Base-Promoted Three-Component One-Pot Synthesis of 3- (Thiomethyl)indoles with Paraformaldehyde under Aqueous Conditions

Abstract

An ethylenediamine-promoted three-component synthesis of 3-(thiomethyl)indoles from indoles, thiophenols, and paraformaldehyde has been developed. Water is used as the green solvent in a simple and environmentally friendly procedure. Stable and low-toxicity paraformaldehyde is used as a carbon source.

Key words

metal-free - aqueous conditions - paraformaldehyde - multicomponent reaction - thiomethylation - thiomethylindoles

• References and Notes

• 1a Sundberg RJ. The Chemistry of Indoles . Academic Press; London: 1970
• 1b Indoles, Part Four: The Monoterpenoid Indole Alkaloids . Saxton JE. Wiley-Interscience; Hoboken: 1983
• 1c Lounasmaa M. Tolvanen A. Nat. Prod. Rep. 2000; 17: 175
• 1d Faulkner DJ. Nat. Prod. Rep. 1999; 16: 155

For selected recent examples, see:
• 2a Mizoguchi H. Oguri H. Tsuge K. Oikawa H. Org. Lett. 2009; 11: 3016
• 2b Ueda H. Satoh H. Matsumoto K. Sugimoto K. Fukuyama T. Tokuyama H. Angew. Chem. Int. Ed. 2009; 48: 7600
• 2c Jiang B. Yang C.-G. Wang J. J. Org. Chem. 2001; 66: 4865
• 2d Safe S. Papineni S. Chintharlapalli S. Cancer Lett. 2008; 269: 326
• 2e Lee S.-O. Abdelrahim M. Yoon K. Chintharlapalli S. Papineni S. Kim K. Wang H. Safe S. Cancer Res. 2010; 70: 6824
• 2f Queiroz MM. F. Queiroz EF. Zeraik ML. Ebrahimi SN. Marcourt L. Cuendet MI. Castro-Gamboa I. Hamburger M. da Silva Bolzani V. Wolfender J.-L. J. Nat. Prod. 2014; 77: 650

For selected recent examples, see:
• 3a Kagawa N. Malerich JP. Rawai VH. Org. Lett. 2008; 10: 2381
• 3b Shaikh RR. Mazzanti A. Petrini M. Bartoli G. Melchiorre P. Angew. Chem. Int. Ed. 2008; 47: 8707
• 4a Khorshidi A. Shariati S. RSC Adv. 2014; 4: 41469
• 4b Dar AA. Ali S. Khan AT. Tetrahedron Lett. 2014; 55: 486
• 4c Parnes R. Pappo D. Org. Lett. 2015; 17: 2924
• 4d Coker JN. J. Org. Chem. 1962; 27: 1881
• 5a Han X. Wu J. Org. Lett. 2010; 12: 5780
• 5b Suárez A. Martínez F. Sanz R. Org. Biomol. Chem. 2016; 14: 11212
• 5c Wen H. Wang L. Xu L. Hao Z. Shao C.-L. Wang C.-Y. Xiao J. Adv. Synth. Catal. 2015; 357: 4023
• 5d Xiao J. Wen H. Wang L. Xu L. Hao Z. Shao C.-L. Wang C.-Y. Green Chem. 2016; 18: 1032
• 6 For a review, see: Li W. Wu X.-F. Adv. Synth. Catal. 2015; 357: 3393
• 7 Taylor RT. O’Sullivan TJ. In e-EROS: Encyclopedia of Reagents for Organic Synthesis . Wiley-Interscience; Chichester: 2008. ; DOI: 10.1002/047084289X.rp018.pub2
• 8a Li M. He C. Chen F. Gu Y. Adv. Synth. Catal. 2010; 352: 519
• 8b Park K. Heo Y. Lee S. Org. Lett. 2013; 15: 3322
• 8c Ohta Y. Kubota Y. Watabe T. Chiba H. Oishi S. Fujii N. Ohno H. J. Org. Chem. 2009; 74: 6299
• 8d Ohta Y. Chiba H. Oishi S. Fujii N. Ohno H. J. Org. Chem. 2009; 74: 7052
• 8e Natte K. Li W. Zhou S. Neumann H. Wu X.-F. Tetrahedron Lett. 2015; 56: 1118
• 8f Man NY. T. Li W. Stewart SG. Wu X.-F. Chimia 2015; 69: 345
• 9a Garcia JM. Jones GO. Virwani K. Science 2014; 344: 732
• 9b Natte K. Dumrath A. Neumann H. Beller M. Angew. Chem. Int. Ed. 2014; 53: 10090
• 9c Li W. Wu X.-F. J. Org. Chem. 2014; 79: 10410
• 10a Ngai M.-Y. Skucas E. Krische MJ. Org. Lett. 2008; 10: 2705
• 10b Okachi T. Fujimoto K. Onaka M. Org. Lett. 2002; 4: 1667
• 10c Köpfer K. Sam B. Breit B. Krische MJ. Chem. Sci. 2013; 4: 1876
• 10d Li W. Wu X.-F. Eur. J. Org. Chem. 2015; 331
• 11 Wang H. Cai J. Huang H. Deng G.-J. Org. Lett. 2014; 16: 5324
• 12 Cheng XF. Peng Y. Wu J. Deng G.-J. Org. Biomol. Chem. 2016; 14: 2819
• 13 Cheng X. Wang H. Xiao F. Deng G.-J. Green Chem. 2016; 18: 5773
• 14a Xiao F. Chen S. Tian J. Huang H. Liu Y. Deng G.-J. Green Chem. 2016; 18: 1538
• 14b Xiao F. Chen S. Li C. Huang H. Deng G.-J. Adv. Synth. Catal. 2016; 358: 3881
• 14c Xiao F. Tian J. Xing Q. Huang H. Deng G.-J. Liu Y. ChemistrySelect 2017; 2: 428
• 15a Zhang X. Li X. Allan GF. Musto A. Lundeen SG. Sui Z. Bioorg. Med. Chem. Lett. 2006; 16: 3233
• 15b Kang N. Lee J.-M. Jeon A. Oh HB. Moon B. Tetrahedron 2016; 72: 5612
• 16 1-Methyl-3-{[(4-tolyl)thio]methyl}-1H-indole (3aa); Typical Procedure A 10 mL oven-dried reaction vessel was charged with 1-methyl-1H-indole (1a, 50 μL, 0.4 mmol), paraformaldehyde (24 mg, 0.8 mmol), 4-methylbenzenethiol (2a, 24.8 mg, 0.2 mmol). The vessel was sealed, and ethane-1,2-diamine (6.5 μL, 0.1 mmol) and H₂O (0.5 mL) were added from a syringe. The resulting solution was stirred at 130 °C for 4 h. The volatiles were removed under vacuum, and the residue was purified by column chromatography [silica gel, PE–EtOAc ( 100:1)] to give a brown liquid; yield: 41.7 mg (78%). ¹H NMR (400 MHz, CDCl₃): δ = 7.67 (d, J = 7.9 Hz, 1 H), 7.28–7.20 (m, 4 H), 7.14–7.10 (m, 1 H), 7.08–7.06 (m, 2 H), 6.91 (s, 1 H), 4.30 (s, 2 H), 3.69 (s, 3 H), 2.30 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 137.0, 136.0, 133.6, 130.0, 129.5, 127.7, 127.2, 121.8, 119.2, 119.1, 110.2, 109.3, 32.66, 30.34, 21.00. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₇H₁₈NS: 268.11545; found: 268.11554.