Homogeneously catalysed Suzuki coupling reaction in microemulsion systems with recycling of the catalyst [Elektronische Ressource] / vorgelegt von Henriette Nowothnick

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• Publié par: technische_universitat_berlin
• Publié le: 01 janvier 2010
• Nombre de lectures: 31
• Langue: English
• Poids de l'ouvrage: 2 Mo

Extrait

Homogeneously catalysed Suzuki coupling reaction in microemulsion systems with recycling of the catalyst

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Science is wonderfully equipped to answer the question “How?“ but it gets terribly confused when you ask the question “Why?” Erwin Chargaff

Abstract The Suzuki cross coupling reaction of 2Bromobenzonitrile and 4Methylbenzeneboronic acid was investigated in microemulsions (heptane/water/surfactant) and catalysed by the water soluble catalyst complex PdTPPTS. Thereby, the formulation of microemulsions was studied under reaction conditions with the aim of enhancing the rate in comparison to a biphasic system (without surfactant). Furthermore, the use of heptane/water resulted in unselective reaction with the production of homocoupling product of arylboronic acid. As a benchmark, the Suzuki coupling was performed also in acetonitrile as oftenused solvent for CC coupling reactions, showing that no faster rate was observed as in microemulsions and in addition no catalyst recycling was possible. The most promising aspect of using microemulsions as reaction media is the location of miscibility gaps, which were utilised for product isolation, catalyst recycling and the removal of the salts. Therefore, especially nonionic surfactants show the required ability to form liquid three phase systems. It was found that the phase behaviour is shifted during reaction progress. The microemulsion system was tuned in order to obtain the three phases at complete conversion what means that the observation was used as indicator that no online analytic was necessary. A subsequent catalyst recycling was carried out, by removing the heptane phase for isolation of the product, the replacement of the aqueous phase by a new batch to prevent a salinity effect (poisons the catalyst). The catalyst remains in the surfactantrich phase and is enclosed by the surfactant aggregates. Five runs were performed with Novel 1216CO8 as most promising nonionic surfactant because of its narrow range molecular weight distribution. It was found by analysing the aqueous phases of all runs, that Pd losses were not crucial. The most impact on reaction rate was observed by the losses of ligand, with 20 % in each run, what finally decreased the rate, as palladium black was formed in the last run. To demonstrate the adaptability of the three phase system, aryl chlorides were also investigated in the coupling with 4Methylbenzeneboronic acid. Therefore, the water soluble ligand SPhos developed by Buchwald was chosen. With the appropriate ligands for aryl bromides and chlorides almost the same reaction rate was observed under comparable reaction conditions. The activation energy for the coupling of aryl chlorides was estimated to be 62 kJ/mol for the rate determing step. The drawback of the Buchwald ligand, applied in the microemulsion system was demonstrated in the recycling experiments.

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Zusammenfassung Die SuzukiKupplung von 2Brombenzonitril mit pTolylboronsäure wurde unter Verwendung des wasserlöslichen Katalysatorkomplexes PdTPPTS in Mikroemulsionen untersucht. Die Formulierung und das Phasenverhalten von Mikroemulsionen (Heptan, Wasser und Tensid) wurden unter Reaktionsbedingungen untersucht, mit dem Ziel der Steigerung der Reaktionsgeschwindigkeit im Vergleich zu einem Zweiphasensystem (ohne Tensid). In Heptan/Wasser (1:1) wurde ein unselektiver Reaktionsverlauf zum Homokuppelprodukt der Arylboronsäure festgestellt. Als Referenz wurde die Suzuki Kupplung auch in Acetonitril als häufig genutztes Lösungsmittel für derartige Reaktionen durchgeführt. Hierin konnte die Reaktionsgeschwindigkeit nicht merklich gesteigert werden im Vergleich zum Mikroemulsionssystem und des Weiteren ist ein Katalysatorrecycling im polar aprotischen Lösungsmittel nicht möglich. Durch das Auffinden von Mischungslücken bieten Mikroemulsionen als Reaktionsmedium den Vorteil eines einfachen Katalysatorrecyclings, der Produktisolierung und das Entfernen von Salzen. Speziell nichtionische Tenside sind prädestiniert dafür flüssige Dreiphasensysteme zu bilden. Da sich das Phasenverhalten während der Reaktion ändert, wurden die Mikroemulsionen so eingestellt, dass das Dreiphasengebiet erst bei vollständigen Umsätzen erscheint und so als Indikator genutzt werden kann, was heißt, dass keine OnlineAnalytik nötig ist. Das Katalysatorrecycling wird durchgeführt, indem die Öl und die wässrige Phase entfernt und durch frische ersetzt werden. Das Produkt kann dabei aus der Ölphase isoliert werden, während durch den Austausch der wässrigen Phase die Salze entfernt werden, die den Katalysator vergiften können. Der Katalysator verbleibt dabei im Reaktor, in der tensidreichen Phase (Mitte). Fünf aufeinander folgende Reaktionen wurden mit Novel 8 als viel versprechendes Tensid durchgeführt. Die Wasserphasen jedes Recyclingschrittes wurden analysiert, wobei der Phosphorverlust (20 % jeweils) sich entscheidend auf die Reaktionsrate ausgewirkt hat, da mit dem letzten Zyklus Pd schwarz gebildet wurde. Um die allgemeine Anwendbarkeit von Dreiphasensystemen zu testen, wurden auch Arylchloride unter Verwendung des wasserlöslichen BuchwaldLiganden gekuppelt. Mit den jeweils geeigneten Liganden wurden ähnliche Reaktionsverläufe für Arylchloride und bromide erhalten. Die Aktivierungsenergie für die Kupplung von Arylchloriden wurde für den geschwindigkeitsbestimmenden Schritt zu 62 kJ/mol bestimmt. Ein Nachteil des BuchwaldLiganden im Mikroemulsionssystem zeigte sich in den unvollständigen Recyclingschritten.

