PDF herunterladen
Synlett 2009(4): 611-614  
DOI: 10.1055/s-0028-1087562
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

New Efficient Synthesis of 5-Ethoxyoxazoles and Oxazolo[3,2-c]quinazolines via Aza-Wittig Reaction

Nian-Yu Huang, Yi-Bo Nie, Ming-Wu Ding*
Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, Central China Normal University, Wuhan 430079, P. R. of China
Fax: +86(27)67862041; e-Mail: mwding@mail.ccnu.edu.cn;
Weitere Informationen

Publikationsverlauf

Received 23 October 2008
Publikationsdatum:
16. Februar 2009 (online)

    Lizenzen und Reprints Alle Artikel dieser Rubrik

Abstract

5-Ethoxyoxazoles or 2-acylamino propanoates were synthesized by aza-Wittig reaction of iminophosphorane with acyl chloride in the presence of triethylamine. Reactions of 5-alkoxyoxazole with triphenyphosphine produced iminophosphoranes. A tandem aza-Wittig reaction of iminophosphorane with isocyanate or carbon disulfide generated oxazolo[3,2-c]quinazolines in satisfactory yields.

Key words

oxazole - oxazolo[3,2-c]quinazoline - aza Wittig reaction - carbodiimide - imidoyl chloride

    References and Notes

  • 1a Palmer DC. Venkatraman S. Oxazoles: Synthesis, Reactions, and Spectroscopy   Part A:  John Wiley; New York: 2003.  p.1-390  
    Google Scholar
  • 1b Wasserman HH. McCarthy KE. Prowse KS. Chem. Rev.  1986,  86:  845 
    Google Scholar
  • 1c Hartner FW. In Comprehensive Heterocyclic Chemistry II   Vol. 3:  Shinkai I. Pergamon; Oxford UK: 1996.  p.262-318  
    Google Scholar
  • 2 Jacobi PA. Lee K. J. Am. Chem. Soc.  1997,  119:  3409 
    Google Scholar
  • 3a Doyle KJ. Moody CJ. Tetrahedron  1994,  50:  3761 
    Google Scholar
  • 3b Moody CJ. Bagley MC. Synlett  1998,  361 
    Google Scholar
  • 3c Ducept PC. Marsden SP. Synlett  2000,  692 
    Google Scholar
  • 4a Huang W.-S. Zhang Y.-X. Yuan C.-Y. Synth. Commun.  1996,  26:  1149 
    Google Scholar
  • 4b Bossio R. Marcaccini S. Pepino R. Heterocycles  1986,  24:  2003 
    Google Scholar
  • 5a Jacobi PA. Kaczmarek CSR. Udodong UES. Tetrahedron  1987,  43:  5475 
    Google Scholar
  • 5b Nahm S. Weinreb SM. Tetrahedron Lett.  1981,  22:  3815 
    Google Scholar
  • 5c Collins DJ. Hughes TC. Johnson WM. Aust. J. Chem.  1996,  49:  463 
    Google Scholar
  • 6a Chan J. Faul M. Tetrahedron Lett.  2006,  47:  3361 
    Google Scholar
  • 6b Palacios F. Herran E. Alonso C. Rubiales G. Lecea B. Ayerbe M. Cossio FP. J. Org. Chem.  2006,  71:  6020 
    Google Scholar
  • 6c Lertpibulpanya D. Marsden SP. Rodriguez-Garcia I. Kilner CA. Angew. Chem. Int. Ed.  2006,  45:  5000 
    Google Scholar
  • 6d Palacios F. Alonso C. Aparicio D. Rubiales G. Santos JM. Tetrahedron  2007,  63:  523 
    Google Scholar
  • 6e Zanatta N. Schneider JMFM. Schneider PH. Wouters AD. Bonacorso HG. Martins MAP. Wessjohann LA. J. Org. Chem.  2006,  71:  6996 
    Google Scholar
  • 7 Takeuchi H. Yanagida S. Ozaki T. Hagiwara S. Eguchi S. J. Org. Chem.  1989,  54:  431 
    CrossrefGoogle Scholar
  • 8 Molina P. Fresneda PM. Almendros P. Heterocycles  1993,  36:  2255 
    CrossrefGoogle Scholar
  • 9 Zbiral E. Bauer E. Stroh J. Monatsh. Chem.  1971,  102:  168 
    CrossrefGoogle Scholar
  • 10a Ding MW. Xu SZ. Zhao JF. J. Org. Chem.  2004,  69:  8366 
    Google Scholar
  • 10b Zhao JF. Xie C. Xu SZ. Ding MW. Xiao WJ. Org. Biomol. Chem.  2006,  4:  130 
    Google Scholar
  • 10c Yuan JZ. Fu BQ. Ding MW. Yang GF. Eur. J. Org. Chem.  2006,  4170 
    Google Scholar
  • 10d Ding MW. Fu BQ. Cheng L. Synthesis  2004,  1067 
    Google Scholar
  • 10e Li HX. Xie C. Ding MW. Liu ZM. Yang GF. Synlett  2007,  2280 
    Google Scholar
  • 10f Liu MG. Hu YG. Ding MW. Tetrahedron  2008,  64:  9052 
    Google Scholar
11

