Oxidative Cleavage of C2–C3 Bond in Isatin Using (Diacetoxyiodo)benzene: A Facile Synthesis of Carbamates of Alkyl Anthranilates

Abstract

On reaction with (diacetoxyiodo)benzene, isatin and N-acetyl isatin undergo the oxidative C2–C3 bond cleavage to form carbamates of alkyl anthranilates and alkyl 2-acetamidobenzoate, respectively.

Key words

Hofmann rearrangement - phthalimide - isatin - hypervalent iodine - 1,2-dicarbonyl cleavage

• References and Notes


Reviews:
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• 7 General Procedure To the stirred solution of isatin (1 mmol) in an appropriate alcohol (5 mL), (diacetoxyiodo)benzene (1.7 mmol) was added. The reaction mixture was stirred for 9–24 h at r.t. The progress of the reaction was monitored by TLC. After completion of reaction, the solvent was evaporated on rotatory vacuum evaporator, and the crude product was purified by column chromatography using PE and EtOAc to afford 2a–q in moderate yields.
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• 9 Spectral Data for the New Products Compound 2c: Yield 0.1462 g (55%), pale yellow oil. ¹H NMR (300 MHz, CDCl₃): δ = 0.983 (3 H, t, J = 7.8 Hz, CH₃), 1.03 (3 H, t, J = 7.5 Hz, CH₃), 1.67–1.84 (4 H, m, 2 CH₂), 4.12 (2 H, t, J = 9.2 Hz, OCH₂), 4.27 (2 H, t, J = 8.8 Hz, OCH₂), 7.02 (1 H, t, J = 10.4 Hz, ArH), 7.54 (1 H, t, J = 9.6 Hz, ArH), 8.02 (1 H, dd, J = 10.8, 2 Hz, ArH), 8.45 (1 H, d, J = 11.2 Hz, ArH), 10.56 (1 H, br s, NH). ¹³C NMR (75 MHz, CDCl₃): δ = 10.4, 10.6, 22.1, 22.3, 66.9 (2 C), 114.8, 118.8, 121.4, 130.9, 134.5, 142, 153.9, 168.2. Compound 2e: Yield 0.2123 g (65%), yellow oil. ¹H NMR (300 MHz, CDCl₃): δ = 1.25 (6 H, t, J = 9.2 Hz, 2 CH₃), 3.54–3.59 (4 H, m, 2 OCH₂), 3.68 (2 H, t, J = 6.4 Hz, OCH₂), 4.33 (2 H, t, J = 6.4 Hz, OCH₂), 4.45 (2 H, t, J = 6.4 Hz, OCH₂), 7.05 (1 H, t, J = 9.6 Hz, ArH), 7.52 (1 H, td, J = 9.6, 2.0 Hz, ArH), 8.05 (1 H, dd, J = 2.0 Hz, 10.8 Hz, ArH), 8.44 (1 H, d, J = 11.2 Hz, ArH), 10.46 (1 H, br s, NH). ¹³C NMR (75 MHz, CDCl₃): δ = 15.2, 19.5, 64, 64.5, 66.7, 66.8, 68.6, 69.9, 114.7, 118.9, 121.6, 131.1, 134.6, 141.7, 153.6, 168. IR: 3304, 1736, 1689, 1525, 1450, 1385, 1238, 1211, 1260, 752 cm^–1. Compound 2f: Yield 0.1756 g (77%), mp 98 °C. ¹H NMR (400 MHz, CDCl₃): δ = 3.78 (3 H, s, CH₃), 3.92 (3 H, s, CH₃), 7.25 (1 H, ddd, J = 11.1, 6.9, 3.0 Hz, ArH), 7.66 (1 H, dd, J = 3.1, 9.2 Hz, ArH), 8.42 (1 H, dd, J = 5.0, 9.3 Hz ArH), 10.41 (1 H, br s, NH). ¹³C NMR (100 MHz, CDCl₃): δ = 52.3, 52.5, 115.5 (d, ³ J _C–F = 6 Hz), 116.6 (d, ²J _C–F = 24 Hz), 120.5 (d, ³ J _C–F = 7 Hz), 121.6 (d, ² J _C–F = 23 Hz), 138.1 (d, ⁴ J _C–F = 2 Hz), 154.1, 158.3, (d, ¹ J _C–F = 241 Hz), 167.4 (d, ⁴ J _C–F = 2 Hz). IR: 3260, 1733, 1689, 1601, 1526, 1427, 1255, 1214, 1056 cm^–1. ESI-MS: m/z [M⁺] calcd for C₁₀H₁₀FNO₄: 227.0594; found [M + 23]: 250. Compound 2g: Yield 0.1905 g (78%), mp 122 °C. ¹H NMR (400 MHz, CDCl₃): δ = 3.78 (3 H, s, CH₃), 3.92 (3 H, s, CH₃), 7.46 (1 H, dd, J = 9.0, 2.6 Hz, ArH), 7.95 (1 H, d, J = 2.6 Hz, ArH), 8.40 (1 H, d, J = 9.0 Hz, ArH), 10.41 (1 H, s, NH). ¹³C NMR (100 MHz, CDCl₃): δ = 52.4, 52.5, 115.6, 120.2, 126.6, 130.3, 134.4, 140.3, 153.9, 167.4. IR: 3251, 1730, 1686, 1587, 1513, 1447, 1281, 1213 cm^–1. ESI-MS: m/z [M]⁺ calcd for C₁₀H₁₀ClNO₄: 243.0298; found [M + 23]: 266. Compound 2h: Yield 0.1676 g (61%), mp 84 °C. ¹H NMR (400 MHz, CDCl₃): δ = 1.32 (3 H, t, J = 7.1 Hz, CH₃), 1.41 (3 H, t, J = 7.1 Hz, CH₃), 4.22 (2 H, q, J = 7.1 Hz, CH₂), 4.38 (2 H, q, J = 7.1 Hz, CH₂), 7.46 (1 H, dd, J = 9.0, 2.6 Hz, ArH), 7.97 (1 H, d, J = 2.6 Hz, ArH), 8.42 (1 H, d, J = 9.1 Hz, ArH), 10.43 (1 H, br s, NH). ¹³C NMR (100 MHz, CDCl₃): δ = 14.1, 14.4, 61.3, 61.7, 115.9, 120.2, 126.4, 130.3, 134.3, 140.5, 153.5, 167.0. IR: 3233, 1727, 1694, 1588, 1516, 1458, 1237, 1211, 1053 cm^–1. ESI-MS: m/z [M]⁺ for ­C₁₂H₁₄ClNO₄: 271.0611; found [M + 1] and [M + 23]: 272 and 294. Compound 2j: Yield 0.5709 g (57%), mp 88 °C. ¹H NMR (400 MHz, CDCl₃): δ = 1.32 (3 H, t, J = 7.1 Hz, CH₃), 1.41 (3 H, t, J = 7.1 Hz, CH₃), 4.23 (2 H, q, J = 7.1 Hz, CH₂), 4.39 (2 H, q, J = 7.1 Hz, CH₂), 7.60 (1 H, dd, J = 9.0, 2.4 Hz, ArH), 8.12 (1 H, d, J = 2.4 Hz, ArH), 8.36 (1 H, d, J = 9.0 Hz, ArH), 10.44 (1 H, br s, NH). ¹³C NMR (100 MHz, CDCl₃): δ = 14.1, 14.4, 61.3, 61.7, 113.6, 116.2, 120.5, 133.2, 137.1, 141, 153.5, 166.9. IR: 3239, 1730, 1693, 1586, 1511, 1369, 1246, 1212, 1053, 840 cm^–1. ESI-MS: m/z [M⁺] calcd for C₁₂H₁₄BrNO₄: 315.0106; found [M + 23]: 338. Compound 2k: Yield 0.2818 g (77%), mp 104 °C. ¹H NMR (400 MHz, CDCl₃): δ = 3.77 (3 H, s, CH₃), 3.90 (3 H, s, CH₃), 7.55 (1 H, br s, NH), 7.89 (1 H, d, J = 2.2 Hz, ArH), 7. 94 (1 H, d, J = 2.2 Hz, ArH). ¹³C NMR (100 MHz, CDCl₃): δ = 52.8, 53.1, 118.5, 121.5, 128, 132.6, 135.1, 138.8, 153.9, 165.4. IR: 3255, 1729, 1706, 1553, 1512, 1434, 1260, 1228, 1062 cm^–1. ESI-MS: m/z [M]⁺ calcd for C₁₀H₉ ⁸¹Br₂NO₄: 366.8898; found [M + 23]: 390. Compound 2l: Yield 0.2233 g (56%), mp 59 °C. ¹H NMR (400 MHz, CDCl₃): δ = 1.28 (3 H, t, J = 7.1 Hz, CH₃), 1.36 (3 H, t, J = 7.1 Hz, CH₃), 4.21 (2 H, q, J = 7.1 Hz, CH₂), 