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General Procedure for the larger scale synthesis of compound
ica gel chromatography (EtOAc/PE = 5:95). Yield: 129 mg, 86 %, a
2a: To a solution of substrate 1a (1.0 mmol, 236 mg) in DMSO white solid, m.p. 133–134 °C. 1H NMR (600 MHz, CDCl3) δ = 8.37 (d,
(1.0 mL) was slowly added SOCl2 (3.0 mmol, 357 mg) at 25 °C. The
mixture was kept stirring at 25 °C until TLC indicated that the total
consumption of substrate 1a. Then the reaction mixture was
J = 7.8 Hz, 1H), 8.24 (d, J = 8.4 Hz, 1H), 7.89–7.86 (m, 1H), 7.78–7.76
(m, 2H), 7.60 (t, J = 7.8 Hz, 1H), 7.46–7.44 (m, 2H), 2.17 (s, 3H). 13C
NMR (150 MHz, CDCl3) δ = 161.4, 156.8, 137.9, 136.1, 135.3, 131.5,
quenched with saturated NaHCO3 solution (10 mL) and water 131.2, 130.0, 128.8, 128.2, 125.7, 120.9, 111.4, 19.0. HRMS (ESI) calcd.
(30 mL), extracted with EtOAc (3 × 30 mL), purified by flash column
chromatography to afford the desired compound 2a in 92 % yield
(246 mg).
for C16H1235ClO2S+ [M + H+] 303.0241, found 303.0241.
Methyl 2-(4-(methylthio)-1-oxo-1H-isochromen-3-yl)benzoate
(2g): Following the general procedure, compound 2g was purified
by silica gel chromatography (EtOAc/PE = 5:95). Yield: 142 mg, 88 %,
4-(Methylthio)-3-phenyl-1H-isochromen-1-one (2a):[33] Following
the general procedure, compound 2a was purified by silica gel
chromatography (EtOAc/PE = 5:95). Yield: 127 mg, 95 %, a white
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a white solid, m.p. 183–184 °C. H NMR (600 MHz, CDCl3) δ = 8.37
(d, J = 7.8 Hz, 1H), 8.17 (d, J = 8.4 Hz, 1H), 8.11 (d, J = 7.8 Hz, 1H),
7.87–7.84 (m, 1H), 7.65–7.62 (m, 1H), 7.58 (d, J = 7.2 Hz, 1H), 7.56
(d, J = 6.6 Hz, 1H), 7.52 (d, J = 7.8 Hz, 1H), 3.78 (s, 3H), 2.08 (s, 3H).
13C NMR (150 MHz, CDCl3) δ = 166.1, 161.5, 158.7, 137.9, 135.2,
134.7, 131.9, 131.3, 130.5, 130.1, 129.80, 129.75, 128.4, 125.2, 121.0,
110.6, 52.3, 18.2. HRMS (ESI) calcd. for C18H15O4S+ [M + H+]
327.0686, found 327.0688.
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solid, m.p. 127–128 °C. H NMR (600 MHz, CDCl3) δ = 8.36 (dd, J =
7.8, 1.2 Hz, 1H), 8.24 (d, J = 7.8 Hz, 1H), 7.88–7.85 (m, 1H), 7.80–7.78
(m, 2H), 7.59–7.56 (m, 1H), 7.48–7.46 (m, 3H), 2.16 (s, 3H). 13C NMR
(150 MHz, CDCl3) δ = 161.6, 158.0, 138.1, 135.3, 133.2, 130.0, 129.9,
129.8, 128.6, 127.9, 125.6, 120.9, 111.0, 19.1. HRMS (ESI) calcd. for
C
16H13O2S+ [M H+] 269.0631, found 269.0634. 2-(Phenyl-
+
ethynyl)benzoic acid was used as substrate, yield: 120 mg, 90 %.
3-(4-Methyl-2-nitrophenyl)-4-(methylthio)-1H-isochromen-1-
one (2h): Following the general procedure, compound 2h was puri-
fied by silica gel chromatography (EtOAc/PE = 10:90). Yield: 149 mg,
91 %, a yellow solid, m.p. 134–135 °C. 1H NMR (600 MHz, CDCl3) δ =
8.37 (dd, J = 7.8, 1.2 Hz, 1H), 8.13 (d, J = 7.8 Hz, 1H), 8.03 (d, J =
0.6 Hz, 1H), 7.89–7.86 (m, 1H), 7.63–7.60 (m, 1H), 7.56 (dd, J = 7.8,
1.2 Hz, 1H), 7.48 (d, J = 7.8 Hz, 1H), 2.54 (s, 3H), 2.11 (s, 3H). 13C
NMR (150 MHz, CDCl3) δ = 161.1, 155.4, 147.3, 141.8, 137.3, 135.4,
134.0, 132.1, 130.2, 128.9, 126.1, 125.3, 125.1, 121.1, 111.7, 21.3, 18.4.
