© COPYRIGHT by Mobeen Ashraf 2015 ALL RIGHTS RESERVED INVESTIGATING MIXTURES OF ENANTIOMERIC SOLVENTS: THERMO-PHYSICAL PROPERTIES, BINARY PHASE DIAGRAM OF ENANTIOMERS, OPTICAL PURITY AND SOLVENT PARAMETERS OF ETHYL LACTATE ENANTIOMERS By Mobeen Ashraf ABSTRACT A polar-protic enantiomeric solvent, ethyl lactate, is a green solvent because of its non- carcinogenetic, low toxicity, non-corrosivity, 100% biodegradability, high boiling point, and ease of recycling properties. The two stable enantiomers of ethyl lactate are (-)-Ethyl L-Lactate and (+)-Ethyl D-Lactate. Ethyl Lactate is typically synthesized from ethanol and L-Lactic Acid because the D-form is more toxic. However a review of the literature indicated that certain thermo-physical properties such as density, specific optical rotation, specific gravity, refractive index, melting point, and binary phase-diagram of ethyl lactate enantiomers are either scarcely documented or missing altogether. In addition, the MSDS documented melting point of (-)-Ethyl L-Lactate is incorrectly reported. There is very limited to no information on basic physical and chemical properties of (+)-Ethyl D-Lactate in literature such as melting point, refractive index, specific gravity, acidity. No binary phase diagram of ethyl lactate enantiomers have been constructed to distinguish between the melting temperatures of L-form, D-form and racemic mixture of ethyl lactate. Phase behavior and thermo-physical properties of solvents are important in developing an environmental friendly process. Therefore, an investigation was made to measure the melting point (Tm), density (ρ), refractive index (nD), specific optical rotation [α] and optical purity (% enantiomeric excess) of ethyl lactate enantiomers and their mixtures. Binary phase diagram of ethyl lactate enantiomers was constructed to determine the eutectic point in the D/L composition using modulated Differential Scanning Calorimetery (DSC). ii Binary phase diagram of ethyl lactate enantiomers showed an eutectic point temperature of - 26.95°C at 60:40 [(L-form)/(D-form] composition of Ethyl Lactate. DSC results further determined that instead of documenting the melting point of (-)-Ethyl L-Lactate, manufacturers reported the melting point of ethyl lactate’s racemic mixture on the MSDS. The Tm of (-)-Ethyl L- Lactate was -4.23 °C. The D-form has Tm of -4.23 °C and racemate has Tm of -25.64 °C. Optical rotation measurements coupled with GC-MS measurements indicated an optically active impurity in (+)-Ethyl D-Lactate, leading to higher optical activities than the (-)-Ethyl L-Lactate form. Three solvents: (-)-Ethyl L-Lactate, (+)-Ethyl D-Lactate and their racemic mixture were further characterized using solvatochromic techniques. Polarizability/depolarization (π*), hydrogen-bond donating-acidity (α), and hydrogen-bond accepting-basicity (β) of (-)-Ethyl L- Lactate, (+)-Ethyl D-Lactate and racemic mixture were investigated by using UV-Vis spectroscopy over a temperature range of T = (283.15 to 343.15) K. Reichardt’s parameter, ET(30), was also investigated for (-)-Ethyl L-Lactate, (+)-Ethyl D-Lactate and racemic mixture under the same temperature conditions. Reichardt’s betaine dye, N,N-diethyl-4-nitroaniline and 4-nitroaniline were the three solvatochromic probes used to measure the ET(30) scales and the Kamlet-Taft Parameters (α, β, and π*). iii ACKNOWLEDGEMENTS This thesis would not have been possible with the constant support, guidance, patience and encouragement from my adviser Dr. Douglas Fox that he provided throughout the entirety of my project. Amidst of his busy schedule, he was always available to assist me during the most difficult times when writing this thesis. I would also like to thank Dr. Shoaleh Dehghan, who assisted me incorporating Gas- Chromatography Mass Spectrometery (GC-MS) measurements in this work. I thank my fellow lab mate, Solomon Teklai, who has been very supportive and confident on my abilities throughout my graduate studies. I would also like to thank Chemistry Faculty staff at US Naval Academy in Annapolis, MD who gave me a tremendous opportunity to use their instrumentations. Last but not the least, I would thank all of the committee members for their time, valuable comments and guidance. iv TABLE OF CONTENTS ABSTRACT ................................................................................................................................. ii ACKNOWLEDGEMENTS .......................................................................................................... iv TABLE OF CONTENTS .............................................................................................................. v LIST OF ILLUSTRATIONS......................................................................................................... vi LIST OF TABLES ...................................................................................................................... vii INTRODUCTION ........................................................................................................................ 