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Integration of Bromine and Cyanogen Bromide Generators for the Continuous‐Flow Synthesis of Cyclic Guanidines
Author(s) -
Glotz Gabriel,
Lebl René,
Dallinger Doris,
Kappe C. Oliver
Publication year - 2017
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201708533
Subject(s) - bromine , cyanogen bromide , bromide , chemistry , potassium bromide , dichloromethane , solvent , organic chemistry , biochemistry , peptide sequence , gene
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 0.8 m 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.