<p>Continuous flow synthesis provides an efficient, rapidly scalable, safer, and improved synthetic route over traditional batch synthesis owing to enhanced heat and mass transfer. High throughput experimentation (HTE) is a powerful tool to discover novel reaction conditions and optimize challenging transformations in significantly small amount of time and by exploring multiple arrays of reactions. The utilization of desorption electrospray ionization mass spectrometry (DESI-MS) couple to HTE enables the exploration of 384 unique reaction conditions in just ~7 minutes. Chapter 1 highlights the different organic transformations and the target-based synthesis that have been studied using the HTE in the literature. Validation of the HTE-DESI-MS was investigated by performing a large set of aldol reactions on triacetic acid lactone (TAL), a compound well studied for use as a bio-based platform molecule which can be transformed to a range of valuable agrochemicals, commodity chemicals and intermediates for pharmaceutical industry. Two different active pharmaceutical ingredients namely, HSN-608 and Lorazepam have been synthesized using continuous manufacturing. HTE-DESI MS tools were utilized for rapid reaction screening for Sonogashira couplings for the development of telescoped continuous flow synthesis of an alkynyl naphthyridine anti-cancer agent, HSN-608. It is a fms-like tyrosine kinase 3 (FLT-3) inhibitor, a drug-lead compound for potential treatment of acute myeloid leukemia. Furthermore, a 5-step continuous flow synthesis involving N-acylation, cyclization, N-oxidation, polonovski-type rearrangement, and hydrolysis has been developed for Lorazepam, an essential generic active pharmaceutical ingredient under shortage. Different synthetic routes scouting, and impurity profiling was done to propose the novel route that was further developed under continuous flow conditions with optimization of each step.</p>

Emission and fuel consumption are among the key parameters when designing a combustion system. Combustion CFD can assist in this task only if good enough accuracy is achieved regarding combustion and emission predictions. The aim of this master thesis is to evaluate the use of detailed reaction mechanisms (as a substitute for standard combustion model) in terms of computational time and result accuracy. Several mechanisms for n-heptane are tested. Lund University optical engine experimental case is used for this evaluation.Results showed that detailed chemistry can predict ignition accurately but differences are observed in the peak cylinder pressure. The computational time also increased significantly as size and complexity of the mechanism increased. Recommendations are given to improve predictions using detailed chemistry approach which is found to be an interesting approach especially for lift-off length predictions.

Here, we report on a new temperature responsive polymer brush system with a terminal “click” functionality. Bifunctionalized poly(N-isopropylacrylamide) (PNiPAAm) with distinct functional end groups was synthesized by atom transfer radical polymerization (ATRP) and grafted to a modified silicon substrate. The presence of the active terminal alkyne functionality is validated using an azide-modified rhodamine B (N3-RhB) via copper(I) catalyzed alkyne–azide cycloaddition (CuAAC). The optical properties and swelling dynamics of an N3-RhB modified PNiPAAm brush are analyzed in dry state and in situ by VIS-spectroscopic ellipsometry (SE). The best-fit results are obtained using a Gaussian oscillator model and are confirmed by UV/VIS-spectroscopy. We observed evidence of interactions between the aromatic residues of the dye and the PNiPAAm amide groups, which significantly affect the swelling behavior of the modified polymer brush. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Here, we report on a new temperature responsive polymer brush system with a terminal “click” functionality. Bifunctionalized poly(N-isopropylacrylamide) (PNiPAAm) with distinct functional end groups was synthesized by atom transfer radical polymerization (ATRP) and grafted to a modified silicon substrate. The presence of the active terminal alkyne functionality is validated using an azide-modified rhodamine B (N3-RhB) via copper(I) catalyzed alkyne–azide cycloaddition (CuAAC). The optical properties and swelling dynamics of an N3-RhB modified PNiPAAm brush are analyzed in dry state and in situ by VIS-spectroscopic ellipsometry (SE). The best-fit results are obtained using a Gaussian oscillator model and are confirmed by UV/VIS-spectroscopy. We observed evidence of interactions between the aromatic residues of the dye and the PNiPAAm amide groups, which significantly affect the swelling behavior of the modified polymer brush. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.