1084
M. Robin, V. Pique, R. Faure and J.-P. Galy
Vol. 39
In conclusion, we have described the synthesis of N-aryl
(ma, 4H, C-H
), 7.02 (d, 1H, C-H ), 7.32 (ddd, 1H, C-
5-7-8-12
10
13
H ), 7.85 (d, 1H, C-H ), 9.37 (bs, 1H, COOH); C NMR
anthranilic acids carrying an extra fused ring, which are
the key step intermediates in the synthesis of tetracyclic
acridine derivatives [14]. The use of ultrasonic irradiation
is an interesting technique in the synthesis of anthranilic
acid. The extension of such experiments to other hetero-
cycles is now being investigated.
11
13
(DMSO-d ): δ 63.9 (C-2), 64.2 (C-3), 111.7 (C-13a), 111.9 (C-5),
6
113.1 (C-10), 116.3 (C-7), 116.5 (C-12), 117.6 (C-8), 131.8 (C-
13), 133.7 (C-11), 134.2 (C-9a), 143.7 (C-4a; C-8a), 148.3 (C-6),
170.0 (C-14).
Anal. Calcd. for C
Found: C, 66.62; H, 4.91; N, 5.25.
H NO : C, 66.41; H, 4.83; N, 5.16.
15 13 4
N-(2,3-Dihydro-1H-inden-5-ylamino)benzoic Acid (4).
EXPERIMENTAL
Compound 4 was obtained in 70% yield, mp 167 °C, Mol. Wt.:
1
253; H NMR (DMSO-d ): δ 2.00 (q, 2H, (CH ) ), 2.83 (m, 4H,
6
2 2
Reagents and solvents were purchased from common commer-
cial suppliers. Melting points were determined with an
Electrothermal 9300 apparatus and are uncorrected. The NMR
(CH ) ), 6.70 (bs, 1H, C-H ), 6.88 (m, 2H, C-H
), 7.08 (d,
2 1-3
6
4-7-9
13
1H, C-H ), 7.31 (ddd, 1H, C-H ), 7.32 (d, 1H, C-H );
NMR (DMSO-d ): δ 25.2 (C-2), 31.73 (C-3), 32.73 (C-1), 112.0
(C-12a), 113.3 (C-9), 116.6 (C-11), 118.3 (C-4), 120.3 (C-6),
124.8 (C-7), 131.8 (C-12), 134.0 (C-10), 138.4 (C-7a), 138.9 (C-
5), 145.1 (C-3a), 148.0 (C-8a), 169.8 (C-13).
C
10
12
11
6
spectra were recorded on a Bruker AC 200 spectrometer operat-
13
ing at 50.3 MHz for C. 2D NMR spectra, both of homonuclear
(COSY) and heteronuclear (HMBC, HMQC) correlations, were
obtained with a Bruker AMX 400. In all cases TMS was used as
an internal standard.
Anal. Calcd. for C
Found: C, 75.52; H, 5.27; N, 5.55.
H NO : C, 75.87; H, 5.97; N, 5.53.
16 15 2
General Procedure for the Synthesis of Anthranilic Acids 1-6.
N-[(2-Chloro-1-methyl-1H-benzimidazol-5-yl)amino]benzoic
Acid (5).
Just before starting the reaction, the copper catalyst was pre-
pared from 0.8 g of anhydrous copper sulfate in 5 mL of water, to
this solution was added 0.3 g of powdered zinc keeping the tem-
perature almost constant. The copper/zinc precipitate was fil-
tered, washed first with water, then with acetone and dried in the
oven. In a 100 mL round bottom flask were placed a mixture of
amino heterocycle (10 mmoles), 2.21 g of o-bromobenzoic acid
(11 mmoles), 1.7 g of anhydrous potassium carbonate (12
mmoles), 0.06 g of powdered copper/zinc and 25 mL of butan-2-
one. This mixture was sonicated in a bath (80 °C) for 3 hours.
After evaporation of the solvent, the residue was stirred with 80
mL of hot water, filtered and acidified to pH 5 with 2N HCl. The
new precipitate formed was collected by filtration, washed with
water and dried to give 1-6. Spectral data for these compounds
are consistent with the literature.
Compound 5 was obtained in 87% yield, mp: 226°C, Mol.
1
Wt.: 302; H NMR (DMSO-d ): δ 3.79 (s, 3H, (CH ) ), 6.71
6
3 14
(ddd, 1H, C-H ), 7.01 (dd, 1H, C-H ), 7.21 (dd, 1H, C-H ),
11
9
6
7.32 (ddd, 1H, C-H ), 7.45 (d, 1H, C-H ), 7.59 (d, 1H, C-H ),
10
4
7
13
7.88 (dd, 1H, C-H ), 9.60 (bs, 1H, N-H ); C NMR (DMSO-
12
8
d ): δ 30.7 (C-14), 111.3 (C-7), 111.6 (C-12a), 112.9 (C-4),
6
113.0 (C-9), 116.7 (C-11), 119.9 (C-6), 131.8 (C-12), 132.9
(C-7a), 134.3 (C-10), 135.3 (C-5), 140.7 (C-2), 141.8 (C-3a),
148.7 (C-8a), 170.1 (C-13).
