ReactNMR and ReactIR as reaction monitoring and mechanistic elucidation tools: the NCS mediated cascade reaction of α-thioamides to α-thio-β-chloroacrylamides.
On-flow ReactIR and (1)H NMR reaction monitoring, coupled with in situ intermediate characterization, was used to aid in the mechanistic elucidation of the N-chlorosuccinimide mediated transformation of an α-thioamide. Multiple intermediates in this reaction cascade are identified and characterized, and in particular, spectroscopic evidence for the intermediacy of the chlorosulfonium ion in the chlorination of α-thioamides is provided. Further to this, solvent effects on the outcome of the transformation are discussed. This work also demonstrates the utility of using a combination of ReactIR and flow NMR reaction monitoring (ReactNMR) for characterizing complex multicomponent reaction mixtures.
Analytical Sciences Research and Development, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA.
David A
DA
Foley
Christopher W
CW
Doecke
Jonas Y
JY
Buser
Jeremy M
JM
Merritt
Linda
L
Murphy
Marie
M
Kissane
Stuart G
SG
Collins
Anita R
AR
Maguire
Andreas
A
Kaerner
D000178:Acrylamides / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D013055:Spectrophotometry, Infrared; D013388:Succinimides / Q000737:chemistry*; D013854:Thioamides / Q000737:chemistry*
D000178:Acrylamides; D013388:Succinimides; D013854:Thioamides; C015752:N-chlorosuccinimide