Journal of Medicinal Chemistry N-(2-Ethylphenyl)-4-nitrobenzenesulfonamide (72). Method G was used. Yield, 84%; orange solid; mp, 149 °C. IR ν: 1531 (NO2), 1344 (NO2) cm−1. 1H NMR (CDCl3): δ 8.19−8.16 (m, 2H, Ar), 7.83−7.77 (m, 2H, Ar), 7.39−6.77 (m, 4H, Ar), 2.34 (q, 2H, J = 7.5 Hz, CH2), 0.92 (t, 3H, J = 7.5 Hz, CH3). 13C NMR (CDCl3): δ 149.7, 146.2, 140.9, 133.4, 129.2, 128.3, 127.3, 126.9, 126.4, 124.6, 23.22, 14.5. 4-Nitro-N-(2-propylphenyl)benzenesulfonamide (73). Meth- od G was used. Yield, 91%; white solid; mp, 120−121 °C. IR ν: 1530 (NO2), 1343 (NO2) cm−1. 1H NMR (DMSO-d6): δ 9.25−9.22 (m, 2H, Ar), 8.78−8.75 (m, 2H, Ar), 8,26−7.64 (m, 4H, Ar), 3.27 (t, 2H, J = 7.9 Hz, CH2), 2.21−2.13 (m, 2H, CH2), 1.61 (t, 3H, J = 7.3 Hz, CH3). 13C NMR (DMSO-d6): δ 151.0, 146.2, 133.6, 130.2, 129.9, 128.3, 127.2, 126.5, 125.0, 124.6, 32.3, 23.0, 13.9. General Procedure for the Synthesis of Compounds 74−91. The appropriate nitro compound (2.0 mmol) was dissolved in a mixture of EtOH and H2O (40 mL, 10:1). Powdered iron (8.0 mmol) and ﬁve drops of hydrochloric acid (12 M) were added. The mixture was reﬂuxed overnight. After the mixture was cooled at room temperature, the solvent was evaporated. HCl (1 N, 100 mL) was added and the mixture was extracted with ethyl acetate (100 mL). The organic solutions were pooled, washed with brine, dried over anhydrous Na2SO4, and concentrated under reduced pressure. 2-Tolyl 4-Aminobenzenesulfonate (74). Yield, 88%; yellowish solid; mp, 66−67 °C. IR ν: 3387 (NH2), 1592 (NH2) cm−1. 1H NMR (CDCl3): δ 7.55−7.53 (m, 2H, Ar), 7.13−7.10 (m, 3H, Ar), 7.04−7.00 (m, 1H, Ar), 6.62−6.60 (m, 2H, Ar), 4.41 (brs, 2H, NH2), 2.24 (s, 3H, CH3). 13C NMR (CDCl3/DMSO-d6): δ 153.1, 148.3, 131.5, 131.4, 130.3, 126.7, 122.3, 121.4, 113.5, 16.4. 3-Tolyl 4-Aminobenzenesulfonate (75). Yield, 92%; white solid; mp, 67−68 °C. IR ν: 3389 (NH2), 1592 (NH2) cm−1. 1H NMR (CDCl3/MeOD): δ 7.45−7.42 (m, 2H, Ar), 7.05−7.00 (m, 1H, Ar), 6.94−6.91 (m, 1H, Ar), 6.75 (s, 1H, Ar), 6.66−6.58 (m, 3H, Ar), 4.37 (brs, 2H, NH2), 2.15 (s, 3H, CH3). 13C NMR (CDCl3/MeOD): δ 152.2, 149.6, 139.9, 130.5, 129.2, 127.8, 123.0, 121.8, 119.2, 114.1, 21.0. 4-Tolyl 4-Aminobenzenesulfonate (76). Yield, 92%; orange solid; mp, 130−132 °C. IR ν: 3394 (NH2), 1596 (NH2) cm−1. 1H NMR (CDCl3): δ 7.52 (d, 2H, J = 8.5 Hz, Ar), 7.05 (d, 2H, J = 8.5 Hz, Ar), 6.85 (d, 2H, J = 8.5 Hz, Ar), 6.61 (d, 2H, J = 8.5 Hz, Ar), 4.36 (brs, 2H, NH2), 2.28 (s, 3H, CH3). 13C NMR (CDCl3): δ 152.1, 147.6, 136.8, 130.7, 130.0, 122.5, 122.2, 113.8, 20.9. 