Continuous Microflow Bromination of Alkenes Combined with a Circulatory Recycling of a Fluorous Polyether as a Bromine Support

Fukuyama, Takahide; Rahman, Md. Taifur; Kamata, Naoya; Tokizane, Masashi; Fukuda, Y.; Ryu, Ilhyong

doi:10.1556/jfc-d-12-00023

Cited by 10 publications

(6 citation statements)

References 26 publications

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“…Only very few examples of general bromination reactions performed in continuous flow exist in the literature. Electrophilic bromination of aromatic rings with NBS and brominations of alkenes or acetophenone using Br 2 in flow have been described. One very recent published example discusses the benzylic bromination of a 5-methylpyrimidine precursor to rosuvastatin in continuous flow.…”

Section: Introductionmentioning

confidence: 99%

A Scalable Procedure for Light-Induced Benzylic Brominations in Continuous Flow

Cantillo

Frutos²,

Rincón³

et al. 2013

J. Org. Chem.

103

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A continuous-flow protocol for the bromination of benzylic compounds with N-bromosuccinimide (NBS) is presented. The radical reactions were activated with a readily available household compact fluorescent lamp (CFL) using a simple flow reactor design based on transparent fluorinated ethylene polymer (FEP) tubing. All of the reactions were carried out using acetonitrile as the solvent, thus avoiding hazardous chlorinated solvents such as CCl4. For each substrate, only 1.05 equiv of NBS was necessary to fully transform the benzylic starting material into the corresponding bromide. The general character of the procedure was demonstrated by brominating a diverse set of 19 substrates containing different functional groups. Good to excellent isolated yields were obtained in all cases. The novel flow protocol can be readily scaled to multigram quantities by operating the reactor for longer time periods (throughput 30 mmol h(-1)), which is not easily possible in batch photochemical reactors. The bromination protocol can also be performed with equal efficiency in a larger flow reactor utilizing a more powerful lamp. For the bromination of phenylacetone as a model, a productivity of 180 mmol h(-1) for the desired bromide was achieved.

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Section: Introductionmentioning

confidence: 99%

A Scalable Procedure for Light-Induced Benzylic Brominations in Continuous Flow

Cantillo

Frutos²,

Rincón³

et al. 2013

J. Org. Chem.

103

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“…[117] Likewise,C l 2 gas and Br 2 have been employed for the direct chlorination and bromination of organic compounds using microreactors. [118,119] Ty pically,asolution of the substrate in asuitable solvent and elemental halogen are fed into the reactor as separate feeds using asuitable mixer. Asimilar experimental setup was used in ac ontinuous-flow procedure for the photobromination of benzylic compounds using NBS as the bromine source.…”

Section: Halogenation Reactionsmentioning

confidence: 99%

Continuous‐Flow Technology—A Tool for the Safe Manufacturing of Active Pharmaceutical Ingredients

Gutmann¹,

Cantillo²,

Kappe³

2015

Angew Chem Int Ed

1,274

676

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In the past few years, continuous-flow reactors with channel dimensions in the micro- or millimeter region have found widespread application in organic synthesis. The characteristic properties of these reactors are their exceptionally fast heat and mass transfer. In microstructured devices of this type, virtually instantaneous mixing can be achieved for all but the fastest reactions. Similarly, the accumulation of heat, formation of hot spots, and dangers of thermal runaways can be prevented. As a result of the small reactor volumes, the overall safety of the process is significantly improved, even when harsh reaction conditions are used. Thus, microreactor technology offers a unique way to perform ultrafast, exothermic reactions, and allows the execution of reactions which proceed via highly unstable or even explosive intermediates. This Review discusses recent literature examples of continuous-flow organic synthesis where hazardous reactions or extreme process windows have been employed, with a focus on applications of relevance to the preparation of pharmaceuticals.

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“…168 The use of bromine in a flow set-up for the a-bromination of acetophenone was reported by the group of Rutjes, 169 while Fukuyama et al investigated the bromination of alkenes. 170 Stevens and co-workers on the other hand developed a continuous flow system for the in situ generation of hypobromite (KOBr) from bromine for the subsequent bromination of methylsulfones and methanesulfonates. The corresponding tribromoderivatives were isolated in high yields with short reaction times.…”

Section: Halogenationmentioning

confidence: 99%

Taming hazardous chemistry by continuous flow technology

et al. 2016

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Over the last two decades, flow technologies have become increasingly popular in the field of organic chemistry, offering solutions for engineering and/or chemical problems. Flow reactors enhance the mass and heat transfer, resulting in rapid reaction mixing, and enable a precise control over the reaction parameters, increasing the overall process selectivity, efficiency and safety. These features allow chemists to tackle unexploited challenges in their work, with the ultimate objective making chemistry more accessible for laboratory and industrial applications, avoiding the need to store and handle toxic, reactive and explosive reagents. This review covers some of the latest and most relevant developments in the field of continuous flow chemistry with the focus on hazardous reactions.

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Continuous Microflow Bromination of Alkenes Combined with a Circulatory Recycling of a Fluorous Polyether as a Bromine Support

Cited by 10 publications

References 26 publications

A Scalable Procedure for Light-Induced Benzylic Brominations in Continuous Flow

A Scalable Procedure for Light-Induced Benzylic Brominations in Continuous Flow

Continuous‐Flow Technology—A Tool for the Safe Manufacturing of Active Pharmaceutical Ingredients

Taming hazardous chemistry by continuous flow technology

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