Fotokatalyyttinen 3-substituoitujen pyrrolidiinien N-arylointi ja vertailu perinteisiin menetelmiin

Photocatalytic reactions utilize energy harnessed from light for the activation of a catalyst. In photoredox catalysis, an excited photocatalyst can take part in redox reactions with a substrate. The most common photocatalysts could be divided into three classes: metal catalysts, organic dyes, and heterogeneous semiconductors. These catalysts are often employed with a transition metal dual catalyst. The dual catalyst enables the cross-coupling of substrates, and the photocatalyst oxidizes or reduces the dual catalyst. Photocatalytic reactions can offer a milder alternative for the traditional C-N coupling reactions. In the literature review section, the photocatalytic N-arylation of pyrrolidines was examined. The review found that pyrrolidines were successfully N-arylated with all of the catalyst types, and multiple variations on the substituents on the aryl halide. In the majority of the research, electron withdrawing groups (EWG) as substituents enhanced product yields, but electron donating groups (EDG) decreased yields. In an organic dye catalysed reaction, the effects of the substituents were opposite. In addition, the photocatalytic reactions were compared with traditional C-N coupling reactions, such as the Buchwald-Hartwig reaction, Ullmann-type reactions nucleophilic aromatic substitution and the Chan-Lam reaction. These reactions often had harsh reaction conditions. The photocatalytic N-arylation of 3-substituted pyrrolidines was examined in the experimental part of this thesis. The objectives of this study were to investigate the use of photoredox methodologies for the C-N coupling of 3-substituted pyrrolidines to arenes and examine the scope and limitations of the reaction and the effects of substituents. In addition, the aim was to optimize the reaction conditions for multiple parameters and for each product separately, apply the reaction on a flow chemistry appliance, and execute scale-up reactions on both photoreactors. The study found 3-substituted pyrrolidines to be successfully coupled with aryl halides with great variation in the substituents of both starting materials. With optimization, the reactions with lower product yields were able to be improved significantly. The reaction was successfully upscaled, but the adaptation on the flow reactor requires further optimization. Photocatalytic C-N coupling reactions offer a promising alternative for traditional reactions

Interlaboratory development and proposition for a new quality control sample for chemical forensics analysis of chemical warfare agents

A new quality control (QC) test sample for gas chromatography–mass spectrometry (GC–MS) was created and analysed to test the comparability and repeatability of chemical forensics results within the Organisation for the Prohibition of Chemical Weapons (OPCW)–designated laboratories. The QC test sample was designed in collaboration between four laboratories and consists of 27 compounds which evaluate the performance of GC–MS instruments. This solution was analysed with GC–MS(EI) in 11 laboratories, seven of which were OPCW designated. The participating laboratories analysed the sample multiple times on consecutive days, as well as after the analysis of a set of complex matrix samples. Retention times, retention indices, peak areas, peak tailing values, signal-to-noise ratios, and isotope ratios were extracted from the GC–MS data, and statistical multivariate analyses with principal component analysis and Hotelling's T2-tests were conducted. The results from these analyses indicate that differences between GC–MS analyses by multiple laboratories were not statistically significant at the 5% level, as the approximate p-value for the null hypothesis of “no differences between the runs” was 0.69. However, similar data processing methods and data normalisation are essential for enabling the reliable comparison of chemical fingerprints between laboratories. A composition for the QC sample and criteria for acceptable GC–MS performance for chemical forensics are proposed. The composition and criteria differ from the currently used chemical weapons verification analysis QC sample by e.g. broadening the range for retention index calculations by addition of new alkane compounds, including new chemicals with concentrations close to the limit of detection (10–100 ng/ml), and including compounds with higher polarity to emulate real-life forensic samples. The proposed criteria include monitoring of retention indices, isotope ratios, peak tailing, signal-to-noise ratios, peak height, mass spectra, and sensitivity of the instrument. The new compounds and criteria will be the subject of future confidence building exercises to validate their relevancy on a large scale