Advanced
2-Phenylamino-2-oxazolines from N-(2-Hydroxyethyl)-N-phenylthioureas using TsCl/NaOH
2-Phenylamino-2-oxazolines from N-(2-Hydroxyethyl)-N-phenylthioureas using TsCl/NaOH
Journal of the Korean Chemical Society. 2003. Dec, 47(6): 671-674
Copyright © 2003, The Korean Chemical Society
  • Received : September 16, 2003
  • Published : December 20, 2003
Download
PDF
e-PUB
PubReader
PPT
Export by style
Article
Author
Metrics
Cited by
TagCloud
About the Authors
혜선 나
택현 김

Abstract
Keywords
PPT Slide
Lager Image
PPT Slide
Lager Image
PPT Slide
Lager Image
EXPERIMENTAL SECTION
General methods. 1 H NMR and 13 C NMR spectra were recorded using 300 MHz and 75 MHz NMR spectrometer; chemical shifts are reported in ppm using TMS as an internal standard. Melting points were measured in a glass capillary apparatus and uncorrected. Mass spectra were recorded on a HP 5983B GC/Mass spectrometer. Analytical TLC was performed on 0.25 mm precoated silica gel plates. Flash chromatography was carried out with 230-400 mesh silica gel.
General procedure for the preparation of thioureas 2. To a stirred solution of 1,2-aminoalcohol (4.59 mmol) in THF (10 mL) under nitrogen at room temperature was added a solution of phenyl isothiocyanate (0.50 mL, 4.18 mmol) in THF (5 mL) dropwise for 5 min with a syringe. The reaction mixtrue was stirred for 30 min and evaporated. The crude product was purified by flash column chromatography to afford corresponding thiourea.
N-(2-Hydroxyethyl)-N’-phenylthiourea (2a). yield 96%; white solid, mp 108-109 ℃; Rf =0.3 (ethyl acetate/hexane 1:1); IR (CDCl 3 , cm -1 2142 (N=C=N); 1 H NMR (CDCl 3 ) δ 8.13 (1H, bs) 7.44-7.22 (5H, m), 6.58 (1H, bs), 4.04-4.01 (1H, m), 3.92-3.88 (1H, m), 3.48-3.41 (1H, m), 2.35 (1H, bs), 1.20 (3H, d, J =6.2 Hz); 13 C NMR (CDCl 3 ) δ 180.6, 136.2, 130.1, 127.2, 124.9, 67.1, 52.0, 21.1; HRMS calcd for C 10 H 14 N 2 OS: 210.0827. Found 210.0826.
N-(2-Hydroxyethyl)-N’-phenylthiourea (2b). yield 97%; white solid, mp 102-103 ℃; Rf =0.5 (ethyl acetate/hexane 1:1); 1 H NMR (CDCl 3 ) δ 7.82 (1H, bs) 7.46-7.21 (5H, m), 6.52 (1H, bs), 3.97-3.85 (1H, m), 3.80-3.74 (1H, m), 3.51-3.45 (1H, m), 2.01 (1H, bs), 1.58-1.42 (2H, m), 0.98 (3H, t, J =7.4 Hz); 13 C NMR (CDCl 3 ) δ 180.9, 136.1, 130.2, 127.2, 125.0, 72.4, 50.6, 28.1, 9.7; HRMS calcd for C 11 H 16 N 2 OS: 224.0983. Found 224.0974.
N-[(1R, 2S)-2-Hydroxy-1-methyl2-phenylethyl]-N’-phenylthiourea (2c). yield 94%; white solid, mp 137-138 ℃; Rf =0.2-0.3 (ethyl acetate/hexane 3:7); 1 H NMR (CDCl 3 ) δ 7.82 (1H, bs) 7.44-7.17 (10H, m), 6.20 (1H, d, J =7.3 Hz), 5.08-5.07 (1H, m), 4.90 (1H, bs), 2.80 (1H, bs), 1.01 (3H, d, J =6.9 Hz); 13 C NMR (CDCl 3 ) δ 179.6, 140.4, 135.9, 130.1, 128.3, 127.6, 127.2, 126.1, 125.0, 75.6, 56.1, 13.8; HRMS calcd for C 16 H 18 N 2 OS: 286.1140. Found 286.1151.
N-(2-Hydroxyethyl)-N’-phenylthiourea (2d). yield 90%; white solid, mp 141-142 ℃; Rf =0.6 (ethyl acetate/hexane 1:1); 1 H NMR (CDCl 3 ) δ 8.02 (1H, s) 7.44-7.21 (5H, m), 6.60 (1H, d, J =8.1Hz), 4.43-4.42 (1H, m), 4.08-4.05 (1H, m), 1.99 (1H, bs), 1.82-1.25 (8H, m), 13 C NMR (CDCl 3 ) δ 179.2, 136.3, 130.2, 127.0, 124.6, 68.7, 56.4, 31.9, 26.6, 23.7, 19.6; HRMS calcd for C 13 H 18 N 2 OS: 250.1140. Found 250.1136.
