Palladium(II)-Catalyzed Addition Reactions : Synthesis of Aryl Amidines and Aryl Ketones

Palladium-catalyzed reactions have become one of the most important tools in modern organic chemistry due to its ability to catalyze the formation of new carbon-carbon bonds. The aim of the work presented in this thesis was to develop new palladium(II)-catalyzed addition reactions. In this work, cyanamides were investigated as a new substrate to give aryl amidines as products. The first protocol developed employed aryltrifluoroborates as the aryl partner, and the insertion of the aryl group into un-, mono-, and di-substituted cyanamides was successful for a wide variety of aryltrifluoroborates. An alternative method of generating the necessary intermediate for insertion into the cyanamide is the decarboxylative formation of aryl-palladium from aryl carboxylic acids. A protocol was developed for this reaction, but was unfortunately limited to a small number of ortho-substituted electron-rich aryl carboxylic acids. The mechanism was investigated by the means of DFT calculations and ESI-MS studies, and the rate-determining step was suggested to be the 1,2-carbopalladation based upon those results. A translation of the batch protocol to continuous-flow conditions was also demonstrated. The ideal method of generating the aryl-palladium species is by C-H bond activation, and this approach was demonstrated with indoles, giving a variety of 3-amidinoindoles as products. The mechanism was investigated by DFT calculations and a plausible catalytic cycle was proposed. A continuous-flow application of a desulfitative palladium(II)-catalyzed addition to nitriles to give ketones was developed. In addition, different reactor materials were evaluated in the microwave heated reactor cavity. Thus the reaction was shown to proceed with microwave heating in a borosilicate glass and an aluminum oxide reactor, and also in conditions mimicking conventional heating in a silicon carbide reactor. Finally, a protocol was developed for the convenient synthesis of sodium aryl sulfinates from Grignard and lithium reagents using a solid sulfur dioxide source as a safe alternative to the gas. The products of this protocol can be used as aryl-palladium precursors by a desulfitative process

Trace element leaching from alum shale fines and red ash from Kvarntorp during a large column test

Fuel shortage during the Second World War led to oil production in Kvarntorp, Kumla during 1942-1966 by pyrolyzing alum shale rich in pyrite, FeS2, and organic material such as kerogen. This production has led to a lot of waste laying deposited out in the open after the mining closed and has had negative environmental impact in the form of ongoing weathering and leaching of acidic water and leaching of trace elements into its surroundings. Chemical processes are still ongoing in this deposit, with temperatures reaching 700 °C on certain hotspots. Once the deposit cools down, precipitation will be able to enter the deposit and start leaching acidic water containing trace elements that will risk polluting groundwater in the surrounding areas. No one knows how many years it will take for the deposit to cool down, but it has been estimated to take at least 100 years.This study did leaching experiments on weathered fines as well as red ash in large columns while being oxygenated. Analyses consisted of ICP-MS, pH, electrical conductivity, acidity, alkalinity, and sulphate concentration.The results showed high concentrations of many valuable and potentially toxic elements in the leachates especially higher amounts of copper compared to previous studies

Palladium(II)-Catalyzed Addition Reactions : Synthesis of Aryl Amidines and Aryl Ketones

Palladium-catalyzed reactions have become one of the most important tools in modern organic chemistry due to its ability to catalyze the formation of new carbon-carbon bonds. The aim of the work presented in this thesis was to develop new palladium(II)-catalyzed addition reactions. In this work, cyanamides were investigated as a new substrate to give aryl amidines as products. The first protocol developed employed aryltrifluoroborates as the aryl partner, and the insertion of the aryl group into un-, mono-, and di-substituted cyanamides was successful for a wide variety of aryltrifluoroborates. An alternative method of generating the necessary intermediate for insertion into the cyanamide is the decarboxylative formation of aryl-palladium from aryl carboxylic acids. A protocol was developed for this reaction, but was unfortunately limited to a small number of ortho-substituted electron-rich aryl carboxylic acids. The mechanism was investigated by the means of DFT calculations and ESI-MS studies, and the rate-determining step was suggested to be the 1,2-carbopalladation based upon those results. A translation of the batch protocol to continuous-flow conditions was also demonstrated. The ideal method of generating the aryl-palladium species is by C-H bond activation, and this approach was demonstrated with indoles, giving a variety of 3-amidinoindoles as products. The mechanism was investigated by DFT calculations and a plausible catalytic cycle was proposed. A continuous-flow application of a desulfitative palladium(II)-catalyzed addition to nitriles to give ketones was developed. In addition, different reactor materials were evaluated in the microwave heated reactor cavity. Thus the reaction was shown to proceed with microwave heating in a borosilicate glass and an aluminum oxide reactor, and also in conditions mimicking conventional heating in a silicon carbide reactor. Finally, a protocol was developed for the convenient synthesis of sodium aryl sulfinates from Grignard and lithium reagents using a solid sulfur dioxide source as a safe alternative to the gas. The products of this protocol can be used as aryl-palladium precursors by a desulfitative process

Trace element leaching from alum shale fines and red ash from Kvarntorp during a large column test

