Supplementary Material

SYNTHESIS OF A SERIES OF ANTHRANILIC ACIDS 1 Supplementary Material NMR spectra ( 1 H and 13 C), infrared and the typical procedure for preparation of the compounds. GENERAL PROCEDURE FOR THE ANTHRANILIC ACIDS SYNTHESIS All anthranilic acids were synthesized following the same procedure. A mixture of isatin (1 mmol), 5 ml of sodium hydroxide solution 5% w/w and 5 ml of hydrogen peroxide 30% w/v was allowed to stir at room temperature for 15 or 45 minutes (Table I). The end of the reactions was confirmed by TLC, employing 50% hexane ethyl acetate as eluent. After total consumption of the substrate, hydrochloric acid 6 M was added dropwise until precipitation of the product, which was filtered under vacuum. The final ph of the resulting solution was 1 to 3 and was measured with an universal indicator paper. The yields, reaction times and solution ph values are shown in Table I. SPECTROSCOPIC AND SPECTROMETRIC METHODS 1 H and 13 C NMR were obtained on a Bruker DRX-200 model, operating at 200 MHz for 1 H nuclei and 50 MHz for 13 C in DMSO-d 6. Chemical shifts (δ) are expressed in parts per million (ppm) and values of coupling constants (J), in Hertz (Hz). IR spectra were recorded on a Nicolet Magna 760 (KBr). 1 H and 13 C NMR data and melting point of the products 5-BROMO-ANTHRANILIC ACID IV ν max (KBr), cm 1 : 3493, 3379, 3060, 2991, 2879, 2838, 2706, 2625, 1671, 1610, 1584, 1547, 1480, 1421, 1312, 1292, 1239, 1159, 1127, 1083, 903, 812, 789, 688, 628, 554, 516, 441; NMR 1 H δ H (200 MHz, DMSO): 7.61 (1H, d, J 4 Hz), 7.21 (1H, dd, J 4 and 8 Hz), 6.76 (1H, d, J 8 Hz). NMR 13 C δ C (50 MHz, DMSO-d 6 ): 168.32, 150.55, 136.08, 132.81, 118.67, 111.14, 104.54; Melting Point: 212 C 5-CHLORO-ANTHRANILIC ACID IV ν max (KBr), cm 1 : 3504, 3470, 3390, 3359, 3011, 2884, 2840, 1674, 1613, 1589,1552, 1483, 1421, 1291, 1238, 1157, 1133, 1088, 882, 810, 788, 705, 651, 655, 518, 442; NMR ¹H δ H (200 MHz, DMSO): 7.61 (1H, d, J 4 Hz), 7.21 (1H, dd, J 4 and 8 Hz), 6.72 (1H, d, J 8 Hz); NMR 13 C δ C (50 MHz, DMSO-d 6 ): 168.41, 150.24, 133.39, 129.83, 118.22, 117.51, 110.48; Melting Point: 212 C 5-NITRO-ANTHRANILIC ACID IV ν max (KBr), cm -1 : 3542, 3482, 3414, 3368, 3305, 3216, 3088, 1694, 1639, 1629, 1491, 1428, 1327, 1290, 1245, 1168, 1141,1075, 920, 827, 749, 696, 644, 569, 521, 505; NMR 1 H δ H (200 MHz, DMSO): 8.56 (1H, d, J 2 Hz), 8.04 (1H, dd, J 2 and 10 Hz); 7.85 (2H, s); 6.83 (1H, d, J 10 Hz); NMR 13 C δ C (50 MHz, DMSO-d 6 ): 168.07, 156.11, 135.03, 128.70, 128.62, 116.44, 108.45; Melting Point: 280 C 5-METHYL-ANTHRANILIC ACID IV ν max (KBr), cm 1 : 3425, 3325, 3022, 2953, 2926, 1674, 1599, 1569, 1493, 1421, 1303, 1241, 1214, 1162, 913, 818, 792, 758, 675, 620, 553, 524, 475, 439; NMR 1 H δ H (200 MHz, DMSO-d 6 ): 7.49 (1H, d, J 2 Hz),

