PAPER
Regioselective C–N and C–S Bond Formation
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13C NMR (75 MHz, CD3OD): d = 35.1, 44.2, 105.3, 107.8, 114.9,
126.4, 128.5, 128.7, 133.5, 139.2, 151.5, 152.0, 169.2.
13C NMR (75 MHz, DMSO-d6): d = 45.8, 112.0, 127.0, 127.2,
128.6, 129.1, 135.2, 137.9, 154.5.
3,4-Dimethoxy-N-phenethylanthranilic Acid (17)
Coupling with Thiols; General Procedure
1H NMR (300 MHz, CDCl3): d = 2.90 (t, J = 7.3 Hz, 2 H), 3.67 (t,
J = 7.3 Hz, 2 H), 3.72 (s, 3 H), 3.90 (s, 3 H), 6.43 (d, J = 9.0 Hz,
1 H), 7.19–7.30 (m, 5 H), 7.84 (d, J = 9.0 Hz, 1 H).
A mixture of thiol (11.4 mmol), 2-bromobenzoic acid (8.8 mmol),
K2CO3 (1.21 g, 8.8 mmol), Cu powder (51 mg, 0.8 mmol), Cu2O (38
mg, 0.4 mmol) and 2-ethoxyethanol (3 mL) was heated to 130 °C
for 4 h. The reaction was cooled to r.t. and the solvent was removed
under reduced pressure. The residue was poured into H2O (30 mL),
treated with charcoal and the mixture was filtrated through Celite.
Acidification of the filtrate with diluted HCl (pH 5) gave a precipi-
tate, which was dissolved in aq Na2CO3 (5%, 100 mL) and the so-
lution was filtrated through Celite and subjected to precipitation as
described above. Precipitation upon acidification gave pure sul-
fides.
13C NMR (75 MHz, CDCl3): d = 37.7, 49.0, 56.5, 60.7, 103.3, 109.6,
126.9, 129.1, 129.5, 129.8, 138.8, 139.9, 146.4, 158.6, 173.0.
Anal. Calcd for C17H19NO4: C, 67.76; H, 6.36; N, 4.65. Found: C,
67.43; H, 6.67; N, 4.60.
4-Chloro-N-phenethylanthranilic Acid (19)
1H NMR (300 MHz, CDCl3): d = 2.98 (t, J = 7.1 Hz, 2 H), 3.44 (t,
J = 7.1 Hz, 2 H), 6.58 (dd, J = 8.6, 2.0 Hz, 1 H), 6.68 (d, J = 2.0 Hz,
1 H), 7.22–7.28 (m, 3 H), 7.31–7.37 (m, 2 H), 7.73 (br s, 1 H), 7.88
(d, J = 8.8 Hz, 1 H).
2-(Phenylthio)benzoic Acid (34)20
1H NMR (300 MHz, CDCl3): d = 6.84 (d, J = 8.1 Hz, 1 H), 7.18 (dd,
J = 7.7, 7.7 Hz, 1 H), 7.31 (ddd, J = 7.3, 7.3, 1.5 Hz, 1 H), 7.45–
7.49 (m, 3 H), 7.59–7.65 (m, 2 H), 8.17 (dd, J = 7.7, 1.2 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 36.0, 45.1, 107.9, 111.8, 115.9,
127.4, 129.4, 129.5, 134.6, 139.3, 142.7, 152.8, 173.9.
13C NMR (75 MHz, CDCl3): d = 124.9, 125.9, 127.8, 130.0, 130.5,
132.7, 132.9, 133.9, 136.5, 145.4, 172.7.
Anal. Calcd for C15H14ClNO2: C, 65.34; H, 5.12; N, 5.08. Found: C,
65.01; H, 5.50; N, 5.00.
2-(4-Fluorophenylthio)benzoic Acid (36)
5-Bromo-N-phenethylanthranilic Acid (21)
1H NMR (300 MHz, DMSO-d6): d = 6.78 (dd, J = 8.3, 1.0 Hz, 1 H),
7.30 (ddd, J = 7.6, 7.6, 1.0 Hz, 1 H), 7.40–7.50 (m, 3 H), 7.65–7.72
(m, 2 H), 8.02 (dd, J = 7.8, 1.5 Hz, 1 H).
1H NMR (300 MHz, CDCl3): d = 2.99 (t, J = 7.3 Hz, 2 H), 3.48 (t,
J = 7.3 Hz, 2 H), 6.60 (ddd, J = 7.3, 7.1, 1.0 Hz, 1 H), 6.72 (d,
J = 8.3 Hz, 1 H), 7.20–7.43 (m, 5 H), 7.99 (dd, J = 8.1, 1.7 Hz, 1 H).
13C NMR (75 MHz, DMSO-d6): d = 117.2 (d, JC–F = 21.7 Hz),
124.6, 126.4, 127.3, 127.7 (d, JC–F = 3.0 Hz), 130.9, 132.5, 137.9 (d,
JC–F = 8.6 Hz),142.0, 163.2 (d, JC–F = 247.8 Hz), 167.3.
13C NMR (75 MHz, CDCl3): d = 36.1, 45.0, 109.4, 112.0, 115.4,
127.2, 129.3, 129.5, 133.3, 136.3, 139.7, 152.2, 175.0.
Anal. Calcd for C15H14BrNO2: C, 56.27; H, 4.41; N, 4.37. Found: C,
56.10; H, 4.80; N, 4.05.
Anal. Calcd for C13H9FO2S: C, 62.89; H, 3.65. Found: C, 62.78; H,
3.81.
