Influence of microwave irradiation and ionic liquids on multi component reactions

The present thesis focuses on the influence of microwave irradiation and ionic liquids on the outcome of two well-known three component reactions, the Groebke reaction and the Povarov reaction. The first part of the thesis deals with the influence of microwaves and ionic liquids on the Groebke reaction. The reaction of 2-aminopyridines with aldehydes and isocyanides using montmorillonite as a catalyst in toluene under microwave conditions at 160°C delivers the corresponding imidazo[1,2-a]pyridines within only seven minutes with yields ranging from 16 to 98%. The organic solvent can be replaced by ionic liquids like imidazolium and guanidinium salts. With guanidinium salts, it is possible to perform the Groebke reaction in the absence of any other catalyst and solvent under microwave conditions. The second part of this work is about the extension of the scope of typical Groebke reactions by replacing the aldehyde component with a bifunctional 2-carboxybenzaldehyde. The reaction of 2-aminopyridines with isocyanides and 2-carboxybenzaldehydes with 20 mol% methanesulfonic acid as a catalyst in toluene under microwave conditions at 160°C affords the corresponding pyrido[2?,1?:2,3]imidazo[4,5-c]isoquinolin-5(6H)-ones with yields ranging between 35 and 68%. The new method can easily be performed, is robust, and highly efficient. The third part of the thesis is focused on the intermolecular Povarov reaction. Using the reaction between aniline, benzaldehyde, and 2,3-dihydrofuran as a model reaction, the influence of ionic liquids, such as imidazolium and guanidinium salts, and microwaves on the outcome of the Povarov reaction was evaluated. It was established that the model reaction can be promoted by imidazolium salts like [bmim]BF4 under thermal as well as under microwave conditions. The reaction temperature has a strong impact on the chemical yield and the diastereoselectivity of the model reaction. At lower temperatures the formation of the endo-isomer is favored. However, the influence of microwave irradiation on yield and selectivity is not very pronounced. The Povarov reaction can also be promoted by a great number of guanidinium salts. Reactions that were performed under thermal conditions in a sealed vial demonstrated that both the chemical yield and the diastereoselectivity of the reaction are strongly influenced by a) the structure of the guanidinium ion and the nature of the anion of the guanidinium salt, and b) the concentration of the guanidinium salt. Remarkably, the Povarov can also be performed successfully in the presence of only catalytic amounts of a guanidinium salt. Finally, it was demonstrated that the guanidinium salts can be recycled and reused several times without loss of reactivity.Die vorliegende Dissertation beschäftigt sich vor allem mit dem Einfluss von Mikrowellenstrahlung und ionischen Flüssigkeiten auf zwei Dreikomponenten-Reaktionen, die Groebke- und die Povarov-Reaktion. Im ersten Teil der Dissertation wird der Einfluss von Mikrowellen und ionischen Flüssigkeiten auf die Groebke-Reaktion untersucht. Die Umsetzung von 2-Aminopyridinen mit Aldehyden und Isocyaniden mit Montmorillonit als Katalysator in Toluol unter Mikrowellenbedingungen bei 160°C liefert die entsprechenden Imidazo[1,2-a]pyridine innerhalb von nur sieben Minuten mit Ausbeuten zwischen 16 und 98%. Das organische Lösungsmittel kann durch ionische Flüssigkeiten wie Imidazolium- und Guanidiniumsalze ersetzt werden. Mit Guanidiniumsalzen ist es möglich, die Groebke-Reaktion in Abwesenheit irgendeines zusätzlichen Katalysators oder Lösungsmittels unter Mikrowellenbedingungen durchzuführen. Der zweite Teil dieser Arbeit befasst sich mit der Erweiterung des Anwendungsbereichs der klassischen Groebke-Reaktion durch Ersatz der Aldehydkomponente durch einen bifunktionalen 2-Carboxybenzaldehyd. Die Reaktion von 2-Aminopyridinen mit Isocyaniden und 2-Carboxybenzaldehyden in Gegenwart von 20 mol% Methansulfonsäure als Katalysator in Toluol unter Mikrowellenbedingungen bei 160°C ergibt die entsprechenden Pyrido[2?,1?:2,3]imidazo[4,5-c]isochinolin-5(6H)-one mit Ausbeuten zwischen 35 und 68%. Die neue Methode kann leicht durchgeführt werden, ist robust und hoch effizient. Der dritte Teil dieser Dissertation beschäftigt sich mit der intermolekularen Povarov-Reaktion. Am Beispiel der Umsetzung zwischen Anilin, Benzaldehyd und 2,3-Dihydrofuran als Modellreaktion wurde der Einfluss von ionischen Flüssigkeiten wie Imidazolium- und Guanidiniumsalzen sowie von Mikrowellen auf den Verlauf der Povarov-Reaktion untersucht. Man fand, dass die Modellreaktion sowohl unter thermischen als auch unter Mikrowellenbedingungen durch Imidazoliumsalze wie [bmim]BF4 katalysiert werden kann. Die Reaktionstemperatur übt einen starken Einfluss auf die chemische Ausbeute und die Diastereoselektivität der Modellreaktion aus. Bei niedrigen Temperaturen wird die Bildung des endo-Isomers bevorzugt. Dagegen ist der Einfluss der Mikrowellenstrahlung auf Ausbeute und Selektivität nicht sehr ausgeprägt. Die Povarov-Reaktion kann auch durch viele Guanidiniumsalze initiiert werden. Am Beispiel der Umsetzungen unter thermischen Bedingungen in einem verschlossenen Röhrchen ließ sich zeigen, dass sowohl a) die Struktur des Guanidiniumions und die Art des Anions des Guanidiniumsalzes als auch b) die Konzentration des Guanidiniumsalzes einen starken Einfluss auf die chemische Ausbeute und die Diastereoselektivität ausüben. Bemerkenswert ist, dass sich die Povarov-Reaktion auch in Gegenwart von nur katalytischen Mengen eines Guanidiniumsalzes erfolgreich realisieren lässt. Abschließend wurde gezeigt, dass die Guanidiniumsalze recycelt und mehrere Male ohne Verlust der Reaktivität wiederverwendet werden können