2 GABRIEL F. RIO, BÁRBARA V. SILVA, SABRINA T. MARTINEZ and ANGELO C. PINTO 7.04 (1H, dd, J 2 and 8 Hz), 6.64 (1H, d, J 8 Hz), 2.12 (3H, s); NMR 13 C δ C (50 MHz, DMSO): 169.57, 149.39, 134.80, 130.69, 122.90, 116.52, 109.49, 19.84; Melting Point: 173 C 5-IODO-ANTHRANILIC ACID IV ν max (KBr), cm 1 : 3501, 3416, 3388, 3008, 2934, 2891, 2843, 2724, 2624, 1898, 1759, 1678, 1614, 1578, 1542, 1476, 1419, 1321, 1290, 1228, 1162, 1124, 1076, 1043, 914, 865, 811, 786, 688, 620, 558, 517, 448, 421; NMR 1 H δh (200 MHz, DMSO): 7.91 (1H, d, J 2 Hz), 7.44 (1H, dd, J 2 and 8 Hz); 6.60 (1H, d, J 8 Hz); NMR 13 C δc (50 MHz, DMSO-d6): 168.19, 150.85, 141.39, 138.86, 119.02, 112.00, 74.09; Melting Point: 210 C 5-FLUORO-ANTHRANILIC ACID IV ν max (KBr), cm 1 : 3503, 3381, 3078, 2893, 2587, 1674, 1591, 1562, 1491, 1434, 1417, 1310, 1291, 1238, 1199, 1151, 935, 883, 828, 799, 788, 757, 676, 559; NMR 1 H δh (200 MHz, DMSO): 7.36 (1H, dd, J 4 and 10 Hz), 7.14 (1H, ddd, J 2, 4 and 10 Hz), 6.75 (1H, dd, J 4 and 10 Hz); NMR 13 C δc (50 MHz, DMSO-d6): 168.59, 151.44 (d, J 229.5 Hz), 148.31, 121.72 (d, J 22 Hz), 117.83 (d, J 7 Hz), 115.41 (d, J 22 Hz), 109.29 (d, J 7 Hz); Melting Point: 180 C 4-FLUORO-ANTHRANILIC ACID IV ν max (KBr), cm 1 : 3506, 3385, 3064, 2911, 2854, 2720, 2647, 2614, 2538, 1664, 1600, 1570, 1497, 1429, 1324, 1254, 1179, 1142, 1114, 979, 892, 837, 762, 688, 613, 530, 462, 447; NMR 1 H δh (200 MHz, DMSO): 7.77-7.69 (1H, m), 6.48 (1H, dd, J 2 e 10 Hz), 6.29 (1H, td, J 2 and 10 Hz); NMR 13 C δc (50 MHz, DMSO-d6): 168.79, 165.69 (d, J 246 Hz), 153.60 (d, J 13 Hz), 134.13 (d, J 13 Hz), 106.71, 102.32 (d, J 23 Hz), 101.16 (d, J 23 Hz); Melting Point: 196 C 3-CHLOROANTHRANILIC ACID IV ν max (KBr), cm 1 : 3478, 3366, 3100, 3057, 3006, 2907, 2864, 2825, 2715, 2632, 2567, 2539, 1667, 1610, 1586, 1547, 1454, 1420, 1337, 1311, 1250, 1164, 1092, 1077, 919, 892, 855, 749, 708, 612, 574, 547, 459; NMR 1 H δh (200 MHz, DMSO-d6): 7.73 (1H, dd, J 2 and 8 Hz), 7.46 (1H, dd, J 2 and 8 Hz), 6.56 (1H, t, J 8). NMR 13 C δc (50 MHz, DMSO): 169.08, 146.89, 133.68, 130.35, 118.98, 115.06, 111.79; Melting Point: 190 C 3,5-DICHLORO-ANTHRANILIC ACID IV ν max (KBr), cm 1 : 3490, 3371, 3081, 2706, 1678, 1615, 1573, 1541, 1424, 1402, 1250, 1219, 1152, 1075, 876, 839, 788, 702, 600, 552, 461; NMR 1 H δh (200 MHz, DMSO): 7.68 (1H, d, J 2 Hz), 7.59 (1H, d, J 2 Hz); NMR 13 C δc (50 MHz, DMSO-d6): 167.98, 145.94, 132.86, 129.35, 119.92, 117.49, 112.27; Melting Point: 230 C 3,5-DIBROMO-ANTHRANILIC ACID IV ν max (KBr), cm 1 : 3467, 3363, 3083, 1784, 1682, 1599, 1564, 1537, 1452, 1420, 1326, 1306, 1265, 1243, 1223, 1063, 881, 789, 710, 689, 590, 544, 456; NMR 1 H δ H (200 MHz, DMSO): 7.84 (1H, d, J 2 Hz), 7.81 (1H, d, J 2 Hz); NMR 13 C δ C (50 MHz, DMSO-d 6 ): 167.81, 147.08, 138.35, 132.86, 112.98, 110.42, 104.69; Melting Point: 234 C