Anal. Calcd. for C H ClN O : C, 59.71; H, 4.01; N, 11.75.
15 12
3 2
Found: C, 59.84; H, 4.12; N, 11.74.
N-{[2-(Dimethylamino)-benzoxazol-6-yl]amino}-benzoic acid
(6).
N-[(2-Chloro-benzothiazol-6-yl)amino]benzoic Acid (1).
Compound 6 was obtained in 90% yield, mp 224°C, Mol. Wt.:
1
297; H NMR (DMSO-d ): δ 3.09 (s, 6H, 2αCH ), 6.67 (ddd,
6
3
Compound 1 was obtained in 86% yield, mp 186 °C, Mol. Wt.:
1H, J=1.1,7.7 Hz, C-H ), 6.98 (m, 2H, C-H , C-H ), 7.28 (m,
1
11
5
10
305; H NMR (DMSO-d ): δ 6.84 (t, 1H, J=8.4 Hz C-H ), 7.31-
6
10
13
2H, C-H , C-H ), 7.30 (s, 1H, C-H ), 7.86 (dd, 1H, J=7.7 Hz, C-
4
9
7
7.47 (ma, 3H), 7.86-8.00 (ma, 3H), 9.80 (s, 1H, N-H ); C NMR
7
13
H ), 9,54 (s, 1H, N-H ); C NMR (DMSO-d ): δ 37.5 (C-α),
12
8
6
(DMSO-d ): δ 112.65* (C-7), 114.01* (C-9), 118.26 (C-11),
6
105.3 (C-4), 111.6 (C-12a), 113.2 (C-9), 115.8 (C-5), 116.7 (C-
11), 120.2 (C-7), 132.0 (C-12), 133.3 (C-6), 134.5 (C-10), 140.5
(C-3a), 149.0 (C-7a), 149.3 (C-8a), 163.1 (C-2), 170.4 (C-13).
121.17 (C-5), 123.03 (C-4), 131.99 (C-12), 134.08 (C-10), 137.10
(C-7a), 139.14 (C-6), 146.02 (C-3a), 146.07 (C-8a), 150.38 (C-2),
169.91 (C-13), n.o. (C-12a). Anal. Calcd. for C H ClN O S: C,
14
9
2 2
Anal. Calcd. for C H N O : C, 64.64; H, 5.09; N, 14.13.
16 15
3 3
55.12; H, 2.95; N, 9.19. Found: C, 55.32; H, 3.19; N, 8.95.
Found: C, 64.51; H, 5.10; N, 14.26.
N-(1,3-Benzodioxol-5-ylamino)benzoic Acid (2).
Compound 5 was obtained in 45% yield, mp 170 °C, Mol. Wt.:
REFERENCES AND NOTES
1
257); H NMR (DMSO-d ): δ 6.02 (bs, 2H, (CH ) ), 6.70 (m,
6
2 2
2H, C-H ), 6.88 (m, 3H, C-H
), 7.09 (ddd, 1H, C-H ),
[1] Albert, A. Selective Toxicity, 7th ed.; Chapman & Hall:
London, 1985.
6-11
4-7-9
10
13
7.31 (d, 1H, C-H ); C NMR (DMSO-d ): δ 101.24 (C-2),
12
6
[2] W. A. Denny, and B. C. Baguley, Molecular Aspects of Anti-
Cancer Drug-DNA Interactions; S. Neidle and M. J. Waring, Eds.;
Macmillan: London, 1994; pp 270-311.
[3] C. Korth, B. C. H. May, F. E. Cohen and S. B. Prusiner, Proc.
Natl. Acad. Sci. USA, 98, 9836 (2001).
[4a] I. B. Taraporewala, J. W. Cessac, T. C. Chanh, A. V. Delgado
and R. F. Schinazi, J. Med. Chem., 35, 2744 (1992); [b] S. Morel, J-P.
Galy, J. Elguero and J. Barbe, Tetrahedron Lett., 34, 2609 (1993); [c] M.
Robin, R. Faure, A. Périchaud and J-P. Galy, Heterocycles, 53, 387
(2000).
105.28 (C-4), 108.61 (C-7), 111.57 (C-12a), 113.17 (C-6), 116.39
(C-9), 116.56 (C-11), 131.80 (C-12), 134.19 (C-10), 134.38 (C-
5), 143.93 (C-7a), 147.98 (C-3a), 148.54 (C-8a), 170.00 (C-13).
Anal. Calcd. for C H NO : C, 65.37; H, 4.31; N, 5.44.
14 11
4
Found: C, 65.32; H, 4.21; N, 5.25.
N-(2,3-Dihydro-1,4-benzodioxin-6-ylamino)benzoic Acid (3).
Compound 3 was obtained in 81% yield, mp 191 °C, Mol. Wt.:
1
271; H NMR (DMSO-d ): δ 4.22 (bs, 4H, 2(CH ) ), 6.73-6.86
6
2 2-3