[Pyridine–SO₃H]ZnCl₃: A Multipurpose Catalyst for A³ Coupling Synthesis of Propargylamines under Mild Conditions

Abstract

N-Sulfopyridin-1-ium monozinc(II) trichloride ([NSPy]ZnCl₃) was prepared and used as a multipurpose catalyst for the synthesis of propargylamines by the A³ coupling reaction of aromatic aldehydes, alkynes, and secondary amines under mild conditions. In this reaction, the carbonyl group in the aldehyde was activated by the acidic part in the catalyst, and the C–H activation of phenylacetylene was carried out by zinc.

Key words

A³ coupling reaction - C–H bond activation - propargylamines - ionic liquid catalysis - amines - multicomponent reaction

Publication History

Received: 07 June 2023

Accepted after revision: 08 September 2023

Article published online:
25 October 2023

• References and Notes

• 1 Zare A, Moosavi-Zare AR, Hasaninejad A, Parhami A, Khalafi-Nezhad A, Beyzavi MH. Synth. Commun. 2009; 39: 3156
• 2 Zolfigol MA, Khazaei A, Moosavi-Zare AR, Zare A, Khakyzadeh V. Appl. Catal., A 2011; 400: 70
• 3 Moosavi-Zare AR, Zolfigol MA, Daraei M. Synlett 2014; 25: 1173
• 4 Moosavi-Zare AR, Afshar-Hezarkhani H. Org. Prep. Proced. Int. 2020; 52: 410
• 5 Zolfigol MA, Khazaei A, Moosavi-Zare AR, Zare A, Kruger HG, Asgari Z, Khakyzadeh V, Kazem-Rostami M. J. Org. Chem. 2012; 77: 3640
• 6 Khazaei A, Zolfigol MA, Moosavi-Zare AR, Afsar J, Zare A, Khakyzadeh V, Beyzavi MH. Chin. J. Catal. 2013; 34: 1936
• 7 Moosavi-Zare AR, Zolfigol MA, Zarei M, Zare A, Khakyzadeh V, Hasaninejad A. Appl. Catal., A 2013; 467: 61
• 8 Moosavi-Zare AR, Asgari Z, Zare A, Zoligol MA. Sci. Iran., Trans. C 2015; 22: 2254
• 9 Zolfigol MA, Moosavi-Zare AR, Zarei M. C. R. Chim. 2014; 17: 1264
• 10 Moosavi-Zare AR, Zolfigol MA, Rezanejad Z. Chem. Methodol. 2020; 4: 614
• 11 Sajjadifar S, Mansouri G, Nikseresht A, Kakaei Azani F. J. Sulfur Chem. 2018; 39: 294
• 12 Mohammadi S, Abbasi M. Res. Chem. Intermed. 2015; 41: 8877
• 13 Moosavi-Zare AR, Zolfigol MA, Zarei M, Noroozizadeh E, Beyzavi MH. RSC Adv. 2016; 6: 89572
• 14 Kassaee MZ, Bekhradnia AR. Phosphorus, Sulfur Silicon Relat. Elem. 2004; 179: 2025
• 15 Kauffman GS, Harris GD, Dorow RL, Stone BR. P, Parsons RL, Pesti JA, Magnus NA, Fortunak JM, Confalone PN, Nugent WA. Org. Lett. 2000; 2: 3119
• 16 Wright JL, Gregory TF, Kesten SR, Boxer PA, Serpa KA, Meltzer LT, Wise LD, Espitia SA, Konkoy CS, Whittemore ER, Woodward RM. J. Med. Chem. 2000; 43: 3408
• 17 Boulton AA, Davis BA, Durden DA, Dyck LE, Juorio AV, Li X.-M, Paterson IA, Yu PH. Drug Dev. Res. 1997; 42: 150
• 18 Swithenbank C, McNulty PJ, Viste KL. J. Agric. Food Chem. 1971; 19: 417
• 19 Kochman A, Skolimowski J, Gêbicka L, Metodiewa D. Pol. J Pharmacol. Pharm. 2003; 55: 389
• 20 Hoepping A, Johnson KM, George C, Flippen-Anderson J, Kozikowski AP. J. Med. Chem. 2000; 43: 2064
• 21 Park SB, Alper H. Chem. Commun. 2005; 1315
• 22 Baghernejad B, Taromsari SM. H. Asian J. Green Chem. 2022; 6: 194
• 23 Baghernejad B, Harzevili MR. Chem. Methodol. 2021; 5: 90
• 24 Abedini E, Shaterian HR. Eurasian Chem. Commun. 2023; 5: 228
• 25 Salih AR, Al-Messri ZA. K. Eurasian Chem. Commun. 2021; 3: 533
• 26 Nemati F, Elhampour A, Farrokhi H, Natanzi MB. Catal. Commun. 2015; 66: 15
• 27 Sakaguchi S, Kubo T, Ishii Y. Angew. Chem. Int. Ed. 2001; 13: 2534
• 28 Namitharan K, Pitchumani K. Eur. J. Org. Chem. 2010; 411
• 29 Zeng T, Chen W.-W, Cirtiu CM, Moores A, Song G, Li C.-J. Green. Chem. 2010; 12: 570