SYNTHESIS OF A SERIES OF ANTHRANILIC ACIDS 3 3-BROMO-5-METHYL-ANTHRANILIC ACID IV ν max (KBr), cm 1 : 3480, 3365, 2921, 2716, 2604, 1780, 1675, 1620, 1578, 1545, 1480, 1461, 1423, 1332, 1310, 1274, 1235, 1105, 1075, 1001, 938, 893, 868, 789, 705, 593, 553, 481, 456; NMR 1 H δ H (200 MHz, DMSO): 7.58 (1H, d, J 2 Hz), 7.47 (1H, d, J 2 Hz); 2.15 (3H, s); NMR ¹³C δ C (50 MHz, DMSO-d 6 ): 168.92, 145.58, 137.66, 130.93, 124.69, 111.63, 109.53, 19.33; Melting Point: 205 C N-ACETYL-ANTHRANILIC ACID IV ν max (KBr), cm 1 : 3481, 3376, 3181, 3123, 2927, 2918, 2609, 2798, 2789, 2595, 2667, 2539, 2502, 2474, 1702, 1655, 1605, 1581, 1522, 1453, 1430, 1377, 1327, 1312, 1298, 1268, 1243, 1164, 1149, 1088, 1042, 968, 881, 845, 792, 769, 755, 699, 651, 604, 558, 527; NMR 1 H δ H (200 MHz, DMSO-d 6 ): 11.04 (1H, s), 8.45 (1H, d, J 8 Hz), 7.96 (1H, dd, J 2 e 8 Hz), 7.55 (1H, td, J 2 and 8 Hz), 7.11 (1H, td, J 2 and 8 Hz), 2.11 (3H, s); NMR 13 C δ C (50 MHz, DMSO): 169.45, 168.44, 140.85, 133.95, 131.02, 122.51, 119.19, 116.46, 24.96; Melting Point: 184 C N-ALLYL-ANTHRANILIC ACID IV ν max (KBr), cm 1 : 3376, 3084, 3014, 2855, 2855, 2642, 2562, 1668, 1574, 1517, 1443, 1420, 1411, 1319, 1252, 1172, 932, 912, 753, 742, 668, 523; NMR ¹H δ H (200 MHz, DMSO-d 6 ): 7.79 (1 H, dd, J 2 and 8 Hz), 7.33 (1H, td, J 2 and 8 Hz); 6.67 (1 H, d, J 8 Hz); 6.55 (1H, t, J 8 Hz), 6.02-5.83 (1H, m), 5.26-5.10 (2 H, m), 3.85 (2 H, J 4 Hz); NMR 13 C δ C (50 MHz, DMSO-d 6 ): 170.01, 150.71 (C-NH 2 ), 135.31, 134.31, 115.49, 114.31, 111.50, 110.07, 44.38; Melting