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Synlett 2007(2): 0313-0317  
DOI: 10.1055/s-2007-967994
LETTER
© Georg Thieme Verlag Stuttgart · New York

Lawesson’s Reagent and Microwaves: A New Efficient Access to Benzoxazoles and Benzothiazoles from Carboxylic Acids under Solvent-Free Conditions

Julio A. Seijas*, M. Pilar Vázquez-Tato*, M. Raquel Carballido-Reboredo, José Crecente-Campo, Lucía Romar-López
Departamento de Química Orgánica, Universidad de Santiago de Compostela, Facultad de Ciencias, Aptdo. 280, 27080 Lugo, Spain
Fax: +34(982)285872; e-Mail: qoseijas@lugo.usc.es; e-Mail: pilarvt@lugo.usc.es;
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Publikationsverlauf

Received 10 October 2006
Publikationsdatum:
24. Januar 2007 (online)

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Abstract

Lawesson’s reagent acts as an efficient promoter in the solvent-free microwave-assisted synthesis of 2-substituted benzoxazoles from carboxylic acids and 2-aminophenol, and thus, constitutes a general synthetic method for these compounds. This new application of Lawesson’s reagent is valid also for benzothiazoles with very high efficiency level. A variety of aromatic, heteroaromatic and aliphatic carboxylic acids react under the conditions developed with good yields in all cases. Thiobenzoic acid is a good alternative for microwave-assisted synthesis of 2-phenylbenzoxazole and 2-phenylbenzothiazole in the absence of solvents.

Key words

benzothiazoles - benzoxazoles - Lawesson’s reagent - microwaves - thiobenzoic acid

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Lawesson reagent is used as purchased from Fluka (98% purity). Reactions must be carried out in an efficient fume hood.

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General Procedure for the Synthesis of Benzoxazoles 4 or Benzothiazoles 5 - Synthesis of 3-Methylbenzoxazole ( 4f).
A mixture of 3-methylbenzoic acid (6f, 136 mg, 1 mmol), 2-aminophenol (109 mg, 1 mmol) and Lawesson’s reagent (141 mg, 0.35 mmol) was irradiated in an open vessel with microwaves in a monomode oven (Discover CEM, 300W and temperature control set at 190 °C measured with an IR sensor) for 4 min. The crude was dissolved in CH2Cl2 (30 mL) and washed with 10% aq NaOH (2 × 20 mL), dried (Na2SO4) and evaporated to give pure (as per NMR) 2-(3-methylphenyl)benzoxazole (4f), further purification by flash chromatography gave 188 mg (90%) as a white solid. Mp 82-83 °C (EtOH), lit. [44] 81-82 °C. 1H NMR (300 MHz, CDCl3): δ = 8.09 (s, 1 H, ArH), 8.05 (d, 1 H, ArH, J = 7.6 Hz), 7.79-7.76 (m, 1 H, ArH), 7.58-7.55 (m, 1 H, ArH), 7.40 (t, 1 H, ArH, J = 7.6 Hz), 7.35-7.32 (m, 2 H, ArH), 2.45 (s, 3 H, CH3). 13C NMR (75 MHz, CDCl3): δ = 163.5, 151.0, 142.3, 139.0, 132.6, 129.1, 128.4, 127.2, 125.3, 125.0, 124.8, 120.2, 110.8, 21.6. MS (EI): m/z (%) = 209 (100) [M+], 180 (7).

