Technische Universität München Lehrstuhl für Bioverfahrenstechnik Process Integration of Fermentation and Catalysis for the Production of Succinic Acid Derivatives Clara Delhomme Vollständiger Abdruck der von der Fakultät für Maschinenwesen der Technischen Universität München zur Erlangung des akademischen Grades eines Doktor-Ingenieurs genehmigten Dissertation. Vorsitzender: Univ.-Prof. Dr.rer.nat. Sonja Berensmeier Prüfer der Dissertation: 1. Univ.-Prof. Dr.-Ing. Dirk Weuster-Botz 2. Univ.-Prof. Dr.rer.nat. habil. Fritz E. Kühn Die Dissertation wurde am 30.06.2011 bei der Technischen Universität München eingereicht und durch die Fakultät für Maschinenwesen am 19.09.2011 angenommen. Acknowledgements The research presented in this Ph.D Thesis was realized at the Institute of Biochemical Engineering under the supervision of Prof. Dr.-Ing. D. Weuster-Botz and in collaboration with the Institute of Molecular Catalysis of Prof. Dr. F. E. Kühn at the Technische Universität München. It would not have been possible to write this doctoral thesis without the personal and practical support of numerous people, to only some of whom it is possible to give particular mention here. Foremost, I would like to express my sincere gratitude to my advisor Prof. Dr.-Ing. D. Weuster-Botz for giving me the possibility of doing my Ph.D. at the Technische Universität München in Germany and for the support of my Ph.D study and research. His wide knowledge and his logical way of thinking have also been of great value for my thesis. I am deeply grateful to my second examiner, Prof. Dr. F. E. Kühn, for the collaboration during this project. His constructive comments for the chemistry part of my research and his advice have been of great help. I also would like to thank the president of the jury, Prof. Dr. S. Berensmeier for accepting this role and for allowing a good proceeding of the examination. This research would not have been possible without the financial support of the International Graduate School of Science and Engineering of the Technische Universität München. It made also the collaboration possible between the Institute of Biochemical Engineering and the Institute of Molecular Catalysis of the Technische Universität München. I am indebted to Gabriel Salazar-Duarte, Hannes Löwe und Elona Hasanbelli for performing some experiments in the frame of their Bachelor or Master Thesis. I am very grateful to many colleagues at the Institute of Biochemical Engineering of the Technische Universität München for helping me with experiments and simulations, giving me technical assistance with some equipment, for the fruitful discussions and the friendly ambiance at the Institute. I should especially mention Bernd Anselment, Dr. Tanja Kurzrock, Dr. Danielle Dennewald, Dr. Kathrin Hölsch, Dr. Torben Höfel, Dr. Gabi Gebhardt, Markus Amann, Norbert Wert, Georg Kojro and many others. I would also like to express my gratitude to the colleagues of the Institute of Molecular Catalysis and Inorganic Chemistry of the Technische Universität München, with whom I collaborated throughout this project. I must thank them for helping me with the chemical experiments, showing me new methodologies, performing experiments for me, discussing chemical problems and finally for the joyful atmosphere in the laboratories. Among many people, I would like to thank Dr. Mei Zhang-Presse, Serena Goh, Manuel Högerl, Dr. Nadežda Jović, Julia Witt, Dr. Alexandrina D. Rusu and Dr. Gabriele Raudaschl-Sieber. For cross-checking this Thesis, I must acknowledge my father Dr. Jean-Pierre Delhomme, Dr. Danielle Dennewald and Manuel Högerl for taking time to correct this manuscript and making many helpful comments and suggestions. Their help have been extremely useful and appreciated. I would like to warmly thank my family who supported me through the difficult times of these four years of research, for comforting me, advising me and as always believing in me. I wish to acknowledge Bodo Gohla-Neudecker for his unconditional support during these last two years, for his encouragement and for giving me the strength to finish this thesis. My deep gratitude goes to my colleague and friend Dr. Danielle Dennewald for the great time in the office, for the incredible support during the difficult moments and for being the other “French” of the Institute. Finally, I must thank many friends, who encouraged me, called me and helped me with their sincere support. There are too many persons to name but I should mention Guillaume Costanzo, Joël Israel, Aniruddha Barghava, Elodie Planchon, Hélène Nast, Valentina Villa and Vera Zon. Table of contents 1 INTRODUCTION......................................................................................................................... 1 2 MOTIVATION AND OBJECTIVES .......................................................................................... 3 2.1 Motivation ............................................................................................................................... 3 2.2 Objectives ................................................................................................................................ 3 2.3 Methodology............................................................................................................................ 4 2.4 Outline of the thesis ............................................................................................................... 5 3 THEORETICAL BACKGROUND ............................................................................................. 6 3.1 Succinic acid: a platform chemical ........................................................................................ 6 3.1.1 Succinic acid ....................................................................................................................... 6 3.1.2 Current synthesis of succinic acid from oil ....................................................................... 6 3.1.3 Biotechnological production of succinic acid .................................................................... 7 3.1.4 Succinic acid as platform chemical ................................................................................. 10 3.1.5 Reduced derivatives of succinic acid ............................................................................... 10 3.1.6 Succinate esters ................................................................................................................ 11 3.2 Catalysis ............................................................................................................................... 13 3.2.1 Mass transfer .................................................................................................................... 15 3.2.1.1 Pure external mass transfer ......................................................................................... 16 3.2.1.2 Pure internal mass transfer ......................................................................................... 18 3.2.1.3 Simultaneous external and internal mass transfers .................................................. 20 3.2.2 Effect of the temperature ................................................................................................. 20 3.2.3 Effect on the order of reaction ......................................................................................... 22 3.2.4 Effect of the catalyst particle size ................................................................................... 22 3.2.5 Two types of catalysis ...................................................................................................... 22 3.2.5.1 Particularity of enzymatic catalysis ............................................................................ 22 3.2.5.2 Particularity of coordination chemistry catalysis ....................................................... 24 3.2.5.3 Particularity of catalyst immobilization on polymer .................................................. 24 3.3 Hydrogenation ...................................................................................................................... 26 3.3.1 Hydrogenation of succinic or maleic acid in water with metal supported catalysts.... 27 3.3.2 Hydrogenation of succinic anhydride in solvent with metal complexes ....................... 30 3.3.2.1 Hydrogenation using ruthenium complexes ................................................................ 30 3.3.2.2 Reaction mechanism of the hydrogenation of succinic anhydride ............................. 33 3.3.3 Hydrogenation of levulinic acid in water ........................................................................ 34 3.3.3.1 Interest in levulinic acid .............................................................................................. 34 3.3.3.2 Aqueous hydrogenation of levulinic acid .................................................................... 35 3.3.4 Hydrogenation of esters in solvents using metal complexes ......................................... 36 3.3.4.1 Use of phosphine ruthenium complexes ...................................................................... 38 3.3.4.2 Use of other complexes .................................................................................................. 40 3.4 Esterification ........................................................................................................................ 41 3.4.1 Principle and mechanism ...............................................................................................