Two distinct overall research objectives are in this Masters thesis. Very little relates the two chapters apart from the ligands. The first chapter addresses diastereoselective homogeneous copper catalyzed cyclopropanation reactions. Cyclopropanation of styrene and ethyl diazoacetate (EDA) is a standard test reaction for homogeneous catalysts. Sterically bulky salicylaldimine (SAL) ligands should select for the ethyl trans-2-phenylcyclopropanecarboxylate diastereomer. Steric bulk poorly influences trans:cis ratios. Salicylaldiminine ligands do not posses the correct symmetry to affect diastereoselectivity. The SAL ligand belongs to the Cs point group in the solid state. Other ligand motifs are more effective at altering the trans:cis ratios. The second chapter addresses the general route toward successful copper(II) ethylene polymerization catalysts. Catalytic activity of the copper(II) complexes is very low. Polymer chain growth from a copper catalyst is very unlikely. Copper-carbon bonds decompose by homolytic cleavage or C-H activation. Copper-alkyls and aryls readily decompose into brown colored oils and salts with different colors. Ligand transfer to trimethylaluminum (TMA) appears to explain low yield ethylene polymerization.

Sizing (hydrophobization) is one of the most important process steps within the added-value chain of about 1/3rd of the worldwide produced paper & board products. Even though sizing with so-called reactive sizing agents, such as alkenyl succinic anhydride (ASA) was implemented in the paper industry decades ago, there is no total clarity yet about the detailed chemical and physical mechanisms that lead to their performance. Previous research was carried out on the role of different factors influencing the sizing performance, such as bonding between ASA and cellulose, ASA hydrolysis, size revision as well as the most important interactions with stock components, process parameters and additives during the paper making process. However, it was not yet possible to develop a holistic model for the explanation of the sizing performance given in real life application. This thesis describes a novel physico-chemical approach to this problem by including results from previous research and combining these with a wide field of own basic research and a newly developed method that allows tracing back the actual localization of ASA within the sheet structure. The carried out measurements and trial sets for the basic field of research served to evaluate the stock and process parameters that most dominantly influence the sizing performance of ASA. Interactions with additives other than retention aids were not taken into account. The results show that parameters, such as the content of secondary fibers, the degree of refining, the water hardness as well as the suspension conductivity, are of highest significance. The sample sets of the trials with the major impacting parameters were additionally analyzed by a newly developed localization method in order to better understand the main influencing factors. This method is based on optical localization of ASA within the sheet structure by confocal white light microscopy. In order to fulfill the requirements at magnification rates of factor 100 optical zoom, it was necessary to improve the contrast between ASA and cellulose. Therefore, ASA was pretreated with an inert red diazo dye, which does not have any impact on neither the sizing nor the handling properties of ASA. Laboratory hand sheets that were sized with dyed ASA, were analyzed by means of their sizing performance in correlation to measurable ASA agglomerations in the sheet structure. The sizing performance was measured by ultrasonic penetration analysis. The agglomeration behavior of ASA was analyzed automatically by multiple random imaging of a sample area of approx. 8650 µm² with a minimum resolution for particles of 500 nm in size. The gained results were interpreted by full factorial design of experiments (DOE). The trials were carried out with ASA dosages between 0% and 0.8% on laboratory hand sheets, made of 80% bleached eucalyptus short fiber kraft pulp and 20% northern bleached softwood kraft pulp, beaten to SR° 30, produced with a RDA sheet former at a base weight of 100 g/m² oven dry. The results show that there is a defined correlation between the ASA dosage, the sizing performance and the number and area of ASA agglomerates to be found in the sheet structure. It was also possible to show that the agglomeration behavior is highly influenced by external factors like furnish composition and process parameters. This enables a new approach to the explanation of sizing performance, by making it possible to not only examine the performance of the sizing agent, but to closely look at the predominant position where it is located in the sheet structure. These results lead to the explanation that the phenomenon of sizing is by far not a pure chemical process but rather a more physical one. Based on the gained findings it was possible so far to optimize the ASA sizing process in industrial-scale by means of ~ 50% less ASA consumption at a steady degree of sizing and improved physical sheet properties.

