Subscribe to RSS
DOI: 10.1055/s-2003-41405
Acid-Mediated Halogen Exchange in Heterocyclic Arenes: A Highly Effective Iodination Method
Publication History
Publication Date:
28 August 2003 (online)
Abstract
Heterocyclic arenes including pyridyl, quinolyl, and isoquinolyl chlorides have been converted to their corresponding iodides in good to high yields via acid-mediated nucleophilic halogen exchange with sodium iodide. This procedure avoids the use of transition metals, harsh reaction conditions, and affords highly regioselective halide exchange. Chloride substituents in position 2 and 4 of pyridines and quinolines are readily substituted by iodide in 75-91% and conversion of 1-chloroisoquinoline to its iodide derivative was found to proceed with 90% yield. Positions that are not activated for nucleophilic aromatic substitution proved to be inert to halide exchange. Regioselective chloride/iodide exchange in 4,7-dichloroquinoline hydrochloride gave 7-chloro-4-iodoquinoline, an important precursor of anti-malaria drugs, in almost 90% yield.
Key words
chloride/iodide exchange - aryl iodides - nucleophilic aromatic substitution - cross-coupling reactions.
- st-1 For recent review:
Littke AF.Fu GC. Angew. Chem. Int. Ed. 2002, 41: 4176 -
st-2a
Riermeier TH.Zapf A.Beller M. Top. Catal. 1997, 4: 301 -
st-2b
Shirakawa E.Yamasaki K.Hiyama T. Synthesis 1998, 1544 -
st-2c
Littke AF.Fu GC. J. Org. Chem. 1999, 64: 10 -
st-2d
Suzuki A. J. Organomet. Chem. 1999, 576: 147 -
st-2e
Shiota T.Yamamori T. J. Org. Chem. 1999, 64: 453 -
st-2f
Littke AF.Fu GC. Angew. Chem. Int. Ed. 1999, 38: 2411 -
st-2g
Zhang CM.Huang JK.Trudell ML.Nolan ML. J. Org. Chem. 1999, 64: 3804 -
st-2h
Mowery ME.DeShong P. Org. Lett. 1999, 1: 2137 -
st-2i
Bei X.Turner HW.Weinberg WH. Tetrahedron Lett. 1999, 40: 3855 -
st-2j
Bei X.Turner HW.Weinberg WH.Guram AS. J. Org. Chem. 1999, 64: 6797 -
st-2k
Wolfe JP.Singer RA.Yang BH.Buchwald SL. J. Am. Chem. Soc. 1999, 121: 9550 -
st-2l
Huang J.Nolan SP. J. Am. Chem. Soc. 1999, 121: 9889 -
st-2m
Bohm VPW.Herrmann WA. Chem.-Eur. J. 2000, 6: 1017 -
st-2n
Gruber AS.Zim D.Ebeling G.Monteiro AL.Dupont J. Org. Lett. 2000, 1287 -
st-2o
Morales-Morales D.Redon R.Yung C.Jensen CM. Chem. Commun. 2000, 1619 -
st-2p
Bohm VPW.Weskamp T.Gstottmayr CWK.Herrmann WA. Angew. Chem. Int. Ed. 2000, 39: 1602 -
st-2q
Beletskaya IP.Cheprakov AV. Chem. Rev. 2000, 100: 3009 -
st-2r
Littke AF.Dai C.Fu GC. J. Am. Chem. Soc. 2000, 122: 4020 -
st-2s
Zapf A.Ehrentraut A.Beller M. Angew. Chem. Int. Ed. 2000, 39: 4153 -
st-2t
Stambuli JP.Stauffer SR.Shaughnessy KH.Hartwig JF. J. Am. Chem. Soc. 2001, 123: 2677 -
st-2u
Dai C.Fu GC. J. Am. Chem. Soc. 2001, 123: 2719 -
st-2v
Littke AF.Fu GC. J. Am. Chem. Soc. 2001, 123: 6989 -
st-2w
Whitcombe NJ.Hii KK.Gibson SE. Tetrahedron 2001, 57: 7449 -
st-2x
