Journal of the Korean Chemical Society (대한화학회지)

Korean Chemical Society (대한화학회)
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2-Phenylamino-2-oxazolines from N-(2-Hydroxyethyl)-N-phenylthioureas using TsCl/NaOH

TsCl/NaOH 존재하에서 N-(2-Hydroxyethyl)-N'phenylthioureas로부터 2-Phenylamino-2-oxazolines의 합성

  • Na, Hye-Sun (Department of Applied Chemistry and The Research Institute for Catalysis, Chonnam National University) ;
  • Kim, Taek-Hyeon (Department of Applied Chemistry and The Research Institute for Catalysis, Chonnam National University)
  • 나혜선 (전남대학교 공과대학 응용화학공학부 및 촉매연구소) ;
  • 김택현 (전남대학교 공과대학 응용화학공학부 및 촉매연구소)
  • Published : 2003.12.20
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Abstract

Keywords

EXPERIMENTAL SECTION

General methods. 1H NMR and 13C 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 (CDCl3, cm-1 2142 (N=C=N); 1H NMR (CDCl3) 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); 13C NMR (CDCl3) δ 180.6, 136.2, 130.1, 127.2, 124.9, 67.1, 52.0, 21.1; HRMS calcd for C10H14N2OS: 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); 1H NMR (CDCl3) 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); 13C NMR (CDCl3) δ 180.9, 136.1, 130.2, 127.2, 125.0, 72.4, 50.6, 28.1, 9.7; HRMS calcd for C11H16N2OS: 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); 1H NMR (CDCl3) 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); 13C NMR (CDCl3) 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 C16H18N2OS: 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); 1H NMR (CDCl3) 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), 13C NMR (CDCl3) 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 C13H18N2OS: 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); 1H NMR (CDCl3) 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); 13C NMR (CDCl3) 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 C14H22N2OS: 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); 1H NMR (CDCl3) 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); 13C NMR (CDCl3) 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 C24H26N2OS: 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.12mp 133-134 ℃); Rf=0.1 (ethyl acetate/hexane 1:1); IR (CDCl3, cm-1) 1649; 1H NMR (CDCl3) 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); 13C NMR (CDCl3) δ 157.2, 142.3, 128.8, 122.0, 119.9, 76.1, 55.3, 20.4; HRMS calcd for C10H12N2O: 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 (CDCl3, cm-1) 1643; H NMR (CDCl3) 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); 13C NMR (CDCl3) δ 157.3, 128.9, 122.0, 119.7, 81.0, 54.4, 27.8, 9.33; HRMS calcd for C11H14N2O: 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 (CDCl3, cm-1) 1685; 1H NMR (CDCl3) 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); 13C NMR (CDCl3) 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 C16H16N2O: 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 (CDCl3, cm-1) 1683; 1H NMR (CDCl3) 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); 13C NMR (CDCl3) 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 C13H16N2O: 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); 1H NMR (CDCl3) 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 C14H20N2O: 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 (CDCl3, cm-1) 1685; 1H NMR (CDCl3) 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); 13C NMR (CDCl3) 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 C24H24N2O: 356.1889. Found 356.1889.

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