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DOI: 10.1055/s-0030-1258440
On the Knorr Synthesis of 6-Bromo-4-methylquinolin-2(1H)-one
Publication History
Publication Date:
14 February 2011 (online)
Abstract
In the course of our work on infectious diseases, we were led to prepare 6-bromo-2-chloro-4-methylquinoline as a starting material. Since surprisingly little has been reported in the literature, the two synthetic steps to this compound were investigated. The synthesis involves a condensation between β-keto esters and 4-bromoaniline and the cyclization of the resulting anilides into 6-bromoquinolin-2(1H)-one, otherwise known as the Knorr reaction. The ¹H NMR monitoring of the first step allowed us to optimize the conditions leading specifically to the anilide without the occurrence of the alternative crotonate. To illustrate the scope of our finding, few additional anilides featuring electron-attracting groups were prepared. The study of their cyclization revealed some unsuspected steric effect governing this second step. Aside from rectifying a few claims in this chemistry, this study led to a three-step preparation of 6-bromo-2-chloro-4-methylquinoline in 48% overall yield from 4-bromoaniline.
Key words
acylation - cyclization - heterocycles - quinolines - carbocation
- 1
Knorr L. Justus Liebigs Ann. Chem. 1886, 236: 69 - 2
Bergstrom FW. Chem. Rev. 1944, 35: 77 - 3
Lauer WM.Kaslow CE. Org. Synth. Coll. Vol. 3 Wiley; New York: 1955. p.580 - 4
Conrad M.Limpach L. Ber. Dtsch. Chem. Ges. 1887, 20: 944 - 5
Limpach L. Ber. Dtsch. Chem. Ges. 1931, 64: 969 - 6
Reynolds CA.Hauser CR. Org. Synth. Coll. Vol. 3 Wiley; New York: 1955. p.593 - 7
Jones G. In Quinolines Vol. 32:Jones G. Wiley; New York: 1977. p.93 - 8
Coffey S.Thomson JK.Wilson FJ. J. Chem. Soc. 1936, 856 - 9
Hauser CR.Reynolds GA. J. Org. Chem. 1948, 70: 2402 - 10
Staskun B.Israelstam SS. J. Org. Chem. 1961, 26: 3191 - 11
Staskun B. J. Org. Chem. 1964, 29: 1153 - 12
Marull M.Lefebvre O.Schlosser M. Eur. J. Org. Chem. 2004, 54 - 13
Knorr L. Ber. Dtsch. Chem. Ges. 1883, 16: 2593 - 14
Law GH. inventors; US Patent 1982675. ; Chem. Abstr. 1935, 29, 780 - 15
Williams JW.Krynitsky JA. Org. Synth. Coll. Vol. 3 Wiley; New York: 1955. p.10 - 16
Davis SE.Rauckman BS.Chan JH.Roth B. J. Med. Chem. 1989, 32: 1936 - 17
Witzman JS.Nottingham WD. J. Org. Chem. 1991, 56: 1713 - 18
Effenberger F.Hartmann W. Angew. Chem. 1964, 76: 188 - 19
Lopez-Alvarado P.Avendano C.Menendez JC. Synthesis 1998, 186 - 20
Solingapuram Sai KK.Gilbert TM.Klumpp DA.
J. Org. Chem. 2007, 72: 9761 - 21
Stephenson EFM. J. Chem. Soc. 1956, 2557 - 22
Mallams AK.Israelstam SS. J. Org. Chem. 1964, 29: 3548 - 23
Garner R.Suschitzky H. J. Chem. Soc. 1966, 186 - 24
Monti L.Cirelli V. Gazz. Chim. Ital. 1936, 66: 723 ; Chem Abstr 1936, 31, 3487 - 25
Tikotikar NL.Navalgund IM.Munavalli SN.Kulkarni SN.Nargund KS. J. Karnatak Univ. 1956, 1, 43 ; Chem. Abstr. 1956, 52, 8141a - 26
Stenkamp D,Mueller SG,Lehmann-Lintz T,Lustenberger P,Thomas L,Schindler M,Roth GJ,Rudolf K, andLotz RRH. inventors; Patent WO 2005103029. ; Chem. Abstr. 2005, 143, 440274 - 27
Nadaraj V.Selvi ST. Indian J. Chem., Sect. B: Org. Chem. Incl. Med. Chem. 2007, 46: 1203 - 28
Stefani HA.Costa IM.Silva DO. Synthesis 2000, 1526 - 29
Huang J.Liang Y.Pan W.Yang Y.Dong D. Org. Lett. 2007, 9: 5345 - 30
Hamada Y.Sugihara H.Isobe T. Yakugaku Zasshi 1962, 82: 1592 ; Chem. Abstr. 1962, 59, 564g - 31
Suri OP.Satti NK.Suri KA. Synth. Commun. 2000, 30: 3709 - 32
Pierce JB.Ariyan ZS.Ovenden GS. J. Med. Chem. 1982, 25: 131 - 33
Kidwai M.Bansal V. Lett. Org. Chem. 2007, 4: 519 - 34
Kidwai M.Bansal V.Mishra NK.Bhatnagar D. Indian J. Chem., Sect. B: Org. Chem. Incl. Med. Chem. 2009, 48: 746 - 35
Kermack WO.Weatherhead AP. J. Chem. Soc. 1939, 563 - 36
Zhi L,Tegley C,Pio B,Arjan van Oeveren C,Motamedi M,Martinborough E,West S,Higuchi R,Hamann L, andFarmer L. inventors; Patent WO 2001016108. ; Chem. Abstr. 2001, 134, 207727 - 37
Berbasov D.Soloshonok VA. Synthesis 2003, 2005 - 38
Liu J.-T.Lue H.-J. J. Fluorine Chem. 2001, 111: 207 - 39
Strohmeier GA.Fabian WMF.Uray G. Helv. Chim. Acta 2004, 87: 215 - 40
Balaban IE. J. Chem. Soc. 1930, 2346 - 41
Guillou S.Bonhomme FJ.Janin YL. Tetrahedron 2009, 65: 2660 - 42
Guillou S.Nesme O.Ermolenko MS.Janin YL. Tetrahedron 2009, 65: 3529 - 43
Guillou S.Janin YL. Chem. Eur. J. 2010, 16: 4669 - 44
Dains FB.Brown EW. J. Am. Chem. Soc. 1909, 31: 1148 - 45
Akguen E.Portoghese PS.Sajjad M.Nabi HA. J. Labelled Compd. Radiopharm. 2007, 50: 165 - 46
Harries HJ.Hughes RK.Smith T. J. Inorg. Nucl. Chem. 1972, 34: 1609 - 47
Bayer F. inventors; German Patent DE 273321. ; Chem. Abstr. 1914, 8, 2782 - 48
Barros MT.Geraldes CFGC.Maycock CD.Silva MI. J. Mol. Struct. 1986, 142: 435 - 49
Alabaster CT.Bell AS.Campbell SF.Ellis P.Henderson CG.Roberts DA.Ruddock KS.Samuels GMR.Stefaniak MH. J. Med. Chem. 1988, 31: 2048