Oxazoles 4 and 2-Acylaminopropanoates 5
To a stirred solution of azide 1 (1.0 mmol) in CH2Cl2 (10 mL) was added a solution of Ph3P (0.26 g, 1 mmol) in dry CH2Cl2 (5 mL) at r.t. After the reaction mixture was stirred for 2 h, acyl chloride (1.0 mmol) and Et3N (0.30 g, 3.0 mmol) were added at r.t., and the color of the solution turned yellow. After stirring for 4 h, the mixture was filtered to remove the Et3NHCl, and the filtrate was evaporated under reduced pressure. The crude product was purified by flash chromatography (5:1, PE-Et2O) to yield oxazoles 4 or
2-acylaminopropanoates 5.
Spectral Data for Some Unreported Compounds
Compound 4c: light yellow solid, mp 60-61 ˚C. IR (KBr): 1620, 1487, 1282, 1093, 1005 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 7.68-7.21 (m, 4 H, ArH), 6.05 (s, 1 H, ArH), 4.00 (q, J = 7.2 Hz, 2 H, OCH2), 1.30 (t, J = 7.0 Hz, 3 H, CH3). ¹³C NMR (100 MHz, CDCl3): δ = 159.5, 150.9, 134.8, 128.5, 128.4, 126.2, 125.9, 125.7, 100.3, 100.1, 67.6, 14.2, 14.0. MS: m/z (%) = 223 (90) [M+], 195 (73), 167 (23), 139 (100), 111 (64). Anal. Calcd. for C11H10ClNO2: C, 59.07; H, 4.51; N, 6.26. Found: C, 59.01; H, 4.61; N, 6.44.
Compound 4d: white solid, mp 52-54 ˚C. IR (KBr): 1613, 1503, 1282, 1222, 1046, 1008 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 7.91-7.07 (m, 4 H, ArH), 6.18 (s, 1 H, ArH), 4.20-4.13 (m, 2 H, OCH2), 1.48-1.43 (m, 3 H, CH3). ¹³C NMR (100 MHz, CDCl3): δ = 164.1, 161.7, 159.4, 151.0, 126.9, 126.5, 123.6, 115.5, 115.3, 115.2, 114.9, 100.1, 99.7, 67.7, 67.4, 67.2, 13.9, 13.8. MS: m/z (%) = 207 (71) [M+], 178 (45), 151 (36), 134 (17), 123 (100), 107 (25). Anal. Calcd for C11H10FNO2: C, 63.76; H, 4.86; N, 6.76. Found: C, 63.50; H, 4.98; N, 6.71.
Compound 4e: white solid, mp 46-47 ˚C. IR (KBr): 1613, 1503, 1279, 1099, 1046, 1008 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 7.81-7.21 (m, 4 H, ArH), 6.18 (s, 1 H, ArH), 4.16 (q, J = 7.2 Hz, 2 H, OCH2), 2.37 (s, 3 H, CH3), 1.45 (t, J = 7.2 Hz, 3 H, CH3). ¹³C NMR (100 MHz, CDCl3): δ = 159.4, 152.7, 139.5, 129.3, 129.2, 125.2, 125.0, 124.8, 100.4, 100.1, 67.9, 21.4, 21.2, 14.5, 14.3. MS: m/z (%) = 203 (14) [M+], 174 (5), 147 (13), 119 (100), 91 (20). Anal. Calcd for C12H13NO2: C, 70.92; H, 6.45; N, 6.89. Found: C, 70.80; H, 6.60; N, 6.76.
Compound 4f: white solid, mp 51-52 ˚C. IR (KBr): 1616, 1506, 1254, 1024 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 7.84 (d, J = 8.8 Hz, 2 H, ArH), 6.91 (d, J = 8.8 Hz, 2 H, ArH), 6.15 (s, 1 H, ArH), 4.10 (q, J = 7.2 Hz, 2 H, OCH2), 3.78 (s, 3 H, OCH3), 1.41 (t, J = 7.2 Hz, 3 H, CH3). ¹³C NMR (100 MHz, CDCl3): δ = 160.3, 159.1, 152.2, 126.5, 120.1, 113.7, 99.9, 67.6, 54.8, 14.1. MS: m/z (%) = 219 (24) [M+], 190 (20), 163 (3), 135 (100), 118 (3), 107 (6). Anal. Calcd for C12H13NO3: C, 65.74; H, 5.98; N, 6.39. Found: C, 65.67; H, 6.05; N, 6.44.
Compound 4g: white solid, mp 50-51 ˚C. IR (KBr): 1601, 1556, 1481, 1282, 1043, 1005 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 7.86-7.28 (m, 4 H, ArH), 6.18 (s, 1 H, ArH), 4.13 (q, J = 7.0 Hz, 2 H, OCH2), 1.42 (t, J = 7.0 Hz, 3 H, CH3). ¹³C NMR (100 MHz, CDCl3): δ = 159.7, 150.6, 134.4, 129.7, 129.0, 124.9, 122.9, 100.6, 67.8, 14.2. MS: m/z (%) = 223 (19) [M+], 195 (22), 167 (16), 139 (100). Anal. Calcd for C11H10ClNO2: C, 59.07; H, 4.51; N, 6.26. Found: C, 59.19; H, 4.70; N, 6.32.
