Regioselective Friedel–Crafts Reactions of N-Substituted Glyoxylamide with Indoles Catalyzed by Brønsted Acid

Zhen Zhan; Renjun Li; Yang Zheng; Yan Zhou; Li Hai; Yong Wu

doi:10.1055/s-0035-1560462

Synlett, Inhaltsverzeichnis

Synlett 2015; 26(16): 2261-2266
DOI: 10.1055/s-0035-1560462

letter

Regioselective Friedel–Crafts Reactions of N-Substituted Glyoxylamide with Indoles Catalyzed by Brønsted Acid

Zhen Zhan

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Department of Medicinal Chemistry West China School of Pharmacy, Sichuan University, Chengdu 610041, P. R. of China eMail: wyong@scu.edu.cn

,

Renjun Li

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Department of Medicinal Chemistry West China School of Pharmacy, Sichuan University, Chengdu 610041, P. R. of China eMail: wyong@scu.edu.cn

,

Yang Zheng

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Department of Medicinal Chemistry West China School of Pharmacy, Sichuan University, Chengdu 610041, P. R. of China eMail: wyong@scu.edu.cn

,

Yan Zhou

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Department of Medicinal Chemistry West China School of Pharmacy, Sichuan University, Chengdu 610041, P. R. of China eMail: wyong@scu.edu.cn

,

Li Hai

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Department of Medicinal Chemistry West China School of Pharmacy, Sichuan University, Chengdu 610041, P. R. of China eMail: wyong@scu.edu.cn

,

Yong Wu*

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Department of Medicinal Chemistry West China School of Pharmacy, Sichuan University, Chengdu 610041, P. R. of China eMail: wyong@scu.edu.cn

› Institutsangaben

Abstract

Alle Artikel dieser Rubrik

Dedicated with admiration to Professor K. Peter C. Vollhardt

Abstract

An efficient regioselective Friedel–Crafts reaction of a series of N-substituted glyoxylamide with indoles catalyzed by Brønsted acid was developed. The reactions proceeded smoothly at room temperature and the corresponding N-substituted 2-hydroxy-2-(1H-indol-3-yl) acetamides were afforded in moderate to good yields (up to 89%). When 2 M HCl was used, the bisindole compounds were obtained in good to excellent yield (up to 91%) resulting from a double Friedel–Crafts reaction.

Key words

regioselective Friedel–Crafts reaction - Brønsted acid - N-substituted glyoxylamide - indole - N-substituted 2-hydroxy-2-(1H-indol-3-yl) acetamide - bisindole compound

Volltext

Referenzen

References and Notes

For reviews on indoles, see:

1a Sundberg RJ. Indoles. Academic Press; San Diego: 1996
1b Faulkner DJ. Nat. Prod. Rep. 2001; 18: 1
1c Denhart DJ, Deskus JA, Ditta JL, Gao Q, King HD, Kozlowski ES, Meng Z, LaPaglia MA, Mattson GK, Molski TF, Taber MT, Lodge NJ, Mattson RJ, Macor JE. Bioorg. Med. Chem. Lett. 2009; 19: 4031

For selected examples, see:

2a Galliford CV, Scheidt KA. Angew. Chem. Int. Ed. 2007; 46: 8748
2b Marti C, Carreira EM. Eur. J. Org. Chem. 2003; 2209
2c Prathima PS, Rajesh P, Rao JV, Kailash US, Sridhar B, Rao MM. Eur. J. Med. Chem. 2014; 84: 155
2d Engel JB, Schoenhals T, Weidler C, Haeusler S, Krockenberger M, Rieger L, Dietl J, Wischhusen J, Honig A. Oncol. Rep. 2009; 22: 361
2e Wang Y, Tang X, Shao Z, Ren J, Liu D, Proksch P, Lin W. J. Antibiot. 2014; 67: 395
2f Kamal A, Srikanth YV, Khan MN, Shaik TB, Ashraf M. Bioorg. Med. Chem. Lett. 2010; 20: 5229

