Journal of the Korean Chemical Society (대한화학회지)

Korean Chemical Society (대한화학회)
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Practical and Versatile Synthesis of Thioflavones from 2-Bromobenzoyl Chlorides

  • Lee, Jae In (Department of Chemistry, College of Natural Science, Duksung Women’s University) ;
  • Choi, Jin Sun (Department of Chemistry, College of Natural Science, Duksung Women’s University)
  • Received : 2015.02.09
  • Accepted : 2015.03.16
  • Published : 2015.06.20
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Abstract

Keywords

EXPERIMENTAL

Preparation of 4,6-pyrimidyl di(2-bromo-4-chlorobenzoate) (2b)

2-Bromo-4-chlorobenzoyl chloride (2.54 g, 10.0 mmol) was added to a suspended solution of 4,6-dihydroxypyrimidine (560 mg, 5.0 mmol) and triethylamine (1.40 mL, 10.0 mmol) in methylene chloride (40 mL) at room temperature. After stirring for 3 h, methylene chloride was evaporated in vacuo. The mixture was dissolved in anhydrous THF and triethylamine hydrochloride was filtered off. The residue was recrystallized twice in 75% EtOAc/n-hexane to give 2b (2.32 g, 85%). mp 134−136 ℃; 1H NMR (300 MHz, CDCl3) δ 8.99 (s, 1H), 8.11 (d, J = 8.5 Hz, 2H), 7.80 (d, J = 0.8 Hz, 2H), 7.47 (dd, J1 = 8.5 Hz, J2 = 0.8 Hz, 2H), 7.40 (s, 1H); 13C NMR (75 MHz, CDCl3) δ 166.6, 161.1, 159.2, 140.4, 135.0, 133.6, 128.0, 127.1, 124.3, 105.4; FTIR (KBr) 1762 (C=O) cm−1.

Preparation of 1-(2-bromo-4-chlorophenyl)-3-(4-methoxyphenyl)-2-propyn-1-one (3bj)

4-Methoxyphenylethynylmagnesium bromide, generated from 4-methoxyphenylacetylene (529 mg, 4.0 mmol) and ethylmagnesium bromide (1.0 M, 4.0 mL, 4.0 mmol) in THF (10 mL), was slowly added to a solution of 2b (1.09 g, 2.0 mmol) in THF (15 mL) at 0 ℃ under argon atmosphere. The mixture was stirred for 0.5 h at 0 ℃ and then quenched with saturated NH4Cl solution (5 mL). After evaporating THF, the mixture was poured into saturated NH4Cl solution (30 mL) and extracted with methylene chloride (3×20 mL). The combined organic phases were dried over MgSO4, filtered, and concentrated in vacuo. The residue was recrystallized twice in 10% EtOAc/n-hexane to give 3bj (1.16 g, 83%). mp 131−133 ℃; 1H NMR (300 MHz, CDCl3) δ 8.01 (d, J = 8.4 Hz, 1H), 7.72 (d, J = 1.8 Hz, 1H), 7.60 (d, J = 8.9 Hz, 2H), 7.43 (dd, J1 = 8.4 Hz, J2 = 1.9 Hz, 1H), 6.93 (d, J = 8.9 Hz, 2H), 3.86 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 176.4, 162.0, 138.9, 136.1, 135.3, 134.6, 133.5, 127.7, 121.9, 114.5, 111.5, 96.1, 87.9, 55.5; FTIR (KBr) 2196 (C≡C), 1641 (C=O) cm−1; Ms m/z (%) 352 (M++4, 21), 350 (M++2, 85), 348 (M+, 67), 324 (13), 322 (54), 320 (42), 159 (100).

Preparation of 7-chloro-4'-methoxythioflavone (5bj)

A solution of 3bj (1.05 g, 3.0 mmol) in EtOH (20 mL) was added to a suspended solution of sodium hydrosulfide hydrate (60% dispersion in mineral oil, 336 mg, 3.6 mmol) in EtOH (15 mL) at room temperature. Stirring was continued at this temperature for 0.5 h and the resulting reddish solution was refluxed for 1.5 h more. After evaporating EtOH, the mixture was poured into saturated NH4Cl solution (30 mL) and extracted with methylene chloride (3×20 mL). The combined organic phases were dried over MgSO4, filtered, and concentrated in vacuo. The residue was recrystallized twice in 10% EtOAc/n-hexane to give 5bj (772 mg, 85%). mp 173−174 ℃; 1H NMR (300 MHz, CDCl3) δ 8.45 (d, J = 8.7 Hz, 1H), 7.62 (d, J = 1.9 Hz, 1H), 7.63 (d, J = 8.9 Hz, 2H), 7.47 (dd, J1 = 8.6 Hz, J2 = 2.0 Hz, 1H), 7.16 (s, 1H), 7.01 (d, J = 8.9 Hz, 2H), 3.88 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 180.1, 162.0, 152.5, 138.9, 138.2, 130.1, 129.3, 128.4, 128.3 (overlapped), 125.7, 122.2, 114.7, 55.5; FTIR (KBr) 1625 (C=O) cm−1; Ms m/z (%) 304 (M++2, 40), 302 (M+, 100), 276 (15), 274 (47), 261 (11), 259 (34), 132 (41).

