Regioselective Electrophilic Aromatic Bromination: Theoretical Analysis and Experimental Verification

Abstract

Electrophilic aromatic bromination is the most common synthetic method used to prepare aryl bromides, which are very useful intermediates in organic synthesis. To understand the experimental results in electrophilic aromatic brominations, ab initio calculations are used here for a tentative analysis of the positional selectivity. The calculated results agree well with the corresponding experimental data, and the reliability of the resulting positional selectivity was verified by the corresponding experimental data.

Design, Synthesis, and Investigation of the Pharmacokinetics and Anticancer Activities of Indenoisoquinoline Derivatives That Stabilize the G-Quadruplex in the MYC Promoter and Inhibit Topoisomerase I

“…As outlined in Scheme , treatment of furfural ( 5 ) with aq bromine under acidic conditions, followed by addition of sulfamic acid ( 6 ) to the reaction mixture, led to 5-bromopyridine-2,3-diol ( 7 ), which was converted to intermediate 8 in low (12%) yield with dibromomethane in the presence of potassium carbonate and cupric oxide. , The bromide of 8 was replaced by a methyl group using Suzuki–Miyaura cross coupling to afford the desired methylated substance 9 . Regioselective bromination of the methylpyridine 9 on the aromatic ring with NBS in AcOH/CH 3 CN at room temperature afforded the bromopyridine derivative 10 , − which was followed by nucleophilic aromatic substitution with CuCN in DMF at reflux to yield intermediate 11 . Free radical bromination of the methyl group of 11 with NBS in the presence of benzoyl peroxide in refluxing carbon tetrachloride produced the desired primary bromide 12 .…”

A metal-free, eco-friendly protocol for the oxidative halogenation of aromatic compounds by using highly efficient and reusable graphene oxide

“…Over the past few decades, a variety of powerful halogenating agents that are also operationally safe have been successfully developed to replace the use of halogens. [3][4][5][6][7][8][9][10][11] Many reagent systems have been reported in addition to Br 2 (with or without a catalyst), such as pyridinium tribromide, 12 KBr/sodium peroxyborate, 13 tetrabutylammonium tribromide, 14 cetyltrimethylammonium tribromide, 15 HBr/DMSO, 16 and LiBr/CAN (ceric ammonium nitrate), 17 among others. Most of these techniques use the electrophilic species Br + , which is produced in situ by the interaction of bromide ion with an oxidant.…”

Electrochemical Umpolung of Bromide: Transition-Metal-Free Bromination of Indole C–H Bond

“…Aromatic bromides are an important class of compounds, which are commonly utilized as the coupling partner in transition-metal-catalyzed cross-coupling reactions [ 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 ]. Thus, the development of a synthetic method of arylbromides has attracted tremendous efforts [ 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 ]. Among them, much progress has been made on palladium-catalyzed regioselective bromination of C–H bonds using different agents.…”