Compound 4h: white solid, mp 45-46 ˚C. IR (KBr): 1610, 1497, 1478, 1282, 1229, 1043, 1027 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 7.91-7.11 (m, 4 H, ArH), 6.27 (s, 1 H, ArH), 4.16 (q, J = 7.0 Hz, 2 H, OCH2), 1.43 (t, J = 7.0 Hz,
3 H, CH3). ¹³C NMR (100 MHz, CDCl3): δ = 160.4, 159.6, 157.9, 148.3, 130.7, 130.6, 128.1, 123.9, 116.4, 116.2, 115.5, 115.4, 100.4, 67.7, 14.1. MS: m/z (%) = 207 (16) [M+], 179 (13), 151 (6), 123 (100), 95 (22). Anal. Calcd for C11H10FNO2: C, 63.76; H, 4.86; N, 6.76. Found: C, 63.70; H, 4.98; N, 6.83.
Compound 4i: light yellow solid, mp 52-54 ˚C. IR (KBr): 2130 (N3), 1610 (C=O), 1594, 1493, 1304, 1285, 1033, 1005 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 7.88-7.17 (m, 4 H, ArH), 6.28 (s, 1 H, ArH), 4.19 (q, J = 7.0 Hz, 2 H, OCH2), 1.47 (t, J = 7.0 Hz, 3 H, CH3). MS: m/z (%) = 230 (50) [M+], 202 (39), 173 (55), 145 (57), 118 (29), 90 (100). Anal. Calcd for C11H10N4O2: C, 57.39; H, 4.38; N, 24.34. Found: C, 57.45; H, 4.50; N, 24.49.
Compound 4k: light yellow oil. ¹H NMR (600 MHz, CDCl3): δ = 7.80-7.21 (m, 4 H, ArH), 4.22 (q, J = 7.0 Hz,
2 H, OCH2), 2.37 (s, 3 H, CH3), 2.11 (s, 3 H, CH3), 1.40 (t, J = 7.2 Hz, 3 H, CH3). MS: m/z (%) = 217 (5) [M+], 136 (2), 119 (62), 91 (100).
Compound 4l: white solid, mp 83-85 ˚C. ¹H NMR (600 MHz, CDCl3): δ = 7.85-7.37 (m, 4 H, ArH), 4.23 (q, J = 7.2 Hz, 2 H, OCH2), 2.11 (s, 3 H, CH3), 1.40 (t, J = 7.2 Hz, 3 H, CH3). MS: m/z (%) = 237 (75) [M+], 207 (13), 138 (100), 110 (43). Anal. Calcd for C12H12ClNO2: C, 60.64; H, 5.09; N, 5.89. Found: C, 60.47; H, 5.24; N, 5.95.
Compound 5a: white solid, mp 76-77 ˚C. IR (KBr): 3347 (NH), 1749 (C=O), 1642, 1528, 1493, 1213, 1181 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 7.82-7.42 (m, 5 H, ArH), 6.84 (d, J = 6.4 Hz, 1 H, NH), 4.82-4.76 (m, 1 H, NCH), 4.24 (q, J = 7.0 Hz, 2 H, OCH2), 1.52 (d, J = 6.8 Hz, 3 H, CH3), 1.31 (t, J = 7.2 Hz, 3 H, CH3). ¹³C NMR (100 MHz, CDCl3): δ = 173.2, 166.7, 133.9, 131.6, 128.5, 127.0, 61.6, 48.5, 18.6, 14.1. MS: m/z (%) = 221 (4) [M+], 148 (66), 105 (100), 77 (24). Anal. Calcd for C12H15NO3: C, 65.14; H, 6.83; N, 6.33. Found: C, 65.33; H, 6.98; N, 6.43.
Compound 5b: white solid, mp 117-118 ˚C. IR (KBr): 3290 (NH), 1742 (C=O), 1635, 1556, 1203, 1162, 1024 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 7.72-7.23 (m, 4 H, ArH), 6.75 (d, J = 6.8 Hz, 1 H, NH), 4.82-4.74 (m, 1 H, NCH), 4.24 (q, J = 7.2 Hz, 2 H, OCH2), 2.40 (s, 3 H, CH3), 1.52 (d, J = 7.2 Hz, 3 H, CH3), 1.31 (t, J = 7.2 Hz, 3 H, CH3).
MS: m/z (%) = 235 (6) [M+], 162 (29), 119 (100), 91 (13). Anal. Calcd for C13H17NO3: C, 66.36; H, 7.28; N, 5.95. Found: C, 66.44; H, 7.40; N, 5.99.
Compound 5c: white solid, mp 98-99 ˚C. IR (KBr): 3293 (NH), 1742, 1626, 1544, 1487, 1216, 1166, 1093, 1017
cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 7.75 (d, J = 8.4 Hz, 2 H, ArH), 7.40 (d, J = 8.4 Hz, 2 H, ArH), 6.84 (br, 1 H, NH), 4.80-4.72 (m, 1 H, NCH), 4.25 (q, J = 7.2 Hz, 2 H, OCH2), 1.52 (d, J = 7.2 Hz, 3 H, CH3), 1.32 (t, J = 7.2 Hz, 3 H, CH3). MS: m/z (%) = 255 (4) [M+], 182 (68), 139 (100), 111 (14). Anal. Calcd for C13H17NO3: C, 56.37; H, 5.52; N, 5.48. Found: C, 56.45; H, 5.78; N, 5.59.