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Acknowledgement I would like to express my gratitude to everyone, who made this work come true. First of all to Prof. R. Schomäcker for the inspiration of this research, the freedom in the experimental realisation and his support in many other things. Thanks to Prof. A. Behr for being my second referee and Prof. K. RückBraun for being chairman in the defense. Furthermore, I would like to thank Prof. R. Strey and PD Dr. T. Sottman for the wonderful working atmosphere within the AiF project. I am very grateful to our working group for all your help and support in many ways. To Juan Milano I enjoyed working with you, thanks for the sucessful discussions about our research topics, the brainstorming and that we could push among ourselves, and I know that our friendship is even more important. I would like to thank my diploma student Melissa Sudartono for your trust in working on an advanced process based on mine. To Xiao Xie I am ineffable grateful for a wonderful time also out of lab, your personal support and your friendship. I would like to thank Katja Seifert and I know you will go on completing our process sucessfully. To Gaby Vetter I am grateful for your generous help in the lab. To all my colleagues and friends who made research and life much more easier: Benjamin Beck, Dersy Lugo, Kirsten Langfeld, Sebastian Arndt, Le Anh Thu Nguyen, Verena Strempel, Tobias Hamerla, Hary Soerijanto, Torsten Otremba, Jonas Dimroth, Carlos Carrero, Michael Schwarze, Yasemin Kasaka, Iryna Volovych, Anke Rost, Riny Parapat and my bachelor students Ling Yin and Bilyana Nikolovska. To the families J. Seiffert and K. Leonhardt I am grateful for your personal support. Without you, it would not have been possible to complete this work. I am grateful to Michael Muthig for being there for me. Ich danke meinen Eltern für ihre unschätzbare Unterstützung in all meinen Lebenslagen und dafür, dass ihr immer für mich da seid, egal wo ich bin.

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M einen E ltern

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Table of Content I Abstract i II Zusammenfassung ii 1. Introduction and Motivation ................................................................................3 2. Background...........................................................................................................5 2.1 Crosscoupling reactions................................................................................... 5 2.1.1 The classical catalytic cycle........................................................................ 7 2.1.2 The anionic catalytic cycle .......................................................................... 8 2.2 Heterogeneously catalysed coupling reactions ............................................... 10 2.3 Homogeneously catalysed reactions............................................................... 13 2.3.1 The SHOP process................................................................................... 14 2.3.2 The RhônePoulenc process .................................................................... 15 2.4 The developments in homogeneously performed ........................................... 17 coupling reactions ................................................................................................. 17 2.4.1 Fluorous solvents ..................................................................................... 18 2.4.2 Ionic liquids............................................................................................... 19 2.4.3 Supercritical fluids .................................................................................... 21 2.4.4 Thermomorphic solvent systems .............................................................. 23 2.4.5 Industrial application of the Green Solvents ............................................. 25 2.5 Microemulsions ............................................................................................... 27 2.5.1 Chronology ............................................................................................... 27 2.5.2 Physical Properties and Phase behaviour ................................................ 28 2.4.3 Coupling reactions in Microemulsions ...................................................... 34 3.ExperimentalPart...............................................................................................36 3.1 Analytical part ................................................................................................. 36 3.1.1 UV/VIS measurements ............................................................................. 36 3.1.2 HPLC analysis .......................................................................................... 38 3.1.3 AAS analysis ............................................................................................ 40 3.2 Experimental Setup......................................................................................... 41 3.3 Materials and experimental Procedures.......................................................... 43 4. Microemulsion with ionic surfactants for Suzuki coupling reactions............47 4.1 Phase behaviour of the reaction mixture......................................................... 47

