Abstract
A one-pot and environmentally benign approach to the synthesis
of highly functionalized 3-unsubstituted 2-aroylindoles is described.
Moderate to good yields were obtained through the reaction of easily
accessible N -(2-formylphenyl)trifluoroacetamides and α-bromoacetophenones
in the presence of K2 CO3 . PEG-400 was found
to be an efficient and reusable solvent in the process.
Key words
2-aroylindoles - PEG-400 -
N -(2-formylphenyl)trifluoroacetamides - heterocycles - cyclization
References
1 Humphrey GR.
Kuethe JT.
Chem. Rev.
2006,
106:
2875
2a Romagnoli R.
Baraldi PG.
Sarkar T.
Carrion MD.
Cara CL.
Cruz-Lopez O.
Preti D.
Tabrizi MA.
Tolomeo M.
Grimaudo S.
Di Cristina A.
Zonta N.
Balzarini J.
Brancale A.
Hsieh H.-P.
Hamel E.
J.
Med. Chem.
2008,
51:
1464
2b Mahboobi S.
Pongratz H.
Hufsky H.
Hockemeyer J.
Frieser M.
Lyssenko A.
Paper DH.
Bürgermeister J.
Böhmer F.-D.
Fiebig
H.-H.
Burger AM.
Baasner S.
Beckers T.
J. Med. Chem.
2001,
44:
4535
2c Beckers T.
Reissmann T.
Schmidt M.
Burger AM.
Fribig HH.
Vanhoefer U.
Pongratz H.
hufsky H.
Hockemeyer J.
Frieser M.
mahboobi S.
Cancer Res.
2002,
62:
3113
2d Brancale A.
Silvestri R.
Med. Res. Rev.
2007,
27:
209
3 Mahboobi S.
Sellmer A.
Höcher H.
Garhammer C.
Pongratz H.
Maier T.
Ciossek T.
Beckers T.
J. Med. Chem.
2007,
50:
4405
4 Mahboobi S.
Teller S.
Pongratz H.
Hufsky H.
Sellmer A.
Botzki A.
Uecker A.
Beckers T.
Baasner S.
Schächtele C.
Uberall F.
Kassack MU.
Dove S.
Böhmer F.-D.
J. Med. Chem.
2002,
45:
1002
5 Willson TM.
Brown PJ.
Sternbach DD.
Henke BR.
J.
Med. Chem.
2000,
43:
527
6 Cruz-López O.
Díaz-Mochón JJ.
Campos JM.
Entrena A.
Núñez MT.
Labeaga L.
Orjales A.
Gallo MA.
Espinosa A.
ChemMedChem
2007,
2:
88
7a Saulnier MG.
Gribble GW.
J. Org. Chem.
1982,
47:
757
7b Katritzky AR.
Akutagawa K.
Tetrahedron
Lett.
1985,
26:
5935
7c Takeda Y.
Kikuchi A.
Terashima M.
Heterocycles
1993,
35:
573
7d Kazunari N, William SR, Kiyoshi K, Chikara U, Hiroki K, and Stephane C. inventors; PCT Int. Appl. WO 9935130.
7e Thomas B, Siavosh M, Herwig P, Markus F, Harald H, Jörg H, and Udo V. inventors; PCT Int.
Appl. WO 2003037861.
8a Arthuis M.
Pontikis R.
Florent J.-C.
Org. Lett.
2009,
11:
4608
8b Abbiati G.
Casoni A.
Canevari V.
Nava D.
Rossi E.
Org.
Lett.
2006,
8:
4839
8c Labadie SS.
Teng E.
J. Org. Chem.
1994,
59:
4250
8d Cenini S.
Bettettini E.
Fedele M.
Tollari S.
J. Mol. Catal. A: Chem.
1996,
111:
37
9a Black DSt. C.
Wong LCH.
Chem. Commun.
1980,
4:
200
9b Jones AW.
Purwono B.
Bowyer PK.
Mitchell PSR.
Kumar N.
Nugent SJ.
Jolliffe KA.
Black DSt. C.
Tetrahedron
2004,
60:
10779
10a Jones CD.
Suarez T.
J.
Org. Chem.
1972,
37:
3622
10b Shiang J, Litz K, Celia JA, Chichak KS, and Ye Q. inventors; PCT
Int. Appl. WO 2008014037.
11 The only reaction condition reported
by Jones’ group was that DMF was used as the solvent. We
examined different solvents including acetone, acetonitrile, toluene,
DMF and PEG-400, and different bases including NaHCO3 ,
Na2 CO3 , K2 CO3 and Et3 N.
Only a trace amount of 2-aroylindole was obtained.
12 Clark MP, Brugel TA, Sabat M, Golebiowski A, Bookland RG, and De B.. inventors; PCT Int. Appl. US 2008 0139588.
13a Chandrasekhar S.
Reddy NR.
Sultana SS.
Narsihmulu C.
Reddy KV.
Tetrahedron
2006,
62:
338
13b Namboodiri VV.
Varma RS.
Green
Chem.
2001,
3:
146
14 No attempt was made to free the PEG-400
of salts because the salts did not hamper the rate of the reaction
15 Han R.
Chen S.
Lee SJ.
Qi F.
Wu X.
Kim BH.
Heterocycles
2006,
68:
1675
16 Murakami Y.
Heterocycles
1984,
22:
1211
