Three-Component Friedel-Crafts Reaction of Indoles, Glyoxylate, and Amine under Solvent-Free and Catalyst-Free Conditions - Synthesis of (3-Indolyl)glycine Derivatives

Jun-Ling Zhao; Li Liu; Hai-Bo Zhang; Yan-Chao Wu; Dong Wang; Yong-Jun Chen

doi:10.1055/s-2005-922764

Subscribe to RSS

Please copy the URL and add it into your RSS Feed Reader.

https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00000083.xml

Share / Bookmark

Facebook Linkedin Weibo

Download PDF

Synlett 2006(1): 0096-0100
DOI: 10.1055/s-2005-922764

LETTER

Three-Component Friedel-Crafts Reaction of Indoles, Glyoxylate, and Amine under Solvent-Free and Catalyst-Free Conditions - Synthesis of (3-Indolyl)glycine Derivatives

Jun-Ling Zhao^a,b, Li Liu*^a, Hai-Bo Zhang^a,b, Yan-Chao Wu^a,b, Dong Wang*^a, Yong-Jun Chen*^a
^a Center for Molecular Science, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100080, P. R. of China
Fax: +86(10)62554449; e-Mail: yjchen@mail.iccas.ac.cn; e-Mail: dwang210@mail.iccas.ac.cn;
^b Graduate School of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing 100080, P. R. of China

Further Information

Publication History

Received 21 September 2005
Publication Date:
16 December 2005 (online)

Abstract
Full Text
References

Buy Article Permissions and Reprints All articles of this category

Abstract

Solvent-free and catalyst-free three-component reactions of indoles, amines, and ethyl glyoxylate gave alkylation products in good to high yields (61-93%), providing a convenient synthesis of (3-indolyl)glycine derivatives.

Key words

solvent-free - catalyst-free - indole - three-component alkylation - amine

References and Notes

1a Kawasaki T. Ohno K. Enoki H. Umemoto Y. Sakamoto M. Tetrahedron Lett. 2002, 43: 4245

Crossref Search in Google Scholar
1b Kawasaki T. Enoki H. Matsumura K. Ohyama M. Inagawa M. Sakamoto M. Org. Lett. 2000, 2: 3027

Crossref Search in Google Scholar
1c Yang CG. Wang J. Tang XX. Jiang B. Tetrahedron: Asymmetry 2002, 13: 383

Crossref Search in Google Scholar
2 Blaszczak LC, and Turner J. inventors; US Patent, 4492694.
3 Katz AH. Demerson CA. Shaw CC. Asselin AA. Humber LG. Conway KM. Gavin G. Guinosso C. Jensen NP. Mobilio D. Noureldin R. Schmid J. Shah U. Van Engen D. Chau TT. Weichman BM. J. Med. Chem. 1988, 31: 1244

Crossref Search in Google Scholar
4 Jiang B. Huang Z.-G. Synthesis 2005, 2198 ; and references cited therein

Thieme Connect
5a Lei F. Chen Y.-J. Sui Y. Liu L. Wang D. Synlett 2003, 1160

Crossref
5b Chen YJ. Lei F. Liu L. Wang D. Tetrahedron 2003, 59: 7609

Crossref Search in Google Scholar
6a Olah GA. Friedel-Crafts and Related Reactions Vol. III, Part 1: Interscience; New York: 1964.

Thieme Connect Search in Google Scholar
6b Olah GA. Khrisnamurti R. Surya Prakashi GK. Comprehensive Organic Synthesis Vol. 3: Trost BM. Pergamon; New York: 1991. p.293

Thieme Connect Search in Google Scholar
6c For a review on the stereoselective Friedel-Crafts alkylation reaction, see: Bandini M. Melloni A. Umani-Ronchi A. Angew. Chem. Int. Ed. 2004, 43: 550

Thieme Connect Search in Google Scholar
6d Review on alkylation of indoles, see: Bandini M. Melloni A. Tommasi S. Umani-Ronchi A. Synlett 2005, 1199

Thieme Connect
7a Endo A. Yanagisawa A. Abe M. Tohma S. Kan T. Fukuyama T. J. Am. Chem. Soc. 2002, 124: 6552

Crossref Search in Google Scholar
7b Chen YJ. Ge C.-S. Wang D. Synlett 2000, 1429

Crossref
7c Jørgensen KA. Synthesis 2003, 1117

Crossref
7d Shirakawa S. Berger R. Leighton JL. J. Am. Chem. Soc. 2005, 127: 2858

Crossref Search in Google Scholar
8a Dessole G. Herrera RP. Ricci A. Synlett 2004, 2374

Crossref PubMed
8b Török B. Abid M. London G. Esquibel J. Török M. Mhadgut SC. Yan P. Surya Prakash GK. Angew. Chem. Int. Ed. 2005, 44: 3086

Crossref PubMed Search in Google Scholar
9a Tanaka T. Solvent-free Organic Synthesis Wiley-VCH; Weinheim: 2003.

