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Synlett 2008(3): 410-412
DOI: 10.1055/s-2007-1000875
DOI: 10.1055/s-2007-1000875
LETTER
© Georg Thieme Verlag Stuttgart · New York
A Novel One-Pot Synthesis of N-Acylindoles from Primary Aromatic Amides
Weitere Informationen
Received
10 September 2007
Publikationsdatum:
21. Dezember 2007 (online)
Publikationsverlauf
Publikationsdatum:
21. Dezember 2007 (online)
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Abstract
A novel one-pot synthesis of N-acylindoles via tandem cycloalkylation-annelation is described. This approach is based on the use of a strong solid-acid catalyst, montmorillonite K-10, and microwave irradiation under solvent-free conditions. The tandem cycloalkylation of amides and annelation of intermediate pyrroles were completed in minutes and provided good yields with high selectivities for the indoles. The safe, easy to handle catalyst, and the convenience of the product isolation make this process an attractive, environmentally benign alternative for the synthesis of N-acylindoles.
Keywords
amides - solid-acid catalysis - microwave heating - N-acylindole
-
1a
Gribble GW. J. Chem. Soc., Perkin Trans. 1 2000, 1045 ; and references cited therein -
1b
Fürstner A.Szillat H.Gabor B.Mynott R. J. Am. Chem. Soc. 1998, 120: 8305 -
1c
Török M.Abid M.Mhadgut SC.Török B. Biochemistry 2006, 45: 5377 -
1d
Zhang Y.Wada T.Sasabe H. Chem. Commun. 1996, 621 -
1e
Sundberg RJ. Indoles Academic Press; London: 1996. -
1f
Robinson B. The Fischer Indole Synthesis John Wiley and Sons; Chichester: 1982. -
1g
Török B.Abid M.London G.Esquibel J.Török M.Mhadgut SC.Yan P.Prakash GKS. Angew. Chem. Int. Ed. 2005, 44: 3086 -
2a
Kohling P.Schmidt AM.Eilbracht P. Org. Lett. 2003, 5: 3213 -
2b
Katritzky AR.Fali CN.Li J. J. Org. Chem. 1997, 62: 4148 -
2c
Fayol A.Fang Y.-Q.Lautens M. Org. Lett. 2006, 8: 4203 -
2d
Wagaw S.Yang BH.Buchwald SL. J. Am. Chem. Soc. 1998, 120: 6621 -
2e
Bremner JB.Samosorn S.Ambrus JI. Synthesis 2004, 2653 -
2f
Myznikov YE.Koldobskii GI.Vasil’eva IN.Ostrovskii VA. Zh. Org. Khim. 1988, 24: 1550 -
2g
Hayakawa K.Yasukouchi T.Kanematsu K. Tetrahedron Lett. 1986, 27: 1837 -
2h
Martin P. Helv. Chim. Acta 1984, 67: 1647 -
2i
Terashima M.Fujioka M. Heterocycles 1982, 19: 91 -
2j
Ikeda M.Ohno K.Uno T.Tamura Y. Tetrahedron Lett. 1980, 21: 3 -
2k
Itahara T. Synthesis 1979, 151 -
2l
Itahara T. Heterocycles 1986, 24: 2557 -
2m
Aggarwal R.Benedetti F.Berti F.Buchini S.Colombatti A. Chem. Eur. J. 2003, 9: 3132 -
2n
Bourgeois P.Mesdouze J.Philogene E. J. Heterocycl. Chem. 1983, 20: 1043 -
3a
Fischer E. Ber. Dtsch. Chem. Ges. 1886, 19: 1563 -
3b
Hughes DL. Org. Prep. Proced. Int. 1993, 25: 607 -
3c
Reissert A. Ber. Dtsch. Chem. Ges. 1896, 29: 655 -
3d
Blasko G.Kerekes P.Makleit S. Alkaloids 1987, 31: 1 -
3e
Madelung W. Ber. Dtsch. Chem. Ges. 1912, 45: 3521 -
3f
Brown RK. In Indoles Part 1:Houlihan WJ. Wiley; New York: 1972. p.385 -
3g
Zeni G.Larock RC. Chem. Rev. 2004, 104: 2285 -
3h
Kondo Y.Sakamoto T.Yamanaka H. Heterocycles 1989, 29: 1013 -
3i
Arcadi A.Cacchi S.Marinelli F. Tetrahedron Lett. 1989, 30: 2581 -
3j
Cacchi S.Fabrizi G.Marinelli F.Moro L.Pace P. Synlett 1997, 1363 -
3k
Cacchi S.Fabrizi G.Parisi LM. Synthesis 2004, 1889 -
3l
Kabalka GW.Wang L.Pagni RM. Tetrahedron 2001, 57: 8017 -
4a
Itahara T. Synthesis 1979, 151 -
4b
Bremner JB.Samosorn S.Ambrus JI. Synthesis 2004, 2653 -
5a
Corma A. Chem. Rev. 1995, 95: 559 -
5b
Gates BC. Catalysis by Solid Acids, In Encyclopedia of Catalysis Vol. 2:Horváth I. Wiley; New York: 2003. p.104 -
6a
Balogh M.Laszlo P. Organic Chemistry Using Clays Springer; Berlin, Heidelberg: 1993. -