N-[(1S)-1-(Dimethylhydroxymethyl)-2-methylpropyl]-N’-phenylthiourea (2e). yield 85%; white solid, mp 206-207 ℃; Rf =0.7 (ethyl acetate/hexane 1:1); 1 H NMR (CDCl 3 ) δ 8.74 (1H, s) 7.43-7.26 (5H, m), 6.58 (1H, d, J =10.0), 4.42 (1H, dd, J =10.0, 2.7Hz), 2.20-2.10 (2H, m), 1.24 (6H, s), 1.01 (3H, d, J =6.8 Hz); 0.78 (3H, d, J =6.8 Hz); 13 C NMR (CDCl 3 ) δ 181.2, 136.2, 129.8, 126.9, 125.0, 74.1, 65.3, 29.3, 28.8, 26.9, 22.2, 17.4; HRMS calcd for C 14 H 22 N 2 OS: 266.1453. Found 266.266.1453.
N-[(1S)-1-(Diphenylhydroxymethyl)-2-methylpropyl]-N’-phenylthiourea (2f). yield 99%; white solid, mp 75-76 ℃; Rf =0.2-0.3 (ethyl acetate/hexane 1:4); 1 H NMR (CDCl 3 ) δ 8.15 (1H, bs) 7.58-7.16 (15H, m), 6.76 (1H, d, J =7.5 Hz), 5.54 (1H, d, J =7.9 Hz), 2.98 (1H, bs), 1.97-1.89 (1H, m), 0.86 (3H, d, J =8.0 Hz), 0.71 (3H, d, J =6.8 Hz); 13 C NMR (CDCl 3 ) δ 181.3, 145.2, 144.7, 135.8, 130.0, 128.5, 128.4, 127.4, 127.2, 125.7, 125.6, 125.4, 82.9, 63.7, 31.0, 23.6, 18.5; HRMS calcd for C 24 H 26 N 2 OS: 390.1766. Found 390.390.1764.
Cyclization of N-(2-hydroxyethyl)thioureas. To a stirred solution of thiourea (0.88 mmol) in THF (10 mL) under nitrogen at room temperature was added a solution of NaOH (88 mg, 2.2 mmol) in water (3 mL) and TsCl (0.18 g, 0.97 mmol) in THF (5 mL) dropwise for 5 min with a syringe. The reaction mixture was stirred for 30 min at room temperature, quenched with water (30 mL), and extracted with ether (50 mL×3). The organic layer was dried, filtered, evaporated. The crude product was purified by flash column chromatography to give the cyclized product.
4,5-Dihydro-5-methyl-N-phenyl-2-oxazolamine (3a). yield 96%; white solid, mp 133-134 ℃ (lit. 12 mp 133-134 ℃); Rf =0.1 (ethyl acetate/hexane 1:1); IR (CDCl 3 , cm -1 ) 1649; 1 H NMR (CDCl 3 ) δ 7.28-6.95 (5H, m), 4.79-4.72 (1H, m), 3.95-3.89 (1H, m), 3.43-3.37 (1H, m), 1.42 (3H, d, J =6.2 Hz); 13 C NMR (CDCl 3 ) δ 157.2, 142.3, 128.8, 122.0, 119.9, 76.1, 55.3, 20.4; HRMS calcd for C 10 H 12 N 2 O: 176.0950. Found 176.0949.
4,5-Dihydro-5-methyl-N-phenyl-2-oxazolamine (3b). yield 85%; white solid, mp 83-85 ℃ Rf =0.2 (ethyl acetate); IR (CDCl 3 , cm -1 ) 1643; H NMR (CDCl 3 ) δ 7.33-6.95 (5H, m), 4.57-4.53 (1H, m), 3.97-3.90 (1H, m), 3.53-3.47 (1H, m), 1.82-1.63 (2H, m), 1.05 (2H, t, J =7.4 Hz); 13 C NMR (CDCl 3 ) δ 157.3, 128.9, 122.0, 119.7, 81.0, 54.4, 27.8, 9.33; HRMS calcd for C 11 H 14 N 2 O: 190.1106. Found 190.1106.
(4R,5S)-Dihydro-4-methyl-5-phenyl-N-phenyl-2-oxazolamine (3c). yield 75%; oil; Rf =0.2-0.3 (ethyl acetate/hexane 1:1); IR (CDCl 3 , cm -1 ) 1685; 1 H NMR (CDCl 3 ) δ 7.39-6.99 (10H, m), 5.64 (1H, d, J =8.4 Hz), 4.41-4.37 (1H, m), 0.08 (3H, d, J =6.7 Hz); 13 C NMR (CDCl 3 ) δ 156.5, 142.0, 136.4, 128.8, 128.3, 128.0, 126.1, 122.2, 120.3, 83.6, 59.6, 18.1; HRMS calcd for C 16 H 16 N 2 O: 252.1263. Found 252.1262.
