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Paper 2 Rapid Commun. Mass Spectrom., 2012, 26, 1070–1080
Probing the mechanism and dynamic reversibility of
trianglimine formation using real-time electrospray ionization
time-of-flight mass spectrometry
Hany F. Nour, Ana M. López-Periago and Nikolai Kuhnert*
Reproduced by permission of John Wiley and Sons
Copyright Clearance Center (CCC), License number, 2951290933234
Objectives of the work
The objective of this work is to study the mechanism of trianglimine formation in real-time using ESI˗
TOF/MS. Trianglimines were reported a decade ago and the mechanism of their formation was believed
to proceed through a stepwise pathway; however, no intermediates were ever isolated or detected and
characterized. The [3+3]˗cyclocondensation reaction was monitored in real-time by ESI˗TOF/MS. All
reaction intermediates participating in the cyclocondensation reaction were observed and their structures
were unambiguously assigned based on their high resolution m/z values. The dynamic reversibility of
trianglimines was investigated by conducting two crossover experiments. In the first experiment two
different trianglimines were mixed in DCM and stirred at room temperature. In the second experiment the
dialdehyde building blocks forming the macrocycles were mixed in DCM along with trans-(1R,2R)-1,2-
diaminocyclohexane and the reaction was stirred at room temperature. At equilibration and after 46 h,
statistical mixtures, with almost similar composition, of mixed macrocycles and open chain intermediates
were obtained from the two reaction pathways.
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