Sizing (hydrophobization) is one of the most important process steps within the added-value chain of about 1/3rd of the worldwide produced paper & board products. Even though sizing with so-called reactive sizing agents, such as alkenyl succinic anhydride (ASA) was implemented in the paper industry decades ago, there is no total clarity yet about the detailed chemical and physical mechanisms that lead to their performance. Previous research was carried out on the role of different factors influencing the sizing performance, such as bonding between ASA and cellulose, ASA hydrolysis, size revision as well as the most important interactions with stock components, process parameters and additives during the paper making process. However, it was not yet possible to develop a holistic model for the explanation of the sizing performance given in real life application. This thesis describes a novel physico-chemical approach to this problem by including results from previous research and combining these with a wide field of own basic research and a newly developed method that allows tracing back the actual localization of ASA within the sheet structure. The carried out measurements and trial sets for the basic field of research served to evaluate the stock and process parameters that most dominantly influence the sizing performance of ASA. Interactions with additives other than retention aids were not taken into account. The results show that parameters, such as the content of secondary fibers, the degree of refining, the water hardness as well as the suspension conductivity, are of highest significance. The sample sets of the trials with the major impacting parameters were additionally analyzed by a newly developed localization method in order to better understand the main influencing factors. This method is based on optical localization of ASA within the sheet structure by confocal white light microscopy. In order to fulfill the requirements at magnification rates of factor 100 optical zoom, it was necessary to improve the contrast between ASA and cellulose. Therefore, ASA was pretreated with an inert red diazo dye, which does not have any impact on neither the sizing nor the handling properties of ASA. Laboratory hand sheets that were sized with dyed ASA, were analyzed by means of their sizing performance in correlation to measurable ASA agglomerations in the sheet structure. The sizing performance was measured by ultrasonic penetration analysis. The agglomeration behavior of ASA was analyzed automatically by multiple random imaging of a sample area of approx. 8650 µm² with a minimum resolution for particles of 500 nm in size. The gained results were interpreted by full factorial design of experiments (DOE). The trials were carried out with ASA dosages between 0% and 0.8% on laboratory hand sheets, made of 80% bleached eucalyptus short fiber kraft pulp and 20% northern bleached softwood kraft pulp, beaten to SR° 30, produced with a RDA sheet former at a base weight of 100 g/m² oven dry. The results show that there is a defined correlation between the ASA dosage, the sizing performance and the number and area of ASA agglomerates to be found in the sheet structure. It was also possible to show that the agglomeration behavior is highly influenced by external factors like furnish composition and process parameters. This enables a new approach to the explanation of sizing performance, by making it possible to not only examine the performance of the sizing agent, but to closely look at the predominant position where it is located in the sheet structure. These results lead to the explanation that the phenomenon of sizing is by far not a pure chemical process but rather a more physical one. Based on the gained findings it was possible so far to optimize the ASA sizing process in industrial-scale by means of ~ 50% less ASA consumption at a steady degree of sizing and improved physical sheet properties.:Acknowledgment I Abstract III Table of Content V List of Illustrations XI List of Tables XVI List of Formulas XVII List of Abbreviations XVIII 1 Introduction and Problem Description 1 1.1 Initial Situation 1 1.2 Objective 2 2 Theoretical Approach 3 2.1 The Modern Paper & Board Industry on the Example of Germany 3 2.1.1 Raw Materials for the Production of Paper & Board 5 2.2 The Sizing of Paper & Board 8 2.2.1 Introduction to Paper & Board Sizing 8 2.2.2 The Definition of Paper & Board Sizing 10 2.2.3 The Global Markets for Sized Paper & Board Products and Sizing Agents 11 2.2.4 Physical and Chemical Background to the Mechanisms of Surface-Wetting and Penetration 13 2.2.4.1 Surface Wetting 14 2.2.4.2 Liquid Penetration 15 2.2.5 Surface and Internal Sizing 17 2.2.6 Sizing Agents 18 2.2.6.1 Alkenyl Succinic Anhydride (ASA) 19 2.2.6.2 Rosin Sizes 19 2.2.6.3 Alkylketen Dimer (AKD) 23 2.2.6.4 Polymeric Sizing Agents (PSA) 26 2.2.7 Determination of the Sizing Degree (Performance Analysis) 28 2.2.7.1 Cobb Water Absorption 29 2.2.7.2 Contact Angle Measurement 30 2.2.7.3 Penetration Dynamics Analysis 31 2.2.7.4 Further Qualitative Analysis Methods 33 2.2.7.4.1 Ink Stroke 33 2.2.7.4.2 