Table 1. Preparation and analysis
Com-
pound
Syntheses and yields
Mp (°C)
NMR
1H NMR at 300 MHz, 13C NMR at 75 MHz
1a
2a
Anthranilic acid (2.74 g, 20.0 mmol) was stirred at 120 °C in DMF (15 mL) with
chloroacetonitrile (1.5 mL, 24 mmol) and NaHCO3 (1.68 g, 20.0 mmol) for 90 min. The
mixture was poured into ice-water (150 mL) and stirred until a solid formed. The
product was filtered off and allowed dry to yield an off-white solid (3.22 g, 91%).
63 (64)31
dH (acetone-d6): 5.13 (s, 2H), 6.48 (2H, br s), 6.61 (1H, dt, J 0.7, 8.2), 6.85 (1H, dd,
J 0.7, 8.4), 7.32 (1H, dt, J 1.5, 8.4), 7.79 (1H, dt, J 1.5, 8.2); dC (acetone-d6): 48.4
(CH2–CN), 107.5 (ArC–COO), 115.3 (CH), 115.5 (CN), 116.7 (CH), 130.8 (CH), 135.0
(CH), 152.2 (ArC–NH2), 166.3 (ArCOO). Assigment was based on DEPT/HMBC.
Method 1: Compound 13 (11.5 g, 60 mmol) was stirred in DMSO (40 mL) at 80 °C with 185 (184)32
NaCN (3.0 g, 61 mmol) for 18 h. The mixture was poured into ice-water (250 mL) and
acidified with concd HCl (10 mL). The solid, which slowly formed was filtered off and
dried (8.01 g, 76%). Method 2: Compound 6 (1.08 g, 5.00 mmol) was partially dissolved
in acetone (10 mL). NaOH (0.40 g, 10 mmol) dissolved in water (10 mL) was added
and the mixture stirred for 15 h. The acetone was evaporated and the remaining
solution was diluted with water, filtered, and acidified (HCl), upon which the product
precipitated and could be filtered off (0.82 g, 93%).
dH (DMSO-d6): 4.48 (2H, d, J 6.4), 6.75 (1H, t, J 7.9), 6.89 (1H, d, J 8.3), 7.49 (1H, dt,
J 1.5, 8.3), 7.86 (1H, dd, J 1.5, 7.9), 8.04 (1H, t, J 6.4), 12.89 (1H, br s); dC (DMSO-
d6): 30.9 (CH2), 111.7 (CH), 112.0 (C), 116.5 (CH), 118.2 (C), 131.8 (CH), 134.5 (CH),
148.7 (C), 169.5 (C).
2b
Method 1: Anthranilic acid (2.74 g, 20.0 mmol) was dissolved in water (20 mL)
containing NaOH (0.80 g, 20 mmol). A solution of Na2CO3Æ10 H2O (5.72 g, 20.0 mmol
in 20 mL water) was added followed by ethyl chloroacetate (5.0 mL, 40.6 mmol). The
mixture was heated under reflux for 15 h. On cooling, a crop of 2b (2.05 g, 46%)
precipitated from the neutral solution. Method 2: The diacid 2c (19.5 g, 0.100 mol) was
heated to reflux in abs EtOH (100 mL) with concd H2SO4 (1.5 mL) for 3 h. On cooling,
the product 2b precipitated and could be collected (21.6 g, 97%).
152 (152)11
dH (DMSO-d6): 1.21 (3H, t, J 7.2), 4.14 (2H, q, J 7.2), 6.58–6.63 (2H, m), 7.35 (1H, dt,
J 1.5, 7.9), 7.80 (1H, dd, J 1.1, 7.9), 8.17 (1H, br s), 12.72 (1H, br s); dC (DMSO-d6)
14.1 (CH3), 60.6 (CH2), 110.7 (C), 111.5 (CH), 115.0 (CH), 131.7 (CH), 134.4 (CH),
150.0 (C), 169.8 (C), 170.5 (C).
6
Isatoic anhydride (16.3 g, 0.100 mol) was dissolved in DMF (120 mL). Chloroaceto-
nitrile (14 mL, 0.22 mol) and K2CO3 (13.8 g, 0.100 mol) were added and the mixture
was stirred at 100 °C for 90 min under evolution of gas (CO2). After letting the mixture
cool to rt, it was poured into water. The solid product, which soon formed, was
collected (20.2 g, 94%).