Fuel shortage during the Second World War led to oil production in Kvarntorp, Kumla during 1942-1966 by pyrolyzing alum shale rich in pyrite, FeS2, and organic material such as kerogen. This production has led to a lot of waste laying deposited out in the open after the mining closed and has had negative environmental impact in the form of ongoing weathering and leaching of acidic water and leaching of trace elements into its surroundings. Chemical processes are still ongoing in this deposit, with temperatures reaching 700 °C on certain hotspots. Once the deposit cools down, precipitation will be able to enter the deposit and start leaching acidic water containing trace elements that will risk polluting groundwater in the surrounding areas. No one knows how many years it will take for the deposit to cool down, but it has been estimated to take at least 100 years.This study did leaching experiments on weathered fines as well as red ash in large columns while being oxygenated. Analyses consisted of ICP-MS, pH, electrical conductivity, acidity, alkalinity, and sulphate concentration.The results showed high concentrations of many valuable and potentially toxic elements in the leachates especially higher amounts of copper compared to previous studies

Palladium(II)-Catalyzed Addition Reactions : Synthesis of Aryl Amidines and Aryl Ketones

Palladium-catalyzed reactions have become one of the most important tools in modern organic chemistry due to its ability to catalyze the formation of new carbon-carbon bonds. The aim of the work presented in this thesis was to develop new palladium(II)-catalyzed addition reactions. In this work, cyanamides were investigated as a new substrate to give aryl amidines as products. The first protocol developed employed aryltrifluoroborates as the aryl partner, and the insertion of the aryl group into un-, mono-, and di-substituted cyanamides was successful for a wide variety of aryltrifluoroborates. An alternative method of generating the necessary intermediate for insertion into the cyanamide is the decarboxylative formation of aryl-palladium from aryl carboxylic acids. A protocol was developed for this reaction, but was unfortunately limited to a small number of ortho-substituted electron-rich aryl carboxylic acids. The mechanism was investigated by the means of DFT calculations and ESI-MS studies, and the rate-determining step was suggested to be the 1,2-carbopalladation based upon those results. A translation of the batch protocol to continuous-flow conditions was also demonstrated. The ideal method of generating the aryl-palladium species is by C-H bond activation, and this approach was demonstrated with indoles, giving a variety of 3-amidinoindoles as products. The mechanism was investigated by DFT calculations and a plausible catalytic cycle was proposed. A continuous-flow application of a desulfitative palladium(II)-catalyzed addition to nitriles to give ketones was developed. In addition, different reactor materials were evaluated in the microwave heated reactor cavity. Thus the reaction was shown to proceed with microwave heating in a borosilicate glass and an aluminum oxide reactor, and also in conditions mimicking conventional heating in a silicon carbide reactor. Finally, a protocol was developed for the convenient synthesis of sodium aryl sulfinates from Grignard and lithium reagents using a solid sulfur dioxide source as a safe alternative to the gas. The products of this protocol can be used as aryl-palladium precursors by a desulfitative process

Palladium-Mediated Synthesis of [Carbonyl-11C]acyl Amidines from Aryl Iodides and Aryl Bromides and Their One-Pot Cyclization to 11C-Labeled Oxadiazoles

Positron emission tomography (PET) is a highly valuable imaging technique with many clinical applications. The possibility to study physiological and biochemical processes in vivo also makes PET an important tool in drug discovery. Of importance is the possibility of labelling the compound of interest with a positron-emitting radionuclide, such as carbon-11. Carbonylation reactions with [11C]carbon monoxide ([11C]CO) has been used to label a number of molecules containing a carbonyl derivative, such as amides and esters, with carbon-11. Presented herein is the palladium-mediated carbonylative synthesis of [carbonyl-11C]acyl amidines and their subsequent cyclization to 11C labeled 1,2,4-oxadiazoles. Starting from amidines, [11C]CO, and either aryl iodides or aryl bromides, [carbonyl-11C]acyl amidines were synthesized and isolated in good to very good radiochemical yields (RCY). The 11C-labeled 1,2,4-oxadiazoles were synthesized without the isolation of the intermediate [carbonyl-11C]acyl amidines and isolated in useful RCYs, including the NF-E2-related factor 2 activator DDO-7263. 3-Phenyl-5-(4-tolyl)-1,2,4-(5-11C)oxadiazole was synthesized and isolated with a clinically relevant molar activity. The broadened substrate scope, together with the good RCY and high Am, demonstrates the utility of this method for the incorporation of carbon-11 into acyl amidines and 1,2,4-oxadiazoles, structural motifs of pharmacological interest

Acyl Amidines by Pd-Catalyzed Aminocarbonylation : One-Pot Cyclizations and C-11 Labeling

A protocol for the carbonylative synthesis of acyl amidines from aryl halides, amidines, and carbon monoxide catalyzed by Pd(0) is reported herein. Notably, carbon monoxide is generated ex situ from a solid CO source, and several productive palladium ligands were identified with complementary benefits and substrate scope. Furthermore, sequential one-pot, two-step protocols for the synthesis of 1,2,4-triazoles and 1,2,4-oxadiazoles via acyl amidine intermediates are reported. In addition, this approach was extended to isotopic labeling using [11C]carbon monoxide to allow, for the first time, synthesis of 11C-labeled acyl amidines as well as a 11C-labeled 1,2,4-oxadiazole

Microwave Heated Continuous Flow Palladium(II)-Catalyzed Desulfitative Synthesis of Aryl Ketones

A protocol for Pd­(II)-catalyzed desulfitative synthesis of aryl ketones from sodium aryl sulfinates and nitriles in continuous flow has been developed. The reactions proceed with microwave heating using microwave transparent tube reactors, affording the desired aryl ketones in fair to good yields. Microwave transparent aluminum oxide reactors were identified as a safe and thermostable alternative to borosilicate glass reactors