Mei et al.
FIGURE 7. Formation of intertwined rods in the crystal structure of anthranilic acid 17 (top) and schematic illustration of the packing of the
trans-syn dimers (bottom).
1
)
31.3, 35.7, 110.0, 114.8, 116.7, 126.6, 127.6, 128.1, 129.8, 133.1,
20, as an off-white solid in 96% yield. H NMR (300 MHz, CDCl
3
)
1
35.9, 139.4, 147.1, 151.4, 173.7.
δ ) 6.73 (dd, J ) 7.3 Hz, 7.6 Hz, 1H), 6.85 (d, J ) 8.6 Hz, 1H),
N-(2-Biphenyl)anthranilic Acid (11).24 Acid 11 was obtained
7.23-7.29 (m, 1H), 7.46-7.51 (m, 4H), 7.75 (d, J ) 7.6 Hz, 1H),
13
from 2-chlorobenzoic acid, 1, and 2-aminobiphenyl, 10, as a white
7.89-7.92 (m, 1H), 8.08 (m, 2H), 9.60 (bs, 1H). C NMR (75
1
solid in 85% yield. H NMR (300 MHz, CDCl
H), 6.72 (dd, J ) 7.2 Hz, 7.7 Hz, 1H), 7.20-7.52 (m, 11H), 7.94
d, J ) 8.3 Hz, 1H), 9.18 (bs, 1H). 13C NMR (75 MHz, CDCl
) δ
111.4, 114.7, 117.7, 123.7, 124.8, 128.0, 128.6, 129.0, 129.7,
3
) δ ) 4.74 (bs,
3
MHz, CDCl ) δ )110.5, 114.2, 117.5, 122.8, 123.5, 126.5, 126.5,
1
(
127.1, 129.1, 130.8, 133.1, 135.5, 136.0, 136.9, 151.2, 174.2.
N-(1-Pyrenyl)anthranilic Acid (23). Amination of 2-chloroben-
zoic acid, 1, and 1-aminopyrene, 22, afforded anthranilic acid 23
3
)
1
1
31.7, 133.1, 135.6, 136.9, 138.2, 139.5, 149.3, 174.2.
as an off-white solid in 73% yield. H NMR (300 MHz, DMSO-
N-(2,6-Dimethylphenyl)anthranilic Acid (13).25 Amination of
d ) δ ) 6.94 (dd, J ) 7.4 Hz, 7.4 Hz, 1H), 7.14 (d, J ) 8.3 Hz,
6
2-chlorobenzoic acid, 1, and 2,6-dimethylaniline, 12, afforded acid
1H), 7.43 (dd, J ) 8.0 Hz, 7.4 Hz, 1H), 8.09-8.41 (m, 10H), 10.7
1
13
13 as a white powder in 65% yield. H NMR (300 MHz, CDCl
3
)
(bs, 1H). C NMR (75 MHz, DMSO-d ) δ ) 114.2, 118.1, 122.0,
6
δ ) 2.21 (s, 6H), 6.22 (d, J ) 8.5 Hz, 1H), 6.66 (dd, J ) 7.1 Hz,
122.1, 124.8, 124.9, 125.4, 125.7, 125.8, 126.4, 126.7, 127.2, 128.0,
128.2, 131.4, 131.7, 133.6, 134.6, 135.2, 148.8, 172.7. Anal. Calcd
for C H NO : C, 81.88; H, 4.48; N, 4.15. Found: C, 81.63; H,
7
1
.1 Hz, 1H), 7.10-7.20 (m, 3H), 7.24 (dd, J ) 7.6 Hz, 7.8 Hz,
H), 8.04 (d, J ) 7.6 Hz, 1H), 8.88 (bs, 1H). 13C NMR (75 MHz,
23
15
2
CD
35.9, 137.0, 149.9, 173.8.
N-(3-Methylphenyl)anthranilic Acid (15). Compound 15 was
obtained from 2-chlorobenzoic acid, 1, and 3-methylaniline, 14, as
3
OD) δ ) 18.5, 112.0, 115.7, 126.3, 128.3, 132.8, 134.1, 135.6,
4.74; N, 4.32.