For selected examples, see:

3a Peddibhotla S. Curr. Bioact. Compd. 2009; 5: 20
3b Galliford CV, Scheidt KA. Angew. Chem. 2007; 119: 8902
3c Leze MP, LeBorgne M, Marchand P, Loquet D, Kogler M, LeBaut G, Palusczak A, Hartmann RW. J. Enzyme Inhib. Med. Chem. 2004; 19: 549
3d Borgne ML, Marchand P, Seiller BD, Robert JM, Baut GL, Hartmann RW, Palzer M. Bioorg. Med. Chem. Lett. 1999; 9: 9
3e Deng J, Sanchez T, Neamati N, Briggs JM. J. Med. Chem. 2006; 49: 1684
3f Contractor R, Samudio IJ, Estrov Z, Harris D, McCubrey JA, Safe SH, Andreeff M, Konopleva M. Cancer Res. 2005; 65: 2890

For selected examples, see:

4a Kumar A, Sharma S, Maurya RA. Tetrahedron Lett. 2009; 50: 5937
4b Yadav JS, Abraham SB, Reddy VS, Sabitha G. Synthesis 2001; 2165
4c Li B, Li Z, Meng X. Carbohydr. Res. 2010; 345: 1708
4d Ube H, Fukuchi S, Terada M. Tetrahedron: Asymmetry 2010; 21: 1203
4e Liu J, He T, Wang L. Tetrahedron 2011; 67: 3420
4f Righi M, Bartoccini F, Lucarini S, Piersanti G. Tetrahedron 2011; 67: 7923
4g Lee YJ, Han YR, Park W, Nam SH, Oh KB, Lee HS. Bioorg. Med. Chem. Lett. 2010; 20: 6882
4h Gao QH, Zhang JJ, Wu X, Liu S, Wu AX. Org. Lett. 2015; 17: 134

5a Shirakawa S, Kobayashi S. Org. Lett. 2006; 8: 4939
5b Soueidan M, Collin J, Gil R. Tetrahedron Lett. 2006; 47: 5467

For selected examples, see:

6a Choudhary VR, Jha R, Choudhary PA. J. Chem. Sci. 2005; 117: 635
6b Dong HM, Lu HH, Lu LQ, Chen CB, Xiao WJ. Adv. Synth. Catal. 2007; 349: 1597
6c Zhuang W, Jørgensen KA. Chem. Common. 2002; 1336
6d Xu XH, Kusuda A, Tokunaga E, Shibata N. Green Chem. 2011; 13: 46
6e Hui YH, Zhang Q, Jiang J, Lin LL, Liu XH, Feng XM. J. Org. Chem. 2009; 74: 6878
6f Li HM, Wang YQ, Deng L. Org. Lett. 2006; 8: 18

7a Bartoli G, Bosco M, Foglia G, Giuliani A, Marcantoni E, Sambri L. Synthesis 2004; 895
7b Huo CD, Sun CG, Wang C, Jia XD, Chang WJ. ACS Sustainable Chem. Eng. 2013; 1: 549

For selected examples, see:

8a Parvathaneni SP, Pamanji R, Janapala VR, Uppalapati SK, Balasubramanian S, Mandapati MR. Eur. J. Med. Chem. 2014; 84: 155
8b Pankaj C, Singh CS. Chem. Eur. J. 2010; 16: 7709
8c Kurosh RM, Negin D. J. Mol. Catal. A: Chem. 2014; 392: 97
8d Kurosh RM, Masoumeh SK, Homayun TA. Tetrahedron 2010; 66: 2316

For selected examples, see:

9a Gibbs TJ. K, Tomkinson NC. O. Org. Biomol. Chem. 2005; 3: 4043
9b Yadav JS, SubbaReddy BV, Gayathri KU, Meraj S, Prasad AR. Synthesis 2006; 4121
9c Kinthada LK, Ghosh S, De S, Bhunia S, Dey D, Bisai A. Org. Biomol. Chem. 2013; 11: 6984
9d Chakrabarty M, Mukherjee R, Mukherji A, Arima S, Harigaya Y. Heterocycles 2006; 68: 1659
9e Abe T, Nakamura S, Yanada R, Choshi T, Hibino S, Ishikura M. Org. Lett. 2013; 15: 3622

