Iodine-Catalyzed C–N Bond Formation: Synthesis of 3-Aminoquinoxalinones under Ambient Conditions

Abstract

A metal-free cross-dehydrogenative coupling between quinoxalinones (sp C-H) and amines (N-H) in the presence of catalytic iodine is reported. The reaction yields 3-aminoquinoxalinones in moderate to high yields under ambient conditions in dioxane as solvent and aqueous tert-butyl hydroperoxide (TBHP) as the terminal oxidant. The reaction is highly versatile and exhibits good functional group tolerance with a range of primary and secondary amines. It provides a practical access to pharmaceutically active 3-aminoquinoxalinone derivatives. Preliminary mechanistic studies reveal in situ iodination of the amine as the putative mode of activation.

Electrochemical Dehydrogenative Cross‐Coupling of Quinoxalin‐2(1H)‐ones with Amines for the Synthesis of 3‐Aminoquinoxalinones

“…In this regard, Gulevskaya et al reported the first direct oxidative CÀH amination of quinoxalin-2(1H)-ones without the prefunctionalized steps. More recently, Jain et al successfully developed an iodine-catalyzed synthesis of 3-aminoquinoxalinones (Scheme 1), [7] wherein, 2 equiv. Recently, Cui [5] and Phan [6] independently reported the copper-catalyzed CÀH amination of quinoxalin-2(1H)-ones for the synthesis of 3-aminoquinoxalinones (Scheme 1).…”

“…Despite the significant progress, only limited examples for the synthesis of 3-aminoquinoxalinones via direct CÀH amination under metal-free conditions have been reported. More recently, Jain et al successfully developed an iodine-catalyzed synthesis of 3-aminoquinoxalinones (Scheme 1), [7] wherein, 2 equiv. of TBHP as the oxidant was necessary for this transformation.…”

“…: 190-195 8C; 1 H NMR (400 MHz, CDCl 3 ) d 2.41 (s, 3H), 2.65 (t, J = 4.8 Hz, 4H), 4.09 (s, 4H), 7.11-7.13 (m, 1H), 7.22-7.25 (m, 2H), 7.53-7.56 (m, 1H), 10.70 (br, 1H); 13 C NMR (100 MHz, DMSO-d 6 ): d 45.7, 46.1, 54.7, 114.8, 123.6, 125.2, 125.6, 129.8, 132.7, 151.5, 152.5.3-(4-Acetylpiperazin-1-yl)quinoxalin-2(1H)-one (3 d)[7] Yellowish solid; 212 mg; Yield 78%; m.p. : 208-209 8C; 1 H NMR (400 MHz, CDCl 3 ) d 1.30 (d, J = 6.4 Hz, 6H), 2.71-2.77 (m, 2H), 3.82-3.86 (m, 2H), 4.90 (d, J = 12.8 Hz, 2H), 7.15-7.17 (m, 1H), 7.24-7.26 (m, 2H), 7.55-7.57 (m, 1H), 11.34-11.40 (m, 1H); 13 C NMR (100 MHz, DMSO-d 6 ) d 14.5, 47.3, 66.6, 110.1, 118.8, 120.4, 120.9, 125.0, 127.9, 146.5, 147.7.3-(4-Methylpiperazin-1-yl)quinoxalin-2(1H)-one (3 c) [20] White solid; 51 mg; Yield 21%; m.p.…”

Copper‐catalyzed C‐N coupling reaction of tosylhydrazones

“…While Pd (OAc) 2 was used as a catalyst for this reaction, no product 3a was obtained (entry 2). Next, given that the C‐N coupling reactions in the presence of I 2 had been reported, I 2 was used as catalyst, but the reaction gave no desired product 3a (entry 3). Therefore, various copper salts, such as CuBr, CuCl, CuI, Cu (OAc) 2 , and CuCl 2 , were used in the C‐N coupling reaction.…”

Simple and Green Procedures for the Synthesis of 3,5‐Bis(alkylthio)‐1,2,4‐thiadiazoles via Oxidative Dimerization of Dithiocarbamates

“…Molecular iodine has been applied as efficient, ecofriendly and readily available catalyst for many transformations in synthetic organic chemistry. [24] Due to the oxidative changes from the molecular iodine, this compound was extensively applied as catalyst for CÀ C, [25] CÀ O, [26] CÀ N, [27] CÀ S, [28] and N-S [29] bond formations. In addition, recently it was applied as catalyst for the preparation of 3,4-disubstituted-5-imino-1,2,4-thiadiazoles from N-arylbenzamidines and isothiocyanate, [30] aminosubstituted 1,2,4-thiadiazoles from substituted N-carbamothioylamidines or N-carbamothioylguanidines, [31] and 1,2,4-thiadiazoles from nitriles and thioamides.…”