4.2 Analytical methods .......................................................................................... 50 4.3 Impact of formulating the microemulsions....................................................... 51 4.4 Recycling of the catalyst ................................................................................. 56 5. Suzuki coupling of aryl bromides using nonionic surfactants..................... 59 5.1 Introduction ..................................................................................................... 59 5.2 Phase behaviour ............................................................................................. 59 5.3 Impact of reaction conditions .......................................................................... 62 5.3.1 Influence of solvent and catalyst concentration ........................................ 63 5.3.2 Influence of Ligands ................................................................................. 69 5.4 Impact of composition ..................................................................................... 71 5.4.1 Influence of surfactant concentration, γ .................................................... 71 5.4.2 Influence of oil to water ratio, α ................................................................ 73 5.4.3 Influence of base ...................................................................................... 77 5.4.4 Phase and Product distribution................................................................. 83 5.5 Recycling of the catalyst ................................................................................. 85 5.6 Hydrogenation of the Suzuki coupling product................................................ 91 6. Suzuki coupling with aryl chlorides as starting materials ..............................94 6.1 Introduction ..................................................................................................... 94 6.2 Experimental procedure .................................................................................. 98 6.2.1 Standard reaction ..................................................................................... 99 6.2.2 Recycling procedure............................................................................... 100 6.3 Impact of reactants........................................................................................ 103 6.3.1 Influence of aryl halide............................................................................ 103 6.3.2 Influence of boronic acid concentration .................................................. 107 6.3.3 Temperature dependency and kinetic approaches................................. 108 6.4 Recycling of the catalyst ............................................................................... 113 7.ConclusionandOutlook..................................................................................116 10.Literature.........................................................................................................121 11.Appendix.........................................................................................................126

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1. Introduction and Motivation

1. Introduction and Motivation Catalytic processes are the key to sustainable synthesis in industry. In the production of basic and fine chemicals, homogeneously catalysed reactions have been established since decades. Their obtainable high selectivities cause low amounts of side products, what is an economical advantage on the one hand and an important environmental aspect on the other hand. Markets dominating in the production of fine chemicals are agrochemicals (35%), followed by pharmaceuticals (30%) and flavours (23%). Palladium catalysed coupling reactions have been evolved to versatile tools in organic chemistry during the last three decades because of easy carboncarbon or carbonheteroatombond formation. Coupling reactions are useful for reducing multistage sequences of synthesis. Therefore, they are an important tool for the synthesis of pharmaceuticals and agrochemicals but also used for synthesis of liquid crystals. These fine chemicals should be producible with high selectivity and energy efficient. Following fine chemicals produced by CC coupling reactions have been employed in industry so far: the herbicide Prosulforon (Heck) by Novartis, Naproxen (Heck) for the treatment of pain or inflammation by Albemarle, the mycoticum Terbafin (Sonogashira) by Novartis, the fungicid Boscalid (Suzuki) by BASF with a capacity of 1000 t per year, Losartan as antihypertensive drug by Merck and the associated precursor 4’Methyl2biphenylcarbonitrile, respectively by Clariant. Challenges in homogeneous catalysis are still the separation of product and catalyst. If a noble metall catalyst and/or an expensive ligand are used, a catalyst

recycling will be essential. Research on recycling of the catalyst attracks interest but is established in industry only rarely. In a biphasic solvent mixture, in which substrates and product are, respectively, dissolved in one solvent whereas the catalyst is dissolved in the other, a catalyst recycling can be accomplished by easy decantation. For this purpose, sucessful applications of catalysis in twophase systems in industry are the SHOP and the RhônePoulenc Process. Nowadays, new solvents are applied to enhance recyclability and because of environmental aspects, solvents, which are toxic or nonvolatile should be replaced with the aim of waste prevention rather than waste treatment. Therefore, several research groups focus on different ideas: the use of ionic liquids, supercritical fluids

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