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;
Further Information

Publication History

Received 10 October 2006
Publication Date:
24 January 2007 (online)

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.

    References and Notes

  • 1 Pinar A. Yurdakul P. Yildiz I. Temiz-Arpaci O. Acan NL. Aki-Sener E. Yalcin I. Biochem. Biophys. Res. Commun.  2004,  317:  670 
  • 2 Rida SM. Ashour FA. El-Hawash SAM. ElSemary MM. Badr MH. Shalaby MA. Eur. J. Med. Chem.  2005,  40:  949 
  • 3 Sum P.-E. How D. Torres N. Newman H. Petersen PJ. Mansoura TS. Bioorg. Med. Chem. Lett.  2003,  13:  2607 
  • 4 Mahran MA. El-Nassry SMF. Allam SR. El-Zawawy LA. Pharmazie  2003,  58:  527 
  • 5 Sondhi SM. Singh N. Kumar A. Lozach O. Meijer L. Bioorg. Med. Chem.  2006,  14:  3758 
  • 6 Sato F. Inoue Y. Omodani T. Imano K. Okazaki H. Takemura T. Komiya M. Bioorg. Med. Chem. Lett.  2002,  12:  551 
  • 7 Reiser A. Leyshon LJ. Saunders D. Mijovic MV. Bright A. Bogie J. J. Am. Chem. Soc.  1972,  94:  2414 
  • 8 Ke WJ. Xu HS. Liu XF. Luo XH. Heterocycles  2000,  53:  1821 
  • 9 Kelleher KA, and Stanhope MT. inventors; US  2002069453.  2002; Chem. Abstr. 2002, 137, 7475
  • 10 Song KC. Kim JS. Park SM. Chung K.-C. Ahn S. Chang S.-K. Org. Lett.  2006,  8:  3413 
  • 11 Luan XH. Cerqueira NMFSA. Oliveira AMAG. Raposo MMM. Rodrigues LMCP. Campos AMFO. Adv. Colour Sci. Tech.  2002,  5:  18 
  • 12 Hoveyda HR. Rettig SJ. Orvig C. Inorg. Chem.  1993,  32:  4909 
  • 13 Dolbier WR. Burkholder CR. Medebielle M. J. Fluorine Chem.  1999,  95:  127 
  • 14 So Y.-H. Heeschen JP. J. Org. Chem.  1997,  62:  3552 
  • 15 Cohen VI. J. Heterocycl. Chem.  1979,  16:  13 
  • 16 Kumar RV. Asian J. Chem.  2004,  16:  1241 
  • 17a Microwaves in Organic Synthesis   Loupy A. Wiley-VCH; Weinheim: 2002. 
  • 17b Kappe CO. Stadler A. Microwaves in Organic and Medicinal Chemistry   Wiley-VCH; Weinheim: 2005. 
  • 18 Kumar R. Selvam C. Kaur G. Chakraborti AK. Synlett  2005,  1401 
  • 19 Chakraborti AK. Selvam C. Kaur G. Bhagat S. Synlett  2004,  851 
  • 20 Bougrin K. Loupy A. Soufiaoui M. Tetrahedron  1998,  54:  8055 
  • 21 Rostamizadeh S. Derfshian E. J. Chem. Res., Synop.  2001,  227 
  • 22 Njoya Y. Gellis A. Crozet MP. Vanelle P. Sulfur Lett.  2003,  26:  67 
  • 23 Evindar G. Batey RA. J. Org. Chem.  2006,  71:  1802 
  • 24 Pottorf RS. Chadha NK. Katkevics M. Ozola V. Suna E. Ghane H. Regberg T. Player MR. Tetrahedron Lett.  2003,  44:  175 
  • 25 Kamila S. Zhang H. Biehl ER. Heterocycles  2005,  65:  2119 
  • 26 Paul S. Gupta M. Gupta R. Synth. Commun.  2002,  32:  3541 
  • 27 Villemin D. Hammadi M. Martin B. Synth. Commun.  1996,  26:  2895 
  • 28 Kodomari M. Tamaru Y. Aoyama T. Synth. Commun.  2004,  34:  3029 
  • 29 Rann BC. Jana R. Dey SS. Chem. Lett.  2004,  33:  274 