6-Benzyl-3,4-dimeth­oxy-10-methyl­pyrido[2′,1′:2,3]imidazo[4,5-c]isoquinolin-5(6H)-one

Pyrido[2′,1′:2,3]imidazo[4,5-c]isoquinolin-5(6H)-ones such as the title compound, C24H21N3O3, can be obtained in a few minutes in a microwave-assisted three-component reaction from 2-amino­pyridines, isocyanides and 2-carboxy­benz­aldehydes. In the title compound, the pyrido[2′,1′:2,3]imidazo[4,5-c]isoquinolin-5(6H)-one ring system is almost planar (mean deviation 0.068 Å). The dihedral angle between the benzyl ring and the pyrido[2′,1′:2,3]imidazo[4,5-c]isoquinolin-5(6H)-one ring system is 78.2°. The crystal structure is stabilized by inter­molecular C—H⋯O and C—H⋯N hydrogen bonds

Lyotropic Liquid Crystalline Mesophase of Sulfuric Acid-Nonionic Surfactant Stabilizes Lead(II) Oxide in Sulfuric Acid Concentrations Relevant to Lead Acid Batteries

Concentrated sulfuric acid (SA) and nonionic surfactant (C12H25(OCH2CH2)10OH, C12E10) form lyotropic liquid crystalline (LLC) mesophases in a broad range of SA concentrations; the SA/C12E10 mole ratio may vary from 2 to 11 in the LLC mesophases in the presence of a small amount of water. The mesophase is hexagonal at low SA concentration and cubic at higher concentrations. Three different compositions were prepared (one hexagonal and two cubic) with the SA/C12E10 mole ratio of 2.5, 6, and 9, denoted as 2.5LC, 6LC, and 9LC, respectively. They all display electrochemical SA activity in Pt and Pb systems. Most interestingly, they show the electrochemical formation of stable PbO species in a deeply acidic medium as evidenced by the X-ray diffraction, cyclic voltammetry, and linear sweep voltammetry experiments. The preferable properties of PbO over PbSO4 for lead acid batteries (LABs) make it uniquely positioned as a superior gel electrolyte for the LABs that would mitigate sulfation. © 2017 American Chemical Society

