FUNCTIONAL PLA BASED SYSTEMS A Dissertation Presented to The Graduate Faculty of The University of Akron In Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy Colin Wright December, 2015 FUNCTIONAL PLA BASED SYSTEMS Colin Wright Dissertation Approved: Accepted: ________________________________ ____________________________________ Advisor Department Chair Dr. Coleen Pugh Dr. Coleen Pugh ________________________________ ____________________________________ Committee Chair Dean of the College Dr. Robert Weiss Dr. Eric Amis ________________________________ ____________________________________ Committee Member Dean of the Graduate School Dr. Mathew Becker Dr. Chand Midha ________________________________ ____________________________________ Committee Member Date Dr. William Landis ________________________________ Committee Member Dr. Yang Yun ii ABSTRACT Poly(lactic acid) (PLA), is used in a wide variety of applications. It is a well studied polymer and offers many advantages, such as being derived from renewable resources, being biodegradable, FDA approved for biomedical applications, and commercially available. The main synthetic drawback is that the only sites for post-polymerization functionalization are at the two end groups. By incorporating 3-hydroxy-2- bromopropionic acid as a co-monomer with lactic acid, a site for post-polymerization functionalization can be added. Since the halogen is alpha to a carbonyl, it is activated toward nucleophlic substitution, radical formation, and enolate chemistry. The spacing on the backbone of our polymer allows for additional functionalization including rearrangement, electrophilic aromatic substitution, and cationic ring-opening polymerization. iii DEDICATION I would like to dedicate this dissertation to my parents for encouraging me to attend graduate school. iv ACKNOWLEDGMENTS I would like to thank my mother and father for their unfailing support of me during my time in academia. I would like to thank the entire Pugh research group for their help. Specifically, William Storms-Miller and Abishek Banerjee for starting this project and for all their help and advice. I would like to thank Dr. Matthew Becker, Dr. Robert Weiss, Dr. Yang Yun, and Dr. William Landis for sitting on my thesis committee. Thank you for reading this thesis, listening to my presentation and your thoughtful comments. v TABLE OF CONTENTS Page LIST OF FIGURES .......................................................................................................... xii LIST OF SCHEMES ...................................................................................................... xvii LIST OF TABLES ........................................................................................................... xix LIST OF EQUATIONS .....................................................................................................xx CHAPTER I. THE PROBLEM ........................................................................................................1 II. LITERATURE REVIEW ...........................................................................................4 2.1 Poly(caprolactone) .........................................................................................4 2.2 Poly(glycolic acid) .........................................................................................5 2.3 Poly(lactic acid) .............................................................................................5 2.4 Step Growth Polymerization ..........................................................................7 2.4.1 Acid-catalyzed Condensation of Lactic Acid .........................................7 2.4.2 Carbodiimide Coupling of Lactic Acid ...................................................8 2.4.3 Limitations of PLA Made by Step-Growth Polymerizations .................9 2.4.4 Lactides .................................................................................................10 2.4.5 Formation of Lactides ...........................................................................10 2.4.6 Ring-Opening Polymerization of Lactides ...........................................11 2.4.7 Limits of ROP .......................................................................................12 2.5 Enzymatic Polymerization of Lactic Acid ...................................................13 vi 2.6 Modification of PLA ....................................................................................14 2.6.1 Blending ................................................................................................15 2.6.2 Nanofillers .............................................................................................15 2.6.3 Copolymers ...........................................................................................16 2.6.4 Chemical Reactions on PLA .................................................................18 2.6.5 Chain End Modification ........................................................................19 2.7 Introduction of Functional Groups onto Polyesters .....................................20 2.7.1 Alkyl Groups .........................................................................................20 2.7.2 Alkyne Group ........................................................................................21 2.7.3 Azide Group ..........................................................................................21 2.7.4 Amino Group ........................................................................................23 2.7.5 Carboxylic Acid ....................................................................................24 2.7.6 Cyano Group .........................................................................................24 2.7.7 Hydroxyl Group ....................................................................................26 2.7.8 Vinyl Group ..........................................................................................27 2.7.9 Mercapto Group ....................................................................................29 2.8 Radical Grafting ...........................................................................................29 2.9 Motivation and Scope ..................................................................................31 2.10 Routes for Post-polymerization Functionalization ....................................33 2.10.1 Nucleophilic Substitution ....................................................................33 2.10.2 Radical Chemistry ...............................................................................34 2.10.3 Enolate Chemistry ...............................................................................36 2.10.4 Cationic ROP using an Oxocarbenium Ion .........................................37 vii 2.10.5 Electrophilic Aromatic Substitution of an Oxocarbenium Ion ...........38 2.11 Goal of the Project .....................................................................................39 2.12 Summary ....................................................................................................39 III. EXPERIMENTAL ...................................................................................................40 3.1 Materials. .....................................................................................................40 3.2 Techniques. ..................................................................................................41 3.3 Reactions ......................................................................................................42 3.3.1 Synthesis of Poly[(lactic acid)-co-(2-bromo-3-hydroxypropionic acid)]. ..............................................................................................................42 3.3.2 Large Scale Synthesis (10 g) of Poly[(lactic acid)-co-(2-bromo-3- hydroxypropionic acid)]. .................................................................................43 3.3.3 Synthesis of Poly[(lactic acid)-co-(2-iodo-3-hydroxypropionic acid)]. ..............................................................................................................44 3.3.4 Synthesis of Poly[(lactic acid)-co-(2-azido-3-hydroxypropionic acid)-co-(2-bromo-3-hydroxypropionic acid)] by Reaction of Poly [(lactic acid)-co-(2-bromo-3-hydroxypropionic acid)] with Sodium Azide. ..45 3.3.5 Attempted Copper-Catalyzed Huisgen Alkyne-Azide Cycloaddition of Poly[(lactic acid)-co-(2-azido-3-hydroxypropionic acid)-co-(2-bromo- 3-hydroxypropionic acid)] with Propargyl Alcohol. ......................................47 3.3.6 Huisgen Alkyne-Azide Cycloaddition of Poly[(lactic acid)-co-(2- azido-3-hydroxypropionic acid)-co-(2-bromo-3-hydroxypropionic acid)] with Dimethyl Acetylenedicarboxylate. .........................................................48 3.3.7 Synthesis of Methyl 2-Bromo-3-hydroxypropionate. ...........................49 3.3.8 Synthesis of Methyl 3-Acetoxy-2-bromopropionate. ...........................50 3.3.9 Test of the Stability of Methyl 3-Acetoxy-2-bromopropionate in the Presence of PMDETA. ....................................................................................50 3.3.10 Synthesis of Poly[(lactic acid)-co-(2-bromo-3-hydroxypropionic acid)]. ..............................................................................................................51 viii 3.3.11 Synthesis of Poly[(lactic acid)-co-(2-iodo-3-hydroxypropionic acid)]. ..............................................................................................................52