Point: 119 C N-BENZYL-ANTHRANILIC ACID IV ν max (KBr), cm 1 : 3376, 3029, 2916, 2865, 1663, 1576, 1518, 1495, 1441, 1411, 1363, 1625, 1277, 1249, 1236, 1176, 1166, 1154, 907, 836, 753, 728, 694, 658, 556, 527, 488, 457; NMR 1 H δ H (200 MHz, DMSO-d 6 ): 7.81 (1H, dd, J 2 and 8 Hz), 7.34-7.25 (5H, m), 6.65 (1H, d, J 8 Hz), 6.55 (1H, t, J 8 Hz), 4.44 (2H, s); NMR 13 C δ C (50 MHz, DMSO-d 6 ): 169.96, 150.64, 139.32, 134.31, 131.65, 128.48, 127.00, 114.46, 111.63, 110.30, 45.85; Melting Point: 182 C 5-IODO-N-ALLYL-ANTHRANILIC ACID IV ν max (KBr), cm 1 : 3372, 3075, 2923, 2851, 2623, 2543, 1668, 1567, 1503, 1441, 1422, 1402, 1310, 1233, 1168, 1105, 991, 932, 899, 807, 787, 688, 585, 516; NMR 1 H δ H (200 MHz, DMSO-d 6 ): 8.00 (1 H, d, J 2 Hz), 7.56 (1 H, dd, J 2 and 8 Hz), 6.54 (1H, d, J 8 Hz), 5.99-5.80 (1H, m), 5.22-5.09 (1H, m), 3.85 (2 H, J 6 Hz); NMR 13 C δ C (50 MHz, DMSO-d 6 ): 168.71, 150.05, 142.04, 139.28, 134.80, 115.67, 114.54, 112.56, 74.33, 44.27; Melting Point: 163 C 5-IODO- N-BENZYL-ANTHRANILIC ACID IV ν max (KBr), cm 1 : 3370, 3082, 3066, 3028, 2921, 2892, 2856, 2721, 2621, 2539, 1902, 1671, 1564, 1499, 1466, 1440, 1402, 1360, 1312, 1238, 1165, 1105, 1078, 1026, 898, 837, 809, 786, 749, 697, 684, 642, 594, 560, 517, 505, 426; NMR 1 H δ H (200 MHz, DMSO-d 6 ): 8.2 (1H, d, J 2 Hz), 7.52 (1H, dd, J 2 and 10 Hz); 7.33-7.23 (5H, m), 6.52 (1H, d, J 10 Hz), 4.44 (1H, s); NMR 13 C δ C (50 MHz, DMSO-d 6 ): 168.63, 149.93, 142.00, 139.87, 138.87, 129.21, 128.52, 126.94, 114.94, 112.81 74.52, 45.66; Melting Point: 163 C