Immersion Test 33 2.2.7.4.3 Floating Test 34 2.2.7.4.4 Hercules Sizing Tester (HST) 34 2.2.8 Sizing Agent Detection (Qualitative Analysis) and Determination of the Sizing Agent Content (Quantitative Analysis) 35 2.2.8.1 Destructive Methods 35 2.2.8.2 Non Destructive Methods 36 2.3 Alkenyl Succinic Anhydride (ASA) 36 2.3.1.1 Chemical Composition and Production of ASA 37 2.3.1.2 Mechanistic Reaction Models 39 2.3.1.3 ASA Application 42 2.3.1.3.1 Emulsification 42 2.3.1.3.2 Dosing 44 2.3.1.4 Mechanistic Steps of ASA Sizing 46 2.3.2 Physico-Chemical Aspects during ASA Sizing 48 2.3.2.1 Reaction Plausibility 48 2.3.2.1.1 Educt-Product Balance / Kinetics 48 2.3.2.1.2 Energetics 51 2.3.2.1.3 Sterics 52 2.3.2.2 Phenomena based on Sizing Agent Mobility 53 2.3.2.2.1 Sizing Agent Orientation 54 2.3.2.2.2 Intra-Molecular Orientation 55 2.3.2.2.3 Sizing Agent Agglomeration 55 2.3.2.2.4 Fugitive Sizing / Sizing Loss / Size Reversion 56 2.3.2.2.5 Sizing Agent Migration 58 2.3.2.2.6 Sizing Reactivation / Sizing Agent Reorientation 59 2.3.3 Causes for Interactions during ASA Sizing 60 2.3.3.1 Process Parameters 61 2.3.3.1.1 Temperature 61 2.3.3.1.2 pH-Value 62 2.3.3.1.3 Water Hardness 63 2.3.3.2 Fiber Types 64 2.3.3.3 Filler Types 65 2.3.3.4 Cationic Additives 66 2.3.3.5 Anionic Additives 67 2.3.3.6 Surface-Active Additives 68 2.4 Limitations of State-of-the-Art ASA-Sizing Analysis 69 2.5 Optical ASA Localization 71 2.5.1 General Background 71 2.5.2 Confocal Microscopy 72 2.5.2.1 Principle 72 2.5.2.2 Features, Advantage and Applicability for Paper-Component Analysis 74 2.5.3 Dying / Staining 75 3 Discussion of Results 77 3.1 Localization of ASA within the Sheet Structure 77 3.1.1 Choice of Dyes 77 3.1.1.1 Dye Type 78 3.1.1.2 Evaluation of Dye/ASA Mixtures 80 3.1.1.2.1 Maximum Soluble Dye Concentration 80 3.1.1.2.2 Thin Layer Chromatography 81 3.1.1.2.3 FTIR-Spectroscopy 82 3.1.1.3 Evaluation of the D-ASA Emulsion 84 3.1.1.4 Paper Chromatography with D-ASA & F-ASA Emulsions 85 3.1.1.5 Evaluation of the D-ASA Emulsion’s Sizing Efficiency 86 3.1.2 The Localization Method 87 3.1.2.1 The Correlation between ASA Distribution and Agglomeration 88 3.1.2.2 Measurement Settings 89 3.1.2.3 Manual Analysis 90 3.1.2.4 Automated Analysis 92 3.1.2.4.1 Automated Localization / Microscopy Measurement 92 3.1.2.4.2 Automated Analysis / Image-Processing 93 3.1.2.5 Result Interpretation and Example Results 96 3.1.2.6 Reproducibility 97 3.1.2.7 Sample Mapping 98 3.1.3 Approaches to Localization-Method Validation 102 3.1.3.1 Raman Spectroscopy 102 3.1.3.2 Confocal Laser Scanning Fluorescent Microscopy 102 3.1.3.3 Decolorization 103 3.2 Factors Impacting the Sizing Behavior of ASA 104 3.2.1 ASA Type 105 3.2.2 Emulsion Parameters 107 3.2.2.1 Hydrolyzed ASA Content 107 3.2.2.2 ASA/Starch Ratio 109 3.2.2.3 Emulsion Age 110 3.2.3 Stock Parameters 111 3.2.3.1 Long Fiber/Short Fiber Ratio 111 3.2.3.2 Furnish Type 112 3.2.3.3 Degree of Refining 114 3.2.3.4 Filler Type/Content 116 3.2.4 Process Parameters 119 3.2.4.1 Temperature 119 3.2.4.2 pH-Value 120 3.2.4.3 Conductivity 122 3.2.4.4 Water Hardness 123 3.2.4.5 Shear Rate 125 3.2.4.6 Dwell Time 127 3.2.4.7 Dosing Position & Dosing Order 128 3.2.4.8 Drying 130 3.2.4.9 Aging 131 3.3 Factors Impacting the Localization Behavior of ASA 132 3.3.1 Degree of Refining 132 3.3.2 Sheet Forming Conductivity 135 3.3.3 Water Hardness 136 3.3.4 Retention Aid (PAM) 137 3.3.5 Contact Curing 138 3.3.6 Accelerated Aging 139 3.4 Main Optimization Approach 141 3.4.1 Optimization of ASA Sizing Performance Characteristics 142 3.4.2 Emulsion Modification 144 3.4.2.1 Lab Trials / RDA Sheet Forming 146 3.4.2.2 TPM Trials 147 3.4.2.3 Industrial-Scale Trials 149 3.4.2.4 Correlation between Sizing Performance Optimization and Agglomeration Behavior on the Example of PAAE 152 3.5 Holistic Approach to Sizing Performance Explanation 154 4 Experimental Approach 157 4.1 Characterization of Methods, Measurements and Chemicals used for the Optical Localization-Analysis of ASA 157 4.1.1 Characterization of used Chemicals 157 4.1.1.1 Preparation of Dyed-ASA Solutions 157 4.1.1.2 Thin Layer Chromatography 157 4.1.1.3 Fourier Transformed Infrared Spectroscopy 157 4.1.1.4 Emulsification of ASA 158 4.1.1.5 Paper Chromatography 159 4.1.1.6 Particle Size Measurement 159 4.1.2 Optical Analysis of ASA Agglomerates 160 4.1.2.1 Microscopy 160 4.1.2.2 Automated Analysis 163 4.1.2.2.1 Adobe Photoshop 163 4.1.2.2.2 Adobe Illustrator 164 4.1.2.3 Confocal Laser Scanning Fluorescent Microscopy 166 4.2 Characterization of Used Standard Methods and Measurements 166 4.2.1 Stock and Paper Properties 166 4.2.1.1 Stock pH, Conductivity and Temperature Measurement 166 4.2.1.2 Dry Content / Consistency Measurement 167 4.2.1.3 Drainability (Schopper-Riegler) Measurement 167 4.2.1.4 Base Weight Measurement 168 4.2.1.5 Ultrasonic Penetration Measurement 168 4.2.1.6 Contact Angle Measurement 169 4.2.1.1 Cobb Measurement 169 4.2.1.2 Air Permeability Measurements 170 4.2.1.3 Tensile Strength Measurements 170 4.2.2 Preparation of Sample Sheets 171 4.2.2.1 Stock Preparation 171 4.2.2.2 Laboratory Refining (Valley Beater) 