D">8d</A> Yavari I. Hossaini Z. Sabbaghan M. Tetrahedron Lett.  2006,  47:  6037 

<A NAME="RD28907ST-8E">8e</A> Yavari I. Djahaniani H. Tetrahedron Lett.  2005,  46:  7491 

<A NAME="RD28907ST-9">9</A>

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.

<A NAME="RD28907ST-10">10</A> Scriven EFV. Org. Synth., Coll. Vol. III   Wiley; New York: 1955.  p.735 

<A NAME="RD28907ST-11A">11a</A> Lee CC. Leung MK. Lee GH. Liu YH. Peng SM. J. Org. Chem.  2006,  71:  8417 

<A NAME="RD28907ST-11B">11b</A> Zhang L. J. Am. Chem. Soc.  2005,  127:  16804 

<A NAME="RD28907ST-12A">12a</A> Murakami M. Miyamoto Y. Ito Y. J. Am. Chem. Soc.  2001,  123:  6441 

<A NAME="RD28907ST-12B">12b</A> Grieco PA. Takigawa T. Schillinger WJ. J. Org. Chem.  1980,  45:  2247 

<A NAME="RD28907ST-13">13</A> Padwa A. Flick AC. Lee HI. Org. Lett.  2005,  7:  2925