Abstract
Convenient, scalable and high-yielding approaches to 2,5- and
2,4-dibromo-1,3-thiazole are reported that offer significant improvements
over previously reported approaches. 2,5-Dibromo-1,3-thiazole was
generated in two steps from commercially inexpensive 2-amino-1,3-thiazole,
whereas 2,4-dibromo-1,3-thiazole was generated in a single step
from commercially inexpensive 1,3-thiazolidine-2,4-dione. As part
of this study, convenient approaches to 2-bromo- and 2-iodo-1,3-thiazole
were also developed.
Key words
halogenation - bromine - iodine - 1,3-thiazole - heterocycles
References
For reviews of applications involving
thiophene-containing compounds, see, for example:
<A NAME="RM104011SS-1A">1a </A>
Campaigne E. In Comprehensive Heterocyclic Chemistry
Vol.
4:
Katritzky AR.
Rees CW.
Pergamon Press;
Oxford:
1984.
p.863
<A NAME="RM104011SS-1B">1b </A>
Russell DK.
Press JB. In Comprehensive Heterocyclic Chemistry II
Vol.
2:
Katritzky AR.
Rees CW.
Scriven EFV.
Pergamon Press;
Oxford:
1996.
p.679
<A NAME="RM104011SS-1C">1c </A>
Schatz J. In Science of Synthesis
Vol.
9:
Maas G.
Thieme;
Stuttgart:
2000.
p.422
For reviews of applications involving
1,3-thiazole-containing compounds, see, for example:
<A NAME="RM104011SS-2A">2a </A>
Dondoni A.
Merino P. In Comprehensive
Heterocyclic Chemistry II
Vol. 3:
Katritzky AR.
Rees CW.
Scriven EFV.
Pergamon
Press;
Oxford:
1996.
p.373
<A NAME="RM104011SS-2B">2b </A>
Kikelj D.
Urleb U. In Science
of Synthesis
Vol. 11:
Schaumann E.
Thieme;
Stuttgart:
2000.
p.627
<A NAME="RM104011SS-3">3 </A>
Limberakis C.
Mullins RJ.
Azman AM. In Palladium in Heterocyclic
Chemistry
2nd ed.:
Li JJ.
Gribble GW.
Elsevier;
Oxford:
2007.
p.251 (thiophenes) and 345 (1,3-thiazoles)
<A NAME="RM104011SS-4">4 </A> For a recent review, see:
Seed A.
Chem. Soc. Rev.
2007,
36:
2046
For a summary of available approaches
to the preparation of halothiophenes, see, for example:
<A NAME="RM104011SS-5A">5a </A>
Rajappa S. In Comprehensive Heterocyclic Chemistry
Vol.
4:
Katritzky AR.
Rees CW.
Pergamon Press;
Oxford:
1984.
p.765
<A NAME="RM104011SS-5B">5b </A>
Rajappa S.
Natekar MV. In Comprehensive Heterocyclic Chemistry II
Vol.
2:
Katritzky AR.
Rees CW.
Scriven EFV.
Pergamon Press;
Oxford:
1996.
p.502
<A NAME="RM104011SS-5C">5c </A>
Gronowitz S.
Hörnfeldt AB.
Thiophenes : Best Synthetic
Methods.
Elsevier Ltd.;
Oxford:
2004.
<A NAME="RM104011SS-6A">6a </A>
Ganapathi K.
Venkataraman A.
Proc.
Indian Acad. Sci., Sect. A
1945,
22:
362
<A NAME="RM104011SS-6B">6b </A> Others have obtained 70% yield
using this procedure, see:
van Zwieten PA.
Huisman HO.
Recl.
Trav. Chim. Pays-Bas
1962,
554
<A NAME="RM104011SS-7">7 </A> The most attractive literature approach
to 2-iodo-1,3-thiazole proceeds from inexpensive 2-amino-1,3-thiazole
in 40% yield, see:
Neenan TX.
Whitesides GM.
J. Org. Chem.
1988,
53:
2489
<A NAME="RM104011SS-8A">8a </A>
2-Bromo-1,3-thiazole
is an article of commerce (e.g., $118/mol from
Oakwood Products, Inc. as of the submission date of this paper).
<A NAME="RM104011SS-8B">8b </A>
The most attractive
literature approach to 2-bromo-1,3-thiazole proceeds from commercially
inexpensive 2-amino-1,3-thiazole ($17/mol from
Alfa Aesar) in 75% yield.6a Use of 2-amino-1,3-thiazole
purchased from Acros Organics resulted in an isolated yield of only
40%, whereas 2-amino-1,3-thiazole purchased from Alfa Aesar
gave 86% yield. Removal of the copper salts by filtration
through Celite, followed by extraction of the filtrate, resulted
in a 7% decrease in isolated yield of 2-bromo-1,3-thiazole
compared to steam distillation of the crude material. Alternate
approaches to 2-bromo-1,3-thiazole have also been reported. See,
for example:
<A NAME="RM104011SS-8C">8c </A>
Boga C.