171 4.2.2.3 RDA Sheet Forming 171 4.2.2.4 Additive Dosing 173 4.2.2.5 Contact Curing 174 4.2.2.6 Hot Air Curing 174 4.2.2.7 Sample Aging 174 4.2.2.8 Preparation of Hydrolyzed ASA 175 4.2.2.9 Trial Paper Machine 175 4.2.2.10 Industrial-Scale Board Machine 177 4.3 Characterization of used Materials 178 4.3.1 Fibers 178 4.3.1.1 Reference Stock System 178 4.3.1.2 OCC Fibers 179 4.3.1.3 DIP Fibers 179 4.3.2 Fillers 180 4.3.3 Chemical Additives 180 4.3.3.1 ASA 180 4.3.3.2 Starches 181 4.3.3.3 Retention Aids 181 4.3.3.4 Poly Aluminum Compounds 181 4.3.3.5 Wet Strength Resin 181 4.3.4 Characterization of used Additives 182 4.3.4.1 Solids Content 182 4.4 Description of Implemented Advanced Data Analysis- and Visualization Methods 183 4.4.1 Design of Experiments (DOE183 4.4.2 Contour Plots 184 4.4.3 Box-Whisker Graphs 185 5 Conclusion 186 6 Outlook for Further Work 191 7 Bibliography 192 Appendix 207 7.1 Localization Method Reproducibility 207 7.2 DOE - Coefficient Lists 208 7.2.1 Trial 3.3.4 – Impact of Retention Aid (PAM) on Agglomeration Behavior and Sizing Performance 208 7.2.2 Trial 3.3.5 – Impact of Contact Curing on Agglomeration Behavior and Sizing Performance 208 7.2.3 Trial 3.3.6 – Impact of Accelerated Aging on Agglomeration Behavior and Sizing Performance 209

3,5-Dibromo-2-aminobenzamide was reacted with 1,3-cyclohexanedione derivatives in the presence of iodine as catalyst in toluene under reflux to afford novel 6,8-dibromo-2-[3-(2´-alkyl-1´,2´,3´,4´-tetrahydro-6´,8´-dibromo-4´-oxoquinazoline-2yl)propyl]quinazolin-4(3H)-ones in high yields. Suzuki-Miyaura cross-coupling of the latter with arylboronic acids in the presence of Pd(PPh3)2Cl2–Xphos catalyst complex and K2CO3 as a base in dioxane-water mixture (3:1, v/v) afforded the corresponding polyaryl-substituted bis-heterocycles in a single step operation. The resultant compounds were characterized using a combination of NMR (1H and 13C) and IR spectroscopic techniques, as well as mass spectrometry. The electronic absorption and emission properties of these polyaryl-substituted bis-heterocycles comprising 2,3-dihydroquinazolin-4(1H)-one and quinazolin-4(3H)-one moieties linked by a flexible carbon chain were measured in dimethylsulfoxide (DMSO) and acetic acid by means of UV-Vis and fluorescence spectroscopic techniques. The absorption spectra of the resultant polyaryl-substituted bis-heterocycles showed blue-shift in acetic acid and red-shift in DMSO, while their emission spectra are blue-shifted in DMSO and red-shifted in acetic acid. The 4-methoxy groups on aryl-substituents caused red shift on π‒π* transition of the aryl-substituents. Moreover, it was also observed that as the propyl linkage becomes more substituted, the absorption and emission intensities decrease. / Chemistry / M. Sc. (Chemistry)

Les cyclopropanes sont des unités qui sont très importantes en raison de leur présence dans de nombreux produits naturels, dans certaines molécules synthétiques ayant une activité biologique, ainsi que dans plusieurs intermédiaires synthétiques. Les travaux décrits dans cet ouvrage portent sur l’halogénocyclopropanation stéréosélective d’alcools allyliques en présence d’un ligand chiral stœchiométrique de type dioxaborolane et de carbénoïdes de zinc substitués dérivés de composés organozinciques et d’haloformes. Nous avons ainsi développé des conditions pour l’iodo-, la chloro- et la fluorocyclopropanation stéréosélective. Une étude mécanistique portant sur la nature des carbénoïdes alpha-chlorés et alpha-bromés a révélé qu’il y a un échange des halogènes portés par ces carbénoïdes. Lors de la chlorocyclopropanation, le carbénoïde le plus réactif (alpha-chloré) réagit de façon prédominante en vertu du principe de Curtin-Hammet. Les iodocyclopropanes énantioenrichis ont pu être fonctionnalisés via une réaction d’échange lithium-iode suivie du traitement avec des électrophiles, ou via une réaction de transmétallation au zinc suivie d’un couplage de Negishi. Ainsi, toute une gamme de cyclopropanes 1,2,3-substitués énantioenrichis a pu être synthétisée. Dans l’optique de développer de nouvelles méthodologies de fonctionnalisation des cyclopropanes, nous nous sommes par la suite tournés vers le couplage croisé de type Hiyama-Denmark des cyclopropylsilanols. Dans cette voie synthétique, le groupement silanol a deux fonctions : il sert de groupement proximal basique lors de la cyclopropanation de Simmons-Smith et il subit la transmétallation au cours du couplage croisé. Dans l’étape du couplage croisé, la nature des ligands liés à l’atome de silicium s’est avérée cruciale au bon déroulement de la réaction. Ainsi, l’échange de ligands avec le diéthyl éthérate de trifluoroborane générant le cyclopropyltrifluorosilane in situ est requis pour obtenir de bons rendements. Le dernier volet de cet ouvrage porte sur la cyclisation d’iodures d’alkyle par substitution aromatique par voie homolytique catalysée par le nickel. Une série de composés de type tétrahydronaphtalène et thiochromane ont été préparés selon cette méthode. Une étude mécanistique a confirmé la nature radicalaire de cette réaction et suggère fortement