10a Deng J, Zhang SL, Ding P, Jiang HL, Wang W, Li J. Adv. Synth. Catal. 2010; 352: 833
10b Sasaki S, Ikekame Y, Tanayama M, Yamauchi T, Higashiyama K. Synlett 2012; 23: 2699

N-Substituted glyoxylamides 1 were prepared according to the reported procedures, see:

11a Chen WS, Liu YZ, Chen ZR. Eur. J. Org. Chem. 2005; 1665
11b Wu WB, Yuan XQ, Hu J, Wu XX, Wei Y, Liu ZW, Lu JZ, Ye JX. Org. Lett. 2013; 15: 17

Indoles 2 were purchased from ASTATECH and J&K Scientific Ltd. except ethyl 2-[(1-methyl-1H-indol-6-yl)oxy]acetate and 2-[(1-methyl-1H-indol-6-yl) oxy]acetamide. Ethyl 2-[(1-methyl-1H-indol-6-yl)oxy]acetate was synthesized according to the literature procedures, see:

12a Finefield JM, Williams RM. J. Org. Chem. 2010; 75: 2785
12b Akao A, Nonoyama N, Mase T, Yasuda N. Org. Process Res. Dev. 2006; 10: 1178
12c Choy PY, Lau CP, Kwong FY. J. Org. Chem. 2011; 76: 80
12d Ontoria JM, Marco SD, Conte I, Francesco ME. D, Gardelli C, Koch U, Matassa VG, Poma M, Steinkühler C, Volpari C, Harper S. J. Med. Chem. 2004; 47: 6443

2-[(1-methyl-1H-indol-6-yl) oxy]acetamide was synthesized from ethyl 2-[(1-methyl-1H-indol-6-yl)oxy]acetate according to the literature procedures, see:

12e Kreutter KD, Lu TB, Lee L, Giardino EC, Patel S, Huang H, Xu GZ, Fitzgerald M, Haertlein BJ, Mohan V, Crysler C, Eisennagel S, Dasgupta M, McMillan M, Spurlino JC, Huebert ND, Maryanoff BE, Tomczuk BE, Damiano BP, Player MR. Bioorg. Med. Chem. Lett. 2008; 18: 2865