Yin JJ.Rainka MP.Zhang XX.Buchwald SL. J. Am. Chem. Soc. 2002, 124: 1162 -
st-2y
Bedford RB.Cazin CSJ.Hazelwood SL. Chem. Commun. 2002, 2608 -
st-2z
Bedford RB.Cazin CSJ.Hazelwood SL. Chem. Commun. 2002, 2610 - st-3
Seevers RH.Counsell RE. Chem Rev. 1982, 82: 575 -
st-4a
Meyer G.Rollin Y.Perichon J. Tetrahedron Lett. 1986, 27: 3497 -
st-4b
Yang SH.Li CS.Cheng CH. J. Org. Chem. 1987, 52: 691 -
st-4c
Bozell JJ.Vogt CE. J. Am. Chem. Soc. 1988, 110: 2655 -
st-4d
Merkushev EB. Synthesis 1988, 923 -
st-4e
Barluenga J.Gonzalez JM.Garcia-Martin MA.Campos PJ.Asensio G. J. Org. Chem. 1993, 58: 2058 -
st-4f
Milne JE.Jarowicki K.Kocienski PJ. Synlett 2002, 607 - st-5
Klapars A.Buchwald SL. J. Am. Chem. Soc. 2002, 124: 14844 - st-6
Zanon J.Klapars A.Buchwald SL. J. Am. Chem. Soc. 2003, 125: 2890 - st-7
Schlosser M.Cottet F. Eur. J. Org. Chem. 2002, 4181 -
st-8a
Couve-Bonnaire S.Carpentier J.-F.Castanet Y.Mortreux A. Tetrahedron Lett. 1999, 40: 3717 -
st-8b
Koseki Y.Omino K.Anzai S.Nagasaka T. Tetrahedron Lett. 2000, 41: 2377 -
st-8c
Song JJ.Yee NK. J. Org. Chem. 2001, 66: 605 -
st-8d
Couve-Bonnaire S.Carpentier J.-F.Mortreux A.Castanet Y. Tetrahedron Lett. 2001, 42: 3689 -
st-8e
Mello JV.Finney NS. Org. Lett. 2001, 3: 4263 -
st-8f
Hanrahan JR.Mewett KN.Chebib M.Burden PM.Johnston GAR. J. Chem. Soc., Perkin Trans. 1 2001, 2389 -
st-8g
Bach T.Heuser S. Synlett 2002, 2089 -
st-8h
Yue WS.Li JJ. Org. Lett. 2002, 4: 2201 -
st-8i
Mongin F.Trecourt F.Gervais B.Mongin O.Queguiner G. J. Org. Chem. 2002, 67: 3272 -
st-8j
Sugimoto O.Yamada S.Tanji K.-I. Tetrahedron Lett. 2002, 43: 3355 -
st-8k
Schlosser M.Bobbio C. Eur. J. Org. Chem. 2002, 4174 -
st-8l
Lu X.Petersen JL.Wang KK. J. Org. Chem. 2002, 67: 5412 -
st-9a
Matsubara J.Otsubo K.Morita S.Ohtani T.Kawano T.Uchida M. Heterocycles 1996, 43: 133 -
st-9b
Blurton P.Brickwood A.Dhanak D. Heterocycles 1997, 45: 2395 -
st-9c
Arzel E.Rocca P.Marsais F.Godard A.Queguiner G. Tetrahedron Lett. 1998, 39: 6465 -
st-9d
Arzel E.Rocca P.Marsais F.Godard A.Queguiner G. Tetrahedron 1999, 55: 12149 -
st-9e
Arzel E.Rocca P.Grellier P.Labaeied M.Frappier F.Gueritte F.Gaspard C.Marsais F.Godard A.Queguiner G. J. Med. Chem. 2001, 44: 949 -
st-9f
Gershon H.Clarke DD.McMahon JJ.Gershon M. Monatsh. Chem. 2002, 133: 1325 -
st-11a
O’Neill PM.Bray PG.Hawley SR.Ward SA.Park BK. Pharmacol. Ther. 1998, 77: 29 -
st-11b
Blauer G.Akkawi M.Fleischhacker W.Hiessboeck R. Chirality 1998, 10: 556 -
st-11c
Egan TJ.Hunter R.Kaschula CH.Marques HM.Misplon A.Walden J. J. Med. Chem. 2000, 43: 283
References
Only starting material was recovered after treatment of 3-chloropyridine hydrochloride with NaI.
st-12Small amounts of starting materials were recovered in both cases.
st-13All known compounds show 1H NMR and 13C NMR spectroscopy and mass spectrometry data consistent with the given structures.