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DOI: 10.1055/s-2006-926243
Facile Generation of a Library of 5-Aryl-2-arylsulfonyl-1,3-thiazoles
Publikationsverlauf
Publikationsdatum:
06. Februar 2006 (online)
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Abstract
Treatment of N,N-diformylaminomethyl aryl ketones with phosphorus pentasulfide/triethylamine in chloroform gives 5-arylthiazoles directly in good yield. The 5-aryl-1,3-thiazole core has been successfully functionalised at the 2-position to yield, over two steps, a large array of 5-aryl-2-arylsulfonyl-1,3-thiazoles in a parallel fashion.
Key words
heterocycles - 1,3-thiazole - lithiation - phosphorus pentasulfide
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Wiley RH.England DC.Behr LC. Org. React. 1951, 6: 367 - 2
Pivsa-Art S.Satoh T.Kawamura Y.Miura M.Nomura M. Bull. Chem. Soc. Jpn. 1998, 71: 467 - 3
Kondo Y.Komine T.Sakamoto T. Org. Lett. 2000, 2: 3111 - 4
Oscarsson K.Oscarsson S.Vrang L.Hamelink E.Hallberg A.Samuelsson B. Bioorg. Med. Chem. 2003, 11: 1235 - 5
Bold G.Fässler A.Capraro H.-G.Cozens R.Klimmait T.Lazdins J.Mestan J.Poncioni B.Rösel J.Stover D.Tintelnot-Blomley M.Acemoglu F.Beck W.Boss E.Eschbach M.Hürlimann T.Masso E.Roussel S.Ucci-Stoll K.Wyss D.Lang M. J. Med. Chem. 1998, 41: 3387 - 6
Sezen B.Sames D. Org. Lett. 2003, 5: 3607 - 7
Hodgetts KJ.Kershaw MT. Org. Lett. 2002, 4: 1363 - 8
Jensen J.Skjærbæk N.Vedso P. Synthesis 2001, 128 - 9
Yinglin H.Hongwen H. Synthesis 1990, 615 - 10
Bachstez M. Chem. Ber. 1914, 47: 3163 - 17
Noyce DS.Fike SA. J. Org. Chem. 1973, 38: 3321 - 18
Cronje S.Raubenheimer HG.Spies HSC.Esterhuysen C.Schmidbaur H.Schier A.Kruger GJ. J. Chem. Soc., Dalton Trans. 2003, 14: 2859
References and Notes
General Procedure for the Preparation of Thiazoles 3.
The bisformamide derivative (1 mmol) was dissolved in CHCl3 (5 mL). Then, Et3N (0.28 mL, 0.20 g, 2 equiv) was added to the stirred mixture, followed by phosphorus pentasulfide (0.44 g, 2 mmol, 2 equiv). The mixture was stirred at 60 °C for the appropriate time (typically 45-60 min). After cooling to r.t., H2O (3 mL) was added and the mixture stirred for 1 h. CH2Cl2 (15 mL) was then added and layers separated. The organic layer was washed with H2O and brine, dried (Na2SO4 or MgSO4) and the solvent removed in vacuo. The crude product was purified by flash chromatography [silica; Et2O-PE (60-80) mixtures as eluant] or on silica preparative TLC plates.
We were also able to convert 6 into the thiazole 7 by the same method in 67% yield (Scheme [2] ).
Scheme 2
Spectroscopic data of 3 (Ar1 = 4-MeOC6H4): 1H NMR (250 MHz, CDCl3): δ = 3.84 (s, 3 H), 7.50 (m, 2 H), 6.94 (m, 2 H), 7.98 (s, 1 H), 8.70 (s, 1 H). 13C NMR (62.5 MHz, CDCl3): δ = 55.53, 114.7, 123.8, 128.4, 138.2, 139.4, 151.4, 160.0.
