A para‐C–H Functionalization of Aniline Derivatives via In situ Generated Bulky Hypervalent Iodinium Reagents

Abstract

A practical para‐C‐H functionalization of aniline derivatives has been developed using an in situ generated bulky hypervalent iodinium reagent. Para‐iodo, bromo, chloro, nitro, trifluormethyl aniline derivatives can be obtained efficiently, in many cases in 10 min in a transition metal‐free manner. Medicinal chemicals or intermediates can be purified without column chromatography or recrystallization, which significantly reduces the waste and simplifies the work‐up process.

Copper‐Catalyzed Regioselective Halogenation of Anilides with N‐Fluorobenzenesulfonimide

“…N ‐(4‐bromophenyl)acetamide 3 a : [25] white solid (38.5 mg, 90 %); R f =0.2 (petroleum ether/ethyl acetate=5 : 1); 1 H NMR (400 MHz, CDCl 3 ) δ 7.46–7.37 (m, 4H), 7.21 (br, 1H), 2.18 (s, 3H); 13 C{ 1 H} NMR (101 MHz, DMSO‐ d 6 ) δ 168.4, 138.6, 131.4, 120.8, 114.5, 24.0; MS (C 8 H 8 BrNO): 214 [M+1] + .…”

“…5,152.0 (d,J = 248.5 Hz),127.7 (d,J = 3.1 Hz),125.6 (d,J = 10.4 Hz),122.8,118.4 (d,J = 23.2 Hz),115.7 (d,J = 9.1 Hz),24.7; MS (C 8 H 7 BrFNO): 232 [M + 1] + . [25] white solid (29.8 mg, 61 %); R f = 0.2 (petroleum ether/ethyl acetate = 5 : 1); 1 H NMR (400 MHz, CDCl 3 ) δ 7.53 (d, J = 2.2 Hz, 1H), 7.43 (d,J = 8.5 Hz,1H),7.27 (br,1H),6.74 (dd,J = 8.5,2.3 Hz,1H),3.89 (s,3H), 2.18 (s, 3H); 13 C{ 1 H} NMR (101 MHz, CDCl 3 ) δ 169. 0, 156.1, 138.6, 133.0, 112.8, 106.0, 104.3, 56.2, 24.6; MS (C 9 H 10 BrNO 2 ): 244 [M + 1] + .…”

“…16 (d,J = 8.8 Hz,1H),6H),1H),7.16 (br,1H), 5.22 (s, 2H); 13 C{ 1 H} NMR (101 MHz, CDCl 3 ) δ 152.9, 135.6, 133.5, 128.8, 128.7, 128.2, 127.9, 122.5, 120.6, 67.6; MS (C 14 H 9 Cl 2 NO): 278 [M + 1] + . [25] white solid (38.5 mg, 90 %); R f = 0.2 (petroleum ether/ethyl acetate = 5 : 1); 1 H NMR (400 MHz, CDCl 3 ) δ 7.46-7.37 (m, 4H), 7.21 (br, 1H), 2.18 (s, 3H); 13 C{ 1 H} NMR (101 MHz, DMSO-d 6 ) δ 168. 4, 138.6, 131.4, 120.8, 114.5, 24.0 [26] white solid (33.9 mg, 70 %); R f = 0.3 (petroleum ether/ethyl acetate = 5 : 1); 1 H NMR (400 MHz, CDCl 3 ) δ 7.45-7.39 (m, 4H), 7.30 (br, 1H), 2.33 (t, J = 7.5 Hz, 2H), 1.81-1.70 (m, 2H), 1.00 (t, J = 7.4 Hz, 3H); 13 C{ 1 H} NMR (101 MHz, CDCl 3 ) δ 171.…”

“…3 g: [25] white solid (43.3 mg, 95 %); R f = 0.2 (petroleum ether/ethyl acetate = 5 : 1); 1 H NMR (400 MHz, CDCl 3 ) δ 7.71 (d, J = 9.3 Hz, 1H), 7.33 (d, J = 7.0 Hz, 2H), 6.91 (br, 1H), 2.24 (s, 3H), 2.21 (s, 3H); 13 C{ 1 H} NMR (101 MHz, CDCl 3 ) δ 168. 8, 134.7, 133.2, 132.0, 129.6, 125.3, 118.3, 24.1, 17.6; MS (C 9 H 10 BrNO): 228 [M + 1] + .…”

C–H Functionalization of Aromatic Amides

“…In 2018, Li's team reported a general method for para‐ halogenation/trifluoromethylation/nitrification through para‐ C–H functionalization of aromatic amines (Scheme ) . PhI(TFA) 2 was used as oxidant, EtOH as solvent, and no transition metal catalyst was necessary.…”