Vecchio ED.
Forlani L.
Todesco PE.
J. Organomet.
Chem.
2000,
601:
233 (80% GC-MS
yield from expensive 1,3-thiazole)
<A NAME="RM104011SS-8D">8d </A>
Wibaut JP.
Jansen HE.
Recl.
Trav. Chim. Pays-Bas
1934,
53:
77 (20% yield
from 2-amino-1,3-thiazole)
<A NAME="RM104011SS-9A">9a </A>
2-Iodo-1,3-thiazole
does not appear to be commercially available
<A NAME="RM104011SS-9B">9b </A> 2-Iodo-1,3-thiazole has
also been prepared from 2-trimethylstannyl-1,3-thiazole in excellent
yield (90%), see:
Dondoni A.
Mastellari AR.
Medici A.
Negrini E.
Pedrini P.
Synthesis
1986,
757
<A NAME="RM104011SS-9C">9c </A> Another high-yielding
approach to 2-iodo-1,3-thiazole, proceeding from expensive 1,3-thiazole
via an experimentally less convenient 2-metalation and iodination
strategy has also been reported. See:
Shilai M.
Kondo Y.
Sakamoto T.
J.
Chem. Soc., Perkin Trans. 1
2001,
442
<A NAME="RM104011SS-10A">10a </A>
Clark RF.
Zhang T.
Wang X.
Wang R.
Zhang X.
Camp HS.
Beutel BA.
Sham HL.
Gu YG.
Bioorg. Med. Chem. Lett.
2007,
17:
1961
<A NAME="RM104011SS-10B">10b </A>
Clark RF.
Zhang T.
Xin Z.
Liu G.
Wang Y.
Hansen TM.
Wang X.
Wang R.
Zhang X.
Frevert EU.
Camp HS.
Beutel BA.
Sham HL.
Gu YG.
Bioorg. Med. Chem. Lett.
2006,
16:
6078
<A NAME="RM104011SS-10C">10c </A>
Gu YG.
Weitzberg M.
Clark RF.
Xu X.
Li Q.
Lubbers NL.
Yang Y.
Beno DWA.
Widomski DL.
Zhang T.
Hansen TM.
J. Med. Chem.
2007,
50:
1078
<A NAME="RM104011SS-10D">10d </A>
Gu YG.
Weitzberg M.
Clark RF.
Xu X.
Li Q.
Zhang T.
Hansen TM.
Liu G.
Xin Z.
Wang X.
Wang R.
McNally T.
Camp H.
Beutel BA.
Sham HL.
J.
Med. Chem.
2006,
49:
3770
<A NAME="RM104011SS-10E">10e </A>
Berry CR.
Zificsak CA.
Gibbs AC.
Hlasta DJ.
Org.
Lett.
2007,
9:
4099
<A NAME="RM104011SS-11A">11a </A>
Lee C.-H.
Yamamoto T.
Mol.
Cryst. Liq. Cryst.
2001,
363:
77
<A NAME="RM104011SS-11B">11b </A>
Takihana Y.
Shiotsuki M.
Sanda F.
Masuda T.
Macromolecules
2004,
37:
7578
<A NAME="RM104011SS-12A">12a </A>
Dondoni A.
Fogagnolo M.
Medidci A.
Negrini E.
Synthesis
1987,
185
<A NAME="RM104011SS-12B">12b </A>
Mitschke U.
Osteritz EM.
Debärdemaeker T.
Sokolowski M.
Bäuerle P.
Chem. Eur. J.
1998,
4:
2211
<A NAME="RM104011SS-12C">12c </A>
Stanetty P.
Schnurch M.
Mihovilovic MD.
J.
Org. Chem.
2006,
71:
3754
<A NAME="RM104011SS-13A">13a </A>
Gronowitz S.
Peters D.
Heterocycles
1990,
30:
645
<A NAME="RM104011SS-13B">13b </A>
Bey E.
Marchais-Oberwinkler S.
Werth R.
Negri M.
Al-Soud YA.
Kruchten P.
Oster A.
Frotscher M.
Birk B.
Hartmann RW.
J. Med. Chem.
2008,
51:
6725
<A NAME="RM104011SS-13C">13c </A>
Strotman NA.
Chobanian HR.
He J.
Guo Y.
