Bromination of Aromatic Compounds using Bromine in a Microreactor

Abstract

2,4,5‐Trifluorobromobenzene is a valuable intermediate with important application in the synthesis of biologically active peptides and fluorescent reagents. A continuous‐flow system has been successfully developed for the synthesis of 2,4,5‐trifluorobromobenzene in a microreactor using FeBr3 as a catalyst, which is steadily generated in situ from the reaction of Br2 and Fe. The procedure is efficient and easy‐to‐handle, and 2,4,5‐trifluorobromobenzene can be obtained within minutes in high yields.

The synthesis of bupropion hydrochloride under greener and safer conditions utilizing flow technologies

“…Although the use of molecular bromine utilising flow technology has been well documented, [22][23][24] the employment of polymer bound pyridinium tribromide caught our interest as its use would largely mitigate the toxicity and corrosion risks associated with molecular bromine, thereby improving the safety profile of the process. Critically speaking though, its use would require the employment of packed-bed reactor (PBR) technologies which present engineering challenges, particularly as the reagent is consumed stoichiometrically, and polymer bound reagents also generally have significantly higher costs than analogous non-supported reagents.…”

“…A variety of bromination reactions utilizing flow conditions have been reported, often making use of molecular bromine. [20][21][22][23][24] Several greener, more sustainable alternatives including photochemical brominations with N-bromosuccinimide, in situ generated metal bromide (FeBr 3 ) and ionic salt bromination sources such as KOBr and NaBr have been reported with enhanced safety while affording comparable yields. [21][22][23][24][25][26][27][28][29][30] Critically speaking, if reagent lifecycles are considered, the use of molecular bromine, despite its associated hazards, has a cost and sustainability advantage over most "greener" alternatives as they inevitably have their genesis with molecular bromine itself.…”

Bringing Green Organic Electrochemistry to Undergraduates: A Designed Comparison Organic Experiment of Bromination

“…The structure of the product can be confirmed by gas chromatography (Figure 2), liquid chromatography (Figure 3), and nuclear magnetic resonance. 1 H NMR (400 MHz, CDCl 3 ) δ 7.25 (s, 4H), 5.82 (s,2H), 1.58 (s, 6H). 13…”

“…As one of the most important substitution reactions, bromination plays a vital part in modern organic synthesis, especially the bromination of aromatic compounds, whose products can be used as not only the precursors of organometallic reagents but also intermediates of drug molecules, material molecules, or other active natural products. − Thus, significant advances in achieving sustainable bromination have been reflected in related literature nowadays. − However, what undergraduates learn about bromination in experimental courses nowadays is basically composed of the most basic and traditional synthesis schemes, such as the synthesis of n -butyl bromide and 1-bromo-2-(dibromomethyl) naphthalene (Scheme a, eqs 1 and 2), and they barely have sources to learn about new and green approaches of bromination, which limits the possibilities of exposure to modern synthesis. Therefore, it is critical to design a complete experimental plan for trainees to master disparate routes to a common product as well as evaluate sustainability and superiority of both traditional and new methods.…”

Application of Flow Chemistry in Halogenation

“…溶液作为料液 1 通过玻璃注射器注入 T 型混合器, 将 Br 2 的 DCE 溶液作为料液 2 通过玻璃注射器注入, 与铁 原位生成形成三溴化铁, 进入 T 型混合器, 混合后进入 管式反应器, 最后用 Na 2 S 2 O 3 水溶液对反应混合物进行 淬灭. 该方法成功、稳定地合成了 2,4,5-三氟溴苯, 操作 简便, 效率高, 且反应只需几分钟, 具有很好的工业化 前景[40] .…”