l’action catalytique du nickel. De plus, des études de spectrométrie RMN DOSY ont montré une association entre le complexe de nickel et le substrat ainsi que la base employés dans cette réaction. / Cyclopropanes are important subunits because of their presence in numerous bioactive natural products and synthetic molecules as well as synthetic intermediates. In this work we have investigated the stereoselective halocyclopropanation of allylic alcohols using a dioxaborolane-type stoichiometric chiral ligand and substituted zinc carbenoids derived from organozinc compounds and haloforms. We have thus developed conditions for the stereoselective iodo-, chloro- and fluorocyclopropanation reactions. A mechanistic study on the nature of alpha-chloro and alpha-bromomethylzinc carbenoids has revealed that halogen scrambling is taking place in the case of these carbenoids. During the chlorocyclopropanation reaction, the most reactive carbenoid (alpha-chloromethyl zinc) reacts predominantly, in line with the Curtin-Hammet principle. The enantioenriched iodocyclopropanes have been functionalized through a lithium-iodine exchange followed by treatment with electrophiles or transmetallation to zinc and Negishi cross-coupling. Therefore, a wide array of enantioenriched 1,2,3-substituted cyclopropanes have been synthesized using these methods. In order to develop new methodologies for the functionalization of cyclopropanes, we have studied the Hiyama-Denmark cross-coupling of cyclopropylsilanols. In this approach, the silanol group bears two functions: it serves as a proximal basic group in the Simmons-Smith cyclopropanation and it is involved in the transmetallation event during the cross-coupling reaction. In the cross-coupling step, the nature of the ligands bound to the silicon atom is crucial to the efficiency of the reaction. Hence, the in situ formation of the cyclopropyltrifluorosilane via a ligand exchange with boron trifluoride etherate is required for good yields. The final chapter of this work is on the nickel-catalyzed cyclization of alkyl iodides via a homolytic aromatic substitution mechanism. A series of tetrahydronaphthalene and thiochroman related compounds have been synthesized using this methodology. A mechanistic study has confirmed the radical nature of this reaction and strongly suggests the catalytic role of nickel. DOSY NMR spectrometric investigations have demonstrated an association between substrate, the base employed in this reaction and the nickel complex.

3,5-Dibromo-2-aminobenzamide was reacted with 1,3-cyclohexanedione derivatives in the presence of iodine as catalyst in toluene under reflux to afford novel 6,8-dibromo-2-[3-(2´-alkyl-1´,2´,3´,4´-tetrahydro-6´,8´-dibromo-4´-oxoquinazoline-2yl)propyl]quinazolin-4(3H)-ones in high yields. Suzuki-Miyaura cross-coupling of the latter with arylboronic acids in the presence of Pd(PPh3)2Cl2–Xphos catalyst complex and K2CO3 as a base in dioxane-water mixture (3:1, v/v) afforded the corresponding polyaryl-substituted bis-heterocycles in a single step operation. The resultant compounds were characterized using a combination of NMR (1H and 13C) and IR spectroscopic techniques, as well as mass spectrometry. The electronic absorption and emission properties of these polyaryl-substituted bis-heterocycles comprising 2,3-dihydroquinazolin-4(1H)-one and quinazolin-4(3H)-one moieties linked by a flexible carbon chain were measured in dimethylsulfoxide (DMSO) and acetic acid by means of UV-Vis and fluorescence spectroscopic techniques. The absorption spectra of the resultant polyaryl-substituted bis-heterocycles showed blue-shift in acetic acid and red-shift in DMSO, while their emission spectra are blue-shifted in DMSO and red-shifted in acetic acid. The 4-methoxy groups on aryl-substituents caused red shift on π‒π* transition of the aryl-substituents. Moreover, it was also observed that as the propyl linkage becomes more substituted, the absorption and emission intensities decrease. / Chemistry / M. Sc. (Chemistry)

<p>Air pollutants pose a high risk for humans, and the environment, and this pollution is one of the major environmental problems facing modern society. Active air sampling is the technique that has been traditionally used to monitor nonpolar aromatic air pollutants. However, active high volume samplers (HiVols) require a power supply, maintenance and specialist operators, and the equipment is often expensive. Thus, there is a need to develop new, less complicated sampling techniques that can increase the monitoring frequency, the geographical distribution of the measurements, and the number of sites used in air monitoring programs. In the work underlying this thesis, the use of semipermeable membrane devices (SPMDs) as tools for monitoring gas phase concentrations of nonpolar aromatic compound was evaluated using the compound classes polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs), alkylated PAHs (alkyl-PAHs) and nitrated PAHs (nitro-PAHs) as test compounds. </p><p>High wind-speeds increased the uptake and release in SPMDs of PAHs and PCBs with log K_OA values > 7.9, demonstrating that the uptake of most nonpolar aromatic compounds is controlled by the boundary layer at the membrane-air interface. The use of a metal umbrella to shelter the SPMDs decreased the uptake of PAHs and PCBs by 38 and 55 percent, respectively, at high wind/turbulence, and thus reduced the wind effect. Further, the use of performance reference compounds (PRCs) to assess the site effect of wind on the uptake in SPMDs reduced the between-site differences to less than 50 percent from as much as three times differences in uptake of PCBs and PAHs. However, analytical interferences reduced the precision of some PRCs, showing the importance of using robust analytical quality control.