105–106a
dH (DMSO-d6): 4.50 (2H, d, J 6.4), 5.17 (2H, s), 6.81 (1H, t, J 8.3), 6.97 (1H, d, J 8.0),
7.59 (1H, dt, J 1.5, 8.0), 7.77 (1H, t, J 6.4), 7.87 (1H, dd, J 1.5, 8.3); dC (DMSO-d6):
31.0 (CH2), 49.4 (CH2), 109.3 (C), 112.3 (CH), 116.2 (C), 116.9 (CH), 118.1 (C), 131.5
(CH), 135.9 (CH), 148.8 (C), 165.9 (C).
7
Compound 1a (1.76 g, 10.0 mmol) was dissolved in dioxane (5 mL) with 2,6-lutidine 202–204
(2.0 mL), and cooled to 0 °C. SOCl2 (0.50 mL, 6.9 mmol) was added dropwise and the (dec)b
mixture stirred for 1 h at 0–25 °C. The mixture was poured into ice-water (100 mL),
and the solid grayish product was filtered off (1.52 g, 91%).
dH (DMSO-d6): 4.55 (2H, d, J 6.5), 6.85 (1H, t, J 7.8), 7.03 (1H, d, J 8.0), 7.67 (1H, dt,
J 1.3, 8.0), 7.91 (1H, t, J 6.5), 7.98 (1H, dd, J 1.3, 7.8); dC (DMSO-d6): 31.0, 109.4,
112.3, 117.0, 117.9, 132.5, 149.8, 163.8.
10
The salt 9 (2.01 g, 10.0 mmol) was stirred with allyl bromide (1.5 mL, 18 mmol) in
DMSO (20 mL) for 5 h at 65 °C. The mixture was poured into ice-water (150 mL) and 49.5)24
the solid that eventually formed was collected. After drying, this material was heated
in heptane (150 mL). The acid 8 could be filtered off and the filtrate was evaporated to
yield the product (1.68 g, 77%).
46–47 (49–
dH (DMSO-d6): 2.12 (3H, s), 4.79 (2H, dt, J 1.5, 5.4), 5.30 (1H, dd, J 1.5, 10.4), 5.41
(1H, dd, J 1.5, 17.1), 5.95–6.08 (1H, m), 7.19 (1H, dt, J 0.9, 7.8), 7.60 (1H, dt, J 1.6,
7.8), 7.92 (1H, dd, J 1.6, 7.9), 8.19 (1H, dd, J 0.9, 7.8); dC (DMSO-d6): 24.5(CH3), 65.4
(CH2), 118.0 (C), 118.3(CH2), 121.3 (CH), 123.2 (CH), 130.4 (CH), 132.4 (CH), 133.9
(CH), 139.6 (C), 166.7 (C), 168.4 (C).
13
N-Acetylanthranilic acid (17.9 g, 0.100 mol) was refluxed in AcOH (50 mL) with
paraformaldehyde (4.0 g) for 3 h. The solvent was evaporated in vacuo (with addition
of toluene). The residue was boiled in MeCN (200 mL), and the solution evaporated
(after filtration) to yield a beige solid (16.7 g, 85%).
122c
dH (DMSO-d6): 2.35 (3H, s), 5.78 (2H, s), 7.42 (1H, m), 7.73 (2H, m), 7.95 (1H, d,
J 7.9); dC (DMSO-d6): 22.3 (CH3), 75.5 (CH2), 119.3 (C), 123.6 (CH), 126.1 (CH),
129.6 (CH), 134.3 (CH), 141.0 (C), 162.8 (C), 169.4 (C).
a Anal. Calcd for C11H9N3O2: C, 61.39; H, 4.22; N, 19.53. Found: C, 61.59; H, 4.22; N, 19.46.
b Anal. Calcd for C18H14N4O3: C, 64.66; H, 4.22; N, 16.76. Found: C, 64.26; H, 4.35; N, 16.34.
c Recryst. from diisopropyl ether. Anal. calcd for C10H9NO3: C, 62.82; H, 4.74; N, 7.33. Found: C, 62.80; H, 4.88; N, 7.25.