Relationship Between Sleep Duration and Coronary Artery Disease in Older Adults

Purpose: Insomnia, a frequent geriatric syndrome, is thought to be linked with coronary artery disease and increased mortality. The aim of our study was to examine the relationship between sleep duration and coronary artery disease (CAD) and cardiovascular risk factors. Materials and Methods: In this study, patients who applied to the geriatric outpatient clinic for comprehensive geriatric assessment were retrospectively evaluated. Patients were divided into two groups according to the six hours of ideal sleep assumption: those who slept less than six hours and those who slept six hours or more. Results: A total of 2255 patients (age 72±6 years, 63.3% female) were included in this study. Patients who were sleeping less than 6 hours were older (14.4% vs. 10.3%; p=0.005) and most of them were female (69.5% vs. 60.2%; p<001). Coronary artery disease (31.9% vs. 25.9%; p= 0.003), falls (31.8% vs. 25.3%; p=0.002) and depression (25.7% vs. 21.3%; p=0.022) were more common, while hypertension ( 68.5% and 72.5%; p=0.049) were less common in the short sleep duration group. The regression analysis showed that short sleep duration was significantly associated with CAD (OR:1.39; 95% CI:1.14-1.7; p=0.001), falls history (OR:1.25; 95% CI:1.02-1.5; p=0.026), age (OR:1.01; 95% CI:1.01-1.04; p=0.001), male gender (OR:0.63; 95% CI:0.51-0.76; p<0.001), and hypertension (OR:0.74; %95 CI:0.6-0.9; p=0.003). Conclusion: Similar to the literature, CAD was observed more frequently in patients who slept less than 6 hours in our results. Considering this relationship between short sleep duration and CAD, it is important to question sleep duration in comprehensive geriatric assessment

Water recovery with combined membrane system in textile industry, treatment and management of concentrates by hybrid advanced oxidation/membrane filtration

In this study, in addition to textile wastewater treatment by UF/NFtight/TO membrane combination of which efficiency is known, management has been performed for membrane concentrates generated with advanced oxidation combined process (Fenton and photo-Fenton (UVA-365-UVC-254))/submerged UF system of membrane concentrates generated within 75-80% water recovery ratio by oxidizing them in optimum operating conditions which were determined before. Ultimately in the studies, the conclusion has been reached that concentrate flows, generated as a result of the treatment with UF/NFtight/TO membrane configuration, were the highest performance innovative process by decreasing the sequential operated photo-Fenton (UVC-254)/UH050 hybrid process in ratios of 9.88 H2O2/TOK and 7.27 H2O2/Fe2+, in the filtration flux of 44 L/m(2). h, COD value to 167 mg/L with 86% COD removal, and TOK value to 104 mg/L with 74.2% TOC removal, after the oxidation with Fenton, photo-Fenton (UVA-365) and (UVC-254)/submerged UF system processes. When hazardous characteristics, removal/recovery methods and reuse alternatives of the concentrate remained after the oxidation of membrane concentrates generated were evaluated, it has been seen that all other concentrates of textile industry wastewater, except the concentrate generated by the treatment with photo-Fenton (UVA-365), had characteristics of hazardousness When removal/recovery methods were evaluated in detail, the conclusion has been reached that these concentrates could be removed with alternative options such as regular storage, burning and canalizing to central wastewater treatment system as long as necessary arrangements (moisture content, dehydration, suitable flow and/or mixture ratios) are made

The Groebke-Blackburn-Bienayme Reaction

Imidazo[1,2a]pyridine is a well‐known scaffold in many marketed drugs, such as Zolpidem, Minodronic acid, Miroprofen and DS‐1 and it also serves as a broadly applied pharmacophore in drug discovery. The scaffold revoked a wave of interest when Groebke, Blackburn and Bienaymé reported independently a new three component reaction resulting in compounds with the imidazo[1,2‐a]‐heterocycles as a core structure. During the course of two decades the Groebke Blackburn Bienaymé (GBB‐3CR) reaction has emerged as a very important multicomponent reaction (MCR), resulting in over a hundred patents and a great number of publications in various fields of interest. Now two compounds derived from GBB‐3CR chemistry received FDA approval. To celebrate the first 20 years of GBB‐chemistry , we present an overview of the chemistry of the GBB‐3CR, including an analysis of each of the three starting material classes, solvents and catalysts. Additionally, a list of patents and their applications and a more in‐depth summary of the biological targets that were addressed, including structural biology analysis, is given