</p><p>SPMDs were shown to be efficient samplers of gas phase nonpolar aromatic compounds, and were able to determine local, continental and indoor spatial distributions of PAHs, alkyl- PAHs and nitro-PAHs. In addition, the use of the SPMDs, which do not require electricity, made sampling possible at remote/rural areas where the infrastructure was limited. SPMDs were also used to determine the source of PAH pollution, and different approaches were discussed. Finally, SPMDs were used to estimate the importance of the gas phase exposure route to the uptake of PAHs in plants. The results demonstrate that SPMDs have several advantages compared with HiVols, including integrative capacity over long times, reduced costs, and no need of special operators, maintenance or power supply for sampling. However, calibration data of SPMDs in air are limited, and spatial differences are often only semi-quantitatively determined by comparing amounts and profiles in the SPMDs, which have limited their use in air monitoring programs. In future work, it is therefore important that SPMDs are properly sheltered, PRCs are used in the sampling protocols, and that calibrated sampling rate data, or the SPMD-air partition data, of specific compounds are further developed to make determination of time weighted average (TWA) concentrations possible.</p>

Air pollutants pose a high risk for humans, and the environment, and this pollution is one of the major environmental problems facing modern society. Active air sampling is the technique that has been traditionally used to monitor nonpolar aromatic air pollutants. However, active high volume samplers (HiVols) require a power supply, maintenance and specialist operators, and the equipment is often expensive. Thus, there is a need to develop new, less complicated sampling techniques that can increase the monitoring frequency, the geographical distribution of the measurements, and the number of sites used in air monitoring programs. In the work underlying this thesis, the use of semipermeable membrane devices (SPMDs) as tools for monitoring gas phase concentrations of nonpolar aromatic compound was evaluated using the compound classes polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs), alkylated PAHs (alkyl-PAHs) and nitrated PAHs (nitro-PAHs) as test compounds. High wind-speeds increased the uptake and release in SPMDs of PAHs and PCBs with log KOA values &gt; 7.9, demonstrating that the uptake of most nonpolar aromatic compounds is controlled by the boundary layer at the membrane-air interface. The use of a metal umbrella to shelter the SPMDs decreased the uptake of PAHs and PCBs by 38 and 55 percent, respectively, at high wind/turbulence, and thus reduced the wind effect. Further, the use of performance reference compounds (PRCs) to assess the site effect of wind on the uptake in SPMDs reduced the between-site differences to less than 50 percent from as much as three times differences in uptake of PCBs and PAHs. However, analytical interferences reduced the precision of some PRCs, showing the importance of using robust analytical quality control. SPMDs were shown to be efficient samplers of gas phase nonpolar aromatic compounds, and were able to determine local, continental and indoor spatial distributions of PAHs, alkyl- PAHs and nitro-PAHs. In addition, the use of the SPMDs, which do not require electricity, made sampling possible at remote/rural areas where the infrastructure was limited. SPMDs were also used to determine the source of PAH pollution, and different approaches were discussed. Finally, SPMDs were used to estimate the importance of the gas phase exposure route to the uptake of PAHs in plants. The results demonstrate that SPMDs have several advantages compared with HiVols, including integrative capacity over long times, reduced costs, and no need of special operators, maintenance or power supply for sampling. However, calibration data of SPMDs in air are limited, and spatial differences are often only semi-quantitatively determined by comparing amounts and profiles in the SPMDs, which have limited their use in air monitoring programs. In future work, it is therefore important that SPMDs are properly sheltered, PRCs are used in the sampling protocols, and that calibrated sampling rate data, or the SPMD-air partition data, of specific compounds are further developed to make determination of time weighted average (TWA) concentrations possible.