14Spectroscopic data of 3 (Ar1 = 2-furyl): 1H NMR (250 MHz, CDCl3): δ = 6.46 (dd, J = 3.5, 1.8 Hz, 1 H), 6.57 (dd, J = 3.5, 0.6 Hz, 1 H), 7.45 (dd, J = 1.8, 0.6 Hz, 1 H), 8.05 (s, 1 H), 8.71 (s, 1 H). 13C NMR (62.5 MHz, CDCl3): δ = 107.6, 111.94, 129.2, 138.7, 142.8, 146.4, 151.4.
15Spectroscopic data of 4 (Ar1 = 3-NO2C6H4, Ar2 = 3-BrC6H4): 1H NMR (250 MHz, CDCl3): δ = 7.33 (m, 1 H), 7.52-7.68 (m, 3 H), 7.72-7.87 (m, 2 H), 7.97 (s, 1 H), 8.12-8.22 (m, 1 H), 8.28 (m, 1 H). 13C NMR (62.5 MHz, CDCl3): δ = 121.3, 123.0, 123.6, 130.32, 130.36, 131.3, 132.3, 132.7, 133.1, 133.4, 136.3, 138.4, 140.4, 148.85, 148.86.
16Spectroscopic data of 4 (Ar1 = 4-MeC6H4, Ar2 = Ph): 1H NMR (250 MHz, CDCl3): δ = 2.35 (s, 3 H), 7.11-7.23 (m, 2 H), 7.29-7.51 (m, 5 H), 7.65 (m, 2 H), 7.82 (s, 1 H). 13C NMR (62.5 MHz, CDCl3): δ = 21.3, 126.5, 128.2, 129.5, 129.8, 132.2, 133.6, 138.3, 138.5, 141.2, 164.2.
19MP-carbonate resin (loading: 3.14 mmol/g) was purchased from Argonaut Technologies.
20
General Procedure for the Oxidation of Thioethers 4 to Sulfones 5.
To a solution of the thioether (1 equiv, 0.2 M) in CH2Cl2, dry MCPBA (5 or 10 equiv) was added. The resulting mixture was stirred for 3 h at 40 °C (recommended for sterically hindered thioethers) or 6 h at r.t. To the mixture diluted with CH2Cl2 (35 mL/mmol of thioether), MP-carbonate resin was added (4 equiv relative to the amount of peracid used) and stirred for 2 h. The resin was filtered off and washed twice with CH2Cl2. The solvent was removed in vacuo to give the expected sulfones in pure form. In a few cases, crude sulfones required further purification by preparative TLC (silica; Et2O-PE (60-80) 7:3 as eluant).
Sulfones derived from 5-furylsubstituted thiazoles could not be isolated, probably due to side reactions affecting the furan ring under the acidic conditions used for the oxidation step.
22Spectroscopic data of 5 (Ar1 = 4-MeOC6H4, Ar2 = 4-MeC6H4): 1H NMR (250 MHz, CDCl3): δ = 2.43 (s, 3 H), 3.84 (s, 3 H), 6.89-7.01 (m, 2 H), 7.31-7.42 (m, 2 H), 7.43-7.53 (m, 2 H), 7.91-8.10 (m, 3 H). 13C NMR (62.5 MHz, CDCl3): δ = 21.8, 55.6, 115.0, 122.2, 128.7, 130.2, 136.2, 139.5, 145.6, 146.9, 161.0, 164.2.
23Spectroscopic data of 5 (Ar1 = 2-thienyl, Ar2 = 2-MeC6H4): 1H NMR (250 MHz, CDCl3): δ = 2.65 (s, 3 H), 7.01 (dd, J = 5.0, 3.7 Hz, 1 H), 7.18-7.52 (m, 5 H), 7.84 (s, 1 H), 8.16 (m, 1 H). 13C NMR (62.5 MHz, CDCl3): δ = 20.9, 127.0, 127.7, 127.9, 128.6, 130.6, 131.1, 133.1, 134.7, 137.2, 139.6, 139.9, 140.2, 164.7.