4.35 (2 H, q, J = 7.1 Hz, CH₂), 7.49 (1 H, br s, NH), 7.88 (1 H, d, J = 2.3 Hz, ArH), 7.94 (1 H, d, J = 2.3 Hz, ArH). ¹³C NMR (100 MHz, CDCl₃): δ = 14.1, 14.4, 62, 62.1, 118.3, 121.4, 128.3, 129.4, 132.6, 135.1, 138.7, 153.5, 165. IR: 3240, 1698, 1512, 1450, 1382, 1255, 1190, 1063 cm^–1. ESI-MS: m/z [M⁺] calcd for C₁₂H₁₃ ⁸¹Br₂NO₄: 394.9211; found [M + 23]: 418. Compound 2n: Yield 0.1546 g (55%), mp 70 °C. ¹H NMR (400 MHz, CDCl₃): δ = 1.35 (3 H, t, J = 7.1 Hz, CH₃), 1.46 (3 H, t, J = 7.1 Hz, CH₃), 4.28 (2 H, q, J = 7.1 Hz, CH₂), 4.45 (2 H, q, J = 7.1 Hz, CH₂), 8.35 (1 H, dd, J = 9.4, 2.8 Hz, ArH), 8.66 (1 H, d, J = 9.4 Hz, ArH), 8.91 (1 H, d, J = 2.7 Hz, ArH), 10.89 (1 H, br s, NH). ¹³C NMR (100 MHz, CDCl₃): δ = 14.4 (2 C), 62.0, 62.4, 114.3, 118.8, 127.0, 129.2, 140, 147.2, 153.1, 166.6. IR: 3253, 1734, 1682, 1584, 1505, 1462, 1243, 1202, 1003 cm^–1. ESI-MS: m/z [M⁺] calcd for C₁₂H₁₄N₂O₆: 282.0852; found [M + 1] and [M + 18]: 283 and 305. Compound 2p: Yield 0.0942 g (37%), pale yellow oil. ¹H NMR (400 MHz, CDCl₃): δ = 1.31 (3 H, t, J = 7.1 Hz, CH₃), 1.41 (3 H, t, J = 7.1 Hz, CH₃), 2.31 (3 H, s, CH₃), 4.22 (2 H, q, J = 7.0 Hz, CH₂), 4.36 (2 H, q, J = 7.1 Hz, CH₂), 7.32 (1 H, dd, J = 8.6, 2.0 Hz, ArH), 7.80 (1 H, d, J = 1.8 Hz, ArH), 8.31 (1 H, d, J = 8.6 Hz, ArH), 10.36 (1 H, br s, NH). ¹³C NMR (100 MHz, CDCl₃): δ = 14.2, 14.5, 20.5, 61.0, 61.2, 114.6, 118.8, 130.7, 130.8, 135.2, 139.5, 153.7, 168.1. IR: 3303, 1727, 1687, 1591, 1523, 1470, 1241, 1206, 747 cm^–1. Compound 2q: Yield 0.112 g (31%), pale yellow oil. ¹H NMR (400 MHz, CDCl₃): δ = 2.36 (3 H, s, CH₃), 4.56 (2 H, q, J = 8.4 Hz, CH₂), 4.70 (2 H, q, J = 8.28 Hz, CH₂), 7.43 (1 H, dd, J = 8.6, 1.92 Hz, ArH), 7.84 (1 H, d, J = 1.72 Hz, ArH), 8.29 (1 H, d, J = 8.6 Hz, ArH), 10.27 (1 H, br s, NH). IR: 3290, 1751, 1707, 1596, 1539, 1457, 1286, 1167, 785 cm^–1. Compound 4a: Yield 0.1325 g (68%), mp 94 °C. ¹H NMR (400 MHz, CDCl₃): δ = 2.23 (3 H, s, CH₃), 3.92 (3 H, s, OCH₃), 7.07 (1 H, td, J = 1.2, 8.2 Hz, ArH), 7.53 (1 H, td, J = 1.6, 8.6 Hz, ArH), 8.01 (1 H, dd, J = 1.6, 8.0 Hz, ArH), 8.69 (1 H, dd, J = 0.76, 8.6 Hz, ArH), 11.04 (1 H, br s, NH). ¹³C NMR (100 MHz, CDCl₃): δ = 25.4, 52.3, 114.7, 120.3, 122.4, 130.7, 134.6, 141.6, 168.7, 169. IR: 3270, 2921, 2853, 1687, 1584, 1450, 1367, 1260, 1080, 756 cm^–1. Compound 4b: Yield 0.1296 g (62%), mp 62 °C. ¹H NMR (400 MHz, CDCl₃): δ = 1.41 (3 H, t, J = 7.1 Hz, CH₃), 2.23 (3 H, s, CH₃), 4.37 (3 H, s, J = 7.1 Hz, CH₃), 7.06 (1 H, td, J = 1.1, 8.2 Hz, ArH), 7.52 (1 H, td, J = 1.6, 8.7 