Dormer PG.
Jones CM.
Steves JE.
J. Org. Chem.
2010,
75:
1733
<A NAME="RM104011SS-14">14 </A>
Gol’dfarb YL.
Gromova GP.
Belen’kii LI.
Chem. Heterocycl. Compd. (Engl. Transl.)
1986,
22:
663
<A NAME="RM104011SS-15A">15a </A>
Beyerman HC.
Berben PH.
Bontekoe JS.
Recl. Trav.
Chim. Pays-Bas
1954,
73:
325
<A NAME="RM104011SS-15B">15b </A>
Roussel P.
Metzger J.
Bull. Soc. Chim. Fr.
1962,
2075
<A NAME="RM104011SS-16">16 </A>
2-Amino-5-bromo-1,3-thiazole is commercially
available ($3509/mol from Accela ChemBio, Inc.)
<A NAME="RM104011SS-17">17 </A>
English JP.
Clark JH.
Clapp JW.
Seeger D.
Ebel RH.
J.
Am. Chem. Soc.
1946,
68:
453
<A NAME="RM104011SS-18">18 </A>
Nußbaumer T.
Neidlein R.
Heterocycles
2000,
52:
349
<A NAME="RM104011SS-19A">19a </A>
Ammer C.
Bach T.
Chem.
Eur. J.
2010,
16:
14083
<A NAME="RM104011SS-19B">19b </A>
Dondoni A.
Fantin G.
Fogagnolo M.
Medici A.
Pedrini P.
J.
Org. Chem.
1988,
53:
1748
<A NAME="RM104011SS-19C">19c </A>
Gebauer J.
Arseniyadis S.
Cossy J.
Org.
Lett.
2007,
9:
3425
<A NAME="RM104011SS-19D">19d </A>
Huang S.-T.
Gordon DM.
Tetrahedron Lett.
1998,
39:
9335
<A NAME="RM104011SS-19E">19e </A>
Karama U.
Hoefle G.
Eur. J. Org. Chem.
2003,
1042
<A NAME="RM104011SS-19F">19f </A>
Kelly TR.
Lang F.
Tetrahedron
Lett.
1995,
36:
9293
<A NAME="RM104011SS-19G">19g </A>
Kovalenko VN.
Sokolov NA.
Kulinkovich OG.
Russ. J. Org. Chem.
2010,
46:
1702
<A NAME="RM104011SS-19H">19h </A>
Moulin E.
Nevado C.
Gagnepain J.
Kelter G.
Fiebig H.-H.
Fürstner A.
Tetrahedron
2010,
66:
6421
<A NAME="RM104011SS-19I">19i </A>
Nickson TE.
J. Fluorine Chem.
1991,
55:
173
<A NAME="RM104011SS-19J">19j </A>
Shao J.
Panek JS.
Org. Lett.
2004,
6:
3083
<A NAME="RM104011SS-19K">19k </A>
Siméon FG.
Brown AK.
Zoghbi SS.
Patterson VM.
Innis RB.
Pike VW.
J. Med. Chem.
2007,
50:
3256
<A NAME="RM104011SS-19L">19l </A>
Ung AT.
Pyne SG.
Tetrahedron:
Asymmetry
1998,
9:
1395
<A NAME="RM104011SS-19M">19m </A>
Boudet N.
Sase S.
Sinha P.
Liu C.-Y.
Krasovskiy A.
Knochel P.
J. Am. Chem. Soc.
2007,
129:
12358
<A NAME="RM104011SS-19N">19n </A>
Gross S.
Heuser S.
Ammer C.
Heckmann G.
Bach T.
Synthesis
2011,
199
<A NAME="RM104011SS-19O">19o </A>
Delgado O.
Heckmann G.
Müller HM.
Bach T.
J. Org. Chem.
2006,
71:
4599
<A NAME="RM104011SS-19P">19p </A>
Spieß A.
Heckmann G.
Bach T.
Synlett
2004,
131
<A NAME="RM104011SS-19Q">19q </A>
Nicolaou KC.
He Y.
Roschangar F.
King NP.
Vourloumis D.
Li T.
Angew. Chem.
Int. Ed.
1998,
37:
84
<A NAME="RM104011SS-19R">19r </A>
Nicolaou KC.
King NP.
Finlay MRV.
He Y.
Roschangar F.
Vourloumis D.
Vallberg H.
Sarabia F.
Ninkovic S.
Hepworth D.
Bioorg.
Med. Chem.
1999,
7:
665
<A NAME="RM104011SS-19S">19s </A>
Martin T.
Laguerre C.
Hoarau C.
Marsais F.
Org. Lett.