Crossref
9b For a review, see: Cave GWV. Raston CL. Scott JL. Chem. Commun. 2001, 2159

Crossref
10 Anastas PT. Warner JC. Green Chemistry-Theory and Practice Oxford University Press; New York: 1998.
11a Kappe CO. Angew. Chem. Int. Ed. 2004, 43: 6250

Crossref Search in Google Scholar
11b Varma RS. Pure Appl. Chem. 2001, 73: 193

Crossref Search in Google Scholar
11c Gholap AR. Venkatesan K. Daniel T. Green Chem. 2004, 6: 147

Crossref Search in Google Scholar
12 Cimarelli C. Mazzanti A. Palmieri G. Volpini E. J. Org. Chem. 2001, 66: 4759

Crossref Search in Google Scholar

13

4b: colorless oil. IR: 3399, 3051, 2981, 1732, 1602, 1547, 1504, 1239, 1185, 1023 cm^-1. ¹H NMR: δ = 7.88 (d, J = 7.8 Hz, 1 H), 7.37-7.16 (m, 6 H), 6.77 (t, J = 7.3 Hz, 1 H), 6.70 (d, J = 8.6 Hz, 2 H), 5.44 (s, 1 H), 4.35-4.15 (m, 2 H), 3.75 (s, 3 H), 1.27 (t, J = 7.1 Hz, 3 H). ¹³C NMR: δ = 172.7, 146.7, 137.4, 129.3, 127.7, 126.4, 122.1, 119.7, 119.6, 118.1, 113.4, 111.0, 109.6, 61.6, 54.3, 32.9, 14.2. HRMS: m/z calcd for C₁₉H₂₀N₂O₂ (M⁺): 308.1525, found: 308.1521.
4c: colorless oil. IR: 3400, 2958, 2870, 1729, 1602, 1503, 1460, 1306, 1200, 1020 cm^-1. ¹H NMR: δ = 7.97 (s, 1 H), 7.83-7.81 (m, 1 H), 7.26-7.10 (m, 5 H), 6.74 (t, J = 7.2 Hz, 1 H), 6.65 (d, J = 7.8 Hz, 2 H), 5.30 (s, 1 H), 4.32-4.07 (m, 2 H), 2.43 (s, 3 H), 1.20 (t, J = 7.1 Hz, 3 H). ¹³C NMR: δ = 172.5, 146.7, 135.2, 133.4, 129.3, 126.8, 121.4, 119.9, 118.8, 118.0, 113.2, 110.6, 107.5, 61.5, 54.1, 14.2, 12.1. HRMS: m/z calcd for C₁₉H₂₀N₂O₃ (M⁺): 308.1525, found: 308.1528.
4d: light yellow oil. IR: 3407, 2983, 2832, 1729, 1603, 1503, 1487, 1309, 1211, 1024 cm^-1. ¹H NMR: δ = 8.24 (s, 1 H), 7.28-7.12 (m, 5 H), 6.89 (dd, J = 8.8, 2.4 Hz, 1 H), 6.76 (t, J = 7.3 Hz, 1 H), 6.67 (d, J = 7.7 Hz, 2 H), 5.37 (s, 1 H), 4.32-4.17 (m, 2 H), 3.88 (s, 3 H), 1.25 (t, J = 7.1 Hz, 3 H). ¹³C NMR: δ = 172.8, 154.3, 146.7, 131.6, 129.4, 126.2, 123.9, 118.2, 113.5, 112.9, 112.0, 101.1, 61.6, 55.9, 54.4, 21.1, 14.2. HRMS: m/z calcd for C₁₉H₂₀N₂O₃ (M⁺): 324.1474, found: 324.1476.
4e: white solid; mp 123-125 °C. IR: 3409, 3381, 2985, 1710, 1602, 1506, 1455, 1314, 1270, 1021 cm^-1. ¹H NMR: δ = 8.27 (s, 1 H), 7.95 (d, J = 1.8 Hz, 1 H), 7.24 (dd, J = 8.6, 1.8 Hz, 1 H), 7.16-7.04 (m, 4 H), 6.72 (m, 1 H), 6.60 (dd, J = 8.6, 1.0 Hz, 2 H), 5.29 (s, 1 H), 4.26-4.08 (m, 2 H), 1.20 (t, J = 7.1 Hz, 3 H). ¹³C NMR: δ = 172.5, 146.4, 135.2, 129.4, 127.5, 125.4, 124.5, 122.2, 118.4, 115.3, 113.6, 113.3, 113.0, 112.1, 61.9, 54.2, 14.1. HRMS: m/z calcd for C₁₈H₁₇N₂O₂ (M⁺): 372.0473, found: 372.0477.
