Highly Efficient One-Pot Synthesis of Novel Propargylamine-Based Sulfonamides by an A³-Coupling Reaction

Abstract

Novel propargylamine-based sulfonamides were synthesized in excellent yields by the copper(I) iodide catalyzed three-component coupling of propargylsulfonamides, morpholine, and aldehydes.

Key words

propargylsulfonamides - multicomponent reaction - coupling - copper catalysis

• References and Notes

• 1 Akritopoulou-Zanze I, Hajduk PJ. Drug Discovery Today 2009; 14: 291
• 2 Chakraborty TK, Ghosh S, Jayaprakash S. Curr. Med. Chem. 2002; 9: 421
• 3 Belluti F, Fontana G, Dal Bo L, Carenini N, Giommarelli C, Zunino F. Bioorg. Med. Chem. 2010; 18: 3543
• 4 Schneider G, Fechner U. Nat. Rev. Drug Discovery 2005; 4: 649
• 5 León R, Garcia AG, Marco-Contelles J. Med. Res. Rev. 2013; 33: 139
• 6 Bolea I, Gella A, Unzeta M. J. Neural Transm. 2013; 120: 893
• 7 Zheng H, Fridkin M, Youdim MB. Neurochem. Res. 2010; 35: 2117
• 8 McCormack PL. CNS Drugs 2014; 28: 1083
• 9 Koepp MJ, Patsalos PN, Sander JW. Epilepsy Res. 2002; 50: 277
• 10 Shen C.-H, Wang Y.-F, Kovalevsky AY, Harrison RW, Weber IT. FEBS J. 2010; 277: 3699
• 11 Wonnenberg B, Tschernig T, Voss M, Bischoff M, Meier C, Schirmer SH, Langer F, Bals R, Beisswenger C. Int. J. Med. Microbiol. 2014; 304: 725
• 12 Johnson BK, Colvin CJ, Needle DB, Mba Medie F, Champion PA. D, Abramovitch RB. Antimicrob. Agents Chemother. 2015; 59: 4436
• 13 Smith SW, Fu GC. Angew. Chem. 2008; 120: 9474
• 14 Hattori G, Sakata K, Matsuzawa H, Tanabe Y, Miyake Y, Nishibayashi Y. J. Am. Chem. Soc. 2010; 132: 10592
• 15 Miyake Y, Uemura S, Nishibayashi Y. ChemCatChem 2009; 1: 342
• 16 Olivi N, Spruyt P, Peyrat J.-F, Alami M, Brion J.-D. Tetrahedron Lett. 2004; 45: 2607
• 17 Koradin C, Polborn K, Knochel P. Angew. Chem. Int. Ed. 2002; 41: 2535
• 18 Koradin C, Gommermann N, Polborn K, Knochel P. Chem. Eur. J. 2003; 9: 2797
• 19 Periasamy M, Obula Reddy P, Satyanarayana I, Mohan L, Edukondalu A. J. Org. Chem. 2016; 81: 987
• 20 Zani L, Bolm C. Chem. Commun. 2006; 4263
• 21 Li Z, Jiang Z, Su W. Green Chem. 2015; 17: 2330
• 22 Price GA, Brisdon AK, Flower KR, Pritchard RG, Quayle P. Tetrahedron Lett. 2014; 55: 151
• 23 Nemati F, Elhampour A, Farrokhi H, Natanzi MB. Catal. Commun. 2015; 66: 15
• 24 Afraj SN, Chen C, Lee G.-H. RSC Adv. 2014; 4: 26301
• 25 Berrichi A, Bachir R, Benabdallah M, Choukchou-Braham N. Tetrahedron Lett. 2015; 56: 1302
• 26 Peshkov VA, Pereshivko OP, Van der Eycken EV. Chem. Soc. Rev. 2012; 41: 3790
• 27 N-Benzyl-N-(4-aryl-4-morpholin-4-ylbut-2-yn-1-yl)-4-toluenesulfonamides (8a–g); General Procedure Morpholine (7; 1 mmol), the appropriate aldehyde 6 (1 mmol), and the appropriate N-propargylsulfonamide 5 (1 mmol) were added to a suspension of CuI (0.1 mmol) and K₂CO₃ (0.1 mmol) in toluene (4.0 mL), and the mixture was stirred at 110 °C for 48 h. When the reaction was complete (TLC), the product was purified by column chromatography [silica gel, hexane–EtOAc (4:1)]. N-Benzyl-N-(4-morpholin-4-yl-4-phenylbut-2-yn-1-yl)-4-toluenesulfonamide (8a) Yellow oil; yield: 412 mg (87%). ¹H NMR (400 MHz, CDCl₃): δ = 2.35–2.40 (m, 7 H), 3.68–3.72 (m, 4 H), 4.14–4.20 (ABdd, J = 18.6, 2.0 Hz, 2 H), 4.41 (br s, 1 H), 4.43 (ABd, J = 14.0 Hz, 1 H), 4.48 (ABd, J = 14.0 Hz, 1 H), 7.24 (d, J = 8.0 Hz, 2 H), 7.34–7.40 (m, 10 H), 7.84 (d, J = 6.6 Hz, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = 21.55, 35.95, 49.69, 50.02, 61.44, 66.90, 80.75, 81.53, 127.78, 127.94, 128.17, 128.23, 128.37, 128.38, 128.73, 128.76, 129.67, 134.99, 136.25, 143.50. N-Benzyl-N-[4-morpholin-4-yl-4-(4-tolyl)but-2-yn-1-yl]-4-toluenesulfonamide (8b) Yellow oil; yield: 405 mg (83%). ¹H NMR (400 MHz, CDCl₃): δ = 2.33–2.36 (m, 7 H), 2.39 (s, 3 H), 3.68–3.76 (m, 4 H), 4.13–4.19 (ABdd, J = 18.8, 2.0 Hz, 2 H), 4.28–4.35 (br s, 1 H), 4.41 (ABd, J = 14.0 Hz, 1 H), 4.47 (ABd, J = 14.0 Hz, 1 H), 7.15 (d, J = 8.0 Hz, 2 H), 7.21–7.26 (m, 4 H), 7.33–7.40 (m, 5 H), 7.83 (d, J = 8.4 Hz, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = 21.17, 21.55, 35.97, 49.69, 50.00, 61.20, 66.93, 80.44, 81.85, 127.78, 128.16, 128.30, 128.31, 128.75, 128.91, 129.68, 134.15, 135.02, 136.28, 137.63, 143.47.