The aim of the present study was the development of analytical methods which can be used for gaining a deeper insight into the mechanisms of hair treatment with cosmetic formulations like shampoos. The efficacy of such a formulation is affected by the amount of different active agents remaining on the hair after treatment. Due to the complex composition of most of the formulations various dependencies and interactions of the ingredients are possible. Beneath that a variety of parameters of the treatment process influence the substantivity. Finally the degree of hair damage present at the treatment process is significant. So the process of hair treatment with cosmetic formulations is very complex. The understanding of this process enables a systematic development of products with better or novel effectivity. The developed analytical methods provide the possibility of a parallel determination of different active agents and their interaction of the adsorption behaviour. Furthermore the determination of influencing variables like treatment conditions or hair damage can be performed. So it is possible to generate the knowledge necessary for excellent scientific product development. The general methodology for the method development consists of an extraction from hair followed by a selective and sensitive quantitation of the active agents located in the extract using LC/MS and LC/MS/MS. Analytical methods for the determination of the complex composed surface active agents Sodium Laureth Sulfate, Cocamidopropyl Betaine and Alkyl Polyglucoside were developed. During the evaluation process it could be figured out that significant swelling of the hair fibre does not occur during a hair wash lasting 2 min or less. Hence the active agents are mainly adsorbed at the hair surface. During method development it was found that the composition of these agents is changing during hair treatment resulting in a difference of the singles substance distribution on hair and in the shampoo. Additionally an analytical method for selective and sensitive quantitation of the cationic polysaccharides Polyquaternium-10 and Guar Hydroxypropyltrimonium Chloride using LC/MS was developed. The parallel quantitation of Polyquaternium-10 and Guar Hydroxypropyltrimonium Chloride enables to study their interaction of the adsorption behaviour. Beneath that the quantitation of substances with low active contentes, like Ubiquinone 50, Piroctone Olamine and Benzophenone?4, was carried out. The extraction behaviour of these substances showed that an extraction time of 7 min assisted by an ultrasonic treatment is optimal. Longer extraction leads to a significant increase of the active hair surface due to swelling. The result is a higher adsorption capacity of the hair fibre and thus a decreased analyte concentration in the extract. The reproducibility of the using treatment protocol was approved by parallel quantitation of several active agents. Due to variation of several treatment parameters their influence on substantivity was studied: the flow rate, temperature and hardness of the water for rinsing and the time for massaging in the formulation. Furthermore, it was shown that the degree of hair damage and further shampoo ingredients influence the substantivity of active agents. Finally it was demonstrated that the adsorption behaviour can be significantly influenced by the application strategy. / Das Ziel der vorliegenden Arbeit war es, mit der Entwicklung von analytischen Methoden eine Möglichkeit zu schaffen, um die Mechanismen bei der Haarbehandlung mit kosmetischen Formulierungen, wie Shampoos besser verstehen zu können. Die Pflegeleistung einer solchen Formulierung wird unter anderem davon bestimmt, wie viel der unterschiedlichen eingesetzten Wirkstoffe nach der Behandlung auf dem Haar verbleiben. Durch die Komplexität der kosmetischen Formulierungen kommt es zu vielfältigen Abhängigkeiten und Beeinflussungen der Substantivität der einzelnen Substanzen voneinander. Darüber hinaus gibt es eine Vielzahl von Parametern bei der Haarbehandlung, die die Substantivität beeinflussen. Schließlich spielt auch der Zustand des Haares eine entscheidende Rolle. Alles in allem handelt es sich bei der Behandlung des Haares mit kosmetischen Formulierungen um sehr komplexe Prozesse. Das Verständnis dieser Prozesse ermöglicht eine gezielte Entwicklung von Produkten mit besserem und zum Teil neuartigem Leistungsspektrum. Die entwickelten Analysenmethoden erlauben die parallele Bestimmung der auf dem Haar adsorbierten Menge verschiedener Wirkstoffe. Dadurch kann die gegenseitige Beeinflussung der Wirkstoffadsorption untersucht werden. Darüber hinaus ermöglicht das Methodenspektrum eine Bestimmung der Einflussgröße äußerer Parameter, wie der Waschbedingungen und innerer Parameter, wie der Haarschädigung. Damit ist es möglich, das notwendige Wissen für eine fortschrittliche, wissenschaftliche Produktentwicklung zu gewinnen. Der allgemeine Ansatz für die Entwicklung der Methoden beinhaltet eine Extraktion der Wirkstoffe vom Haar, gefolgt von einer selektiven und empfindlichen Quantifizierung im Extrakt mittels LC-MS und LC-MS/MS. Es wurden Analysenmethoden für die komplex zusammengesetzten oberflächenaktiven Wirkstoffe Sodium Laureth Sulfate, Cocamidopropyl Betaine und Alkyl Polyglucoside entwickelt. Dabei wurde durch Untersuchungen der Extraktion vom Haar bewiesen, dass die zweiminütige Haarwäsche nicht zu einem signifikanten Aufquellen des Haares führt, so dass die Wirkstoffe hauptsächlich an der Haaroberfläche adsorbiert werden. Außerdem wurde gezeigt, dass sich die Zusammensetzung dieser Wirkstoffe während der Haarwäsche ändert, so dass sich die Einzelsubstanzverteilung auf dem Haar von der im Shampoo unterscheidet. Des Weiteren wurde die selektive und empfindliche Quantifizierung der kationischen Polymere Polyquaternium-10 und Guar Hydroxypropyltrimonium Chloride durchgeführt. Die parallele Quantifizierung beider Konditionierungsstoffe ermöglicht die Untersuchung, in welchem Umfang sich beide Polymere in ihrem Adsorptionsverhalten beeinflussen. Bei der Methodenentwicklung für die Quantifizierung der Wirkstoffe Ubiquinone, Piroctone Olamine und Benzophenone-4 zeigte sich, dass eine Extraktion über 7 min im Ultraschallbad die besten Ergebnisse brachte. Bei längerer Extraktionszeit vergrößert sich die Oberfläche des Haares durch Quellung, so dass sich der Anteil an adsorbierten Analyten wieder erhöht. Die Reproduzierbarkeit der Haarwäsche mit dem verwendeten Waschprotokoll wurde bestätigt, indem verschiedene Wirkstoffe parallel auf dem Haar quantifiziert wurden. Durch Veränderung der Waschparameter Einmassierzeit sowie Durchflussmenge, Temperatur und Härte des Spülwassers wurde der Einfluss dieser Parameter auf die Substantivität der Wirkstoffe untersucht. Darüber wurde gezeigt, dass sowohl der Schädigungsgrad des Haares als auch andere auf dem Haar befindliche Shampoo-Bestandteile einen Einfluss auf die Substantivität von Wirkstoffen haben. Schließlich wurde an einem Beispiel gezeigt, dass man die Substantivität von Wirkstoffen nicht nur durch die Zusammensetzung der kosmetischen Formulierung, sondern auch durch die Art der Anwendung entscheidend beeinflussen kann.

