Integration of Bromine and Cyanogen Bromide Generators for the Continuous-Flow Synthesis of Cyclic Guanidines

被引:43
作者
Glotz, Gabriel [1 ,2 ]
Lebl, Rene [1 ,2 ]
Dallinger, Doris [2 ]
Kappe, C. Oliver [1 ,2 ]
机构
[1] Res Ctr Pharmaceut Engn GmbH RCPE, Ctr Continuous Flow Synth & Proc CC FLOW, Inffeldgasse 13, A-8010 Graz, Austria
[2] Karl Franzens Univ Graz, NAWI Graz, Inst Chem, Heinrichstr 28, A-8010 Graz, Austria
关键词
bromine; chemical generators; continuous flow; cyanogen bromide; guanidines; IN-SITU GENERATION; ANHYDROUS DIAZOMETHANE; SAFE GENERATION; CHLORINE; REACTOR; OPTIMIZATION; MICROREACTOR; CHEMISTRY; OLEFINS; AZIDE;
D O I
10.1002/anie.201708533
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
A continuous-flow process for the in situ on-demand generation of cyanogen bromide (BrCN) from bromine and potassium cyanide that makes use of membrane-separation technology is described. In order to circumvent the handling, storage, and transportation of elemental bromine, a continuous bromine generator using bromate-bromide synproportionation can optionally be attached upstream. Monitoring and quantification of BrCN generation was enabled through the implementation of in-line FTIR technology. With the Br-2 and BrCN generators connected in series, 0.2 mmol BrCN per minute was produced, which corresponds to a 0.8m solution of BrCN in dichloromethane. The modular Br-2/BrCN generator was employed for the synthesis of a diverse set of biologically relevant five-and six-membered cyclic amidines and guanidines. The set-up can either be operated in a fully integrated continuous format or, where reactive crystallization is beneficial, in semi-batch mode.
引用
收藏
页码:13786 / 13789
页数:4
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