4f: light yellow oil. IR: 3381, 2982, 2221, 1730, 1604, 1506, 1471, 1230, 1195, 1099 cm^-1. ¹H NMR: δ = 8.65 (s, 1 H), 8.22 (s, 1 H), 7.44-7.43 (m, 2 H), 7.36 (d, J = 2.0 Hz,
1 H),7.16-7.12 (m, 2 H), 6.75 (t, J = 7.3 Hz, 1 H), 6.63 (d, J = 8.1 Hz, 2 H), 5.37 (s, 1 H), 4.30-4.11 (m, 2 H), 1.22 (t, J = 7.1 Hz, 3 H). ¹³C NMR: δ = 171.8, 146.0, 129.3, 125.7, 125.6, 125.5, 125.4, 120.5, 118.6, 113.8, 113.6, 112.4, 103.3, 62.1, 54.1, 14.1. HRMS: m/z calcd for C₁₉H₁₇N₃O₂ (M⁺): 319.1321, found: 319.1326.
4j: white solid; mp 117-119 °C. IR: 3311, 3280, 2978, 2835, 1732, 1565, 1452, 1230, 1196, 1099 cm^-1. ¹H NMR: δ = 8.70 (s, 1 H), 7.82 (d, J = 1.8 Hz, 1 H), 7.35-7.22 (m, 6 H), 7.11-7.07 (m, 2 H), 4.66 (s, 1 H), 4.26-4.11 (m, 2 H), 3.86 (d, J = 13.0 Hz, 1 H), 3.81 (d, J = 13.0 Hz, 1 H), 2.60 (br s, 1 H), 1.23 (t, J = 7.1 Hz, 3 H). ¹³C NMR: δ = 173.2, 139.1, 135.0, 128.6, 128.5, 127.7, 127.4, 125.2, 124.3, 122.1, 113.2, 112.9, 112.5, 61.4, 57.2, 51.7, 14.2. HRMS: m/z calcd for C₁₉H₂₀N₂O₂Br (M + H): 387.0702, found: 387.0708.
4m: light yellow oil. IR: 3409, 2979, 2932, 1729, 1592, 1495, 1450, 1187, 1025, 747 cm^-1. ¹H NMR: δ = 8.09 (s, 1 H), 7.56 (d, J = 7.6 Hz, 1 H), 7.36-7.22 (m, 6 H), 7.08-7.00 (m, 2 H), 4.70 (s, 1 H), 4.25-4.09 (m, 2 H), 3.84 (d, J = 13.0 Hz, 1 H), 3.79 (d, J = 13.0 Hz, 1 H), 2.46 (s, 3 H), 1.94 (s, 1 H), 1.21 (t, J = 7.1 Hz, 3 H). ¹³C NMR: δ = 173.5, 139.7, 136.0, 128.4, 128.4, 127.1, 125.7, 122.9, 122.7, 120.4, 120.1, 117.2, 113.8, 61.1, 57.6, 51.5, 16.6, 14.2. HRMS: m/z calcd for C₂₀H₂₂N₂O₂ (M⁺): 322.1681, found: 322.1677.
4n: white solid; mp 98-99 °C. IR: 3403, 3182, 2960, 2858, 1729, 1495, 1460, 1301, 1221, 1183 cm^-1. ¹H NMR: δ = 7.97 (s, 1 H), 7.74 (d, J = 7.3 Hz, 1 H), 7.30-7.22 (m, 6 H), 7.13-7.07 (m, 2 H), 4.67 (s, 1 H), 4.23-4.00 (m, 2 H), 3.78 (d, J = 13.2 Hz, 1 H), 3.72 (d, J = 13.2 Hz, 1 H), 3.24-3.13 (m, 1 H), 2.20 (s, 1 H), 1.29-1.26 (m, 6 H), 1.14 (t, J = 7.1 Hz, 3 H). ¹³C NMR: δ = 173.2, 143.2, 140.0, 135.2, 128.3, 127.0, 126.8, 121.3, 119.8, 119.5, 110.5, 106.5, 60.9, 56.5, 51.0, 25.4, 23.2, 22.1, 14.1. HRMS: m/z calcd for C₂₂H₂₆N₂O₂ (M⁺): 350.1994, found: 350.1999.

14

The scale-up experiment was performed on a gram scale: To a stirred mixture of 1a (1.0 g, 8.5 mmol) and benzylamine (3b; 1.43 mL, 1.4 g, 12.8 mmol), 2 (1.3 g, 12.8 mmol) was added at ambient temperature. The reaction mixture was stirred for 40 min. The crude product was purified by flash chromatography on silica gel (petroleum ether-EtOAc, 4:1) to give ethyl 2-(1H-indol-3-yl)-2-(benzylamino)acetate (4g, [4] 2.06 g, 78%).