1
N-(4-Methoxyphenyl)anthranilic Acid (25).16 Anthranilic acid
5 was obtained from 2-chlorobenzoic acid, 1, and 4-methoxya-
niline, 24, as a white powder in 84% yield. H NMR (300 MHz,
) δ ) 3.83 (s, 3H), 6.68 (dd, J ) 7.3 Hz, 7.3 Hz, 1H), 6.93
dd, J ) 8.6 Hz, 8.6 Hz, 3H), 7.18 (d, J ) 8.6 Hz, 2H), 7.26-7.32
m, 1H), 8.0 (d, J ) 8.6 Hz, 1H), 9.60 (bs, 1H). C NMR (75
) δ ) 55.2, 111.4, 112.8, 114.8, 116.3, 125.1, 131.9,
33.0, 134.2, 148.9, 156.1, 170.2.
N-(4-Nitrophenyl)anthranilic Acid (27).16 Anthranilic acid 27
was produced from 2-chlorobenzoic acid, 1, and 4-nitroaniline, 26,
25
2
1
1
a white solid in 80% yield. H NMR (300 MHz, CDCl
3
) δ ) 2.39
CDCl
3
(
s, 3H), 6.79 (bs, 1H), 6.97 (d, J ) 7.31 Hz, 1H), 7.00-7.15 (m,
(
(
2
1
1
H), 7.25-7.30 (m, 2H), 7.38 (m, 1H), 8.10 (m, 1H), 9.25 (bs,
13
H). 13C NMR (75 MHz, DMSO-d
22.0, 123.8, 129.2, 132.5, 134.0, 138.9, 140.5, 147.5.
6
) δ ) 21.0, 113.9, 117.3, 118.3,
MHz, DMSO-d
6
1
N-(3-tert-Butylphenyl)anthranilic Acid (17). Acid 17 was
produced by amination of 2-chlorobenzoic acid, 1, and 3-tert-
butylaniline, 16, as a white solid in 85% yield. H NMR (300 MHz,
CDCl
1
1
as a yellow solid in 87% yield. H NMR (300 MHz, CD
3
OD) δ )
3
) δ )1.34 (s, 9H), 6.74 (dd, J ) 0.7 Hz, 7.4 Hz, 1H), 7.10
7
2
.22 (dd, J ) 7.1 Hz, 7.8 Hz, 1H), 7.50 (m, 2H), 7.68-7.78 (m,
H), 8.26 (d, J ) 8.1 Hz, 1H), 8.36-8.36 (m, 2H). C NMR (75
OD) δ ) 118.1, 118.2, 118.8, 122.2, 127.1, 133.7, 135.3,
(
d, J ) 7.3 Hz, 1H), 7.16-7.37 (m, 5H), 8.05 (dd, J ) 1.5 Hz, 8.1
13
13
Hz, 1H), 9.29 (bs, 1H). C NMR (75 MHz, DMSO-d
3
1
6
) δ ) 31.0,
4.4, 112.4, 113.5, 117.2, 118.7, 118.9, 120.3, 129.0, 132.0, 134.1,
40.1, 147.4, 152.2, 170.1. Anal. Calcd for C17 20ClNO : C, 66.77;
MHz, CD
3
142.6, 145.4, 150.0, 171.5.
H
2
N-(3-Chlorophenyl)anthranilic Acid (29).28 Amination of
-chlorobenzoic acid, 1, and 3-chloroaniline, 28, gave anthranilic
acid, 29, as an off-white solid in 99% yield. H NMR (300 MHz,
H, 6.59; N, 4.58. Found: C, 67.27; H, 7.16; N, 4.93. (The HCl salt
was formed by addition of hydrogen chloride (diethyl ether, 2.0
M) for elemental analysis.)
2
1
CDCl ) δ ) 6.82 (dd, J ) 7.3 Hz, 7.6 Hz, 1H), 7.08 (d, J ) 7.8
3
N-[3-(3′,5′-Dimethylbiphenyl)]anthranilic Acid (19).26 Anthra-
nilic acid 19 was obtained from 2-chlorobenzoic acid, 1, and
Hz, 1H), 7.14 (d, J ) 7.8 Hz, 1H), 7.26-7.30 (m, 3H), 7.40 (dd,
J ) 7.6 Hz, 7.8 Hz, 1H), 8.06 (d, J ) 7.3 Hz, 1H), 9.32 (bs, 1H).