13 N-Substituted 2-Hydroxy-2-(1H-indol-3-yl) Acetamides 3; General Procedure To a stirred mixture of N-substituted glyoxylamide (1.0 mmol), indoles (1.1 mmol) in dioxane (8 mL) was added AcOH (5.0 mmol) at 25 °C for 0.5 h. After the completion of the reaction (monitored by TLC), the mixture was diluted with H₂O and extracted with EtOAc (4 × 20 mL). The organic layer was washed with sat. brine, dried over anhydrous Na₂SO₄, and the solvent was evaporated to dryness. The crude residue was purified by flash chromatography on silica gel (CH₂Cl₂–MeOH, 80:1) to afford pure N-substituted 2-hydroxy-2-(1H-indol-3-yl) acetamides 3 (61–89% yield). 2,2-Di(1H-indol-3-yl)-N,N-phenyl Acetamide Derivatives 4; General Procedure To a stirred mixture of N-substituted glyoxylamide (1.0 mmol), indoles (2.0 mmol) in dioxane (8 mL) was added HCl (2 mol/L, 0.1 mmol) at 25 °C for 0.5 h. After completion of the reaction (monitored by TLC), the mixture was diluted with H₂O and extracted with EtOAc (3 × 20 mL). The organic layer was washed with sat. brine, dried over anhydrous Na₂SO₄, and the solvent was evaporated to dryness. The crude residue was purified by flash chromatography on silica gel (CH₂Cl₂–MeOH, 100:1) to afford pure 2,2-di(1H-indol-3-yl)-N,N-phenyl acetamide derivatives 4 (69–91% yield). Analytical Data of Some Typical Compounds 2-Hydroxy-2-(1H-indol-3-yl)-N-phenylacetamide (3a) Yield 84%; yellow solid, mp 150–152 °C. ¹H NMR (400 MHz, DMSO-d ₆): δ = 11.00 (s, 1 H), 9.90 (s, 1 H), 7.70 (s, 3 H), 7.33–7.28 (m, 4 H), 7.03–6.96 (m, 3 H), 6.08 (s, 1 H), 5.32 (s, 1 H). ¹³C NMR (150 MHz, DMSO-d ₆): δ = 171.9, 138.9, 136.6, 128.8, 128.0, 126.0, 124.3, 123.6, 121.4, 119.9, 118.9, 114.8, 111.7, 68.9. ESI-HRMS: m/z [M + Na⁺] calcd for C₁₆H₁₄N₂O₂Na: 289.0947; found: 289.0961. Anal. Calcd: C, 72.17; H, 5.30; N, 10.52. Found: C, 72.10; H, 5.35; N, 10.53. 2,2-Di(1H-indol-3-yl)-N-phenylacetamide (4a) Yield 89%; yellow solid, mp 139–141 °C. ¹H NMR (400 MHz, DMSO-d ₆): δ = 10.90 (s, 2 H), 10.34 (s, 1 H), 7.65–7.57 (m, 4 H), 7.35 (m, 2 H), 7.28 (t, J = 8.0 Hz, 2 H), 7.19 (s, 2 H), 7.07–7.00 (m, 3 H), 6.95 (t, J = 8.0 Hz, 2 H) 5.55 (s, 1 H). ¹³C NMR (150 MHz, DMSO-d ₆): δ = 171.0, 138.9, 137.0, 128.8, 126.9, 126.1, 124.1, 121.5, 120.4, 119.3, 118.0, 112.8, 111.0, 42.0. ESI-HRMS: m/z [M + Na⁺]: calcd for C₂₄H₁₉N₃ONa: 388.1420; found: 388.1425. Anal. Calcd: C, 78.88; H, 5.24; N, 11.50. Found: C, 78.79; H, 4.23; N, 9.49. 2-[(3-{2-[(4-chlorophenyl)amino]-1-(1H-indol-3-yl)-2-oxoethyl}-1-methyl-1H-indol-6-yl)oxy]acetate (3d′) Yield 84%; brown solid, mp 194–196 °C. ¹H NMR (600 MHz, DMSO-d ₆): δ = 10.92 (s, 1 H), 10.47 (s, 1 H), 7.67 (d, J = 8.4 Hz, 2 H), 7.57 (d, J = 8.4 Hz, 1 H), 7.47 (d, J = 8.4 Hz, 1 H), 7.36–7.18 (m, 2 H), 7.18 (m, 1 H), 7.07–7.04 (m, 2 H), 6.96–6.94 (m, 2 H), 6.69–6.67 (m, 1 H), 5.48 (s, 1 H), 4.77 (s, 2 H), 4.17 (q, J = 7.2 Hz, 2 H), 3.67 (s, 3 H), 1.21 (t, J = 7.2 Hz, 3 H). ¹³C NMR (150 MHz, DMSO-d ₆): δ = 171.9, 169.2, 154.5, 139.3, 137.8, 136.9, 132.5, 131.0, 128.5, 127.0, 122.9, 122.1, 121.6, 121.0, 120.7, 119.8, 112.5, 109.9, 98.6, 65.6, 42.6, 40.7, 32.4, 14.2. ESI-HRMS: m/z [M + Na⁺] calcd for C₂₉H₂₆ClN₃O₄Na: 538.1504; found: 538.1501. Anal. Calcd: C, 67.50; H, 5.08; N, 8.14. Found: C, 67.56; H, 5.00; N, 8.19.

Zusatzmaterial

Supporting Information