3a,4,5,6,7,7a-Hexahydro-N-phenyl-2-benzox azolamine (3d). yield 71%; white solid; mp 124-125 ℃; Rf =0.2 (ethyl acetate); IR (CDCl 3 , cm -1 ) 1683; 1 H NMR (CDCl 3 ) δ 7.29-6.98 (5H, m), 4.60-4.55 (1H, m), 3.83-3.61 (1H, m), 1.83-1.55 (8H, m); 13 C NMR (CDCl 3 ) δ 156.5, 144.4, 128.8, 124.8, 122.2, 121.7, 78.2, 55.4, 28.8, 26.8, 20.3, 20.0; HRMS calcd for C 13 H 16 N 2 O: 216.1263. Found 216.1268.
(4S)-4, 5-Dihydro-5, 5-dimethyl-4-(1-methylethyl)-N-phenyl-2-oxazolamine (3e). yield 80%; Rf =0.3 (ethyl acetate/hexane 7:3); 1 H NMR (CDCl 3 ) δ 7.33-6.96 (5H, m), 4.6 (1H, bs), 3.22 (1H, d, J =8.1), 1.84-1.77 (1H, m), 1.48 (3H, s), 1.25 (3H, s), 1.01 (3H, d, J =6.0 Hz), 0.92 (3H, d, J =6.6 Hz); HRMS calcd for C 14 H 20 N 2 O: 232.1576. Found 232.1575.
(4S)-4, 5-Dihydro-5, 5-dimethyl-4-(1-methylethyl)-N-phenyl-2-oxazolamine (3f). yield 99%; white solid, mp 75-76 ℃; Rf =0.5 (ethyl acetate/hexane 7:3); IR (CDCl 3 , cm -1 ) 1685; 1 H NMR (CDCl 3 ) δ 7.50-6.97 (15H, m), 4.57 (1H, d, J =3.3 Hz), 1.85-1.75 (1H, m), 0.93 (3H, d, J =6.8 Hz), 0.66 (3H, d, J =6.5 Hz); 13 C NMR (CDCl 3 ) δ 154.6, 144.7, 141.4, 140.3, 128.8, 128.3, 127.8, 127.2, 126.6, 126.2, 122.0, 119.5, 92.1, 74.2, 30.9, 21.5, 16.4; HRMS calcd for C 24 H 24 N 2 O: 356.1889. Found 356.1889.
Acknowledgements
This work was supported by the grant No. (R05-2002-000-00043-0) from the Basic Research Program of the Korea Science and Engineering Foundation.
References
Wong W. C. , Wang D. , Forray C. , Vaysse P. J. -J. , Branchek T. A. , Gluchowski C. 1994 Bioorg. Med. Chem. Lett. 4 2317 - 2322    DOI : 10.1016/0960-894X(94)85032-1
Bricca G. , Dontenwill M. , Molines A. , Feldman J. , Tibirica E. , Belcourt A. , Bousquet P. 1989 Eur. J. Pharmacol. 163 373 - 377    DOI : 10.1016/0014-2999(89)90210-0
Hirashima A. , Pan C. , Katafuchi Y. , Taniguchi E. , Eto M. 1996 J. Pesticide Sci. 21 419 - 424    DOI : 10.1584/jpestics.21.419
Najer H. , Chabrier P. , Giudielli R. 1959 Bull. Soc. Chim. Fr. , 54, 9889. 1611 - 1617
Adcock B. , Lawson A , Miles D. H. 1961 J. Chem. Soc. 5120 - 5127    DOI : 10.1039/jr9610005120
Heine H. W. , Kenyon W. G. , Johnson E. M. 1961 J. Am. Chem. Soc. 83 2570 - 2574    DOI : 10.1021/ja01472a033
Wittekind R. R. , Rosenau J. D. , Poos G. I. 1961 J. Org. Chem. 26 444 - 446    DOI : 10.1021/jo01061a041
Klayman D. L. , Shine R. J. , Murray, Jr. A. E. 1970 J. Pharm. Sci. 59 1515 - 1518    DOI : 10.1002/jps.2600591037
Dains F. B. , Brewster R. Q. , Malm I. L. , Miller A. W. , Maneval R. V. , Sultzaberger J. A. 1925 J. Am. Chem. Soc. 47 1918 - 1989    DOI : 10.1021/ja01684a029
Kim Y. I. , Kim Y. H. 1997 Synlett 1324 - 1326    DOI : 10.1055/s-1997-1030
Kim T. H. , Lee M. , Lee G.-J. , Kim J. N. 2001 Tetrahedron 57 7137 - 7141    DOI : 10.1016/S0040-4020(01)00682-2
You S.-W. , Lee K.-J. 2001 Bull. Korean Chem. Soc. 22 1270 - 1272
Fell J. B. , Coppola G. M. 1995 Synth. Commun. 25 43 - 47    DOI : 10.1080/00397919508010787
Lee G.-J. , Kim T. H. , Kim J. N. , Lee U. 2002 Tetrahedron: Asymmetry 13 9 - 12    DOI : 10.1016/S0957-4166(02)00044-7