Journal article
Monitoring Mechanistic Details in the Synthesis of Pyrimidines via Real-Time, Ultrafast Multidimensional NMR Spectroscopy
Journal of the American Chemical Society, Vol.134(5), pp.2706-2715
Feb/2012
Abstract
Recent years have witnessed unprecedented advances in the development of fast multidimensional NMR acquisition techniques. This progress could open valuable new opportunities for the elucidation of chemical and biochemical processes. This study demonstrates one such capability, with the first real-time Two-dimensional (2D) dynamic analysis of a complex organic reaction relying on unlabeled substrates. Implementing such measurements required the development of new ultrafast 2D methods, capable of monitoring multiple spectral regions of interest as the reaction progressed. The alternate application of these acquisitions in an interleaved, excitation-optimized fashion, allowed us to extract new structural and dynamic insight concerning the reaction between aliphatic ketones and triflic anhydride in the presence of nitriles to yield alkylpyrimidines. Up to 2500 2D NMR data sets were thus collected over the course of this nearly 100 min long reaction, in an approach resembling that used in functional magnetic resonance imaging. With the aid of these new frequency-selective low-gradient strength experiments, supplemented by chemical shift calculations of the spectral coordinates observed in the 2D heteronuclear correlations, previously postulated intermediates involved in the alkylpyrimidine formation process could be confirmed, and hitherto undetected ones were revealed. The potential and limitations of the resulting methods are discussed.
Details
- Title
- Monitoring Mechanistic Details in the Synthesis of Pyrimidines via Real-Time, Ultrafast Multidimensional NMR Spectroscopy
- Creators
- Zulay D. Pardo (null)Gregory L. Olsen (null)Fernandez-Valle, Maria Encarnacion Fernandez-Valle (null)Lucio Frydman (null) - 972WIS_INST___136Roberto Martinez-Alvarez (null)Antonio Herrera (null)
- Resource Type
- Journal article
- Publication Details
- Journal of the American Chemical Society, Vol.134(5), pp.2706-2715; Feb/2012
- Number of pages
- 10
- Language
- English
- DOI
- https://doi.org/10.1021/ja210154g
- Grant note
- MICINN [CTQ2010-14936]; Israel Science Foundation (ISF) [447/09]; ERC [246754]; EU'S BioNMR [261863]; Helen and Kimmel Award for Innovative Investigation; Feinberg Graduate School; Fulbright Foundation; Universidad Complutense de MadridThe authors acknowledge financial support from MICINN (grant CTQ2010-14936), the Israel Science Foundation (ISF 447/09), ERC Advanced grant no. 246754, EU'S BioNMR grant no. 261863, a Helen and Kimmel Award for Innovative Investigation, and the generosity of the Perlman Family Foundation. G.O. acknowledges postdoctoral support from the Feinberg Graduate School (Dean Fellowship) and from the Fulbright Foundation. Z.P. acknowledges Universidad Complutense de Madrid for a predoctoral fellowship. We gratefully acknowledge Dr. Israel Fernandez and Angel Sanchez (UCM) for theoretical calculations and predictions of 13C chemical shifts._ALMAME_DELIMITER_
- Record Identifier
- 993265234303596
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