HRMS (ESI) calcd. for C17H14NO4S+ [M + H+] 328.0638, found
328.0639.
7-Methyl-4-(methylthio)-3-phenyl-1H-isochromen-1-one (2b):
Following the general procedure, compound 2b was purified by
silica gel chromatography (EtOAc/PE = 5:95). Yield: 131 mg, 93 %, a
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white solid, m.p. 142–143 °C. H NMR (600 MHz, CDCl3) δ = 8.17 (s,
1H), 8.11 (d, J = 8.4 Hz, 1H), 7.80–7.78 (m, 2H), 7.67 (dd, J = 8.4,
1.8 Hz, 1H), 7.47–7.46 (m, 3H), 2.51 (s, 3H), 2.15 (s, 3H). 13C NMR
(150 MHz, CDCl3) δ = 161.8, 157.2, 138.9, 136.5, 135.6, 133.2, 129.9,
129.8, 129.7, 127.9, 125.6, 120.8, 111.0, 21.3, 19.1. HRMS (ESI) calcd.
for C17H15O2S+ [M + H+] 283.0787, found 283.0787. 5-Methyl-2-
(phenylethynyl)benzoic acid was used as substrate, yield: 129 mg,
92 %.
4-(Methylthio)-3-(naphthalen-1-yl)-1H-isochromen-1-one (2i):
Following the general procedure, compound 2i was purified by sil-
ica gel chromatography (EtOAc/PE = 5:95). Yield: 138 mg, 87 %, a
7-Fluoro-4-(methylthio)-3-phenyl-1H-isochromen-1-one
(2c):
Following the general procedure, compound 2c was purified by
silica gel chromatography (EtOAc/PE = 5:95). Yield: 127 mg, 89 %, a
white solid, m.p. 147–148 °C. 1H NMR (600 MHz, CDCl3) δ = 8.26
(dd, J = 9.0, 4.8 Hz, 1H), 8.00 (dd, J = 8.4, 3.0 Hz, 1H), 7.79–7.78 (m,
2H), 7.59–7.56 (m, 1H), 7.48–7.46 (m, 3H), 2.15 (s, 3H). 13C NMR
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white solid, m.p. 153–154 °C. H NMR (600 MHz, CDCl3) δ = 8.42 (d,
J = 7.8 Hz, 1H), 8.23 (d, J = 8.4 Hz, 1H), 7.98 (d, J = 8.4 Hz, 1H), 7.92–
7.89 (m, 2H), 7.75 (d, J = 8.4 Hz, 1H), 7.64–7.61 (m, 2H), 7.57–7.55
(m, 1H), 7.53–7.50 (m, 1H), 7.50–7.47 (m, 1H), 2.06 (s, 3H). 13C NMR
(150 MHz, CDCl3) δ = 161.7, 158.0, 137.7, 135.4, 133.4, 131.4, 131.2,
130.3, 130.2, 128.8, 128.6, 128.1, 127.0, 126.3, 125.5, 125.1, 124.9,
121.3, 113.5, 19.2. HRMS (ESI) calcd. for C20H15O2S+ [M + H+]
319.0787, found 319.0788.
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(150 MHz, CDCl3) δ = 162.2 (d, JC-F = 249.6 Hz), 160.7 (d, JC-F
=
5
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3.3 Hz), 157.5 (d, JC-F = 2.6 Hz), 134.7 (d, JC-F = 2.4 Hz), 132.8,
130.1, 129.7, 128.4 (d, 3JC-F = 7.8 Hz), 128.0, 123.4 (d, 2JC-F = 22.7 Hz),
122.6 (d, 3JC-F = 8.1 Hz), 115.4 (d, 2JC-F = 23.3 Hz), 110.5, 19.0. HRMS
(ESI) calcd. for C16H12FO2S+ [M + H+] 287.0537, found 287.0538.
