Multikilogram per Hour Continuous Photochemical Benzylic Brominations Applying a Smart Dimensioning Scale-up Strategy

被引：59

作者：

Steiner, Alexander ^{[1
,2
]}

Roth, Philippe M. C. ^{[3
]}

Strauss, Franz J. ^{[4
,5
]}

Gauron, Guillaume ^{[3
]}

Tekautz, Gunter ^{[4
,5
]}

Winter, Marc ^{[3
]}

Williams, Jason D. ^{[1
,2
]}

Kappe, C. Oliver ^{[1
,2
]}

机构：

[1] Res Ctr Pharmaceut Engn GmbH RCPE, Ctr Continuous Flow Synth & Proc CC FLOW, A-8010 Graz, Austria

[2] Karl Franzens Univ Graz, Inst Chem, A-8010 Graz, Austria

[3] Corning SAS, Corning Reactor Technol, F-77215 Avon, France

[4] Microinnova Engn GmbH, A-8412 Allerheiligen, Austria

[5] Microinnova Engn GmbH, A-8412 Wildon, Austria

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2020年 / 24卷 / 10期

关键词：

flow photochemistry; scale-up; bromine generator; photochemical halogenation; radical chemistry; PHOTOREDOX CATALYSIS; ORGANIC-COMPOUNDS; FLOW; LIGHT; EFFICIENT; REACTOR; FUTURE; SAFETY; UV;

D O I：

10.1021/acs.oprd.0c00239

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

Although continuous flow technology can facilitate the scale-up of photochemical processes it is not yet routinely implemented on production scale in the fine chemical industries. This can be attributed to additional challenges compared to thermal processes, mostly in the homogeneous irradiation of the flow reactor. Here, we detail the process of bringing a previously developed photochemical benzylic bromination, utilizing in situ bromine generation, from lab to pilot scale. The process setup is discussed in detail, alongside a comprehensive risk assessment and discussion of problems encountered in the investigation of key reaction parameters. Ultimately, an assay yield of 88% was obtained in 22 s irradiated residence time, resulting in a productivity of 4.1 kg h(-1) (space-time yield = 82 kg L-1 h(-1)) representing a 14-fold scale-up versus the lab-scale process.

引用

页码：2208 / 2216

页数：9

共 58 条

[1] Scalability of Visible-Light-Induced Nickel Negishi Reactions: A Combination of Flow Photochemistry, Use of Solid Reagents, and In-Line NMR Monitoring [J].