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- Quantitative NMR spectroscopy (2)
- Automated Data Evaluation (1)
- Carbamazepine (1)
- Chemometrics (1)
- Click Chemistry (1)
- Cocrystals (1)
- EURAMET.QM-K111 (1)
- Gas-phase NMR spectroscopy (1)
- Hydroformylation (1)
- Mechanochemistry (1)
Mechanochemistry is increasingly used as a ‘green alternative’ for synthesizing various materials including pharmaceutical cocrystals. Herein, we present the mechanochemical synthesis of three new cocrystals containing the API carbamazepine (cocrystals CBZ:Indometacin 1:1, CBZ:Benzamide 1:1, and CBZ:Nifedipine 1:1). The mechanochemical reaction was investigated in situ documenting a fast and complete reaction within one minute. Online NMR spectroscopy proved the direct influence of the dissolution behaviour of the coformers to the dissolution behaviour of the API carbamazepine. The dissolution behaviour of the organic cocrystals is compared to the behaviour of the pure drug indicating a general applicability of this approach for detailed cocrystal dissolution studies.
This key comparison aims to assess the core capabilities of the participants in gas analysis. Such competences include, among others, the capabilities to prepare Primary Standard gas Mixtures (PSMs), perform the necessary purity analysis on the materials used in the gas mixture preparation, the verification of the composition of newly prepared PSMs against existing ones, and the capability of calibrating the composition of a gas mixture. According to the Strategy for Key Comparisons of the Gas Analysis Working Group, this key comparison is classified as an RMO track A key comparison.
The artefacts were binary mixtures of propane in nitrogen at a nominal amount-of-substance fraction level of 1000 μmol/mol. The values and uncertainties from the gravimetric gas mixture preparation were used as key comparison reference values (KCRVs). Each transfer standard had its own KCRV. The results are generally good. All results are within ± 1 % of the KCRV.
Driven mostly by the search for chemical syntheses under biocompatible conditions, so called "click" chemistry rapidly became a growing field of research. The resulting simple one-pot reactions are so far only scarcely accompanied by an adequate optimization via comparably straightforward and robust analysis techniques possessing short set-up times. Here, we report on a fast and reliable calibration-free online NMR monitoring approach for technical mixtures. It combines a versatile fluidic system, continuous-flow measurement of 1H spectra with a time interval of 20 s per spectrum, and a robust, fully automated algorithm to interpret the obtained data. As a proof-of-concept, the thiol-ene coupling between N-boc cysteine methyl ester and allyl alcohol was conducted in a variety of non-deuterated solvents while its time-resolved behaviour was characterized with step tracer experiments. Overlapping signals in online spectra during thiol-ene coupling could be deconvoluted with a spectral model using indirect hard modeling and were subsequently converted to either molar ratios (using a calibrationfree approach) or absolute concentrations (using 1-point calibration). For various solvents the kinetic constant k for pseudo-first order reaction was estimated to be 3.9 h-1 at 25 °C. The obtained results were compared with direct integration of non-overlapping signals and showed good agreement with the implemented mass balance.
Reaction monitoring in disperse systems, such as emulsions, is of significant technical importance in various disciplines like biotechnological engineering, chemical industry, food science, and a growing number other technical fields. These systems pose several challenges when it comes to process analytics, such as heterogeneity of mixtures, changes in optical behavior, and low optical activity. Concerning this, online nuclear magnetic resonance (NMR) spectroscopy is a powerful technique for process monitoring in complex reaction mixtures due to its unique direct comparison abilities, while at the same time being non-invasive and independent of optical properties of the sample. In this study the applicability of online-spectroscopic methods on the homogeneously catalyzed hydroformylation system of 1-dodecene to tridecanal is investigated, which is operated in a mini-plant scale at Technische Universität Berlin. The design of a laboratory setup for process-like calibration experiments is presented, including a 500 MHz online NMR spectrometer, a benchtop NMR device with 43 MHz proton frequency as well as two Raman probes and a flow cell assembly for an ultraviolet and visible light (UV/VIS) spectrometer. Results of high-resolution online NMR spectroscopy are shown and technical as well as process-specific problems observed during the measurements are discussed.
A major industrial reaction based on homogeneous catalysis is hydroformylation for the production of aldehydes from alkenes and syngas. Hydroformylation in microemulsions, which is currently under investigation at Technische Universität Berlin on a mini-plant scale, was identified as a cost efficient approach which also enhances product selectivity. Herein, we present the application of online Raman spectroscopy on the reaction of 1-dodecene to 1-tridecanal within a microemulsion. To achieve a good representation of the operation range in the mini-plant with regard to concentrations of the reactants a design of experiments was used. Based on initial Raman spectra partial least squares regression (PLSR) models were calibrated for the prediction of 1-dodecene and 1-tridecanal. Limits of predictions arise from nonlinear correlations between Raman intensity and mass fractions of compounds in the microemulsion system. Furthermore, the prediction power of PLSR models becomes limited due to unexpected by-product formation. Application of the lab-scale derived calibration spectra and PLSR models on online spectra from a mini-plant operation yielded promising estimations of 1-tridecanal and acceptable predictions of 1-dodecene mass fractions suggesting Raman spectroscopy as a suitable technique for process analytics in microemulsions.
Quantitative NMR spectroscopy for gas analysis for production of primary reference gas mixtures
(2017)
Due to its direct correlation to the number of spins within a sample quantitative NMR spectroscopy (qNMR) is a promising method with absolute comparison abilities in complex systems in technical, as well as metrological applications. Most of the samples studied with qNMR are in liquid state in diluted solutions, while gas-phase applications represent a rarely applied case. Commercially available NMR equipment was used for purity assessment of liquid and liquefied hydrocarbons serving as raw materials for production of primary reference gas standards. Additionally, gas-phase studies were performed within an online NMR flow probe, as well as in a high-pressure NMR setup to check feasibility as verification method for the composition of gas mixtures.