Article

Kinetic analysis and subambient temperature on-line on-column derivatization of an active aldehyde

Merck Research Laboratories, RY818-C220, PO Box 2000, Rahway, NJ 07065-0914, USA.
Journal of Chromatography A (Impact Factor: 4.26). 06/2003; 995(1-2):67-78. DOI: 10.1016/S0021-9673(03)00532-6
Source: PubMed

ABSTRACT The chromatographic analysis of aldehydes under typical reversed-phase conditions may be a challenging task due to an equilibrium process leading to the formation of a gem diol species regardless of acidic or basic conditions. Initially, a reversed-phase HPLC gradient elution was developed to determine the amount of a n acetylenic aldehyde in a reaction mixture. Significant fronting was observed under acidic and basic conditions even at -5 degrees C. In order to circumvent this problem, a reversed-phase HPLC gradient method on a C18 column at subambient temperature was developed using diethylamine as a mobile phase additive for on-line on-column derivatization of the aldehyde moiety. The on-line on-column reaction rate for the derivatization of the aldehyde with diethylamine was determined as a function of column temperature. An Arrhenius plot was constructed and the activation energy was calculated. The chromatographic behavior of the derivatized acetylenic aldehyde and products formed in-situ in the chromatographic system were studied at various temperatures ranging from -10 to 60 degrees C. It was found that the reaction products could be controlled by adjusting the column temperature. Different reaction pathways were identified as a function of temperature. The products and the reaction pathways were characterized by NMR, LC-MS and UV spectra.

Download full-text

Full-text

Available from: Michel Journet, Jun 21, 2015
0 Followers
 · 
115 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Boronic acid and boronic ester intermediates are the basis for Suzuki coupling and Petasis reactions that are widely used in pharmaceutical synthetic schemes. The analysis of these compounds utilizing traditional reversed phase liquid chromatography (RPLC) is complicated by the potential of on‐column hydrolysis. In order to effectively develop and optimize RPLC methods for accurate analysis of these compounds, a better understanding of the potential on‐column hydrolysis needs to be achieved. Kinetic studies of this type of on‐column hydrolysis were performed utilizing a stop flow kinetic approach. The rate of on‐column hydrolysis was determined as a function of initial organic composition, mobile phase pH, and column temperature. In addition, the Arrhenius activation energy was calculated. A fast reversed phase liquid chromatography method was then developed and optimized to minimize on‐column hydrolysis effects based on the garnered information. The method was applied to successfully resolve ten different boronic acid and boronic pinacol ester functionalized compounds within five minutes. Thus, the wide range applicability of fast RPLC technology for accurate analysis of this specific class of compounds was demonstrated.
    Journal of Liquid Chromatography &amp Related Technologies 11/2006; 29(19):2795-2806. DOI:10.1080/10826070600959013 · 0.64 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The determination of trace analytes in complex natural matrices often requires extensive sample extraction and preparation prior to chromatographic analysis. Correct sample preparation can reduce analysis time, sources of error, enhance sensitivity, and enable unequivocal identification, confirmation, and quantification. This overview considers general aspects on sample preparation techniques for trace analysis in various matrices. The discussed extraction/enrichment techniques cover classical methods, such as Soxhlet and liquid-liquid extractions along with more recently developed techniques like pressurized liquid extraction, liquid phase microextraction (LPME), accelerated microwave extraction, and ultrasound-assisted extraction. This overview also deals with more selective methodologies, such as solid phase extraction (SPE), solid phase microextraction (SPME), and stir bar sorptive extraction (SBSE). The adopted approach considers the equilibriums involved in each technique. The applicability of each technique in environmental, food, biological, and pharmaceutical analyses is discussed, particularly for the determination of trace organic compounds by chromatographic methods.
    Journal of Liquid Chromatography &amp Related Technologies 07/2010; 33:1174-1207. DOI:10.1080/10826076.2010.484371 · 0.64 Impact Factor
  • HPLC for Pharmaceutical Scientists, 05/2006: pages 347 - 454; , ISBN: 9780470087954