5af, 5ag, 5aj, and 7: All products were identified by means of mp, 1H/13C NMR, FTIR, and mass spectrometry and consistent with the previous results.18a,c

7-Chloro-3-thienyl-4H-1-benzothiopyran-4-one (5bl): mp 150−151 ℃; 1H NMR (300 MHz, CDCl3) δ 8.44 (d, J = 8.6 Hz, 1H), 7.77 (dd, J1 = 2.9 Hz, J2 = 1.4 Hz, 1H), 7.61 (d, J = 1.9 Hz, 1H), 7.45−7.50 (m, 2H), 7.42 (dd, J1 = 5.1 Hz, J2 = 1.3 Hz, 1H), 7.21 (s, 1H); 13C NMR (75 MHz, CDCl3) δ 180.2, 146.5, 138.5, 138.4, 137.3, 130.2, 129.4, 128.4, 127.8, 125.6, 125.3, 125.2, 122.1; FTIR (KBr) 1615 (C=O) cm−1; Ms m/z (%) 280 (M++2, 41), 278 (M+, 98), 252 (41), 250 (100), 170 (47).

7,4'-Dimethylthioflavone (5ch): mp 129 ℃; 1H NMR (300 MHz, CDCl3) δ 8.42 (d, J = 8.3 Hz, 1H), 7.58 (d, J = 8.2 Hz, 2H), 7.43 (s, 1H), 7.34 (d, J = 8.3 Hz, 1H), 7.29 (d, J = 8.0 Hz, 2H), 7.19 (s, 1H), 2.47 (s, 3H), 2.42 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 180.8, 152.7, 142.4, 141.2, 137.9, 133.8, 129.9, 129.2, 128.8, 128.5, 126.8, 126.2, 122.9, 21.6, 21.4; FTIR (KBr) 1638 (C=O) cm−1; Ms m/z (%) 266 (M+, 100), 238 (86), 150 (34), 121 (21).

7-Methyl-2'-methoxythioflavone (5ci): mp 118−119 ℃; 1H NMR (300 MHz, CDCl3) δ 8.44 (d, J = 8.3 Hz, 1H), 7.42−7.46 (m, 2H), 7.40 (s, 1H), 7.33 (d, J = 8.3 Hz, 1H), 7.12 (s, 1H), 7.06 (d, J = 7.6 Hz, 1H), 7.01 (d, J = 8.4 Hz, 1H), 3.85 (s, 3H), 2.46 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 180.7, 156.5, 149.9, 142.2, 138.9, 131.5, 130.3, 129.1, 128.7, 128.4, 126.8, 125.9, 125.6, 120.9, 111.7, 55.8, 21.6; FTIR (KBr) 1620 (C=O) cm−1; Ms m/z (%) 282 (M+, 100), 151 (72), 121 (25).

7-Methyl-3-pyridyl-4H-1-benzothiopyran-4-one (5cm): mp 154−155 ℃; 1H NMR (300 MHz, CDCl3) δ 8.94 (d, J = 1.9 Hz, 1H), 8.75 (dd, J1 = 4.8 Hz, J2 = 1.3 Hz, 1H), 8.43 (d, J = 8.3 Hz, 1H), 7.95−7.99 (m, 1H), 7.42−7.46 (m, 1H), 7.46 (s, 1H), 7.38 (d, J = 8.3 Hz, 1H), 7.19 (s, 1H), 2.50 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 180.4, 151.6, 149.0, 147.7, 142.9, 137.3, 134.3, 132.7, 129.7, 128.6, 126.2, 124.3, 123.8, 123.2, 21.6; FTIR (KBr) 1636 (C=O) cm−1; Ms m/z (%) 253 (M+, 100), 225 (74), 150 (29), 121 (24).

6-Methoxy-3'-chlorothioflavone (5dg): mp 189−190 ℃; 1H NMR (300 MHz, CDCl3) δ 7.98 (d, J = 2.7 Hz, 1H), 7.68 (s, 1H), 7.55−7.59 (m, 2H), 7.41-7.50 (m, 2H), 7.25−7.29 (m, 1H), 7.22 (s, 1H), 3.95 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 180.4, 159.7, 151.2, 138.4, 135.3, 132.3, 130.7, 130.5, 129.4, 127.8, 127.1, 125.2, 123.0, 122.4, 108.8, 55.8; FTIR (KBr) 1625 (C=O) cm-1; Ms m/z (%) 304 (M++2, 39), 302 (M+, 100), 272 (28), 123 (20).

6,3',5'-Trimethoxythioflavone (5dk): mp 154−155 ℃; 1H NMR (300 MHz, CDCl3) δ 7.98 (d, J = 2.8 Hz, 1H), 7.56 (d, J = 8.8 Hz, 1H), 7.24 (s, 1H), 7.26 (dd, J1 = 8.5 Hz, J2 = 2.1 Hz, 1H), 6.82 (d, J = 2.2 Hz, 2H), 6.58 (t, J = 2.2 Hz, 1H), 3.94 (s, 3H), 3.85 (s, 6H); 13C NMR (75 MHz, CDCl3) δ 180.5, 161.3, 159.6, 153.0, 138.6, 132.4, 129.7, 127.8, 122.6, 122.2, 108.9, 105.1, 102.7, 55.7, 55.6; FTIR (KBr) 1626 (C=O) cm−1; Ms m/z (%) 328 (M+, 100), 298 (33), 123 (12).

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