6b
Szöllösi G.Török B.Baranyi L.Bartók M. J. Catal. 1998, 179: 619 -
6c
Török B.London G.Bartók M. Synlett 2000, 631 -
6d
Abid M.Török B. Adv. Synth. Catal. 2005, 347: 1797 -
6e
Landge SM.Schmidt A.Outerbridge V.Török B. Synlett 2007, 1600 -
6f
Dasgupta S.Török B. Org. Prep. Proced. Int 2008, 40: 1 -
7a
Varma RS.Dahiya R.Kumar S. Tetrahedron Lett. 1997, 38: 2039 -
7b
Walla P.Kappe CO. Chem. Commun. 2004, 594 -
7c
Loupy A. Microwaves in Organic Synthesis Wiley-VCH; Weinheim: 2005. -
7d
Kappe CO.Stadler A. Microwaves in Organic and Medicinal Chemistry Wiley-VCH; Weinheim: 2005. -
7e
Landge SM.Atanassova V.Thimmaiah M.Török B. Tetrahedron Lett. 2007, 48: 5161 -
8a
Banik BK.Samajdar S.Banik I. J. Org. Chem. 2004, 69: 213 -
9a
De’Silva C.Walker DA. J. Org. Chem. 1998, 63: 6715 -
9b
McIntosh JM. J. Org. Chem. 1988, 53: 447 -
9c
Abid M.Landge S.Török B. Org. Prep. Proced. Int. 2006, 38: 495 -
9d
Abid M.Spaeth A.Török B. Adv. Synth. Catal. 2006, 348: 2191 -
9e
Abid M.Teixeira L.Török B. Tetrahedron Lett. 2007, 48: 4047 - 10 All reactants including the catalyst, montmorillonite K-10, were purchased from Aldrich and used without further purification. The 1H NMR and 13C NMR spectra were obtained on a 300 MHz Varian NMR spectrometer in CDCl3. Tetramethylsilane or the residual solvent signal was used as reference. The mass spectrometric identification of the products was carried out on an Agilent 6850 GC and 5973 MS system (70 eV electron impact ionization) using a 30 m long DB-5 type column (J&W Scientific). The melting points were uncorrected and were recorded on a MEL-TEMP apparatus.
General Procedure for the Synthesis of N
-Acylindoles: An amide (1.0 mmol) and 2,5-dimethoxytetrahydrofuran (2.0 mmol) were dissolved in 3 mL of CH2Cl2 in a round-bottomed flask, then K-10 (500 mg) was added. After 5 min stirring, the solvent was removed to obtain the mixture of reactants adsorbed on the catalyst surface. The dry mixture was transferred into a glass reaction vial and irradiated in the microwave reactor (CEM Discover Benchmate, 80 °C). During optimization, the progress of the reaction was monitored by TLC and GC-MS to determine the necessary reaction times. After satisfactory conversion, CH2Cl2 was added to the cold mixture, and the product was separated from the catalyst by filtration. The products were isolated as crystals or oils and purified by flash chromatography. All products showed satisfactory spectral data (MS, 1H and 13C NMR). Here, the full spectral characterization is given for only the previously unknown products. Such data for the known compounds synthesized in this study are available from the authors.
1-(4-Fluorobenzoyl) indole (Table 1, Entry 5): mp 82.9-84.3 °C (MeOH); 1H NMR (300.12 MHz, CDCl3): δ = 8.36 (d, J = 7.8 Hz, 1 H), 7.79-7.74 (m, 2 H), 7.61 (d, J = 7.8 Hz, 1 H), 7.41-7.29 (m, 2 H), 7.27-7.18 (m, 3 H), 6.61 (d, J = 3.9 Hz, 1 H) ppm; 13C NMR (75.474 MHz, CDCl3): d = 166.6, 132.0, 131.8, 127.4, 126.9, 125.1, 124.2, 123.6, 121.1, 120.1, 116.4, 115.8, 108.9 ppm; MS for C15H10FNO(239): m/z (%) = 239 (40) [M+], 123 (100), 116 (5), 95 (30), 75 (15).
Biphenyl-4-yl(1
H
-indole-1-yl)methanone (Table 1, Entry 8): mp 98.2-100.1 °C (MeOH); 1H NMR (300.12 MHz, CDCl3): δ = 8.43 (d, J = 8.1 Hz, 1 H), 7.84-7.80 (m, 2 H), 7.76-7.67 (m, 2 H), 7.66-7.60 (m, 3 H), 7.52 (m, 3 H), 7.37-7.32 (m, 3 H), 6.65 (d, J = 3.6 Hz, 1 H) ppm; 13C NMR (75.474 MHz, CDCl3): δ = 166.0, 144.9, 130.0, 129.1, 128.4, 128.4, 127.7, 127.6, 127.4, 126.9, 121.0, 116.5, 108.7 ppm; MS for C21H15NO(297): m/z (%) = 297 (30) [M+], 181 (100), 152 (60), 116 (15), 77 (5)