4 GABRIEL F. RIO, BÁRBARA V. SILVA, SABRINA T. MARTINEZ and ANGELO C. PINTO Figure 1 - IR of 5-chloro-anthranilic acid.

SYNTHESIS OF A SERIES OF ANTHRANILIC ACIDS 5 Figure 2-1 H NMR of 5-chloro-anthranilic acid.

6 GABRIEL F. RIO, BÁRBARA V. SILVA, SABRINA T. MARTINEZ and ANGELO C. PINTO Figure 3-13 C NMR of 5-chloro-anthranilic acid.

SYNTHESIS OF A SERIES OF ANTHRANILIC ACIDS 7 Figure 4 - IR of 5-bromo-anthranilic acid.

8 GABRIEL F. RIO, BÁRBARA V. SILVA, SABRINA T. MARTINEZ and ANGELO C. PINTO Figure 5-1 H NMR of 5-bromo-anthranilic acid.

SYNTHESIS OF A SERIES OF ANTHRANILIC ACIDS 9 Figure 6-13 C NMR of 5-bromo-anthranilic acid.

10 GABRIEL F. RIO, BÁRBARA V. SILVA, SABRINA T. MARTINEZ and ANGELO C. PINTO Figure 7 - IR of 5-nitro-anthranilic acid.

SYNTHESIS OF A SERIES OF ANTHRANILIC ACIDS 11 Figure 8-1 H NMR of 5-nitro-anthranilic acid.

12 GABRIEL F. RIO, BÁRBARA V. SILVA, SABRINA T. MARTINEZ and ANGELO C. PINTO Figure 9-13 C NMR of 5-nitro-anthranilic acid.

SYNTHESIS OF A SERIES OF ANTHRANILIC ACIDS 13 Figure 10 - IR of 5-methyl-anthranilic acid.

14 GABRIEL F. RIO, BÁRBARA V. SILVA, SABRINA T. MARTINEZ and ANGELO C. PINTO Figure 11-1 H NMR of 5-methyl-anthranilic acid.

SYNTHESIS OF A SERIES OF ANTHRANILIC ACIDS 15 Figure 12-13 C NMR of 5-methyl-anthranilic acid.

16 GABRIEL F. RIO, BÁRBARA V. SILVA, SABRINA T. MARTINEZ and ANGELO C. PINTO Figure 13 - IR of 5-iodo-anthranilic acid.

SYNTHESIS OF A SERIES OF ANTHRANILIC ACIDS 17 Figure 14-1 H NMR of 5-iodo-anthranilic acid.

18 GABRIEL F. RIO, BÁRBARA V. SILVA, SABRINA T. MARTINEZ and ANGELO C. PINTO Figure 15-13 C NMR of 5-iodo-anthranilic acid.

SYNTHESIS OF A SERIES OF ANTHRANILIC ACIDS 19 Figure 16 - IR of 5-fluoro-anthranilic acid.

20 GABRIEL F. RIO, BÁRBARA V. SILVA, SABRINA T. MARTINEZ and ANGELO C. PINTO Figure 17-1 H NMR of 5-fluoro-anthranilic acid.

SYNTHESIS OF A SERIES OF ANTHRANILIC ACIDS 21 Figure 18-13 C NMR of 5-fluoro-anthranilic acid.

22 GABRIEL F. RIO, BÁRBARA V. SILVA, SABRINA T. MARTINEZ and ANGELO C. PINTO Figure 19 - IR of 4-fluoro-anthranilic acid.

SYNTHESIS OF A SERIES OF ANTHRANILIC ACIDS 23 Figure 20-1 H NMR of 4-fluoro-anthranilic acid.

24 GABRIEL F. RIO, BÁRBARA V. SILVA, SABRINA T. MARTINEZ and ANGELO C. PINTO Figure 21-13 C NMR of 4-fluoro-anthranilic acid.

SYNTHESIS OF A SERIES OF ANTHRANILIC ACIDS 25 Figure 22 - IR of 3-chloro-anthranilic acid.

26 GABRIEL F. RIO, BÁRBARA V. SILVA, SABRINA T. MARTINEZ and ANGELO C. PINTO Figure 23-1 H NMR of 3-chloro-anthranilic acid.

SYNTHESIS OF A SERIES OF ANTHRANILIC ACIDS 27 Figure 24-13 C NMR of 3-chloro-anthranilic acid.

28 GABRIEL F. RIO, BÁRBARA V. SILVA, SABRINA T. MARTINEZ and ANGELO C. PINTO Figure 25 - IR of 3,5-dichloro-anthranilic acid.

SYNTHESIS OF A SERIES OF ANTHRANILIC ACIDS 29 Figure 26-1 H NMR of 3,5-dichloro-anthranilic acid.

30 GABRIEL F. RIO, BÁRBARA V. SILVA, SABRINA T. MARTINEZ and ANGELO C. PINTO Figure 27-13 C NMR of 3,5-dichloro-anthranilic acid.