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Data of Previously Undescribed Compounds.
2-(2,3-Dimethoxyphenyl)benzoxazole (4c): mp 75-76 °C (hexane). 1H NMR (300 MHz, CDCl3): δ = 7.83-7.77 (m, 1 H, ArH), 7.69 (dd, 1 H, ArH, J = 7.9, 1.5 Hz), 7.60-7.53 (m, 1 H, ArH), 7.35-7.29 (m, 2 H, ArH), 7.14 (t, 1 H, ArH, J = 8.0 Hz), 7.03 (dd, 1 H, ArH, J = 8.2, 1.4 Hz), 3.99 (s, 3 H, OCH3), 3.87 (s, 3 H, OCH3). 13C NMR (75 MHz, CDCl3): δ = 161.7, 154.0, 150.9, 149.0, 142.2, 125.3, 124.6, 124.5, 122.6, 122.0, 120.4, 115.6, 110.8, 61.7, 56.3. MS (EI): m/z (%) = 255 (100) [M+], 240 (18), 226 (56), 212 (10), 197 (13), 169 (2). Anal. Calcd for C15H13NO3: C, 70.58; H, 5.13; N, 5.49. Found: C, 70.41; H, 5.09; N, 5.38.
2-(2,4,5-Trimethoxyphenyl)benzoxazole (4e): mp 146-148 °C (hexane). 1H NMR (300 MHz, CDCl3): δ = 7.72-7.69 (m, 1 H, ArH), 7.59 (s, 1 H, ArH), 7.50-7.46 (m, 1 H, ArH), 7.26-7.21 (m, 2 H, ArH), 6.53 (s, 1 H, ArH), 3.91, 3.87 and 3.86 (3 s, 3 × 3 H, 3 × OCH3). 13C NMR (75 MHz, CDCl3): δ = 163.3, 155.2, 154.2, 149.1, 143.0, 140.5, 125.0, 124.9, 118.9, 110.5, 108.3, 101.5, 100.9, 56.7, 56.2. MS (EI): m/z (%) = 285 (100) [M+], 271 (29), 256 (76), 242 (19), 240 (17), 227 (7), 212 (13). Anal. Calcd for C16H15NO4: C, 67.36; H, 5.30; N, 4.91. Found: C, 67.66; H, 4.96; N, 5.11.
2-[(3,4-Dimethoxyphenyl)methyl]benzoxazole (4n): mp 66-68 °C (hexane). 1H NMR (300 MHz, CDCl3): δ = 7.68-7.64 (m, 1 H, ArH), 7.43-7.40 (1 H, m, ArH), 7.27-7.22 (m, 2 H, ArH), 6.91-6.87 (m, 2 H), 6.80 (d, 1 H, ArH, 8.0 Hz), 4.17 (s, 2 H, CH2), 3.83 and 3.81 (2 s, 2 × 3 H, 2 × OCH3). 13C NMR (75 MHz, CDCl3): δ = 165.7, 151.2, 149.4, 148.6, 141.6, 127.4, 124.9, 124.4, 121.4, 120.0, 112.4, 111.7, 110.6, 56.1, 35.0. MS (EI): m/z (%) = 269 (100) [M+], 254 (42), 226 (7), 183 (5), 151 (20). Anal. Calcd for C16H15NO3: C, 71.36; H, 5.61; N, 5.20. Found: C, 71.05; H, 5.73; N, 5.16.
2-(2,4,5-Trimethoxyphenyl)benzothiazole (5e): mp 200-201 °C (EtOH). 1H NMR (300 MHz, CDCl3): δ = 8.07 (s, 1 H, ArH), 8.04 (d, 1 H, ArH, J = 7.9 Hz), 7.89 (d, 1 H, J = 7.9 Hz), 7.46 (ddd, 1 H, ArH, J = 8.2, 7.0, 1.2 Hz), 7.34 (dd, 1 H, ArH, J = 7.9, 0.9 Hz), 6.62 (s, 1 H, ArH), 4.04, 4.01 and 3.97 (3 s, 3 × 3 H, 3 × OCH3). 13C NMR (75 MHz, CDCl3): δ = 163.3, 153.0, 152.4, 152.3, 143.0, 136.0, 126.0, 124.4, 122.5, 121.4, 114.6, 111.5, 97.4, 56.8, 56.7, 56.3. MS (EI): m/z (%) = 301 (100) [M+], 286 (11), 272 (30), 256 (11), 228 (11), 215 (4), 186 (5), 160 (2). Anal. Calcd for C16H15NO3S: C, 63,77; H, 5,02; N, 4,65. Found: C, 64.05; H, 4.73; N, 4.87.
2-[(3,4-Dimethoxyphenyl)methyl]benzothiazole (5n): mp 68-69 °C (hexane). 1H NMR (300 MHz, CDCl3): δ = 7.97 (dd, 1 H, ArH, J = 8.8, 0.9 Hz), 7.73 (dd, 1 H, J = 7.9, 1.3 Hz), 7.40 (td, 1 H, ArH, J = 7.9, 1.2 Hz), 7.28 (t, 1 H, ArH, J = 7.6 Hz), 6.90-6.85 (m, 2 H, ArH), 6.80 (d, 1 H, ArH, J = 7.9 Hz), 4.34 (s, 2 H, CH2), 3.82 and 3.81 (2 s, 2 × 3 H, 2 × OCH3). 13C NMR (75 MHz, CDCl3): δ = 171.9, 153.5, 149.4, 148.6, 135.8, 129.9, 126.1, 125.0, 122.9, 121.7, 121.5, 112.6, 111.6, 56.03, 56.00, 40.4. MS (EI): m/z (%) = 285 (100) [M+], 270 (9), 242 (13), 227 (11), 199 (14), 151 (10). Anal. Calcd for C16H15NO2S: C, 67.34; H, 5.30; N, 4.91. Found: C, 67.14; H, 5.28; N, 4.85.