4-Methoxyphenyl 4-Aminobenzenesulfonate (77). To a solution of the nitro compound 59 (2.0 mmol) in ethanol (40 mL) was added stannous chloride dihydrate (12.0 mmol), and the mixture was reﬂuxed for 6 h. After the mixture was cooled at room temperature, the solvent was evaporated. The residue was then taken up in 300 mL of 1 N NaOH and extracted with ether (200 mL). The combined organic extracts were washed with brine, dried over Na2SO4, and concentrated under reduced pressure. Yield, 97%; orange solid; mp, 161−162 °C. IR ν: 1594 (NH2) cm−1. 1H NMR (DMSO- d6): δ 7.38 (d, 2H, J = 8.8 Hz, Ar), 6.89 (s, 4H, Ar), 6.62 (d, 2H, J = 8.8 Hz, Ar), 6.37 (brs, 2H, NH2), 3.72 (s, 3H, CH3). 13C NMR (DMSO-d6): δ 157.7, 154.5, 142.8, 130.4, 123.3, 117.9, 114.6, 112.8, 55.5. 4-(Dimethylamino)phenyl 4-Aminobenzenesulfonate (78). Yield, 98%; white solid; mp, 192−194 °C. IR ν: 1593 (NH2) cm−1. 1H NMR (acetone-d6): δ 7.46−7.43 (m, 2H, Ar), 6.82−6.73 (m, 4H, Ar), 6.63−6.60 (m, 2H, Ar), 5.76 (brs, 2H, NH2), 2.90 (s, 6H, 2 × CH3). 13C NMR (acetone-d6): δ 154.8, 150.1, 141.3, 131.3, 123.6, 121.7, 113.8, 113.1, 40.5. 4-(tert-Butyldimethylsilyloxy)phenyl 4-Aminobenzenesulfo- nate (79). The crude product was puriﬁed by ﬂash chromatography (silica gel, hexanes/ethyl acetate (90:10) to hexanes/ethyl acetate (70:30)). Yield, 66%; orange solid; mp, 91−93 °C. IR ν: 1644 (NH2) cm−1. 1H NMR (CDCl3): δ 7.50 (d, 2H, J = 8.7 Hz, Ar), 6.84−6.81 (m, 2H, Ar), 6.71−6.68 (m, 2H, Ar), 6.60 (d, 2H, J = 8.7 Hz, Ar), 4.33 (brs, 2H, NH2), 0.95 (s, 9H, 3 × CH3), 0.19 (s, 6H, 2 × CH3). 13C NMR (CDCl3): δ 154.3, 152.0, 143.8, 130.8, 123.5, 122.4, 120.6, 113.7, 25.6, 18.2, −4.5. Article 2-Tolyl 3-Aminobenzenesulfonate (80). Yield, 56%; yellow solid; mp, 86 °C. IR ν: 3463 (NH2), 3364 (NH2) cm−1. 1H NMR (CDCl3): δ 7.27−6.89 (m, 8H, Ar), 4.52 (brs, 2H, NH2), 2.11 (s, 3H, CH3). 13C NMR (CDCl3): δ 148.4, 145.9, 137.0, 131.7, 131.6, 130.2, 127.0, 126.9, 122.3, 121.0, 118.8, 114.5, 16.3. 2-Ethylphenyl 3-Aminobenzenesulfonate (81). Yield, 46%; orange solid; mp, 52 °C. IR ν: 3478 (NH2), 3385 (NH2) cm−1. 1H NMR (CDCl3): δ 7.31−6.88 (m, 8H, Ar), 4.73 (brs, 2H, NH2), 2.53 (q, 2H, J = 7.5 Hz, CH2), 1.11 (t, 3H, J = 7.5 Hz, CH3). 13C NMR (CDCl3): δ 147.9, 145.2, 137.3, 137.1, 130.2, 129.9, 127.2, 126.9, 122.1, 121.4, 119.2, 114.9, 22.8, 14.0. 2-Propylphenyl 3-Aminobenzenesulfonate (82). Yield, 8.7%; orange oil. IR ν: 3489 (NH2), 3397 (NH2) cm−1. 1H NMR (CDCl3): δ 7.26−7.00 (m, 8H, Ar), 4.87 (brs, 2H, NH2), 2.45 (t, 2H, J = 7.8 Hz, CH2), 1.56−1.46 (m, 2H, CH2), 0.87 (t, 3H, J = 7.3 Hz, CH3). 13C NMR (CDCl3): δ 148.1, 144.8, 137.3, 135.8, 130.6, 130.3, 127.0, 126.9, 122.1, 121.6, 119.5, 115.2, 31.8, 23.0, 13.9. 4-(tert-Butyldimethylsilyloxy)phenyl 3-Aminobenzenesulfo- nate (83). Yield, 73%; yellow solid; mp, 101 °C. IR ν: 3495 (NH2), 3391 (NH2) cm−1. 1H NMR (CDCl3): δ 8.29 (s, 1H, Ar), 7.98−7.96 (m, 1H, Ar), 7.62−7.60 (m, 1H, Ar), 7.54−7.46 (m, 1H, Ar), 6.87− 6.80 (m, 2H, Ar), 6.74−6.68 (m, 2H, Ar), 4.42 (brs, 2H, NH2), 0.95 (s, 9H, 3 × CH3), 0.16 (s, 6H, 2 × CH3). 