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Synlett 2009(8): 1255-1260  
DOI: 10.1055/s-0029-1216735
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

A Novel Consecutive Three-Component Coupling-Addition-SNAr (CASNAR) Synthesis of 4H-Thiochromen-4-ones

Benjamin Willy, Thomas J. J. Müller*
Institut für Organische Chemie und Makromolekulare Chemie, Lehrstuhl für Organische Chemie, Heinrich-Heine-Universität Düsseldorf, Universitätsstr. 1, 40225 Düsseldorf, Germany
Fax: +49(211)8114324; e-Mail: ThomasJJ.Mueller@uni-duesseldorf.de;
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Publication History

Received 5 February 2009
Publication Date:
17 April 2009 (online)

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Abstract

4H-Thiochromen-4-ones and 4H-thiopyrano[2,3-b]pyridin-4-ones are readily synthesized in good yields by a consecutive one-pot, three-component coupling-addition-S N Ar (CASNAR) sequence starting from aroyl chlorides, alkynes, and sodium sulfide nonahydrate.

Key words

alkynes - catalysis - CC coupling - heterocycles - multicomponent reactions

19

Representative Procedure - Synthesis of 2-Phenyl-4 H -thiochromen-4-one (1c; Table 2, Entry 3)
In a 10 mL microwave tube PdCl2 (PPh3)2 (15 mg, 0.02 mmol) and CuI (8 mg, 0.04 mmol) were dissolved in degassed THF (4 mL). Then, to this orange soln acid chloride 3c (1.25 mmol), alkyne 4c (1.00 mmol), and Et3N (1.05 mmol) were added. The reaction mixture was stirred at r.t. for 1 h. Finally, Na2S˙9H2O (5) followed by EtOH (1 mL) were added to this suspension, and the reaction mixture was heated at 90 ˚C in the microwave cavity for 90 min. After cooling to r.t., the solvent was removed under reduced pressure, and the crude products were purified by SiO2 flash column chromatography (hexane-EtOAc) to afford the analytically pure 4H-thiochromen-4-one 1c in 174 mg (73%) yield as a yellow solid, mp 122 ˚C.
¹H NMR (500 MHz, CDCl3): δ = 7.06 (s, 1 H), 7.48-7.58 (m, 4 H), 7.62-7.71 (m, 4 H), 8.54-8.57 (m, 1 H) ppm. ¹³C NMR (125 MHz, CDCl3): δ = 123.4 (CH), 126.5 (CH), 127.0 (2 CH), 127.8 (CH), 128.6 (CH), 129.3 (2 CH), 130.8 (CH), 130.9 (Cquat), 131.6 (CH), 136.6 (Cquat), 137.7 (Cquat), 153.1 (Cquat), 180.8 (Cquat) ppm. MS (EI, 70 eV): m/z (%) = 239 (18), 238 (100) [M]+ , 211 (14), 210 (83), 165 (14), 136 (59), 108 (45), 105 (12), 92 (11), 82 (12), 69 (17). Anal. Calcd for C20H18O3S (338.4): C, 75.60; H, 4.23. Found: C, 75.51; H, 4.41.
2-(3,4-Dimethoxyphenyl)-4 H -thiochromen-4-one (1f) ¹H NMR (500 MHz, CDCl3): δ = 3.94 (s, 3 H), 3.96 (s, 3 H), 6.96 (d, ³ J = 8.4 Hz, 1 H), 7.19 (d, 4 J = 2.2 Hz, 1 H), 7.22 (s, 1 H), 7.31 (dd, ³ J = 8.4 Hz, 4 J = 2.2 Hz, 1 H), 7.54 (ddd, ³ J = 8.2 Hz, ³ J = 6.8 Hz, 4 J = 1.3 Hz, 1 H), 7.61 (ddd, ³ J = 8.2 Hz, ³ J = 6.8 Hz, 4 J = 1.3 Hz, 1 H), 7.63-7.67 (m, 1 H), 8.53 (dd, ³ J = 8.0 Hz, 4 J = 1.2 Hz, 1 H) ppm. ¹³C NMR (125 MHz, CDCl3): δ = 56.05 (CH3), 56.06 (CH3), 109.6 (CH), 111.3 (CH), 120.0 (CH), 122.3 (CH), 126.4 (CH), 127.7 (CH), 128.5 (CH), 129.1 (Cquat), 130.9 (Cquat), 131.5 (CH), 137.6 (Cquat), 149.5 (Cquat), 151.4 (Cquat), 152.9 (Cquat), 180.9 (Cquat) ppm. Anal. Calcd for C17H14O3S (298.4): C, 68.44; H, 4.73. Found: C, 68.46; H, 4.57.

2-Ferrocenyl-4 H -thiochromen-4-one (1h) ¹H NMR (500 MHz, CDCl3): δ = 4.19 (s, 5 H), 4.52 (t, ³ J = 1.9 Hz, 2 H), 4.81 (t, ³ J = 1.9 Hz, 2 H), 7.12 (s, 1 H), 7.49-7.53 (m, 1 H), 7.58-7.60 (m, 2 H), 8.50 (dd, ³ J = 8.0 Hz, 1 H) ppm. ¹³C NMR (125 MHz, CDCl3): δ = 67.4 (2 CH), 70.8 (5 CH), 71.1 (2 CH), 80.0 (Cquat), 119.8 (CH), 126.1 (CH), 127.4 (CH), 128.5 (CH), 131.2 (Cquat), 131.3 (CH), 137.4 (Cquat), 154.8 (Cquat), 180.2 (Cquat) ppm. Anal. Calcd for C19H14FeOS (346.2): C, 65.91; H, 4.08. Found: C, 65.64; H, 4.04.
2-Cyclopropyl-4 H -thiopyrano[2,3- b ]pyridin-4-one (8a)1Η ΝΜΡ (500 ΜΗζ, ΧΔΧλ3): δ = 1.06−1.09 (µ, 2 Η), 1.17∠1.21 (µ, 2 Η), 1.98∠2.03 (µ, 1 Η), 6.78 (σ, 1 Η), 7.43 (δδ, 3ϑ = 8.1 Ηζ, 4ϑ = 4.5 Ηζ, 1 Η), 8.68 (δδ, 3ϑ = 8.1 Ηζ, 4ϑ = 1.9 Ηζ, 1 Η), 8.73 (δδ, 3ϑ = 4.5 Ηζ, 4ϑ = 1.9 Ηζ, 1 Η). 13Χ ΝΜΡ (125 ΜΗζ, ΧΔΧλ3): δ = 10.6 (2 ΧΗ2), 18.0 (ΧΗ), 121.0 (ΧΗ), 122.6 (ΧΗ), 128.3 (Χθυατ), 136.6 (ΧΗ), 152.4 (ΧΗ), 158.6 (Χθυατ), 160.9 (Χθυατ), 180.8 (Χθυατ). Αναλ. Χαλχδ. ϕορ Χ11Η9ΝΟΣ (203.26): Χ, 65.00; Η, 4.46; Ν, 6.89. Φουνδ: Χ, 64.72; Η, 4.46; Ν, 6.73.