4-(Methylthio)-3-(thiophen-2-yl)-1H-isochromen-1-one (2j): Fol-
lowing the general procedure, compound 2j was purified by silica
gel chromatography (EtOAc/PE = 5:95). Yield: 123 mg, 90 %, a yel-
low-green solid, m.p. 139–140 °C. 1H NMR (600 MHz, CDCl3) δ =
8.32 (dd, J = 7.8, 1.2 Hz, 1H), 8.22 (d, J = 7.8 Hz, 1H), 8.07 (dd, J =
3.6, 1.2 Hz, 1H), 7.85–7.82 (m, 1H), 7.55–7.51 (m, 2H), 7.16 (dd, J =
5.4, 4.8 Hz, 1H), 2.32 (s, 3H). 13C NMR (150 MHz, CDCl3) δ = 160.8,
152.5, 138.6, 135.3, 134.0, 131.4, 131.3, 129.9, 128.1, 126.9, 125.5,
4-(Methylthio)-3-(4-nitrophenyl)-1H-isochromen-1-one (2d): Fol-
lowing the general procedure, compound 2d was purified by silica
gel chromatography (EtOAc/PE = 10:90). Yield: 129 mg, 83 %, a yel-
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low solid, m.p. 168–169 °C. H NMR (600 MHz, CDCl3) δ = 8.38 (dd,
J = 7.8, 0.6 Hz, 1H), 8.34–8.32 (m, 2H), 8.26 (d, J = 7.8 Hz, 1H), 8.03–
8.01 (m, 2H), 7.93–7.91 (m, 1H), 7.66–7.64 (m, 1H), 2.20 (s, 3H). 13C
NMR (150 MHz, CDCl3) δ = 160.8, 155.3, 148.3, 139.1, 137.3, 135.6,
130.9, 130.1, 129.4, 125.9, 123.1, 121.1, 113.1, 19.1. HRMS (ESI) calcd.
for C16H12NO4S+ [M + H+] 314.0482, found 314.0483.
120.4, 108.0, 18.6. HRMS (ESI) calcd. for C14H10NaO2S2 [M + Na+]
+
297.0014, found 297.0016.
3-(4-Methoxyphenyl)-4-(methylthio)-1H-isochromen-1-one (2e):
Following the general procedure, compound 2e was purified by
silica gel chromatography (EtOAc/PE = 5:95). Yield: 138 mg, 93 %, a
white solid, m.p. 119–120 °C. 1H NMR (600 MHz, [D6]DMSO) δ =
8.23 (dd, J = 7.8, 1.2 Hz, 1H), 8.18 (d, J = 8.4 Hz, 1H), 8.02–7.99 (m,
1H), 7.74–7.72 (m, 2H), 7.69–7.66 (m, 1H), 7.09–7.07 (m, 2H), 3.85 (s,
3H), 2.20 (s, 3H). 13C NMR (150 MHz, [D6]DMSO) δ = 160.7, 160.4,
157.5, 137.6, 135.7, 131.2, 129.2, 128.6, 125.4, 125.2, 120.1, 113.3,
109.4, 55.3, 18.5. HRMS (ESI) calcd. for C17H15O3S+ [M + H+]
299.0736, found 299.0738.
3-(tert-Butyl)-4-(methylthio)-1H-isochromen-1-one (2k): Follow-
ing the general procedure, compound 2k was purified by silica gel
chromatography (EtOAc/PE = 1:99). Yield: 70 mg, 56 %, a white
solid, m.p. 73–74 °C. 1H NMR (600 MHz, CDCl3) δ = 8.29 (dd, J = 7.8,
1.2 Hz, 1H), 8.18 (d, J = 7.8 Hz, 1H), 7.82–7.79 (m, 1H), 7.52–7.50 (m,
1H), 2.24 (s, 3H), 1.59 (s, 9H). 13C NMR (150 MHz, CDCl3) δ = 168.2,
161.7, 138.9, 135.0, 129.6, 127.8, 124.8, 120.6, 109.7, 39.1, 29.6, 19.7.
HRMS (ESI) calcd. for C14H17O2S+ [M + H+] 249.0944, found
249.0944.
3-(4-Chlorophenyl)-4-(methylthio)-1H-isochromen-1-one (2f):
Following the general procedure, compound 2f was purified by sil-
4-(Methylthio)-3-(trimethylsilyl)-1H-isochromen-1-one (2l): Fol-
lowing the general procedure, compound 2l was purified by silica
Eur. J. Org. Chem. 0000, 0–0
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