13C NMR (CDCl3): δ 154.5, 146.1, 143.6, 136.1, 130.0, 123.3, 120.8, 120.7, 118.9, 114.6, 25.6, 18.2, −4.5. 2-Ethylphenyl 4-Aminobenzenesulfonate (84). Yield, 95%; orange solid; mp, 71 °C. IR ν: 3467 (NH2), 3375 (NH2) cm−1. 1H NMR (CDCl3): δ 7.48−7.45 (m, 2H, Ar), 7.30−7.20 (m, 3H, Ar), 7.01−6.98 (m, 1H, Ar), 6.68−6.65 (m, 2H, Ar), 6.41 (brs, 2H, NH2), 2.46 (q, 2H, J = 7.5 Hz, CH2), 1.05 (t, 3H, J = 7.5 Hz, CH3). 13C NMR (CDCl3): δ 154.7, 147.6, 136.8, 130.3, 129.8, 127.0, 121.9, 118.7, 112.8, 22.2, 14.1. 2-Propylphenyl 4-Aminobenzenesulfonate (85). Yield, 93%; white solid; mp, 93−94 °C. IR ν: 3473 (NH2), 3378 (NH2) cm−1. 1H NMR (CDCl3): δ 7.59 (d, 2H, J = 8.4 Hz, Ar), 7.18−7.03 (m, 4H, Ar), 6.66 (d, 2H, J = 8.4 Hz, Ar), 4.51 (brs, 2H, NH2), 2.44 (t, 2H, J = 7.8 Hz, CH2), 1.55−1.48 (m, 2H, CH2), 0.87 (t, 3H, J = 7.3 Hz, CH3). 13C NMR (CDCl3): δ 151.7, 148.2, 135.9, 130.6, 130.5, 126.8, 123.7, 122.3, 122.3, 114.1, 31.8, 23.0, 14.0. 3-Amino-N-2-tolylbenzenesulfonamide (86). Yield, 41%; brown solid; mp, 102−103 °C. IR ν: 3404 (NH2), 3341 (NH2) cm−1. 1H NMR (DMSO-d6): δ 9.40 (s, 1H, NH), 7.26−6.76 (m, 8H, Ar), 5.64 (brs, 2H, NH2), 2.04 (s, 3H, CH3). 13C NMR (DMSO-d6): δ 148.8, 141.3, 135.2, 134.1, 130.6, 129.5, 126.3, 126.2, 126.2, 117.6, 113.7, 111.4, 17.7. 3-Amino-N-(2-ethylphenyl)benzenesulfonamide (87). Yield, 52%; yellow solid; mp, 145−147 °C. IR ν: 3453 (NH2), 3371 (NH2) cm−1. 1H NMR (CDCl3/DMSO-d6): δ 8.06 (s, 1H, NH), 7.40−6.83 ((tm, ,38HH,,JA=r),75.4.27H(zb,rCs,H2H3),. N13HC2)N2M.3R1 ((qC, D2HC,l3J/D= M7.4SOH-zd,6)C:Hδ2)1,417.0.81, 146.0, 139.2, 132.4, 131.5, 130.0, 129.3, 128.7, 125.8, 119.8, 116.0, 113.6, 22.7, 13.7. 3-Amino-N-(2-propylphenyl)benzenesulfonamide (88). Yield, 91%; yellow solid; mp, 144−145 °C. IR ν: 3400 (NH2), 3254 (NH2) cm−1. 1H NMR (CDCl3): δ 8.37 (s, 1H, NH), 7.27−6.72 (m, 8H, Ar), 4.81 (brs, 2H, NH2), 2.24−2.19 (m, 2H, CH2), 1.22−1.10 (m, 2H, CH2), 0.61−0.56 (m, 3H, CH3). 13C NMR (CDCl3): δ 147.2, 145.3, 140.0, 132.8, 132.0, 130.3, 129.7, 129.5, 126.1, 120.0, 118.3, 114.4, 32.6, 22.9, 14.4. 4-Amino-N-2-tolylbenzenesulfonamide (89). Yield, 89%; orange solid; mp, 148−149 °C. IR ν: 3478 (NH2), 3380 (NH2) cm−1. 1H NMR (DMSO-d6): δ 9.04 (s, 1H, NH), 7.28 (d, 2H, J = 8.6 Hz, Ar), 7.13−7.00 (m, 4H, Ar), 6.55 (d, 2H, J = 8.6 Hz, Ar), 5.95 (brs, 2H, NH2), 2.03 (s, 3H, CH3). 13C NMR (DMSO-d6): δ 152.7, 135.6, 133.7, 130.6, 128.6, 126.2, 126.1, 125.9, 125.6, 112.6, 17.7. 4-Amino-N-(2-ethylphenyl)benzenesulfonamide (90). Yield, 57%; orange solid; mp, 171 °C. IR ν: 3479 (NH2), 3380 (NH2) cm−1. 1H NMR (DMSO-d6): δ 9.04 (s, 1H, NH), 7.31 (d, 2H, J = 8.5 Hz, Ar), 7.19−6.93 (m, 4H, Ar), 6.57 (d, 2H, J = 8.5 Hz, Ar), 5.95 (brs, 2H, NH2), 2,54 (q, 2H, J = 7.5 Hz, CH2), 1.01 (t, 3H, J = 7.5 Hz, 6206 dx.doi.org/10.1021/jm3006492 | J. Med. Chem. 2012, 55, 6194−6208