4-Fluoro-N-benzylanthranilic Acid (23)
2-(4-Methoxyphenylthio)benzoic Acid (38)21
1H NMR (300 MHz, CDCl3): d = 4.44 (d, J = 4.6 Hz, 2 H), 6.27–
6.36 (m 2 H), 7.29–7.37 (m, 5 H), 8.00 (dd, J = 9.0, 6.8 Hz, 1 H),
8.11 (br s, 1 H).
1H NMR (300 MHz, DMSO-d6): d = 3.91 (s, 3 H), 6.74 (d, J = 8.1
Hz, 1 H), 7.16 (d, J = 8.5 Hz, 2 H), 7.25 (dd, J = 7.3, 7.3 Hz, 1 H),
7.43 (dd, J = 7.3, 7.3 Hz, 1 H), 7.56 (d, J = 8.5 Hz, 2 H), 8.01 (d,
J = 7.6 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 47.7, 98.8 (d, JC–F = 25.7 Hz),
103.9 (d, JC–F = 22.7 Hz), 106.4 (d, JC–F = 1.5 Hz), 127.6, 128.1,
129.5, 136.1 (d, JC–F = 11.8 Hz), 138.6, 154.4 (d, JC–F = 12.8 Hz),
168.6 (d, JC–F = 253.1 Hz), 174.0.
13C NMR (75 MHz, DMSO-d6): d = 55.4, 115.7, 122.0, 124.1,
125.9, 126.8, 130.9, 132.3, 137.4, 143.4, 160.3, 167.3.
Anal. Calcd for C14H12FNO2: C, 68.56; H, 4.93; N, 5.71. Found: C,
68.11; H, 4.92; N, 5.98.
2-(2,6-Dimethylphenylthio)benzoic Acid (40)
1H NMR (300 MHz, DMSO-d6): d = 2.40 (s, 6 H), 6.49 (d, J = 8.1
Hz, 1 H), 7.26 (dd, J = 7.3, 7.3 Hz, 1 H), 7.36–7.44 (m, 4 H), 8.04
(dd, J = 7.6, 1.2 Hz, 1 H).
13C NMR (75 MHz, DMSO-d6): d = 21.1, 124.0, 124.2, 127.7,
128.7, 129.7, 130.4, 131.3, 132.4, 140.8, 143.3, 167.5.
5-Methoxy-N-benzylanthranilic Acid (27)
1H NMR (300 MHz, CD3OD): d = 3.75 (s, 3 H), 4.51 (s, 2 H), 6.73
(d, J = 9.3 Hz, 1 H), 7.09 (dd, J = 9.0, 3.2 Hz, 1 H), 7.33 (m, 1 H),
7.36–7.40 (m, 4 H), 7.48 (d, J = 3.2 Hz, 1 H).
13C NMR (75 MHz, DMSO-d6): d = 46.3, 55.4, 110.4, 113.2, 114.6,
122.5, 126.9, 127.0, 128.5, 139.7, 145.7, 148.9, 169.7.
Anal. Calcd for C15H14SO2: C, 69.74; H, 5.46. Found: C, 69.57; H,
5.66.
Anal. Calcd for C15H15NO3: C, 70.02; H, 5.88; N, 5.44. Found: C,
69.88; H, 6.01; N, 5.47.
5-Bromo-2-(phenylthio)benzoic Acid (42)
1H NMR (300 MHz, CDCl3): d = 6.67 (d, J = 8.8 Hz, 1 H), 7.37 (dd,
J = 8.8, 2.2 Hz, 1 H), 7.44–7.50 (m, 3 H), 7.54–7.60 (m, 2 H), 8.25
(d, J = 2.4 Hz, 1 H).
5-Carboxy-N-benzylanthranilic Acid (29)
1H NMR (300 MHz, DMSO-d6): d = 4.63 (s, 2 H), 6.83 (d, J = 8.8
Hz, 1 H), 7.35–7.44 (m, 5 H), 7.90 (d, J = 8.8 Hz, 1 H), 8.54 (s,
1 H), 8.89 (br s, 1 H).
13C NMR (75 MHz, CDCl3): d = 118.3, 127.2, 129.5, 130.3, 130.7,
132.1, 135.3, 136.5, 136.7, 144.8, 171.2.
13C NMR (75 MHz, DMSO-d6): d = 45.7, 110.1, 111.4, 116.3,
127.1, 128.6, 134.1, 134.9, 138.7, 153.4, 166.8, 169.6.
Anal. Calcd for C13H9BrO2S: C, 50.50; H, 2.93. Found: C, 50.12; H,
3.21.
Anal. Calcd for C15H13NO4: C, 66.41; H, 4.83; N, 5.16. Found: C,
66.13; H, 4.96; N, 5.02.
2-(Phenylthio)-5-methoxybenzoic Acid (44)
1H NMR (300 MHz, CDCl3): d = 3.85 (s, 3 H), 6.93 (dd, J = 13.4,
9.0 Hz, 2 H), 7.41–7.53 (m, 3 H), 7.54–7.56 (m, 2 H), 7.69 (s, 1 H).
5-Nitro-N-benzylanthranilic Acid (31)19
13C NMR (75 MHz, CDCl3): d = 56.2, 116.6, 121.1, 128.1, 129.3,
130.3, 131.0, 134.2, 134.5, 135.2, 157.9, 171.9.
1H NMR (300 MHz, CD3OD): d = 4.77 (s, 2 H), 6.99 (d, J = 9.3 Hz,
1 H), 7.46–7.55 (m, 5 H), 8.28 (d, J = 9.0 Hz, 1 H), 8.99 (br s, 1 H).
Synthesis 2007, No. 22, 3519–3527 © Thieme Stuttgart · New York