12

Iminophosphorane 6 To a stirred solution of 4i (1.15 g, 5 mmol) in CH2Cl2 (15 mL) was added a solution of Ph3P (1.31 g, 5 mmol) in dry CH2Cl2 (10 mL). After the reaction mixture was stirred for 2 h, the solvent was removed under reduced pressure, and the residue was recrystallized from Et2O and EtOH (1:1; v/v) to give the iminophosphorane 6 (2.22 g, yield 96%); light yellow crystals; mp 175-177 ˚C. IR (KBr): 1606, 1468, 1435, 1353, 1271, 1118, 1035cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 7.86-6.53 (m, 19 H, ArH), 6.23 (s, 1 H, ArH), 4.14 (q, J = 7.0 Hz, 2 H, OCH2), 1.45 (t, J = 7.0 Hz, 3 H, CH3). MS: m/z (%) = 464 (100) [M+], 435 (65), 380 (92), 277 (18), 261 (10), 201 (11), 183 (16), 145 (16). Anal. Calcd for C29H25N2O2P: C, 74.99; H, 5.42; N, 6.03. Found: C, 74.77; H, 5.60; N, 6.12.

13

Oxazolo[3,2- c ]quinazolines 8 To a solution of iminophosphorane 6 (0.46 g, 1 mmol) in dry CH2Cl2 (10 mL) was added aryl isocyanate (1 mmol) under nitrogen at r.t. The solution turned red immediately. After stirred for 1 h, the solvent was evaporated under reduced pressure, and the residue was recrystallized from Et2O and EtOH (1:1, v/v) to give oxazolo[3,2-c]quinazolines 8 as red crystals.
Compound 8a: red crystals, mp 151 ˚C (dec.). IR (KBr): 1764, 1690, 1640, 1560, 1474, 1440, 1307, 1251 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 7.68-6.94 (m, 10 H, ArH), 4.39 (q, J = 7.0 Hz, 2 H, OCH2), 1.58 (t, J = 7.0 Hz, 3 H, CH3). ¹³C NMR (150 MHz, CDCl3): δ = 157.5, 153.2, 150.8, 147.2, 143.4, 135.5, 129.1, 128.4, 125.6, 123.3, 121.7, 120.4, 102.7, 87.9, 70.5, 14.3. MS: m/z (%) = 305 (53) [M+], 248 (29), 231 (100), 205 (60), 166 (15), 104 (10), 90 (22). Anal. Calcd for C18H15N3O2: C, 70.81; H, 4.95; N, 13.76. Found: C, 70.90; H, 4.99; N, 13.91.
Compound 8b: red crystals, mp 105-107 ˚C. IR (KBr): 1765, 1689, 1639, 1605, 1471, 1442, 1219, 1165 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 7.62-6.78 (m, 9 H, ArH), 4.34 (q, J = 7.0 Hz, 2 H, OCH2), 2.35 (s, 3 H, CH3), 1.56 (t, J = 7.0 Hz, 3 H, CH3). ¹³C NMR (150 MHz, CDCl3): δ = 157.4, 153.6, 150.8, 148.2, 143.6, 137.8, 135.3, 128.1, 125.4, 124.0, 122.2, 121.6, 120.3, 119.8, 102.3, 87.7, 70.3, 21.6, 14.2. MS: m/z (%) = 319 (6) [M+], 291 (100), 262 (13), 248 (46), 235 (28), 91 (5). Anal. Calcd for C19H17N3O2: C, 71.46; H, 5.37; N, 13.16. Found: C, 71.59; H, 5.50; N, 13.20.