• 30 Wei C, Li Z, Li C.-J. Org. Lett. 2003; 5: 4473
• 31 Wei C, Li C.-J. J. Am. Chem. Soc. 2003; 125: 9584
• 32 Li C.-J, Wei C. Chem. Commun. 2002; 268
• 33 Traverse JF, Hoveyda AH, Snapper ML. Org. Lett. 2003; 5: 3273
• 34 Ramu E, Varal R, Sreelatha N, Adapa SR. Tetrahedron Lett. 2007; 48: 7184
• 35 Sotoudehnia Z, Albadi J, Momeni AR. Appl. Organomet. Chem. 2018; e4625
• 36 Tzouras NV, Neofotistos SP, Vougioukalakis GC. ACS Omega 2019; 4: 10279
• 37 Sarode PB, Bahekar SP, Chandak HS. Synlett. 2016; 27: 2209
• 38 Layek S, Agrahari B, Kumari S, Anuradha Anuradha, Pathak DD. Catal. Lett. 2018; 148: 2675
• 39 Jiang B, Si Y.-G. Tetrahedron Lett. 2003; 44: 6767
• 40 Jiang B, Si Y.-G. Angew. Chem. Int. Ed. 2004; 43: 216
• 41 Lee KY, Lee CG, Na JE, Kim JN. Tetrahedron Lett. 2005; 46: 69
• 42 Pinet S, Pandya SU, Chavant PY, Ayling A, Vallee Y. Org. Lett. 2002; 4: 1463
• 43 Procedure for the preparation of [Pyridine–SO₃H]Cl. A solution of pyridine (0.395 g, 5 mmol) in CH₂Cl₂ (40 mL) was added dropwise to a stirring solution of chlorosulfonic acid (0.58 g, 5 mmol) in dry CH₂Cl₂ (40 mL) over a period of 10 min at 0 °C. After the addition was completed, the reaction mixture was stirred for 20 min, stand for 5 min, and the CH₂Cl₂ was decanted. Afterward, the liquid residue was triturated with CH₂Cl₂ (3×10 mL) and dried under powerful vacuum at 90 °C to give [Pyridine–SO₃H]Cl as a viscous colorless oil in 95 % yield (0.929 g) [7].
• 44 Procedure for the preparation of [NSPy]ZnCl₃ . To a round-bottomed flask (50 mL) containing [Pyridine–SO₃H]Cl (0.975 g, 5 mmol), Zinc chloride (0.682 g, 5 mmol) was added over a period of 10 minutes at 85 °C and then stirred for 2 hours at 80 °C to give [NSPy]ZnCl₃.
• 45 Propargylamines 1–9; General ProcedureA round-bottomed flask (25 mL) equipped with a reflux condenser was charged with CHCl₃ (10 mL). The appropriate aromatic aldehyde (1 mmol), phenylacetylene (1 mmol), amine (1 mmol), and [NSPy]ZnCl₃ (15 mol%) were added, and the mixture was stirred for the appropriate time at r.t. When the reaction was complete (TLC), the solvent was removed, and the product was purified by plate chromatography.4-[1-(4-Chlorophenyl)-3-phenylprop-2-yn-1-yl]morpholine (1)Pale yellow oil; yield: 92%. ¹H NMR (250 MHz, CDCl₃): δ = 2.61 (t, J = 6.8 Hz, 4 H), 3.72 (t, J = 6.8 Hz, 4 H), 4.77 (s, 1 H), 7.34 (d, J = 4.75 Hz, 5 H), 7.50 (s, 1 H), 7.58 (d, J = 7.75 Hz, 3 H). ¹³C NMR (62.5 MHz, CDCl₃): δ = 49.7, 61.3, 67.0, 84.3, 88.8, 122.6, 128.3, 129.8, 131.7, 133.5, 136.4.4-[1-(3-Nitrophenyl)-3-phenylprop-2-yn-1-yl]morpholine (2)Pale yellow oil; yield: 91%. ¹H NMR (250 MHz, DMSO-d ₆): δ = 2.46 (s, 2 H), 2.58 (d, J = 10.50 Hz, 2 H), 3.58 (s, 4 H), 5.15 (s, 1 H), 7.40 (s, 3 H), 7.51 (s, 2 H), 7.68 (t, J = 8.00 Hz, 1 H), 8.00 (d, J = 7.50 Hz, 1 H), 8.16 (d, J = 8.00 Hz, 1 H), 8.36 (s, 1 H). ¹³C NMR (62.5 MHz, DMSO-d ₆): δ = 49.7, 60.4, 66.6, 84.5, 89.2, 122.2, 123.1, 123.2, 129.1, 129.3, 130.3, 132.0, 135.2, 140.5, 148.2. 4-[1-(2,5-Dimethoxyphenyl)-3-phenylprop-2-yn-1-yl]morpholine (5)Pale yellow oil; yield: 84%. ¹H NMR (250 MHz, DMSO-d ₆): δ = 2.52 (t, J = 4.50 Hz, 4 H), 3.39–3.53 (m, 4 H), 3.68 (s, 3 H), 3.74 (s, 3 H), 5.00 (s, 1 H), 6.86 (d, J = 8.75 Hz, 1 H), 6.95 (d, J = 8.75 Hz, 1 H), 7.08 (s, 1 H), 7.34 (s, 3 H), 7.43 (s, 2 H). ¹³C NMR (62.5 MHz, DMSO-d ₆): δ = 50.3, 55.0, 55.7, 56.9, 66.6, 86.6, 87.0, 113.4, 113.6, 116.1, 122.7, 127.1, 129.0, 131.8, 151.5, 153.3.