  • 30 Janssen MJ. In The Chemistry of Carboxylic Acid and Esters   Patai S. Wiley; Chichester: 1969.  p.705-764  
  • 31 Filippi J.-J. Fernandez X. Lizzani-Cuvelier L. Loiseau A.-M. Tetrahedron Lett.  2003,  44:  6647 
  • 32 Wu X. Mahalingam AK. Alterman M. Tetrahedron Lett.  2005,  46:  1501 
  • 33 Valette L. Poulain S. Fernandez X. Lizzani-Cuvelier L. J. Sulfur Chem.  2005,  26:  155 
  • 34 Deng S.-L. Chen R.-Y. Monatsh. Chem.  2004,  135:  1113 
  • 35 Huang H.-M. Yu H.-T. Chen P.-L. Han J. Meng J.-B. Youji Huaxue  2004,  24:  502 ; Chem. Abstr. 2004, 141, 295952
  • 36 Kiryanov AA. Sampson P. Seed AJ. J. Org. Chem.  2001,  66:  7925 
  • 37 Jesberger M. Davis TP. Barner L. Synthesis  2003,  1929 
  • 38 Pedersen U. Thorsen M. El-Khrisy EEAM. Clausen K. Lawesson SO. Tetrahedron  1982,  38:  3267 
  • 39 Shi W. Shafaei-Fallah M. Anson CE. Rothenberger A. J. Chem. Soc., Dalton Trans.  2005,  3909 
  • 42 Yoshifuji M. Nagase R. Kawashima T. Inamoto N. Heterocycles  1978,  10:  57 
  • 43 Brewster K. Chittenden RA. Harrison JM. Inch TD. Brown C. J. Chem. Soc., Perkin Trans. 1  1976,  1291 
  • 44 El-Sheikh MI. Marks A. Biehl ER. J. Org. Chem.  1981,  46:  3256 
  • 45 Yoshifuji M. Nagase R. Inamoto N. Bull. Chem. Soc. Jpn.  1982,  55:  873 
  • 46 Tauer E. Grellmann KH. J. Org. Chem.  1981,  46:  4252 
  • 47 Bayh O. Awad H. Mongin F. Hoarau C. Bischoff L. Trecourt F. Queguiner G. Marsais F. Blanco F. Abarca B. Ballesteros R. J. Org. Chem.  2005,  70:  5190 
  • 48 Prakash O. Batra A. Sharma V. Saini RK. Verma RS. J. Indian Chem. Soc.  2003,  80:  1031 
  • 49 Shimada T. Yamamoto Y. J. Am. Chem. Soc.  2003,  125:  6646 
  • 50 Itoya K. Sawada H. Kakimoto M. Imai Y. Macromolecules  1995,  28:  2611 
  • 51 Bywater WG. Coleman WR. Kamm O. Merritt H. J. Am. Chem. Soc.  1945,  67:  905 
  • 53 Osuka A. Uno Y. Horiuchi H. Suzuki H. Synthesis  1984,  145 
  • 54 Mortimer CG. Wells G. Crochard J.-P. Stone EL. Bradshaw TD. Stevens MFG. Westwell AD. J. Med. Chem.  2006,  49:  179 
  • 55 Ulrich H. In Science of Synthesis   Vol. 11:  Schaumann E. Thieme; Stuttgart: 2001.  p.835-912  
  • 56 Deligeorgiev TC. Dyes Pigm.  1990,  12:  243 
  • 57 Itoh T. Nagata K. Ishikawa H. Ohsawa A. Heterocycles  2004,  63:  2769 
  • 58 Tzanopoulou S. Pirmettis IC. Patsis G. Raptopoulou C. Terzis A. Papadopoulos M. Pelecanou M. Inorg. Chem.  2006,  45:  902 
  • 59 Boger DL. J. Org. Chem.  1978,  43:  2296 
  • 60 Elderfield RC. McClenachan EC. J. Am. Chem. Soc.  1960,  82:  1982 
  • 61 DuBrow PL. Hoerr CW. Harwood HJ. J. Am. Chem. Soc.  1952,  74:  6241 
  • 62 Shabana R. Atrees SS. Phosphorus, Sulfur Silicon Relat. Elem.  1995,  105:  57 
40

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

41

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).

52

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.