1 Objective ......................................................................................................................... 5 Optical Rotation [α] .......................................................................................................... 6 Density (ρ) ....................................................................................................................... 9 Refractive Index (nD) ...................................................................................................... 10 Differential Scanning Calorimetry (DSC) ....................................................................... 11 Solvatochromism ........................................................................................................... 16 Gas-Chromatography-Mass Spectrometry (GC-MS) ..................................................... 24 EXPERIMENTAL SECTION...................................................................................................... 25 RESULTS AND DISCUSSION .................................................................................................. 29 Optical Rotation [α] and Density (ρ) ............................................................................... 29 Refractive Index (nD) ...................................................................................................... 32 Differential Scanning Calorimetry (DSC) ........................................................................ 33 Solvatochromism ........................................................................................................... 36 Gas Chromatography-Mass Spectrometry (GC-MS) ...................................................... 31 CONCLUSIONS ........................................................................................................................ 43 APPENDIX A: GC-MS RESULTS ........................................................................................... 45 APPENDIX B: MODULATED DSC THERMOGRAMS .............................................................. 51 APPENDIX C: ABSORPTION SPECTRA ................................................................................ 56 REFERENCES ......................................................................................................................... 62 v LIST OF ILLUSTRATIONS Figure 1. The Molecular Structure of Ethyl Lactate ............................................................ 2 2. Two Enantiomeric forms of Ethyl Lactate ............................................................. 3 3. Schematic Diagram of a Polarimeter ................................................................... 7 4. Binary Phase Diagram of Enantiomers showing the Eutectic Point ................... 13 5. DSC Thermogram showing Various Thermal Events ........................................ 14 6. Structures of Solvatochromic Probes used in this Study to Investigate Solvent Polarity and Hydrogen-Bonding Characteristics ................................................ 17 7. Molecular Structure of the Zwitterionic Reichardt’s Betaine Dye showing its Inherent Properties .......................................................................................... 19 8. Molecular Structure of Zwitterionic Dichlorosubstituted Reichardt’s Betaine Dye .......................................................................................................................... 20 9. Resonance Forms of 4-Nitroaniline ................................................................... 21 10. HBA Sites in 4-Nitroaniline ................................................................................ 21 11. HBA Sites in N,N-Diethyl-4-Nitroaniline ............................................................. 22 12. Binary Phase Diagram of Ethyl Lactate Enantiomers ......................................... 33 13. Plot Showing Temperature Dependence of ET(30) Polarity Scale in (-)-Ethyl L- Lactate, (+)-Ethyl D-Lactate and Racemic Ethyl-D,L-Lactate Mixture ................ 36 14. Plot Showing Temperature Dependence of HBA (β) for (-)-Ethyl L-Lactate, (+)- Ethyl D-Lactate and Racemic Ethyl-D,L-Lactate Mixture ................................... 38 15. Plot Showing Temperature Dependence of HBD (α) for (-)-Ethyl L-Lactate, (+)- Ethyl D-Lactate and Racemic Ethyl-D,L-Lactate Mixture ................................... 39 16. Plot showing Temperature Dependence of Polarizability (π*) for (-)-Ethyl L- Lactate, (+)-Ethyl D-Lactate and