Les cyclopropanes sont des unités qui sont très importantes en raison de leur présence dans de nombreux produits naturels, dans certaines molécules synthétiques ayant une activité biologique, ainsi que dans plusieurs intermédiaires synthétiques. Les travaux décrits dans cet ouvrage portent sur l’halogénocyclopropanation stéréosélective d’alcools allyliques en présence d’un ligand chiral stœchiométrique de type dioxaborolane et de carbénoïdes de zinc substitués dérivés de composés organozinciques et d’haloformes. Nous avons ainsi développé des conditions pour l’iodo-, la chloro- et la fluorocyclopropanation stéréosélective. Une étude mécanistique portant sur la nature des carbénoïdes alpha-chlorés et alpha-bromés a révélé qu’il y a un échange des halogènes portés par ces carbénoïdes. Lors de la chlorocyclopropanation, le carbénoïde le plus réactif (alpha-chloré) réagit de façon prédominante en vertu du principe de Curtin-Hammet. Les iodocyclopropanes énantioenrichis ont pu être fonctionnalisés via une réaction d’échange lithium-iode suivie du traitement avec des électrophiles, ou via une réaction de transmétallation au zinc suivie d’un couplage de Negishi. Ainsi, toute une gamme de cyclopropanes 1,2,3-substitués énantioenrichis a pu être synthétisée. Dans l’optique de développer de nouvelles méthodologies de fonctionnalisation des cyclopropanes, nous nous sommes par la suite tournés vers le couplage croisé de type Hiyama-Denmark des cyclopropylsilanols. Dans cette voie synthétique, le groupement silanol a deux fonctions : il sert de groupement proximal basique lors de la cyclopropanation de Simmons-Smith et il subit la transmétallation au cours du couplage croisé. Dans l’étape du couplage croisé, la nature des ligands liés à l’atome de silicium s’est avérée cruciale au bon déroulement de la réaction. Ainsi, l’échange de ligands avec le diéthyl éthérate de trifluoroborane générant le cyclopropyltrifluorosilane in situ est requis pour obtenir de bons rendements. Le dernier volet de cet ouvrage porte sur la cyclisation d’iodures d’alkyle par substitution aromatique par voie homolytique catalysée par le nickel. Une série de composés de type tétrahydronaphtalène et thiochromane ont été préparés selon cette méthode. Une étude mécanistique a confirmé la nature radicalaire de cette réaction et suggère fortement l’action catalytique du nickel. De plus, des études de spectrométrie RMN DOSY ont montré une association entre le complexe de nickel et le substrat ainsi que la base employés dans cette réaction. / Cyclopropanes are important subunits because of their presence in numerous bioactive natural products and synthetic molecules as well as synthetic intermediates. In this work we have investigated the stereoselective halocyclopropanation of allylic alcohols using a dioxaborolane-type stoichiometric chiral ligand and substituted zinc carbenoids derived from organozinc compounds and haloforms. We have thus developed conditions for the stereoselective iodo-, chloro- and fluorocyclopropanation reactions. A mechanistic study on the nature of alpha-chloro and alpha-bromomethylzinc carbenoids has revealed that halogen scrambling is taking place in the case of these carbenoids. During the chlorocyclopropanation reaction, the most reactive carbenoid (alpha-chloromethyl zinc) reacts predominantly, in line with the Curtin-Hammet principle. The enantioenriched iodocyclopropanes have been functionalized through a lithium-iodine exchange followed by treatment with electrophiles or transmetallation to zinc and Negishi cross-coupling. Therefore, a wide array of enantioenriched 1,2,3-substituted cyclopropanes have been synthesized using these methods. In order to develop new methodologies for the functionalization of cyclopropanes, we have studied the Hiyama-Denmark cross-coupling of cyclopropylsilanols. In this approach, the silanol group bears two functions: it serves as a proximal basic group in the Simmons-Smith cyclopropanation and it is involved in the transmetallation event during the cross-coupling reaction. In the cross-coupling step, the nature of the ligands bound to the silicon atom is crucial to the efficiency of the reaction. Hence, the in situ formation of the cyclopropyltrifluorosilane via a ligand exchange with boron trifluoride etherate is required for good yields. The final chapter of this work is on the nickel-catalyzed cyclization of alkyl iodides via a homolytic aromatic substitution mechanism. A series of tetrahydronaphthalene and thiochroman related compounds have been synthesized using this methodology. A mechanistic study has confirmed the radical nature of this reaction and strongly suggests the catalytic role of nickel. DOSY NMR spectrometric investigations have demonstrated an association between substrate, the base employed in this reaction and the nickel complex.