Hz, ArH), 8.03 (1 H, dd, J =1.6, 8.0 Hz, ArH), 8.69 (1 H, dd, J = 1.6, 8.0 Hz, ArH), 11.09 (1 H, br s, NH). ¹³C NMR (100 MHz, CDCl₃): δ = 14.1, 25.4, 61.3, 115, 120.2, 122.3, 130.7, 134.5, 141.6, 168.3, 169. IR: 3252, 2923, 2852, 1705, 1681, 1590, 1442, 1360, 1261, 1085, 752 cm^–1. Compound 4c: Yield 0.1571 g (69%). ¹H NMR (400 MHz, CDCl₃): δ = 2.23 (3 H, s, CH₃), 3.94 (3 H, s, OCH₃), 7.48 (1 H, dd, J = 2.6, 9.0 Hz, ArH), 7.99 (1 H, d, J = 2.6 Hz, ArH), 8.69 (1 H, d, J = 9.0 Hz, ArH), 10.96 (1 H, br s, NH). ¹³C NMR (100 MHz, CDCl₃): δ = 25.4, 52.6, 116, 121.7, 127.4, 130.3, 134.5, 140.1, 169. IR: 3273, 2923, 2853, 1688, 1600, 1511, 1469, 1359, 1250, 1106, 835, 788, 733 cm^–1. Compound 4d: Yield 0.1466 g (60%). ¹H NMR (400 MHz, CDCl₃): δ = 1.42 (3 H, t, J = 7.0 Hz, CH₃), 2.23 (3 H, s, CH₃), 4.39 (2 H, q, J = 7.0 Hz, CH₂), 7.48 (1 H, dd, J = 2.6, 9.0 Hz, ArH), 8.00 (1 H, d, J = 2.6 Hz, ArH), 8.69 (1 H, d, J = 9.0 Hz, ArH), 11.02 (1 H, br s, NH). ¹³C NMR (100 MHz, CDCl₃): δ = 14.1, 25.4, 61.8, 116.3, 121.7, 127.4, 130.3, 134.3, 140.1, 167.2, 169. IR: 3266, 2922, 2852, 1699, 1681, 1523, 1400, 1366, 1234, 838, 789, 734 cm^–1. Compound 4e: Yield 0.1958 g (72%), mp 122 °C. ¹H NMR (400 MHz, CDCl₃): δ = 2.24 (3 H, s, CH₃), 3.93 (3 H, s, OCH₃), 7.62 (1 H, dd, J = 2.3, 9.0 Hz, ArH), 8.14 (1 H, d, J = 2.4 Hz, ArH), 8.63 (1 H, d, J = 9.0 Hz, ArH), 10.97 (1 H, br s, NH). ¹³C NMR (100 MHz, CDCl₃): δ = 25.4, 52.6, 114.7, 116.3, 122, 133.3, 137.3, 140.6, 167.6, 169. IR: 3282, 2922, 2852, 1696, 1680, 1597, 1465, 1361, 1257, 1086, 834, 787, 754 cm^–1. Compound 4f: Yield 0.1746 g (61%), mp 120 °C. ¹H NMR (400 MHz, CDCl₃): δ = 1.42 (3 H, t, J = 7.1 Hz, CH₃), 2.23 (3 H, s, CH₃), 4.37 (2 H, q, J = 7.1 Hz, CH₂), 7.60 (1 H, dd, J = 2.4, 9.0 Hz, ArH), 8.14 (1 H, d, J = 2.4 Hz, ArH), 8.64 (1 H, d, J = 9.0 Hz, ArH), 11.02 (1 H, br s, NH). ¹³C NMR (100 MHz, CDCl₃): δ = 14.1, 25.4, 61.8, 114.7, 116.6, 122, 133.2, 137.2, 140.6, 167.1, 169. IR: 3260, 2922, 2852, 1698, 1677, 1599, 1469, 1365, 1255, 1089, 836, 788, 719 cm^–1. Compound 4g: Yield 0.0789 g (48%), mp 68 °C. ¹H NMR (400 MHz, CDCl₃): δ = 2.22 (3 H, s, CH₃), 2.32 (3 H, s, CH₃), 3.92 (3 H, s, OCH₃), 7.35 (1 H, dd, J = 2.0, 8.5 Hz, ArH), 7.82 (1 H, d, J = 2.0 Hz, ArH), 8.57 (1 H, d, J = 8.5 Hz, ArH), 10.92 (1 H, br s, NH). ¹³C NMR (100 MHz, CDCl₃): δ = 0.6, 25.4, 52.2, 114.7, 120.3, 130.8, 131.9, 135.4, 139.2, 168.8, 168.9. IR: 3270, 2922, 2853, 1683, 1594, 1455, 1367, 1266, 1087, 838, 790, 722 cm^–1.
• 10 Papadopoulou M, Varvoglis A. J. Chem. Res., Synop. 1983; 66