2009,
11:
3690
<A NAME="RM104011SS-20A">20a </A>
Athmani S.
Bruce A.
Iddon B.
J. Chem. Soc., Perkin Trans.
1
1992,
215
<A NAME="RM104011SS-20B">20b </A>
Kienle M.
Dunst C.
Knochel P.
Org.
Lett.
2009,
11:
5158
<A NAME="RM104011SS-20C">20c </A>
Dunst C.
Kienle M.
Knochel P.
Synthesis
2010,
2313
<A NAME="RM104011SS-20D">20d </A>
Nicolaou KC.
Sasmal PK.
Rassias G.
Reddy MV.
Altmann K.-H.
Wartmann M.
O’Brate A.
Giannakakou P.
Angew.
Chem. Int. Ed.
2003,
42:
3515
<A NAME="RM104011SS-20E">20e </A>
Palmer JT.
Bryant C.
Wang D.-X.
Davis DE.
Setti EL.
Rydzewski RM.
Venkatraman S.
Tian Z.-Q.
Burrill LC.
Mendonca RV.
Springman E.
McCarter J.
Chung T.
Cheung H.
Janc J. W.
McGrath M.
Somoza J. R.
Enriquez P.
Yu Z. W.
Strickley R. M.
Liu L.
Venuti M. C.
Percival M. D.
Falgueyret J.-P.
Prasit P.
Oballa R.
Riendeau D.
Young R. N.
Wesolowski G.
Rodan S. B.
Johnson C.
Kimmel D. B.
Rodan G.
J.
Med. Chem.
2005,
48:
7520
<A NAME="RM104011SS-20F">20f </A>
Satoh A.
Nagatomi Y.
Hirata Y.
Ito S.
Suzuki G.
Kimura T.
Maehara S.
Hikichi H.
Satow A.
Hata M.
Ohta H.
Kawamoto H.
Bioorg.
Med. Chem. Lett.
2009,
19:
5464
<A NAME="RM104011SS-21A">21a </A>
Bach T.
Heuser S.
Tetrahedron
Lett.
2000,
41:
1707
<A NAME="RM104011SS-21B">21b </A>
Bach T.
Heuser S.
Angew. Chem. Int. Ed.
2001,
40:
3184
<A NAME="RM104011SS-21C">21c </A>
Gebauer J.
Arseniyadis S.
Cossy J.
Eur.
J. Org. Chem.
2008,
2701
<A NAME="RM104011SS-22A">22a </A>
Bach T.
Heuser S.
J.
Org. Chem.
2002,
67:
5789
<A NAME="RM104011SS-22B">22b </A>
Cosford NDP.
Tehrani L.
Roppe J.
Schweiger E.
Smith ND.
Anderson J.
Bristow L.
Brodkin J.
Jiang X.
McDonald I.
Rao S.
Washburn M.
Varney M. A.
J.
Med. Chem.
2003,
46:
204
<A NAME="RM104011SS-23A">23a </A>
Delgado O.
Martin Müller H.
Bach T.
Chem. Eur.
J.
2008,
14:
2322
<A NAME="RM104011SS-23B">23b </A>
Hoffman TJ.
Dash J.
Rigby JH.
Arseniyadis S.
Cossy J.
Org. Lett.
2009,
11:
2756
<A NAME="RM104011SS-24">24 </A>
Wellmar U.
Hörnfeldt A.-B.
Gronowitz S.
J.
Heterocycl. Chem.
1995,
32:
1159
<A NAME="RM104011SS-25">25 </A>
Le Flohic A.
Meyer C.
Cossy J.
Tetrahedron
2006,
62:
9017
<A NAME="RM104011SS-26">26 </A>
POBr3 is commercially
available ($766/mol from Alfa Aesar).
<A NAME="RM104011SS-27">27 </A>
Kato Y.
Okada S.
Tomimoto K.
Mase T.
Tetrahedron Lett.
2001,
42:
4849
<A NAME="RM104011SS-28">28 </A>
Katritzky AR.
Laurenzo KS.
Relyea DI.
Can. J. Chem.
1988,
66:
1617
<A NAME="RM104011SS-29">29 </A>
L’Helgoual’ch J.-M.
Seggio A.
Chevallier F.
Yonehara M.
Jeanneau E.
Uchiyama M.
Mongin F.
J. Org. Chem.
2008,
73:
177
<A NAME="RM104011SS-30">30 </A>
Klein G.
Prijs B.
Helv. Chim. Acta
1954,
37:
2057
<A NAME="RM104011SS-31">31 </A>
Reynaud P.
Robba M.
Moreau RC.
Bull.
Soc. Chim. Fr.
1962,
1735