3-amino-3′,5′-dimethylbiphenyl, 18, as an off-white solid in 99%
13
C NMR (75 MHz, CDCl ) δ ) 114.2, 114.7, 118.5, 118.8, 119.9,
3
1
yield. H NMR (300 MHz, CDCl
3
) δ ) 2.39 (s, 6H), 4.43 (s, 2H),
1
22.1, 130.9, 132.0, 133.9, 134.0, 142.6, 145.8, 169.9.
6
8
2
1
.77 (dd, J ) 7.1 Hz, 7.6 Hz, 1H), 7.02 (s, 1H), 7.22-7.50 (m,
N-(4-Carboxyphenyl)anthranilic Acid (31).27 Anthranilic acid
1 was obtained from 2-chlorobenzoic acid, 1, and 4-aminobenzoic
H), 8.06 (d, J ) 8.0 Hz, 1H). 1 C NMR (75 MHz, CDCl
3
3
) δ )
3
1.7, 113.7, 114.4, 115.9, 117.5, 121.9, 122.1, 123.1, 125.2, 128.7,
29.3, 129.8, 133.9, 135.3, 138.5, 140.9, 143.0, 149.1. Anal. Calcd
acid, 30, using two equivalents of K
2
CO
OD) δ ) 7.00-7.06 (m, 1H), 7.37
d, J ) 8.8 Hz, 2H), 7.56-7.59 (m, 2H), 7.98 (d, J ) 8.8 Hz, 2H),
8.04 (d, J ) 8.3 Hz, 1H), 9.91 (bs, 1H).
OD) δ ) 115.3, 116.2, 117.9, 119.6, 123.5, 131.2, 132.0, 134.1,
3
as a white solid in 98%
1
yield. H NMR (300 MHz, CD
3
for C21
.23; N, 4.32.
N-(1-Naphthyl)anthranilic Acid (21).27 Anthranilic acid 21 was
obtained from 2-chlorobenzoic acid, 1, and 1-aminonaphthalene,
2
H19NO : C, 79.50; H, 5.99; N, 4.42. Found: C, 79.10; H,
(
6
13
3
C NMR (75 MHz, CD -
144.6, 145.6, 167.1, 169.7.
N-(4-Methoxyphenyl)-4-nitroanthranilic Acid (33).26 Anthra-
nilic acid 33 was obtained from 2-chloro-4-nitrobenzoic acid, 32,
and 4-methoxyaniline, 24, as a yellow solid in 99% yield. H NMR
OD) δ ) 3.98 (s, 3H), 5.07 (bs, 1H), 7.05-7.20
m, 3H), 7.32 (d, J ) 8.5 Hz, 2H), 7.40 (d, J ) 8.8 Hz, 1H), 8.05
(24) Graboyes, H.; Anderson, E. L.; Levinson, S. H.; Resnick, T. M. J.
Heterocycl. Chem. 1975, 12, 1225-1231.
1
(
25) Thilo, D.; Von Kaulla, K. N. J. Med. Chem. 1970, 13, 503-510.
(26) Dokorou, V.; Demertzis, M. A.; Jasinski, J. P.; Kovala-Demertzi,
(300 MHz, CD
3
D. J. Organomet. Chem. 2004, 689, 317-325.
(
(27) Szczepankiewicz, B. G.; Liu, G.; Hajduk, P. J.; Abad-Zapatero, C.;
Pei, Z.; Xin, Z.; Lubben, T. H.; Trevillyan, J. M.; Stashko, M. A.; Ballaron,
S. J.; Liang, H.; Huang, F.; Hutchins, C. W.; Fesik, S. W.; Jirousek, M. R.
J. Am. Chem. Soc. 2003, 125, 4087-4096.
(28) Dheyongera, J. P.; Geldenhuys, W. J.; Dekker, T. G.; Van der Schyf,
C. J. Bioorg. Med. Chem. 2005, 13, 689-698.
148 J. Org. Chem., Vol. 71, No. 1, 2006