SYNTHESIS OF A SERIES OF ANTHRANILIC ACIDS 31 Figure 28 - IR of 3,5-dibromo-anthranilic acid.

32 GABRIEL F. RIO, BÁRBARA V. SILVA, SABRINA T. MARTINEZ and ANGELO C. PINTO Figure 29-1 H NMR of 3,5-dibromo-anthranilic acid.

SYNTHESIS OF A SERIES OF ANTHRANILIC ACIDS 33 Figure 30-13 C NMR of 3,5-bromo-anthranilic acid.

34 GABRIEL F. RIO, BÁRBARA V. SILVA, SABRINA T. MARTINEZ and ANGELO C. PINTO Figure 31 - IR of 3-bromo-5-methyl-anthranilic acid.

SYNTHESIS OF A SERIES OF ANTHRANILIC ACIDS 35 Figure 32-1 H NMR of 3-bromo-5-methyl-anthranilic acid.

36 GABRIEL F. RIO, BÁRBARA V. SILVA, SABRINA T. MARTINEZ and ANGELO C. PINTO Figure 33-13 C NMR of 3-bromo-5-methyl-anthranilic acid.

SYNTHESIS OF A SERIES OF ANTHRANILIC ACIDS 37 Figure 34 - IR of N-acetyl-anthranilic acid.

38 GABRIEL F. RIO, BÁRBARA V. SILVA, SABRINA T. MARTINEZ and ANGELO C. PINTO Figure 35-1 H NMR of N-acetyl-anthranilic acid.

SYNTHESIS OF A SERIES OF ANTHRANILIC ACIDS 39 Figure 36-13 C NMR of N-acetyl-anthranilic acid.

40 GABRIEL F. RIO, BÁRBARA V. SILVA, SABRINA T. MARTINEZ and ANGELO C. PINTO Figure 37 - IR of N-allyl-anthranilic acid.

SYNTHESIS OF A SERIES OF ANTHRANILIC ACIDS 41 Figure 38-1 H NMR of N-allyl-anthranilic acid.

42 GABRIEL F. RIO, BÁRBARA V. SILVA, SABRINA T. MARTINEZ and ANGELO C. PINTO Figure 39-13 C NMR of N-allyl-anthranilic acid.

SYNTHESIS OF A SERIES OF ANTHRANILIC ACIDS 43 Figure 40 - IR of ácido N-benzyl-anthranilic acid.

44 GABRIEL F. RIO, BÁRBARA V. SILVA, SABRINA T. MARTINEZ and ANGELO C. PINTO Figure 41-1 H NMR of N-benzyl-anthranilic acid.

SYNTHESIS OF A SERIES OF ANTHRANILIC ACIDS 45 Figure 42-13 C NMR of N-benzyl-anthranilic acid.

46 GABRIEL F. RIO, BÁRBARA V. SILVA, SABRINA T. MARTINEZ and ANGELO C. PINTO Figure 43 - IR of N-allyl-5-iodo-anthranilic acid.

SYNTHESIS OF A SERIES OF ANTHRANILIC ACIDS 47 Figure 44-1 H NMR of N-allyl-5-iodo-anthranilic acid.

48 GABRIEL F. RIO, BÁRBARA V. SILVA, SABRINA T. MARTINEZ and ANGELO C. PINTO Figure 45-13 C NMR of N-benzyl-5-iodo-anthranilic acid.

SYNTHESIS OF A SERIES OF ANTHRANILIC ACIDS 49 Figure 46 - IR of N-benzyl-5-iodo-anthranilic acid.

50 GABRIEL F. RIO, BÁRBARA V. SILVA, SABRINA T. MARTINEZ and ANGELO C. PINTO Figure 47-1 H NMR of N-benzyl-5-iodo-anthranilic acid.

SYNTHESIS OF A SERIES OF ANTHRANILIC ACIDS 51 Figure 48-13 C NMR of N-benzyl-5-iodo-anthranilic acid.