Compound 8c: red crystals, mp 157 ˚C (dec.). IR (KBr): 1642, 1605, 1558, 1530, 1478, 1441, 1308, 1254, 1032
cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 7.64-6.92 (m, 9 H, ArH), 4.33 (q, J = 7.2 Hz, 2 H, OCH2), 1.56 (t, J = 7.2 Hz, 3 H, CH3). ¹³C NMR (100 MHz, CDCl3): δ = 157.6, 152.8, 150.6, 135.7, 129.9, 128.2, 128.1, 126.1, 125.5, 124.4, 121.7, 121.0, 102.9, 88.0, 70.6, 14.3. MS: m/z (%) = 339 (100) [M+], 311 (68), 265 (88), 255 (81), 230 (53), 192 (10), 125 (24). Anal. Calcd for C18H14ClN3O2: C, 63.63; H, 4.15; N, 12.37. Found: C, 63.89; H, 4.22; N, 12.51.
Compound 8d: red crystals, mp 156 ˚C (dec.). IR (KBr): 1665, 1644, 1610, 1562, 1485, 1441, 1308, 1207, 1032
cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 7.65-6.89 (m, 9 H, ArH), 4.36 (q, J = 7.0 Hz, 2 H, OCH2), 1.57 (t, J = 7.0 Hz, 3 H, CH3). ¹³C NMR (100 MHz, CDCl3): δ = 159.1, 157.4, 156.7, 153.7, 144.7, 143.8, 135.4, 125.3, 124.5, 124.5, 121.7, 119.8, 114.8, 114.6, 102.3, 87.6, 70.3, 14.3. MS: m/z (%) = 323 (32) [M+], 295 (26), 266 (33), 250 (100), 239 (89), 223 (36), 125 (45). Anal. Calcd for C18H14FN3O2: C, 66.87; H, 4.36;N, 13.00. Found: C, 66.73; H, 4.54; N, 13.25.

14

Oxazolo[3,2- c ]quinazoline 10 To a solution of iminophosphorane 6 (0.46 g, 1 mmol) in MeCN (10 mL) was added CS2 (1.50 g, 20 mmol). The mixture was heated to reflux for 10 h, the solvent was evaporated under reduced pressure, and the residue was recrystallized from EtOH to give oxazolo[3,2-c]quinazoline 10; yellow crystals, mp 138-139 ˚C. IR (KBr): 1654, 1635, 1484, 1434, 1321, 1298, 1176, 1054 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 7.94-7.38 (m, 5 H, ArH), 4.47 (q, J = 7.2 Hz, 2 H, OCH2), 1.61 (t, J = 7.2 Hz, 3 H, CH3). ¹³C NMR (100 MHz, CDCl3): δ = 157.4, 148.4, 138.4, 135.7, 128.2, 126.8, 125.0, 121.5, 115.5, 91.3, 71.0, 14.2. MS: m/z (%) = 246 (37) [M+], 218 (25), 190 (28), 162 (100), 134 (34). Anal. Calcd for C12H10N2O2S: C, 58.52; H, 4.09; N, 11.37. Found: C, 58.59; H, 4.21; N, 11.41.